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Sample records for peripheral immune challenge

  1. Repetitive immunization enhances the susceptibility of mice to peripherally administered prions.

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    Juliane Bremer

    Full Text Available The susceptibility of humans and animals to prion infections is determined by the virulence of the infectious agent, by genetic modifiers, and by hitherto unknown host and environmental risk factors. While little is known about the latter two, the activation state of the immune system was surmised to influence prion susceptibility. Here we administered prions to mice that were repeatedly immunized by two initial injections of CpG oligodeoxynucleotides followed by repeated injections of bovine serum albumin/alum. Immunization greatly reduced the required dosage of peripherally administered prion inoculum necessary to induce scrapie in 50% of mice. No difference in susceptibility was observed following intracerebral prion challenge. Due to its profound impact onto scrapie susceptibility, the host immune status may determine disease penetrance after low-dose prion exposure, including those that may give rise to iatrogenic and variant Creutzfeldt-Jakob disease.

  2. 25-Hydroxyvitamin D and Peripheral Immune Mediators

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    Thorsen, Steffen; Pipper, Christian; Skogstrand, Kristin

    2017-01-01

    Background: We aimed to examine if 25-hydroxyvitamin D (25(OH)D) was related to the peripheral immunological and inflammatory signature both at birth, and in newly diagnosed patients with childhood type 1 diabetes (T1D) and their healthy controls; (2) Methods: The birth cohort consisted of 470...... patients and 500 healthy controls. Dried blood samples were collected from the neonates in the period 1981–1999. The newly diagnosed cohort consisted of 460 patients and 453 siblings. Serum samples were collected in the period 1997–2005. A variety of peripheral immune mediators were measured and compared...... to total 25(OH)D levels (25(OH)D2 + 25(OH)D3). For each immune mediator, the relative change (RC) in the mean level was modeled by robust log-normal regression and correction for multiple testing was performed; (3) Results: Two associations were identified; there was a negative association between 25(OH...

  3. Peripheral Developing Odontoma or Peripheral Ameloblastic Fibroodontoma: A Rare Challenging Case

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    Saede Atarbashi Moghadam

    2016-01-01

    Full Text Available Peripheral odontogenic lesions are considered to be rare within the classification of odontogenic tumors. They share the same microscopic characteristics of their central counterparts. Here, we report an ulcerated mass of the maxillary gingiva that on histopathological examination was diagnosed as peripheral developing odontoma or peripheral ameloblastic fibroodontoma. The diagnosis of this tumor is challenging and may lead to unnecessary treatment.

  4. Role of the peripheral innate immune system in the development of Alzheimer's disease.

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    Le Page, Aurélie; Dupuis, Gilles; Frost, Eric H; Larbi, Anis; Pawelec, Graham; Witkowski, Jacek M; Fulop, Tamas

    2017-12-21

    Alzheimer's disease is one of the most devastating neurodegenerative diseases. The exact cause of the disease is still not known although many scientists believe in the beta amyloid hypothesis which states that the accumulation of the amyloid peptide beta (Aβ) in brain is the initial cause which consequently leads to pathological neuroinflammation. However, it was recently shown that Aβ may have an important role in defending the brain against infections. Thus, the balance between positive and negative impact of Aβ may determine disease progression. Microglia in the brain are innate immune cells, and brain-initiated inflammatory responses reflected in the periphery suggests that Alzheimer's disease is to some extent also a systemic inflammatory disease. Greater permeability of the blood brain barrier facilitates the transport of peripheral immune cells to the brain and vice versa so that a vicious circle originating on the periphery may contribute to the development of overt clinical AD. Persistent inflammatory challenges by pathogens in the periphery, increasing with age, may also contribute to the central propagation of the pathological changes seen clinically. Therefore, the activation status of peripheral innate immune cells may represent an early biomarker of the upcoming impact on the brain. The modulation of these cells may thus become a useful mechanism for modifying disease progression. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Molecular dialogues between the ischemic brain and the peripheral immune system: Dualistic roles in injury and repair

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    An, Chengrui; Shi, Yejie; Li, Peiying; Hu, Xiaoming; Gan, Yu; Stetler, Ruth A.; Leak, Rehana K.; Gao, Yanqin; Sun, Bao-Liang; Zheng, Ping; Chen, Jun

    2014-01-01

    Immune and inflammatory responses actively modulate the pathophysiological processes of acute brain injuries such as stroke. Soon after the onset of stroke, signals such as brain-derived antigens, danger-associated molecular patterns (DAMPs), cytokines, and chemokines are released from the injured brain into the systemic circulation. The injured brain also communicates with peripheral organs through the parasympathetic and sympathetic branches of the autonomic nervous system. Many of these diverse signals not only activate resident immune cells in the brain, but also trigger robust immune responses in the periphery. Peripheral immune cells then migrate toward the site of injury and release additional cytokines, chemokines, and other molecules, causing further disruptive or protective effects in the ischemic brain. Bidirectional communication between the injured brain and the peripheral immune system is now known to regulate the progression of stroke pathology as well as tissue repair. In the end, this exquisitely coordinated crosstalk helps determine the fate of animals after stroke. This article reviews the literature on ischemic brain-derived signals through which peripheral immune responses are triggered, and the potential impact of these peripheral responses on brain injury and repair. Pharmacological strategies and cell-based therapies that target the dialogue between the brain and peripheral immune system show promise as potential novel treatments for stroke. PMID:24374228

  6. Peripheral innate immune challenge exaggerated microglia activation, increased the number of inflammatory CNS macrophages, and prolonged social withdrawal in socially defeated mice.

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    Wohleb, Eric S; Fenn, Ashley M; Pacenta, Ann M; Powell, Nicole D; Sheridan, John F; Godbout, Jonathan P

    2012-09-01

    Repeated social defeat (RSD) activates neuroendocrine pathways that have a significant influence on immunity and behavior. Previous studies from our lab indicate that RSD enhances the inflammatory capacity of CD11b⁺ cells in the brain and promotes anxiety-like behavior in an interleukin (IL)-1 and β-adrenergic receptor-dependent manner. The purpose of this study was to determine the degree to which mice subjected to RSD were more responsive to a secondary immune challenge. Therefore, RSD or control (HCC) mice were injected with saline or lipopolysaccharide (LPS) and activation of brain CD11b⁺ cells and behavioral responses were determined. Peripheral LPS (0.5 mg/kg) injection caused an extended sickness response with exaggerated weight loss and prolonged social withdrawal in socially defeated mice. LPS injection also amplified mRNA expression of IL-1β, tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS), and CD14 in enriched CD11b⁺ cells isolated from socially defeated mice. In addition, IL-1β mRNA levels in enriched CD11b⁺ cells remained elevated in socially defeated mice 24 h and 72 h after LPS. Moreover, microglia and CNS macrophages isolated from socially defeated mice had the highest CD14 expression after LPS injection. Both social defeat and LPS injection increased the percentage of CD11b⁺/CD45(high) macrophages in the brain and the number of inflammatory macrophages (CD11b⁺/CD45(high)/CCR2⁺) was highest in RSD-LPS mice. Anxiety-like behavior was increased by social defeat, but was not exacerbated by the LPS challenge. Nonetheless, reduced locomotor activity and increased social withdrawal were still present in socially defeated mice 72 h after LPS. Last, LPS-induced microglia activation was most evident in the hippocampus of socially defeated mice. Taken together, these findings demonstrate that repeated social defeat enhanced the neuroinflammatory response and caused prolonged sickness following innate immune challenge

  7. Evidence of inflammatory immune signaling in chronic fatigue syndrome: A pilot study of gene expression in peripheral blood

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    Vernon Suzanne D

    2008-09-01

    Full Text Available Abstract Background Genomic profiling of peripheral blood reveals altered immunity in chronic fatigue syndrome (CFS however interpretation remains challenging without immune demographic context. The object of this work is to identify modulation of specific immune functional components and restructuring of co-expression networks characteristic of CFS using the quantitative genomics of peripheral blood. Methods Gene sets were constructed a priori for CD4+ T cells, CD8+ T cells, CD19+ B cells, CD14+ monocytes and CD16+ neutrophils from published data. A group of 111 women were classified using empiric case definition (U.S. Centers for Disease Control and Prevention and unsupervised latent cluster analysis (LCA. Microarray profiles of peripheral blood were analyzed for expression of leukocyte-specific gene sets and characteristic changes in co-expression identified from topological evaluation of linear correlation networks. Results Median expression for a set of 6 genes preferentially up-regulated in CD19+ B cells was significantly lower in CFS (p = 0.01 due mainly to PTPRK and TSPAN3 expression. Although no other gene set was differentially expressed at p Conclusion Dissection of blood microarray profiles points to B cell dysfunction with coordinated immune activation supporting persistent inflammation and antibody-mediated NK cell modulation of T cell activity. This has clinical implications as the CD19+ genes identified could provide robust and biologically meaningful basis for the early detection and unambiguous phenotyping of CFS.

  8. Molecular dialogs between the ischemic brain and the peripheral immune system: dualistic roles in injury and repair.

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    An, Chengrui; Shi, Yejie; Li, Peiying; Hu, Xiaoming; Gan, Yu; Stetler, Ruth A; Leak, Rehana K; Gao, Yanqin; Sun, Bao-Liang; Zheng, Ping; Chen, Jun

    2014-04-01

    Immune and inflammatory responses actively modulate the pathophysiological processes of acute brain injuries such as stroke. Soon after the onset of stroke, signals such as brain-derived antigens, danger-associated molecular patterns (DAMPs), cytokines, and chemokines are released from the injured brain into the systemic circulation. The injured brain also communicates with peripheral organs through the parasympathetic and sympathetic branches of the autonomic nervous system. Many of these diverse signals not only activate resident immune cells in the brain, but also trigger robust immune responses in the periphery. Peripheral immune cells then migrate toward the site of injury and release additional cytokines, chemokines, and other molecules, causing further disruptive or protective effects in the ischemic brain. Bidirectional communication between the injured brain and the peripheral immune system is now known to regulate the progression of stroke pathology as well as tissue repair. In the end, this exquisitely coordinated crosstalk helps determine the fate of animals after stroke. This article reviews the literature on ischemic brain-derived signals through which peripheral immune responses are triggered, and the potential impact of these peripheral responses on brain injury and repair. Pharmacological strategies and cell-based therapies that target the dialog between the brain and peripheral immune system show promise as potential novel treatments for stroke. Published by Elsevier Ltd.

  9. CNS infiltration of peripheral immune cells: D-Day for neurodegenerative disease?

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    Rezai-Zadeh, Kavon; Gate, David; Town, Terrence

    2009-12-01

    While the central nervous system (CNS) was once thought to be excluded from surveillance by immune cells, a concept known as "immune privilege," it is now clear that immune responses do occur in the CNS-giving rise to the field of neuroimmunology. These CNS immune responses can be driven by endogenous (glial) and/or exogenous (peripheral leukocyte) sources and can serve either productive or pathological roles. Recent evidence from mouse models supports the notion that infiltration of peripheral monocytes/macrophages limits progression of Alzheimer's disease pathology and militates against West Nile virus encephalitis. In addition, infiltrating T lymphocytes may help spare neuronal loss in models of amyotrophic lateral sclerosis. On the other hand, CNS leukocyte penetration drives experimental autoimmune encephalomyelitis (a mouse model for the human demyelinating disease multiple sclerosis) and may also be pathological in both Parkinson's disease and human immunodeficiency virus encephalitis. A critical understanding of the cellular and molecular mechanisms responsible for trafficking of immune cells from the periphery into the diseased CNS will be key to target these cells for therapeutic intervention in neurodegenerative diseases, thereby allowing neuroregenerative processes to ensue.

  10. Aging of immune system: Immune signature from peripheral blood lymphocyte subsets in 1068 healthy adults.

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    Qin, Ling; Jing, Xie; Qiu, Zhifeng; Cao, Wei; Jiao, Yang; Routy, Jean-Pierre; Li, Taisheng

    2016-05-01

    Aging is a major risk factor for several conditions including neurodegenerative, cardiovascular diseases and cancer. Functional impairments in cellular pathways controlling genomic stability, and immune control have been identified. Biomarker of immune senescence is needed to improve vaccine response and to develop therapy to improve immune control. To identify phenotypic signature of circulating immune cells with aging, we enrolled 1068 Chinese healthy volunteers ranging from 18 to 80 years old. The decreased naïve CD4+ and CD8+ T cells, increased memory CD4+ or CD8+ T cells, loss of CD28 expression on T cells and reverse trend of CD38 and HLA-DR, were significant for aging of immune system. Conversely, the absolute counts and percentage of NK cells and CD19+B cells maintained stable in aging individuals. The Chinese reference ranges of absolute counts and percentage of peripheral lymphocyte in this study might be useful for future clinical evaluation.

  11. CNS recruitment of CD8+ T lymphocytes specific for a peripheral virus infection triggers neuropathogenesis during polymicrobial challenge.

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    Christine M Matullo

    2011-12-01

    Full Text Available Although viruses have been implicated in central nervous system (CNS diseases of unknown etiology, including multiple sclerosis and amyotrophic lateral sclerosis, the reproducible identification of viral triggers in such diseases has been largely unsuccessful. Here, we explore the hypothesis that viruses need not replicate in the tissue in which they cause disease; specifically, that a peripheral infection might trigger CNS pathology. To test this idea, we utilized a transgenic mouse model in which we found that immune cells responding to a peripheral infection are recruited to the CNS, where they trigger neurological damage. In this model, mice are infected with both CNS-restricted measles virus (MV and peripherally restricted lymphocytic choriomeningitis virus (LCMV. While infection with either virus alone resulted in no illness, infection with both viruses caused disease in all mice, with ∼50% dying following seizures. Co-infection resulted in a 12-fold increase in the number of CD8+ T cells in the brain as compared to MV infection alone. Tetramer analysis revealed that a substantial proportion (>35% of these infiltrating CD8+ lymphocytes were LCMV-specific, despite no detectable LCMV in CNS tissues. Mechanistically, CNS disease was due to edema, induced in a CD8-dependent but perforin-independent manner, and brain herniation, similar to that observed in mice challenged intracerebrally with LCMV. These results indicate that T cell trafficking can be influenced by other ongoing immune challenges, and that CD8+ T cell recruitment to the brain can trigger CNS disease in the apparent absence of cognate antigen. By extrapolation, human CNS diseases of unknown etiology need not be associated with infection with any particular agent; rather, a condition that compromises and activates the blood-brain barrier and adjacent brain parenchyma can render the CNS susceptible to pathogen-independent immune attack.

  12. Behavioural conditioning of immune functions: how the central nervous system controls peripheral immune responses by evoking associative learning processes.

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    Riether, Carsten; Doenlen, Raphaël; Pacheco-López, Gustavo; Niemi, Maj-Britt; Engler, Andrea; Engler, Harald; Schedlowski, Manfred

    2008-01-01

    During the last 30 years of psychoneuroimmunology research the intense bi-directional communication between the central nervous system (CNS) and the immune system has been demonstrated in studies on the interaction between the nervous-endocrine-immune systems. One of the most intriguing examples of such interaction is the capability of the CNS to associate an immune status with specific environmental stimuli. In this review, we systematically summarize experimental evidence demonstrating the behavioural conditioning of peripheral immune functions. In particular, we focus on the mechanisms underlying the behavioural conditioning process and provide a theoretical framework that indicates the potential feasibility of behaviourally conditioned immune changes in clinical situations.

  13. Involvement of TRPM2 in peripheral nerve injury-induced infiltration of peripheral immune cells into the spinal cord in mouse neuropathic pain model.

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    Kouichi Isami

    Full Text Available Recent evidence suggests that transient receptor potential melastatin 2 (TRPM2 expressed in immune cells plays an important role in immune and inflammatory responses. We recently reported that TRPM2 expressed in macrophages and spinal microglia contributes to the pathogenesis of inflammatory and neuropathic pain aggravating peripheral and central pronociceptive inflammatory responses in mice. To further elucidate the contribution of TRPM2 expressed by peripheral immune cells to neuropathic pain, we examined the development of peripheral nerve injury-induced neuropathic pain and the infiltration of immune cells (particularly macrophages into the injured nerve and spinal cord by using bone marrow (BM chimeric mice by crossing wildtype (WT and TRPM2-knockout (TRPM2-KO mice. Four types of BM chimeric mice were prepared, in which irradiated WT or TRPM2-KO recipient mice were transplanted with either WT-or TRPM2-KO donor mouse-derived green fluorescence protein-positive (GFP(+ BM cells (TRPM2(BM+/Rec+, TRPM2(BM-/Rec+, TRPM2(BM+/Rec-, and TRPM2(BM-/Rec- mice. Mechanical allodynia induced by partial sciatic nerve ligation observed in TRPM2(BM+/Rec+ mice was attenuated in TRPM2(BM-/Rec+, TRPM2(BM+/Rec-, and TRPM2(BM-/Rec- mice. The numbers of GFP(+ BM-derived cells and Iba1/GFP double-positive macrophages in the injured sciatic nerve did not differ among chimeric mice 14 days after the nerve injury. In the spinal cord, the number of GFP(+ BM-derived cells, particularly GFP/Iba1 double-positive macrophages, was significantly decreased in the three TRPM2-KO chimeric mouse groups compared with TRPM2(BM+/Rec+ mice. However, the numbers of GFP(-/Iba1(+ resident microglia did not differ among chimeric mice. These results suggest that TRPM2 plays an important role in the infiltration of peripheral immune cells, particularly macrophages, into the spinal cord, rather than the infiltration of peripheral immune cells into the injured nerves and activation of spinal

  14. Cognitive deficits develop 1month after diffuse brain injury and are exaggerated by microglia-associated reactivity to peripheral immune challenge.

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    Muccigrosso, Megan M; Ford, Joni; Benner, Brooke; Moussa, Daniel; Burnsides, Christopher; Fenn, Ashley M; Popovich, Phillip G; Lifshitz, Jonathan; Walker, Fredrick Rohan; Eiferman, Daniel S; Godbout, Jonathan P

    2016-05-01

    Traumatic brain injury (TBI) elicits immediate neuroinflammatory events that contribute to acute cognitive, motor, and affective disturbance. Despite resolution of these acute complications, significant neuropsychiatric and cognitive issues can develop and progress after TBI. We and others have provided novel evidence that these complications are potentiated by repeated injuries, immune challenges and stressors. A key component to this may be increased sensitization or priming of glia after TBI. Therefore, our objectives were to determine the degree to which cognitive deterioration occurred after diffuse TBI (moderate midline fluid percussion injury) and ascertain if glial reactivity induced by an acute immune challenge potentiated cognitive decline 30 days post injury (dpi). In post-recovery assessments, hippocampal-dependent learning and memory recall were normal 7 dpi, but anterograde learning was impaired by 30 dpi. Examination of mRNA and morphological profiles of glia 30 dpi indicated a low but persistent level of inflammation with elevated expression of GFAP and IL-1β in astrocytes and MHCII and IL-1β in microglia. Moreover, an acute immune challenge 30 dpi robustly interrupted memory consolidation specifically in TBI mice. These deficits were associated with exaggerated microglia-mediated inflammation with amplified (IL-1β, CCL2, TNFα) and prolonged (TNFα) cytokine/chemokine expression, and a marked reactive morphological profile of microglia in the CA3 of the hippocampus. Collectively, these data indicate that microglia remain sensitized 30 dpi after moderate TBI and a secondary inflammatory challenge elicits robust microglial reactivity that augments cognitive decline. Traumatic brain injury (TBI) is a major risk factor in development of neuropsychiatric problems long after injury, negatively affecting quality of life. Mounting evidence indicates that inflammatory processes worsen with time after a brain injury and are likely mediated by glia. Here

  15. Microglia Transcriptome Changes in a Model of Depressive Behavior after Immune Challenge.

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    Dianelys Gonzalez-Pena

    Full Text Available Depression symptoms following immune response to a challenge have been reported after the recovery from sickness. A RNA-Seq study of the dysregulation of the microglia transcriptome in a model of inflammation-associated depressive behavior was undertaken. The transcriptome of microglia from mice at day 7 after Bacille Calmette Guérin (BCG challenge was compared to that from unchallenged Control mice and to the transcriptome from peripheral macrophages from the same mice. Among the 562 and 3,851 genes differentially expressed between BCG-challenged and Control mice in microglia and macrophages respectively, 353 genes overlapped between these cells types. Among the most differentially expressed genes in the microglia, serum amyloid A3 (Saa3 and cell adhesion molecule 3 (Cadm3 were over-expressed and coiled-coil domain containing 162 (Ccdc162 and titin-cap (Tcap were under-expressed in BCG-challenged relative to Control. Many of the differentially expressed genes between BCG-challenged and Control mice were associated with neurological disorders encompassing depression symptoms. Across cell types, S100 calcium binding protein A9 (S100A9, interleukin 1 beta (Il1b and kynurenine 3-monooxygenase (Kmo were differentially expressed between challenged and control mice. Immune response, chemotaxis, and chemokine activity were among the functional categories enriched by the differentially expressed genes. Functional categories enriched among the 9,117 genes differentially expressed between cell types included leukocyte regulation and activation, chemokine and cytokine activities, MAP kinase activity, and apoptosis. More than 200 genes exhibited alternative splicing events between cell types including WNK lysine deficient protein kinase 1 (Wnk1 and microtubule-actin crosslinking factor 1(Macf1. Network visualization revealed the capability of microglia to exhibit transcriptome dysregulation in response to immune challenge still after resolution of sickness

  16. Immunizations challenge healthcare personnel and affects immunization rates.

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    Strohfus, Pamela K; Kim, Susan C; Palma, Sara; Duke, Russell A; Remington, Richard; Roberts, Caleb

    2017-02-01

    This study measured 1. medical office immunization rates and 2. health care personnel competency in managing vaccine practices before and after evidence-based immunization education was provided. This descriptive study compared 32 family medicine and pediatric offices and 178 medical assistants, licensed practical nurses, registered nurses, nurse practitioners, and physicians in knowledge-based testing pre-education, post-education, and 12-months post-education. Immunization rates were assessed before and 18-months post-education. Immunization rates increased 10.3% - 18months post-education; knowledge increased 7.8% - 12months post-education. Family medicine offices, licensed practical nurses, and medical assistants showed significant knowledge deficits before and 12-months post-education. All demographic groups scored less in storage/handling 12-months post-education. This study is one of the first studies to identify competency challenges in effective immunization delivery among medical assistants, licensed practical nurses, and family medicine offices. Formal and continuous education in immunization administration and storage/handling is recommended among these select groups. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Chemotherapy ± cetuximab modulates peripheral immune responses in metastatic colorectal cancer.

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    Xynos, Ioannis D; Karadima, Maria L; Voutsas, Ioannis F; Amptoulach, Sousana; Skopelitis, Elias; Kosmas, Christos; Gritzapis, Angelos D; Tsavaris, Nikolas

    2013-01-01

    To identify changes in peripheral immune responses in patients with metastatic colorectal cancer (mCRC) treated with irinotecan/5-fluorouracil/leucovorin (IFL) alone or in combination with cetuximab (C-IFL). Peripheral blood mononuclear cells (PBMCs) collected from healthy donors (n = 20) and patients with mCRC receiving treatment with either IFL (n = 30) or C-IFL (n = 30) were tested for cytokine production upon polyclonal stimulation with anti-CD3 monoclonal antibody, T cell proliferation in the autologous mixed lymphocyte reaction (auto-MLR) and T regulatory cell (Treg) frequency. The respective results were evaluated over two treatment cycles and further assessed in relation to response to treatment. PBMCs prior to treatment exhibited significantly lower production of IL-2, IFN-γ, IL-12 and IL-18 cytokines and lower auto-MLR responses, whereas Treg frequency, IL-4, IL-10 cytokines were increased compared to healthy donors. During treatment, IL-2, IFN-γ, IL-12, IL-18 and auto-MLR responses increased, while Treg frequency and IL-10 secretion decreased significantly compared to the baseline. Responders to treatment exhibited a significantly higher increase in IL-2, IFN-γ, IL-12 and IL-18 production and auto-MLR responses, and higher decrease in IL-4, IL-10 secretion and Treg frequency. Among all patient subgroups analysed, responders to C-IFL demonstrated significantly higher increase in auto-MLR responses, IL-12 and IL-18 secretion and higher decrease in Treg frequency. The disturbed immune parameters observed in patients with mCRC at presentation can be significantly improved during treatment with IFL and this effect can be potentiated by the addition of cetuximab. Monitoring of the peripheral immune system function could be used as surrogate marker in predicting treatment-related outcome. Copyright © 2013 S. Karger AG, Basel.

  18. CHARACTERISATION OF CELL-MEDIATED IMMUNE RESPONSE IN PIGS IN A CLINICAL CHALLENGE EXPERIMENT OF A VACCINE AGAINST MYCOPLASMA HYOSYNOVIAE

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    Rasmussen, Josephine Skovgaard; Riber, Ulla; Lauritsen, Klara Tølbøll

    be due to increased systemic infection in the placebo group. Cell-mediated immune response was further characterised by four colour flow cytometry analysis of peripheral blood mononuclear cells (PBMCs) before Mhs challenge (day -1) and at days 6 and 9 after challenge. IFN-γ producing cells were found...... to be CD4 and especially CD4CD8 double positive T-cells simultaneously expressing CD25. Interestingly, the proportion of CD4CD8 double positive T-cells within the total population of CD4 positive cells increased in the vaccine group after challenge, indicating that generation of specific T-cell memory had...

  19. The effect of maternal and paternal immune challenge on offspring immunity and reproduction in a cricket.

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    McNamara, K B; van Lieshout, E; Simmons, L W

    2014-06-01

    Trans-generational immune priming is the transmission of enhanced immunity to offspring following a parental immune challenge. Although within-generation increased investment into immunity demonstrates clear costs on reproductive investment in a number of taxa, the potential for immune priming to impact on offspring reproductive investment has not been thoroughly investigated. We explored the reproductive costs of immune priming in a field cricket, Teleogryllus oceanicus. To assess the relative importance of maternal and paternal immune status, mothers and fathers were immune-challenged with live bacteria or a control solution and assigned to one of four treatments in which one parent, neither or both parents were immune-challenged. Families of offspring were reared to adulthood under a food-restricted diet, and approximately 10 offspring in each family were assayed for two measures of immunocompetence. We additionally quantified offspring reproductive investment using sperm viability for males and ovary mass for females. We demonstrate that parental immune challenge has significant consequences for the immunocompetence and, in turn, reproductive investment of their male offspring. A complex interaction between maternal and paternal immune status increased the antibacterial immune response of male offspring. This increased immune response was associated with a reduction in son's sperm viability, implicating a trans-generational resource trade-off between investment into immunocompetence and reproduction. Our data also show that these costs are sexually dimorphic, as daughters did not demonstrate a similar increase in immunity, despite showing a reduction in ovary mass. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

  20. Mapping the Fetomaternal Peripheral Immune System at Term Pregnancy.

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    Fragiadakis, Gabriela K; Baca, Quentin J; Gherardini, Pier Federico; Ganio, Edward A; Gaudilliere, Dyani K; Tingle, Martha; Lancero, Hope L; McNeil, Leslie S; Spitzer, Matthew H; Wong, Ronald J; Shaw, Gary M; Darmstadt, Gary L; Sylvester, Karl G; Winn, Virginia D; Carvalho, Brendan; Lewis, David B; Stevenson, David K; Nolan, Garry P; Aghaeepour, Nima; Angst, Martin S; Gaudilliere, Brice L

    2016-12-01

    Preterm labor and infections are the leading causes of neonatal deaths worldwide. During pregnancy, immunological cross talk between the mother and her fetus is critical for the maintenance of pregnancy and the delivery of an immunocompetent neonate. A precise understanding of healthy fetomaternal immunity is the important first step to identifying dysregulated immune mechanisms driving adverse maternal or neonatal outcomes. This study combined single-cell mass cytometry of paired peripheral and umbilical cord blood samples from mothers and their neonates with a graphical approach developed for the visualization of high-dimensional data to provide a high-resolution reference map of the cellular composition and functional organization of the healthy fetal and maternal immune systems at birth. The approach enabled mapping of known phenotypical and functional characteristics of fetal immunity (including the functional hyperresponsiveness of CD4 + and CD8 + T cells and the global blunting of innate immune responses). It also allowed discovery of new properties that distinguish the fetal and maternal immune systems. For example, examination of paired samples revealed differences in endogenous signaling tone that are unique to a mother and her offspring, including increased ERK1/2, MAPK-activated protein kinase 2, rpS6, and CREB phosphorylation in fetal Tbet + CD4 + T cells, CD8 + T cells, B cells, and CD56 lo CD16 + NK cells and decreased ERK1/2, MAPK-activated protein kinase 2, and STAT1 phosphorylation in fetal intermediate and nonclassical monocytes. This highly interactive functional map of healthy fetomaternal immunity builds the core reference for a growing data repository that will allow inferring deviations from normal associated with adverse maternal and neonatal outcomes. Copyright © 2016 by The American Association of Immunologists, Inc.

  1. Overcoming Challenges to Childhood Immunizations Status.

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    Sabnis, Svapna S; Conway, James H

    2015-10-01

    Vaccines are one of the greatest public health achievements, preventing both mortality and morbidity. However, overall immunization rates are still below the 90% target for Healthy People 2020. There remain significant disparities in immunization rates between children of different racial/ethnic groups, as well as among economically disadvantaged populations. There are systemic issues and challenges in providing access to immunization opportunities. In addition, vaccine hesitancy contributes to underimmunization. Multiple strategies are needed to improve immunization rates, including improving access to vaccines and minimizing financial barriers to families. Vaccine status should be assessed and vaccines given at all possible opportunities. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Sequential activation of microglia and astrocyte cytokine expression precedes increased Iba-1 or GFAP immunoreactivity following systemic immune challenge.

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    Norden, Diana M; Trojanowski, Paige J; Villanueva, Emmanuel; Navarro, Elisa; Godbout, Jonathan P

    2016-02-01

    Activation of the peripheral immune system elicits a coordinated response from the central nervous system. Key to this immune to brain communication is that glia, microglia, and astrocytes, interpret and propagate inflammatory signals in the brain that influence physiological and behavioral responses. One issue in glial biology is that morphological analysis alone is used to report on glial activation state. Therefore, our objective was to compare behavioral responses after in vivo immune (lipopolysaccharide, LPS) challenge to glial specific mRNA and morphological profiles. Here, LPS challenge induced an immediate but transient sickness response with decreased locomotion and social interaction. Corresponding with active sickness behavior (2-12 h), inflammatory cytokine mRNA expression was elevated in enriched microglia and astrocytes. Although proinflammatory cytokine expression in microglia peaked 2-4 h after LPS, astrocyte cytokine, and chemokine induction was delayed and peaked at 12 h. Morphological alterations in microglia (Iba-1(+)) and astrocytes (GFAP(+)), however, were undetected during this 2-12 h timeframe. Increased Iba-1 immunoreactivity and de-ramified microglia were evident 24 and 48 h after LPS but corresponded to the resolution phase of activation. Morphological alterations in astrocytes were undetected after LPS. Additionally, glial cytokine expression did not correlate with morphology after four repeated LPS injections. In fact, repeated LPS challenge was associated with immune and behavioral tolerance and a less inflammatory microglial profile compared with acute LPS challenge. Overall, induction of glial cytokine expression was sequential, aligned with active sickness behavior, and preceded increased Iba-1 or GFAP immunoreactivity after LPS challenge. © 2015 Wiley Periodicals, Inc.

  3. The potential of immunostimulatory CpG DNA for inducing immunity against genital herpes: opportunities and challenges.

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    Harandi, Ali M

    2004-07-01

    Herpes simplex virus type 2 (HSV-2) invades human genital tract mucosa and following local replications can be rapidly transmitted via peripheral nerve axons to the sacral ganglia where it can establish latency. Reactivation of the latent viral reservoir results in recurrent ulcers in the genital region. Innate immunity, the first line of defence during both primary and recurrent genital herpes infections, is crucial during the period of acute infection to limit early virus replication and to facilitate the development of an appropriate specific acquired immunity. Recent developments in immunology reveal that the mammalian innate immune systems use Toll-like receptor (TLR) to specifically sense evolutionary conserved molecules such as bacterial DNA in pathogens. Recently, local-vaginal delivery of CpG containing oligodeoxynucleotide (ODN), a synthetic mimic of bacterial DNA, holds substantial promise as a strong inducer of innate immunity against genital herpes infections in the animal models of the disease. These preclinical observations provide a scientific ground work for introduction of this novel intervention strategy to clinic. This review aims to highlight recent developments and future challenges in use of immunostimulatory CpG ODN for inducing immunity against genital herpes infection and disease.

  4. Lipid Accumulation in Peripheral Blood Dendritic Cells and Anticancer Immunity in Patients with Lung Cancer

    Directory of Open Access Journals (Sweden)

    Ryo Arai

    2018-01-01

    Full Text Available We studied the subsets of peripheral blood dendritic cells (DCs and lipid accumulation in DCs to investigate the involvement of DCs in the decreased anticancer immunity of advanced lung cancer patients. We analyzed the population of DC subsets in peripheral blood using flow cytometry. We then determined lipid accumulation in the DCs using BODIPY 650/665, a fluorophore with an affinity for lipids. Compared with healthy controls, the number of DCs in the peripheral blood of treatment-naive cancer patients was significantly reduced. In patients with stage III + IV disease, the numbers of myeloid DCs (mDCs and plasmacytoid DCs were also significantly reduced. Lipid accumulation in DCs evaluated based on the fluorescence intensity of BODIPY 650/665 was significantly higher in stage III + IV lung cancer patients than in the controls. In the subset analysis, the fluorescence was highest for mDCs. The intracellularly accumulated lipids were identified as triglycerides. A decreased mixed leukocyte reaction was observed in the mDCs from lung cancer patients compared with those from controls. Taken together, the results show that lung cancer patients have a notably decreased number of peripheral blood DCs and their function as antigen-presenting cells is decreased due to their high intracellular lipid accumulation. Thereby, anticancer immunity is suppressed.

  5. Neutrophilic respiratory tract inflammation and peripheral blood neutrophilia after grain sorghum dust extract challenge.

    Science.gov (United States)

    Von Essen, S G; O'Neill, D P; McGranaghan, S; Olenchock, S A; Rennard, S I

    1995-11-01

    To determine if inhalation of grain sorghum dust in the laboratory would cause neutrophilic upper and lower respiratory tract inflammation in human volunteers, as well as systemic signs of illness. Prospective. University of Nebraska Medical Center. Thirty normal volunteers. Inhalation challenge with 20 mL of a nebulized solution of filter-sterilized grain sorghum dust extract (GSDE). One group received prednisone, 20 mg for 2 days, prior to the challenge. Bronchoscopy with bronchoalveolar lavage (BAL) was performed 24 h after challenge, with samples collected as bronchial and alveolar fractions. Findings included visible signs of airways inflammation, quantified as the bronchitis index. The percentage of bronchial neutrophils was significantly increased in those challenged with GSDE vs the control solution, Hanks' balanced salt solution (40.3 +/- 4.5% vs 14.3 +/- 5.1%, p grain dust extract. To explain the increase in peripheral blood neutrophil counts, the capacity of the peripheral blood neutrophils to migrate in chemotaxis experiments was examined. The results demonstrate an increase in peripheral blood neutrophils and an increase in chemotactic responsiveness. Inhalation challenge with a grain dust extract causes respiratory tract inflammation and a peripheral blood neutrophilia. One reason for this may be an increase in activated peripheral blood neutrophils.

  6. Immune response of patients with recurrent aphthous stomatitis challenged with a symbiotic.

    Science.gov (United States)

    Mimura, Maria Angela Martins; Borra, Ricardo Carneiro; Hirata, Cleonice Hitomi Watashi; de Oliveira Penido, Norma

    2017-10-01

    There are indications that Th1 polarization of immune response plays an important role in the pathogenesis of recurrent aphthous stomatitis (RAS), and that the use of probiotics can stimulate immune regulatory activity, influencing the course of the disease. The aim of this study was to characterize the initial immune profile of RAS patients and evaluate clinical and serological response following a challenge with symbiotic treatment containing fructooligosaccharide, Lactobacillus, and Bifidobacterium. The immune responses of the 45 patients with RAS, submitted to symbiotic or placebo for 120 days, in relation to 30 RAS-free controls, were evaluated over a period of 6 months. Peripheral blood was collected from all patients at 0 (T0), 120 (T4), and 180 days (T6) after the start of treatment and Th1 (IL12-p70, IFN-γ), Th2 (IL-4), Treg (IL-10), Th17 (IL-17A), inflammatory (TNF-α, IL-6)-associated cytokines, and clinical parameters were quantified. At T0, significant differences were found in the serological levels of the IFN-γ, IL-4, and IL-6 cytokines of the RAS patients in comparison with the controls. It was observed that the cytokine profile of the RAS group was comprised of 2 distinct clusters: a pure Th2 and a Mixed (Th1/Th2) subtype and that symbiotic treatment induced an improvement in pain and an increase in IFN-γ levels, producing a reduction in Th2 response. In RAS, symbiotic treatment based on a fructooligosaccharide, Lactobacillus, and Bifidobacterium composition produced an alteration in the Th2 serological immune profile in the direction of Th1 and improved pain symptomatology. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Individual differences in the peripheral immune system promote resilience versus susceptibility to social stress.

    Science.gov (United States)

    Hodes, Georgia E; Pfau, Madeline L; Leboeuf, Marylene; Golden, Sam A; Christoffel, Daniel J; Bregman, Dana; Rebusi, Nicole; Heshmati, Mitra; Aleyasin, Hossein; Warren, Brandon L; Lebonté, Benoit; Horn, Sarah; Lapidus, Kyle A; Stelzhammer, Viktoria; Wong, Erik H F; Bahn, Sabine; Krishnan, Vaishnav; Bolaños-Guzman, Carlos A; Murrough, James W; Merad, Miriam; Russo, Scott J

    2014-11-11

    Depression and anxiety disorders are associated with increased release of peripheral cytokines; however, their functional relevance remains unknown. Using a social stress model in mice, we find preexisting individual differences in the sensitivity of the peripheral immune system that predict and promote vulnerability to social stress. Cytokine profiles were obtained 20 min after the first social stress exposure. Of the cytokines regulated by stress, IL-6 was most highly up-regulated only in mice that ultimately developed a susceptible behavioral phenotype following a subsequent chronic stress, and levels remained elevated for at least 1 mo. We confirmed a similar elevation of serum IL-6 in two separate cohorts of patients with treatment-resistant major depressive disorder. Before any physical contact in mice, we observed individual differences in IL-6 levels from ex vivo stimulated leukocytes that predict susceptibility versus resilience to a subsequent stressor. To shift the sensitivity of the peripheral immune system to a pro- or antidepressant state, bone marrow (BM) chimeras were generated by transplanting hematopoietic progenitor cells from stress-susceptible mice releasing high IL-6 or from IL-6 knockout (IL-6(-/-)) mice. Stress-susceptible BM chimeras exhibited increased social avoidance behavior after exposure to either subthreshold repeated social defeat stress (RSDS) or a purely emotional stressor termed witness defeat. IL-6(-/-) BM chimeric and IL-6(-/-) mice, as well as those treated with a systemic IL-6 monoclonal antibody, were resilient to social stress. These data establish that preexisting differences in stress-responsive IL-6 release from BM-derived leukocytes functionally contribute to social stress-induced behavioral abnormalities.

  8. Evidence that shock-induced immune suppression is mediated by adrenal hormones and peripheral beta-adrenergic receptors.

    Science.gov (United States)

    Cunnick, J E; Lysle, D T; Kucinski, B J; Rabin, B S

    1990-07-01

    Our previous work has demonstrated that presentations of mild foot-shock to Lewis rats induces a suppression of splenic and peripheral blood lymphocyte responses to nonspecific T-cell mitogens. The present study demonstrated that adrenalectomy prevented the shock-induced suppression of the mitogenic response of peripheral blood T-cells but did not attenuate the suppression of splenic T-cells. Conversely, the beta-adrenergic receptor antagonists, propranolol and nadolol, attenuated the shock-induced suppression of splenic T-cells in a dose-dependent manner but did not attenuate suppression of the blood mitogen response. These data indicate that distinct mechanisms mediate the shock-induced suppression of T-cell responsiveness to mitogens in the spleen and the peripheral blood. The results indicate that the peripheral release of catecholamines is responsible for splenic immune suppression and that adrenal hormones, which do not interact with beta-adrenergic receptors, are responsible for shock-induced suppression of blood mitogenic responses.

  9. The role of the immune system in the generation of neuropathic pain.

    Science.gov (United States)

    Calvo, Margarita; Dawes, John M; Bennett, David L H

    2012-07-01

    Persistent pain is a sequela of several neurological conditions with a primary immune basis, such as Guillain-Barré syndrome and multiple sclerosis. Additionally, diverse forms of injury to the peripheral or the central nervous systems--whether traumatic, metabolic, or toxic--result in substantial recruitment and activation of immune cells. This response involves the innate immune system, but evidence also exists of T-lymphocyte recruitment, and in some patient cohorts antibodies to neuronal antigens have been reported. Mediators released by immune cells, such as cytokines, sensitise nociceptive signalling in the peripheral and central nervous systems. Preclinical data suggest an immune pathogenesis of neuropathic pain, but clinical evidence of a central role of the immune system is less clear. An important challenge for the future is to establish to what extent this immune response initiates or maintains neuropathic pain in patients and thus whether it is amenable to therapy. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Immune-Challenged Fish Up-Regulate Their Metabolic Scope to Support Locomotion.

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    Camille Bonneaud

    Full Text Available Energy-based trade-offs occur when investment in one fitness-related trait diverts energy away from other traits. The extent to which such trade-offs are shaped by limits on the rate of conversion of energy ingested in food (e.g. carbohydrates into chemical energy (ATP by oxidative metabolism rather than by the amount of food ingested in the first place is, however, unclear. Here we tested whether the ATP required for mounting an immune response will lead to a trade-off with ATP available for physical activity in mosquitofish (Gambusia holbrooki. To this end, we challenged fish either with lipopolysaccharide (LPS from E. coli or with Sheep Red Blood Cells (SRBC, and measured oxygen consumption at rest and during swimming at maximum speed 24h, 48h and 7 days post-challenge in order to estimate metabolic rates. Relative to saline-injected controls, only LPS-injected fish showed a significantly greater resting metabolic rate two days post-challenge and significantly higher maximal metabolic rates two and seven days post-challenge. This resulted in a significantly greater metabolic scope two days post-challenge, with LPS-fish transiently overcompensating by increasing maximal ATP production more than would be required for swimming in the absence of an immune challenge. LPS-challenged fish therefore increased their production of ATP to compensate physiologically for the energetic requirements of immune functioning. This response would avoid ATP shortages and allow fish to engage in an aerobically-challenging activity (swimming even when simultaneously mounting an immune response. Nevertheless, relative to controls, both LPS- and SRBC-fish displayed reduced body mass gain one week post-injection, and LPS-fish actually lost mass. The concomitant increase in metabolic scope and reduced body mass gain of LPS-challenged fish indicates that immune-associated trade-offs are not likely to be shaped by limited oxidative metabolic capacities, but may instead

  11. Gene expression patterns in CD4+ peripheral blood cells in healthy subjects and stage IV melanoma patients.

    Science.gov (United States)

    Felts, Sara J; Van Keulen, Virginia P; Scheid, Adam D; Allen, Kathleen S; Bradshaw, Renee K; Jen, Jin; Peikert, Tobias; Middha, Sumit; Zhang, Yuji; Block, Matthew S; Markovic, Svetomir N; Pease, Larry R

    2015-11-01

    Melanoma patients exhibit changes in immune responsiveness in the local tumor environment, draining lymph nodes, and peripheral blood. Immune-targeting therapies are revolutionizing melanoma patient care increasingly, and studies show that patients derive clinical benefit from these newer agents. Nonetheless, predicting which patients will benefit from these costly therapies remains a challenge. In an effort to capture individual differences in immune responsiveness, we are analyzing patterns of gene expression in human peripheral blood cells using RNAseq. Focusing on CD4+ peripheral blood cells, we describe multiple categories of immune regulating genes, which are expressed in highly ordered patterns shared by cohorts of healthy subjects and stage IV melanoma patients. Despite displaying conservation in overall transcriptome structure, CD4+ peripheral blood cells from melanoma patients differ quantitatively from healthy subjects in the expression of more than 2000 genes. Moreover, 1300 differentially expressed genes are found in transcript response patterns following activation of CD4+ cells ex vivo, suggesting that widespread functional discrepancies differentiate the immune systems of healthy subjects and melanoma patients. While our analysis reveals that the transcriptome architecture characteristic of healthy subjects is maintained in cancer patients, the genes expressed differentially among individuals and across cohorts provide opportunities for understanding variable immune states as well as response potentials, thus establishing a foundation for predicting individual responses to stimuli such as immunotherapeutic agents.

  12. Peripheral and gastrointestinal immune systems of healthy cattle raised outdoors at pasture or indoors on a concentrate-based ration

    Directory of Open Access Journals (Sweden)

    Reilly Petrina

    2010-03-01

    Full Text Available Abstract Background Despite an increasing preference of consumers for beef produced from more extensive pasture-based production systems and potential human health benefits from the consumption of such beef, data regarding the health status of animals raised on pasture are limited. The objective of this study was to characterise specific aspects of the bovine peripheral and the gastrointestinal muscosal immune systems of cattle raised on an outdoor pasture system in comparison to animals raised on a conventional intensive indoor concentrate-based system. Results A number of in vitro functional tests of immune cells suggested subtle differences between the animals on the outdoor versus indoor production systems. There was a decrease in the number of neutrophils and monocytes engaged in phagocytosis in outdoor cattle (P P P P P P P Conclusion Despite distinctly contrasting production systems, only subtle differences were identified in the peripheral immune parameters measured between cattle raised at pasture in comparison to animals raised on a conventional intensive indoor concentrate-based production system.

  13. Challenges associated with peripheral arterial disease in women

    Directory of Open Access Journals (Sweden)

    Barochiner J

    2014-03-01

    Full Text Available Jessica Barochiner, Lucas S Aparicio, Gabriel D Waisman Hypertension Section, Internal Medicine Department, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina Abstract: Peripheral arterial disease (PAD is an increasingly recognized disorder that is associated with functional impairment, quality-of-life deterioration, increased risk of cardiovascular ischemic events, and increased risk of total and cardiovascular mortality. Although earlier studies suggested that PAD was more common in men, recent reports based on more sensitive tests have shown that the prevalence of PAD in women is at least the same as in men, if not higher. PAD tends to present itself asymptomatically or with atypical symptoms more frequently in women than in men, and is associated with comorbidities or situations particularly or exclusively found in the female sex, such as osteoporosis, hypothyroidism, the use of oral contraceptives, and a history of complications during pregnancy. Fat-distribution patterns and differential vascular characteristics in women may influence the interpretation of diagnostic methods, whereas sex-related vulnerability to drugs typically used in subjects with PAD, differences in risk-factor distribution among sexes, and distinct responses to revascularization procedures in men and women must be taken into account for proper disease management. All these issues pose important challenges associated with PAD in women. Of note, this group has classically been underrepresented in research studies. As a consequence, several sex-related challenges regarding diagnosis and management issues should be acknowledged, and research gaps should be addressed in order to successfully deal with this major health issue. Keywords: peripheral arterial disease, women, diagnosis, management

  14. Effect of Diet and Exercise on the Peripheral Immune System in Young Balb/c Mice

    Science.gov (United States)

    Martínez-Carrillo, B. E.; Jarillo-Luna, R. A.; Campos-Rodríguez, R.; Valdés-Ramos, R.; Rivera-Aguilar, V.

    2015-01-01

    Although diet and exercise clearly have an influence on immune function, studies are scarce on the effect caused by exercise and the consumption of a carbohydrate-rich or fat-rich diet on the peripheral immune system. The aim of the present study was to evaluate the effect of exercise and the two aforementioned unbalanced diets on young Balb/c mice, especially in relation to BMI, the level of glucose, and the percentage of lymphocyte subpopulations in peripheral blood. The changes found were then related to the synthesis of leptin and adiponectin as well as the production of oxidative stress. The increase in BMI found with the carbohydrate-rich and fat-rich diets showed correlation with the levels of leptin and adiponectin. An increase in leptin and a decrease in adiponectin directly correlated with an increase in total lymphocytes and CD4+ cells and with a decrease in B cells. The increase in leptin also correlated with an increase in CD8+ cells. Glycemia and oxidative stress increased with the two unbalanced diets, negatively affecting the proliferation of total lymphocytes and the percentage of B cells, apparently by causing alterations in proteins through carbonylation. These alterations caused by an unbalanced diet were not modified by moderate exercise. PMID:26634209

  15. Elevational variation in body-temperature response to immune challenge in a lizard

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    Francisco Javier Zamora-Camacho

    2016-04-01

    Full Text Available Immunocompetence benefits animal fitness by combating pathogens, but also entails some costs. One of its main components is fever, which in ectotherms involves two main types of costs: energy expenditure and predation risk. Whenever those costs of fever outweigh its benefits, ectotherms are expected not to develop fever, or even to show hypothermia, reducing costs of thermoregulation and diverting the energy saved to other components of the immune system. Environmental thermal quality, and therefore the thermoregulation cost/benefit balance, varies geographically. Hence, we hypothesize that, in alpine habitats, immune-challenged ectotherms should show no thermal response, given that (1 hypothermia would be very costly, as the temporal window for reproduction is extremely small, and (2 fever would have a prohibitive cost, as heat acquisition is limited in such habitat. However, in temperate habitats, immune-challenged ectotherms might show a febrile response, due to lower cost/benefit balance as a consequence of a more suitable thermal environment. We tested this hypothesis in Psammodromus algirus lizards from Sierra Nevada (SE Spain, by testing body temperature preferred by alpine and non-alpine lizards, before and after activating their immune system with a typical innocuous pyrogen. Surprisingly, non-alpine lizards responded to immune challenge by decreasing preferential body-temperature, presumably allowing them to save energy and reduce exposure to predators. On the contrary, as predicted, immune-challenged alpine lizards maintained their body-temperature preferences. These results match with increased costs of no thermoregulation with elevation, due to the reduced window of time for reproduction in alpine environment.

  16. Peripheral and gastrointestinal immune systems of healthy cattle raised outdoors at pasture or indoors on a concentrate-based ration.

    Science.gov (United States)

    Lejeune, Alexandre; Monahan, Frank J; Moloney, Aidan P; Earley, Bernadette; Black, Alistair D; Campion, Deirdre P; Englishby, Tanya; Reilly, Petrina; O'Doherty, John; Sweeney, Torres

    2010-03-31

    Despite an increasing preference of consumers for beef produced from more extensive pasture-based production systems and potential human health benefits from the consumption of such beef, data regarding the health status of animals raised on pasture are limited. The objective of this study was to characterise specific aspects of the bovine peripheral and the gastrointestinal muscosal immune systems of cattle raised on an outdoor pasture system in comparison to animals raised on a conventional intensive indoor concentrate-based system. A number of in vitro functional tests of immune cells suggested subtle differences between the animals on the outdoor versus indoor production systems. There was a decrease in the number of neutrophils and monocytes engaged in phagocytosis in outdoor cattle (P outdoor animals (P outdoor animals with elevated levels of serum pepsinogen (P outdoor animals in comparison to the indoor animals. Lower levels of copper and iodine were measured in the outdoor animals in comparison to indoor animals (P < 0.001). Despite distinctly contrasting production systems, only subtle differences were identified in the peripheral immune parameters measured between cattle raised at pasture in comparison to animals raised on a conventional intensive indoor concentrate-based production system.

  17. Effects of blood transportation on human peripheral mononuclear cell yield, phenotype and function: implications for immune cell biobanking.

    Directory of Open Access Journals (Sweden)

    Anita Posevitz-Fejfár

    Full Text Available Human biospecimen collection, processing and preservation are rapidly emerging subjects providing essential support to clinical as well as basic researchers. Unlike collection of other biospecimens (e.g. DNA and serum, biobanking of viable immune cells, such as peripheral blood mononuclear cells (PBMC and/or isolated immune cell subsets is still in its infancy. While certain aspects of processing and freezing conditions have been studied in the past years, little is known about the effect of blood transportation on immune cell survival, phenotype and specific functions. However, especially for multicentric and cooperative projects it is vital to precisely know those effects. In this study we investigated the effect of blood shipping and pre-processing delay on immune cell phenotype and function both on cellular and subcellular levels. Peripheral blood was collected from healthy volunteers (n = 9: at a distal location (shipped overnight and in the central laboratory (processed immediately. PBMC were processed in the central laboratory and analyzed post-cryopreservation. We analyzed yield, major immune subset distribution, proliferative capacity of T cells, cytokine pattern and T-cell receptor signal transduction. Results show that overnight transportation of blood samples does not globally compromise T- cell subsets as they largely retain their phenotype and proliferative capacity. However, NK and B cell frequencies, the production of certain PBMC-derived cytokines and IL-6 mediated cytokine signaling pathway are altered due to transportation. Various control experiments have been carried out to compare issues related to shipping versus pre-processing delay on site. Our results suggest the implementation of appropriate controls when using multicenter logistics for blood transportation aiming at subsequent isolation of viable immune cells, e.g. in multicenter clinical trials or studies analyzing immune cells/subsets. One important conclusion might

  18. Peripheral inflammation/immune indicators of chemosensitivity and prognosis in breast cancer patients treated with neoadjuvant chemotherapy

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    Qian Y

    2018-03-01

    Full Text Available Yi Qian,1,* Jing Tao,1,2,* Xiuqing Li,3 Hua Chen,1 Qi Lu,1 Junzhe Yang,1 Hong Pan,1 Cong Wang,4 Wenbin Zhou,1 Xiaoan Liu1 1Department of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China; 2Department of General Surgery, Nanjing Pukou Hospital, Nanjing, China; 3Department of Pathology, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, China; 4Department of Pathology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China *These authors contributed equally to this work Introduction: Neoadjuvant chemotherapy (NAC has become a standard treatment for locally advanced breast cancer. The present study was designed to investigate the predictive value of different peripheral inflammation/immune biomarker responses to NAC and prognosis in breast cancer patients. Materials and methods: A total of 180 breast cancer patients treated with NAC in the First Affiliated Hospital with Nanjing Medical University between January 2008 and March 2015 were enrolled in the study. The associations between inflammation/immune indicators and pathological complete response (pCR were determined, and the prognostic value of inflammation/immune indicators was also evaluated. Results: In the univariate analysis, patients with a high pretreatment peripheral lymphocyte count (>2.06×109/L showed a higher pCR rate than those with a low lymphocyte count (23.9% vs 10.4%, P=0.023. The pCR rate of patients with a neutrophil: lymphocyte ratio ≤2.15 was significantly higher than that of patients with a high neutrophil: lymphocyte ratio (20% vs 7.8%; P=0.03. However, multivariate analysis revealed that only the high lymphocyte count was predictive for pCR (odds ratio: 4.375, 95% CI: 1.429–13.392, P=0.010. In the survival analysis, patients with a higher neutrophil count (>2.65×109/L were confirmed to have a shorter disease-free survival (hazard ratio: 4.322, 95% CI: 1.028–18.174, P=0.046, and the

  19. Humoral and cell-mediated immune responses in DNA immunized mink challenged with wild-type canine distemper virus.

    Science.gov (United States)

    Nielsen, Line; Søgaard, Mette; Karlskov-Mortensen, Peter; Jensen, Trine Hammer; Jensen, Tove Dannemann; Aasted, Bent; Blixenkrone-Møller, Merete

    2009-07-30

    The aim of the study was to investigate the different phases of the immune response after DNA immunization with the hemagglutinin and nucleoprotein genes from canine distemper virus (CDV). Although attenuated live CDV vaccines have effectively reduced the incidence of disease, canine distemper is still a problem worldwide. The broad host range of CDV creates a constant viral reservoir among wildlife animals. Our results demonstrated early humoral and cell-mediated immune responses (IFN-gamma) in DNA vaccinated mink compared to mock-vaccinated mink after challenge with a Danish wild-type CDV. The DNA vaccine-induced immunity protected the natural host against disease development.

  20. Graphene and the immune system: Challenges and potentiality.

    Science.gov (United States)

    Orecchioni, Marco; Ménard-Moyon, Cécilia; Delogu, Lucia Gemma; Bianco, Alberto

    2016-10-01

    In the growing area of nanomedicine, graphene-based materials (GBMs) are some of the most recent explored nanomaterials. For the majority of GBM applications in nanomedicine, the immune system plays a fundamental role. It is necessary to well understand the complexity of the interactions between GBMs, the immune cells, and the immune components and how they could be of advantage for novel effective diagnostic and therapeutic approaches. In this review, we aimed at painting the current picture of GBMs in the background of the immune system. The picture we have drawn looks like a cubist image, a sort of Picasso-like portrait looking at the topic from all perspectives: the challenges (due to the potential toxicity) and the potentiality like the conjugation of GBMs to biomolecules to develop advanced nanomedicine tools. In this context, we have described and discussed i) the impact of graphene on immune cells, ii) graphene as immunobiosensor, and iii) antibodies conjugated to graphene for tumor targeting. Thanks to the huge advances on graphene research, it seems realistic to hypothesize in the near future that some graphene immunoconjugates, endowed of defined immune properties, can go through preclinical test and be successfully used in nanomedicine. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Peripheral dendritic cells are essential for both the innate and adaptive antiviral immune responses in the central nervous system

    International Nuclear Information System (INIS)

    Steel, Christina D.; Hahto, Suzanne M.; Ciavarra, Richard P.

    2009-01-01

    Intranasal application of vesicular stomatitis virus (VSV) causes acute infection of the central nervous system (CNS). However, VSV encephalitis is not invariably fatal, suggesting that the CNS may contain a professional antigen-presenting cell (APC) capable of inducing or propagating a protective antiviral immune response. To examine this possibility, we first characterized the cellular elements that infiltrate the brain as well as the activation status of resident microglia in the brains of normal and transgenic mice acutely ablated of peripheral dendritic cells (DCs) in vivo. VSV encephalitis was characterized by a pronounced infiltrate of myeloid cells (CD45 high CD11b + ) and CD8 + T cells containing a subset that was specific for the immunodominant VSV nuclear protein epitope. This T cell response correlated temporally with a rapid and sustained upregulation of MHC class I expression on microglia, whereas class II expression was markedly delayed. Ablation of peripheral DCs profoundly inhibited the inflammatory response as well as infiltration of virus-specific CD8 + T cells. Unexpectedly, the VSV-induced interferon-gamma (IFN-γ) response in the CNS remained intact in DC-deficient mice. Thus, both the inflammatory and certain components of the adaptive primary antiviral immune response in the CNS are dependent on peripheral DCs in vivo.

  2. Costs of an immune challenge and terminal investment in a long-lived bird.

    Science.gov (United States)

    Hanssen, Sveinn Are

    2006-10-01

    An induced immune challenge can have two counteracting effects on an individual's reproductive investment. (1) The resource demand could increase to "fuel" the immunologic reaction, which in turn can lead to an adaptive decrease in investment in resource-costly activities, such as reproduction. One the other hand, (2) the individual could assume that the immune activity it experiences is indicative of a serious infection. The latter can lead to an adaptive increase in reproductive investment in response to the reduced prospects of survival and future reproduction, so called "terminal investment." To measure such life-history-related consequences of increased immune activity, one group of incubating female Common Eiders (Somateria mollissima) was injected with a nonpathogenic antigen (sheep red blood cells, SRBC) while controls were injected with sterile saline. The eider is a long-lived sea-duck. Females, who incubate the eggs and care for young without assistance from the male, engage in facultative anorexia during incubation leading to a large reduction in body mass. Eiders can abandon their young to other females at the cost of reduced young survival. The immune challenge resulted in a larger mass loss, a prolonged incubation period, and reduced return rate, demonstrating both short- and long-term costs of immune challenge. Additionally, in response to what might have been interpreted as reduced survival chances in immune-challenged females, these females more often tended their own brood after hatching, despite having suffered higher costs during incubation.

  3. Are attractive male crickets better able to pay the costs of an immune challenge?

    Science.gov (United States)

    Telemeco, Melissa S.C.; Bartholomay, Lyric C.

    2015-01-01

    Reproduction and immunity are fitness-related traits that trade-off with each other. Parasite-mediated theories of sexual selection suggest, however, that higher-quality males should suffer smaller costs to reproduction-related traits and behaviours (e.g., sexual display) from an immune challenge because these males possess more resources with which to deal with the challenge. We used Gryllus texensis field crickets to test the prediction that attractive males should better maintain the performance of fitness-related traits (e.g., calling effort) in the face of an immune challenge compared with unattractive males. We found no support for our original predictions. However, that immune activation causes attractive males to significantly increase their calling effort compared with unattractive males suggests that these males might terminally invest in order to compensate for decreased future reproduction. PMID:26713249

  4. Current Challenges and Achievements in Maternal Immunization Research

    Directory of Open Access Journals (Sweden)

    Flor M. Munoz

    2018-03-01

    Full Text Available Maternal immunization has the potential to significantly improve maternal and child health worldwide by reducing maternal and infant morbidity and mortality associated with disease caused by pathogens that are particularly relevant in the perinatal period and in early life, and for which no alternative effective preventive strategies exist. Research on all aspects related to vaccines for administration during pregnancy is ongoing with support of multiple stakeholders and global participation. Substantial progress has been made, and the availability of new vaccines licensed exclusively for use in pregnant women to protect their infants has become an achievable goal. This review provides an update of the current challenges and achievements in maternal immunization research, focusing on recent milestones that advance the field and the prospects to make maternal immunization a feasible and accessible strategy to improve global health.

  5. Peripheral erythrocytes decrease upon specific respiratory challenge with grass pollen allergen in sensitized mice and in human subjects.

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    Galateja Jordakieva

    Full Text Available BACKGROUND AND AIMS: Specific hyper-responsiveness towards an allergen and non-specific airway hyperreactivity both impair quality of life in patients with respiratory allergic diseases. We aimed to investigate cellular responses following specific and non-specific airway challenges locally and systemically in i sensitized BALB/c mice challenged with grass pollen allergen Phl p 5, and in ii grass pollen sensitized allergic rhinitis subjects undergoing specific airway challenge in the Vienna Challenge Chamber (VCC. METHODS AND RESULTS: BALB/c mice (n = 20 were intraperitoneally immunized with grass pollen allergen Phl p 5 and afterwards aerosol challenged with either the specific allergen Phl p 5 (n = 10 or the non-specific antigen ovalbumin (OVA (n = 10. A protocol for inducing allergic asthma as well as allergic rhinitis, according to the united airway concept, was used. Both groups of exposed mice showed significantly reduced physical activity after airway challenge. Specific airway challenge further resulted in goblet cell hyperplasia, enhanced mucous secretion, intrapulmonary leukocyte infiltration and lymphoid follicle formation, associated with significant expression of IL-4, IL-5 and IL-13 in splenocytes and also partially in lung tissue. Concerning circulating blood cell dynamics, we observed a significant drop of erythrocyte counts, hemoglobin and hematocrit levels in both mouse groups, challenged with allergen or OVA. A significant decrease in circulating erythrocytes and hematocrit levels after airway challenges with grass pollen allergen was also found in grass pollen sensitized human rhinitis subjects (n = 42 at the VCC. The effects on peripheral leukocyte counts in mice and humans however were opposed, possibly due to the different primary inflammation sites. CONCLUSION: Our data revealed that, besides significant leukocyte dynamics, particularly erythrocytes are involved in acute hypersensitivity reactions to respiratory allergens

  6. Are attractive male crickets better able to pay the costs of an immune challenge?

    Directory of Open Access Journals (Sweden)

    Clint D. Kelly

    2015-12-01

    Full Text Available Reproduction and immunity are fitness-related traits that trade-off with each other. Parasite-mediated theories of sexual selection suggest, however, that higher-quality males should suffer smaller costs to reproduction-related traits and behaviours (e.g., sexual display from an immune challenge because these males possess more resources with which to deal with the challenge. We used Gryllus texensis field crickets to test the prediction that attractive males should better maintain the performance of fitness-related traits (e.g., calling effort in the face of an immune challenge compared with unattractive males. We found no support for our original predictions. However, that immune activation causes attractive males to significantly increase their calling effort compared with unattractive males suggests that these males might terminally invest in order to compensate for decreased future reproduction.

  7. Immune transfer studies in canine allogeneic marrow graft donor-recipient pairs

    International Nuclear Information System (INIS)

    Grosse-Wilde, H.; Krumbacher, K.; Schuening, F.D.; Doxiadis, I.; Mahmoud, H.K.; Emde, C.; Schmidt-Weinmar, A.; Schaefer, U.W.

    1986-01-01

    Transfer of immunity occurring with bone marrow grafting was studied using the dog as a preclinical model. Allogeneic bone marrow transplantation (BMT) was performed between DLA-identical beagle litter-mates. The donors were immunized with tetanus toxoid (TT) or sheep red blood cells (SRBC), and their humoral response was monitored by hemagglutination. The recipients of bone marrow from TT-immunized donors showed a marked increase of antibody titer one week posttransplantation, while in the recipients of marrow from SRBC immunized donors the antibody titers were considerably lower. Within the following 60 days the antibody titers in both groups diminished gradually to pregrafting levels. Control experiments in which cell-free plasma from donors immunized with TT and SRBC respectively was transfused indicated that the initial rise of specific antibody titers after marrow grafting is likely to be due to a passive transfer of humoral immunity. A single challenge of these marrow graft recipients with the respective antigen 15-18 weeks posttransplantation led to a secondary type of humoral immune response. It could be demonstrated that transfer of memory against TT or SRBC was independent from the actual antibody titer and the time of vaccination of the donor. One dog was immunized with TT after serving as marrow donor. When the donor had shown an antibody response, a peripheral blood leukocytes (PBL) transfusion was given to his chimera. Subsequent challenge of the latter resulted in a secondary type of specific antibody response. This indicates that specific cellular-bound immunological memory can be transferred after BMT from the donor to his allogeneic bone marrow chimera by transfusion of peripheral blood leukocytes. The data may be of importance in clinical BMT to protect patients during the phase of reduced immune reactivity by transfer of memory cells

  8. Brain Region–Specific Alterations in the Gene Expression of Cytokines, Immune Cell Markers and Cholinergic System Components during Peripheral Endotoxin–Induced Inflammation

    Science.gov (United States)

    Silverman, Harold A; Dancho, Meghan; Regnier-Golanov, Angelique; Nasim, Mansoor; Ochani, Mahendar; Olofsson, Peder S; Ahmed, Mohamed; Miller, Edmund J; Chavan, Sangeeta S; Golanov, Eugene; Metz, Christine N; Tracey, Kevin J; Pavlov, Valentin A

    2014-01-01

    Inflammatory conditions characterized by excessive peripheral immune responses are associated with diverse alterations in brain function, and brain-derived neural pathways regulate peripheral inflammation. Important aspects of this bidirectional peripheral immune–brain communication, including the impact of peripheral inflammation on brain region–specific cytokine responses, and brain cholinergic signaling (which plays a role in controlling peripheral cytokine levels), remain unclear. To provide insight, we studied gene expression of cytokines, immune cell markers and brain cholinergic system components in the cortex, cerebellum, brainstem, hippocampus, hypothalamus, striatum and thalamus in mice after an intraperitoneal lipopolysaccharide injection. Endotoxemia was accompanied by elevated serum levels of interleukin (IL)-1β, IL-6 and other cytokines and brain region–specific increases in Il1b (the highest increase, relative to basal level, was in cortex; the lowest increase was in cerebellum) and Il6 (highest increase in cerebellum; lowest increase in striatum) mRNA expression. Gene expression of brain Gfap (astrocyte marker) was also differentially increased. However, Iba1 (microglia marker) mRNA expression was decreased in the cortex, hippocampus and other brain regions in parallel with morphological changes, indicating microglia activation. Brain choline acetyltransferase (Chat ) mRNA expression was decreased in the striatum, acetylcholinesterase (Ache) mRNA expression was decreased in the cortex and increased in the hippocampus, and M1 muscarinic acetylcholine receptor (Chrm1) mRNA expression was decreased in the cortex and the brainstem. These results reveal a previously unrecognized regional specificity in brain immunoregulatory and cholinergic system gene expression in the context of peripheral inflammation and are of interest for designing future antiinflammatory approaches. PMID:25299421

  9. Expression of variant surface antigens by Plasmodium falciparum parasites in the peripheral blood of clinically immune pregnant women indicates ongoing placental infection

    DEFF Research Database (Denmark)

    Ofori, Michael F; Staalsoe, Trine; Bam, Victoria

    2003-01-01

    Placenta-sequestered Plasmodium falciparum parasites that cause pregnancy-associated malaria (PAM) in otherwise clinically immune women express distinct variant surface antigens (VSA(PAM)) not expressed by parasites in nonpregnant individuals. We report here that parasites from the peripheral blood...... of clinically immune pregnant women also express VSA(PAM), making them a convenient source of VSA(PAM) expressors for PAM vaccine research....

  10. The challenges and beauty of peripheral nerve regrowth.

    Science.gov (United States)

    Zochodne, Douglas W

    2012-03-01

    This review provides an overview of selected aspects of peripheral nerve regeneration and potential avenues to explore therapeutically. The overall coordinated and orchestrated pattern of recovery from peripheral nerve injury has a beauty of execution and progress that rivals all other forms of neurobiology. It involves changes at the level of the perikaryon, coordination with important peripheral glial partners, the Schwann cells, a controlled inflammatory response, and growth that overcomes surprising intrinsic roadblocks. Both regenerative axon growth and collateral sprouting encompass fascinating aspects of this story. Better understanding of peripheral nerve regeneration may also lead to enhanced central nervous system recovery. © 2012 Peripheral Nerve Society.

  11. Peripheral neuropathies associated with antibodies directed to intracellular neural antigens.

    Science.gov (United States)

    Antoine, J-C

    2014-10-01

    Antibodies directed to intracellular neural antigens have been mainly described in paraneoplastic peripheral neuropathies and mostly includes anti-Hu and anti-CV2/CRMP5 antibodies. These antibodies occur with different patterns of neuropathy. With anti-Hu antibody, the most frequent manifestation is sensory neuronopathy with frequent autonomic involvement. With anti-CV2/CRMP5 the neuropathy is more frequently sensory and motor with an axonal or mixed demyelinating and axonal electrophysiological pattern. The clinical pattern of these neuropathies is in keeping with the cellular distribution of HuD and CRMP5 in the peripheral nervous system. Although present in high titer, these antibodies are probably not directly responsible for the neuropathy. Pathological and experimental studies indicate that cytotoxic T-cells are probably the main effectors of the immune response. These disorders contrast with those in which antibodies recognize a cell surface antigen and are probably responsible for the disease. The neuronal cell death and axonal degeneration which result from T-cell mediated immunity explains why treating these disorders remains challenging. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  12. Chronic social stress induces peripheral and central immune activation, blunted mesolimbic dopamine function, and reduced reward-directed behaviour in mice

    Directory of Open Access Journals (Sweden)

    Giorgio Bergamini

    2018-02-01

    Full Text Available Psychosocial stress is a major risk factor for depression, stress leads to peripheral and central immune activation, immune activation is associated with blunted dopamine (DA neural function, DA function underlies reward interest, and reduced reward interest is a core symptom of depression. These states might be inter-independent in a complex causal pathway. Whilst animal-model evidence exists for some specific steps in the pathway, there is currently no animal model in which it has been demonstrated that social stress leads to each of these immune, neural and behavioural states. Such a model would provide important existential evidence for the complex pathway and would enable the study of causality and mediating mechanisms at specific steps in the pathway. Therefore, in the present mouse study we investigated for effects of 15-day resident-intruder chronic social stress (CSS on each of these states. Relative to controls, CSS mice exhibited higher spleen levels of granulocytes, inflammatory monocytes and T helper 17 cells; plasma levels of inducible nitric oxide synthase; and liver expression of genes encoding kynurenine pathway enzymes. CSS led in the ventral tegmental area to higher levels of kynurenine and the microglia markers Iba1 and Cd11b and higher binding activity of DA D1 receptor; and in the nucleus accumbens (NAcc to higher kynurenine, lower DA turnover and lower c-fos expression. Pharmacological challenge with DA reuptake inhibitor identified attenuation of DA stimulatory effects on locomotor activity and NAcc c-fos expression in CSS mice. In behavioural tests of operant responding for sucrose reward validated as sensitive assays for NAcc DA function, CSS mice exhibited less reward-directed behaviour. Therefore, this mouse study demonstrates that a chronic social stressor leads to changes in each of the immune, neural and behavioural states proposed to mediate between stress and disruption of DA-dependent reward processing. The

  13. Correlation of rectal temperature and peripheral temperature from implantable radio-frequency microchips in Holstein steers challenged with lipopolysaccharide under thermoneutral and high ambient temperatures.

    Science.gov (United States)

    Reid, E D; Fried, K; Velasco, J M; Dahl, G E

    2012-12-01

    Early detection of disease can speed treatment, slow spread of disease in a herd, and improve health status of animals. Immune stimulation increases rectal temperature (RT). Injectable radio-frequency implants (RFI) can provide temperature at the site of implantation. The fidelity of peripheral site temperature, determined by RFI, relative to RT is unknown in cattle. We hypothesized that during lipopolysaccharide (LPS) challenge, temperature at 3 peripheral sites would be similar to RT in steers (n = 4; BW 77 ± 2.1 kg). The 3 sites were 1) subcutaneous (SC) at the base of the ear (ET); 2) SC posterior to the poll (PT); and 3) SC beneath the umbilical fold (UT). Steers were housed in controlled temperature (CT) rooms (between 18 and 21°C; n = 2/room). Rectal temperature, ET, PT, and UT were recorded every 8 h daily. On d 7, 21, 22, 36, and 37, RT and RFI were taken every 5 min for 6 h, every 15 min for 3 h, and every 30 min for 15 h. To test RFI during a simulated immune challenge, LPS (E. coli 055:B5) was injected intravenously (i.v.) at 1000 h on d 22 and 37. Basal temperatures (°C) were RT (38.7 ± 0.20), ET (37.1 ± 0.86), PT (36.7 ± 0.57), and UT (36.3 ± 0.97). Rectal temperature increased to 39.9 ± 0.30°C after LPS, but ET, PT, and UT decreased. Heat stress also increases RT, which makes it difficult to identify sick animals using RT. The second hypothesis tested was that ET positively correlates to RT and negatively correlates to RT during LPS under heat stress. Four steers (127 ± 7.3 kg) were housed in CT chambers (n = 2/chamber), implanted with a RFI, and allowed 2 wk to acclimate. One chamber remained at 20°C, the other was increased to 34°C starting at 0800 h for a period of 48 h. The LPS was administered i.v. to all steers at 1000 h on d 2. After a 2-wk recovery at 20°C, the temperature was increased in the other chamber, resulting in a crossover design with each steer serving as its own control. Pearson's correlation coefficients for ET and

  14. Gene expression in peripheral immune cells following cardioembolic stroke is sexually dimorphic.

    Directory of Open Access Journals (Sweden)

    Boryana Stamova

    Full Text Available Epidemiological studies suggest that sex has a role in the pathogenesis of cardioembolic stroke. Since stroke is a vascular disease, identifying sexually dimorphic gene expression changes in blood leukocytes can inform on sex-specific risk factors, response and outcome biology. We aimed to examine the sexually dimorphic immune response following cardioembolic stroke by studying the differential gene expression in peripheral white blood cells.Blood samples from patients with cardioembolic stroke were obtained at ≤3 hours (prior to treatment, 5 hours and 24 hours (after treatment after stroke onset (n = 23; 69 samples and compared with vascular risk factor controls without symptomatic vascular diseases (n = 23, 23 samples (ANCOVA, false discovery rate p≤0.05, |fold change| ≥1.2. mRNA levels were measured on whole-genome Affymetrix microarrays. There were more up-regulated than down-regulated genes in both sexes, and females had more differentially expressed genes than males following cardioembolic stroke. Female gene expression was associated with cell death and survival, cell-cell signaling and inflammation. Male gene expression was associated with cellular assembly, organization and compromise. Immune response pathways were over represented at ≤3, 5 and 24 h after stroke in female subjects but only at 24 h in males. Neutrophil-specific genes were differentially expressed at 3, 5 and 24 h in females but only at 5 h and 24 h in males.There are sexually dimorphic immune cell expression profiles following cardioembolic stroke. Future studies are needed to confirm the findings using qRT-PCR in an independent cohort, to determine how they relate to risk and outcome, and to compare to other causes of ischemic stroke.

  15. RNAi nanomedicines: challenges and opportunities within the immune system

    International Nuclear Information System (INIS)

    Weinstein, Shiri; Peer, Dan

    2010-01-01

    RNAi, as a novel therapeutic modality, has an enormous potential to bring the era of personalized medicine one step further from notion into reality. However, delivery of RNAi effector molecules into their target tissues and cells remain extremely challenging. Major attempts have been made in recent years to develop sophisticated nanocarriers that could overcome these hurdles. This review will present the recent progress with the challenges and opportunities in this emerging field, focusing mostly on the in vivo applications with special emphasis on the strategies for RNAi delivery into immune cells. (topical review)

  16. Induction of complex immune responses and strong protection against retrovirus challenge by adenovirus-based immunization depends on the order of vaccine delivery.

    Science.gov (United States)

    Kaulfuß, Meike; Wensing, Ina; Windmann, Sonja; Hrycak, Camilla Patrizia; Bayer, Wibke

    2017-02-06

    In the Friend retrovirus mouse model we developed potent adenovirus-based vaccines that were designed to induce either strong Friend virus GagL 85-93 -specific CD8 + T cell or antibody responses, respectively. To optimize the immunization outcome we evaluated vaccination strategies using combinations of these vaccines. While the vaccines on their own confer strong protection from a subsequent Friend virus challenge, the simple combination of the vaccines for the establishment of an optimized immunization protocol did not result in a further improvement of vaccine effectivity. We demonstrate that the co-immunization with GagL 85-93 /leader-gag encoding vectors together with envelope-encoding vectors abrogates the induction of GagL 85-93 -specific CD8 + T cells, and in successive immunization protocols the immunization with the GagL 85-93 /leader-gag encoding vector had to precede the immunization with an envelope encoding vector for the efficient induction of GagL 85-93 -specific CD8 + T cells. Importantly, the antibody response to envelope was in fact enhanced when the mice were adenovirus-experienced from a prior immunization, highlighting the expedience of this approach. To circumvent the immunosuppressive effect of envelope on immune responses to simultaneously or subsequently administered immunogens, we developed a two immunizations-based vaccination protocol that induces strong immune responses and confers robust protection of highly Friend virus-susceptible mice from a lethal Friend virus challenge.

  17. Analyses of 123 Peripheral Human Immune Cell Subsets: Defining Differences with Age and between Healthy Donors and Cancer Patients Not Detected in Analysis of Standard Immune Cell Types

    Directory of Open Access Journals (Sweden)

    Lauren M. Lepone

    2016-03-01

    Full Text Available Recent advances in human immunology have led to the identification of novel immune cell subsets and the biological function of many of these subsets has now been identified. The recent US Food and Drug Administration approval of several immunotherapeutics for the treatment of a variety of cancer types and the results of ongoing immunotherapy clinical studies requires a more thorough interrogation of the immune system. We report here the use of flow cytometry-based analyses to identify 123 immune cell subsets of peripheral blood mononuclear cells. The use of these panels defines multiple differences in younger (< 40 years vs. older (≥ 40 years individuals and between aged-matched apparently healthy individuals and metastatic cancer patients, aspects not seen in the analysis of the following standard immune cell types: CD8, CD4, natural killer, natural killer-T, regulatory T, myeloid derived suppressor cells, conventional dendritic cells (DCs, plasmacytoid DCs and B cells. The use of these panels identifying 123 immune cell subsets may aid in the identification of patients who may benefit from immunotherapy, either prior to therapy or early in the immunotherapeutic regimen, for the treatment of cancer or other chronic or infectious diseases.

  18. The interbranchial lymphoid tissue likely contributes to immune tolerance and defense in the gills of Atlantic salmon.

    Science.gov (United States)

    Aas, Ida Bergva; Austbø, Lars; Falk, Knut; Hordvik, Ivar; Koppang, Erling Olaf

    2017-11-01

    Central and peripheral immune tolerance is together with defense mechanisms a hallmark of all lymphoid tissues. In fish, such tolerance is especially important in the gills, where the intimate contact between gill tissue and the aqueous environment would otherwise lead to continual immune stimulation by innocuous antigens. In this paper, we focus on the expression of genes associated with immune regulation by the interbranchial lymphoid tissue (ILT) in an attempt to understand its role in maintaining immune homeostasis. Both healthy and virus-challenged fish were investigated, and transcript levels were examined from laser-dissected ILT, gills, head kidney and intestine. Lack of Aire expression in the ILT excluded its involvement in central tolerance and any possibility of its being an analogue to the thymus. On the other hand, the ILT appears to participate in peripheral immune tolerance due to its relatively high expression of forkhead box protein 3 (Foxp3) and other genes associated with regulatory T cells (Tregs) and immune suppression. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Schistosoma mansoni: is acquired immunity induced by highly x-irradiated cercariae dependent on the size of the challenging dose

    International Nuclear Information System (INIS)

    Hsue, S.Y.; Hsue, H.F.; Osborne, J.W.; Johnson, S.C.

    1982-01-01

    A high degree of immunity, as shown by a 91% reduction of the number of worms recovered was found in five groups of mice that were immunized five times with highly X-irradiated cercariae and then challenged with 10, 20, 50, 100, or 500 normal Schistosoma mansoni cercariae. The results indicated that there were no significant differences in worm reduction in immunized mice challenged with different numbers of cercariae; consequently the immunity induced by this immunization method did not appear to be challenge-dose-dependent. However, the results also showed that when immunized mice were challenged with 500, 100, 50, 20, and 10 cercariae, 0, 13, 26, 56, and 68%, respectively, of the experimental animals were free of worms. Thus, the percentage of worm-negative cases increased as the number of challenge cercariae decreased. When viewed in this manner, the acquired immunity may be considered challenge-dose-dependent as well. If this method of vaccination is used for schistosomiasis control, we may anticipate that in both hypo- and hyperendemic areas, the intensity of infection and the severity of the disease will be reduced owing to a reduction in worms burdens, and in hypoendemic areas, there will be a number of worm-free cases

  20. Physiological actions of corticosterone and its modulation by an immune challenge in reptiles.

    Science.gov (United States)

    Meylan, Sandrine; Haussy, Claudy; Voituron, Yann

    2010-11-01

    Hormones are an important interface between genome and environment, because of their ability to modulate the animal's phenotype. In particular, corticosterone, the stress hormone in lizards, is known to reallocate energy from non-essential functions to affect morphological, physiological and behavioral traits that help the organism to deal with acute or chronic stressors. However, the effects of corticosterone on life history stages are still unclear primarily because of the dependence of life history stages on both internal and external factors. Using a cross-design, we tested the effect of elevated levels of exogenous corticosterone on the physiology of pregnant females in different immune contexts in a wild population of common lizards (Lacerta vivipara). Immune challenge was induced by the injection of sheep red blood cells (SRBC) and corticosterone levels were increased using a transdermal administration of corticosterone. Thereafter, reproductive traits, metabolism and cellular immune responses were measured. The elevation of corticosterone in pregnant females significantly altered reproductive and physiological performance. The corticosterone treatment decreased clutch success, juvenile size and body condition, but enhanced measures of physiological performance, such as metabolism and catalase activity. These first results reinforce the understanding of the physiological actions of corticosterone in reptiles. The data also demonstrated different direct impacts of immune challenge by SRBC on inflammatory response and antioxidant activity. The injection of SRBC stimulated the SOD activity in larger females. Finally, we demonstrated experimentally the modulation of the corticosterone action by the immune challenge on stamina and hatching date. Copyright © 2010 Elsevier Inc. All rights reserved.

  1. Dendritic cells in peripheral tolerance and immunity

    DEFF Research Database (Denmark)

    Gad, Monika; Claesson, Mogens Helweg; Pedersen, Anders Elm

    2003-01-01

    Dendritic cells capable of influencing immunity exist as functionally distinct subsets, T cell-tolerizing and T cell-immunizing subsets. The present paper reviews how these subsets of DCs develop, differentiate and function in vivo and in vitro at the cellular and molecular level. In particular...

  2. Dynamics of immune system gene expression upon bacterial challenge and wounding in a social insect (Bombus terrestris.

    Directory of Open Access Journals (Sweden)

    Silvio Erler

    2011-03-01

    Full Text Available The innate immune system which helps individuals to combat pathogens comprises a set of genes representing four immune system pathways (Toll, Imd, JNK and JAK/STAT. There is a lack of immune genes in social insects (e.g. honeybees when compared to Diptera. Potentially, this might be compensated by an advanced system of social immunity (synergistic action of several individuals. The bumble bee, Bombus terrestris, is a primitively eusocial species with an annual life cycle and colonies headed by a single queen. We used this key pollinator to study the temporal dynamics of immune system gene expression in response to wounding and bacterial challenge.Antimicrobial peptides (AMP (abaecin, defensin 1, hymenoptaecin were strongly up-regulated by wounding and bacterial challenge, the latter showing a higher impact on the gene expression level. Sterile wounding down-regulated TEP A, an effector gene of the JAK/STAT pathway, and bacterial infection influenced genes of the Imd (relish and JNK pathway (basket. Relish was up-regulated within the first hour after bacterial challenge, but decreased strongly afterwards. AMP expression following wounding and bacterial challenge correlates with the expression pattern of relish whereas correlated expression with dorsal was absent. Although expression of AMPs was high, continuous bacterial growth was observed throughout the experiment.Here we demonstrate for the first time the temporal dynamics of immune system gene expression in a social insect. Wounding and bacterial challenge affected the innate immune system significantly. Induction of AMP expression due to wounding might comprise a pre-adaptation to accompanying bacterial infections. Compared with solitary species this social insect exhibits reduced immune system efficiency, as bacterial growth could not be inhibited. A negative feedback loop regulating the Imd-pathway is suggested. AMPs, the end product of the Imd-pathway, inhibited the up-regulation of the

  3. Challenges to immunization: the experiences of homeless youth

    Directory of Open Access Journals (Sweden)

    Doroshenko Alexander

    2012-07-01

    Full Text Available Abstract Background Homelessness is a critical social issue, both a product of, and contributing to, poor mental and physical health. Over 150,000 young Canadians live on the streets. Homeless youth experience a high incidence of infectious diseases, many of which are vaccine preventable. Early departure from school and limited access to public health services makes them a particularly vulnerable high-risk group. This study explores challenges to obtaining essential vaccines experienced by homeless youth. Methods A qualitative research study to explore knowledge, attitudes, beliefs, and experiences surrounding immunization of hard-to-reach homeless youth was designed. Participants were recruited for focus groups from Phoenix House and Shelter, a non-profit, community-based organization assisting homeless youth in Halifax, Nova Scotia, Canada. An experienced facilitator guided the recorded discussions. Transcripts of audiotapes were analyzed using a constant comparative method until data revealed a set of exemplars and themes that best captured participants’ knowledge, attitudes, beliefs and experiences surrounding immunization and infectious diseases. Results Important themes emerged from our analysis. Considerable variability in knowledge about immunization and vaccine preventable diseases was found. The homeless youth in the study had limited awareness of meningitis in contrast to a greater knowledge about sexually transmitted infections and influenza, gained during the H1N1/09 public health campaign. They recognized their poverty as a risk for contracting infectious diseases, along with their inability to always employ known strategies to prevent infectious diseases, due to circumstances. They showed considerable insight into the detrimental effects of poor hygiene, sleeping locations and risk behaviour. Interviewed homeless youth regarded themselves as good compliers of health professional advice and offered valuable suggestions to improve

  4. Molecular and Functional Neuroscience in Immunity.

    Science.gov (United States)

    Pavlov, Valentin A; Chavan, Sangeeta S; Tracey, Kevin J

    2018-04-26

    The nervous system regulates immunity and inflammation. The molecular detection of pathogen fragments, cytokines, and other immune molecules by sensory neurons generates immunoregulatory responses through efferent autonomic neuron signaling. The functional organization of this neural control is based on principles of reflex regulation. Reflexes involving the vagus nerve and other nerves have been therapeutically explored in models of inflammatory and autoimmune conditions, and recently in clinical settings. The brain integrates neuro-immune communication, and brain function is altered in diseases characterized by peripheral immune dysregulation and inflammation. Here we review the anatomical and molecular basis of the neural interface with immunity, focusing on peripheral neural control of immune functions and the role of the brain in the model of the immunological homunculus. Clinical advances stemming from this knowledge within the framework of bioelectronic medicine are also briefly outlined.

  5. Flow cytometric assessment of chicken T cell-mediated immune responses after Newcastle disease virus vaccination and challenge

    DEFF Research Database (Denmark)

    Dalgaard, T. S.; Norup, L. R.; Pedersen, A.R.

    2010-01-01

    . Despite a delayed NDV-specific antibody response to vaccination, L133 appeared to be better protected than L130 in the subsequent infection challenge as determined by the presence of viral genomes. Peripheral blood was analyzed by flow cytometry and responses in vaccinated/challenged birds were studied...... by 5-color immunophenotyping as well as by measuring the proliferative capacity of NDV-specific T cells after recall stimulation. Immunophenotyping identified L133 as having a significantly lower CD4/CD8 ratio and a lower frequency of γδ T cells than L130 in the peripheral T cell compartment...

  6. Neonatal immune challenge does not affect body weight regulation in rats.

    Science.gov (United States)

    Spencer, Sarah J; Mouihate, Abdeslam; Galic, Michael A; Ellis, Shaun L; Pittman, Quentin J

    2007-08-01

    The perinatal environment plays a crucial role in programming many aspects of adult physiology. Myriad stressors during pregnancy, from maternal immune challenge to nutritional deficiency, can alter long-term body weight set points of the offspring. In light of the increasing concern over body weight issues, such as obesity and anorexia, in modern societies and accumulating evidence that developmental stressors have long-lasting effects on other aspects of physiology (e.g., fever, pain), we explored the role of immune system activation during neonatal development and its impact on body weight regulation in adulthood. Here we present a thorough evaluation of the effects of immune system activation (LPS, 100 microg/kg ip) at postnatal days 3, 7, or 14 on long-term body weight, adiposity, and body weight regulation after a further LPS injection (50 microg/kg ip) or fasting and basal and LPS-induced circulating levels of the appetite-regulating proinflammatory cytokine leptin. We show that neonatal exposure to LPS at various times during the neonatal period has no long-term effects on growth, body weight, or adiposity. We also observed no effects on body weight regulation in response to a short fasting period or a further exposure to LPS. Despite reductions in circulating leptin levels in response to LPS during the neonatal period, no long-term effects on leptin were seen. These results convincingly demonstrate that adult body weight and weight regulation are, unlike many other aspects of adult physiology, resistant to programming by a febrile-dose neonatal immune challenge.

  7. The impact of donor characteristics on the immune cell composition of mixture allografts of granulocyte-colony-stimulating factor-mobilized marrow harvests and peripheral blood harvests.

    Science.gov (United States)

    Wang, Yu-Tong; Zhao, Xiang-Yu; Zhao, Xiao-Su; Xu, Lan-Ping; Zhang, Xiao-Hui; Wang, Yu; Liu, Kai-Yan; Chang, Ying-Jun; Huang, Xiao-Jun

    2015-12-01

    The association of donor characteristics with immune cell composition in allografts remains poorly understood. In this retrospective study, the effects of donor characteristics on immune cell composition in allografts were investigated. The correlations of donor characteristics with the immune cell composition in mixture allografts of granulocyte-colony-stimulating factor-mobilized marrow harvests and peripheral blood harvests of 390 healthy donors (male, 240; female, 150; median age, 40 years old) were analyzed. The median doses of CD3+ T cells, CD4+ T cells, CD8+ T cells, CD3+CD4-CD8- T cells, and monocytes in mixture allografts were 160.57 × 10(6), 89.29 × 10(6), 56.16 × 10(6), 10.87 × 10(6), and 137.94 × 10(6)/kg, respectively. Multivariate analysis showed that younger donor age was associated with a higher dose of CD3+ T cells (p = 0.006), CD3+CD8+ T cells (p donor weight with CD3+ T cells (p blood lymphocyte pre-peripheral blood apheresis was correlated with the yield of CD3+ T cells (p blood monocyte count before marrow harvest predicted the monocyte dose (p = 0.002). The results suggested that older and overweight donors should not be chosen. The monocyte and lymphocyte counts before harvest could predict the yield of immune cells in allografts. © 2015 AABB.

  8. Phenotypic and Functional Characterization of Peripheral Blood Lymphocytes from Various Age- and Sex-Specific Groups of Owl Monkeys (Aotus nancymaae).

    Science.gov (United States)

    Nehete, Pramod N; Nehete, Bharti P; Chitta, Sriram; Williams, Lawrence E; Abee, Christian R

    2017-02-01

    Owl monkeys (Aotus nancymaae) are New World NHP that serve an important role in vaccine development and as a model for human disease conditions such as malaria. Despite the past contributions of this animal model, limited information is available about the phenotype and functional properties of peripheral blood lymphocytes in reference to sex and age. Using a panel of human antibodies and a set of standardized human immune assays, we identified and characterized various peripheral blood lymphocyte subsets, evaluated the immune functions of T cells, and analyzed cytokines relative to sex and age in healthy owl monkeys. We noted age- and sex-dependent changes in CD28+ (an essential T cell costimulatory molecule) and CD95+ (an apoptotic surface marker) T cells and various levels of cytokines in the plasma. In immune assays of freshly isolated peripheral blood mononuclear cells, IFNγ and perforin responses were significantly higher in female than in male monkeys and in young adults than in juvenile and geriatric groups, despite similar lymphocyte (particularly T cell) populations in these groups. Our current findings may be useful in exploring Aotus monkeys as a model system for the study of aging, susceptibility to infectious diseases, and age-associated differences in vaccine efficacy, and other challenges particular to pediatric and geriatric patients.

  9. Recruiting older patients with peripheral arterial disease: evaluating challenges and strategies.

    Science.gov (United States)

    Brostow, Diana P; Hirsch, Alan T; Kurzer, Mindy S

    2015-01-01

    Peripheral arterial disease (PAD) is a group of syndromes characterized by chronic and progressive atherosclerosis with a high burden of physical disability and cardiovascular morbidity and mortality. Recruiting patients for clinical research is therefore challenging. In this article, we describe and evaluate our methods for recruiting participants for a cross-sectional feasibility study of PAD, nutritional status, and body composition. We used convenience and purposive sampling approaches to identify potential participants. Between May 2012 and April 2013, 1,446 patients were identified, and 165 patients (11.4%) responded to recruitment requests. The final enrollment was 64 participants (64/1,446; 4.4%), and four subjects (6.3%) subsequently withdrew from the study. Recruiting PAD patients presents a variety of challenges, due largely to the burdens of living with coexistent illnesses, and patients' reluctance or inability to travel for research. In this article, we delineate suggestions for improving the efficacy of recruitment methods in future PAD studies.

  10. A leukocyte activation test identifies food items which induce release of DNA by innate immune peripheral blood leucocytes.

    Science.gov (United States)

    Garcia-Martinez, Irma; Weiss, Theresa R; Yousaf, Muhammad N; Ali, Ather; Mehal, Wajahat Z

    2018-01-01

    Leukocyte activation (LA) testing identifies food items that induce a patient specific cellular response in the immune system, and has recently been shown in a randomized double blinded prospective study to reduce symptoms in patients with irritable bowel syndrome (IBS). We hypothesized that test reactivity to particular food items, and the systemic immune response initiated by these food items, is due to the release of cellular DNA from blood immune cells. We tested this by quantifying total DNA concentration in the cellular supernatant of immune cells exposed to positive and negative foods from 20 healthy volunteers. To establish if the DNA release by positive samples is a specific phenomenon, we quantified myeloperoxidase (MPO) in cellular supernatants. We further assessed if a particular immune cell population (neutrophils, eosinophils, and basophils) was activated by the positive food items by flow cytometry analysis. To identify the signaling pathways that are required for DNA release we tested if specific inhibitors of key signaling pathways could block DNA release. Foods with a positive LA test result gave a higher supernatant DNA content when compared to foods with a negative result. This was specific as MPO levels were not increased by foods with a positive LA test. Protein kinase C (PKC) inhibitors resulted in inhibition of positive food stimulated DNA release. Positive foods resulted in CD63 levels greater than negative foods in eosinophils in 76.5% of tests. LA test identifies food items that result in release of DNA and activation of peripheral blood innate immune cells in a PKC dependent manner, suggesting that this LA test identifies food items that result in release of inflammatory markers and activation of innate immune cells. This may be the basis for the improvement in symptoms in IBS patients who followed an LA test guided diet.

  11. Sex-biased terminal investment in offspring induced by maternal immune challenge in the house wren (Troglodytes aedon).

    Science.gov (United States)

    Bowers, E Keith; Smith, Rebecca A; Hodges, Christine J; Zimmerman, Laura M; Thompson, Charles F; Sakaluk, Scott K

    2012-07-22

    The reproductive costs associated with the upregulation of immunity have been well-documented and constitute a fundamental trade-off between reproduction and self-maintenance. However, recent experimental work suggests that parents may increase their reproductive effort following immunostimulation as a form of terminal parental investment as prospects for future reproduction decline. We tested the trade-off and terminal investment hypotheses in a wild population of house wrens (Troglodytes aedon) by challenging the immune system of breeding females with lipopolysaccharide, a potent but non-lethal antigen. Immunized females showed no evidence of reproductive costs; instead, they produced offspring of higher phenotypic quality, but in a sex-specific manner. Relative to control offspring, sons of immunized females had increased body mass and their sisters exhibited higher cutaneous immune responsiveness to phytohaemagglutinin injection, constituting an adaptive strategy of sex-biased allocation by immune-challenged females to enhance the reproductive value of their offspring. Thus, our results are consistent with the terminal investment hypothesis, and suggest that maternal immunization can induce pronounced transgenerational effects on offspring phenotypes.

  12. Peripheral Tumor Necrosis Factor-Alpha (TNF-α) Modulates Amyloid Pathology by Regulating Blood-Derived Immune Cells and Glial Response in the Brain of AD/TNF Transgenic Mice.

    Science.gov (United States)

    Paouri, Evi; Tzara, Ourania; Kartalou, Georgia-Ioanna; Zenelak, Sofia; Georgopoulos, Spiros

    2017-05-17

    Increasing evidence has suggested that systemic inflammation along with local brain inflammation can play a significant role in Alzheimer's disease (AD) pathogenesis. Identifying key molecules that regulate the crosstalk between the immune and the CNS can provide potential therapeutic targets. TNF-α is a proinflammatory cytokine implicated in the pathogenesis of systemic inflammatory and neurodegenerative diseases, such as rheumatoid arthritis (RA) and AD. Recent studies have reported that anti-TNF-α therapy or RA itself can modulate AD pathology, although the underlying mechanism is unclear. To investigate the role of peripheral TNF-α as a mediator of RA in the pathogenesis of AD, we generated double-transgenic 5XFAD/Tg197 AD/TNF mice that develop amyloid deposits and inflammatory arthritis induced by human TNF-α (huTNF-α) expression. We found that 5XFAD/Tg197 mice display decreased amyloid deposition, compromised neuronal integrity, and robust brain inflammation characterized by extensive gliosis and elevated blood-derived immune cell populations, including phagocytic macrophages and microglia. To evaluate the contribution of peripheral huTNF-α in the observed brain phenotype, we treated 5XFAD/Tg197 mice systemically with infliximab, an anti-huTNF-α antibody that does not penetrate the blood-brain barrier and prevents arthritis. Peripheral inhibition of huTNF-α increases amyloid deposition, rescues neuronal impairment, and suppresses gliosis and recruitment of blood-derived immune cells, without affecting brain huTNF-α levels. Our data report, for the first time, a distinctive role for peripheral TNF-α in the modulation of the amyloid phenotype in mice by regulating blood-derived and local brain inflammatory cell populations involved in β-amyloid clearance. SIGNIFICANCE STATEMENT Mounting evidence supports the active involvement of systemic inflammation, in addition to local brain inflammation, in Alzheimer's disease (AD) progression. TNF-α is a

  13. PERIPHERAL IMMUNE SYSTEM SUPPRESSION IN EARLY ABSTINENT ALCOHOL DEPENDENT INDIVIDUALS: LINKS TO STRESS AND CUE-RELATED CRAVING

    Science.gov (United States)

    Fox, Helen C; Milivojevic, Verica; Angarita, Gustavo A; Stowe, Raymond; Sinha, Rajita

    2017-01-01

    Background Peripheral immune system cytokines may play an integral role in underlying sensitized stress response and alcohol craving during early withdrawal. To date, the nature of these immune changes during early abstinence have not been examined. Methods Thirty-nine early abstinent, treatment-seeking alcohol dependent individuals and 46 socially drinking controls were exposed to three guided imageries: stress, alcohol cue and neutral. These were presented randomly across consecutive days. Plasma measures of tumor necrosis factor alpha (TNFα), tumor necrosis factor receptor 1 (TNFR1), interleukin-6 (IL-6), and interleukin-10 (IL-10), were collected at baseline, immediately after imagery and at various recovery time-points. Ratings of alcohol craving, negative mood and anxiety were also obtained at the same time-points. Results The alcohol group demonstrated decreased basal IL-10 compared with controls particularly following exposure to alcohol cue. They also showed a dampened TNFα and TNFR1 response to stress and cue, respectively, and a generalized suppression of IL-6. In the alcohol group, these immune system adaptations occurred alongside significant elevations in anxiety, negative mood and alcohol craving. Conclusions Findings demonstrate that broad immuno-suppression is still observed in alcohol dependent individuals after three weeks of abstinence and may be linked to motivation for alcohol. PMID:28675117

  14. Expression of Cyclin D1 protein and CCN DI with PNKP genes in peripheral blood mononuclear cells in clean-up worker of Chernobyl accident with different state of immune system

    International Nuclear Information System (INIS)

    Bazika, D.A.; Kubashko, A.V.; Yil'jenko, Yi.M.; Belyajev, O.A.; Pleskach, O.Ya.

    2015-01-01

    The investigate of Cyclin D1+cells levels changes, associated CCND1 and PNKP genes in peripheral blood mononuclear cells in cleanup workers of Chornobyl accident with different state of immune system in depends on the dose irradiation. Analyzed data of the nuclear controller of cell cycle- Cyclin D1 protein expression changes and related CCND1 and PNKP genes in peripheral blood mononuclear cells in cleanup workers Chornobyl accident with different status of immune system in remote period after exposure is represented. Reveled changes in expression of Cyclin D1+cells and regulation of related genes may point on possible radiation-associated firm molecular disturbances occurred during elimination of consequences of Chornobyl accident, that could be a potential basis for cell and humoral communicative links breach in immune system result ing in elevation of stochastic effects like oncopathology in cleanup workers of Chornobyl accident in remote peri od after exposure

  15. Dose-dependent effects of an immune challenge at both ultimate and proximate levels in Drosophila melanogaster.

    Science.gov (United States)

    Nystrand, M; Dowling, D K

    2014-05-01

    Immune responses are highly dynamic. The magnitude and efficiency of an immune response to a pathogen can change markedly across individuals, and such changes may be influenced by variance in a range of intrinsic (e.g. age, genotype, sex) and external (e.g. abiotic stress, pathogen identity, strain) factors. Life history theory predicts that up-regulation of the immune system will come at a physiological cost, and studies have confirmed that increased investment in immunity can reduce reproductive output and survival. Furthermore, males and females often have divergent reproductive strategies, and this might drive the evolution of sex-specific life history trade-offs involving immunity, and sexual dimorphism in immune responses per se. Here, we employ an experiment design to elucidate dose-dependent and sex-specific responses to exposure to a nonpathogenic immune elicitor at two scales--the 'ultimate' life history and the underlying 'proximate' immune level in Drosophila melanogaster. We found dose-dependent effects of immune challenges on both male and female components of reproductive success, but not on survival, as well as a response in antimicrobial activity. These results indicate that even in the absence of the direct pathogenic effects that are associated with actual disease, individual life histories respond to a perceived immune challenge--but with the magnitude of this response being contingent on the initial dose of exposure. Furthermore, the results indicate that immune responses at the ultimate life history level may indeed reflect underlying processes that occur at the proximate level. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

  16. Immunity booster

    International Nuclear Information System (INIS)

    Stefanescu, Ioan; Titescu, Gheorghe; Tamaian, Radu; Haulica, Ion; Bild, Walther

    2002-01-01

    The immunity booster is, according to its patent description, microbiologically pure water with an D/(D+H) isotopic concentration of 100 ppm, with physical-chemical characteristics similar to those of distilled water. It is obtained by sterilization of a mixture of deuterium depleted water, with a 25 ppm isotopic concentration, with distilled water in a volume ratio of 4:6. Unlike natural immunity boosters (bacterial agents as Bacillus Chalmette-Guerin, Corynebacterium parvum; lipopolysaccharides; human immunoglobulin) or synthetical products (levamysol; isoprinosyne with immunostimulating action), which cause hypersensitivity and shocks, thrill, fever, sickness and the immunity complex disease, the water of 100 ppm D/(D + H) isotopic concentration is a toxicity free product. The testing for immune reaction of the immunity booster led to the following results: - an increase of cell action capacity in the first immunity shielding stage (macrophages), as evidenced by stimulation of a number of essential characterizing parameters, as well as of the phagocytosis capacity, bactericide capacity, and opsonic capacity of serum; - an increase of the number of leucocyte particularly of the granulocyte in peripheral blood, produced especially when medullar toxic agents like caryolysine are used; - it hinders the effect of lowering the number of erythrocytes in peripheral blood produced by experimentally induced chronic inflammation; - an increase of nonspecific immunity defence capacity against specific bacterial aggression of both Gram-positive bacteria (Streptococcus pneumoniae 558 ) and of the Gram-negative ones (Klebsiella pneumoniae 507 ); - an increase of immunity - stimulating activity (proinflamatory), like that of levamisole as evidenced by the test of stimulation of experimentally induced inflammation by means of carrageenan. The following advantages of the immunity booster are stressed: - it is toxicity free and side effect free; - can be orally administrated as

  17. Interrelation secretory activity of stomach and immunes changes of peripheral blood when ulcerogenesis stomach.

    Science.gov (United States)

    Matveeva, L V; Mosina, L M

    2016-01-01

    Incidence of gastric ulcer is high in almost all countries of the world. On the development and course of the disease affect the state acid- and enzymes production stomach, immune status. The purpose was to determine the presence and power of correlative links secretory activity of the stomach and immune changes in the peripheral blood during exacerbation of ulcer disease stomach. Surveyed in obtaining informed consent 42 patients with gastric ulcer in the acute phase prior to the eradication and antisecretory therapy and 40 healthy volunteers. On the state of function acid- and enzymes production of the gastric mucosa judged by the results of a 2-hour intragastric pH-metry and serum concentration pepsinogen, gastrin before the start of active treatment. Immunophenotype lymphocytes on CD-antigens (CD3, CD4, CD8, CD16, CD19, CD45, CD56) was measured by immunofluorescence, levels immunoglobulin isotype M, G, A, E - ELISA method. When short-term intragastric pH-metry of the stomach hyperacidity patients recorded 6.7 times more likely than healthy, normacidity - 12.3 times less. Reduction of acid production was observed up to 8.6 times more, indicating the development of mucosal atrophy. Basal pH in the antrum was lower by 54.5% than in the control group, with stimulation increased by 33.6%, but remained lower than the values of healthy individuals by 48.7%. When ELISA amount pepsinogen patients showed significant increase in serum levels of PG-I relative to the control group at 33.4%, PG-II - 52%. In assessing the immune status of patients were identified changes in system phagocytes, cellular and humoral links, most pronounced for severe current peptic ulcer disease. The results indicate the presence of positive and negative correlative links mild to moderate force between indicators of secretory activity of gastric mucosal innate and adaptive immunity in patients with acute exacerbation of peptic ulcer disease. The presence and nature of these relationships should

  18. Challenges of the urban peripheral landscapes

    Directory of Open Access Journals (Sweden)

    Catharina Pinheiro Cordeiro dos Santos Lima

    2016-01-01

    Full Text Available The peripheral regions of Sao Paulo reveal a profound contradiction in their landscapes – on the one hand, remnants of their original biophysical basis and, on the other, increasing pressure for the territory’s occupation. The northwest sector of the periphery, for example, presents environmentally sensitive areas which are at the same time under great pressure for occupation by those who do so by choice (the property market and those who have none (irregular and high-risk occupation. The poor inhabitants of these regions have increasingly organized themselves to achieve basic rights through community associations, social movements, and cultural groups ever since the recent re-democratization process in Brazil. It is precisely in these urban spaces, which are precarious in many ways, that significant subjectivities have emerged in participatory processes, expressing an awareness of environmental issues with an implicit desire for more humanized landscapes. These processes often include children and their teachers as protagonists. For thirteen years, the Landscape, Art and Culture Laboratory (LABPARC of the Faculty of Architecture and Urbanism (FAU at USP has been working with educators and children from municipal public schools, developing projects, research, and university extension work in the region. This article aims to discuss this experience with the objective of showing the gains achieved and the challenges that may arise within the perspective of a collective construction of the city, where urban interventions can be harmonized with water sources, streams, steep slopes, forests, and fauna.

  19. Peripheral biomarkers revisited: integrative profiling of peripheral samples for psychiatric research.

    Science.gov (United States)

    Hayashi-Takagi, Akiko; Vawter, Marquis P; Iwamoto, Kazuya

    2014-06-15

    Peripheral samples, such as blood and skin, have been used for decades in psychiatric research as surrogates for central nervous system samples. Although the validity of the data obtained from peripheral samples has been questioned and other state-of-the-art techniques, such as human brain imaging, genomics, and induced pluripotent stem cells, seem to reduce the value of peripheral cells, accumulating evidence has suggested that revisiting peripheral samples is worthwhile. Here, we re-evaluate the utility of peripheral samples and argue that establishing an understanding of the common signaling and biological processes in the brain and peripheral samples is required for the validity of such models. First, we present an overview of the available types of peripheral cells and describe their advantages and disadvantages. We then briefly summarize the main achievements of omics studies, including epigenome, transcriptome, proteome, and metabolome analyses, as well as the main findings of functional cellular assays, the results of which imply that alterations in neurotransmission, metabolism, the cell cycle, and the immune system may be partially responsible for the pathophysiology of major psychiatric disorders such as schizophrenia. Finally, we discuss the future utility of peripheral samples for the development of biomarkers and tailor-made therapies, such as multimodal assays that are used as a battery of disease and trait pathways and that might be potent and complimentary tools for use in psychiatric research. © 2013 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved.

  20. Immunity's fourth dimension: approaching the circadian-immune connection.

    Science.gov (United States)

    Arjona, Alvaro; Silver, Adam C; Walker, Wendy E; Fikrig, Erol

    2012-12-01

    The circadian system ensures the generation and maintenance of self-sustained ~24-h rhythms in physiology that are linked to internal and environmental changes. In mammals, daily variations in light intensity and other cues are integrated by a hypothalamic master clock that conveys circadian information to peripheral molecular clocks that orchestrate physiology. Multiple immune parameters also vary throughout the day and disruption of circadian homeostasis is associated with immune-related disease. Here, we discuss the molecular links between the circadian and immune systems and examine their outputs and disease implications. Understanding the mechanisms that underlie circadian-immune crosstalk may prove valuable for devising novel prophylactic and therapeutic interventions. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Hypocretin/orexin loss changes the hypothalamic immune response.

    Science.gov (United States)

    Tanaka, Susumu; Takizawa, Nae; Honda, Yoshiko; Koike, Taro; Oe, Souichi; Toyoda, Hiromi; Kodama, Tohru; Yamada, Hisao

    2016-10-01

    Hypocretin, also known as orexin, maintains the vigilance state and regulates various physiological processes, such as arousal, sleep, food intake, energy expenditure, and reward. Previously, we found that when wild-type mice and hypocretin/ataxin-3 littermates (which are depleted of hypothalamic hypocretin-expressing neurons postnatally) were administered lipopolysaccharide (LPS), the two genotypes exhibited significant differences in their sleep/wake cycle, including differences in the degree of increase in sleep periods and in recovery from sickness behaviour. In the present study, we examined changes in the hypothalamic vigilance system and in the hypothalamic expression of inflammatory factors in response to LPS in hypocretin/ataxin-3 mice. Peripheral immune challenge with LPS affected the hypothalamic immune response and vigilance states. This response was altered by the loss of hypocretin. Hypocretin expression was inhibited after LPS injection in both hypocretin/ataxin-3 mice and their wild-type littermates, but expression was completely abolished only in hypocretin/ataxin-3 mice. Increases in the number of histidine decarboxylase (HDC)-positive cells and in Hdc mRNA expression were found in hypocretin/ataxin-3 mice, and this increase was suppressed by LPS. Hypocretin loss did not impact the change in expression of hypothalamic inflammatory factors in response to LPS, except for interferon gamma and colony stimulating factor 3. The number of c-Fos-positive/HDC-positive cells in hypocretin/ataxin-3 mice administered LPS injections was elevated, even during the rest period, in all areas, suggesting that there is an increase in the activity of histaminergic neurons in hypocretin/ataxin-3 mice following LPS injection. Taken together, our results suggest a novel role for hypocretin in the hypothalamic response to peripheral immune challenge. Our findings contribute to the understanding of the pathophysiology of narcolepsy. Copyright © 2016 Elsevier Inc. All

  2. Zymosan-induced immune challenge modifies the stress response of hypoxic air-breathing fish (Anabas testudineus Bloch): Evidence for reversed patterns of cortisol and thyroid hormone interaction, differential ion transporter functions and non-specific immune response.

    Science.gov (United States)

    Simi, S; Peter, Valsa S; Peter, M C Subhash

    2017-09-15

    Fishes have evolved physiological mechanisms to exhibit stress response, where hormonal signals interact with an array of ion transporters and regulate homeostasis. As major ion transport regulators in fish, cortisol and thyroid hormones have been shown to interact and fine-tune the stress response. Likewise, in fishes many interactions have been identified between stress and immune components, but the physiological basis of such interaction has not yet delineated particularly in air-breathing fish. We, therefore, investigated the responses of thyroid hormones and cortisol, ion transporter functions and non-specific immune response of an obligate air-breathing fish Anabas testudineus Bloch to zymosan treatment or hypoxia stress or both, to understand how immune challenge modifies the pattern of stress response in this fish. Induction of experimental peritonitis in these fish by zymosan treatment (200ngg -1 ) for 24h produced rise in respiratory burst and lysozomal activities in head kidney phagocytes. In contrast, hypoxia stress for 30min in immune-challenged fish reversed these non-specific responses of head kidney phagocytes. The decline in plasma cortisol in zymosan-treated fish and its further suppression by hypoxia stress indicate that immune challenge suppresses the cortisol-driven stress response of this fish. Likewise, the decline in plasma T 3 and T 4 after zymosan-treatment and the rise in plasma T 4 after hypoxia stress in immune-challenged fish indicate a critical role for thyroid hormone in immune-stress response due to its differential sensitivity to both immune and stress challenges. Further, analysis of the activity pattern of ion-dependent ATPases viz. Na + /K + -ATPase, H + /K + -ATPase and Na + /NH 4 + -ATPase indicates a functional interaction of ion transport system with the immune response as evident in its differential and spatial modifications after hypoxia stress in immune-challenged fish. The immune-challenge that produced differential

  3. Menstrual blood closely resembles the uterine immune micro-environment and is clearly distinct from peripheral blood.

    Science.gov (United States)

    van der Molen, R G; Schutten, J H F; van Cranenbroek, B; ter Meer, M; Donckers, J; Scholten, R R; van der Heijden, O W H; Spaanderman, M E A; Joosten, I

    2014-02-01

    Is menstrual blood a suitable source of endometrial derived lymphocytes? Mononuclear cells isolated from menstrual samples (menstrual blood mononuclear cells (MMC)) are clearly distinct from peripheral blood mononuclear cells (PBMC) and show a strong resemblance with biopsy-derived endometrial mononuclear cells. A critical event in the onset of pregnancy is the implantation of the embryo in the uterine wall. The immune cell composition in the endometrium at the time of implantation is considered pivotal for success. Despite advancing knowledge on the composition of the immune cell population in the uterus, the role of endometrial immune cells in reproductive disorders is still not fully resolved, mainly due to the fact that this type of research requires invasive techniques. Here, we collected menstrual fluid and validated this unique non-invasive technique to obtain and study the endometrium-derived immune cells which would be present around the time of implantation. Five healthy non-pregnant females with regular menstruation cycles and not using oral contraceptives collected their menstrual blood using a menstrual cup in five consecutive cycles. Sampling took place over the first 3 days of menses, with 12 h intervals. Peripheral blood samples, taken before and after each menstruation, were obtained for comparative analysis. MMC and PBMC samples were characterized for the different lymphocyte subsets by flow cytometry, with emphasis on NK cells and T cells. Next, the functional capacity of the MMC-derived NK cells was determined by measuring intracellular production of IFN-γ, granzyme B and perforin after culture in the presence of IL-2 and IL-15. In support of their endometrial origin, MMC samples contained the typical composition of mononuclear cells expected of endometrial tissue, were phenotypically similar to the reported phenotype for biopsy-derived endometrial cells, and were distinct from PBMC. Increased percentages of NK cells and decreased percentages

  4. Vaccination with an Attenuated Mutant of Ehrlichia chaffeensis Induces Pathogen-Specific CD4+ T Cell Immunity and Protection from Tick-Transmitted Wild-Type Challenge in the Canine Host.

    Directory of Open Access Journals (Sweden)

    Jodi L McGill

    Full Text Available Ehrlichia chaffeensis is a tick-borne rickettsial pathogen and the causative agent of human monocytic ehrlichiosis. Transmitted by the Amblyomma americanum tick, E. chaffeensis also causes disease in several other vertebrate species including white-tailed deer and dogs. We have recently described the generation of an attenuated mutant strain of E. chaffeensis, with a mutation in the Ech_0660 gene, which is able to confer protection from secondary, intravenous-administered, wild-type E. chaffeensis infection in dogs. Here, we extend our previous results, demonstrating that vaccination with the Ech_0660 mutant protects dogs from physiologic, tick-transmitted, secondary challenge with wild-type E. chaffeensis; and describing, for the first time, the cellular and humoral immune responses induced by Ech_0660 mutant vaccination and wild-type E. chaffeensis infection in the canine host. Both vaccination and infection induced a rise in E. chaffeensis-specific antibody titers and a significant Th1 response in peripheral blood as measured by E. chaffeensis antigen-dependent CD4+ T cell proliferation and IFNγ production. Further, we describe for the first time significant IL-17 production by peripheral blood leukocytes from both Ech_0660 mutant vaccinated animals and control animals infected with wild-type E. chaffeensis, suggesting a previously unrecognized role for IL-17 and Th17 cells in the immune response to rickettsial pathogens. Our results are a critical first step towards defining the role of the immune system in vaccine-induced protection from E. chaffeensis infection in an incidental host; and confirm the potential of the attenuated mutant clone, Ech_0660, to be used as a vaccine candidate for protection against tick-transmitted E. chaffeensis infection.

  5. Human recombinant antibodies against Plasmodium falciparum merozoite surface protein 3 cloned from peripheral blood leukocytes of individuals with immunity to malaria demonstrate antiparasitic properties

    DEFF Research Database (Denmark)

    Lundquist, Rasmus; Nielsen, Leif Kofoed; Jafarshad, Ali

    2006-01-01

    against MSP-3 residues 194 to 257 (MSP-3(194-257)) on the molecular level. mRNA from peripheral blood leukocytes from clinically immune individuals was used as a source of Fab (fragment antibody) genes. A Fab-phage display library was made, and three distinct antibodies designated RAM1, RAM2, and RAM3...

  6. Aging exacerbates depressive-like behavior in mice in response to activation of the peripheral innate immune system.

    Science.gov (United States)

    Godbout, Jonathan P; Moreau, Maïté; Lestage, Jacques; Chen, Jing; Sparkman, Nathan L; O'Connor, Jason; Castanon, Nathalie; Kelley, Keith W; Dantzer, Robert; Johnson, Rodney W

    2008-09-01

    Exposure to peripheral infections may be permissive to cognitive and behavioral complications in the elderly. We have reported that peripheral stimulation of the innate immune system with lipopolysaccharide (LPS) causes an exaggerated neuroinflammatory response and prolonged sickness behavior in aged BALB/c mice. Because LPS also causes depressive behavior, the purpose of this study was to determine whether aging is associated with an exacerbated depressive-like response. We confirmed that LPS (0.33 mg/kg intraperitoneal) induced a protracted sickness response in aged mice with reductions in locomotor and feeding activities 24 and 48 h postinjection, when young adults had fully recovered. When submitted to the forced swim test 24 h post-LPS, both young adult and aged mice exhibited an increased duration of immobility. However, when submitted to either the forced swim test or the tail suspension test 72 h post-LPS, an increased duration of immobility was evident only in aged mice. This prolonged depressive-like behavior in aged LPS-treated mice was associated with a more pronounced induction of peripheral and brain indoleamine 2,3-dioxygenase and a markedly higher turnover rate of brain serotonin (as measured by the ratio of 5-hydroxy-indoleacetic acid over 5-hydroxy-tryptamine) compared to young adult mice at 24 post-LPS injection. These results provide the first evidence that age-associated reactivity of the brain cytokine system could play a pathophysiological role in the increased prevalence of depression observed in the elderly.

  7. Biomedical engineering strategies for peripheral nerve repair: surgical applications, state of the art, and future challenges.

    Science.gov (United States)

    Pfister, Bryan J; Gordon, Tessa; Loverde, Joseph R; Kochar, Arshneel S; Mackinnon, Susan E; Cullen, D Kacy

    2011-01-01

    Damage to the peripheral nervous system is surprisingly common and occurs primarily from trauma or a complication of surgery. Although recovery of nerve function occurs in many mild injuries, outcomes are often unsatisfactory following severe trauma. Nerve repair and regeneration presents unique clinical challenges and opportunities, and substantial contributions can be made through the informed application of biomedical engineering strategies. This article reviews the clinical presentations and classification of nerve injuries, in addition to the state of the art for surgical decision-making and repair strategies. This discussion presents specific challenges that must be addressed to realistically improve the treatment of nerve injuries and promote widespread recovery. In particular, nerve defects a few centimeters in length use a sensory nerve autograft as the standard technique; however, this approach is limited by the availability of donor nerve and comorbidity associated with additional surgery. Moreover, we currently have an inadequate ability to noninvasively assess the degree of nerve injury and to track axonal regeneration. As a result, wait-and-see surgical decisions can lead to undesirable and less successful "delayed" repair procedures. In this fight for time, degeneration of the distal nerve support structure and target progresses, ultimately blunting complete functional recovery. Thus, the most pressing challenges in peripheral nerve repair include the development of tissue-engineered nerve grafts that match or exceed the performance of autografts, the ability to noninvasively assess nerve damage and track axonal regeneration, and approaches to maintain the efficacy of the distal pathway and targets during the regenerative process. Biomedical engineering strategies can address these issues to substantially contribute at both the basic and applied levels, improving surgical management and functional recovery following severe peripheral nerve injury.

  8. Challenges and Strategies for Proteome Analysis of the Interaction of Human Pathogenic Fungi with Host Immune Cells.

    Science.gov (United States)

    Krüger, Thomas; Luo, Ting; Schmidt, Hella; Shopova, Iordana; Kniemeyer, Olaf

    2015-12-14

    Opportunistic human pathogenic fungi including the saprotrophic mold Aspergillus fumigatus and the human commensal Candida albicans can cause severe fungal infections in immunocompromised or critically ill patients. The first line of defense against opportunistic fungal pathogens is the innate immune system. Phagocytes such as macrophages, neutrophils and dendritic cells are an important pillar of the innate immune response and have evolved versatile defense strategies against microbial pathogens. On the other hand, human-pathogenic fungi have sophisticated virulence strategies to counteract the innate immune defense. In this context, proteomic approaches can provide deeper insights into the molecular mechanisms of the interaction of host immune cells with fungal pathogens. This is crucial for the identification of both diagnostic biomarkers for fungal infections and therapeutic targets. Studying host-fungal interactions at the protein level is a challenging endeavor, yet there are few studies that have been undertaken. This review draws attention to proteomic techniques and their application to fungal pathogens and to challenges, difficulties, and limitations that may arise in the course of simultaneous dual proteome analysis of host immune cells interacting with diverse morphotypes of fungal pathogens. On this basis, we discuss strategies to overcome these multifaceted experimental and analytical challenges including the viability of immune cells during co-cultivation, the increased and heterogeneous protein complexity of the host proteome dynamically interacting with the fungal proteome, and the demands on normalization strategies in terms of relative quantitative proteome analysis.

  9. Allograft immunity in vitro. I. Cultivation conditions and mixed lymphocyte interaction of mouse peripheral lymphocytes

    Science.gov (United States)

    Häyry, P.; Defendi, V.

    1970-01-01

    We have adapted mouse peripheral lymphocytes to culture as a preliminary step in designing a model for the study of allograft immunity in vitro. The isolation of peripheral leucocytes is facilitated by using Plasmagel® as an erythrocyte-agglutinating agent. The yield of leucocytes can be considerably increased by intravenous injection of the donor animals with supernatant fluid from Bordetella pertussis cultures and the lymphocytes thus mobilized react both to phytohaemagglutinin (PHA) and allogeneic stimulus, as do lymphocytes from untreated animals. Preparations which contain more than 25–50 RBC/WBC are refractory in the mixed lymphocyte interaction (MLI). The optimum cell density for the proliferative response is approximately 1–3 × 106 lymphocytes/ml. Various nutritive milieu were tested and found to have little influence on the MLI; both normal and suspension media behaved in a similar manner. PHA causes a vigorous proliferative response in mouse peripheral lymphocytes, the 3H–TdR incorporation values in PHA-containing cultures at peak point of stimulation (3rd day) being up to 1000 times those observed for control cultures. The allogeneic response in the MLI takes place later (6th to 7th day) and is weaker, about one-tenth the PHA response, when strains differing at the H-2 locus are used as cell donors. Because the specific proliferative response to allogeneic stimulus in mixed culture, regardless of the way it is measured, is indistinguishable from the response produced by other non-specific factors, these other factors must be critically excluded. It appears that supplementing the culture medium with low concentrations of certain lots of foetal calf or agamma-newborn-calf serum permits the study of the specific response at an optimum sensitivity. PMID:4315207

  10. Role of Microbiota in Sexually Dimorphic Immunity

    NARCIS (Netherlands)

    Elderman, Marlies; de Vos, Paul; Faas, Marijke

    2018-01-01

    Sex differences in peripheral immune responses are well recognized. This is associated with sex differences in many immunological diseases. As the intestinal microbiota is known to influence the immune system, such sex differences in immune responses may be a consequence of sex-specific microbiota.

  11. Dietary N-Carbamylglutamate Supplementation Boosts Intestinal Mucosal Immunity in Escherichia coli Challenged Piglets.

    Directory of Open Access Journals (Sweden)

    Fengrui Zhang

    Full Text Available N-carbamylglutamate (NCG has been shown to enhance performance in neonatal piglets. However, few studies have demonstrated the effect of NCG on the intestinal mucosal barrier. This study was conducted to determine the effects of dietary NCG supplementation on intestinal mucosal immunity in neonatal piglets after an Escherichia coli (E. coli challenge. New-born piglets (4 d old were assigned randomly to one of four treatments (n = 7, including (I sham challenge, (II sham challenge +50 mg/kg NCG, (III E. coli challenge, and (IV E. coli challenge +50 mg/kg NCG. On d 8, pigs in the E. coli challenge groups (III and IV were orally challenged with 5 mL of E. coli K88 (10(8 CFU/mL, whereas pigs in the sham challenge groups (I and II were orally dosed with an equal volume of water. On d 13, all piglets were sacrificed, and samples were collected and examined. The results show that average daily gain in the E. coli challenged piglets (III and IV was decreased (PE.coli<0.05. However, it tended to be higher in the NCG treated piglets (II and IV. Ileum secretory IgA, as well as IFN-γ, IL-2, IL-4 and IL-10 in ileal homogenates, were increased in E. coli challenged piglets (III and IV. Similarly, ileum SIgA and IL-10 levels, and CD4(+ percentage in NCG treated piglets (II and IV were higher than no-NCG treated piglets (PNCG<0.05. However, the IL-2 level was only decreased in the piglets of E. coli challenge + NCG group (IV compared with E. coli challenge group (III (P<0.05. No change in the IL-2 level of the sham challenged piglets (III was observed. In conclusion, dietary NCG supplementation has some beneficial effects on intestinal mucosal immunity in E. coli challenged piglets, which might be associated with stimulated lymphocyte proliferation and cytokine synthesis. Our findings have an important implication that NCG may be used to reduce diarrhea in neonatal piglets.

  12. Immunization with plasmid DNA encoding the hemagglutinin and the nucleoprotein confers robust protection against a lethal canine distemper virus challenge.

    Science.gov (United States)

    Dahl, Lotte; Jensen, Trine Hammer; Gottschalck, Elisabeth; Karlskov-Mortensen, Peter; Jensen, Tove Dannemann; Nielsen, Line; Andersen, Mads Klindt; Buckland, Robin; Wild, T Fabian; Blixenkrone-Møller, Merete

    2004-09-09

    We have investigated the protective effect of immunization of a highly susceptible natural host of canine distemper virus (CDV) with DNA plasmids encoding the viral nucleoprotein (N) and hemagglutinin (H). The combined intradermal and intramuscular routes of immunization elicited high virus-neutralizing serum antibody titres in mink (Mustela vison). To mimic natural exposure, we also conducted challenge infection by horizontal transmission from infected contact animals. Other groups received a lethal challenge infection by administration to the mucosae of the respiratory tract and into the muscle. One of the mink vaccinated with N plasmid alone developed severe disease after challenge. In contrast, vaccination with the H plasmid together with the N plasmid conferred solid protection against disease and we were unable to detect CDV infection in PBMCs or in different tissues after challenge. Our findings show that DNA immunization by the combined intradermal and intramuscular routes can confer solid protective immunity against naturally transmitted morbillivirus infection and disease.

  13. Prolonged protection against Intranasal challenge with influenza virus following systemic immunization or combinations of mucosal and systemic immunizations with a heat-labile toxin mutant.

    Science.gov (United States)

    Zhou, Fengmin; Goodsell, Amanda; Uematsu, Yasushi; Vajdy, Michael

    2009-04-01

    Seasonal influenza virus infections cause considerable morbidity and mortality in the world, and there is a serious threat of a pandemic influenza with the potential to cause millions of deaths. Therefore, practical influenza vaccines and vaccination strategies that can confer protection against intranasal infection with influenza viruses are needed. In this study, we demonstrate that using LTK63, a nontoxic mutant of the heat-labile toxin from Escherichia coli, as an adjuvant for both mucosal and systemic immunizations, systemic (intramuscular) immunization or combinations of mucosal (intranasal) and intramuscular immunizations protected mice against intranasal challenge with a lethal dose of live influenza virus at 3.5 months after the second immunization.

  14. Transcriptome analysis describing new immunity and defense genes in peripheral blood mononuclear cells of rheumatoid arthritis patients.

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    Vitor Hugo Teixeira

    Full Text Available BACKGROUND: Large-scale gene expression profiling of peripheral blood mononuclear cells from Rheumatoid Arthritis (RA patients could provide a molecular description that reflects the contribution of diverse cellular responses associated with this disease. The aim of our study was to identify peripheral blood gene expression profiles for RA patients, using Illumina technology, to gain insights into RA molecular mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: The Illumina Human-6v2 Expression BeadChips were used for a complete genome-wide transcript profiling of peripheral blood mononuclear cells (PBMCs from 18 RA patients and 15 controls. Differential analysis per gene was performed with one-way analysis of variance (ANOVA and P values were adjusted to control the False Discovery Rate (FDR<5%. Genes differentially expressed at significant level between patients and controls were analyzed using Gene Ontology (GO in the PANTHER database to identify biological processes. A differentially expression of 339 Reference Sequence genes (238 down-regulated and 101 up-regulated between the two groups was observed. We identified a remarkably elevated expression of a spectrum of genes involved in Immunity and Defense in PBMCs of RA patients compared to controls. This result is confirmed by GO analysis, suggesting that these genes could be activated systemically in RA. No significant down-regulated ontology groups were found. Microarray data were validated by real time PCR in a set of nine genes showing a high degree of correlation. CONCLUSIONS/SIGNIFICANCE: Our study highlighted several new genes that could contribute in the identification of innovative clinical biomarkers for diagnostic procedures and therapeutic interventions.

  15. Early death after feline infectious peritonitis virus challenge due to recombinant vaccinia virus immunization.

    Science.gov (United States)

    Vennema, H; de Groot, R J; Harbour, D A; Dalderup, M; Gruffydd-Jones, T; Horzinek, M C; Spaan, W J

    1990-01-01

    The gene encoding the fusogenic spike protein of the coronavirus causing feline infectious peritonitis was recombined into the genome of vaccinia virus. The recombinant induced spike-protein-specific, in vitro neutralizing antibodies in mice. When kittens were immunized with the recombinant, low titers of neutralizing antibodies were obtained. After challenge with feline infectious peritonitis virus, these animals succumbed earlier than did the control group immunized with wild-type vaccinia virus (early death syndrome). Images PMID:2154621

  16. Incorporation of a recombinant Eimeria maxima IMP1 antigen into nanoparticles confers protective immunity against E. Maxima challenge infection.

    Science.gov (United States)

    Jenkins, Mark C; Stevens, Laura; O'Brien, Celia; Parker, Carolyn; Miska, Katrzyna; Konjufca, Vjollca

    2018-02-14

    The purpose of this study was to determine if conjugating a recombinant Eimeria maxima protein, namely EmaxIMP1, into 20 nm polystyrene nanoparticles (NP) could improve the level of protective immunity against E. maxima challenge infection. Recombinant EmaxIMP1 was expressed in Escherichia coli as a poly-His fusion protein, purified by NiNTA chromatography, and conjugated to 20 nm polystyrene NP (NP-EmaxIMP1). NP-EMaxIMP1 or control non-recombinant (NP-NR) protein were delivered per os to newly-hatched broiler chicks with subsequent booster immunizations at 3 and 21 days of age. In battery cage studies (n = 4), chickens immunized with NP-EMaxIMP1 displayed complete protection as measured by weight gain (WG) against E. maxima challenge compared to chickens immunized with NP-NR. WG in the NP-EMaxIMP1-immunized groups was identical to WG in chickens that were not infected with E. maxima infected chickens. In floor pen studies (n = 2), chickens immunized with NP-EMaxIMP1 displayed partial protection as measured by WG against E. maxima challenge compared to chickens immunized with NP-NR. In order to understand the basis for immune stimulation, newly-hatched chicks were inoculated per os with NP-EMaxIMP1 or NP-NR protein, and the small intestine, bursa, and spleen, were examined for NP localization at 1 h and 6 h post-inoculation. Within 1 h, both NP-EMaxIMP1 and NP-NR were observed in all 3 tissues. An increase was observed in the level of NP-EmaxIMP1 and NP-NR in all tissues at 6 h post-inoculation. These data indicate that 20 nm NP-EmaxIMP1 or NP-NR reached deeper tissues within hours of oral inoculation and elicited complete to partial immunity against E. maxima challenge infection. Published by Elsevier Ltd.

  17. Acute injury in the peripheral nervous system triggers an alternative macrophage response

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    Ydens Elke

    2012-07-01

    Full Text Available Abstract Background The activation of the immune system in neurodegeneration has detrimental as well as beneficial effects. Which aspects of this immune response aggravate the neurodegenerative breakdown and which stimulate regeneration remains an open question. To unravel the neuroprotective aspects of the immune system we focused on a model of acute peripheral nerve injury, in which the immune system was shown to be protective. Methods To determine the type of immune response triggered after axotomy of the sciatic nerve, a model for Wallerian degeneration in the peripheral nervous system, we evaluated markers representing the two extremes of a type I and type II immune response (classical vs. alternative using real-time quantitative polymerase chain reaction (RT-qPCR, western blot, and immunohistochemistry. Results Our results showed that acute peripheral nerve injury triggers an anti-inflammatory and immunosuppressive response, rather than a pro-inflammatory response. This was reflected by the complete absence of classical macrophage markers (iNOS, IFNγ, and IL12p40, and the strong up-regulation of tissue repair markers (arginase-1, Ym1, and Trem2. The signal favoring the alternative macrophage environment was induced immediately after nerve damage and appeared to be established within the nerve, well before the infiltration of macrophages. In addition, negative regulators of the innate immune response, as well as the anti-inflammatory cytokine IL-10 were induced. The strict regulation of the immune system dampens the potential tissue damaging effects of an over-activated response. Conclusions We here demonstrate that acute peripheral nerve injury triggers an inherent protective environment by inducing the M2 phenotype of macrophages and the expression of arginase-1. We believe that the M2 phenotype, associated with a sterile inflammatory response and tissue repair, might explain their neuroprotective capacity. As such, shifting the

  18. Hypoxia Stress Modifies Na/K-ATPase, H/K-ATPase, , and Isoform Expression in the Brain of Immune-Challenged Air-Breathing Fish

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    MC Subhash Peter

    2017-11-01

    Full Text Available Fishes are equipped to sense stressful stimuli and are able to respond to environmental stressor such as hypoxia with varying pattern of stress response. The functional attributes of brain to hypoxia stress in relation to ion transport and its interaction during immune challenge have not yet delineated in fish. We, therefore, explored the pattern of ion transporter functions and messenger RNA (mRNA expression of α1-subunit isoforms of Na + /K + -ATPase (NKA in the brain segments, namely, prosencephalon (PC, mesencephalon (MC, and metencephalon (MeC in an obligate air-breathing fish exposed either to hypoxia stress (30 minutes forced immersion in water or challenged with zymosan treatment (25-200 ng g −1 for 24 hours or both. Zymosan that produced nonspecific immune responses evoked differential regulation of NKA, H + /K + -ATPase (HKA, and Na + / NH 4 + - ATPase (NNA in the varied brain segments. On the contrary, hypoxia stress that demanded activation of NKA in PC and MeC showed a reversed NKA activity pattern in MeC of immune-challenged fish. A compromised HKA and NNA regulation during hypoxia stress was found in immune-challenged fish, indicating the role of these brain ion transporters to hypoxia stress and immune challenges. The differential mRNA expression of α1-subunit isoforms of NKA, nkaα1a , nkaα1b , and nkaα1c , in hypoxia-stressed brain showed a shift in its expression pattern during hypoxia stress-immune interaction in PC and MC. Evidence is thus presented for the first time that ion transporters such as HKA and NNA along with NKA act as functional brain markers which respond differentially to both hypoxia stress and immune challenges. Taken together, the data further provide evidence for a differential Na + , K + , H + , and NH 4 + ion signaling that exists in brain neuronal clusters during hypoxia stress-immune interaction as a result of modified regulations of NKA, HKA, and NNA transporter functions and nkaα1 isoform

  19. Optimal Thawing of Cryopreserved Peripheral Blood Mononuclear Cells for Use in High-Throughput Human Immune Monitoring Studies

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    Ramu A. Subbramanian

    2012-07-01

    Full Text Available Cryopreserved peripheral blood mononuclear cells (PBMC constitute an important component of immune monitoring studies as they allow for efficient batch- testing of samples as well as for the validation and extension of original studies in the future. In this study, we systematically test the permutations of PBMC thawing practices commonly employed in the field and identify conditions that are high and low risk for the viability of PBMC and their functionality in downstream ELISPOT assays. The study identifies the addition of ice-chilled washing media to thawed cells at the same temperature as being a high risk practice, as it yields significantly lower viability and functionality of recovered PBMC when compared to warming the cryovials to 37 °C and adding a warm washing medium. We found thawed PBMC in cryovials could be kept up to 30 minutes at 37 °C in the presence of DMSO before commencement of washing, which surprisingly identifies exposure to DMSO as a low risk step during the thawing process. This latter finding is of considerable practical relevance since it permits batch-thawing of PBMC in high-throughput immune monitoring environments.

  20. Host transcriptional responses following ex vivo re-challenge with Mycobacterium tuberculosis vary with disease status.

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    Elaine A Yu

    Full Text Available The identification of immune correlates that are predictive of disease outcome for tuberculosis remains an ongoing challenge. To address this issue, we evaluated gene expression profiles from peripheral blood mononuclear cells following ex vivo challenge with Mycobacterium tuberculosis, among participants with active TB disease (ATBD, n = 10, latent TB infection (LTBI, n = 10, and previous active TB disease (after successful treatment; PTBD, n = 10, relative to controls (n = 10. Differential gene expression profiles were assessed by suppression-subtractive hybridization, dot blot, real-time polymerase chain reaction, and the comparative cycle threshold methods. Comparing ATBD to control samples, greater fold-increases of gene expression were observed for a number of chemotactic factors (CXCL1, CXCL3, IL8, MCP1, MIP1α. ATBD was also associated with higher IL1B gene expression, relative to controls. Among LTBI samples, gene expression of several chemotactic factors (CXCL2, CXCL3, IL8 was similarly elevated, compared to individuals with PTBD. Our results demonstrated that samples from participants with ATBD and LTBI have distinct gene expression profiles in response to ex vivo M. tuberculosis infection. These findings indicate the value in further characterizing the peripheral responses to M. tuberculosis challenge as a route to defining immune correlates of disease status or outcome.

  1. Host transcriptional responses following ex vivo re-challenge with Mycobacterium tuberculosis vary with disease status.

    Science.gov (United States)

    Yu, Elaine A; John, Serene H; Tablante, Elizabeth C; King, Christine A; Kenneth, John; Russell, David G; Mehta, Saurabh

    2017-01-01

    The identification of immune correlates that are predictive of disease outcome for tuberculosis remains an ongoing challenge. To address this issue, we evaluated gene expression profiles from peripheral blood mononuclear cells following ex vivo challenge with Mycobacterium tuberculosis, among participants with active TB disease (ATBD, n = 10), latent TB infection (LTBI, n = 10), and previous active TB disease (after successful treatment; PTBD, n = 10), relative to controls (n = 10). Differential gene expression profiles were assessed by suppression-subtractive hybridization, dot blot, real-time polymerase chain reaction, and the comparative cycle threshold methods. Comparing ATBD to control samples, greater fold-increases of gene expression were observed for a number of chemotactic factors (CXCL1, CXCL3, IL8, MCP1, MIP1α). ATBD was also associated with higher IL1B gene expression, relative to controls. Among LTBI samples, gene expression of several chemotactic factors (CXCL2, CXCL3, IL8) was similarly elevated, compared to individuals with PTBD. Our results demonstrated that samples from participants with ATBD and LTBI have distinct gene expression profiles in response to ex vivo M. tuberculosis infection. These findings indicate the value in further characterizing the peripheral responses to M. tuberculosis challenge as a route to defining immune correlates of disease status or outcome.

  2. Challenges Evaluating Chemotherapy-Induced Peripheral Neuropathy in Childhood Cancer Survivors.

    Science.gov (United States)

    Mohrmann, Caroline; Armer, Jane; Hayashi, Robert J

    Children treated for cancer are exposed to a variety of chemotherapeutic agents with known toxicity to the peripheral nervous system. The side effect of peripheral neuropathy can cause changes in sensation, function, and even cause pain. Although peripheral neuropathy is recognized by pediatric oncology nurses as an important and significant side effect, measuring neuropathy can be quite complex for clinical care and research efforts. With more children surviving a cancer diagnosis today, this issue is increasingly important for childhood cancer survivors. This article has reviewed existing literature examining peripheral neuropathy in childhood cancer survivors with particular interest paid to measurement tools available and needs for future research. It is important for nurses to choose appropriate measures for clinical care and research methods in order to have an impact on patients experiencing this condition.

  3. Localized skin changes at the site of immunization with highly irradiated cercariae of Schistosoma mansoni are associated with enhanced resistance to a challenge infection

    International Nuclear Information System (INIS)

    Miller, K.L.; Smithers, S.R.

    1982-01-01

    The level of immunity to a percutaneous cercarial challenge with Schistosoma mansoni was assayed 4-6 weeks after immunization of mice with highly irradiated (20 krad.) cercariae or schistosomula. When immunization and challenge occurred through the same skin site, resistance, particularly that which occurred in the skin, was greater than that observed when immunization and challenge occurred in different sites. The enhanced resistance is believed to be due to localized changes in the skin; 4 weeks after exposure to irradiated cercariae, abdominal skin is characterized by a thickened epidermis, changes in the ground substance and a cellular infiltration of the dermis. A convenient mouse model is described in which one or both ear pinnae are exposed to irradiated cercariae and a percutaneous challenge is given via the abdomen, thus eliminating the effects of local skin changes. In this model, the majority of the challenge infection which succumbs to the immune response appears to be killed in the skin. (author)

  4. Participation of hypothalamic CB1 receptors in reproductive axis disruption during immune challenge.

    Science.gov (United States)

    Surkin, P N; Di Rosso, M E; Correa, F; Elverdin, J C; Genaro, A M; De Laurentiis, A; Fernández-Solari, J

    2017-08-01

    Immune challenge inhibits reproductive function and endocannabinoids (eCB) modulate sexual hormones. However, no studies have been performed to assess whether the eCB system mediates the inhibition of hormones that control reproduction as a result of immune system activation during systemic infections. For that reason, we evaluated the participation of the hypothalamic cannabinoid receptor CB1 on the hypothalamic-pituitary-gonadal (HPG) axis activity in rats submitted to immune challenge. Male adult rats were treated i.c.v. administration with a CB1 antagonist/inverse agonist (AM251) (500 ng/5 μL), followed by an i.p. injection of lipopolysaccharide (LPS) (5 mg/kg) 15 minutes later. Plasmatic, hypothalamic and adenohypophyseal pro-inflammatory cytokines, hormones and neuropeptides were assessed 90 or 180 minutes post-LPS. The plasma concentration of tumour necrosis factor α and adenohypophyseal mRNA expression of Tnfα and Il1β increased 90 and 180 minutes post i.p. administration of LPS. However, cytokine mRNA expression in the hypothalamus increased only 180 minutes post-LPS, suggesting an inflammatory delay in this organ. CB1 receptor blockade with AM251 increased LPS inflammatory effects, particularly in the hypothalamus. LPS also inhibited the HPG axis by decreasing gonadotrophin-releasing hormone hypothalamic content and plasma levels of luteinising hormone and testosterone. These disruptor effects were accompanied by decreased hypothalamic Kiss1 mRNA expression and prostaglandin E2 content, as well as by increased gonadotrophin-inhibitory hormone (Rfrp3) mRNA expression. All these disruptive effects were prevented by the presence of AM251. In summary, our results suggest that, in male rats, eCB mediate immune challenge-inhibitory effects on reproductive axis at least partially via hypothalamic CB1 activation. In addition, this receptor also participates in homeostasis recovery by modulating the inflammatory process taking place after LPS

  5. The role of the immune system in Alzheimer disease: Etiology and treatment.

    Science.gov (United States)

    Jevtic, Stefan; Sengar, Ameet S; Salter, Michael W; McLaurin, JoAnne

    2017-11-01

    The immune system is now considered a major factor in Alzheimer Disease (AD). This review seeks to demonstrate how various aspects of the immune system, both in the brain and peripherally, interact to contribute to AD. We highlight classical nervous system immune components, such as complement and microglia, as well as novel aspects of the peripheral immune system that can influence disease, such as monocytes and lymphocytes. By detailing the roles of various immune cells in AD, we summarize an emerging perspective for disease etiology and future therapeutic targets. Copyright © 2017. Published by Elsevier B.V.

  6. Cytokine production in BALB/c mice immunized with radiation attenuated third stage larvae of the filarial nematode, Brugia pahangi

    International Nuclear Information System (INIS)

    Bancroft, A.J.; Devaney, E.; Grencis, R.K.; Else, K.J.

    1993-01-01

    BALB/c mice immunized with radiation-attenuated third stage larvae of the filarial nematode Brugia pahangi are strongly immune to challenge infection. Investigation of the profile of cytokines secreted by spleen cells from immune mice stimulated in vitro with either parasite Ag or with Con A revealed high levels of IL-5 and IL-9 and moderate levels of IL-4. In contrast, secretion of IFN-γ by spleen cells from immune animals was negligible. Spleen cells from control mice secreted low levels of all cytokines assayed. Levels of parasite-specific IgE were significantly elevated in immune animals and a peripheral blood eosinophilia was observed, which exhibited a biphasic distribution. Our results are consistent with the preferential expansion of Th2 cells in immune animals and provide the basis for dissecting the means by which radiation-attenuated larvae of filarial nematodes stimulate immunity. 5l refs., 3 figs., 3 tabs

  7. From painful busyness to emotional immunization: Nurses' experiences of ethical challenges.

    Science.gov (United States)

    Storaker, Anne; Nåden, Dagfinn; Sæteren, Berit

    2017-08-01

    The professional values presented in ethical guidelines of the Norwegian Nurses Organisation and International Council of Nurses describe nurses' professional ethics and the obligations that pertain to good nursing practice. The foundation of all nursing shall be respect for life and the inherent dignity of the individual. Research proposes that nurses lack insight in ethical competence and that ethical issues are rarely discussed on the wards. Furthermore, research has for some time confirmed that nurses experience moral distress in their daily work and that this has become a major problem for the nursing profession. The purpose of this article is to obtain a deeper understanding of the ethical challenges that nurses face in daily practice. The chosen research questions are "What ethical challenges do nurses experience in their daily practice?" We conducted a qualitative interview study using a hermeneutical approach to analyzing data describing nurses' experiences. Ethical considerations: The Norwegian Social Science Data services approved the study. Furthermore, the head of the hospital gave permission to conduct the investigation. The requirement of anonymity and proper data storage in accordance with the World Medical Association Declaration of Helsinki was met. The context for the study comprised three different clinical wards at a university hospital in Norway. Nine qualified nurses were interviewed. The results were obtained through a systematic development beginning with the discovery of busyness as a painful phenomenon that can lead to conflicts in terms of ethical values. Furthermore, the consequences compromising professional principles in nursing care emerged and ended in moral blindness and emotional immunization of the healthcare providers. Emotional immunization occurred as a new dimension involving moral blindness and immunity in relation to being emotionally touched.

  8. Nociception and role of immune system in pain.

    Science.gov (United States)

    Verma, Vivek; Sheikh, Zeeshan; Ahmed, Ahad S

    2015-09-01

    Both pain and inflammation are protective responses. However, these self-limiting conditions (with well-established negative feedback loops) become pathological if left uncontrolled. Both pain and inflammation can interact with each other in a multi-dimensional manner. These interactions are known to create an array of 'difficult to manage' pathologies. This review explains in detail the role of immune system and the related cells in peripheral sensitization and neurogenic inflammation. Various neuro-immune interactions are analyzed at peripheral, sensory and central nervous system levels. Innate immunity plays a critical role in central sensitization and in establishing acute pain as chronic condition. Moreover, inflammatory mediators also exhibit psychological effects, thus contributing towards the emotional elements associated with pain. However, there is also a considerable anti-inflammatory and analgesic role of immune system. This review also attempts to enlist various novel pharmacological approaches that exhibit their actions through modification of neuro-immune interface.

  9. Bortezomib-induced painful peripheral neuropathy: an electrophysiological, behavioral, morphological and mechanistic study in the mouse.

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    Valentina A Carozzi

    Full Text Available Bortezomib is the first proteasome inhibitor with significant antineoplastic activity for the treatment of relapsed/refractory multiple myeloma as well as other hematological and solid neoplasms. Peripheral neurological complications manifesting with paresthesias, burning sensations, dysesthesias, numbness, sensory loss, reduced proprioception and vibratory sensitivity are among the major limiting side effects associated with bortezomib therapy. Although bortezomib-induced painful peripheral neuropathy is clinically easy to diagnose and reliable models are available, its pathophysiology remains partly unclear. In this study we used well-characterized immune-competent and immune-compromised mouse models of bortezomib-induced painful peripheral neuropathy. To characterize the drug-induced pathological changes in the peripheral nervous system, we examined the involvement of spinal cord neuronal function in the development of neuropathic pain and investigated the relevance of the immune response in painful peripheral neuropathy induced by bortezomib. We found that bortezomib treatment induced morphological changes in the spinal cord, dorsal roots, dorsal root ganglia (DRG and peripheral nerves. Neurophysiological abnormalities and specific functional alterations in Aδ and C fibers were also observed in peripheral nerve fibers. Mice developed mechanical allodynia and functional abnormalities of wide dynamic range neurons in the dorsal horn of spinal cord. Bortezomib induced increased expression of the neuronal stress marker activating transcription factor-3 in most DRG. Moreover, the immunodeficient animals treated with bortezomib developed a painful peripheral neuropathy with the same features observed in the immunocompetent mice. In conclusion, this study extends the knowledge of the sites of damage induced in the nervous system by bortezomib administration. Moreover, a selective functional vulnerability of peripheral nerve fiber subpopulations

  10. Radioimmunotoxicological effect of enriched uranium on central and peripheral immune cells and the protective action of IL-1 and IL-2

    International Nuclear Information System (INIS)

    Zhu Shoupeng; Lai Guanhua; Wang Liuyi

    1993-01-01

    With accumulation of enriched uranium 235 U-UO 2 F 2 in organism, it was found that enriched uranium had injurious effect on the immune function of central and peripheral immune cells. After intravenous injection of enriched uranium the spontaneous 3 H-TdR incorporation in thymocytes and bone marrow cells decreased. Though the sensitivity of immune cells to 235 U-UO 2 F 2 was different, the thymocytes were destroyed more markedly. Also the proliferation ability of T and B lymphocytes were both inhibited by enriched uranium 235 U. As compared with them, spleen B lymphocytes were inhibited more markedly than T lymphocytes. At the same time spleen lymphocytes IL-1 production and IL 2 consumption were diminished. It should be noted that the inhibition of spleen B lymphocytes proliferation by enriched uranium 235 U-UO 2 F 2 was partially restored by exogenous IL-1 or IL-2. The recovery rate of protective action at the very most was 67.1 +- 11.2% with exogenous IL-1 and 50.2 +- 8.0% with IL-2. Moreover, both exogenous IL-1 and IL-2 had synergetic effect, and the recovery rate was elevated to 83.1 +-12.3%

  11. Global Vaccine and Immunization Research Forum: Opportunities and challenges in vaccine discovery, development, and delivery.

    Science.gov (United States)

    Ford, Andrew Q; Touchette, Nancy; Hall, B Fenton; Hwang, Angela; Hombach, Joachim

    2016-03-18

    The World Health Organization, the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, and the Bill & Melinda Gates Foundation convened the first Global Vaccine and Immunization Research Forum (GVIRF) in March 2014. This first GVIRF aimed to track recent progress of the Global Vaccine Action Plan research and development agenda, identify opportunities and challenges, promote partnerships in vaccine research, and facilitate the inclusion of all stakeholders in vaccine research and development. Leading scientists, vaccine developers, and public health officials from around the world discussed scientific and technical challenges in vaccine development, research to improve the impact of immunization, and regulatory issues. This report summarizes the discussions and conclusions from the forum participants. Copyright © 2016. Published by Elsevier Ltd.. All rights reserved.

  12. The skin as an organ of immunity

    NARCIS (Netherlands)

    Bos, J. D.

    1997-01-01

    During evolution, the skin has developed a specific immunological environment that is known as the skin immune system (SIS). A substantial number of immunological phenomena exemplify the special place the skin occupies as a peripheral immune organ. These include the continuous exposure to sun rays,

  13. Immunization with Brucella VirB proteins reduces organ colonization in mice through a Th1-type immune response and elicits a similar immune response in dogs.

    Science.gov (United States)

    Pollak, Cora N; Wanke, María Magdalena; Estein, Silvia M; Delpino, M Victoria; Monachesi, Norma E; Comercio, Elida A; Fossati, Carlos A; Baldi, Pablo C

    2015-03-01

    VirB proteins from Brucella spp. constitute the type IV secretion system, a key virulence factor mediating the intracellular survival of these bacteria. Here, we assessed whether a Th1-type immune response against VirB proteins may protect mice from Brucella infection and whether this response can be induced in the dog, a natural host for Brucella. Splenocytes from mice immunized with VirB7 or VirB9 responded to their respective antigens with significant and specific production of gamma interferon (IFN-γ), whereas interleukin-4 (IL-4) was not detected. Thirty days after an intraperitoneal challenge with live Brucella abortus, the spleen load of bacteria was almost 1 log lower in mice immunized with VirB proteins than in unvaccinated animals. As colonization reduction seemed to correlate with a Th1-type immune response against VirB proteins, we decided to assess whether such a response could be elicited in the dog. Peripheral blood mononuclear cells (PBMCs) from dogs immunized with VirB proteins (three subcutaneous doses in QuilA adjuvant) produced significantly higher levels of IFN-γ than cells from control animals upon in vitro stimulation with VirB proteins. A skin test to assess specific delayed-type hypersensitivity was positive in 4 out of 5 dogs immunized with either VirB7 or VirB9. As both proteins are predicted to locate in the outer membrane of Brucella organisms, the ability of anti-VirB antibodies to mediate complement-dependent bacteriolysis of B. canis was assessed in vitro. Sera from dogs immunized with either VirB7 or VirB9, but not from those receiving phosphate-buffered saline (PBS), produced significant bacteriolysis. These results suggest that VirB-specific responses that reduce organ colonization by Brucella in mice can be also elicited in dogs. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  14. Wallerian degeneration: the innate-immune response to traumatic nerve injury

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    Rotshenker Shlomo

    2011-08-01

    Full Text Available Abstract Traumatic injury to peripheral nerves results in the loss of neural functions. Recovery by regeneration depends on the cellular and molecular events of Wallerian degeneration that injury induces distal to the lesion site, the domain through which severed axons regenerate back to their target tissues. Innate-immunity is central to Wallerian degeneration since innate-immune cells, functions and molecules that are produced by immune and non-immune cells are involved. The innate-immune response helps to turn the peripheral nerve tissue into an environment that supports regeneration by removing inhibitory myelin and by upregulating neurotrophic properties. The characteristics of an efficient innate-immune response are rapid onset and conclusion, and the orchestrated interplay between Schwann cells, fibroblasts, macrophages, endothelial cells, and molecules they produce. Wallerian degeneration serves as a prelude for successful repair when these requirements are met. In contrast, functional recovery is poor when injury fails to produce the efficient innate-immune response of Wallerian degeneration.

  15. Cross-immunity among allogeneic tumors of rats immunized with solid tumors

    International Nuclear Information System (INIS)

    Ogasawara, Masamichi

    1979-01-01

    Several experiments were done for the study of cross-immunity among allogeneic rat tumors by immunization using gamma-irradiated or non-irradiated solid tumors. Each group of rats which were immunized with gamma-irradiation solid tumor inocula from ascites tumor cell line of tetra-ploid Hirosaki sarcoma, Usubuchi sarcoma or AH 130, showed an apparent resistance against the intraperitoneal challenge with Hirosaki sarcoma. A similar resistance was demonstrated in the case of the challenge with Usubuchi sarcoma into rats immunized with non-irradiated methylcholanthrene (MCA)-induced tumors. In using solid MCA tumors as immunogen and Hirosaki sarcoma as challenge tumor, it was also demonstrated in 2 out of 3 groups immunized with non-irradiated tumors. In the experiment of trying to induce cross-immunity between 2 MCA tumors by immunization with irradiated solid tumor only, the inhibitory effect on the growth was observed in the early stage in the treated groups as compared with the control one. From the above results, it may be considered that the immunization with irradiated solid tumors fromas cites cell lines and non-irradiated solid MCA tumors induced strong cross-immunity in general, but that the immunization with only irradiated solid MCA tumors induced weak cross-immunity commonly. (author)

  16. Intramammary Immunization of Pregnant Mice with Staphylococcal Protein A Reduces the Post-Challenge Mammary Gland Bacterial Load but Not Pathology.

    Directory of Open Access Journals (Sweden)

    Jully Gogoi-Tiwari

    Full Text Available Protein A, encoded by the spa gene, is one of the major immune evading MSCRAMM of S. aureus, demonstrated to be prevalent in a significant percentage of clinical bovine mastitis isolates in Australia. Given its' reported significance in biofilm formation and the superior performance of S. aureus biofilm versus planktonic vaccine in the mouse mastitis model, it was of interest to determine the immunogenicity and protective potential of Protein A as a potential vaccine candidate against bovine mastitis using the mouse mastitis model. Pregnant Balb/c mice were immunised with Protein A emulsified in an alum-based adjuvant by subcutaneous (s/c or intramammary (i/mam routes. While humoral immune response of mice post-immunization were determined using indirect ELISA, cell-mediated immune response was assessed by estimation of interferon-gamma (IFN-γ produced by protein A-stimulated splenocyte supernatants. Protective potential of Protein A against experimental mastitis was determined by challenge of immunized versus sham-vaccinated mice by i/mam route, based upon manifestation of clinical symptoms, total bacterial load and histopathological damage to mammary glands. Significantly (p<0.05 higher levels of IgG1 isotype were produced in mice immunized by the s/c route. In contrast, significantly higher levels of the antibody isotype IgG2a were produced in mice immunized by the i/mam route (p<0.05. There was significant reduction (p<0.05 in bacterial loads of the mammary glands of mice immunized by Protein A regardless of the route of immunization, with medium level of clinical symptoms observed up to day 3 post-challenge. However, Protein A vaccine failed to protect immunized mice post-challenge with biofilm producing encapsulated S. aureus via i/mam route, regardless of the route of immunization, as measured by the level of mammary tissue damage. It was concluded that, Protein A in its' native state was apparently not a suitable candidate for inclusion

  17. Tumors of peripheral nerves

    International Nuclear Information System (INIS)

    Ho, Michael; Lutz, Amelie M.

    2017-01-01

    Differentiation between malignant and benign tumors of peripheral nerves in the early stages is challenging; however, due to the unfavorable prognosis of malignant tumors early identification is required. To show the possibilities for detection, differential diagnosis and clinical management of peripheral nerve tumors by imaging appearance in magnetic resonance (MR) neurography. Review of current literature available in PubMed and MEDLINE, supplemented by the authors' own observations in clinical practice. Although not pathognomonic, several imaging features have been reported for a differentiation between distinct peripheral nerve tumors. The use of MR neurography enables detection and initial differential diagnosis in tumors of peripheral nerves. Furthermore, it plays an important role in clinical follow-up, targeted biopsy and surgical planning. (orig.) [de

  18. Correlation of STATs family expression in oral lichen planus tissue with peripheral blood PD-1 and PD-L1 expression as well as immune function

    Directory of Open Access Journals (Sweden)

    Hong Zhang

    2016-12-01

    Full Text Available Objective: To study the correlation of STATs family expression in oral lichen planus tissue with peripheral blood PD-1 and PD-L1 expression as well as immune function. Methods: A total of 47 patients diagnosed with oral lichen planus in our hospital between May 2015 and March 2016 were selected as the oral lichen planus group (OLP group of the study, and healthy volunteers receiving physical examination during the same period were selected as the control group of the study. Peripheral blood mononuclear cells were collected to detect the expression of PD-1, PD-L1 and immune cell surface marker molecules, serum was collected to detect the content of Th1 and Th2 cytokines as well as immunoglobulin, and oral lichen planus lesion tissue and adjacent normal tissue were collected to determine STATs family expression. Results: p-STAT1, p-STAT3 and p-STAT5a expression in lesion tissue were significantly higher than those in normal tissue while p-STAT2, p-STAT4 and p-STAT5b expression were not significantly different from those in normal tissue; PD-1 and PD-L1 mRNA expression as well as the mean fluorescence intensity of CD19+ in peripheral blood mononuclear cells of OLP group were significantly higher than those of control group and positively correlated with p-STAT1, p-STAT3 and p-STAT5a expression while the mean fluorescence intensity of CD3+, CD4+, CD8+ and CD16+CD56+ were significantly lower than those of control group and negatively correlated with p-STAT1, p-STAT3 and p-STAT5a expression; serum IFN-γ and IL-2 content of OLP group were significantly lower than those of control group and negatively correlated with p-STAT1, p-STAT3 and p-STAT5a expression while IL-4, IL-10, IgG, IgM and IgA content were significantly higher than those of control group and positively correlated with p-STAT1, p-STAT3 and p-STAT5a expression. Conclusion: p-STAT1, p-STAT3 and p-STAT5a expression abnormally increase in oral lichen planus tissues, and the Th1/Th2 cellular

  19. Immune protection of microneme 7 (EmMIC7) against Eimeria maxima challenge in chickens.

    Science.gov (United States)

    Huang, Jingwei; Zhang, Zhenchao; Li, Menghui; Song, Xiaokai; Yan, Ruofeng; Xu, Lixin; Li, Xiangrui

    2015-10-01

    In the present study, the immune protective effects of recombinant microneme protein 7 of Eimeria maxima (rEmMIC7) and a DNA vaccine encoding this antigen (pVAX1-EmMIC7) on experimental challenge were evaluated. Two-week-old chickens were randomly divided into five groups. Experimental groups of chickens were immunized with 100 μg DNA vaccine pVAX1-MIC7 or 200 μg rEmMIC7, while control groups of chickens were injected with pVAX1 plasmid or sterile phosphate buffered saline (PBS). The results showed that the anti-EmMIC7 antibody titres in chickens of both rEmMIC7 and pVAX1-MIC7 groups were significantly higher as compared to PBS and pVAX1 control (P maxima challenge in chickens and it could be an effective antigen candidate for the development of new vaccines against E. maxima.

  20. Comparison of casein and whey in diets on performance, immune responses and metabolomic profile of weaning pigs challenged with E.coli F4

    DEFF Research Database (Denmark)

    Sugiharto, Sugiharto; Jensen, Bent Borg; Hedemann, Mette Skou

    2014-01-01

    challenged with E. coli F4. Two factorial experiments involving 24 weanling pigs were conducted. Diets containing casein or whey, and challenge with E. coli O149:F4 or not, were the two factors. Blood was sampled at the day before challenge and 4 and 7 days postchallenge. For measurement of mucosal immune...... of pigs. Challenge of the pigs with E. coli F4 increased the diarrhea and appeared to modulate the immune function of the piglets through changes in T cells populations and plasma metabolite profile....... with unchallenged pigs. The challenge reduced (PE...

  1. Peripheral nervous system neuroimmunology seen by a neuro-pathologist.

    Science.gov (United States)

    Vallat, J-M

    2014-10-01

    In most dysimmune neuropathies, historically the microscopical lesions were described prior to immunological studies. The latter along with neuropathological studies have found some immune, albeit incomplete, explanations of the mechanisms of these lesions which we will describe in two main syndromes: the primitive auto-immune inflammatory peripheral polyneuropathies (GBS and CIDP) and polyneuropathies induced by a monoclonal dysglobulinemia. In some patients who have to be discussed case by case pathology (nerve biopsy) will confirm the diagnosis, may help to delineate the molecular anomalies and identify lesional mechanisms. We will review the high variability of nerve lesions which is characteristic of dysimmune neuropathies. Pathological studies confirm that both humoral and cellular immune reactions against Schwann cell and/or axonal antigens are implicated in primitive dysimmune neuropathies due to a dysfunction or failure of immune tolerance mechanisms. In case of a polyneuropathy associated to a monoclonal dysglobulinemia, pathological and immunological studies have shown that in many patients, the dysglobulinemia did harm the peripheral nerve; knowledge of the pathological lesions and their mechanisms is of major interest for orienting specific treatments. Copyright © 2014. Published by Elsevier Masson SAS.

  2. Cross-immunity among mammary carcinomas in C3H/HE mice immunized with gamma-irradiated tumor cells

    International Nuclear Information System (INIS)

    Waga, Takashi

    1980-01-01

    By immunization with gamma-irradiated (13,000 rad) tumor cells, cross-immunity between ascites mammary carcinomas and among solid mammary carcinomas in C3H/He mice was studied. The results were as follows: (1) Two ascites mammary carcinomas designated MM 46 (high vitality) and MM 48 (intermediate vitality) were used in this experiment. The immunization with the tumor of high vitality (MM 46) induced strong cross-immunity against the challenge of the tumor of intermediate vitality (MM 48). The immunization with the tumor of intermediate vitality (MM 48) induced weak cross-immunity against the challenge of the tumor of high vitality (MM 46). (2) Three solid mammary carcinomas designated MT 10 (intermediate vitality), MT 7 (high vitality) and MT X (the highest vitality) were used in this experiment. The immunization with the tumor of high vitality (MT 7) induced strong cross-immunity against the challenge of the tumor of intermediate vitality (MT 10), and induced moderate cross-immunity against the challenge of the tumor of the highest vitality (MT X). The immunization with the tumor of intermediate vitality (MT 10) induced moderate cross-immunity against the challenge of the tumor of high vitality (MT 7), but could not induce any cross-immunity against the challenge of the tumor of the highest vitality (MT X). (author)

  3. A Comparative Study of Peripheral Immune Responses to Taenia solium in Individuals with Parenchymal and Subarachnoid Neurocysticercosis.

    Directory of Open Access Journals (Sweden)

    Iskra Tuero

    2015-10-01

    Full Text Available The ability of Taenia solium to modulate the immune system likely contributes to their longevity in the human host. We tested the hypothesis that the nature of the immune response is related to the location of parasite and clinical manifestations of infection.Peripheral blood mononuclear cells (PBMC were obtained from untreated patients with neurocysticercosis (NCC, categorized as having parenchymal or subarachnoid infection by the presence of cysts exclusively within the parenchyma or in subarachnoid spaces of the brain, and from uninfected (control individuals matched by age and gender to each patient. Using multiplex detection technology, sera from NCC patients and controls and cytokine production by PBMC after T. solium antigen (TsAg stimulation were assayed for levels of inflammatory and regulatory cytokines. PBMC were phenotyped by flow cytometry ex vivo and following in vitro stimulation with TsAg.Sera from patients with parenchymal NCC demonstrated significantly higher Th1 (IFN-γ/IL-12 and Th2 (IL-4/IL-13 cytokine responses and trends towards higher levels of IL-1β/IL-8/IL-5 than those obtained from patients with subarachnoid NCC. Also higher in vitro antigen-driven TNF-β secretion was detected in PBMC supernatants from parenchymal than in subarachnoid NCC. In contrast, there was a significantly higher IL-10 response to TsAg stimulation in patients with subarachnoid NCC compared to parenchymal NCC. Although no differences in regulatory T cells (Tregs frequencies were found ex vivo, there was a trend towards greater expansion of Tregs upon TsAg stimulation in subarachnoid than in parenchymal NCC when data were normalized for the corresponding controls.T. solium infection of the subarachnoid space is associated with an enhanced regulatory immune response compared to infection in the parenchyma. The resulting anti-inflammatory milieu may represent a parasite strategy to maintain a permissive environment in the host or diminish

  4. Omega-3 polyunsaturated fatty acids enrichment alters performance and immune response in infectious bursal disease challenged broilers

    Directory of Open Access Journals (Sweden)

    Maroufyan Elham

    2012-01-01

    Full Text Available Abstract Background Infectious bursal disease (IBD results in economic loss due to mortality, reduction in production efficiency and increasing the usage of antibiotics. This study was carried out to investigate the modulatory roles of dietary n-3 polyunsaturated fatty acids (PUFA enrichment in immune response and performance of IBD challenged broiler chickens. Methods A total of 300 day old male broiler chicks were assigned to four dietary n-3 PUFA ascending levels as the treatment groups (T1: 0.5; T2: 8.0; T3: 11.5; T4: 16.5 using combinations of tuna oil and sunflower oil. All diets were isocaloric and isonitrogenous. On day 28, all birds were challenged with IBD virus. Antibody titer, cytokine production, bursa lesion pre and post-challenge and lymphoid organ weight were recorded. Results On d 42 the highest body weight was observed in the T2 and T3 and the lowest in T4 chickens. Feed conversion ratio of the T2 broilers was significantly better than the other groups. Although productive parameters were not responded to the dietary n-3 PUFA in a dose-dependent manner, spleen weight, IBD and Newcastle disease antibody titers and IL-2 and IFN-γ concentrations were constantly elevated by n-3 PUFA enrichment. Conclusions Dietary n-3 PUFA enrichment may improve the immune response and IBD resistance, but the optimum performance does not coincide with the optimum immune response. It seems that dietary n-3 PUFA modulates the broiler chicken performance and immune response in a dose-dependent manner. Thus, a moderate level of dietary n-3 PUFA enrichment may help to put together the efficiency of performance and relative immune response enhancement in broiler chickens.

  5. Cross-immunity between syngeneic tumors in mice immunized with gamma-irradiated ascites tumors

    International Nuclear Information System (INIS)

    Kudo, Hajime; Waga, Takashi; Sato, Tatsusuke; Ogasawara, Masamichi; Ito, Izumi

    1980-01-01

    C3H/He mice immunized repeatedly with irradiated (13,000 rads 60 Co) MM46 or MM48, both transplantable ascites mammary carcinomas of the same strain, were subcutaneously challenged with the identical or the different tumor. In mice immunized with irradiated MM46, the growth of challenges of not only MM46 but also MM48 was inhibited. On the other hand, in mice immunized with irradiated MM48, the growth of challenges of MM48 was inhibited, but the inhibition of the growth of MM46 was not observed. Cross-immunity, therefore, was shown by immunization with MM46 but not with MM48. These findings were considered to indicate that MM46 expressed cross-immunity against MM48 because of its high resistance to the irradiation, and that MM48 did not show cross-immunity to MM46 because of its low resistance to the irradiation. (author)

  6. Analysis of peripheral blood immune cells after prophylactic immunization with HPV-16/18 ASO4-adjuvanted vaccine

    Directory of Open Access Journals (Sweden)

    Iwona Hus

    2015-04-01

    Full Text Available Persistent infection with oncogenic types of human papillomavirus (HPV is a causal factor for more than 99% of cervical cancers. Recently, prophylactic vaccines have been developed to prevent infections with cancer-associated HPV types (HPV16 and HPV18. The aim of this study was to analyze the changes in the immune system that occur within four weeks of the first dose of HPV-16/18 ASO4-adjuvanted vaccine. Assessment of the percentages of selected cell populations in peripheral blood of 20 healthy volunteers vaccinated with Cervarix was performed using flow cytometry. The analysis revealed an increase in the proportion of activated B and CD4+ T helper cells and an absence of significant differences in cytotoxic CD8+ T lymphocytes, indicating activation of the humoral response after vaccination, without a significant effect on cellular response. There were no significant changes in the NK cell population, and there was a reduction of the percentage of NKT-like cells, which may result from expiry of the primary response at the time of analysis. The presented results are preliminary, and in the context of the increasing use of the anti-HPV vaccine, it would be worth continuing the study in larger groups of patients and at earlier and later time points in combination with the measurement of specific anti-HPV16 and -HPV18 antibody levels. Such an assessment could therefore contribute not only to better understanding of the exact mechanism of action of the vaccine, but also to defining the immunological parameters that determine its effectiveness.

  7. Maternal immunity enhances systemic recall immune responses upon oral immunization of piglets with F4 fimbriae.

    Science.gov (United States)

    Nguyen, Ut V; Melkebeek, Vesna; Devriendt, Bert; Goetstouwers, Tiphanie; Van Poucke, Mario; Peelman, Luc; Goddeeris, Bruno M; Cox, Eric

    2015-06-23

    F4 enterotoxigenic Escherichia coli (ETEC) cause diarrhoea and mortality in piglets leading to severe economic losses. Oral immunization of piglets with F4 fimbriae induces a protective intestinal immune response evidenced by an F4-specific serum and intestinal IgA response. However, successful oral immunization of pigs with F4 fimbriae in the presence of maternal immunity has not been demonstrated yet. In the present study we aimed to evaluate the effect of maternal immunity on the induction of a systemic immune response upon oral immunization of piglets. Whereas F4-specific IgG and IgA could be induced by oral immunization of pigs without maternal antibodies and by intramuscular immunization of pigs with maternal antibodies, no such response was seen in the orally immunized animals with maternal antibodies. Since maternal antibodies can mask an antibody response, we also looked by ELIspot assays for circulating F4-specific antibody secreting cells (ASCs). Enumerating the F4-specific ASCs within the circulating peripheral blood mononuclear cells, and the number of F4-specific IgA ASCs within the circulating IgA(+) B-cells revealed an F4-specific immune response in the orally immunized animals with maternal antibodies. Interestingly, results suggest a more robust IgA booster response by oral immunization of pigs with than without maternal antibodies. These results demonstrate that oral immunization of piglets with F4-specific maternal antibodies is feasible and that these maternal antibodies seem to enhance the secondary systemic immune response. Furthermore, our ELIspot assay on enriched IgA(+) B-cells could be used as a screening procedure to optimize mucosal immunization protocols in pigs with maternal immunity.

  8. The Diabetes Telephone Study: Design and challenges of a pragmatic cluster randomized trial to improve diabetic peripheral neuropathy treatment.

    Science.gov (United States)

    Adams, Alyce S; Bayliss, Elizabeth A; Schmittdiel, Julie A; Altschuler, Andrea; Dyer, Wendy; Neugebauer, Romain; Jaffe, Marc; Young, Joseph D; Kim, Eileen; Grant, Richard W

    2016-06-01

    Challenges to effective pharmacologic management of symptomatic diabetic peripheral neuropathy include the limited effectiveness of available medicines, frequent side effects, and the need for ongoing symptom assessment and treatment titration for maximal effectiveness. We present here the rationale and implementation challenges of the Diabetes Telephone Study, a randomized trial designed to improve medication treatment, titration, and quality of life among patients with symptomatic diabetic peripheral neuropathy. We implemented a pragmatic cluster randomized controlled trial to test the effectiveness of an automated interactive voice response tool designed to provide physicians with real-time patient-reported data about responses to newly prescribed diabetic peripheral neuropathy medicines. A total of 1834 primary care physicians treating patients in the diabetes registry at Kaiser Permanente Northern California were randomized into the intervention or control arm. In September 2014, we began identification and recruitment of patients assigned to physicians in the intervention group who receive three brief interactive calls every 2 months after a medication is prescribed to alleviate diabetic peripheral neuropathy symptoms. These calls provide patients with the opportunity to report on symptoms, side effects, self-titration of medication dose and overall satisfaction with treatment. We plan to compare changes in self-reported quality of life between the intervention group and patients in the control group who receive three non-interactive automated educational phone calls. Successful implementation of this clinical trial required robust stakeholder engagement to help tailor the intervention and to address pragmatic concerns such as provider time constraints. As of 27 October 2015, we had screened 2078 patients, 1447 of whom were eligible for participation. We consented and enrolled 1206 or 83% of those eligible. Among those enrolled, 53% are women and the mean age

  9. Trans-generational plasticity in response to immune challenge is constrained by heat stress.

    Science.gov (United States)

    Roth, Olivia; Landis, Susanne H

    2017-06-01

    Trans-generational plasticity (TGP) is the adjustment of phenotypes to changing habitat conditions that persist longer than the individual lifetime. Fitness benefits (adaptive TGP) are expected upon matching parent-offspring environments. In a global change scenario, several performance-related environmental factors are changing simultaneously. This lowers the predictability of offspring environmental conditions, potentially hampering the benefits of TGP. For the first time, we here explore how the combination of an abiotic and a biotic environmental factor in the parental generation plays out as trans-generational effect in the offspring. We fully reciprocally exposed the parental generation of the pipefish Syngnathus typhle to an immune challenge and elevated temperatures simulating a naturally occurring heatwave. Upon mating and male pregnancy, offspring were kept in ambient or elevated temperature regimes combined with a heat-killed bacterial epitope treatment. Differential gene expression (immune genes and DNA- and histone-modification genes) suggests that the combined change of an abiotic and a biotic factor in the parental generation had interactive effects on offspring performance, the temperature effect dominated over the immune challenge impact. The benefits of certain parental environmental conditions on offspring performance did not sum up when abiotic and biotic factors were changed simultaneously supporting that available resources that can be allocated to phenotypic trans-generational effects are limited. Temperature is the master regulator of trans-generational phenotypic plasticity, which potentially implies a conflict in the allocation of resources towards several environmental factors. This asks for a reassessment of TGP as a short-term option to buffer environmental variation in the light of climate change.

  10. The surgery of peripheral nerves (including tumors)

    DEFF Research Database (Denmark)

    Fugleholm, Kåre

    2013-01-01

    Surgical pathology of the peripheral nervous system includes traumatic injury, entrapment syndromes, and tumors. The recent significant advances in the understanding of the pathophysiology and cellular biology of peripheral nerve degeneration and regeneration has yet to be translated into improved...... surgical techniques and better outcome after peripheral nerve injury. Decision making in peripheral nerve surgery continues to be a complex challenge, where the mechanism of injury, repeated clinical evaluation, neuroradiological and neurophysiological examination, and detailed knowledge of the peripheral...... nervous system response to injury are prerequisite to obtain the best possible outcome. Surgery continues to be the primary treatment modality for peripheral nerve tumors and advances in adjuvant oncological treatment has improved outcome after malignant peripheral nerve tumors. The present chapter...

  11. Dynamic impact of brief electrical nerve stimulation on the neural immune axis-polarization of macrophages toward a pro-repair phenotype in demyelinated peripheral nerve.

    Science.gov (United States)

    McLean, Nikki A; Verge, Valerie M K

    2016-09-01

    Demyelinating peripheral nerves are infiltrated by cells of the monocyte lineage, including macrophages, which are highly plastic, existing on a continuum from pro-inflammatory M1 to pro-repair M2 phenotypic states. Whether one can therapeutically manipulate demyelinated peripheral nerves to promote a pro-repair M2 phenotype remains to be elucidated. We previously identified brief electrical nerve stimulation (ES) as therapeutically beneficial for remyelination, benefits which include accelerated clearance of macrophages, making us theorize that ES alters the local immune response. Thus, the impact of ES on the immune microenvironment in the zone of demyelination was examined. Adult male rat tibial nerves were focally demyelinated via 1% lysophosphatidyl choline (LPC) injection. Five days later, half underwent 1 hour 20 Hz sciatic nerve ES proximal to the LPC injection site. ES had a remarkable and significant impact, shifting the macrophage phenotype from predominantly pro-inflammatory/M1 toward a predominantly pro-repair/M2 one, as evidenced by an increased incidence of expression of M2-associated phenotypic markers in identified macrophages and a decrease in M1-associated marker expression. This was discernible at 3 days post-ES (8 days post-LPC) and continued at the 5 day post-ES (10 days post-LPC) time point examined. ES also affected chemokine (C-C motif) ligand 2 (CCL2; aka MCP-1) expression in a manner that correlated with increases and decreases in macrophage numbers observed in the demyelination zone. The data establish that briefly increasing neuronal activity favorably alters the immune microenvironment in demyelinated nerve, rapidly polarizing macrophages toward a pro-repair phenotype, a beneficial therapeutic concept that may extend to other pathologies. GLIA 2016;64:1546-1561. © 2016 Wiley Periodicals, Inc.

  12. Systemic BCG immunization induces persistent lung mucosal multifunctional CD4 T(EM cells which expand following virulent mycobacterial challenge.

    Directory of Open Access Journals (Sweden)

    Daryan A Kaveh

    Full Text Available To more closely understand the mechanisms of how BCG vaccination confers immunity would help to rationally design improved tuberculosis vaccines that are urgently required. Given the established central role of CD4 T cells in BCG induced immunity, we sought to characterise the generation of memory CD4 T cell responses to BCG vaccination and M. bovis infection in a murine challenge model. We demonstrate that a single systemic BCG vaccination induces distinct systemic and mucosal populations of T effector memory (T(EM cells in vaccinated mice. These CD4+CD44(hiCD62L(loCD27⁻ T cells concomitantly produce IFN-γ and TNF-α, or IFN-γ, IL-2 and TNF-α and have a higher cytokine median fluorescence intensity MFI or 'quality of response' than single cytokine producing cells. These cells are maintained for long periods (>16 months in BCG protected mice, maintaining a vaccine-specific functionality. Following virulent mycobacterial challenge, these cells underwent significant expansion in the lungs and are, therefore, strongly associated with protection against M. bovis challenge. Our data demonstrate that a persistent mucosal population of T(EM cells can be induced by parenteral immunization, a feature only previously associated with mucosal immunization routes; and that these multifunctional T(EM cells are strongly associated with protection. We propose that these cells mediate protective immunity, and that vaccines designed to increase the number of relevant antigen-specific T(EM in the lung may represent a new generation of TB vaccines.

  13. Expression of H5 hemagglutinin vaccine antigen in common duckweed (Lemna minor) protects against H5N1 high pathogenicity avian influenza virus challenge in immunized chickens.

    Science.gov (United States)

    Bertran, Kateri; Thomas, Colleen; Guo, Xuan; Bublot, Michel; Pritchard, Nikki; Regan, Jeffrey T; Cox, Kevin M; Gasdaska, John R; Dickey, Lynn F; Kapczynski, Darrell R; Swayne, David E

    2015-07-09

    A synthetic hemagglutinin (HA) gene from the highly pathogenic avian influenza (HPAI) virus A/chicken/Indonesia/7/2003 (H5N1) (Indo/03) was expressed in aquatic plant Lemna minor (rLemna-HA). In Experiment 1, efficacy of rLemna-HA was tested on birds immunized with 0.2μg or 2.3 μg HA and challenged with 10(6) mean chicken embryo infectious doses (EID50) of homologous virus strain. Both dosages of rLemna-HA conferred clinical protection and dramatically reduced viral shedding. Almost all the birds immunized with either dosage of rLemna-HA elicited HA antibody titers against Indo/03 antigen, suggesting an association between levels of anti-Indo/03 antibodies and protection. In Experiment 2, efficacy of rLemna-HA was tested on birds immunized with 0.9 μg or 2.2 μg HA and challenged with 10(6) EID50 of heterologous H5N1 virus strains A/chicken/Vietnam/NCVD-421/2010 (VN/10) or A/chicken/West Java/PWT-WIJ/2006 (PWT/06). Birds challenged with VN/10 exhibited 100% survival regardless of immunization dosage, while birds challenged with PWT/06 had 50% and 30% mortality at 0.9 μg HA and 2.2 μg HA, respectively. For each challenge virus, viral shedding titers from 2.2 μg HA vaccinated birds were significantly lower than those from 0.9μg HA vaccinated birds, and titers from both immunized groups were in turn significantly lower than those from sham vaccinated birds. Even if immunized birds elicited HA titers against the vaccine antigen Indo/03, only the groups challenged with VN/10 developed humoral immunity against the challenge antigen. None (rLemna-HA 0.9 μg HA) and 40% (rLemna-HA 2.2 μg HA) of the immunized birds challenged with PWT/06 elicited pre-challenge antibody titers, respectively. In conclusion, Lemna-expressed HA demonstrated complete protective immunity against homologous challenge and suboptimal protection against heterologous challenge, the latter being similar to results from inactivated whole virus vaccines. Transgenic duckweed-derived HA could be a

  14. Hippocampal structure and function are maintained despite severe innate peripheral inflammation.

    Science.gov (United States)

    Süß, Patrick; Kalinichenko, Liubov; Baum, Wolfgang; Reichel, Martin; Kornhuber, Johannes; Loskarn, Sandra; Ettle, Benjamin; Distler, Jörg H W; Schett, Georg; Winkler, Jürgen; Müller, Christian P; Schlachetzki, Johannes C M

    2015-10-01

    Chronic peripheral inflammation mediated by cytokines such as TNFα, IL-1β, and IL-6 is associated with psychiatric disorders like depression and anxiety. However, it remains elusive which distinct type of peripheral inflammation triggers neuroinflammation and affects hippocampal plasticity resulting in depressive-like behavior. We hypothesized that chronic peripheral inflammation in the human TNF-α transgenic (TNFtg) mouse model of rheumatoid arthritis spreads into the central nervous system and induces depressive state manifested in specific behavioral pattern and impaired adult hippocampal neurogenesis. TNFtg mice showed severe erosive arthritis with increased IL-1β and IL-6 expression in tarsal joints with highly elevated human TNF-α levels in the serum. Intriguingly, IL-1β and IL-6 mRNA levels were not altered in the hippocampus of TNFtg mice. In contrast to the pronounced monocytosis in joints and spleen of TNFtg mice, signs of hippocampal microgliosis or astrocytosis were lacking. Furthermore, locomotion was impaired, but there was no locomotion-independent depressive behavior in TNFtg mice. Proliferation and maturation of hippocampal neural precursor cells as well as survival of newly generated neurons were preserved in the dentate gyrus of TNFtg mice despite reduced motor activity and peripheral inflammatory signature. We conclude that peripheral inflammation in TNFtg mice is mediated by chronic activation of the innate immune system. However, severe peripheral inflammation, though impairing locomotor activity, does not elicit depressive-like behavior. These structural and functional findings indicate the maintenance of hippocampal immunity, cellular plasticity, and behavior despite peripheral innate inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Lower percentage of CD8+ T cells in peripheral blood of patients with sporotrichosis.

    Science.gov (United States)

    Zhu, Mingji; Xu, Yaqin; An, Lin; Jiang, Jinlan; Zhang, Xu; Jiang, Rihua

    2016-07-01

    To characterize the peripheral immunity and immunity response of patients with sporotrichosis, in this study we determined the lymphocyte subsets in the peripheral blood of Chinese patients with sporotrichosis. In this retrospective study, peripheral blood was collected from 69 sporotrichosis patients (37, fixed cutaneous form; 32 lymphocutaneous) and 66 healthy controls. Lymphocyte subsets were analyzed using flow cytometry. Compared to controls, the percentage of CD8+ T cells was lower in sporotrichosis patients. The percentage of CD8+ T cells in peripheral blood tended to become lower with disease duration and disease severity, although the difference was not statistically significant for either acute, subacute and chronic patients or fixed cutaneous and lymphocutaneous patients. Our data indicate that the decrease of CD8+ T cells in peripheral blood of patients with sporotrichosis is associated with disease severity, although the difference was not statistically significant for either duration or clinical forms of the disease. Combining antifungal agents and immunomodulators in patients with long disease duration and lymphocutaneous may be more beneficial than antifungal monotherapy. Copyright © 2016. Published by Elsevier Inc.

  16. Immune Response Induction and New Effector Mechanisms Possibly Involved in Protection Conferred by the Cuban Anti-Meningococcal BC Vaccine

    Science.gov (United States)

    Pérez, Oliver; Lastre, Miriam; Lapinet, José; Bracho, Gustavo; Díaz, Miriam; Zayas, Caridad; Taboada, Carlos; Sierra, Gustavo

    2001-01-01

    This report explores the participation of some afferent mechanisms in the immune response induced by the Cuban anti-meningococcal vaccine VA-MENGOC-BC. The induction of delayed-type hypersensitivity in nursing babies and lymphocyte proliferation after immunization is demonstrated. The presence of gamma interferon IFN-γ and interleukin-2 (IL-2) mRNAs but absence of IL-4, IL-5, and IL-10 mRNAs were observed in peripheral blood mononuclear cells from immunized subjects after in vitro challenge with outer membrane vesicles. In addition, some effector functions were also explored. The presence of opsonic activity was demonstrated in sera from vaccinees. The role of neutrophils as essential effector cells was shown. In conclusion, we have shown that, at least in the Cuban adult population, VA-MENGOC-BC induces mechanisms with a T-helper 1 pattern in the afferent and effector branches of the immune response. PMID:11401992

  17. Response of ELA-A1 horses immunized with lipopeptide containing an equine infectious anemia virus ELA-A1-restricted CTL epitope to virus challenge.

    Science.gov (United States)

    Ridgely, Sherritta L; Zhang, Baoshan; McGuire, Travis C

    2003-01-17

    Lipopeptide containing an ELA-A1-restricted cytotoxic T lymphocyte (CTL) epitope from the envelope surface unit (SU) protein of the EIAV(WSU5) strain was used to immunize three horses having the ELA-A1 haplotype. Peptide-specific ELA-A1-restricted CTL were induced in all three horses, although these were present transiently in PBMC. These horses were further immunized with lipopeptide containing the corresponding CTL epitope from the EIAV(PV) strain. Then, the three immunized horses and three non-immunized horses were challenged by intravenous inoculation with 300 TCID(50) EIAV(PV). All horses developed cell free viremia, fever and thrombocytopenia. However, there was a statistically lower fever and thrombocytopenia severity score in the immunized group. Shorter duration of plasma viral load in two of the three immunized horses likely explains the less severe clinical disease in this group. Results indicate that lipopeptide immunization had a protective effect against development of clinical disease following virus challenge.

  18. Virus-specific immune memory at peripheral sites of herpes simplex virus type 2 (HSV-2) infection in guinea pigs.

    Science.gov (United States)

    Xia, Jingya; Veselenak, Ronald L; Gorder, Summer R; Bourne, Nigel; Milligan, Gregg N

    2014-01-01

    Despite its importance in modulating HSV-2 pathogenesis, the nature of tissue-resident immune memory to HSV-2 is not completely understood. We used genital HSV-2 infection of guinea pigs to assess the type and location of HSV-specific memory cells at peripheral sites of HSV-2 infection. HSV-specific antibody-secreting cells were readily detected in the spleen, bone marrow, vagina/cervix, lumbosacral sensory ganglia, and spinal cord of previously-infected animals. Memory B cells were detected primarily in the spleen and to a lesser extent in bone marrow but not in the genital tract or neural tissues suggesting that the HSV-specific antibody-secreting cells present at peripheral sites of HSV-2 infection represented persisting populations of plasma cells. The antibody produced by these cells isolated from neural tissues of infected animals was functionally relevant and included antibodies specific for HSV-2 glycoproteins and HSV-2 neutralizing antibodies. A vigorous IFN-γ-secreting T cell response developed in the spleen as well as the sites of HSV-2 infection in the genital tract, lumbosacral ganglia and spinal cord following acute HSV-2 infection. Additionally, populations of HSV-specific tissue-resident memory T cells were maintained at these sites and were readily detected up to 150 days post HSV-2 infection. Unlike the persisting plasma cells, HSV-specific memory T cells were also detected in uterine tissue and cervicothoracic region of the spinal cord and at low levels in the cervicothoracic ganglia. Both HSV-specific CD4+ and CD8+ resident memory cell subsets were maintained long-term in the genital tract and sensory ganglia/spinal cord following HSV-2 infection. Together these data demonstrate the long-term maintenance of both humoral and cellular arms of the adaptive immune response at the sites of HSV-2 latency and virus shedding and highlight the utility of the guinea pig infection model to investigate tissue-resident memory in the setting of HSV-2 latency

  19. Virus-specific immune memory at peripheral sites of herpes simplex virus type 2 (HSV-2 infection in guinea pigs.

    Directory of Open Access Journals (Sweden)

    Jingya Xia

    Full Text Available Despite its importance in modulating HSV-2 pathogenesis, the nature of tissue-resident immune memory to HSV-2 is not completely understood. We used genital HSV-2 infection of guinea pigs to assess the type and location of HSV-specific memory cells at peripheral sites of HSV-2 infection. HSV-specific antibody-secreting cells were readily detected in the spleen, bone marrow, vagina/cervix, lumbosacral sensory ganglia, and spinal cord of previously-infected animals. Memory B cells were detected primarily in the spleen and to a lesser extent in bone marrow but not in the genital tract or neural tissues suggesting that the HSV-specific antibody-secreting cells present at peripheral sites of HSV-2 infection represented persisting populations of plasma cells. The antibody produced by these cells isolated from neural tissues of infected animals was functionally relevant and included antibodies specific for HSV-2 glycoproteins and HSV-2 neutralizing antibodies. A vigorous IFN-γ-secreting T cell response developed in the spleen as well as the sites of HSV-2 infection in the genital tract, lumbosacral ganglia and spinal cord following acute HSV-2 infection. Additionally, populations of HSV-specific tissue-resident memory T cells were maintained at these sites and were readily detected up to 150 days post HSV-2 infection. Unlike the persisting plasma cells, HSV-specific memory T cells were also detected in uterine tissue and cervicothoracic region of the spinal cord and at low levels in the cervicothoracic ganglia. Both HSV-specific CD4+ and CD8+ resident memory cell subsets were maintained long-term in the genital tract and sensory ganglia/spinal cord following HSV-2 infection. Together these data demonstrate the long-term maintenance of both humoral and cellular arms of the adaptive immune response at the sites of HSV-2 latency and virus shedding and highlight the utility of the guinea pig infection model to investigate tissue-resident memory in the

  20. Individual differences in maternal response to immune challenge predict offspring behavior: Contribution of environmental factors

    Science.gov (United States)

    Bronson, Stefanie L.; Ahlbrand, Rebecca; Horn, Paul S.; Kern, Joseph R.; Richtand, Neil M.

    2011-01-01

    Maternal infection during pregnancy elevates risk for schizophrenia and related disorders in offspring. Converging evidence suggests the maternal inflammatory response mediates the interaction between maternal infection, altered brain development, and behavioral outcome. The extent to which individual differences in the maternal response to immune challenge influence the development of these abnormalities is unknown. The present study investigated the impact of individual differences in maternal response to the viral mimic polyinosinic:polycytidylic acid (poly I:C) on offspring behavior. We observed significant variability in body weight alterations of pregnant rats induced by administration of poly I:C on gestational day 14. Furthermore, the presence or absence of maternal weight loss predicted MK-801 and amphetamine stimulated locomotor abnormalities in offspring. MK-801 stimulated locomotion was altered in offspring of all poly I:C treated dams; however, the presence or absence of maternal weight loss resulted in decreased and modestly increased locomotion, respectively. Adult offspring of poly I:C treated dams that lost weight exhibited significantly decreased amphetamine stimulated locomotion, while offspring of poly I:C treated dams without weight loss performed similarly to vehicle controls. Social isolation and increased maternal age predicted weight loss in response to poly I:C but not vehicle injection. In combination, these data identify environmental factors associated with the maternal response to immune challenge and functional outcome of offspring exposed to maternal immune activation. PMID:21255612

  1. Investigation of the cytotoxicity, antioxidative and immune-modulatory effects of Ligusticum porteri (Osha) root extract on human peripheral blood lymphocytes.

    Science.gov (United States)

    Nguyen, Khanh; Sparks, Jean; Omoruyi, Felix O

    2016-11-01

    Ligusticum porteri is a traditional Native American herb. The roots of L. porteri are traditionally used in the treatment of many diseases, however, its cytotoxicity, antioxidative and immune-modulatory effects need to be investigated. In this study, we evaluated the effects of the root extract at different doses on human peripheral blood lymphocytes (PBLs). The lymphocytes were incubated with different concentrations of the root extracts (0, 50, 100, 200, and 400 μg/mL) and harvested every 6 h for 2 d (Peffect of the herb against oxidative damage was determined by inducing oxidative stress with the administration of 50 μmol/L of hydrogen peroxide (H 2 O 2 ). Treatments with L. porteri at 200 and 400 μg/mL increased the viability of PBLs. The deleterious effect of H 2 O 2 was ameliorated by 400 μg/mL L. porteri treatment. Addition of 400 μg/mL L. porteri reduced lipid peroxidation in stressed PBLs by 94% (P0.05). The findings suggest that L. porteri might be a potential immune-modulating agent involving protective effects against oxidative damage.

  2. Immune-mediated neuropathies our experience over 3 years

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    Sadanandavalli Retnaswami Chandra

    2018-01-01

    Full Text Available Introduction: Immune-mediated peripheral neuropathy is the term applied to a spectrum of peripheral nerve disorders where immune dysregulation plays a role. Therefore, they are treatable. We analyzed the cases seen in the past 3 years by us and evaluated the clinical, laboratory, and outcome parameters in these patients. Patients and Methods: Consecutive patients seen by the authors and diagnosed as immune-mediated neuropathy were analyzed for etiology, pathology, and outcome assessed. Results: A total of sixty patients, 31 acute and 29 chronic neuropathies, were identified. Their subtypes treatment and outcome assessed. Males were significantly more in both acute and chronic cases. Miller Fisher 4, AMAN 1, paraplegic type 1, motor dominant type 19, Sensory-motor 1, MADSAM 3, Bifacial 2. Nonsystemic vasculitis was seen in 16 out of 29 chronic neuropathy and HIV, POEMS, and diabetes mellitus one each. Discussion: There is a spectrum of immune-mediated neuropathy which varies in clinical course, response to treatment, etc., Small percentage of uncommon cases are seen. In this group, mortality was nil and morbidity was minimal. Conclusion: Immune-mediated neuropathies are treatable and hence should be diagnosed early for good quality outcome.

  3. Peripheral Immune Alterations in Major Depression: The Role of Subtypes and Pathogenetic Characteristics

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    Frank Euteneuer

    2017-11-01

    Full Text Available Depression has been associated with peripheral inflammatory processes and alterations in cellular immunity. Growing evidence suggests that immunological alterations may neither be necessary nor sufficient to induce depression in general, but seem to be associated with specific features. Using baseline data from the Outcome of Psychological Interventions in Depression trial, this exploratory study examines associations between depression subtypes and pathogenetic characteristics (i.e., melancholic vs non-melancholic depression, chronic vs non-chronic depression, age of onset, cognitive-affective and somatic symptom dimensions with plasma levels of C-reactive protein (CRP, interleukin (IL-6, IL-10, and numbers of leukocyte subpopulations in 98 patients with major depression (MD and 30 age and sex-matched controls. Patients with MD exhibited higher CRP levels, higher neutrophil and monocyte counts, lower IL-10 levels, and an increased neutrophil to lymphocyte ratio (NLR than controls. Patient with later age of onset had higher levels of two inflammatory markers (CRP, NLR and lower cytotoxic T cell counts after adjusting for sociodemographics, lifestyle factors, and antidepressants. Furthermore, lower anti-inflammatory IL-10 levels were related to more severe somatic depressive symptoms. These results confirm and extend previous findings suggesting that increased levels of CRP are associated with a later onset of depression and demonstrate that also NLR as a subclinical inflammatory marker is related to a later onset of depression.

  4. Pretreatment antigen-specific immunity and regulation - association with subsequent immune response to anti-tumor DNA vaccination.

    Science.gov (United States)

    Johnson, Laura E; Olson, Brian M; McNeel, Douglas G

    2017-07-18

    Immunotherapies have demonstrated clinical benefit for many types of cancers, however many patients do not respond, and treatment-related adverse effects can be severe. Hence many efforts are underway to identify treatment predictive biomarkers. We have reported the results of two phase I trials using a DNA vaccine encoding prostatic acid phosphatase (PAP) in patients with biochemically recurrent prostate cancer. In both trials, persistent PAP-specific Th1 immunity developed in some patients, and this was associated with favorable changes in serum PSA kinetics. In the current study, we sought to determine if measures of antigen-specific or antigen non-specific immunity were present prior to treatment, and associated with subsequent immune response, to identify possible predictive immune biomarkers. Patients who developed persistent PAP-specific, IFNγ-secreting immune responses were defined as immune "responders." The frequency of peripheral T cell and B cell lymphocytes, natural killer cells, monocytes, dendritic cells, myeloid derived suppressor cells, and regulatory T cells were assessed by flow cytometry and clinical laboratory values. PAP-specific immune responses were evaluated by cytokine secretion in vitro, and by antigen-specific suppression of delayed-type hypersensitivity to a recall antigen in an in vivo SCID mouse model. The frequency of peripheral blood cell types did not differ between the immune responder and non-responder groups. Non-responder patients tended to have higher PAP-specific IL-10 production pre-vaccination (p = 0.09). Responder patients had greater preexisting PAP-specific bystander regulatory responses that suppressed DTH to a recall antigen (p = 0.016). While our study population was small (n = 38), these results suggest that different measures of antigen-specific tolerance or regulation might help predict immunological outcome from DNA vaccination. These will be prospectively evaluated in an ongoing randomized, phase II trial.

  5. Regulatory T cells, maternal-foetal immune tolerance and recurrent miscarriage: new therapeutic challenging opportunities.

    Science.gov (United States)

    Alijotas-Reig, Jaume; Melnychuk, Taisiia; Gris, Josep Maria

    2015-03-15

    Because maternal alloreactive lymphocytes are not depleted during pregnancy, local and/or systemic mechanisms have to play a key role in altering the maternal immune response. Peripheral T regulatory cells (pTregs) at the maternal-foetal interface are necessary in situ to prevent early abortion, but only those pTregs that have been previously exposed to paternal alloantigens. It has been showed that pregnancy selectively stimulates the accumulation of maternal Foxp3(+)CD4(+)CD25(+) (Foxp3Tregs) cells with foetal specificity. Interestingly, after delivery, foetal-specific pTregs persist at elevated levels, maintain tolerance to pre-existing foetal antigen, and rapidly re-accumulate during subsequent pregnancy. pTreg up-regulation could be hypothesized as a possible future therapeutic strategy in humans. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  6. Peripheral facial weakness (Bell's palsy).

    Science.gov (United States)

    Basić-Kes, Vanja; Dobrota, Vesna Dermanović; Cesarik, Marijan; Matovina, Lucija Zadro; Madzar, Zrinko; Zavoreo, Iris; Demarin, Vida

    2013-06-01

    Peripheral facial weakness is a facial nerve damage that results in muscle weakness on one side of the face. It may be idiopathic (Bell's palsy) or may have a detectable cause. Almost 80% of peripheral facial weakness cases are primary and the rest of them are secondary. The most frequent causes of secondary peripheral facial weakness are systemic viral infections, trauma, surgery, diabetes, local infections, tumor, immune disorders, drugs, degenerative diseases of the central nervous system, etc. The diagnosis relies upon the presence of typical signs and symptoms, blood chemistry tests, cerebrospinal fluid investigations, nerve conduction studies and neuroimaging methods (cerebral MRI, x-ray of the skull and mastoid). Treatment of secondary peripheral facial weakness is based on therapy for the underlying disorder, unlike the treatment of Bell's palsy that is controversial due to the lack of large, randomized, controlled, prospective studies. There are some indications that steroids or antiviral agents are beneficial but there are also studies that show no beneficial effect. Additional treatments include eye protection, physiotherapy, acupuncture, botulinum toxin, or surgery. Bell's palsy has a benign prognosis with complete recovery in about 80% of patients, 15% experience some mode of permanent nerve damage and severe consequences remain in 5% of patients.

  7. Candidate immune biomarkers for radioimmunotherapy.

    Science.gov (United States)

    Levy, Antonin; Nigro, Giulia; Sansonetti, Philippe J; Deutsch, Eric

    2017-08-01

    Newly available immune checkpoint blockers (ICBs), capable to revert tumor immune tolerance, are revolutionizing the anticancer armamentarium. Recent evidence also established that ionizing radiation (IR) could produce antitumor immune responses, and may as well synergize with ICBs. Multiple radioimmunotherapy combinations are thenceforth currently assessed in early clinical trials. Past examples have highlighted the need for treatment personalization, and there is an unmet need to decipher immunological biomarkers that could allow selecting patients who could benefit from these promising but expensive associations. Recent studies have identified potential predictive and prognostic immune assays at the cellular (tumor microenvironment composition), genomic (mutational/neoantigen load), and peripheral blood levels. Within this review, we collected the available evidence regarding potential personalized immune biomarker-directed radiation therapy strategies that might be used for patient selection in the era of radioimmunotherapy. Copyright © 2017. Published by Elsevier B.V.

  8. Peripheral immune abnormalities in two high-risk populations for bipolar disorder

    NARCIS (Netherlands)

    Snijders, G.; Schiweck, C.; Brouwer, R.; Mesman, E.; Grosse, L.; de Wit, H; Nolen, W. A.; Drexhage, H. A.; Hillegers, M. H. J.

    Objective: Mounting data support the hypothesis for a role of the immune system in the pathophysiology of bipolar disorder. The aim of this study was to examine immune alterations in two unique familial high-risk cohorts for bipolar disorder. Methods: The study population comprised bipolar

  9. Cold-adapted influenza and recombinant adenovirus vaccines induce cross-protective immunity against pH1N1 challenge in mice.

    Directory of Open Access Journals (Sweden)

    Mark R Soboleski

    Full Text Available The rapid spread of the 2009 H1N1 pandemic influenza virus (pH1N1 highlighted problems associated with relying on strain-matched vaccines. A lengthy process of strain identification, manufacture, and testing is required for current strain-matched vaccines and delays vaccine availability. Vaccines inducing immunity to conserved viral proteins could be manufactured and tested in advance and provide cross-protection against novel influenza viruses until strain-matched vaccines became available. Here we test two prototype vaccines for cross-protection against the recent pandemic virus.BALB/c and C57BL/6 mice were intranasally immunized with a single dose of cold-adapted (ca influenza viruses from 1977 or recombinant adenoviruses (rAd expressing 1934 nucleoprotein (NP and consensus matrix 2 (M2 (NP+M2-rAd. Antibodies against the M2 ectodomain (M2e were seen in NP+M2-rAd immunized BALB/c but not C57BL/6 mice, and cross-reacted with pH1N1 M2e. The ca-immunized mice did not develop antibodies against M2e. Despite sequence differences between vaccine and challenge virus NP and M2e epitopes, extensive cross-reactivity of lung T cells with pH1N1 peptides was detected following immunization. Both ca and NP+M2-rAd immunization protected BALB/c and C57BL/6 mice against challenge with a mouse-adapted pH1N1 virus.Cross-protective vaccines such as NP+M2-rAd and ca virus are effective against pH1N1 challenge within 3 weeks of immunization. Protection was not dependent on recognition of the highly variable external viral proteins and could be achieved with a single vaccine dose. The rAd vaccine was superior to the ca vaccine by certain measures, justifying continued investigation of this experimental vaccine even though ca vaccine is already available. This study highlights the potential for cross-protective vaccines as a public health option early in an influenza pandemic.

  10. An Improved method for separation of leucocytes from peripheral blood of the little skate (Leucoraja erinacea)

    Science.gov (United States)

    Tomana, Mitsuru; Parton, Angela; Barnes, David W.

    2008-01-01

    Cartilaginous fish, especially sharks, rays and skates (elasmobranchs) hold interest as comparative models in immunology because they are thought to be among the organisms most closely related to the ancestor animal that first developed acquired immunity. The aim of this study was to improve methods used for the purification of viable leucocytes from peripheral blood of elasmobranchs. Here we describe modifications of density gradient centrifugation and medium formulation that improve isolation and analysis of highly-purified leucocytes from peripheral blood of a model elasmobranch, Leucoraja erinacea, the little skate. These techniques contribute to the preparation of elasmobranch immune cells that can be reliably analyzed by a variety of means, including the study of immune function. PMID:18474431

  11. Activation of innate immune genes in caprine blood leukocytes after systemic endotoxin challenge

    DEFF Research Database (Denmark)

    Salvesen, Øyvind; Reiten, Malin R; Heegaard, Peter M. H.

    2016-01-01

    observed peaking at 2 h, corroborating the increasing evidence that ISGs respond immediately to bacterial endotoxins. A slower response was manifested by four extrahepatic acute phase proteins (APP) (SAA3, HP, LF and LCN2) reaching maximum levels at 5 h. We report an immediate induction of ISGs...... insights into the dynamic regulation of innate immune genes, as well as raising new questions regarding the importance of ISGs and extrahepatic APPs in leukocytes after systemic endotoxin challenge....

  12. Innate immunity and the sensing of infection, damage and danger in the female genital tract.

    Science.gov (United States)

    Sheldon, Iain Martin; Owens, Siân-Eleri; Turner, Matthew Lloyd

    2017-02-01

    Tissue homeostasis in the female genital tract is challenged by infection, damage, and even physiological events during reproductive cycles. We propose that the evolutionarily ancient system of innate immunity is sufficient to sense and respond to danger in the non-pregnant female genital tract. Innate immunity produces a rapidly inducible, non-specific response when cells sense danger. Here we provide a primer on innate immunity and discuss what is known about how danger signals are sensed in the endometrium and ovary, the impact of inflammatory responses on reproduction, and how endocrinology and innate immunity are integrated. Endometrial epithelial and stromal cells, and ovarian granulosa cells express pattern recognition receptors, similar to cells of the innate immune system. These pattern recognition receptors, such as the Toll-like receptors, bind pathogen-associated or damage-associated molecular patterns. Activation of pattern recognition receptors leads to inflammation, recruitment of immune cells from the peripheral circulation, and phagocytosis. Although the inflammatory response helps maintain or restore endometrial health, there may also be negative consequences for fertility, including perturbation of oocyte competence. The intensity of the inflammatory response reflects the balance between the level of danger and the systems that regulate innate immunity, including the endocrine environment. Understanding innate immunity is important because disease and inappropriate inflammatory responses in the endometrium or ovary cause infertility. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Humoral immune response of C57Bl/6j and BALB/c mice immunized with irradiated tachyzoites of Toxoplasma gondii RH strain and oral challenge with ME-49 strain

    Energy Technology Data Exchange (ETDEWEB)

    Jimenez Galisteo Junior, Andres [Instituto de Pesquisas Energeticas e Nucleares IPEN/CNEN-SP, Sao Paulo, SP (Brazil). Centro de Biotecnologia; Instituto de Medicina Tropical de Sao Paulo, Sao Paulo, SP (Brazil). Lab. de Protozoologia; E-mail: galisteo@usp.br; Zorgi, Nahiara Esteves; Andrade Junior, Heitor Franco de [Instituto de Medicina Tropical de Sao Paulo, Sao Paulo, SP (Brazil). Lab. de Protozoologia; Alves, Janaina Baptista; Nascimento, Nanci do [Instituto de Pesquisas Energeticas e Nucleares IPEN/CNEN-SP, Sao Paulo, SP (Brazil). Centro de Biotecnologia; Hiramoto, Roberto Mitsuyoshi [instituto Adolfo Lutz, Sao Paulo, SP (Brazil)

    2007-07-01

    Toxoplasmosis, a prevalent widespread infection in man and animals, is mainly transmitted by oral route, through ingestion of oocysts from water and food contaminated with cat feces or infected animal tissue cysts in undercooked meat. Vaccine development implies in effective intestinal immunity, the first site of parasite entry. Radiation (255 Gy/{sup 60}Co) sterilized T. gondii RH strain tachyzoites (RST) induced significant protection when parentally administered, similar to chronically infected and acute disease protected animal. We study the humoral immune response in C57Bl/6j and BALB/c mice immunized with 10{sup 7} RST, by oral (with aluminium hydroxide 3%) or parenteral 3 biweekly administrations. T. gondii antigens specific ELISA for IgG, IgA, IgG1, IgG2a and IgG2b detection was performed in weekly blood samples during immunization. Also we evaluate of the intestinal epithelial of immunized mice the integrity of the radiated parasites by electronic microscopy. After 2 weeks, immunized and control animals were challenged with 10 cysts of ME-49 strain p.o. Protection was determined at the 30th day by brain cyst counting. As it was possible to observe in the intestinal mucosal, the aluminium hydroxide seems to maintain unchanged the parasite morphology and its mechanisms of invasion, probably due to keeping it safe from extreme pH condition of stomach. All immunized groups presented significant protection when challenged with ME-49; however, BALB/c mice showed better protection levels, with only one positive animal on brain microscopic analysis. IgG production in the serum of the animals was higher in groups immunized by i.p route, however, IgA and IgG1 levels were higher in BALB/c mice immunized by oral route. This higher protection found in BALB/c group could probably also be related to the Th2 response, demonstrated by higher IgG1 levels. All these data provide insights in oral immunization schedules for toxoplasmosis prevention, suggesting that oral

  14. Humoral immune response of C57Bl/6j and BALB/c mice immunized with irradiated tachyzoites of Toxoplasma gondii RH strain and oral challenge with ME-49 strain

    International Nuclear Information System (INIS)

    Jimenez Galisteo Junior, Andres

    2007-01-01

    Toxoplasmosis, a prevalent widespread infection in man and animals, is mainly transmitted by oral route, through ingestion of oocysts from water and food contaminated with cat feces or infected animal tissue cysts in undercooked meat. Vaccine development implies in effective intestinal immunity, the first site of parasite entry. Radiation (255 Gy/ 60 Co) sterilized T. gondii RH strain tachyzoites (RST) induced significant protection when parentally administered, similar to chronically infected and acute disease protected animal. We study the humoral immune response in C57Bl/6j and BALB/c mice immunized with 10 7 RST, by oral (with aluminium hydroxide 3%) or parenteral 3 biweekly administrations. T. gondii antigens specific ELISA for IgG, IgA, IgG1, IgG2a and IgG2b detection was performed in weekly blood samples during immunization. Also we evaluate of the intestinal epithelial of immunized mice the integrity of the radiated parasites by electronic microscopy. After 2 weeks, immunized and control animals were challenged with 10 cysts of ME-49 strain p.o. Protection was determined at the 30th day by brain cyst counting. As it was possible to observe in the intestinal mucosal, the aluminium hydroxide seems to maintain unchanged the parasite morphology and its mechanisms of invasion, probably due to keeping it safe from extreme pH condition of stomach. All immunized groups presented significant protection when challenged with ME-49; however, BALB/c mice showed better protection levels, with only one positive animal on brain microscopic analysis. IgG production in the serum of the animals was higher in groups immunized by i.p route, however, IgA and IgG1 levels were higher in BALB/c mice immunized by oral route. This higher protection found in BALB/c group could probably also be related to the Th2 response, demonstrated by higher IgG1 levels. All these data provide insights in oral immunization schedules for toxoplasmosis prevention, suggesting that oral vaccines could

  15. Deep sequencing-based transcriptome profiling analysis of bacteria-challenged Lateolabrax japonicus reveals insight into the immune-relevant genes in marine fish

    Directory of Open Access Journals (Sweden)

    Xiang Li-xin

    2010-08-01

    Full Text Available Abstract Background Systematic research on fish immunogenetics is indispensable in understanding the origin and evolution of immune systems. This has long been a challenging task because of the limited number of deep sequencing technologies and genome backgrounds of non-model fish available. The newly developed Solexa/Illumina RNA-seq and Digital gene expression (DGE are high-throughput sequencing approaches and are powerful tools for genomic studies at the transcriptome level. This study reports the transcriptome profiling analysis of bacteria-challenged Lateolabrax japonicus using RNA-seq and DGE in an attempt to gain insights into the immunogenetics of marine fish. Results RNA-seq analysis generated 169,950 non-redundant consensus sequences, among which 48,987 functional transcripts with complete or various length encoding regions were identified. More than 52% of these transcripts are possibly involved in approximately 219 known metabolic or signalling pathways, while 2,673 transcripts were associated with immune-relevant genes. In addition, approximately 8% of the transcripts appeared to be fish-specific genes that have never been described before. DGE analysis revealed that the host transcriptome profile of Vibrio harveyi-challenged L. japonicus is considerably altered, as indicated by the significant up- or down-regulation of 1,224 strong infection-responsive transcripts. Results indicated an overall conservation of the components and transcriptome alterations underlying innate and adaptive immunity in fish and other vertebrate models. Analysis suggested the acquisition of numerous fish-specific immune system components during early vertebrate evolution. Conclusion This study provided a global survey of host defence gene activities against bacterial challenge in a non-model marine fish. Results can contribute to the in-depth study of candidate genes in marine fish immunity, and help improve current understanding of host

  16. Immune mapping of the peripheral part of the visual analyzer and optic nerve

    Directory of Open Access Journals (Sweden)

    V. G. Likhvantseva

    2014-10-01

    Full Text Available Aim. To perform immune mapping of the peripheral part of visual analyzer and optic nerve in order to identify potential antigenic targets of autoimmune attack. Methods. Eyes enucleated for terminal painful glaucoma (n = 30 were studied. Immunohistochemistry (IHC was performed on paraffin-embedded sections of isolated retina and optic nerve using a broad panel of antibodies, i.e., monoclonal murine anti-MBP (myelin basic protein antibodies, polyclonal rabbit anti-alpha fodrin antibodies, monoclonal murine anti-NSE2 (neuron-specific enolase antibodies, monoclonal murine anti-GFAP (glial fibrillary acidic protein, and polyclonal rabbit anti-S100 antibodies. IHC reaction was visualized using Mouse and Rabbit Specific HRP / AEC Detection IHC Kit. IHC reaction without primary antibodies included was a negative control. IHC reaction was considered as follows: negative — no specific cellular staining or less than 10 % of cells are stained; mild — 10‑30 % of cells are stained (+; moderate — 30‑75 % of cells are stained (++; marked — more than 75 % of cells are stained (+++; overexpression — 100 % of cells intensively express markers. Additionally, staining intensity was considered as mild (+1, moderate (+2, strong (+3 and intense (+4.Results. Immune mapping with a broad panel of monoclonal antibodies identified ocular structures which were stained with IHC markers. Retina was stained with almost all markers of neural differentiation (i.e., antibodies against NSE, GFAP, S100, and α-fodrin excepting anti-MBP autoantibodies. IHC reaction intensity in retinal layers and structures varied and depended on markers. Moderate (2+ staining with antibodies against MBP, NSE, GFAP, and S100 and marked (3+ staining with antibodies against alpha-fodrin was detected in the cytoplasm of optic nerve glia.Conclusion. Complete labelling of retina structures was performed. As a result, IHC profiles of retinal neurons, optic nerve axons

  17. Immune mapping of the peripheral part of the visual analyzer and optic nerve

    Directory of Open Access Journals (Sweden)

    V. G. Likhvantseva

    2014-01-01

    Full Text Available Aim. To perform immune mapping of the peripheral part of visual analyzer and optic nerve in order to identify potential antigenic targets of autoimmune attack. Methods. Eyes enucleated for terminal painful glaucoma (n = 30 were studied. Immunohistochemistry (IHC was performed on paraffin-embedded sections of isolated retina and optic nerve using a broad panel of antibodies, i.e., monoclonal murine anti-MBP (myelin basic protein antibodies, polyclonal rabbit anti-alpha fodrin antibodies, monoclonal murine anti-NSE2 (neuron-specific enolase antibodies, monoclonal murine anti-GFAP (glial fibrillary acidic protein, and polyclonal rabbit anti-S100 antibodies. IHC reaction was visualized using Mouse and Rabbit Specific HRP / AEC Detection IHC Kit. IHC reaction without primary antibodies included was a negative control. IHC reaction was considered as follows: negative — no specific cellular staining or less than 10 % of cells are stained; mild — 10‑30 % of cells are stained (+; moderate — 30‑75 % of cells are stained (++; marked — more than 75 % of cells are stained (+++; overexpression — 100 % of cells intensively express markers. Additionally, staining intensity was considered as mild (+1, moderate (+2, strong (+3 and intense (+4.Results. Immune mapping with a broad panel of monoclonal antibodies identified ocular structures which were stained with IHC markers. Retina was stained with almost all markers of neural differentiation (i.e., antibodies against NSE, GFAP, S100, and α-fodrin excepting anti-MBP autoantibodies. IHC reaction intensity in retinal layers and structures varied and depended on markers. Moderate (2+ staining with antibodies against MBP, NSE, GFAP, and S100 and marked (3+ staining with antibodies against alpha-fodrin was detected in the cytoplasm of optic nerve glia.Conclusion. Complete labelling of retina structures was performed. As a result, IHC profiles of retinal neurons, optic nerve axons

  18. Behavioural and immunological responses to an immune challenge in Octopus vulgaris.

    Science.gov (United States)

    Locatello, Lisa; Fiorito, Graziano; Finos, Livio; Rasotto, Maria B

    2013-10-02

    Behavioural and immunological changes consequent to stress and infection are largely unexplored in cephalopods, despite the wide employment of species such as Octopus vulgaris in studies that require their manipulation and prolonged maintenance in captivity. Here we explore O. vulgaris behavioural and immunological (i.e. haemocyte number and serum lysozyme activity) responses to an in vivo immune challenge with Escherichia coli lipopolysaccharides (LPS). Behavioural changes of immune-treated and sham-injected animals were observed in both sight-allowed and isolated conditions, i.e. visually interacting or not with a conspecific. Immune stimulation primarily caused a significant increase in the number of circulating haemocytes 4h after the treatment, while serum lysozyme activity showed a less clear response. However, the effect of LPS on the circulating haemocytes begins to vanish 24h after injection. Our observations indicate a significant change in behaviour consequent to LPS administration, with treated octopuses exhibiting a decrease of general activity pattern when kept in the isolated condition. A similar decrease was not observed in the sight-allowed condition, where we noticed a specific significant reduction only in the time spent to visually interact with the conspecific. Overall, significant, but lower, behavioural and immunological effects of injection were detected also in sham-injected animals, suggesting a non-trivial susceptibility to manipulation and haemolymph sampling. Our results gain importance in light of changes of the regulations for the use of cephalopods in scientific procedures that call for the prompt development of guidelines, covering many aspects of cephalopod provision, maintenance and welfare. © 2013.

  19. Passive transfer of resistance and the site of immune-dependent elimination of the challenge infection in rats vaccinated with highly irradiated cercariae of Schistosoma mansoni

    International Nuclear Information System (INIS)

    Ford, M.J.; Bickle, Q.D.; Taylor, M.G.; Andrews, B.J.

    1984-01-01

    The immune-dependent elimination of a challenge infection in rats vaccinated with highly-irradiated cercariae of Schistosoma mansoni was analysed by passive transfer of serum, recovery of the challenge from the lungs and livers and by transferring lung-stage schistosomula. Recipients of serum from rats immunized with either unirradiated, 20 or 40 krad.-irradiated cercariae, were equally resistant if the serum was injected on the day of infection or 5-7 days after infection. Vaccinated rat serum transferred to mice and vaccinated rabbit serum transferred to rats conferred comparable protection when injected on day 0 or 5 days after infection of the recipients. This apparent susceptibility of the lung schistosomula to immune attack was confirmed by challenging 20 or 40 krad.-irradiated cercariae vaccinated rats with lung-stage schistosomula derived from mice or rats. All the detectable attrition of a cercarial challenge in vaccinated rats occurred between 7 and 10 days post-challenge, before the parasites reached the liver. Since there was no evidence of damage or attrition in the skin or lungs before day 7 it was concluded that immune-dependent elimination occurred rapidly following a 'window of sensitivity' coinciding with the migration of the parasites from the lungs to the liver. (author)

  20. Nasal Lipopolysaccharide Challenge and Cytokine Measurement Reflects Innate Mucosal Immune Responsiveness.

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    Jaideep Dhariwal

    Full Text Available Practical methods of monitoring innate immune mucosal responsiveness are lacking. Lipopolysaccharide (LPS is a component of the cell wall of Gram negative bacteria and a potent activator of Toll-like receptor (TLR-4. To measure LPS responsiveness of the nasal mucosa, we administered LPS as a nasal spray and quantified chemokine and cytokine levels in mucosal lining fluid (MLF.We performed a 5-way cross-over, single blind, placebo-controlled study in 15 healthy non-atopic subjects (n = 14 per protocol. Doses of ultrapure LPS (1, 10, 30 or 100μg/100μl or placebo were administered by a single nasal spray to each nostril. Using the recently developed method of nasosorption with synthetic adsorptive matrices (SAM, a series of samples were taken. A panel of seven cytokines/chemokines were measured by multiplex immunoassay in MLF. mRNA for intercellular cell adhesion molecule-1 (ICAM-1 was quantified from nasal epithelial curettage samples taken before and after challenge.Topical nasal LPS was well tolerated, causing no symptoms and no visible changes to the nasal mucosa. LPS induced dose-related increases in MLF levels of IL-1β, IL-6, CXCL8 (IL-8 and CCL3 (MIP-1α (AUC at 0.5 to 10h, compared to placebo, p<0.05 at 30 and 100μg LPS. At 100μg LPS, IL-10, IFN-α and TNF-α were also increased (p<0.05. Dose-related changes in mucosal ICAM-1 mRNA were also seen after challenge, and neutrophils appeared to peak in MLF at 8h. However, 2 subjects with high baseline cytokine levels showed prominent cytokine and chemokine responses to relatively low LPS doses (10μg and 30μg LPS.Topical nasal LPS causes dose-dependent increases in cytokines, chemokines, mRNA and cells. However, responsiveness can show unpredictable variations, possibly because baseline innate tone is affected by environmental factors. We believe that this new technique will have wide application in the study of the innate immune responses of the respiratory mucosa.Ultrapure LPS was used

  1. Hypoxia Stress Modifies Na+/K+-ATPase, H+/K+-ATPase, [Formula: see text], and nkaα1 Isoform Expression in the Brain of Immune-Challenged Air-Breathing Fish.

    Science.gov (United States)

    Peter, Mc Subhash; Simi, Satheesan

    2017-01-01

    Fishes are equipped to sense stressful stimuli and are able to respond to environmental stressor such as hypoxia with varying pattern of stress response. The functional attributes of brain to hypoxia stress in relation to ion transport and its interaction during immune challenge have not yet delineated in fish. We, therefore, explored the pattern of ion transporter functions and messenger RNA (mRNA) expression of α1-subunit isoforms of Na + /K + -ATPase (NKA) in the brain segments, namely, prosencephalon (PC), mesencephalon (MC), and metencephalon (MeC) in an obligate air-breathing fish exposed either to hypoxia stress (30 minutes forced immersion in water) or challenged with zymosan treatment (25-200 ng g -1 for 24 hours) or both. Zymosan that produced nonspecific immune responses evoked differential regulation of NKA, H + /K + -ATPase (HKA), and [Formula: see text] (NNA) in the varied brain segments. On the contrary, hypoxia stress that demanded activation of NKA in PC and MeC showed a reversed NKA activity pattern in MeC of immune-challenged fish. A compromised HKA and NNA regulation during hypoxia stress was found in immune-challenged fish, indicating the role of these brain ion transporters to hypoxia stress and immune challenges. The differential mRNA expression of α1-subunit isoforms of NKA, nkaα1a , nkaα1b , and nkaα1c , in hypoxia-stressed brain showed a shift in its expression pattern during hypoxia stress-immune interaction in PC and MC. Evidence is thus presented for the first time that ion transporters such as HKA and NNA along with NKA act as functional brain markers which respond differentially to both hypoxia stress and immune challenges. Taken together, the data further provide evidence for a differential Na + , K + , H + , and [Formula: see text] ion signaling that exists in brain neuronal clusters during hypoxia stress-immune interaction as a result of modified regulations of NKA, HKA, and NNA transporter functions and nkaα1 isoform

  2. Development of a Modular Assay for Detailed Immunophenotyping of Peripheral Human Whole Blood Samples by Multicolor Flow Cytometry

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    Paul F. Rühle

    2016-08-01

    Full Text Available The monitoring of immune cells gained great significance in prognosis and prediction of therapy responses. For analyzing blood samples, the multicolor flow cytometry has become the method of choice as it combines high specificity on single cell level with multiple parameters and high throughput. Here, we present a modular assay for the detailed immunophenotyping of blood (DIoB that was optimized for an easy and direct application in whole blood samples. The DIoB assay characterizes 34 immune cell subsets that circulate the peripheral blood including all major immune cells such as T cells, B cells, natural killer (NK cells, monocytes, dendritic cells (DCs, neutrophils, eosinophils, and basophils. In addition, it evaluates their functional state and a few non-leukocytes that also have been associated with the outcome of cancer therapy. This DIoB assay allows a longitudinal and close-meshed monitoring of a detailed immune status in patients requiring only 2.0 mL of peripheral blood and it is not restricted to peripheral blood mononuclear cells. It is currently applied for the immune monitoring of patients with glioblastoma multiforme (IMMO-GLIO-01 trial, NCT02022384, pancreatic cancer (CONKO-007 trial, NCT01827553, and head and neck cancer (DIREKHT trial, NCT02528955 and might pave the way for immune biomarker identification for prediction and prognosis of therapy outcome.

  3. Immune thrombocytopenia in two unrelated Fanconi anemia patients – a mere coincidence?

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    Anna eKarastaneva

    2015-06-01

    Full Text Available Thrombocytopenia and pancytopenia, occurring in patients with Fanconi anemia (FA, are interpreted either as progression to bone marrow failure or as developing myelodysplasia. On the other hand, immune thrombocytopenia (ITP represents an acquired and often self-limiting benign hematologic disorder, associated with peripheral, immune-mediated, platelet destruction requiring different management modalities than those used in congenital bone marrow failure syndromes, including FA. Here we describe the clinical course of two independent FA patients with atypical - namely immune - thrombocytopenia. While in one patient belonging to complementation group FA-A, the ITP started at 17 months of age and showed a chronically persisting course with severe purpura, responding well to intravenous immunoglobulins (IVIG and later also danazol, a synthetic androgen, the other patient (of complementation group FA-D2 had a self-limiting course that resolved after one administration of IVIG. No cytogenetic aberrations or bone marrow abnormalities other than FA-typical mild dysplasia were detected. Our data show that acute and chronic ITP may occur in FA patients and impose individual diagnostic and therapeutic challenges in this rare congenital bone marrow failure / tumor predisposition syndrome. The management and a potential context of immune pathogenesis with the underlying marrow disorder are discussed.

  4. Immune Thrombocytopenia in Two Unrelated Fanconi Anemia Patients – A Mere Coincidence?

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    Karastaneva, Anna; Lanz, Sofia; Wawer, Angela; Behrends, Uta; Schindler, Detlev; Dietrich, Ralf; Burdach, Stefan; Urban, Christian; Benesch, Martin; Seidel, Markus G.

    2015-01-01

    Thrombocytopenia and pancytopenia, occurring in patients with Fanconi anemia (FA), are interpreted either as progression to bone marrow failure or as developing myelodysplasia. On the other hand, immune thrombocytopenia (ITP) represents an acquired and often self-limiting benign hematologic disorder, associated with peripheral, immune-mediated, platelet destruction requiring different management modalities than those used in congenital bone marrow failure syndromes, including FA. Here, we describe the clinical course of two independent FA patients with atypical – namely immune – thrombocytopenia. While in one patient belonging to complementation group FA-A, the ITP started at 17 months of age and showed a chronically persisting course with severe purpura, responding well to intravenous immunoglobulins (IVIG) and later also danazol, a synthetic androgen, the other patient (of complementation group FA-D2) had a self-limiting course that resolved after one administration of IVIG. No cytogenetic aberrations or bone marrow abnormalities other than FA-typical mild dysplasia were detected. Our data show that acute and chronic ITP may occur in FA patients and impose individual diagnostic and therapeutic challenges in this rare congenital bone marrow failure/tumor predisposition syndrome. The management and a potential context of immune pathogenesis with the underlying marrow disorder are discussed. PMID:26106590

  5. Expression Analysis of Immune Related Genes Identified from the Coelomocytes of Sea Cucumber (Apostichopus japonicus in Response to LPS Challenge

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    Ying Dong

    2014-10-01

    Full Text Available The sea cucumber (Apostichopus japonicus occupies a basal position during the evolution of deuterostomes and is also an important aquaculture species. In order to identify more immune effectors, transcriptome sequencing of A. japonicus coelomocytes in response to lipopolysaccharide (LPS challenge was performed using the Illumina HiSeq™ 2000 platform. One hundred and seven differentially expressed genes were selected and divided into four functional categories including pathogen recognition (25 genes, reorganization of cytoskeleton (27 genes, inflammation (41 genes and apoptosis (14 genes. They were analyzed to elucidate the mechanisms of host-pathogen interactions and downstream signaling transduction. Quantitative real-time polymerase chain reactions (qRT-PCRs of 10 representative genes validated the accuracy and reliability of RNA sequencing results with the correlation coefficients from 0.88 to 0.98 and p-value <0.05. Expression analysis of immune-related genes after LPS challenge will be useful in understanding the immune response mechanisms of A. japonicus against pathogen invasion and developing strategies for resistant markers selection.

  6. MenTORing Immunity: mTOR Signaling in the Development and Function of Tissue-Resident Immune Cells.

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    Jones, Russell G; Pearce, Edward J

    2017-05-16

    Tissue-resident immune cells must balance survival in peripheral tissues with the capacity to respond rapidly upon infection or tissue damage, and in turn couple these responses with intrinsic metabolic control and conditions in the tissue microenvironment. The serine/threonine kinase mammalian/mechanistic target of rapamycin (mTOR) is a central integrator of extracellular and intracellular growth signals and cellular metabolism and plays important roles in both innate and adaptive immune responses. This review discusses the function of mTOR signaling in the differentiation and function of tissue-resident immune cells, with focus on the role of mTOR as a metabolic sensor and its impact on metabolic regulation in innate and adaptive immune cells. We also discuss the impact of metabolic constraints in tissues on immune homeostasis and disease, and how manipulating mTOR activity with drugs such as rapamycin can modulate immunity in these contexts. Copyright © 2017. Published by Elsevier Inc.

  7. The Effect of Cardiac Surgery on Peripheral Blood Lymphocyte Populations

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    Karolína Jankovičová

    2008-01-01

    Full Text Available Background: Cardiac surgery using cardiopulmonary bypass (CPB is associated with some adverse postoperative complications caused by an altered immune response. An alternative approach to cardiac surgery, operating without the use of CPB (i.e. off-pump surgery, seems to display less adverse impacts on the immune response. Patients and Methods: Peripheral blood lymphocytes in 40 patients undergoing cardiac surgery either with CPB (“on-pump” or without CPB (“off-pump” were followed using flow cytometry. The samples of peripheral blood were taken at five intervals: preoperatively, after termination of the surgery, on the first, on the third and on the seventh postoperative day, respectively. Results: The most substantial changes appeared on the first postoperative day in both subgroups of patients. While the percentage of both total T cells and CD4+ T cells were decreased, the percentage of HLA-DR+ activated lymphocytes was increased. These changes were more profound in the “on-pump” subgroup compared to the “off-pump” subgroup. Conclusion: Our results may suggest that the “off-pump” surgical approach reveals less adverse impact on adaptive immune responses.

  8. Sex-related effects of an immune challenge on growth and begging behavior of barn swallow nestlings.

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    Andrea Romano

    Full Text Available Parent-offspring conflicts lead the offspring to evolve reliable signals of individual quality, including parasite burden, which may allow parents to adaptively modulate investment in the progeny. Sex-related variation in offspring reproductive value, however, may entail differential investment in sons and daughters. Here, we experimentally manipulated offspring condition in the barn swallow (Hirundo rustica by subjecting nestlings to an immune challenge (injection with bacterial lipopolysaccharide, LPS that simulates a bacterial infection, and assessed the effects on growth, feather quality, expression of morphological (gape coloration and behavioral (posture begging displays involved in parent-offspring communication, as well as on food allocation by parents. Compared to sham-injected controls, LPS-treated chicks suffered a depression of body mass and a reduction of palate color saturation. In addition, LPS treatment resulted in lower feather quality, with an increase in the occurrence of fault bars on wing feathers. The color of beak flanges, feather growth and the intensity of postural begging were affected by LPS treatment only in females, suggesting that chicks of either sex are differently susceptible to the immune challenge. However, irrespective of the effects of LPS, parents equally allocated food among control and challenged offspring both under normal food provisioning and after a short period of food deprivation of the chicks. These results indicate that bacterial infection and the associated immune response entail different costs to offspring of either sex, but a decrease in nestling conditions does not affect parental care allocation, possibly because the barn swallow adopts a brood-survival strategy. Finally, we showed that physiological stress induced by pathogens impairs plumage quality, a previously neglected major negative impact of bacterial infection which could severely affect fitness, particularly among long

  9. Cold-Adapted Influenza and Recombinant Adenovirus Vaccines Induce Cross-Protective Immunity against pH1N1 Challenge in Mice

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    Soboleski, Mark R.; Gabbard, Jon D.; Price, Graeme E.; Misplon, Julia A.; Lo, Chia-Yun; Perez, Daniel R.; Ye, Jianqiang; Tompkins, S. Mark; Epstein, Suzanne L.

    2011-01-01

    Background The rapid spread of the 2009 H1N1 pandemic influenza virus (pH1N1) highlighted problems associated with relying on strain-matched vaccines. A lengthy process of strain identification, manufacture, and testing is required for current strain-matched vaccines and delays vaccine availability. Vaccines inducing immunity to conserved viral proteins could be manufactured and tested in advance and provide cross-protection against novel influenza viruses until strain-matched vaccines became available. Here we test two prototype vaccines for cross-protection against the recent pandemic virus. Methodology/Principal Findings BALB/c and C57BL/6 mice were intranasally immunized with a single dose of cold-adapted (ca) influenza viruses from 1977 or recombinant adenoviruses (rAd) expressing 1934 nucleoprotein (NP) and consensus matrix 2 (M2) (NP+M2-rAd). Antibodies against the M2 ectodomain (M2e) were seen in NP+M2-rAd immunized BALB/c but not C57BL/6 mice, and cross-reacted with pH1N1 M2e. The ca-immunized mice did not develop antibodies against M2e. Despite sequence differences between vaccine and challenge virus NP and M2e epitopes, extensive cross-reactivity of lung T cells with pH1N1 peptides was detected following immunization. Both ca and NP+M2-rAd immunization protected BALB/c and C57BL/6 mice against challenge with a mouse-adapted pH1N1 virus. Conclusion/Significance Cross-protective vaccines such as NP+M2-rAd and ca virus are effective against pH1N1 challenge within 3 weeks of immunization. Protection was not dependent on recognition of the highly variable external viral proteins and could be achieved with a single vaccine dose. The rAd vaccine was superior to the ca vaccine by certain measures, justifying continued investigation of this experimental vaccine even though ca vaccine is already available. This study highlights the potential for cross-protective vaccines as a public health option early in an influenza pandemic. PMID:21789196

  10. Reinfection immunity in schistosomiasis

    International Nuclear Information System (INIS)

    Kamiya, Haruo

    1987-01-01

    Schistosomiasis is one of the most important parasitic diseases in the world, especially in endemic areas of developing countries. This situation has prompted parasitologist to attempt intensive researches on immune mechanisms, especially those of reinfection immunity associated with eliminating challenge infection. The current knowledge of reinfection immunity against Schistosoma spp. infection was therefore reviewed briefly and discussed with special reference to our data on protective immune responses induced by radiation-attenuated cercarial infection. A recently developed technique of compressed organ autoradiography (COA) has contributed to assessing parasite attrition in immune animals following challenge infection. Our study using COA has demonstrated that major attrition of schistosomula from challenge infection occurs in the skin of CBA/Ca mice vaccinated with 20 Krad gamma radiation-attenuated cercariae of S. mansoni, while in both lungs and liver of similarly vaccinated guinea pig model. Furthermore, gamma-irradiation to cercariae affected their migration potential and surface-antigen profiles. The immunizing stimuli of gamma radiation-attenuated cercariae profoundly affected the expression of responsiveness in vaccinated animals. The change in antigenic profiles and migration potential of those vaccinating population was discussed in relation to the kinetics of reinfection immunity induced in vaccinated amimal models. These works might provide a base line data to develop a practical vaccine for schistosomiasis using defined antigens. It must be emphasized that these vaccines could serve as a practical prophylactic measure for schistosomiasis in the endemic areas, even if the vaccines fail to induce sterilizing immunity. (author). 141 refs

  11. rBCG30-induced immunity and cross-protection against Mycobacterium leprae challenge are enhanced by boosting with the Mycobacterium tuberculosis 30-kilodalton antigen 85B.

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    Gillis, Thomas P; Tullius, Michael V; Horwitz, Marcus A

    2014-09-01

    Leprosy remains a major global health problem and typically occurs in regions in which tuberculosis is endemic. Vaccines are needed that protect against both infections and do so better than the suboptimal Mycobacterium bovis BCG vaccine. Here, we evaluated rBCG30, a vaccine previously demonstrated to induce protection superior to that of BCG against Mycobacterium tuberculosis and Mycobacterium bovis challenge in animal models, for efficacy against Mycobacterium leprae challenge in a murine model of leprosy. rBCG30 overexpresses the M. tuberculosis 30-kDa major secretory protein antigen 85B, which is 85% homologous with the M. leprae homolog (r30ML). Mice were sham immunized or immunized intradermally with BCG or rBCG30 and challenged 2.5 months later by injection of viable M. leprae into each hind footpad. After 7 months, vaccine efficacy was assessed by enumerating the M. leprae bacteria per footpad. Both BCG and rBCG30 induced significant protection against M. leprae challenge. In the one experiment in which a comparison between BCG and rBCG30 was feasible, rBCG30 induced significantly greater protection than did BCG. Immunization of mice with purified M. tuberculosis or M. leprae antigen 85B also induced protection against M. leprae challenge but less so than BCG or rBCG30. Notably, boosting rBCG30 with M. tuberculosis antigen 85B significantly enhanced r30ML-specific immune responses, substantially more so than boosting BCG, and significantly augmented protection against M. leprae challenge. Thus, rBCG30, a vaccine that induces improved protection against M. tuberculosis, induces cross-protection against M. leprae that is comparable or potentially superior to that induced by BCG, and boosting rBCG30 with antigen 85B further enhances immune responses and protective efficacy. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  12. Hypoxia Stress Modifies Na+/K+-ATPase, H+/K+-ATPase, Na+/NH4+-ATPase, and nkaα1 Isoform Expression in the Brain of Immune-Challenged Air-Breathing Fish

    Science.gov (United States)

    Peter, MC Subhash; Simi, Satheesan

    2017-01-01

    Fishes are equipped to sense stressful stimuli and are able to respond to environmental stressor such as hypoxia with varying pattern of stress response. The functional attributes of brain to hypoxia stress in relation to ion transport and its interaction during immune challenge have not yet delineated in fish. We, therefore, explored the pattern of ion transporter functions and messenger RNA (mRNA) expression of α1-subunit isoforms of Na+/K+-ATPase (NKA) in the brain segments, namely, prosencephalon (PC), mesencephalon (MC), and metencephalon (MeC) in an obligate air-breathing fish exposed either to hypoxia stress (30 minutes forced immersion in water) or challenged with zymosan treatment (25-200 ng g−1 for 24 hours) or both. Zymosan that produced nonspecific immune responses evoked differential regulation of NKA, H+/K+-ATPase (HKA), and Na+/NH4+-ATPase (NNA) in the varied brain segments. On the contrary, hypoxia stress that demanded activation of NKA in PC and MeC showed a reversed NKA activity pattern in MeC of immune-challenged fish. A compromised HKA and NNA regulation during hypoxia stress was found in immune-challenged fish, indicating the role of these brain ion transporters to hypoxia stress and immune challenges. The differential mRNA expression of α1-subunit isoforms of NKA, nkaα1a, nkaα1b, and nkaα1c, in hypoxia-stressed brain showed a shift in its expression pattern during hypoxia stress-immune interaction in PC and MC. Evidence is thus presented for the first time that ion transporters such as HKA and NNA along with NKA act as functional brain markers which respond differentially to both hypoxia stress and immune challenges. Taken together, the data further provide evidence for a differential Na+, K+, H+, and NH4+ ion signaling that exists in brain neuronal clusters during hypoxia stress-immune interaction as a result of modified regulations of NKA, HKA, and NNA transporter functions and nkaα1 isoform regulation. PMID:29238219

  13. Pathophysiology of Chemotherapy-Induced Peripheral Neuropathy

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    Hana Starobova

    2017-05-01

    Full Text Available Chemotherapy-induced neuropathy is a common, dose-dependent adverse effect of several antineoplastics. It can lead to detrimental dose reductions and discontinuation of treatment, and severely affects the quality of life of cancer survivors. Clinically, chemotherapy-induced peripheral neuropathy presents as deficits in sensory, motor, and autonomic function which develop in a glove and stocking distribution due to preferential effects on longer axons. The pathophysiological processes are multi-factorial and involve oxidative stress, apoptotic mechanisms, altered calcium homeostasis, axon degeneration and membrane remodeling as well as immune processes and neuroinflammation. This review focusses on the commonly used antineoplastic substances oxaliplatin, cisplatin, vincristine, docetaxel, and paclitaxel which interfere with the cancer cell cycle—leading to cell death and tumor degradation—and cause severe acute and chronic peripheral neuropathies. We discuss drug mechanism of action and pharmacokinetic disposition relevant to the development of peripheral neuropathy, the epidemiology and clinical presentation of chemotherapy-induced neuropathy, emerging insight into genetic susceptibilities as well as current understanding of the pathophysiology and treatment approaches.

  14. Cross-immunity among allogeneic tumors in rats immunized with gamma-irradiated ascites tumors

    International Nuclear Information System (INIS)

    Sato, Tatsusuke; Suga, Michio; Kudo, Hajime; Waga, Takashi; Ogasawara, Masamichi

    1980-01-01

    Non-inbred rats of the Gifu strain were intraperitoneally challenged with Hirosaki sarcoma (Tetraploid type, 10 5 cells) after repeated immunization with gamma-irradiated (13,000 rads 60 Co) allogeneic non-viral tumors of ascites type (Tetraploid or diploid type of Hirosaki sarcoma, Usubuchi sarcoma or AH130). In rats immunized not only with the same tumor as the immunizing tumor but also with a different tumor, the growth of the challenge tumor was markedly inhibited as compared with the control in non-immunized rats. It is considered that these tumors retained common antigen(s) by the resistance to irradiation because of their form of ascites tumor. The marked cross-immunity in rats immunized with AH130 may be explained by the fact that gamma-irradiated AH130 cells were alive longer in the peritoneal cavity than other tumors on account of its high resistance to irradiation. (author)

  15. Atherectomy in Peripheral Artery Disease: A Review.

    Science.gov (United States)

    Bhat, Tariq M; Afari, Maxwell E; Garcia, Lawrence A

    2017-04-01

    Peripheral arterial disease (PAD) is a clinical manifestation of systemic atherosclerosis and is associated with significant morbidity and mortality. The physiological force and shear stress from angioplasty and stenting have made PAD treatment challenging. Atherectomy devices have continued to emerge as a major therapy in the management of peripheral vascular disease. This article presents a review of the current literature for the atherectomy devices used in PAD.

  16. JAK/STAT signaling pathway-mediated immune response in silkworm (Bombyx mori) challenged by Beauveria bassiana.

    Science.gov (United States)

    Geng, Tao; Lv, Ding-Ding; Huang, Yu-Xia; Hou, Cheng-Xiang; Qin, Guang-Xing; Guo, Xi-Jie

    2016-12-20

    Innate immunity was critical in insects defensive system and able to be induced by Janus kinase/signal transducer and activator of transcription cascade transduction (JAK/STAT) signaling pathway. Currently, it had been identified many JAK/STAT signaling pathway-related genes in silkworm, but little function was known on insect innate immunity. To explore the roles of JAK/STAT pathway in antifungal immune response in silkworm (Bombyx mori) against Beauveria bassiana infection, the expression patterns of B. mori C-type lectin 5 (BmCTL5) and genes encoding 6 components of JAK/STAT signaling pathway in silkworm challenged by B. bassiana were analyzed using quantitative real time PCR. Meanwhile the activation of JAK/STAT signaling pathway by various pathogenic micro-organisms and the affect of JAK/STAT signaling pathway inhibitors on antifungal activity in silkworm hemolymph was also detected. Moreover, RNAi assay of BmCTL5 and the affect on expression levels of signaling factors were also analyzed. We found that JAK/STAT pathway could be obviously activated in silkworm challenged with B. bassiana and had no response to bacteria and B. mori cytoplasmic polyhedrosis virus (BmCPV). However, the temporal expression patterns of JAK/STAT signaling pathway related genes were significantly different. B. mori downstream receptor kinase (BmDRK) might be a positive regulator of JAK/STAT signaling pathway in silkworm against B. bassiana infection. Moreover, antifungal activity assay showed that the suppression of JAK/STAT signaling pathway by inhibitors could significantly inhibit the antifungal activity in hemolymph and resulted in increased sensitivity of silkworm to B. bassiana infection, indicating that JAK/STAT signaling pathway might be involved in the synthesis and secretion of antifungal substances. The results of RNAi assays suggested that BmCTL5 might be one pattern recognition receptors for JAK/STAT signaling pathway in silkworm. These findings yield insights for better

  17. Brucella abortus ΔrpoE1 confers protective immunity against wild type challenge in a mouse model of brucellosis.

    Science.gov (United States)

    Willett, Jonathan W; Herrou, Julien; Czyz, Daniel M; Cheng, Jason X; Crosson, Sean

    2016-09-30

    The Brucella abortus general stress response (GSR) system regulates activity of the alternative sigma factor, σ(E1), which controls transcription of approximately 100 genes and is required for persistence in a BALB/c mouse chronic infection model. We evaluated the host response to infection by a B. abortus strain lacking σ(E1) (ΔrpoE1), and identified pathological and immunological features that distinguish ΔrpoE1-infected mice from wild-type (WT), and that correspond with clearance of ΔrpoE1 from the host. ΔrpoE1 infection was indistinguishable from WT in terms of splenic bacterial burden, inflammation and histopathology up to 6weeks post-infection. However, Brucella-specific serum IgG levels in ΔrpoE1-infected mice were 5 times higher than WT by 4weeks post-infection, and remained significantly higher throughout the course of a 12-week infection. Total IgG and Brucella-specific IgG levels peaked strongly in ΔrpoE1-infected mice at 6weeks, which correlated with reduced splenomegaly and bacterial burden relative to WT-infected mice. Given the difference in immune response to infection with wild-type and ΔrpoE1, we tested whether ΔrpoE1 confers protective immunity to wild-type challenge. Mice immunized with ΔrpoE1 completely resisted WT infection and had significantly higher serum titers of Brucella-specific IgG, IgG2a and IFN-γ after WT challenge relative to age-matched naïve mice. We conclude that immunization of BALB/c mice with the B. abortus GSR pathway mutant, ΔrpoE1, elicits an adaptive immune response that confers significant protective immunity against WT infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Prenatal Immune Challenge in Mice Leads to Partly Sex-Dependent Behavioral, Microglial, and Molecular Abnormalities Associated with Schizophrenia

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    Chin W. Hui

    2018-02-01

    Full Text Available Epidemiological studies revealed that environmental factors comprising prenatal infection are strongly linked to risk for later development of neuropsychiatric disorders such as schizophrenia. Considering strong sex differences in schizophrenia and its increased prevalence in males, we designed a methodological approach to investigate possible sex differences in pathophysiological mechanisms. Prenatal immune challenge was modeled by systemic administration of the viral mimic polyinosinic-polycytidylic acid (Poly I:C to C57BL/6 mice at embryonic day 9.5. The consequences on behavior, gene expression, and microglia—brain immune cells that are critical for normal development—were characterized in male vs. female offspring at adulthood. The cerebral cortex, hippocampus, and cerebellum, regions where structural and functional alterations were mainly described in schizophrenia patients, were selected for cellular and molecular analyses. Confocal and electron microscopy revealed most pronounced differences in microglial distribution, arborization, cellular stress, and synaptic interactions in the hippocampus of male vs. female offspring exposed to Poly I:C. Sex differences in microglia were also measured under both steady-state and Poly I:C conditions. These microglial alterations were accompanied by behavioral impairment, affecting for instance sensorimotor gating, in males. Consistent with these results, increased expression of genes related to inflammation was measured in cerebral cortex and hippocampus of males challenged with Poly I:C. Overall, these findings suggest that schizophrenia's higher incidence in males might be associated, among other mechanisms, with an increased microglial reactivity to prenatal immune challenges, hence determining disease outcomes into adulthood.

  19. Peripheral and placental immune responses in goats after primoinfection with Neospora caninum at early, mid and late gestation.

    Science.gov (United States)

    Porto, Wagnner José Nascimento; Horcajo, Pilar; Kim, Pomy de Cássia Peixoto; Regidor-Cerrillo, Javier; Romão, Elton Amorim; Álvarez-García, Gema; Mesquita, Emanuela Polimeni de; Mota, Rinaldo Aparecido; Ortega-Mora, Luis Miguel

    2017-08-15

    Neospora caninum can cause reproductive failure in goats. However, the pathogenesis of neosporosis in this domestic species remains largely unknown. We recently demonstrated that the outcome of experimental infection by N. caninum in pregnant goats is highly dependent on the time of gestation, during which infection occurs. In the present study, we examined the peripheral and placental immune responses in these groups of goats infected with 10 6 tachyzoites of the Nc-Spain7 isolate at early (G1, at day 40 of gestation, dg), mid (G2, 90 dg) and late (G3, 120 dg) gestation, together with a group of non-infected goats as a control group (G4). Seroconversion was observed as early as day 10 post-infection (pi) in all goats from G1 that aborted earlier (10-11 pi). The remaining infected goats had seroconverted by day 14 pi. Similar IFN-γ kinetic profiles were found in sera from goats in G1 and G2 with a significant increase in the IFN-γ levels on days 7 and 10 pi. This increase was not observed in G3. A similar pattern of placental cytokine expression was found in all infected groups. IFN-γ and IL-4 showed the highest increase, followed by a weaker up-regulation in TNF-α and IL-10. The lowest up-regulation was observed for IL-12 expression. In summary, this study provides information regarding the dynamics of immune responses and their relationship with the outcome of N. caninum infection in goats during gestation. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. PATHOGENESIS OF IMMUNE ALTERATIONS AND CORRECTIVE ROLE OF AMLODIPINE IN EXPERIMENTAL CHRONIC RENAL FAILURE

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    M. V. Osikov

    2016-01-01

    Full Text Available The purpose of this study was to assess some mechanisms of changes in immune state, and to evaluate a role of amlodipine, a known calcium channel blocker, as a potential corrective drug in experimental chronic renal failure (CRF. An animal CRF model was produced in rats by a two-stage operative resection of 5/6 of the renal tissue. Amlodipine is used per os at a daily dose of 0.25 mg/kg for 7 days. Flow cytofluorimetric approach was used to discern peripheral blood lymphocytes: CD3+ (mainly, T lymphocytes, CD45RA+ (mainly, B cells, as well as the following cell markers: Annexin 5-FITC+/7-AAD- (early apoptosis, Annexin 5-FITC+/7-AAD+ (late apoptosis and, in part, necrotic cells. Moreover, we have measured serum concentrations of urea, creatinine, phosphate, total calcium, parathyroid hormone (PTH, IL-1β, IL-4, interferon-γ, superoxide dismutase (SOD and catalase activities. Evaluation of Th1- and Th2-dependent immune response was carried out, respectively, by detection of delayed-type hypersensitivity, and scoring the antibody-forming cells in rat spleen induced by immunization with allogeneic erythrocytes. Primary, secondary and final products of lipid peroxidation were evaluated in lipid extracts from peripheral blood lymphocytes. Changes of immune state in CRF included depression of Th1 and Th2 dependent immune response, reduced number of lymphocytes bearing T and В cell markers, increased IL-1β concentrations in blood, along with decreased amounts of IFNγ and IL-4. Probable pathogenesis of the altered immune state may be associated with increased number of peripheral lymphocytes being at early and late stages of apoptosis/necrosis, elevated blood levels of IL-1β, total calcium, parathyroid hormone, reduced concentrations of IFNγ, and increased contents of primary, secondary and final peroxidation products in peripheral blood lymphocytes, being accompanied by inhibition of the SOD and catalase activity in blood plasma

  1. Interplay between behavioural thermoregulation and immune response in mealworms.

    Science.gov (United States)

    Catalán, Tamara P; Niemeyer, Hermann M; Kalergis, Alexis M; Bozinovic, Francisco

    2012-11-01

    Since the preferential body temperature should positively correlate with physiological performance, behavioural fever should enhance an organism's immune response under an immune challenge. Here we have studied the preferential body temperature (T(p)) and its consequences on immune response performance after an immune challenge in larvae of Tenebrio molitor. We evaluated T(p) and immune responses of larvae following a challenge with various concentrations of lipopolysaccharide (LPS), and we studied the correlation between T(p) and two immune traits, namely antibacterial and phenoloxidase (PO) activities. Larvae that were immune challenged with higher LPS concentrations (C(50) and C(100)) preferred in average, warmer temperatures than did larvae challenged with lower concentrations (C(0) and C(25)). T(p) of C(25)-C(100) (challenged)-mealworms was 2.3°C higher than of C(0) (control) larvae. At lower LPS concentration immune challenge (C(0) and C(25)) antibacterial activity correlated positively with T(p), but at C(50) and C(100) correlation was lose. PO activity was higher at higher LPS concentration, but its magnitude of response did not correlate with T(p) Our data suggest that behavioural fever may have a positive effect on host performance by enhancing antibacterial response under a low pathogen load situation. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. LOCAL IMMUNITY BY TISSUE-RESIDENT CD8+ MEMORY T CELLS

    Directory of Open Access Journals (Sweden)

    Thomas eGebhardt

    2012-11-01

    Full Text Available Microbial infection primes a CD8+ cytotoxic T cell response that gives rise to a long-lived population of circulating memory cells able to provide protection against systemic reinfection. Despite this, effective CD8+ T cell surveillance of barrier tissues such as skin and mucosa typically wanes with time, resulting in limited T cell-mediated protection in these peripheral tissues. However, recent evidence suggests that a specialized subset of CD103+ memory T cells can permanently lodge and persist in peripheral tissues, and that these cells can compensate for the loss of peripheral immune surveillance by circulating memory T cells. Here, we review evolving concepts regarding the generation and long-term persistence of these tissue-resident memory T cells (TRM in epithelial and neuronal tissues. We further discuss the role of TRM cells in local infection control and their contribution to localized immune phenomena, in both mice and humans.

  3. Heterosybtypic T-cell immunity to influenza in humans: challenges for universal T-cell influenza vaccines

    Directory of Open Access Journals (Sweden)

    Saranya eSridhar

    2016-05-01

    Full Text Available Influenza A virus (IAV remains a significant global health issue causing annual epidemics, pandemics and sporadic human infections with highly pathogenic avian or swine influenza viruses. Current inactivated and live vaccines are the mainstay of the public health response to influenza although vaccine efficacy is lower against antigenically distinct viral strains. The first pandemic of the 21st century underlined the urgent need to develop new vaccines capable of protection against a broad range of influenza strains. Such universal influenza vaccines are based on the idea of heterosubtypic immunity wherein immune responses to epitopes conserved across IAV strains can confer protection against subsequent infection and disease. T-cells recognising conserved antigens are a key contributor to reducing viral load and limiting disease severity during heterosubtypic infection in animal models. Recent studies undertaken during the 2009 H1N1 pandemic provided key insights into the role of cross-reactive T-cells in mediating heterosubtypic protection in humans. This review focuses on human influenza to discuss the epidemiological observations that underpin cross-protective immunity, the role of T-cells as key players in mediating heterosubtypic immunity including recent data from natural history cohort studies and the ongoing clinical development of T-cell inducing universal influenza vaccines. The challenges and knowledge gaps for developing vaccines to generate long-lived protective T-cell responses is discussed.

  4. The immune system strikes back: cellular immune responses against indoleamine 2,3-dioxygenase

    DEFF Research Database (Denmark)

    Sørensen, Rikke Baek; Berge-Hansen, Linda; Junker, Niels

    2009-01-01

    BACKGROUND: The enzyme indoleamine 2,3-dioxygenase (IDO) exerts an well established immunosuppressive function in cancer. IDO is expressed within the tumor itself as well as in antigen-presenting cells in tumor-draining lymph nodes, where it promotes the establishment of peripheral immune tolerance...... to tumor antigens. In the present study, we tested the notion whether IDO itself may be subject to immune responses. METHODS AND FINDINGS: The presence of naturally occurring IDO-specific CD8 T cells in cancer patients was determined by MHC/peptide stainings as well as ELISPOT. Antigen specific cytotoxic T...... of the major immune suppressive cell populations. CONCLUSION: IDO may serve as an important and widely applicable target for anti-cancer immunotherapeutic strategies. Furthermore, as emerging evidence suggests that IDO constitutes a significant counter-regulatory mechanism induced by pro-inflammatory signals...

  5. On Modelling an Immune System

    OpenAIRE

    Monroy, Raúl; Saab, Rosa; Godínez, Fernando

    2004-01-01

    Immune systems of live forms have been an abundant source of inspiration to contemporary computer scientists. Problem solving strategies, stemming from known immune system phenomena, have been successfully applied to challenging problems of modern computing. However, research in artificial immune systems has overlooked establishing a coherent model of known immune system behaviour. This paper aims reports on an preliminary computer model of an immune system, where each immune system component...

  6. Blockade of the voltage-gated potassium channel Kv1.3 inhibits immune responses in vivo.

    Science.gov (United States)

    Koo, G C; Blake, J T; Talento, A; Nguyen, M; Lin, S; Sirotina, A; Shah, K; Mulvany, K; Hora, D; Cunningham, P; Wunderler, D L; McManus, O B; Slaughter, R; Bugianesi, R; Felix, J; Garcia, M; Williamson, J; Kaczorowski, G; Sigal, N H; Springer, M S; Feeney, W

    1997-06-01

    The voltage activated K+ channel (Kv1.3) has recently been identified as the molecule that sets the resting membrane potential of peripheral human T lymphoid cells. In vitro studies indicate that blockage of Kv1.3 inhibits T cell activation, suggesting that Kv1.3 may be a target for immunosuppression. However, despite the in vitro evidence, there has been no in vivo demonstration that blockade of Kv1.3 will attenuate an immune response. The difficulty is due to species differences, as the channel does not set the membrane potential in rodent peripheral T cells. In this study, we show that the channel is present on peripheral T cells of miniswine. Using the peptidyl Kv1.3 inhibitor, margatoxin, we demonstrate that Kv1.3 also regulates the resting membrane potential, and that blockade of Kv1.3 inhibits, in vivo, both a delayed-type hypersensitivity reaction and an Ab response to an allogeneic challenge. In addition, prolonged Kv1.3 blockade causes reduced thymic cellularity and inhibits the thymic development of T cell subsets. These results provide in vivo evidence that Kv1.3 is a novel target for immunomodulation.

  7. Immunization of Mice with Anthrax Protective Antigen Limits Cardiotoxicity but Not Hepatotoxicity Following Lethal Toxin Challenge

    Directory of Open Access Journals (Sweden)

    T. Scott Devera

    2015-06-01

    Full Text Available Protective immunity against anthrax is inferred from measurement of vaccine antigen-specific neutralizing antibody titers in serum samples. In animal models, in vivo challenges with toxin and/or spores can also be performed. However, neither of these approaches considers toxin-induced damage to specific organ systems. It is therefore important to determine to what extent anthrax vaccines and existing or candidate adjuvants can provide organ-specific protection against intoxication. We therefore compared the ability of Alum, CpG DNA and the CD1d ligand α-galactosylceramide (αGC to enhance protective antigen-specific antibody titers, to protect mice against challenge with lethal toxin, and to block cardiotoxicity and hepatotoxicity. By measurement of serum cardiac Troponin I (cTnI, and hepatic alanine aminotransferase (ALT, and aspartate aminotransferase (AST, it was apparent that neither vaccine modality prevented hepatic intoxication, despite high Ab titers and ultimate survival of the subject. In contrast, cardiotoxicity was greatly diminished by prior immunization. This shows that a vaccine that confers survival following toxin exposure may still have an associated morbidity. We propose that organ-specific intoxication should be monitored routinely during research into new vaccine modalities.

  8. Cost-effectiveness of rotavirus immunization in Vietnam: Results and challenges

    NARCIS (Netherlands)

    Tu, H.A.T.; Rozenbaum, M.; Coyte, P.C.; Li, S.C.; Postma, M.J.

    2011-01-01

    OBJECTIVES: To assess the cost-effectiveness of universal rotavirus immunization, explicitly the use of Rotateq® and affordability of implementing rotavirus immunization based on the Global Alliance for Vaccines and Immunization (GAVI)-subsidized vaccine price in the context of Vietnamese health

  9. Peripheral Lymphoid Volume Expansion and Maintenance Are Controlled by Gut Microbiota via RALDH+ Dendritic Cells.

    Science.gov (United States)

    Zhang, Zongde; Li, Jianjian; Zheng, Wencheng; Zhao, Guang; Zhang, Hong; Wang, Xiaofei; Guo, Yaqian; Qin, Chuan; Shi, Yan

    2016-02-16

    Lymphocyte homing to draining lymph nodes is critical for the initiation of immune responses. Secondary lymphoid organs of germ-free mice are underdeveloped. How gut commensal microbes remotely regulate cellularity and volume of secondary lymphoid organs remains unknown. We report here that, driven by commensal fungi, a wave of CD45(+)CD103(+)RALDH(+) cells migrates to the peripheral lymph nodes after birth. The arrival of these cells introduces high amounts of retinoic acid, mediates the neonatal to adult addressin switch on endothelial cells, and directs the homing of lymphocytes to both gut-associated lymphoid tissues and peripheral lymph nodes. In adult mice, a small number of these RALDH(+) cells might serve to maintain the volume of secondary lymphoid organs. Homing deficiency of these cells was associated with lymph node attrition in vitamin-A-deficient mice, suggesting a perpetual dependence on retinoic acid signaling for structural and functional maintenance of peripheral immune organs. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. MAJOR AND LYMPHOCYTE POPULATIONS OF HUMAN PERIPHERAL BLOOD LYMPHOCYTES AND THEIR REFERENCE VALUES, AS ASSAYED BY MULTI-COLOUR CYTOMETRY

    Directory of Open Access Journals (Sweden)

    S. V. Khaidukov

    2009-01-01

    Full Text Available Abstract. Determination of lymphocyte subpopulations and their phenotypes is an important diagnostic feature, in order to elucidate some disturbances connected with immune system functioning. However, insufficient data are obtained when analyzing only major populations of peripheral lymphocytes. In order to perform clinical diagnostics, the data about minor lymphocytic populations and activated cellular pools seem to be more pertinent.Studies of peripheral blood cell subpopulations of healthy donors performed in different Russian regions allowed to assess quantitative distribution intervals for both major and minor immune cell subpopulations in humans. The results obtained, as compared with data from literature, provide an evidence for similar reference intervals for main immune cell subpopulations in healthy donors, independent on their habitation area.Present work has resulted into development of algorithms for cytometric studies and generation of certain panels of monoclonal antibodies enabling evaluation of all main lymphocyte subpopulations, as well as their minor subsets participating in emerging immune response. The distribution intervals have been estimated for such minor subpopulations, as B1- and B2-lymphocytes, memory B-cells, γδ- and αβT-cells, regulatory and naїve T-cells, cytotoxic and secretory NK-cell polupations.The results of present study, while been performed with peripheral blood of healthy donors, may provide a basis of reference values when studying subpopulation profile of immune cells.

  11. [Change of CD4(+) CD25(+) regulatory T cells and NK Cells in peripheral blood of children with acute leukemia and its possible significance in tumor immunity].

    Science.gov (United States)

    Wu, Ze-Lin; Hu, Guan-Yu; Chen, Fu-Xiong; Lu, Hui-Min; Wu, Zi-Liang; Li, Hua-Mei; Wei, Feng-Gui; Guan, Jing-Ming; Wu, Li-Ping

    2010-06-01

    This study was purposed to investigate the changes of CD4(+) CD25(+) regulatory T cells and NK cells in peripheral blood of acute leukemia children at different stages, the function of immune system and the possible roles of the CD4(+) CD25(+) regulatory T cells as well as NK cells in leukemia immunity. The number and proportion of CD4(+) CD25(+) regulatory T cells and NK cells were detected by flow cytometry in the peripheral blood of 53 acute leukemia children, including 25 patients in new diagnosis and 28 patients in continuous complete remission (CCR), and were compared with that of 20 normal children. The results indicated that the mean proportion of CD4(+) CD25(+) CD127(+) in CD4(+) T cells of peripheral blood in newly diagnosed patients, patients with CCR and normal children were (9.55 +/- 2.41)%, (8.54 +/- 2.51)% and (6.25 +/- 0.85)% respectively, the mean proportions of CD4(+)CD25(+)CD127(+) in newly diagnosed patients and patients with CCR were higher than that in normal children, the mean proportion of CD4(+)CD25(+)CD127(+) in newly diagnosed patients were higher than that in patients with CCR (p cell count in patients with acute leukaemia decreased as compared with normal control, while after achieving CCR, the NK cell count in patients were also less than that in normal control (4.11 +/- 3.87% and 10.41 +/- 7.20% vs 14.06 +/- 5.95%, p regulatory T cells is a simple, reproductive and accurate method, and the CD4(+) CD25(+) CD127(+) T cells can better reflect the proportion of CD4(+)CD25(+) regulatory T cells. The increase of regulatory T cells and decrease of NK cells in pediatric patients with acute leukemia indicate that the function of NK cells may be depressed. Treg T cells play a role in occurrence and development of leukemia, and are involved in down-regulating NK cell function.

  12. Immunity to transplantable nitrosourea-induced neurogenic tumors. III. Systemic adoptive transfer of immunity

    International Nuclear Information System (INIS)

    Shibuya, N.; Hochgeschwender, U.; Kida, Y.; Hochwald, G.M.; Thorbecke, G.J.; Cravioto, H.

    1984-01-01

    The effect of intravenously injected tumor immune spleen cells on growth of 3 X 10 5 gliosarcoma T 9 cells injected intradermally (ID) or intracerebrally (IC) into sublethally irradiated CDF rats was evaluated. Spleen cells from donor rats with sufficient immunity to reject 5 X 10 5 T 9 cells inhibited the growth of T 9 cells mixed with spleen cells in a ratio of 1:25 and injected ID, but could not act after intravenous transfer. However, donor rats which had rejected increasing T 9 challenge doses up to 1 X 10 7 cells produced immune spleen cells which, upon IV transfer, could inhibit growth of ID T 9 challenge but not of EB-679, an unrelated glioma, in recipient rats. Rejection of IC T 9 challenge was also obtained after IV transfer, in recipients of such ''hyperimmune'' spleen cells, but was less (60% maximum) than that noted after ID T 9 challenge (100% maximum). The removal of B cells from the transferred spleen cells did not affect the results, suggesting that the specific immunity was mediated by T cells. The authors conclude that the special immunological circumstances of tumors growing in the brain renders them less accessible to rejection by systemically transferred immune cells, but it is nevertheless possible to effect a significant incidence of rejection of syngeneic tumor growth in the brain by the intravenous transfer of hyperimmune spleen cells

  13. Demographic processes of developmentally peripheral areas in Hungary

    Directory of Open Access Journals (Sweden)

    Pénzes János

    2015-01-01

    Full Text Available The current study investigates the demographic processes and challenges of the Hungarian developmentally peripheral settlements. Demographic challenges can be regarded as important consequences of the social and economic disadvantages in spatial terms. However, the interrelating negative demographic tendencies cause even more backward situation blocking or hindering the development. The objective of the current analysis is to discover the demographic characteristics of the peripheral settlements, to detect the spatial disparities and to point out the correlation between backwardness and the investigated demographic phenomena with the help of the census databases 1980-2011 and local datasets on Roma population. Using methods of multivariate statistical analysis, seven indicators were selected in order to achieve the goals of the paper. Backward areas are primarily characterized by population decrease with significant disparities, but there were growing communities among them as well. Some small villages in Northern and Southwestern Hungary will foreseeably face complete depopulation within few years. Primarily small sized villages faced intense decrease in rate of natural change, but dynamic population growth was also detected. Migration loss tends to correlate with the extent of peripherality, as increasing values of migration balance accompany decreasing ratio of peripheral settlements in the area. The ratio of elderly population shows an expressively two-faced character, with the extremely aging and very juvenile settlements. The ratios of Roma population reflect the scale of peripherality. Extended ethnic change could be predicted in Northeastern and Southwestern Hungary and near the Middle Tisza valley. Presented demographic processes will make the backwardness of most of the peripheral settlements stable.

  14. Roles of neural stem cells in the repair of peripheral nerve injury.

    Science.gov (United States)

    Wang, Chong; Lu, Chang-Feng; Peng, Jiang; Hu, Cheng-Dong; Wang, Yu

    2017-12-01

    Currently, researchers are using neural stem cell transplantation to promote regeneration after peripheral nerve injury, as neural stem cells play an important role in peripheral nerve injury repair. This article reviews recent research progress of the role of neural stem cells in the repair of peripheral nerve injury. Neural stem cells can not only differentiate into neurons, astrocytes and oligodendrocytes, but can also differentiate into Schwann-like cells, which promote neurite outgrowth around the injury. Transplanted neural stem cells can differentiate into motor neurons that innervate muscles and promote the recovery of neurological function. To promote the repair of peripheral nerve injury, neural stem cells secrete various neurotrophic factors, including brain-derived neurotrophic factor, fibroblast growth factor, nerve growth factor, insulin-like growth factor and hepatocyte growth factor. In addition, neural stem cells also promote regeneration of the axonal myelin sheath, angiogenesis, and immune regulation. It can be concluded that neural stem cells promote the repair of peripheral nerve injury through a variety of ways.

  15. Treatment of painful diabetic peripheral neuropathy.

    Science.gov (United States)

    Rosenberg, Casandra J; Watson, James C

    2015-02-01

    Painful diabetic peripheral neuropathy impairs quality of life and can be difficult to treat. To discuss current treatment recommendations for painful diabetic peripheral neuropathy. Literature review. Systematic review of the literature discussing treatment of painful diabetic peripheral neuropathy. Existing treatment guidelines were studied and compared. Painful diabetic peripheral neuropathy occurs in about one in six people with diabetes. This condition impairs quality of life and increases healthcare costs. Treatment recommendations exist, but individual patient therapy can require a trial-and-error approach. Many treatment options have adjuvant benefits or side effects which should be considered prior to initiating therapy. Often, a combination of treatment modalities with various mechanisms of action is required for adequate pain control. Adequate medication titration and a reasonable trial period should be allowed. The treatment of painful diabetic peripheral neuropathy can be challenging, but effective management can improve patient's quality of life. Painful diabetic peripheral neuropathy impairs quality of life and can be difficult to treat. Many treatment options have adjuvant benefits or side effects which should be considered prior to initiating therapy. Often, a combination of treatment modalities with various mechanisms of action is required for adequate pain control. © The International Society for Prosthetics and Orthotics 2014.

  16. Immunization with tegument nucleotidases associated with a subcurative praziquantel treatment reduces worm burden following Schistosoma mansoni challenge

    Directory of Open Access Journals (Sweden)

    Henrique K. Rofatto

    2013-04-01

    Full Text Available Schistosomiasis is a debilitating disease caused by flatworm parasites of the Schistosoma genus and remains a high public health impact disease around the world, although effective treatment with Praziquantel (PZQ has been available since the 1970s. Control of this disease would be greatly improved by the development of a vaccine, which could be combined with chemotherapy. The sequencing of the Schistosoma mansoni transcriptome and genome identified a range of potential vaccine antigens. Among these, three nucleotidases from the tegument of the parasite, presumably involved in purinergic signaling and nucleotide metabolism, were proposed as promising vaccine candidates: an alkaline phosphatase (SmAP, a phosphodiesterase (SmNPP-5 and a diphosphohydrolase (SmNTPDase. Herein, we evaluate the potential of these enzymes as vaccine antigens, with or without subcurative PZQ treatment. Immunization of mice with the recombinant proteins alone or in combination demonstrated that SmAP is the most immunogenic of the three. It induced the highest antibody levels, particularly IgG1, associated with an inflammatory cellular immune response characterized by high TNF-α and a Th17 response, with high IL-17 expression levels. Despite the specific immune response induced, immunization with the isolated or combined proteins did not reduce the worm burden of challenged mice. Nonetheless, immunization with SmAP alone or with the three proteins combined, together with subcurative PZQ chemotherapy was able to reduce the worm burden by around 40%. The immunogenicity and relative exposure of SmAP to the host immune system are discussed, as key factors involved in the apparently synergistic effect of SmAP immunization and subcurative PZQ treatment.

  17. Merck Ad5/HIV induces broad innate immune activation that predicts CD8⁺ T-cell responses but is attenuated by preexisting Ad5 immunity.

    Science.gov (United States)

    Zak, Daniel E; Andersen-Nissen, Erica; Peterson, Eric R; Sato, Alicia; Hamilton, M Kristina; Borgerding, Joleen; Krishnamurty, Akshay T; Chang, Joanne T; Adams, Devin J; Hensley, Tiffany R; Salter, Alexander I; Morgan, Cecilia A; Duerr, Ann C; De Rosa, Stephen C; Aderem, Alan; McElrath, M Juliana

    2012-12-11

    To better understand how innate immune responses to vaccination can lead to lasting protective immunity, we used a systems approach to define immune signatures in humans over 1 wk following MRKAd5/HIV vaccination that predicted subsequent HIV-specific T-cell responses. Within 24 h, striking increases in peripheral blood mononuclear cell gene expression associated with inflammation, IFN response, and myeloid cell trafficking occurred, and lymphocyte-specific transcripts decreased. These alterations were corroborated by marked serum inflammatory cytokine elevations and egress of circulating lymphocytes. Responses of vaccinees with preexisting adenovirus serotype 5 (Ad5) neutralizing antibodies were strongly attenuated, suggesting that enhanced HIV acquisition in Ad5-seropositive subgroups in the Step Study may relate to the lack of appropriate innate activation rather than to increased systemic immune activation. Importantly, patterns of chemoattractant cytokine responses at 24 h and alterations in 209 peripheral blood mononuclear cell transcripts at 72 h were predictive of subsequent induction and magnitude of HIV-specific CD8(+) T-cell responses. This systems approach provides a framework to compare innate responses induced by vectors, as shown here by contrasting the more rapid, robust response to MRKAd5/HIV with that to yellow fever vaccine. When applied iteratively, the findings may permit selection of HIV vaccine candidates eliciting innate immune response profiles more likely to drive HIV protective immunity.

  18. Equine peripheral blood mononuclear cells proliferate in response to tetanus toxoid antigen.

    Science.gov (United States)

    McKelvie, J; Little, S; Foster, A P; Cunningham, F M; Hamblin, A

    1998-01-01

    It has been reported that equine peripheral blood mononuclear cells (PBMNs) do not proliferate in response to tetanus toxoid (TT) (Frayne and Stokes 1995, Research in Veterinary Science 59, 79-81). Here we demonstrate that lymphocyte proliferation responses to TT, which are characteristic of a recall antigen, may be achieved under certain culture conditions. Given that TT vaccination is routinely applied to many horses, TT is a suitable antigen for the investigation of cellular immune responses by peripheral blood mononuclear cells in the horse.

  19. Low Dose Ionizing Radiation Modulates Immune Function

    International Nuclear Information System (INIS)

    Nelson, Gregory A.

    2016-01-01

    In order to examine the effects of low dose ionizing radiation on the immune system we chose to examine an amplified adaptive cellular immunity response. This response is Type IV delayed-type hypersensitivity also called contact hypersensitivity. The agent fluorescein isothiocyanate (FITC) is a low molecular weight, lipophilic, reactive, fluorescent molecule that can be applied to the skin where it (hapten) reacts with proteins (carriers) to become a complete antigen. Exposure to FITC leads to sensitization which is easily measured as a hypersensitivity inflammatory reaction following a subsequent exposure to the ear. Ear swelling, eosinophil infiltration, immunoglobulin E production and cytokine secretion patterns characteristic of a 'Th2 polarized' immune response are the components of the reaction. The reaction requires successful implementation of antigen processing and presentation by antigen presenting Langerhans cells, communication with naïve T lymphocytes in draining lymph nodes, expansion of activated T cell clones, migration of activated T cells to the circulation, and recruitment of memory T cells, macrophages and eosinophils to the site of the secondary challenge. Using this model our approach was to quantify system function rather than relying only on indirect biomarkers of cell. We measured the FITC-induced hypersensitivity reaction over a range of doses from 2 cGy to 2 Gy. Irradiations were performed during key events or prior to key events to deplete critical cell populations. In addition to quantifying the final inflammatory response, we assessed cell populations in peripheral blood and spleen, cytokine signatures, IgE levels and expression of genes associated with key processes in sensitization and elicitation/recall. We hypothesized that ionizing radiation would produce a biphasic effect on immune system function resulting in an enhancement at low doses and a depression at higher doses and suggested that this transition would occur in

  20. Low Dose Ionizing Radiation Modulates Immune Function

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, Gregory A. [Loma Linda Univ., CA (United States)

    2016-01-12

    In order to examine the effects of low dose ionizing radiation on the immune system we chose to examine an amplified adaptive cellular immunity response. This response is Type IV delayed-type hypersensitivity also called contact hypersensitivity. The agent fluorescein isothiocyanate (FITC) is a low molecular weight, lipophilic, reactive, fluorescent molecule that can be applied to the skin where it (hapten) reacts with proteins (carriers) to become a complete antigen. Exposure to FITC leads to sensitization which is easily measured as a hypersensitivity inflammatory reaction following a subsequent exposure to the ear. Ear swelling, eosinophil infiltration, immunoglobulin E production and cytokine secretion patterns characteristic of a “Th2 polarized” immune response are the components of the reaction. The reaction requires successful implementation of antigen processing and presentation by antigen presenting Langerhans cells, communication with naïve T lymphocytes in draining lymph nodes, expansion of activated T cell clones, migration of activated T cells to the circulation, and recruitment of memory T cells, macrophages and eosinophils to the site of the secondary challenge. Using this model our approach was to quantify system function rather than relying only on indirect biomarkers of cell. We measured the FITC-induced hypersensitivity reaction over a range of doses from 2 cGy to 2 Gy. Irradiations were performed during key events or prior to key events to deplete critical cell populations. In addition to quantifying the final inflammatory response, we assessed cell populations in peripheral blood and spleen, cytokine signatures, IgE levels and expression of genes associated with key processes in sensitization and elicitation/recall. We hypothesized that ionizing radiation would produce a biphasic effect on immune system function resulting in an enhancement at low doses and a depression at higher doses and suggested that this transition would occur in the

  1. Mechanisms of protective immunity against Schistosoma mansoni infection in mice vaccinated with irradiated cercariae. V. Anamnestic cellular and humoral responses following challenge infection

    International Nuclear Information System (INIS)

    Correa-Oliveira, R.; Sher, A.; James, S.L.

    1984-01-01

    Mice vaccinated with radiation-attenuated cercariae display low levels of cellular and humoral immune responses toward schistosomulum antigens, as measured in vitro by lymphocyte blastogenesis and quantitation of anti-larval antibodies by indirect immunofluorescence. Both responses wane with time after vaccination. However subsequent challenge infection provokes immune responses of classical anamnestic character, being both more rapid in appearance and of greater magnitude. Antigen responsive cells appear in lymph nodes draining the challenge site within 24 hours after infection. Both circulating anti-schistosomulum surface antibodies as well as cytophilic IgE anti-worm antigen antibodies increase substantially by 1 week after challenge. All of the anamnestic circulating antibodies belong to the IgG class. Those findings support the concept that vaccine-induced resistance to Schistosoma mansoni infection involves sensitized T and B lymphocytes, and point to the possible role of post-challenge anamnestic responses in the effector mechanism of parasite killing in this model

  2. The role of complement in cnidarian-dinoflagellate symbiosis and immune challenge in the sea anemone Aiptasia pallida

    Directory of Open Access Journals (Sweden)

    Angela ePoole

    2016-04-01

    Full Text Available The complement system is an innate immune pathway that in vertebrates, is responsible for initial recognition and ultimately phagocytosis and destruction of microbes. Several complement molecules including C3, Factor B, and mannose binding lectin associated serine proteases (MASP have been characterized in invertebrates and while most studies have focused on their conserved role in defense against pathogens, little is known about their role in managing beneficial microbes. The purpose of this study was to (1 characterize complement pathway genes in the symbiotic sea anemone A. pallida, (2 investigate the evolution of complement genes in invertebrates, and (3 examine the potential dual role of complement genes Factor B and MASP in the onset and maintenance of cnidarian-dinoflagellate symbiosis and immune challenge using qPCR based studies. The results demonstrate that A. pallida has multiple Factor B genes (Ap_Bf-1, Ap_Bf-2a, and Ap_Bf-2b and one MASP gene (Ap_MASP. Phylogenetic analysis indicates that the evolutionary history of complement genes is complex, and there have been many gene duplications or gene loss events, even within members of the same phylum. Gene expression analyses revealed a potential role for complement in both onset and maintenance of cnidarian-dinoflagellate symbiosis and immune challenge. Specifically, Ap_Bf-1 and Ap_MASP are significantly upregulated in the light at the onset of symbiosis and in response to challenge with the pathogen Serratia marcescens suggesting that they play a role in the initial recognition of both beneficial and harmful microbes. Ap_Bf-2b in contrast was generally downregulated during the onset and maintenance of symbiosis and in response to challenge with S. marcescens. Therefore the exact role of Ap_Bf-2b in response to microbes remains unclear, but the results suggests that the presence of microbes leads to repressed expression. Together these results indicate functional divergence between Ap

  3. Longitudinal peripheral blood transcriptional analysis of a patient with severe Ebola virus disease.

    Science.gov (United States)

    Kash, John C; Walters, Kathie-Anne; Kindrachuk, Jason; Baxter, David; Scherler, Kelsey; Janosko, Krisztina B; Adams, Rick D; Herbert, Andrew S; James, Rebekah M; Stonier, Spencer W; Memoli, Matthew J; Dye, John M; Davey, Richard T; Chertow, Daniel S; Taubenberger, Jeffery K

    2017-04-12

    The 2013-2015 outbreak of Ebola virus disease in Guinea, Liberia, and Sierra Leone was unprecedented in the number of documented cases, but there have been few published reports on immune responses in clinical cases and their relationships with the course of illness and severity of Ebola virus disease. Symptoms of Ebola virus disease can include severe headache, myalgia, asthenia, fever, fatigue, diarrhea, vomiting, abdominal pain, and hemorrhage. Although experimental treatments are in development, there are no current U.S. Food and Drug Administration-approved vaccines or therapies. We report a detailed study of host gene expression as measured by microarray in daily peripheral blood samples collected from a patient with severe Ebola virus disease. This individual was provided with supportive care without experimental therapies at the National Institutes of Health Clinical Center from before onset of critical illness to recovery. Pearson analysis of daily gene expression signatures revealed marked gene expression changes in peripheral blood leukocytes that correlated with changes in serum and peripheral blood leukocytes, viral load, antibody responses, coagulopathy, multiple organ dysfunction, and then recovery. This study revealed marked shifts in immune and antiviral responses that preceded changes in medical condition, indicating that clearance of replicating Ebola virus from peripheral blood leukocytes is likely important for systemic viral clearance. Copyright © 2017, American Association for the Advancement of Science.

  4. Peripheral tumors alter neuroinflammatory responses to lipopolysaccharide in female rats.

    Science.gov (United States)

    Pyter, Leah M; El Mouatassim Bih, Sarah; Sattar, Husain; Prendergast, Brian J

    2014-03-13

    Cancer is associated with an increased prevalence of depression. Peripheral tumors induce inflammatory cytokine production in the brain and depressive-like behaviors. Mounting evidence indicates that cytokines are part of a pathway by which peripheral inflammation causes depression. Neuroinflammatory responses to immune challenges can be exacerbated (primed) by prior immunological activation associated with aging, early-life infection, and drug exposure. This experiment tested the hypothesis that peripheral tumors likewise induce neuroinflammatory sensitization or priming. Female rats with chemically-induced mammary carcinomas were injected with either saline or lipopolysaccharide (LPS, 250μg/kg; i.p.), and expression of mRNAs involved in the pathway linking inflammation and depression (interleukin-1beta [Il-1β], CD11b, IκBα, indolamine 2,3-deoxygenase [Ido]) was quantified by qPCR in the hippocampus, hypothalamus, and frontal cortex, 4 or 24h post-treatment. In the absence of LPS, hippocampal Il-1β and CD11b mRNA expression were elevated in tumor-bearing rats, whereas Ido expression was reduced. Moreover, in saline-treated rats basal hypothalamic Il-1β and CD11b expression were positively correlated with tumor weight; heavier tumors, in turn, were characterized by more inflammatory, necrotic, and granulation tissue. Tumors exacerbated CNS proinflammatory gene expression in response to LPS: CD11b was greater in hippocampus and frontal cortex of tumor-bearing relative to tumor-free rats, IκBα was greater in hippocampus, and Ido was greater in hypothalamus. Greater neuroinflammatory responses in tumor-bearing rats were accompanied by attenuated body weight gain post-LPS. The data indicate that neuroinflammatory pathways are potentiated, or primed, in tumor-bearing rats, which may exacerbate future negative behavioral consequences. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Qa-1/HLA-E-restricted regulatory CD8+ T cells and self-nonself discrimination: an essay on peripheral T-cell regulation.

    Science.gov (United States)

    Jiang, Hong; Chess, Leonard

    2008-11-01

    By discriminating self from nonself and controlling the magnitude and class of immune responses, the immune system mounts effective immunity against virtually any foreign antigens but avoids harmful immune responses to self. These are two equally important and related but distinct processes, which function in concert to ensure an optimal function of the immune system. Immunologically relevant clinical problems often occur because of failure of either process, especially the former. Currently, there is no unified conceptual framework to characterize the precise relationship between thymic negative selection and peripheral immune regulation, which is the basis for understanding self-non-self discrimination versus control of magnitude and class of immune responses. In this article, we explore a novel hypothesis of how the immune system discriminates self from nonself in the periphery during adaptive immunity. This hypothesis permits rational analysis of various seemingly unrelated biomedical problems inherent in immunologic disorders that cannot be uniformly interpreted by any currently existing paradigms. The proposed hypothesis is based on a unified conceptual framework of the "avidity model of peripheral T-cell regulation" that we originally proposed and tested, in both basic and clinical immunology, to understand how the immune system achieves self-nonself discrimination in the periphery.

  6. Modulation of the innate immune responses in the striped ...

    African Journals Online (AJOL)

    Thus, most of the innate non-specific immune responses are inducible though they are constitutive of fish immune system exhibiting a basal level of activity even in the absence of pathogen challenge. Keywords: Aeromonas hydrophila, Experimental challenge, Innate immune response, Striped snakehead murrel ...

  7. Cell-mediated immune responses in rainbow trout after DNA immunization against the viral hemorrhagic septicemia virus

    DEFF Research Database (Denmark)

    Utke, Katrin; Kock, Holger; Schuetze, Heike

    2008-01-01

    injection site rather than to injection sites of heterologous vaccines, suggesting the antigen specificity of homing. By demonstrating CMC responses to distinct viral proteins and homing in rainbow trout, these results substantially contribute to the understanding of the teleost immune system.......To identify viral proteins that induce cell-mediated cytotoxicity (CMC) against viral hemorrhagic septicemia virus (VHSV)-infected cells, rainbow trout were immunized with DNA vectors encoding the glycoprotein G or the nucleocapsid protein N of VHSV. The G protein was a more potent trigger...... of cytotoxic cells than the N protein. Peripheral blood leukocytes (PBL) isolated from trout immunized against the G protein killed both VHSV-infected MHC class I matched (RTG-2) and VHSV-infected xenogeneic (EPC) target cells, suggesting the involvement of both cytotoxic T lymphocytes (CTL) and NK cells...

  8. Maintenance of host leukocytes in peripheral immune compartments following lethal irradiation and bone marrow reconstitution: implications for graft versus host disease.

    Science.gov (United States)

    Staley, Elizabeth M; Tanner, Scott M; Daft, Joseph G; Stanus, Andrea L; Martin, Steven M; Lorenz, Robin G

    2013-03-01

    Bone marrow reconstitution is utilized as a tool for disease treatment and as a research technique to elucidate the function of bone marrow derived cells. Clinically successful engraftment is indicated by the development of a functioning immune repertoire. In research, reconstitution is considered successful if >85% of splenic leukocytes are of donor origins. Previous work suggests that splenic reconstitution may not be indicative of reconstitution in the mucosa. We sought to evaluate mucosal reconstitution in animals following a standard bone marrow eradication and reconstitution technique. Bone marrow was harvested from adult B6.SJL donor mice (CD45.1) and injected via either the retro-orbital or intraperitoneal route into lethally irradiated B6 (CD45.2) adult or neonatal recipients respectively. The expression of CD45 by flow cytometry was used to calculate reconstitution with respect to immune compartment and cell type. In reconstituted adult animals 93.2±1.5% of splenic leukocytes expressed the donor CD45.1 antigen thus meeting the standard definition of reconstitution, however only 58.6±13.6% of intestinal lamina propria lymphocytes and 52.4±16.0% of intestinal intraepithelial lymphocytes were of donor origin, confirming splenic reconstitution fails to represent peripheral immune reconstitution. T-cells in the gastrointestinal tract are the most poorly reconstituted, while B-cells appear to be almost universally replaced by donor cells. The inadequate mucosal reconstitution was not corrected by evaluating later time points or by performing the bone marrow transfer during the neonatal period. This demonstration that substantial host T-cells remain in the intestinal mucosa after a "successful" bone marrow transplantation should cause a re-evaluation of data from research bone marrow chimera experiments, as well as the mechanisms for complications after clinical bone marrow transplantation. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Recovery of the immune system after exercise.

    Science.gov (United States)

    Peake, Jonathan M; Neubauer, Oliver; Walsh, Neil P; Simpson, Richard J

    2017-05-01

    The notion that prolonged, intense exercise causes an "open window" of immunodepression during recovery after exercise is well accepted. Repeated exercise bouts or intensified training without sufficient recovery may increase the risk of illness. However, except for salivary IgA, clear and consistent markers of this immunodepression remain elusive. Exercise increases circulating neutrophil and monocyte counts and reduces circulating lymphocyte count during recovery. This lymphopenia results from preferential egress of lymphocyte subtypes with potent effector functions [e.g., natural killer (NK) cells, γδ T cells, and CD8 + T cells]. These lymphocytes most likely translocate to peripheral sites of potential antigen encounter (e.g., lungs and gut). This redeployment of effector lymphocytes is an integral part of the physiological stress response to exercise. Current knowledge about changes in immune function during recovery from exercise is derived from assessment at the cell population level of isolated cells ex vivo or in blood. This assessment can be biased by large changes in the distribution of immune cells between blood and peripheral tissues during and after exercise. Some evidence suggests that reduced immune cell function in vitro may coincide with changes in vivo and rates of illness after exercise, but more work is required to substantiate this notion. Among the various nutritional strategies and physical therapies that athletes use to recover from exercise, carbohydrate supplementation is the most effective for minimizing immune disturbances during exercise recovery. Sleep is an important aspect of recovery, but more research is needed to determine how sleep disruption influences the immune system of athletes. Copyright © 2017 the American Physiological Society.

  10. Eimeria maxima microneme protein 2 delivered as DNA vaccine and recombinant protein induces immunity against experimental homogenous challenge.

    Science.gov (United States)

    Huang, Jingwei; Zhang, Zhenchao; Li, Menghui; Song, Xiaokai; Yan, Ruofeng; Xu, Lixin; Li, Xiangrui

    2015-10-01

    E. maxima is one of the seven species of Eimeria that infects chicken. Until now, only a few antigenic genes of E. maxima have been reported. In the present study, the immune protective effects against E. maxima challenge of recombinant protein and DNA vaccine encoding EmMIC2 were evaluated. Two-week-old chickens were randomly divided into five groups. The experimental group of chickens was immunized with 100 μg DNA vaccine pVAX1-MIC2 or 200 μg rEmMIC2 protein while the control group of chickens was injected with pVAX1 plasmid or sterile PBS. The results showed that the anti-EmMIC2 antibody titers of both rEmMIC2 protein and pVAX1-MIC2 groups were significantly higher as compared to PBS and pVAX1 control (Pmaxima challenge and it could be an effective antigen candidate for the development of new vaccines against E. maxima. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. The Challenging Task of Governing Cross-Border Investment in Peripheral Regions: Polish Investors in Northeast Germany

    Directory of Open Access Journals (Sweden)

    Kinder Sebastian

    2014-12-01

    Full Text Available The article investigates the challenging task of governing cross-border investment in peripheral regions. The main objective is to identify common opportunities and obstacles in the Pomerania Euroregion by taking the case study of Polish citizens/ entrepreneurs investing in northeast Germany. This relatively new phenomenon is accompanied by large uncertainties and risks, and lacks further empirical insights. At the same time it breaks new ground, creates alternatives, calls for the development of efficient modes of cross-border cooperation and addresses mutual governance issues on an inter-regional basis between manifold stakeholders on both sides of the border. The case study summarises findings from fieldwork, elaborates a quantitative and qualitative assessment of cross-border governance measures within formal and informal institutions, and tries to formulate policy recommendations for prospective approaches

  12. Animal models of prenatal immune challenge and their contribution to the study of schizophrenia: a systematic review

    Directory of Open Access Journals (Sweden)

    D.S. Macêdo

    2012-03-01

    Full Text Available Prenatal immune challenge (PIC in pregnant rodents produces offspring with abnormalities in behavior, histology, and gene expression that are reminiscent of schizophrenia and autism. Based on this, the goal of this article was to review the main contributions of PIC models, especially the one using the viral-mimetic particle polyriboinosinic-polyribocytidylic acid (poly-I:C, to the understanding of the etiology, biological basis and treatment of schizophrenia. This systematic review consisted of a search of available web databases (PubMed, SciELO, LILACS, PsycINFO, and ISI Web of Knowledge for original studies published in the last 10 years (May 2001 to October 2011 concerning animal models of PIC, focusing on those using poly-I:C. The results showed that the PIC model with poly-I:C is able to mimic the prodrome and both the positive and negative/cognitive dimensions of schizophrenia, depending on the specific gestation time window of the immune challenge. The model resembles the neurobiology and etiology of schizophrenia and has good predictive value. In conclusion, this model is a robust tool for the identification of novel molecular targets during prenatal life, adolescence and adulthood that might contribute to the development of preventive and/or treatment strategies (targeting specific symptoms, i.e., positive or negative/cognitive for this devastating mental disorder, also presenting biosafety as compared to viral infection models. One limitation of this model is the incapacity to model the full spectrum of immune responses normally induced by viral exposure.

  13. Azadirachta indica (neem) leaf dietary effects on the immunity response and disease resistance of Asian seabass, Lates calcarifer challenged with Vibrio harveyi.

    Science.gov (United States)

    Talpur, Allah Dad; Ikhwanuddin, Mhd

    2013-01-01

    The present study was aimed to address the possible evaluation of Azadirachta indica (neem) leaf-supplemented diets on innate immune response in Asian seabass, Lates calcarifer fingerlings against Vibrio harveyi infection. Fish were fed for two weeks diets containing six graded levels of neem leaf at 0 g, 1 g, 2 g, 3 g, 4 g and 5 g per kg feed. Fish fed neem leaf-supplemented diet displayed significant differences (p growth rate (SGR) and feed conversion ratio (FCR) compared to the control group fed without neem leaf-supplemented diet. Various innate immune parameters were examined pre-challenge and post-challenge. Fish was injected intraperitoneally with a lethal dose of V. harveyi containing 10(8) cells mL(-1). Supplementation of neem leaf diet significantly increased phagocytic activity, superoxide anion production, serum lysozyme, serum bactericidal activity, serum anti-protease activity throughout the experimental period when compared with the control group. Dietary doses of neem leaf diet significantly influenced the immune parameters, haematological parameters and blood biochemical indices of treated fish. The results suggested that fish fed neem leaf-supplemented diet improved the immune system and increased survival rate in L. calcarifer fingerlings against V. harveyi infection. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Immune Modulation in Normal Human Peripheral Blood Mononuclear Cells (PBMCs) (Lymphocytes) in Response to Benzofuran-2-Carboxylic Acid Derivative KMEG during Spaceflight

    Science.gov (United States)

    Okoro, Elvis; Mann, Vivek; Ellis, Ivory; Mansoor, Elvedina; Olamigoke, Loretta; Marriott, Karla Sue; Denkins, Pamela; Williams, Willie; Sundaresan, Alamelu

    2017-08-01

    Microgravity and radiation exposure during space flight have been widely reported to induce the suppression of normal immune system function, and increase the risk of cancer development in humans. These findings pose a serious risk to manned space missions. Interestingly, recent studies have shown that benzofuran-2-carboxylic acid derivatives can inhibit the progression of some of these devastating effects on earth and in modeled microgravity. However, these studies had not assessed the impacts of benzofuran-2- carboxylic acid and its derivatives on global gene expression under spaceflight conditions. In this study, the ability of a specific benzofuran-2-carboxylic acid derivative (KMEG) to confer protection from radiation and restore normal immune function was investigated following exposure to space flight conditions on the ISS. Normal human peripheral blood mononuclear cells (lymphocytes) treated with 10 µ g/ml of KMEG together with untreated control samples were flown on Nanoracks hardware on Spacex-3 flight. The Samples were returned one month later and gene expression was analyzed. A 1g-ground control experiment was performed in parallel at the Kennedy spaceflight center. The first overall subtractive unrestricted analysis revealed 78 genes, which were differentially expressed in space flight KMEG, untreated lymphocytes as compared to the corresponding ground controls. However, in KMEG-treated space flight lymphocytes, there was an increased expression of a group of genes that mediate increased transcription, translation and innate immune system mediating functions of lymphocytes as compared to KMEG-untreated samples. Analysis of genes related to T cell proliferation in spaceflight KMEG-treated lymphocytes compared to 1g-ground KMEG- treated lymphocytes revealed six T cell proliferation and signaling genes to be significantly upregulated (p trafficking, promote early response, mediating C-myc related proliferation, promote antiapoptotic activity and protects

  15. The peripheral NK cell repertoire after kidney transplantation is modulated by different immunosuppressive drugs

    Directory of Open Access Journals (Sweden)

    Christine eNeudoerfl

    2013-02-01

    Full Text Available In the context of kidney transplantation, little is known about the involvement of NK cells in the immune reaction leading to either rejection or immunological tolerance under immunosuppression. Therefore, the peripheral NK cell repertoire of patients after kidney transplantation was investigated in order to identify NK cell subsets that may be associated with the individual immune status at the time of their protocol biopsies for histopathological evaluation of the graft. Alterations in the peripheral NK cell repertoire could be correlated to the type of immunosuppression, i.e. calcineurin-inhibitors like CyclosporinA vs. Tacrolimus with or without addition of mTOR inhibitors. Here, we could demonstrate that the NK cell repertoire in peripheral blood of kidney transplant patients differs significantly from healthy individuals. The presence of donor-specific antibodies was associated with reduced numbers of CD56dim NK cells. Moreover, in patients, down-modulation of CD16 and CD6 on CD56dim NK cells was observed with significant differences between CyclosporinA- and Tac-treated patients. Tac-treatment was associated with decreased CD69, HLA-DR and increased CD94/NKG2A expression in CD56dim NK cells indicating that the quality of the immunosuppressive treatment impinges on the peripheral NK cell repertoire. In vitro studies with PBMC of healthy donors showed that this modulation of CD16, CD6, CD69, and HLA-DR could also be induced experimentally. The presence of calcineurin or mTOR inhibitors had also functional consequences regarding degranulation and IFN--production against K562 target cells, respectively. In summary, we postulate that the NK cell composition in peripheral blood of kidney transplanted patients represents an important hallmark of the efficacy of immunosuppression and may be even informative for the immune status after transplantation in terms of rejection vs. drug-induced allograft tolerance. Thus,NK cells can serve as sensors

  16. Lesion-Specific Immune Response in Granulomas of Patients with Pulmonary Tuberculosis: A Pilot Study.

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    Selvakumar Subbian

    Full Text Available The formation and maintenance of granulomas is central to the host response to Mycobacterium tuberculosis (Mtb infection. It is widely accepted that the lungs of patients with tuberculosis (TB usually contain multiple infection foci, and that the granulomas evolve and differentiate independently, resulting in considerable heterogeneity. Although gene expression profiles of human blood cells have been proposed as biomarkers of Mtb infection and/or active disease, the immune profiles of discrete lesion types has not been studied extensively. Using histology, immunopathology and genome-wide transcriptome analysis, we explored the immunological profile of human lung TB granulomas. We show that although the different granulomas share core similarities in their immunological/inflammatory characteristics, they also exhibit significant divergence. Despite similar numbers of CD68+ macrophages in the different lesions, the extent of immune reactivity, as determined by the density of CD3+ T cells in the macrophage rich areas, and the extent of fibrosis, shows considerable variation. Both quantitative and qualitative differences among significantly differentially expressed genes (SDEG were noted in each of the lesion types studied. Further, network/pathway analysis of SDEG revealed differential regulation of inflammatory response, immune cell trafficking, and cell mediated immune response in the different lesions. Our data highlight the formidable challenges facing ongoing efforts to identify peripheral blood biomarkers due to the diversity of lesion types and complexity of local immune responses in the lung.

  17. Peripheral formalin injection induces unique spinal cord microglial phenotypic changes

    Science.gov (United States)

    Fu, Kai-Yuan; Tan, Yong-Hui; Sung, Backil; Mao, Jianren

    2014-01-01

    Microglia are resident immune cells of brain and activated by peripheral tissue injury. In the present study, we investigated the possible induction of several microglial surface immunomolecules in the spinal cord, including leukocyte common antigen (LCA/CD45), MHC class I antigen, MHC class II antigen, Fc receptor, and CD11c following formalin injection into the rat’s hind paw. CD45 and MHC class I were upregulated in the activated microglia, which was evident on day 3 with the peak expression on day 7 following peripheral formalin injection. There was a very low basal expression of MHC class II, CD11c, and the Fc receptor, which did not change after the formalin injection. These results, for the first time, indicate that peripheral formalin injection can induce phenotypic changes of microglia with distinct upregulation of CD45 and MHC class I antigen. The data suggest that phenotypic changes of the activated microglia may be a unique pattern of central changes following peripheral tissue injury. PMID:19015000

  18. Incorporation of a recombinant Eimeria maxima IMP1 antigen into nanoparticles confers protective immunity against E. maxima challenge infection

    Science.gov (United States)

    The purpose of this study was to determine if incorporating a recombinant Eimeria maxima protein, namely rEmaxIMP1, into gold nanoparticles (NP) could improve the level of protective immunity against E. maxima challenge infection. Recombinant EmaxIMP1 was expressed in Escherchia coli as a poly-His f...

  19. Neuroendocrine and Immune Responses Undertake Different Fates following Tryptophan or Methionine Dietary Treatment: Tales from a Teleost Model

    Directory of Open Access Journals (Sweden)

    Rita Azeredo

    2017-09-01

    Full Text Available Methionine and tryptophan appear to be fundamental in specific cellular pathways involved in the immune response mechanisms, including stimulation of T-regulatory cells by tryptophan metabolites or pro-inflammatory effects upon methionine supplementation. Thus, the aim of this study was to evaluate the immunomodulatory effect of these amino acids on the inflammatory and neuroendocrine responses in juveniles of European seabass, Dicentrarchus labrax. To achieve this, goal fish were fed for 14 days methionine and tryptophan-supplemented diets (MET and TRP, respectively, 2× dietary requirement level or a control diet meeting the amino acids requirement levels (CTRL. Fish were sampled for immune status assessment and the remaining fish were challenged with intraperitoneally injected inactivated Photobacterium damselae subsp. piscicida and sampled either 4 or 24 h post-injection. Respiratory burst activity, brain monoamines, plasma cortisol, and immune-related gene expression showed distinct and sometimes opposite patterns regarding the effects of dietary amino acids. While neuroendocrine intermediates were not affected by any dietary treatment at the end of the feeding trial, both supplemented diets led to increased levels of plasma cortisol after the inflammatory insult, while brain monoamine content was higher in TRP-fed fish. Peripheral blood respiratory burst was higher in TRP-fed fish injected with the bacteria inoculum but only compared to those fed MET. However, no changes were detected in total antioxidant capacity. Complement factor 3 was upregulated in MET-fed fish but methionine seemed to poorly affect other genes expression patterns. In contrast, fish fed MET showed increased immune cells numbers both before and after immune challenge, suggesting a strong enhancing effect of methionine on immune cells proliferation. Differently, tryptophan effects on inflammatory transcripts suggested an inhibitory mode of action. This, together

  20. Prenatal immune challenge is an environmental risk factor for brain and behavior change relevant to schizophrenia: evidence from MRI in a mouse model.

    Directory of Open Access Journals (Sweden)

    Qi Li

    Full Text Available OBJECTIVES: Maternal infection during pregnancy increases risk of severe neuropsychiatric disorders, including schizophrenia and autism, in the offspring. The most consistent brain structural abnormality in patients with schizophrenia is enlarged lateral ventricles. However, it is unknown whether the aetiology of ventriculomegaly in schizophrenia involves prenatal infectious processes. The present experiments tested the hypothesis that there is a causal relationship between prenatal immune challenge and emergence of ventricular abnormalities relevant to schizophrenia in adulthood. METHOD: We used an established mouse model of maternal immune activation (MIA by the viral mimic PolyI:C administered in early (day 9 or late (day 17 gestation. Automated voxel-based morphometry mapped cerebrospinal fluid across the whole brain of adult offspring and the results were validated by manual region-of-interest tracing of the lateral ventricles. Parallel behavioral testing determined the existence of schizophrenia-related sensorimotor gating abnormalities. RESULTS: PolyI:C-induced immune activation, in early but not late gestation, caused marked enlargement of lateral ventricles in adulthood, without affecting total white and grey matter volumes. This early exposure disrupted sensorimotor gating, in the form of prepulse inhibition. Identical immune challenge in late gestation resulted in significant expansion of 4(th ventricle volume but did not disrupt sensorimotor gating. CONCLUSIONS: Our results provide the first experimental evidence that prenatal immune activation is an environmental risk factor for adult ventricular enlargement relevant to schizophrenia. The data indicate immune-associated environmental insults targeting early foetal development may have more extensive neurodevelopmental impact than identical insults in late prenatal life.

  1. Immune system alterations in amyotrophic lateral sclerosis

    DEFF Research Database (Denmark)

    Hovden, H; Frederiksen, J L; Pedersen, S W

    2013-01-01

    Amyotrophic lateral sclerosis is a disease of which the underlying cause and pathogenesis are unknown. Cumulatative data clearly indicates an active participation by the immune system in the disease. An increasingly recognized theory suggests a non-cell autonomous mechanism, meaning that multiple...... cells working together are necessary for the pathogenesis of the disease. Observed immune system alterations could indicate an active participation in this mechanism. Damaged motor neurons are able to activate microglia, astrocytes and the complement system, which further can influence each other...... and contribute to neurodegeneration. Infiltrating peripheral immune cells appears to correlate with disease progression, but their significance and composition is unclear. The deleterious effects of this collaborating system of cells appear to outweigh the protective aspects, and revealing this interplay might...

  2. Fusion of a viral antigen to invariant chain leads to augmented T-cell immunity and improved protection in gene-gun DNA-vaccinated mice

    DEFF Research Database (Denmark)

    Grujic, Mirjana; Holst, Peter J; Christensen, Jan P

    2009-01-01

    It has recently been demonstrated that a recombinant replication-deficient human adenovirus 5 (Ad5) vector expressing lymphocytic choriomeningitis virus (LCMV) glycoprotein (GP) fused to the p31 invariant (Ii) chain confers broad, long-lasting T-cell immunity that completely protects C57BL/6 mice...... with the unlinked construct. In contrast, substantial protection against peripheral challenge was not observed. Additional experiments with T-cell subset-depleted or perforin-deficient mice revealed that virus control in vaccinated mice depends critically on cytotoxic CD8(+) T cells. Finally, priming with the naked...

  3. [Comparison of immune response after oral and intranasal immunization with recombinant Lactobacillus casei expressing ETEC F41].

    Science.gov (United States)

    Liu, Jiankui; Wei, Chunhua; Hou, Xilin; Wang, Guihua; Yu, Liyun

    2009-04-01

    In order to represent a promising strategy for mucosal vaccination, oral or intranasal immunization of Specific Pathogen Free (SPF) BALB/c mice were performed. The mucosal immunity, systemic immune and protective immune responses were compared after immunization with the recombinant Lactobacillus casei (L. casei) harboring enterotoxigenic Escherichia coli (ETEC) F41. The recombinant fusion proteins were detected by Western blot. Surface localization of the fusion protein was verified by immunofluorescence microscopy and flow cytometry. Six-week-old female SPF BALB/c mice (160 heads) were divided into 4 groups for immunization and control. Oral and intranasal immunization of mice was performed with the recombinant strain L. casei harboring pLA-F41 or pLA. For oral immunization, the mice were inoculated daily on days 0 to 4, 7 to 11, 21 to 25, and 49 to 53. A lighter schedule was used for nasal immunization (days 0 to 2, 7 to 9, 21 and 49). Specific anti-F41 IgG antibody in the serum and specific anti-F41 secret immunoglobulin A (sIgA) antibody in the lung, intestines, vagina fluid and feces of mice were detected by indirect ELISA. The mice orally or intranasally immunized with pLA-F41/L. casei and pLA/IL. casei were challenged with standard-type ETEC F41 (C83919) (2 x 10(3) LD50). Mice immunized with pLA-F41/L. casei could produce remarkable anti-F41 antibody level. More than 90% survived in oral immunization group whereas more than 85% survived in intranasal immunization group after challenged with C83919, all dead in the control group. Ninety percent of the pups survived in oral immunization group whereas 80% survived in intranasal immunization group after challenged with C83919, but only a 5% survival rate for pups that were either immunized with a control pLA vector or unimmunized. Oral or intranasal immunization with recombinant L. casei displaying ETEC F41 antigens on the surface induced effective and similar systemic and mucosal immune responses against the

  4. Innate immune receptor Toll-like receptor 4 signalling in neuropsychiatric diseases.

    Science.gov (United States)

    García Bueno, B; Caso, J R; Madrigal, J L M; Leza, J C

    2016-05-01

    The innate immunity is a stereotyped first line of defense against pathogens and unspecified damage signals. One of main actors of innate immunity are the Toll-like receptors (TLRs), and one of the better characterized members of this family is TLR-4, that it is mainly activated by Gram-negative bacteria lipopolysaccharide. In brain, TLR-4 organizes innate immune responses against infections or cellular damage, but also possesses other physiological functions. In the last years, some evidences suggest a role of TLR-4 in stress and stress-related neuropsychiatric diseases. Peripheral and brain TLR-4 activation triggers sickness behavior, and its expression is a risk factor of depression. Some elements of the TLR-4 signaling pathway are up-regulated in peripheral samples and brain post-mortem tissue from depressed and suicidal patients. The "leaky gut" hypothesis of neuropsychiatric diseases is based on the existence of an increase of the intestinal permeability which results in bacterial translocation able to activate TLR-4. Enhanced peripheral TLR-4 expression/activity has been described in subjects diagnosed with schizophrenia, bipolar disorder and in autistic children. A role for TLR-4 in drugs abuse has been also proposed. The therapeutic potential of pharmacological/genetic modulation of TLRs signaling pathways in neuropsychiatry is promising, but a great preclinical/clinical scientific effort is still needed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Distribution of Peripheral Memory T Follicular Helper Cells in Patients with Schistosomiasis Japonica.

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    Xiaojun Chen

    Full Text Available Schistosomiasis is a helminthic disease that affects more than 200 million people. An effective vaccine would be a major step towards eliminating the disease. Studies suggest that T follicular helper (Tfh cells provide help to B cells to generate the long-term humoral immunity, which would be a crucial component of successful vaccines. Thus, understanding the biological characteristics of Tfh cells in patients with schistosomiasis, which has never been explored, is essential for vaccine design.In this study, we investigated the biological characteristics of peripheral memory Tfh cells in schistosomiasis patients by flow cytometry. Our data showed that the frequencies of total and activated peripheral memory Tfh cells in patients were significantly increased during Schistosoma japonicum infection. Moreover, Tfh2 cells, which were reported to be a specific subpopulation to facilitate the generation of protective antibodies, were increased more greatly than other subpopulations of total peripheral memory Tfh cells in patients with schistosomiasis japonica. More importantly, our result showed significant correlations of the percentage of Tfh2 cells with both the frequency of plasma cells and the level of IgG antibody. In addition, our results showed that the percentage of T follicular regulatory (Tfr cells was also increased in patients with schistosomiasis.Our report is the first characterization of peripheral memory Tfh cells in schistosomasis patients, which not only provides potential targets to improve immune response to vaccination, but also is important for the development of vaccination strategies to control schistosomiasis.

  6. Gliadin-Specific T-Cells Mobilized in the Peripheral Blood of Coeliac Patients by Short Oral Gluten Challenge: Clinical Applications

    Directory of Open Access Journals (Sweden)

    Stefania Picascia

    2015-12-01

    Full Text Available Celiac disease (CD is a common lifelong food intolerance triggered by dietary gluten affecting 1% of the general population. Gliadin-specific T-cell lines and T-cell clones obtained from intestinal biopsies have provided great support in the investigation of immuno-pathogenesis of CD. In the early 2000 a new in vivo, less invasive, approach was established aimed to evaluate the adaptive gliadin-specific T-cell response in peripheral blood of celiac patients on a gluten free diet. In fact, it has been demonstrated that three days of ingestion of wheat-containing food induces the mobilization of memory T lymphocytes reactive against gliadin from gut-associated lymphoid tissue into peripheral blood of CD patients. Such antigen-specific T-cells releasing interferon-γ can be transiently detected by using the enzyme-linked immunospot (ELISPOT assays or by flow cytometry tetramer technology. This paper discusses the suitability of this in vivo tool to investigate the repertoire of gluten pathogenic peptides, to support CD diagnosis, and to assess the efficacy of novel therapeutic strategies. A systematic review of all potential applications of short oral gluten challenge is provided.

  7. Pregnancy: an immune challenge

    Directory of Open Access Journals (Sweden)

    Maria Angelica Ehara Watanabe

    2014-12-01

    Full Text Available Several studies demonstrate the importance of immunological aspects of pregnancy. During pregnancy, the embryo is implanted in the womb, where it will develop until the end of pregnancy. Amongst the immune aspects, the importance of the modulation of T lymphocytes, natural killers (NK cells and many cytokines in maternal organism can be mentioned. The maternal tolerance to the fetus appears to be mediated by specific maternal hormones and by the expression of human leukocyte antigen G (HLA-G - characteristic in pregnancy. Other studies suggest that fetal rejection and complications during pregnancy may occur because of the presence of minor histocompatibility antigens (mHAg, acquired by blood sharing of the mother with the fetus, and because of the presence of maternal antibodies against the sperm and against the fetus. The purpose of this review is to describe the immunological aspects that allow maternal tolerance to the fetus during pregnancy, as well as possible causes for rejection of the embryo and complications during pregnancy.

  8. Branched-chain amino acid supplementation and the immune response of long-distance athletes.

    Science.gov (United States)

    Bassit, Reinaldo A; Sawada, Letícia A; Bacurau, Reury F P; Navarro, Franciso; Martins, Eivor; Santos, Ronaldo V T; Caperuto, Erico C; Rogeri, Patrícia; Costa Rosa, Luís F B P

    2002-05-01

    Intense long-duration exercise has been associated with immunosuppression, which affects natural killer cells, lymphokine-activated killer cells, and lymphocytes. The mechanisms involved, however, are not fully determined and seem to be multifactorial, including endocrine changes and alteration of plasma glutamine concentration. Therefore, we evaluated the effect of branched-chain amino acid supplementation on the immune response of triathletes and long-distance runners. Peripheral blood was collected prior to and immediately after an Olympic Triathlon or a 30k run. Lymphocyte proliferation, cytokine production by cultured cells, and plasma glutamine were measured. After the exercise bout, athletes from the placebo group presented a decreased plasma glutamine concentration that was abolished by branched-chain amino acid supplementation and an increased proliferative response in their peripheral blood mononuclear cells. Those cells also produced, after exercise, less tumor necrosis factor, interleukins-1 and -4, and interferon and 48% more interleukin-2. Supplementation stimulated the production of interleukin-2 and interferon after exercise and a more pronounced decrease in the production of interleukin-4, indicating a diversion toward a Th1 type immune response. Our results indicate that branched-chain amino acid (BCAA) supplementation recovers the ability of peripheral blood mononuclear cells proliferate in response to mitogens after a long distance intense exercise, as well as plasma glutamine concentration. The amino acids also modify the pattern of cytokine production leading to a diversion of the immune response toward a Th1 type of immune response.

  9. Cannabinoids and Innate Immunity: Taking a Toll on Neuroinflammation

    Directory of Open Access Journals (Sweden)

    Eric J. Downer

    2011-01-01

    Full Text Available The biologically active components of cannabis have therapeutic potential in neuroinflammatory disorders due to their anti-inflammatory propensity. Cannabinoids influence immune function in both the peripheral and the central nervous system (CNS, and the components of the cannabinoid system, the cannabinoid receptors and their endogenous ligands (endocannabinoids, have been detected on immune cells as well as in brain glia. Neuroinflammation is the complex innate immune response of neural tissue to control infection and eliminate pathogens, and Toll-like receptors (TLRs, a major family of pattern recognition receptors (PRRs that mediate innate immunity, have emerged as players in the neuroinflammatory processes underpinning various CNS diseases. This review will highlight evidence that cannabinoids interact with the immune system by impacting TLR-mediated signaling events, which may provide cues for devising novel therapeutic approaches for cannabinoid ligands.

  10. [The liver and the immune system].

    Science.gov (United States)

    Jakab, Lajos

    2015-07-26

    The liver is known to be the metabolic centre of the organism and is under the control of the central nervous system. It has a peculiar tissue structure and its anatomic localisation defines it as part of the immune system having an individual role in the defence of the organism. The determinant of its particular tissue build-up is the sinusoid system. In addition to hepatocytes, one cell row "endothelium", stellate cells close to the external surface, Kupffer cells tightly to its inner surface, as well as dendritic cells and other cell types (T and B lymphocytes, natural killer and natural killer T-cells, mast cells, granulocytes) are present. The multitudes and variety of cells make it possible to carry out the tasks according to the assignment of the organism. The liver is a member of the immune system having immune cells largely in an activated state. Its principal tasks are the assurance of the peripheral immune tolerance of the organism with the help of the haemopoetic cells and transforming growth factor-β. The liver takes part in the determination of the manner of the non-specific immune response of the organism. In addition to acute phase reaction of the organism, the liver has a role in the adaptive/specific immune response. These functions include retardation of the T and B lymphocytes and the defence against harmful pathogens. With the collaboration of transforming growth factor-β, immunoglobulins and their subclasses are inhibited just as the response of the T lymphocytes. The only exception is the undisturbed immunoglobulin A production. Particularly important is the intensive participation of the liver in the acute phase reaction of the organism, which is organised and guided by the coordinated functions of the cortico-hypothalamo-hypophysis-adrenal axis. Beside cellular elements, hormones, adhesion molecules, chemokines and cytokines are also involved in the cooperation with the organs. Acute phase reactants play a central role in these processes

  11. Controlled progressive innate immune stimulation regimen prevents the induction of sickness behavior in the open field test.

    Science.gov (United States)

    Chen, Qun; Tarr, Andrew J; Liu, Xiaoyu; Wang, Yufen; Reed, Nathaniel S; Demarsh, Cameron P; Sheridan, John F; Quan, Ning

    2013-01-01

    Peripheral immune activation by bacterial mimics or live replicating pathogens is well known to induce central nervous system activation. Sickness behavior alterations are often associated with inflammation-induced increases in peripheral proinflammatory cytokines (eg, interleukin [IL]-1β and IL-6). However, most researchers have used acute high dose endotoxin/bacterial challenges to observe these outcomes. Using this methodology may pose inherent risks in the translational interpretation of the experimental data in these studies. Studies using Escherichia coli have yet to establish the full kinetics of repeated E. coli peripheral injections. Therefore, we sought to examine the effects of repeated low dose E. coli on sickness behavior and local peripheral inflammation in the open field test. Results from the current experiments showed a behavioral dose response, where increased amounts of E. coli resulted in correspondingly increased sickness behavior. Furthermore, animals that received a subthreshold dose (ie, one that did not cause sickness behavior) of E. coli 24 hours prior were able to withstand a larger dose of E. coli on the second day (a dose that would normally cause sickness behavior in mice without prior exposure) without inducing sickness behavior. In addition, animals that received escalating subthreshold doses of E. coli on days 1 and 2 behaviorally tolerated a dose of E. coli 25 times higher than what would normally cause sickness behavior if given acutely. Lastly, increased levels of E. coli caused increased IL-6 and IL-1β protein expression in the peritoneal cavity, and this increase was blocked by administering a subthreshold dose of E. coli 24 hours prior. These data show that progressive challenges with subthreshold levels of E. coli may obviate the induction of sickness behavior and proinflammatory cytokine expression.

  12. Beneficial autoimmunity at body surfaces - immune surveillance and rapid type 2 immunity regulate tissue homeostasis and cancer.

    Science.gov (United States)

    Dalessandri, Tim; Strid, Jessica

    2014-01-01

    Epithelial cells (ECs) line body surface tissues and provide a physicochemical barrier to the external environment. Frequent microbial and non-microbial challenges such as those imposed by mechanical disruption, injury or exposure to noxious environmental substances including chemicals, carcinogens, ultraviolet-irradiation, or toxins cause activation of ECs with release of cytokines and chemokines as well as alterations in the expression of cell-surface ligands. Such display of epithelial stress is rapidly sensed by tissue-resident immunocytes, which can directly interact with self-moieties on ECs and initiate both local and systemic immune responses. ECs are thus key drivers of immune surveillance at body surface tissues. However, ECs have a propensity to drive type 2 immunity (rather than type 1) upon non-invasive challenge or stress - a type of immunity whose regulation and function still remain enigmatic. Here, we review the induction and possible role of type 2 immunity in epithelial tissues and propose that rapid immune surveillance and type 2 immunity are key regulators of tissue homeostasis and carcinogenesis.

  13. Probiotics Improve Inflammation-Associated Sickness Behavior by Altering Communication between the Peripheral Immune System and the Brain.

    Science.gov (United States)

    D'Mello, Charlotte; Ronaghan, Natalie; Zaheer, Raza; Dicay, Michael; Le, Tai; MacNaughton, Wallace K; Surrette, Michael G; Swain, Mark G

    2015-07-29

    Patients with systemic inflammatory diseases (e.g., rheumatoid arthritis, inflammatory bowel disease, chronic liver disease) commonly develop debilitating symptoms (i.e., sickness behaviors) that arise from changes in brain function. The microbiota-gut-brain axis alters brain function and probiotic ingestion can influence behavior. However, how probiotics do this remains unclear. We have previously described a novel periphery-to-brain communication pathway in the setting of peripheral organ inflammation whereby monocytes are recruited to the brain in response to systemic TNF-α signaling, leading to microglial activation and subsequently driving sickness behavior development. Therefore, we investigated whether probiotic ingestion (i.e., probiotic mixture VSL#3) alters this periphery-to-brain communication pathway, thereby reducing subsequent sickness behavior development. Using a well characterized mouse model of liver inflammation, we now show that probiotic (VSL#3) treatment attenuates sickness behavior development in mice with liver inflammation without affecting disease severity, gut microbiota composition, or gut permeability. Attenuation of sickness behavior development was associated with reductions in microglial activation and cerebral monocyte infiltration. These events were paralleled by changes in markers of systemic immune activation, including decreased circulating TNF-α levels. Our observations highlight a novel pathway through which probiotics mediate cerebral changes and alter behavior. These findings allow for the potential development of novel therapeutic interventions targeted at the gut microbiome to treat inflammation-associated sickness behaviors in patients with systemic inflammatory diseases. This research shows that probiotics, when eaten, can improve the abnormal behaviors (including social withdrawal and immobility) that are commonly associated with inflammation. Probiotics are able to cause this effect within the body by changing how

  14. AB115. Preliminary study on the immune status of patients with prostate cancer

    OpenAIRE

    He, Jingliang; He, Leye

    2014-01-01

    Objective To preliminarily assess the immune status of patients with prostate cancer through detecting various immune indexs and then analyse the relationship between immune status and clinical factors such as clinical stage, pathological classification and endocrine therapy. Methods Flow cytometry was used to detect the percentage of CD4, CD8and NK cells in peripheral blood lymphocyte (PBL) of 28 patients with PCa, 16 BPH patients and ten healthy men (HM). The expression of perforin and gran...

  15. Adoptive regulatory T-cell therapy preserves systemic immune homeostasis after cerebral ischemia.

    Science.gov (United States)

    Li, Peiying; Mao, Leilei; Zhou, Guoqing; Leak, Rehana K; Sun, Bao-Liang; Chen, Jun; Hu, Xiaoming

    2013-12-01

    Cerebral ischemia has been shown to result in peripheral inflammatory responses followed by long-lasting immunosuppression. Our recent study demonstrated that intravenous delivery of regulatory T cells (Tregs) markedly protected against transient cerebral ischemia by suppressing neutrophil-derived matrix metallopeptidase 9 production in the periphery. However, the effect of Tregs on systemic inflammatory responses and immune status has not been fully characterized. Cerebral ischemia was induced by middle cerebral artery occlusion for 60 minutes in mice or 120 minutes in rats. Tregs were isolated from donor animals by CD4 and CD25 double selection and transferred intravenously to ischemic recipients at 2 hours after middle cerebral artery occlusion. Animals were euthanized on different days after reperfusion. The effects of Tregs on systemic inflammation and immune status were evaluated using flow cytometry, ELISAs, and immunohistochemistry. Systemic administration of purified Tregs raises functional Tregs in the blood and peripheral organs, including spleen and lymph nodes. These exogenous Tregs remain in the blood and peripheral organs for ≥12 days. Functionally, Treg adoptive transfer markedly inhibits middle cerebral artery occlusion-induced elevation of inflammatory cytokines (interleukin-6 and tumor necrosis factor α) in the blood. Furthermore, Treg treatment corrects long-term lymphopenia and improves cellular immune functions after ischemic brain injury. As a result, Treg-treated animals exhibit decreased bacterial loads in the blood during recovery from cerebral ischemic attack. Treg treatment did not exacerbate poststroke immunosuppression. On the contrary, Treg-treated animals displayed improved immune status after focal cerebral ischemia.

  16. Lysozyme as an alternative to antibiotics improves growth performance and tumor necrosis factor-a levels during an indirect immune challenge

    Science.gov (United States)

    Lysozyme is a 1,4-ß-N-acetylmuramidase that has antimicrobial properties. The objective of this study was to determine the effect of lysozyme and antibiotics on growth performance and immune response during an indirect disease challenge. Two replicates of 720 pigs each were weaned from the sow at ...

  17. Regulation of non-classical immune parameters in immune thrombocytopenic purpura mice by a spleen-invigorating, qi-replenishing and blood-containing formula

    Directory of Open Access Journals (Sweden)

    Tiantian Li

    2015-04-01

    Conclusions: The SQBF had a similar effect to prednisone with regards to enhancing peripheral blood platelet counts in ITP mice. Furthermore, it decreased β-EP levels and increased VIP and SIgA, and protected the thymus. This shows that, on base of the brain-gut axis functions, some non-classical immune vascular active factors or neurotransmitters are also involved in immune responses, and also have relationship with the onset of ITP and bleeding and/or hemostasis. It needs further study to determine whether a change in these active factors is related to immediate hemostasis.

  18. Effects of feeding Bt MON810 maize to pigs for 110 days on peripheral immune response and digestive fate of the cry1Ab gene and truncated Bt toxin.

    Directory of Open Access Journals (Sweden)

    Maria C Walsh

    Full Text Available BACKGROUND: The objective of this study was to evaluate potential long-term (110 days and age-specific effects of feeding genetically modified Bt maize on peripheral immune response in pigs and to determine the digestive fate of the cry1Ab gene and truncated Bt toxin. METHODOLOGY/PRINCIPAL FINDINGS: Forty day old pigs (n = 40 were fed one of the following treatments: 1 isogenic maize-based diet for 110 days (isogenic; 2 Bt maize-based diet (MON810 for 110 days (Bt; 3 Isogenic maize-based diet for 30 days followed by Bt maize-based diet for 80 days (isogenic/Bt; and 4 Bt maize-based diet (MON810 for 30 days followed by isogenic maize-based diet for 80 days (Bt/isogenic. Blood samples were collected during the study for haematological analysis, measurement of cytokine and Cry1Ab-specific antibody production, immune cell phenotyping and cry1Ab gene and truncated Bt toxin detection. Pigs were sacrificed on day 110 and digesta and organ samples were taken for detection of the cry1Ab gene and the truncated Bt toxin. On day 100, lymphocyte counts were higher (P<0.05 in pigs fed Bt/isogenic than pigs fed Bt or isogenic. Erythrocyte counts on day 100 were lower in pigs fed Bt or isogenic/Bt than pigs fed Bt/isogenic (P<0.05. Neither the truncated Bt toxin nor the cry1Ab gene were detected in the organs or blood of pigs fed Bt maize. The cry1Ab gene was detected in stomach digesta and at low frequency in the ileum but not in the distal gastrointestinal tract (GIT, while the Bt toxin fragments were detected at all sites in the GIT. CONCLUSIONS/SIGNIFICANCE: Perturbations in peripheral immune response were thought not to be age-specific and were not indicative of Th 2 type allergenic or Th 1 type inflammatory responses. There was no evidence of cry1Ab gene or Bt toxin translocation to organs or blood following long-term feeding.

  19. The effects of cynodon dactylon on the immune response of NMRI-MICE after challenge with REV1

    Directory of Open Access Journals (Sweden)

    Behrooz Ilkhanizadeh

    2016-10-01

    Full Text Available Cynodon dactylon is used in Iranian traditional medicine as a healing agent for reducing the complications of diabetes mellitus. We proposed that Cynodon dactylon may perform its effects through moderating humoral and cellular immune responses. We aimed to determine the possible effects of hydroalcholic extract of Cynodon dactylonon humoral and cellular immune responses following the Rev1 challenge in the mouse model. 20 NMRI male mice were randomly grouped in two equal groups and immunized with Rev1[0.1 ml Rev1+0.9 PBS[. Mice in the treatment group orally received 400 mg/kg hydroalcoholic extract of Cynodon dactylon every day from the beginning of the study for 2 weeks. Blood samples were obtained from the animals 5 days after the last injection. Moreover, 48 hr before bleeding time, Rev1[0.1 ml Rev1+0.9 PBS[was injected into the left hind foot pad of mice. The levels of anti-Rev1 antibody and the specific cellular immune responses were measured by microhemagglutination test and footpad thickness, respectively. Moreover, susceptibility of macrophages respiratory burst and proliferation of immune cells were measured in order withNitroblue tetrazolium[NBT] and Microculture Tetrazolium Assay [MTT]. The concentrations of IL-1, TNFα, Il-6, and IL-10 in the serum were determined using commercially available ELISA kits. We found a significant increase in anti-Rev1 antibody levels and simultaneously a significant decrease in the level of cellular immunity[DTH] in the treatment group compared to the control group. Lymphocyte proliferation index in splenocytes was significantly increased in the treatment group. However, the level of respiratory burst in phagocytic population of splenocytes dramatically decreased in the treatment group compared to the control. A significant decrease in IL-6, TNF-α , IL-1 and increaseIl-10 serum levels were also seen in the treatment group. Cynodon dactylon extract could have an anti-inflammatory effect through

  20. Transcriptome analysis of Pacific white shrimp (Litopenaeus vannamei) challenged by Vibrio parahaemolyticus reveals unique immune-related genes.

    Science.gov (United States)

    Qin, Zhendong; Babu, V Sarath; Wan, Quanyuan; Zhou, Meng; Liang, Risheng; Muhammad, Asim; Zhao, Lijuan; Li, Jun; Lan, Jiangfeng; Lin, Li

    2018-06-01

    Pacific white shrimp (Litopenaeus vannamei) is an important cultural species worldwide. However, Vibrio spp. infections have caused a great economic loss in Pacific white shrimp culture industry. The immune responses of Pacific white shrimp to the Vibrio spp. is not fully characterized. In this study, the transcriptomic profiles of L. vannamei hemocytes were explored by injecting with or without Vibrio parahaemolyticus. Totally, 42,632 high-quality unigenes were obtained from RNAseq data. Comparative genome analysis showed 2258 differentially expressed genes (DEGs) following the Vibrio challenge, including 1017 up-regulated and 1241 down-regulated genes. Eight DEGs were randomly selected for further validation by quantitative real-time RT-PCR (qRT-PCR) and the results showed that are consistent with the RNA-seq data. Due to the lack of predictable adaptive immunity, shrimps rely on an innate immune system to defend themselves against invading microbes by recognizing and clearing them through humoral and cellular immune responses. Here we focused our studies on the humoral immunity, five genes (SR, MNK, CTL3, GILT, and ALFP) were selected from the transcriptomic data, which were significantly up-regulated by V. parahaemolyticus infection. These genes were widely expressed in six different tissues and were up-regulated by both Gram negative bacteria (V. parahaemolyticus) and Gram positive bacteria (Staphylococcus aureus). To further extend our studies, we knock-down those five genes by dsRNA in L. vannamei and analyzed the functions of specific genes against V. parahaemolyticus and S. aureus by bacterial clearance analysis. We found that the ability of L. vannamei was significantly reduced in bacterial clearance when treated with those specific dsRNA. These results indicate that those five genes play essential roles in antibacterial immunity and have its specific functions against different types of pathogens. The obtained data will shed a new light on the immunity

  1. β3-Adrenergic receptors, adipokines and neuroendocrine activation during stress induced by repeated immune challenge in male and female rats.

    Science.gov (United States)

    Csanova, Agnesa; Hlavacova, Natasa; Hasiec, Malgorzata; Pokusa, Michal; Prokopova, Barbora; Jezova, Daniela

    2017-05-01

    The main hypothesis of the study is that stress associated with repeated immune challenge has an impact on β 3 -adrenergic receptor gene expression in the brain. Sprague-Dawley rats were intraperitoneally injected with increasing doses of lipopolysaccharide (LPS) for five consecutive days. LPS treatment was associated with body weight loss and increased anxiety-like behavior. In LPS-treated animals of both sexes, β 3 -receptor gene expression was increased in the prefrontal cortex but not the hippocampus. LPS treatment decreased β 3 -receptor gene expression in white adipose tissue with higher values in males compared to females. In the adipose tissue, LPS reduced peroxisome proliferator-activated receptor-gamma, leptin and adiponectin gene expression, but increased interleukin-6 expression, irrespective of sex. Repeated immune challenge resulted in increased concentrations of plasma aldosterone and corticosterone with higher values of corticosterone in females compared to males. Concentrations of dehydroepiandrosterone (DHEA) in plasma were unaffected by LPS, while DHEA levels in the frontal cortex were lower in the LPS-treated animals compared to the controls. Thus, changes of DHEA levels in the brain take place irrespective of the changes of this neurosteroid in plasma. We have provided the first evidence on stress-induced increase in β 3 -adrenergic receptor gene expression in the brain. Greater reduction of β 3 -adrenergic receptor expression in the adipose tissue and of the body weight gain by repeated immune challenge in male than in female rats suggests sex differences in the role of β 3 -adrenergic receptors in the metabolic functions. LPS-induced changes in adipose tissue regulatory factors and hormone concentrations might be important for coping with chronic infections.

  2. Evidence from Human and Animal Studies: Pathological Roles of CD8(+) T Cells in Autoimmune Peripheral Neuropathies.

    Science.gov (United States)

    Yang, Mu; Peyret, Corentin; Shi, Xiang Qun; Siron, Nicolas; Jang, Jeong Ho; Wu, Sonia; Fournier, Sylvie; Zhang, Ji

    2015-01-01

    Autoimmune peripheral neuropathies such as Guillain-Barre Syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) affect millions of people worldwide. Despite significant advances in understanding the pathology, the molecular and cellular mechanisms of immune-mediated neuropathies remain elusive. T lymphocytes definitely play an important role in disease pathogenesis and CD4(+) T cells have been the main area of research for decades. This is partly due to the fact that the most frequent animal model to study autoimmune peripheral neuropathy is experimental allergic neuritis (EAN). As it is induced commonly by immunization with peripheral nerve proteins, EAN is driven mainly by CD4(+) T cells. However, similarly to what has been reported for patients suffering from multiple sclerosis, a significant body of evidence indicates that CD8(+) T cells may play a pathogenic role in GBS and CIDP disease development and/or progression. Here, we summarize clinical studies pertaining to the presence and potential role of CD8(+) T cells in autoimmune peripheral neuropathies. We also discuss the findings from our most recent studies using a transgenic mouse line (L31 mice) in which the T cell co-stimulator molecule B7.2 (CD86) is constitutively expressed in antigen presenting cells of the nervous tissues. L31 mice spontaneously develop peripheral neuropathy, and CD8(+) T cells are found accumulating in peripheral nerves of symptomatic animals. Interestingly, depletion of CD4(+) T cells accelerates disease onset and increases disease prevalence. Finally, we point out some unanswered questions for future research to dissect the critical roles of CD8(+) T cells in autoimmune peripheral neuropathies.

  3. Evidence from Human and Animal Studies: Pathological Roles of CD8+ T Cells in Autoimmune Peripheral Neuropathies

    Science.gov (United States)

    Yang, Mu; Peyret, Corentin; Shi, Xiang Qun; Siron, Nicolas; Jang, Jeong Ho; Wu, Sonia; Fournier, Sylvie; Zhang, Ji

    2015-01-01

    Autoimmune peripheral neuropathies such as Guillain-Barre Syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) affect millions of people worldwide. Despite significant advances in understanding the pathology, the molecular and cellular mechanisms of immune-mediated neuropathies remain elusive. T lymphocytes definitely play an important role in disease pathogenesis and CD4+ T cells have been the main area of research for decades. This is partly due to the fact that the most frequent animal model to study autoimmune peripheral neuropathy is experimental allergic neuritis (EAN). As it is induced commonly by immunization with peripheral nerve proteins, EAN is driven mainly by CD4+ T cells. However, similarly to what has been reported for patients suffering from multiple sclerosis, a significant body of evidence indicates that CD8+ T cells may play a pathogenic role in GBS and CIDP disease development and/or progression. Here, we summarize clinical studies pertaining to the presence and potential role of CD8+ T cells in autoimmune peripheral neuropathies. We also discuss the findings from our most recent studies using a transgenic mouse line (L31 mice) in which the T cell co-stimulator molecule B7.2 (CD86) is constitutively expressed in antigen presenting cells of the nervous tissues. L31 mice spontaneously develop peripheral neuropathy, and CD8+ T cells are found accumulating in peripheral nerves of symptomatic animals. Interestingly, depletion of CD4+ T cells accelerates disease onset and increases disease prevalence. Finally, we point out some unanswered questions for future research to dissect the critical roles of CD8+ T cells in autoimmune peripheral neuropathies. PMID:26528293

  4. Stromal cell contributions to the homeostasis and functionality of the immune system.

    Science.gov (United States)

    Mueller, Scott N; Germain, Ronald N

    2009-09-01

    A defining characteristic of the immune system is the constant movement of many of its constituent cells through the secondary lymphoid tissues, mainly the spleen and lymph nodes, where crucial interactions that underlie homeostatic regulation, peripheral tolerance and the effective development of adaptive immune responses take place. What has only recently been recognized is the role that non-haematopoietic stromal elements have in many aspects of immune cell migration, activation and survival. In this Review, we summarize our current understanding of lymphoid compartment stromal cells, examine their possible heterogeneity, discuss how these cells contribute to immune homeostasis and the efficient initiation of adaptive immune responses, and highlight how targeting of these elements by some pathogens can influence the host immune response.

  5. Metabolic gene expression changes in astrocytes in Multiple Sclerosis cerebral cortex are indicative of immune-mediated signaling

    KAUST Repository

    Zeis, T.

    2015-04-01

    Emerging as an important correlate of neurological dysfunction in Multiple Sclerosis (MS), extended focal and diffuse gray matter abnormalities have been found and linked to clinical manifestations such as seizures, fatigue and cognitive dysfunction. To investigate possible underlying mechanisms we analyzed the molecular alterations in histopathological normal appearing cortical gray matter (NAGM) in MS. By performing a differential gene expression analysis of NAGM of control and MS cases we identified reduced transcription of astrocyte specific genes involved in the astrocyte–neuron lactate shuttle (ANLS) and the glutamate–glutamine cycle (GGC). Additional quantitative immunohistochemical analysis demonstrating a CX43 loss in MS NAGM confirmed a crucial involvement of astrocytes and emphasizes their importance in MS pathogenesis. Concurrently, a Toll-like/IL-1β signaling expression signature was detected in MS NAGM, indicating that immune-related signaling might be responsible for the downregulation of ANLS and GGC gene expression in MS NAGM. Indeed, challenging astrocytes with immune stimuli such as IL-1β and LPS reduced their ANLS and GGC gene expression in vitro. The detected upregulation of IL1B in MS NAGM suggests inflammasome priming. For this reason, astrocyte cultures were treated with ATP and ATP/LPS as for inflammasome activation. This treatment led to a reduction of ANLS and GGC gene expression in a comparable manner. To investigate potential sources for ANLS and GGC downregulation in MS NAGM, we first performed an adjuvant-driven stimulation of the peripheral immune system in C57Bl/6 mice in vivo. This led to similar gene expression changes in spinal cord demonstrating that peripheral immune signals might be one source for astrocytic gene expression changes in the brain. IL1B upregulation in MS NAGM itself points to a possible endogenous signaling process leading to ANLS and GGC downregulation. This is supported by our findings that, among others

  6. Effects of maternal protein or energy restriction during late gestation on immune status and responses to lipopolysaccharide challenge in postnatal young goats.

    Science.gov (United States)

    He, Z X; Sun, Z H; Yang, W Z; Beauchemin, K A; Tang, S X; Zhou, C S; Han, X F; Wang, M; Kang, J H; Tan, Z L

    2014-11-01

    Knowledge of maternal malnutrition of ruminants and effects on development of the immune system of their offspring is lacking. A study was conducted to investigate the effects of maternal protein or energy restriction during late gestation on immune status of their offspring at different ages. Sixty-three pregnant goats (local breed, Liuyang black goat, 22.2 ± 1.5 kg at d 90 of gestation) were fed control (CON, ME = 9.34 MJ/kg and CP = 12.5%, DM basis), 40% protein restricted (PR), or 40% energy restricted (ER) diets from d 91 of gestation to parturition, after which all animals received an adequate diet for nutritional recovery. Plasma concentrations of complement components (C3, C4), C-reactive protein (CRP) and immunoglobulins (IgG and IgM), jejunum cytokines (IL-2, IL-6, and IL-10) expression levels and morphology in the offspring were measured. Additionally, plasma concentration of complement and IL-6, and cytokines expression levels in gastrointestinal tract obtained at 6 wk from young goats were assessed under saline or lipopolysaccharide (LPS) challenging conditions. Maternal PR or ER decreased (P 0.05) plasma CRP concentration. The IL-10 mRNA expression of jejunum from PR kids was also less (P 0.05) in any plasma or tissue immune parameters among the 3 treatments. However, when given a LPS challenge, ER and PR kids had greater (P = 0.02) IL-6 concentration compared with CON kids. Our results suggest that both PR and ER during late gestation induced short-term as well as long-lasting alterations on immune responses in their offspring, which may make the animals more susceptible to a bacterial pathogen challenge. The present findings expand the existing knowledge in immunological mechanisms responsible for the development of disease in later life.

  7. Flavobacterium psychrophilum - Experimental challenge and immune response

    DEFF Research Database (Denmark)

    Henriksen, Maya Maria Mihályi

    the immune system of the fry is not fully developed. Theoretically, the infection pressure could be subdued by vaccinating larger fish, but no commercial vaccine is yet available. Diagnostic methods are well described and the disease is treated with antibiotics. To prevent disease outbreaks and subsequent......-time PCR (RT-PCR) was used to examine the immune response in the head kidney during the first eight days after infection, and enzyme-linked immunosorbent assay (ELISA) was used to evaluate the production of antibodies 50 days post-exposure. A pro-inflammatory response was observed in both groups infected...... of edemas, but in both cases the tissue was regenerating after 192 hours. However, when the fish had been exposed to both H2O2 and F. psychrophilum, the damage was still evident at this time point. The relative pathogen load measured as 16S rRNA was highest at the first sampling and decreased steadily...

  8. The fight-or-flight response is associated with PBMC expression profiles related to immune defence and recovery in swine.

    Directory of Open Access Journals (Sweden)

    Michael Oster

    Full Text Available Defining phenotypes according to molecular features would promote the knowledge of functional traits like behaviour in both human and animal research. Beside physiological states or environmental factors, an innate predisposition of individual coping strategies was discussed, including the proactive and reactive pattern. According to backtest reactivity, animals assigned as high-resisting (proactive and low-resisting (reactive were immune challenged with tetanus toxoid in a time course experiment. Using the Affymetrix platform and qPCR, individual coping characteristics were reflected as gene expression signatures in porcine peripheral blood mononuclear cells (PBMC at naïve state (day 0 and in response to the model antigen (day 14, day 28, and day 140. Further, the blood cell count was analysed at all stages. On the transcriptional level, processes acting on cell communication, vasculogenesis, and blood coagulation were highlighted in high-resisting animals at naïve state (day 0, temporarily blurred due to immune challenge (day 14 but subsequently restored and intensified (day 28. Notably, similar amounts of white and red blood cells, platelets and haematocrit between high-resisting and low-resisting samples suggest coping-specific expression patterns rather than alterations in blood cell distribution. Taken together, the gene expression patterns indicate that proactive pigs might favour molecular pathways enabling an effective strategy for defence and recovery. This corroborates the previously suggested belief, that proactive animals are prone to an increased number of injuries as an evolutionary inherited mechanism. In contrast to previous assumptions, coping-specific immunity in pigs lacks inherited shifts between cellular and humoral immune responses.

  9. Monounsaturated fats and immune function

    Directory of Open Access Journals (Sweden)

    P. Yaqoob

    1998-04-01

    Full Text Available Animal studies suggest that olive oil is capable of modulating functions of cells of the immune system in a manner similar to, albeit weaker than, fish oils. There is some evidence that the effects of olive oil on immune function in animal studies are due to oleic acid rather than to trace elements or antioxidants. Importantly, several studies have demonstrated effects of oleic acid-containing diets on in vivo immune responses. In contrast, consumption of a monounsaturated fatty acid (MUFA-rich diet by humans does not appear to bring about a general suppression of immune cell functions. The effects of this diet in humans are limited to decreasing aspects of adhesion of peripheral blood mononuclear cells, although there are trends towards decreases in natural killer cell activity and proliferation. The lack of a clear effect of MUFA in humans may be attributable to the higher level of monounsaturated fat used in the animal studies, although it is ultimately of importance to examine the effects of intakes which are in no way extreme. The effects of MUFA on adhesion molecules are potentially important, since these molecules appear to have a role in the pathology of a number of diseases involving the immune system. This area clearly deserves further exploration

  10. Peripheral nerve P2 basic protein and the Guillain-Barre syndrome : In vitro demonstration of P2-specific antibody-secreting cells

    NARCIS (Netherlands)

    Luijten, J.A.F.M.; Jong, W.A.C. de; Demel, R.A.; Heijnen, C.J.; Ballieux, R.E.

    1984-01-01

    An immune response to the peripheral nerve basic protein P2 may be operative in the pathogenesis of the Guillain-Barré syndrome (GBS). A method is described for the purification of P2 of human origin. Purified P2 was used to investigate whether lymphocytes derived from peripheral blood of GBS

  11. Beneficial Autoimmunity at Body Surfaces – Immune Surveillance and Rapid Type 2 Immunity Regulate Tissue Homeostasis and Cancer

    Science.gov (United States)

    Dalessandri, Tim; Strid, Jessica

    2014-01-01

    Epithelial cells (ECs) line body surface tissues and provide a physicochemical barrier to the external environment. Frequent microbial and non-microbial challenges such as those imposed by mechanical disruption, injury or exposure to noxious environmental substances including chemicals, carcinogens, ultraviolet-irradiation, or toxins cause activation of ECs with release of cytokines and chemokines as well as alterations in the expression of cell-surface ligands. Such display of epithelial stress is rapidly sensed by tissue-resident immunocytes, which can directly interact with self-moieties on ECs and initiate both local and systemic immune responses. ECs are thus key drivers of immune surveillance at body surface tissues. However, ECs have a propensity to drive type 2 immunity (rather than type 1) upon non-invasive challenge or stress – a type of immunity whose regulation and function still remain enigmatic. Here, we review the induction and possible role of type 2 immunity in epithelial tissues and propose that rapid immune surveillance and type 2 immunity are key regulators of tissue homeostasis and carcinogenesis. PMID:25101088

  12. Influence of radiotherapy on CD4+ CD25high regulatory cells in peripheral blood of NPC patients

    International Nuclear Information System (INIS)

    Liu Li; Ding Qian; Song Yingqiu; Cao Rubo; Yao Junxia; Huang Shiang

    2006-01-01

    Objective: The current study was designed to investigate the changes in peripheral CD4 + CD25 high regulatory T (CD4 + CD25 high Tr) cells in patients with nasopharyngeal carcinoma (NPC) and the influence of radiotherapy on immunity function. Methods: The peripheral blood was collected from 36 patients with NPC and 30 healthy controls. By using monoclonal antibodies, the blood samples were evaluated with flow cytometry for lymphocyte subsets and Tr cells. Results: The ratio of CD4 + /CD8 + in the NPC group was not significantly less than that in the healthy controls (P>0.05), but the prevalence of the CD4 + CD25 high Tr cells was significantly higher than that of the healthy group [(2.76 ± 1.06)% versus (2.06 ± 0.98)%, P + CD25 high Tr cells was higher than before it [(4.88 ± 1.02)%, P + CD25 high Tr cells in peripheral blood of NPC patients with or without radiotherapy was significantly higher than those in healthy controls, which may be related to immunosupression and tumor progression in such patients. This finding suggests that CD4 + CD25 high Tr cells in peripheral blood of NPC patients can be a useful index for monitoring the immunity function. (authors)

  13. Immunomodulatory capacity of fungal proteins on the cytokine production of human peripheral blood mononuclear cells

    NARCIS (Netherlands)

    Jeurink, P.V.; Lull Noguera, C.; Savelkoul, H.F.J.; Wichers, H.J.

    2008-01-01

    Immunomodulation by fungal compounds can be determined by the capacity of the compounds to influence the cytokine production by human peripheral blood mononuclear cells (hPBMC). These activities include mitogenicity, stimulation and activation of immune effector cells. Eight mushroom strains

  14. Characterization of Peripheral Immune Cell Subsets in Patients with Acute and Chronic Cerebrovascular Disease: A Case-Control Study

    Directory of Open Access Journals (Sweden)

    Peter Kraft

    2015-10-01

    Full Text Available Immune cells (IC play a crucial role in murine stroke pathophysiology. However, data are limited on the role of these cells in ischemic stroke in humans. We therefore aimed to characterize and compare peripheral IC subsets in patients with acute ischemic stroke/transient ischemic attack (AIS/TIA, chronic cerebrovascular disease (CCD and healthy volunteers (HV. We conducted a case-control study of patients with AIS/TIA (n = 116 or CCD (n = 117, and HV (n = 104 who were enrolled at the University Hospital Würzburg from 2010 to 2013. We determined the expression and quantity of IC subsets in the three study groups and performed correlation analyses with demographic and clinical parameters. The quantity of several IC subsets differed between the AIS/TIA, CCD, and HV groups. Several clinical and demographic variables independently predicted the quantity of IC subsets in patients with AIS/TIA. No significant changes in the quantity of IC subsets occurred within the first three days after AIS/TIA. Overall, these findings strengthen the evidence for a pathophysiologic role of IC in human ischemic stroke and the potential use of IC-based biomarkers for the prediction of stroke risk. A comprehensive description of IC kinetics is crucial to enable the design of targeted treatment strategies.

  15. IMMUNITY TO INFECTIONS AFTER HAPLOIDENTICAL HEMATOPOIETIC STEM CELL TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    Franco Aversa

    2016-10-01

    Full Text Available The advantage of using a Human Leukocyte Antigen (HLA-mismatched related donor is that almost every patient who does not have a HLA-identical donor or who urgently needs hematopoietic stem cell transplantation (HSCT has at least one family member with whom shares one haplotype (haploidentical and who is promptly available as a donor. The major challenge of haplo-HSCT is intense bi-directional alloreactivity leading to high incidences of graft rejection and graft-versus-host disease (GVHD. Advances in graft processing and in pharmacologic prophylaxis of GVHD have reduced these risks and have made haplo-HSCT a viable alternative for patients lacking a matched donor. Indeed, the haplo-HSCT  has spread to centers worldwide even though some centers have preferred an approach based on T cell depletion of G-CSF-mobilized peripheral blood progenitor cells (PBPCs, others have focused on new strategies for GvHD prevention, such as G-CSF priming of bone marrow and robust post-transplant immune suppression or post-transplant cyclophosphamide (PTCY. Today, the graft can be a megadose of T-cell depleted PBPCs or standard dose of unmanipulated bone marrow and/or PBPCs.  Although haplo-HSCT modalities are based mainly on high intensity conditioning regimens, recently introduced reduced intensity regimens (RIC   showed promise in decreasing early transplant-related mortality (TRM, and extending the opportunity of HSCT to an elderly population with more comorbidities. Infections are still mostly responsible for toxicity and non-relapse mortality due to prolonged immunosuppression related, or not, to GVHD. Future challenges lie in determining the safest preparative conditioning regimen, minimizing GvHD and promoting rapid and more robust immune reconstitution.

  16. Evaluation of the innate immune response of Angus heifers with genetic marker variation for intramuscular fat deposition following a lipopolysaccharide challenge

    Science.gov (United States)

    This study evaluated the effect of genetic selection for markers related to marbling deposition in Angus heifers on the immune response following a lipopolysaccharide (LPS) challenge. Fall-born heifers (n = 19; ~7 months of age, 274 +/- 24 kg) with genetic variation for marbling were utilized inclu...

  17. Peripheral Ulcerative Keratitis Associated with Autoimmune Disease: Pathogenesis and Treatment

    Directory of Open Access Journals (Sweden)

    Yan Cao

    2017-01-01

    Full Text Available Peripheral ulcerative keratitis (PUK is type of crescent-shaped inflammatory damage that occurs in the limbal region of the cornea. PUK is always combined with an epithelial defect and the destruction of the peripheral corneal stroma. PUK may have a connection to systemic conditions, such as long-standing rheumatoid arthritis (RA, systemic lupus erythematosus (SLE, Wegener granulomatosis (WG, relapsing polychondritis, classic polyarteritis nodosa and its variants, microscopic polyangiitis, and Churg-Strauss syndrome. However, the most common connection is with RA, which is also the focus of this review. The pathogenesis of PUK is still unclear. It is thought that circulating immune complexes and cytokines exert an important influence on the progression of this syndrome. Treatment is applied to inhibit certain aspects of PUK pathogenesis.

  18. Humoral and cell-mediated immune responses in DNA immunized mink challenged with wild-type canine distemper virus

    DEFF Research Database (Denmark)

    Nielsen, Line; Søgaard, Mette; Karlskov-Mortensen, Peter

    2009-01-01

    The aim of the study was to investigate the different phases of the immune response after DNA immunization with the hemagglutinin and nucleoprotein genes from canine distemper virus (CDV). Although attenuated live CDV vaccines have effectively reduced the incidence of disease, canine distemper...

  19. Peripheral neuropathy

    Science.gov (United States)

    ... peripheral; Neuritis - peripheral; Nerve disease; Polyneuropathy; Chronic pain - peripheral neuropathy ... Philadelphia, PA: Elsevier; 2016:chap 107. Shy ME. Peripheral neuropathies. In: Goldman L, Schafer AI, eds. Goldman's Cecil ...

  20. A model for personalized in vivo analysis of human immune responsiveness

    NARCIS (Netherlands)

    Kalscheuer, Hannes; Danzl, Nichole; Onoe, Takashi; Faust, Ted; Winchester, Robert; Goland, Robin; Greenberg, Ellen; Spitzer, Thomas R; Savage, David G; Tahara, Hiroyuki; Choi, Goda; Yang, Yong-Guang; Sykes, Megan

    2012-01-01

    Studies of human immune diseases are generally limited to the analysis of peripheral blood lymphocytes of heterogeneous patient populations. Improved models are needed to allow analysis of fundamental immunologic abnormalities predisposing to disease and in which to assess immunotherapies.

  1. In immune defense: redefining the role of the immune system in chronic disease.

    Science.gov (United States)

    Rubinow, Katya B; Rubinow, David R

    2017-03-01

    The recognition of altered immune system function in many chronic disease states has proven to be a pivotal advance in biomedical research over the past decade. For many metabolic and mood disorders, this altered immune activity has been characterized as inflammation, with the attendant assumption that the immune response is aberrant. However, accumulating evidence challenges this assumption and suggests that the immune system may be mounting adaptive responses to chronic stressors. Further, the inordinate complexity of immune function renders a simplistic, binary model incapable of capturing critical mechanistic insights. In this perspective article, we propose alternative paradigms for understanding the role of the immune system in chronic disease. By invoking allostasis or systems biology rather than inflammation, we can ascribe greater functional significance to immune mediators, gain newfound appreciation of the adaptive facets of altered immune activity, and better avoid the potentially disastrous effects of translating erroneous assumptions into novel therapeutic strategies.

  2. Development of Protective Immunity in New Zealand White Rabbits Challenged with Bacillus anthracis Spores and Treated with Antibiotics and Obiltoxaximab, a Monoclonal Antibody against Protective Antigen.

    Science.gov (United States)

    Henning, Lisa N; Carpenter, Sarah; Stark, Gregory V; Serbina, Natalya V

    2018-02-01

    The recommended management of inhalational anthrax, a high-priority bioterrorist threat, includes antibiotics and antitoxins. Obiltoxaximab, a chimeric monoclonal antibody against anthrax protective antigen (PA), is licensed under the U.S. Food and Drug Administration's (FDA's) Animal Rule for the treatment of inhalational anthrax. Because of spore latency, disease reemergence after treatment cessation is a concern, and there is a need to understand the development of endogenous protective immune responses following antitoxin-containing anthrax treatment regimens. Here, acquired protective immunity was examined in New Zealand White (NZW) rabbits challenged with a targeted lethal dose of Bacillus anthracis spores and treated with antibiotics, obiltoxaximab, or a combination of both. Survivors of the primary challenge were rechallenged 9 months later and monitored for survival. Survival rates after primary and rechallenge for controls and animals treated with obiltoxaximab, levofloxacin, or a combination of both were 0, 65, 100, and 95%, and 0, 100, 95, and 89%, respectively. All surviving immune animals had circulating antibodies to PA and serum toxin-neutralizing titers prior to rechallenge. Following rechallenge, systemic bacteremia and toxemia were not detected in most animals, and the levels of circulating anti-PA IgG titers increased starting at 5 days postrechallenge. We conclude that treatment with obiltoxaximab, alone or combined with antibiotics, significantly improves the survival of rabbits that received a lethal inhalation B. anthracis spore challenge dose and does not interfere with the development of immunity. Survivors of primary challenge are protected against reexposure, have rare incidents of systemic bacteremia and toxemia, and have evidence of an anamnestic response. Copyright © 2018 Henning et al.

  3. Differential immune microenvironments and response to immune checkpoint blockade amongst molecular subtypes of murine medulloblastoma

    Science.gov (United States)

    Pham, Christina D.; Flores, Catherine; Yang, Changlin; Pinheiro, Elaine M.; Yearley, Jennifer H.; Sayour, Elias J.; Pei, Yanxin; Moore, Colin; McLendon, Roger E.; Huang, Jianping; Sampson, John H.; Wechsler-Reya, Robert; Mitchell, Duane A.

    2016-01-01

    PURPOSE Despite significant strides in the identification and characterization of potential therapeutic targets for medulloblastoma (MB), the role of the immune system and its interplay with the tumor microenvironment within these tumors are poorly understood. To address this, we adapted two syngeneic animal models of human Sonic Hedgehog (SHH)-driven and Group 3 MB for preclinical evaluation in immunocompetent C57BL/6 mice. METHODS AND RESULTS Multicolor flow cytometric analyses were used to phenotype and characterize immune infiltrating cells within established cerebellar tumors. We observed significantly higher percentages of dendritic cells, infiltrating lymphocytes, myeloid derived suppressor cells and tumor-associated macrophages in murine SHH model tumors compared with Group 3 tumors. However, murine Group 3 tumors had higher percentages of CD8+ PD-1+ T cells within the CD3 population. PD-1 blockade conferred superior antitumor efficacy in animals bearing intracranial Group 3 tumors compared to SHH group tumors, indicating that immunologic differences within the tumor microenvironment can be leveraged as potential targets to mediate antitumor efficacy. Further analysis of anti-PD-1 monoclonal antibody localization revealed binding to PD-1+ peripheral T cells, but not tumor infiltrating lymphocytes within the brain tumor microenvironment. Peripheral PD-1 blockade additionally resulted in a marked increase in CD3+ T cells within the tumor microenvironment. CONCLUSIONS This is the first immunologic characterization of preclinical models of molecular subtypes of MB and demonstration that response to immune checkpoint blockade differs across subtype classification. Our findings also suggest that effective anti-PD-1 blockade does not require that systemically administered antibodies penetrate the brain tumor microenvironment. PMID:26405194

  4. Differential Immune Microenvironments and Response to Immune Checkpoint Blockade among Molecular Subtypes of Murine Medulloblastoma.

    Science.gov (United States)

    Pham, Christina D; Flores, Catherine; Yang, Changlin; Pinheiro, Elaine M; Yearley, Jennifer H; Sayour, Elias J; Pei, Yanxin; Moore, Colin; McLendon, Roger E; Huang, Jianping; Sampson, John H; Wechsler-Reya, Robert; Mitchell, Duane A

    2016-02-01

    Despite significant strides in the identification and characterization of potential therapeutic targets for medulloblastoma, the role of the immune system and its interplay with the tumor microenvironment within these tumors are poorly understood. To address this, we adapted two syngeneic animal models of human Sonic Hedgehog (SHH)-driven and group 3 medulloblastoma for preclinical evaluation in immunocompetent C57BL/6 mice. Multicolor flow cytometric analyses were used to phenotype and characterize immune infiltrating cells within established cerebellar tumors. We observed significantly higher percentages of dendritic cells, infiltrating lymphocytes, myeloid-derived suppressor cells, and tumor-associated macrophages in murine SHH model tumors compared with group 3 tumors. However, murine group 3 tumors had higher percentages of CD8(+) PD-1(+) T cells within the CD3 population. PD-1 blockade conferred superior antitumor efficacy in animals bearing intracranial group 3 tumors compared with SHH group tumors, indicating that immunologic differences within the tumor microenvironment can be leveraged as potential targets to mediate antitumor efficacy. Further analysis of anti-PD-1 monoclonal antibody localization revealed binding to PD-1(+) peripheral T cells, but not tumor infiltrating lymphocytes within the brain tumor microenvironment. Peripheral PD-1 blockade additionally resulted in a marked increase in CD3(+) T cells within the tumor microenvironment. This is the first immunologic characterization of preclinical models of molecular subtypes of medulloblastoma and demonstration that response to immune checkpoint blockade differs across subtype classification. Our findings also suggest that effective anti-PD-1 blockade does not require that systemically administered antibodies penetrate the brain tumor microenvironment. ©2015 American Association for Cancer Research.

  5. Obesity induced by a high-fat diet is associated with increased immune cell entry into the central nervous system.

    Science.gov (United States)

    Buckman, Laura B; Hasty, Alyssa H; Flaherty, David K; Buckman, Christopher T; Thompson, Misty M; Matlock, Brittany K; Weller, Kevin; Ellacott, Kate L J

    2014-01-01

    Obesity is associated with chronic low-grade inflammation in peripheral tissues caused, in part, by the recruitment of inflammatory monocytes into adipose tissue. Studies in rodent models have also shown increased inflammation in the central nervous system (CNS) during obesity. The goal of this study was to determine whether obesity is associated with recruitment of peripheral immune cells into the CNS. To do this we used a bone marrow chimerism model to track the entry of green-fluorescent protein (GFP) labeled peripheral immune cells into the CNS. Flow cytometry was used to quantify the number of GFP(+) immune cells recruited into the CNS of mice fed a high-fat diet compared to standard chow fed controls. High-fat feeding resulted in obesity associated with a 30% increase in the number of GFP(+) cells in the CNS compared to control mice. Greater than 80% of the GFP(+) cells recruited to the CNS were also CD45(+) CD11b(+) indicating that the GFP(+) cells displayed characteristics of microglia/macrophages. Immunohistochemistry further confirmed the increase in GFP(+) cells in the CNS of the high-fat fed group and also indicated that 93% of the recruited cells were found in the parenchyma and had a stellate morphology. These findings indicate that peripheral immune cells can be recruited to the CNS in obesity and may contribute to the inflammatory response. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Photoperiod- and Triiodothyronine-dependent Regulation of Reproductive Neuropeptides, Proinflammatory Cytokines, and Peripheral Physiology in Siberian Hamsters (Phodopus sungorus).

    Science.gov (United States)

    Banks, Ruth; Delibegovic, Mirela; Stevenson, Tyler J

    2016-06-01

    Seasonal trade-offs in reproduction and immunity are ubiquitous in nature. The mechanisms that govern transitions across seasonal physiological states appear to involve reciprocal switches in the local synthesis of thyroid hormone. In long-day (LD) summer-like conditions, increased hypothalamic triiodothyronine (T3) stimulates gonadal development. Alternatively, short-day (SD) winter-like conditions increase peripheral leukocytes and enhance multiple aspects of immune function. These data indicate that the localized effects of T3 in the hypothalamus and leukocytes are photoperiod dependent. We tested the hypothesis that increased peripheral T3 in SD conditions would increase aspects of reproductive physiology and inhibit immune function, whereas T3 injections in LD conditions would facilitate aspects of immune function (i.e., leukocytes). In addition, we also examined whether T3 regulates hypothalamic neuropeptide expression as well as hypothalamic and splenic proinflammatory cytokine expression. Adult male Siberian hamsters were maintained in LD (15L:9D) or transferred to SD (9L:15D) for 8 weeks. A subset of LD and SD hamsters was treated daily with 5 µg T3 for 2 weeks. LD and SD controls were injected with saline. Daily T3 administration in SD hamsters (SD+T3) resulted in a rapid and substantial decrease in peripheral leukocyte concentrations and stimulated gonadal development. T3 treatment in LD (LD+T3) had no effect on testicular volumes but significantly increased leukocyte concentrations. Molecular analyses revealed that T3 stimulated interleukin 1β messenger RNA (mRNA) expression in the spleen and inhibited RFamide Related Peptide-3 mRNA expression in the hypothalamus. Moreover, there was a photoperiod-dependent decrease in splenic tumor necrosis factor-α mRNA expression. These findings reveal that T3 has tissue-specific and photoperiod-dependent regulation of seasonal rhythms in reproduction and immune function. © 2016 The Author(s).

  7. Effects of smoking on activation markers, Fas expression and apoptosis of peripheral blood lymphocytes

    NARCIS (Netherlands)

    Bijl, Marc; Limburg, Piet; Kallenberg, Cees; Horst, G.

    Background Smoking influences numbers and function of peripheral blood lymphocytes (PBL) by a process that is badly understood. We conducted this study to evaluate whether the immune impairment of smoking might be related to changes in the expression or functionality of Fas, a cell surface molecule

  8. Responses to high-fat challenges varying in fat type in subjects with different metabolic risk phenotypes: a randomized trial.

    Directory of Open Access Journals (Sweden)

    Susan J van Dijk

    Full Text Available The ability of subjects to respond to nutritional challenges can reflect the flexibility of their biological system. Nutritional challenge tests could be used as an indicator of health status but more knowledge on metabolic and immune responses of different subjects to nutritional challenges is needed. The aim of this study was to compare the responses to high-fat challenges varying in fat type in subjects with different metabolic risk phenotypes.In a cross-over design 42 men (age 50-70 y consumed three high-fat shakes containing saturated fat (SFA, monounsaturated fat (MUFA or n-3 polyunsaturated (PUFA. Men were selected on BMI and health status (lean, obese or obese diabetic and phenotyped with MRI for adipose tissue distribution. Before and 2 and 4 h after shake consumption blood was drawn for measurement of expression of metabolic and inflammation-related genes in peripheral blood mononuclear cells (PBMCs, plasma triglycerides (TAG, glucose, insulin, cytokines and ex vivo PBMC immune response capacity. The MUFA and n-3 PUFA challenge, compared to the SFA challenge, induced higher changes in expression of inflammation genes MCP1 and IL1β in PBMCs. Obese and obese diabetic subjects had different PBMC gene expression and metabolic responses to high-fat challenges compared to lean subjects. The MUFA challenge induced the most pronounced TAG response, mainly in obese and obese diabetic subjects.The PBMC gene expression response and metabolic response to high-fat challenges were affected by fat type and metabolic risk phenotype. Based on our results we suggest using a MUFA challenge to reveal differences in response capacity of subjects.ClinicalTrials.gov NCT00977262.

  9. Effects of estrogen on CD4+CD25+ regulatory T cell in peripheral blood during pregnancy

    Institute of Scientific and Technical Information of China (English)

    Yuan-Huan Xiong; Zhen Yuan; Li He

    2013-01-01

    Objective:To investigate the effects of estrogen (E2) level on regulatory T cells (Treg) in peripheral blood during pregnancy. Methods:A total of 30 healthy non-pregnant women were selected as control group, 90 pregnant women of early, middle and late pregnancy and 30 postpartum women at 1 month after parturition were selected as experimental groups including early pregnancy group, middle pregnancy group and late pregnancy group;the proportions of CD4+CD25+Treg and CD4+CD25+CD127-Treg among CD4+T cells were detected by flow cytometry;the serum estrogen content in peripheral blood was detected by electrochemical immune luminescence method. Results: E2 level was coincident with the change of Tregs number during pregnancy. The estrogen content in peripheral blood increased gradually from early pregnancy to late pregnancy, then decreased significantly after parturition, and the level at 1 month after parturition down to the level in non-pregnancy group (P>0.05);the level of E2 in pregnancy groups were significantly higher than those in non-pregnancy group (P0.05);the proportions in middle and late pregnancy groups were significantly higher than those in early pregnancy group (P0.05). There was correlation between Tregs number with estrogen level during pregnancy. The proportion of CD4+CD25+ Treg and CD4+CD25+CD127- Treg were positively correlated with estrogen level. Conclusions:High proportion of CD4+CD25+Treg and CD4+CD25+CD127-Treg is closely related to the high level of E2 during pregnancy. It suggested that high level of estrogen may induce an increase of CD4+CD25+Treg in peripheral blood, and then influence the immune function of pregnant women. The results of this experiment might play an important role of estrogen in immune-modulation during pregnancy.

  10. Lack of mucosal immune reconstitution during prolonged treatment of acute and early HIV-1 infection.

    Directory of Open Access Journals (Sweden)

    Saurabh Mehandru

    2006-12-01

    Full Text Available During acute and early HIV-1 infection (AEI, up to 60% of CD4(+ T cells in the lamina propria of the lower gastrointestinal (GI tract are lost as early as 2-4 wk after infection. Reconstitution in the peripheral blood during therapy with highly active antiretroviral therapy (HAART is well established. However, the extent of immune reconstitution in the GI tract is unknown.Fifty-four AEI patients and 18 uninfected control participants underwent colonic biopsy. Forty of the 54 AEI patients were followed after initiation of antiretroviral therapy (18 were studied longitudinally with sequential biopsies over a 3-y period after beginning HAART, and 22 were studied cross sectionally after 1-7 y of uninterrupted therapy. Lymphocyte subsets, markers of immune activation and memory in the peripheral blood and GI tract were determined by flow cytometry and immunohistochemistry. In situ hybridization was performed in order to identify persistent HIV-1 RNA expression. Of the patients studied, 70% maintained, on average, a 50%-60% depletion of lamina propria lymphocytes despite 1-7 y of HAART. Lymphocytes expressing CCR5 and both CCR5 and CXCR4 were persistently and preferentially depleted. Levels of immune activation in the memory cell population, CD45RO+ HLA-DR+, returned to levels seen in the uninfected control participants in the peripheral blood, but were elevated in the GI tract of patients with persistent CD4+ T cell depletion despite therapy. Rare HIV-1 RNA-expressing cells were detected by in situ hybridization.Apparently suppressive treatment with HAART during acute and early infection does not lead to complete immune reconstitution in the GI mucosa in the majority of patients studied, despite immune reconstitution in the peripheral blood. Though the mechanism remains obscure, the data suggest that there is either viral or immune-mediated accelerated T cell destruction or, possibly, alterations in T cell homing to the GI tract. Although clinically

  11. Consumption of selenium-enriched broccoli increases cytokine production in human peripheral blood mononuclear cells stimulated ex vivo, a preliminary human intervention study.

    Science.gov (United States)

    Bentley-Hewitt, Kerry L; Chen, Ronan K-Y; Lill, Ross E; Hedderley, Duncan I; Herath, Thanuja D; Matich, Adam J; McKenzie, Marian J

    2014-12-01

    Selenium (Se) is a micronutrient essential for human health, including immune function. Previous research indicates that Se supplementation may cause a shift from T helper (Th)1- to Th2-type immune responses. We aim to test the potential health promoting effects of Se-enriched broccoli. In a human trial, 18 participants consumed control broccoli daily for 3 days. After a 3-day wash-out period, the participants were provided with Se-enriched broccoli containing 200 μg of Se per serving for 3 days. Plasma and peripheral blood mononuclear cell (PBMC) samples were collected at the start and end of each broccoli feeding period for analysis of total Se and measurement of cytokine production from PBMC stimulated with antigens ex vivo. Plasma Se content remained consistent throughout the control broccoli feeding period and the baseline of the Se-enriched broccoli period (1.22 μmol/L) and then significantly increased following 3 days of Se-enriched broccoli feeding. Interleukin (IL-2, IL-4, IL-5, IL-13, and IL-22) production from PBMC significantly increased after 3 days of Se-enriched broccoli feeding compared with baseline. This study indicates that consumption of Se-enriched broccoli may increase immune responses toward a range of immune challenges. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Increasing Immunization Compliance by Reducing Provisional Admittance

    Science.gov (United States)

    Davis, Wendy S.; Varni, Susan E.; Barry, Sara E.; Frankowski, Barbara L.; Harder, Valerie S.

    2016-01-01

    Students in Vermont with incomplete or undocumented immunization status are provisionally admitted to schools and historically had a calendar year to resolve their immunization status. The process of resolving these students' immunization status was challenging for school nurses. We conducted a school-based quality improvement effort to increase…

  13. Impact of organic and conventional carrots on intestinal and peripheral immunity

    DEFF Research Database (Denmark)

    Roselli, Marianna; Finamore, Alberto; Brasili, Elisa

    2012-01-01

    ) were grown in three ORG (O1, O2 and O3) and one CV cropping system (D-CV). Italian carrots (Maestro and Excelso varieties) were grown in one ORG and one CV field for each variety. Immune phenotypes of blood, spleen and intestinal lymphocytes, and cytokine serum levels were analyzed in mice fed...... the different carrots for 30 days. Principal component analysis (PCA) was performed in mice fed the Danish carrots. The consumption of the ‘more organic’ O2 and O3 carrots induced some changes in lymphocyte populations, including an increase in regulatory T cells. In Italian carrots more differences between ORG...... and CV were observed in the first as compared to the second year. No relevant differences were observed in cytokine secretion. PCA showed a clear separation among mice fed the O1, O2, O3 and D-CV carrots. CONCLUSIONS: Although a great variability was observed between the two years, an immune stimulation...

  14. Immune Privilege and Eye-Derived T-Regulatory Cells

    Directory of Open Access Journals (Sweden)

    Hiroshi Keino

    2018-01-01

    Full Text Available Certain cellular components of the eye, such as neural retina, are unable to regenerate and replicate after destructive inflammation. Ocular immune privilege provides the eye with immune protection against intraocular inflammation in order to minimize the risk to vision integrity. The eye and immune system use strategies to maintain the ocular immune privilege by regulating the innate and adaptive immune response, which includes immunological ignorance, peripheral tolerance to eye-derived antigens, and intraocular immunosuppressive microenvironment. In this review, we summarize current knowledge regarding the molecular mechanism responsible for the development and maintenance of ocular immune privilege via regulatory T cells (Tregs, which are generated by the anterior chamber-associated immune deviation (ACAID, and ocular resident cells including corneal endothelial (CE cells, ocular pigment epithelial (PE cells, and aqueous humor. Furthermore, we examined the therapeutic potential of Tregs generated by RPE cells that express transforming growth factor beta (TGF-β, cytotoxic T lymphocyte-associated antigen-2 alpha (CTLA-2α, and retinoic acid for autoimmune uveoretinitis and evaluated a new strategy using human RPE-induced Tregs for clinical application in inflammatory ocular disease. We believe that a better understanding of the ocular immune privilege associated with Tregs might offer a new approach with regard to therapeutic interventions for ocular autoimmunity.

  15. Immune Privilege and Eye-Derived T-Regulatory Cells.

    Science.gov (United States)

    Keino, Hiroshi; Horie, Shintaro; Sugita, Sunao

    2018-01-01

    Certain cellular components of the eye, such as neural retina, are unable to regenerate and replicate after destructive inflammation. Ocular immune privilege provides the eye with immune protection against intraocular inflammation in order to minimize the risk to vision integrity. The eye and immune system use strategies to maintain the ocular immune privilege by regulating the innate and adaptive immune response, which includes immunological ignorance, peripheral tolerance to eye-derived antigens, and intraocular immunosuppressive microenvironment. In this review, we summarize current knowledge regarding the molecular mechanism responsible for the development and maintenance of ocular immune privilege via regulatory T cells (Tregs), which are generated by the anterior chamber-associated immune deviation (ACAID), and ocular resident cells including corneal endothelial (CE) cells, ocular pigment epithelial (PE) cells, and aqueous humor. Furthermore, we examined the therapeutic potential of Tregs generated by RPE cells that express transforming growth factor beta (TGF- β ), cytotoxic T lymphocyte-associated antigen-2 alpha (CTLA-2 α ), and retinoic acid for autoimmune uveoretinitis and evaluated a new strategy using human RPE-induced Tregs for clinical application in inflammatory ocular disease. We believe that a better understanding of the ocular immune privilege associated with Tregs might offer a new approach with regard to therapeutic interventions for ocular autoimmunity.

  16. Reduction of porcine circovirus type 2 (PCV2 viremia by a reformulated inactivated chimeric PCV1-2 vaccine-induced humoral and cellular immunity after experimental PCV2 challenge

    Directory of Open Access Journals (Sweden)

    Seo Hwi

    2012-10-01

    Full Text Available Abstract Background The objective of the present study was to elucidate the humoral and cellular immune response mechanisms by which a reformulated inactivated chimeric PCV1-2 vaccine reduces the PCV2 viremia. Forty PCV2 seronegative 3-week-old pigs were randomly divided into the following four groups: vaccinated challenged (T01, vaccinated non-challenged (T02, non-vaccinated challenged (T03, and non-vaccinated non-challenged (T04 animals. The pigs in groups T01 and T02 were immunized with a reformulated inactivated chimeric PCV1-2 vaccine (Fostera™ PCV; Pfizer Animal Health administered as a 2.0 ml dose at 21 days of age. At 35 days of age (0 days post-challenge, the pigs in groups T01 and T03 were inoculated intranasally with 2 ml each of PCV2b. Results A reduction of PCV2 viremia coincided with the appearance of both PCV2-specific neutralizing antibodies (NA and interferon-γ-secreting cells (IFN-γ-SCs in the vaccinated animals. However, the presence of anti-PCV2 IgG antibodies did not correlate with the reduction of PCV2 viremia. Lymphocyte subset analysis indicated that the numbers of CD3+ and CD4+ cells increased in vaccinated animals but the numbers of CD4+ cells decreased transiently in non-vaccinated animals. The observation of a delayed type hypersensitivity response in only the vaccinated animals also supports a CD4+ cell-associated protective cellular immune response induced by the reformulated inactivated chimeric PCV1-2 vaccine. Conclusions The induction of PCV2-specific NA and IFN-γ-SCs, and CD4+ cells by the reformulated inactivated chimeric PCV1-2 vaccine is the important protective immune response leading to reduction of the PCV2 viremia and control of the PCV2 infection. To our knowledge this is the first demonstration of protective humoral and cellular immunity induced by the reformulated inactivated chimeric PCV1-2 vaccine and its effect on reduction of PCV2 viremia by vaccination.

  17. [Bone marrow stromal damage mediated by immune response activity].

    Science.gov (United States)

    Vojinović, J; Kamenov, B; Najman, S; Branković, Lj; Dimitrijević, H

    1994-01-01

    The aim of this work was to estimate influence of activated immune response on hematopoiesis in vitro, using the experimental model of BCG immunized BALB/c mice and in patients with chronic immunoactivation: long-lasting infections, autoimmunity or malignancy. We correlated changes in long term bone marrow cultures (Dexter) and NBT reduction with appearance of anemia in patients and experimental model of immunization by BCG. Increased spontaneous NBT reduction pointed out role of macrophage activation in bone marrow stroma damage. Long-term bone marrow cultures showed reduced number of hematopoietic cells, with predomination of fibroblasts and loss of fat cells. This results correlated with anemia and leucocytosis with stimulated myelopoiesis in peripheral blood. Activation of immune response, or acting of any agent that directly changes extracellular matrix and cellularity of bone marrow, may result in microenviroment bone marrow damage that modify hematopoiesis.

  18. Multivariate analysis of the immune response to a vaccine as an alternative to the repetition of animal challenge studies for vaccines with demonstrated efficacy.

    Science.gov (United States)

    Chapat, Ludivine; Hilaire, Florence; Bouvet, Jérome; Pialot, Daniel; Philippe-Reversat, Corinne; Guiot, Anne-Laure; Remolue, Lydie; Lechenet, Jacques; Andreoni, Christine; Poulet, Hervé; Day, Michael J; De Luca, Karelle; Cariou, Carine; Cupillard, Lionel

    2017-07-01

    The assessment of vaccine combinations, or the evaluation of the impact of minor modifications of one component in well-established vaccines, requires animal challenges in the absence of previously validated correlates of protection. As an alternative, we propose conducting a multivariate analysis of the specific immune response to the vaccine. This approach is consistent with the principles of the 3Rs (Refinement, Reduction and Replacement) and avoids repeating efficacy studies based on infectious challenges in vivo. To validate this approach, a set of nine immunological parameters was selected in order to characterize B and T lymphocyte responses against canine rabies virus and to evaluate the compatibility between two canine vaccines, an inactivated rabies vaccine (RABISIN ® ) and a combined vaccine (EURICAN ® DAPPi-Lmulti) injected at two different sites in the same animals. The analysis was focused on the magnitude and quality of the immune response. The multi-dimensional picture given by this 'immune fingerprint' was used to assess the impact of the concomitant injection of the combined vaccine on the immunogenicity of the rabies vaccine. A principal component analysis fully discriminated the control group from the groups vaccinated with RABISIN ® alone or RABISIN ® +EURICAN ® DAPPi-Lmulti and confirmed the compatibility between the rabies vaccines. This study suggests that determining the immune fingerprint, combined with a multivariate statistical analysis, is a promising approach to characterizing the immunogenicity of a vaccine with an established record of efficacy. It may also avoid the need to repeat efficacy studies involving challenge infection in case of minor modifications of the vaccine or for compatibility studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Transfer of adoptive immunity to tuberculosis in mice

    International Nuclear Information System (INIS)

    Lefford, M.J.

    1975-01-01

    A system is described for studying adoptive immunity to tuberculosis in syngeneic mice. Donor mice were immunized with 10 4 BCG intravenously, and lymphoid cells were harvested 28 days later. Adoptive immunity was measured in recipient mice in terms of the inhibition of growth of BCG in the liver and spleen following intravenous injection. Adoptive immunity was expressed optimally when recipients were sublethally irradiated (500 R), challenged with 10 4 to 10 5 viable organisms, and given sensitized lymphoid cells intravenously. Adoptive immunity was not manifest until 14 days after challenge and was effective against Mycobacterium tuberculosis H37Rv as well as BCG. Immunity could be conferred by spleen, lymph node, peritoneal exudate, and resident peritoneal (washout) cells. The lymphoid cells conferring immunity were shown to be thymus-dependent lymphocytes by virtue of their nonadherence to glass wool and sensitivity to anti-theta serum plus complement. The sensitized cells were relatively susceptible to both in vitro and in vivo x irradiation

  20. Engineering synthetic vaccines using cues from natural immunity

    Science.gov (United States)

    Irvine, Darrell J.; Swartz, Melody A.; Szeto, Gregory L.

    2013-11-01

    Vaccines aim to protect against or treat diseases through manipulation of the immune response, promoting either immunity or tolerance. In the former case, vaccines generate antibodies and T cells poised to protect against future pathogen encounter or attack diseased cells such as tumours; in the latter case, which is far less developed, vaccines block pathogenic autoreactive T cells and autoantibodies that target self tissue. Enormous challenges remain, however, as a consequence of our incomplete understanding of human immunity. A rapidly growing field of research is the design of vaccines based on synthetic materials to target organs, tissues, cells or intracellular compartments; to co-deliver immunomodulatory signals that control the quality of the immune response; or to act directly as immune regulators. There exists great potential for well-defined materials to further our understanding of immunity. Here we describe recent advances in the design of synthetic materials to direct immune responses, highlighting successes and challenges in prophylactic, therapeutic and tolerance-inducing vaccines.

  1. Anxiety and cerebral blood flow during behavioral challenge. Dissociation of central from peripheral and subjective measures

    International Nuclear Information System (INIS)

    Zohar, J.; Insel, T.R.; Berman, K.F.; Foa, E.B.; Hill, J.L.; Weinberger, D.R.

    1989-01-01

    To investigate the relationship between anxiety and regional cerebral blood flow, we administered behavioral challenges to 10 patients with obsessive-compulsive disorder while measuring regional cerebral blood flow with the xenon 133 inhalation technique. Each patient was studied under three conditions: relaxation, imaginal flooding, and in vivo (actual) exposure to the phobic stimulus. Subjective anxiety, obsessive-compulsive ratings, and autonomic measures (heart rate, blood pressure) increased significantly, but respiratory rate and PCO 2 did not change across the three conditions. Regional cerebral blood flow increased slightly (in the temporal region) during imaginal flooding, but decreased markedly in several cortical regions during in vivo exposure, when anxiety was highest by subjective and peripheral autonomic measures. These results demonstrate that intense anxiety can be associated with decreased rather than increased cortical perfusion and that ostensibly related states of anxiety (eg, anticipatory and obsessional anxiety) may be associated with opposite effects on regional cerebral blood flow

  2. Interleukin-22-producing innate immune cells: new players in mucosal immunity and tissue repair?

    NARCIS (Netherlands)

    Vivier, Eric; Spits, Hergen; Cupedo, Tom

    2009-01-01

    Mucosal tissues, lying at the interface with the external environment, are constantly challenged by microbial, physical and chemical assaults. To provide the necessary immune defence to such challenges, lymph nodes and Peyer's patches are formed in utero in response to inductive signals from

  3. Peripheral Neuropathy: A Practical Approach to Diagnosis and Symptom Management.

    Science.gov (United States)

    Watson, James C; Dyck, P James B

    2015-07-01

    Peripheral neuropathy is one of the most prevalent neurologic conditions encountered by physicians of all specialties. Physicians are faced with 3 distinct challenges in caring for patients with peripheral neuropathy: (1) how to efficiently and effectively screen (in less than 2 minutes) an asymptomatic patient for peripheral neuropathy when they have a disorder in which peripheral neuropathy is highly prevalent (eg, diabetes mellitus), (2) how to clinically stratify patients presenting with symptoms of neuropathy to determine who would benefit from specialty consultation and what testing is appropriate for those who do not need consultation, and (3) how to treat the symptoms of painful peripheral neuropathy. In this concise review, we address these 3 common clinical scenarios. Easily defined clinical patterns of involvement are used to identify patients in need of neurologic consultation, the yield of laboratory and other diagnostic testing is reviewed for the evaluation of length-dependent, sensorimotor peripheral neuropathies (the most common form of neuropathy), and an algorithmic approach with dosing recommendations is provided for the treatment of neuropathic pain associated with peripheral neuropathy. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  4. Involvement of CD8+ T cell-mediated immune responses in LcrV DNA vaccine induced protection against lethal Yersinia pestis challenge.

    Science.gov (United States)

    Wang, Shixia; Goguen, Jon D; Li, Fusheng; Lu, Shan

    2011-09-09

    Yersinia pestis (Y. pestis) is the causative pathogen of plague, a highly fatal disease for which an effective vaccine, especially against mucosal transmission, is still not available. Like many bacterial infections, antigen-specific antibody responses have been traditionally considered critical, if not solely responsible, for vaccine-induced protection against Y. pestis. Studies in recent years have suggested the importance of T cell immune responses against Y. pestis infection but information is still limited about the details of Y. pestis antigen-specific T cell immune responses. In current report, studies are conducted to identify the presence of CD8+ T cell epitopes in LcrV protein, the leading antigen of plague vaccine development. Furthermore, depletion of CD8+ T cells in LcrV DNA vaccinated Balb/C mice led to reduced protection against lethal intranasal challenge of Y. pestis. These findings establish that an LcrV DNA vaccine is able to elicit CD8+ T cell immune responses against specific epitopes of this key plague antigen and that a CD8+ T cell immune response is involved in LcrV DNA vaccine-elicited protection. Future studies in plague vaccine development will need to examine if the presence of detectable T cell immune responses, in particular CD8+ T-cell immune responses, will enhance the protection against Y. pestis in higher animal species or humans. Copyright © 2010 Elsevier Ltd. All rights reserved.

  5. Memory and Specificity in the Insect Immune System: Current Perspectives and Future Challenges

    Directory of Open Access Journals (Sweden)

    Dustin Cooper

    2017-05-01

    Full Text Available The immune response of a host to a pathogen is typically described as either innate or adaptive. The innate form of the immune response is conserved across all organisms, including insects. Previous and recent research has focused on the nature of the insect immune system and the results imply that the innate immune response of insects is more robust and specific than previously thought. Priming of the insect innate immune system involves the exposure of insects to dead or a sublethal dose of microbes in order to elicit an initial response. Comparing subsequent infections in primed insects to non-primed individuals indicates that the insect innate immune response may possess some of the qualities of an adaptive immune system. Although some studies demonstrate that the protective effects of priming are due to a “loitering” innate immune response, others have presented more convincing elements of adaptivity. While an immune mechanism capable of producing the same degree of recognition specificity as seen in vertebrates has yet to be discovered in insects, a few interesting cases have been identified and discussed.

  6. FOXP3-specific immunity

    DEFF Research Database (Denmark)

    Andersen, Mads Hald

    2013-01-01

    Forkhead box P3 (FOXP3)-specific cytotoxic CD8(+) T cells are present among human peripheral blood mononuclear cells (PBMCs), especially in cancer patients. Such T lymphocytes are able not only to specifically recognize dendritic cells (DCs) that have been exposed to recombinant FOXP3 and regulat...... and regulatory T cells, but also to kill FOXP3(+) malignant T cells. The natural occurrence of FOXP3-specific cytotoxic T lymphocytes among human PBMCs suggests a general role for these cells in the complex network of immune regulation....

  7. Immune-based strategies for mood disorders: facts and challenges.

    Science.gov (United States)

    Colpo, Gabriela D; Leboyer, Marion; Dantzer, Robert; Trivedi, Mahdukar H; Teixeira, Antonio L

    2018-02-01

    Inflammation seems to play a role in the pathophysiology of mood disorders, including major depressive disorder (MDD) and bipolar disorder (BD). In the last years several studies have shown increased levels of inflammatory and/or immune markers in patients with mood disorders. Accordingly, the immune system has become a target of interest for the development of biomarkers and therapeutics for mood disorders. Areas covered: Here, we review the evidence showing low-grade inflammation in mood disorders and the studies evaluating immune-based strategies for the treatment of these conditions. Expert commentary: Clinical trials with non-steroidal anti-inflammatory drugs, polyunsaturated acids, N-acetylcysteine, anti-cytokines, physical activity and probiotics have provided promising results in terms of antidepressant efficacy in patients with MDD and BD. Regarding stem cells, only studies with animal models have been performed so far with interesting pre-clinical results. Due to the preliminary nature of the results, most of the clinical studies need to be replicated and/or confirmed in larger clinical settings, embracing the highly heterogeneous pathophysiology of mood disorders.

  8. Detection of tetanus toxoid-specific memory T cells in equine lymph nodes but not in peripheral blood.

    Science.gov (United States)

    Frayne, J; Stokes, C R

    1995-07-01

    The use of tetanus toxoid as a recall antigen to investigate equine immune responses would be, in theory, a useful and cost-effective model in vitro. However, by using various regimens for culturing peripheral blood mononuclear cells from horses previously immunised with toxoid no proliferative response to the antigen was obtained in vitro, whereas lymph node mononuclear cells from the same animals proliferated significantly in response to it. The lack of response by the peripheral blood mononuclear cells was not due to the presence of a suppressive factor but to a lack of recognition of the antigen by the T cells of the peripheral blood.

  9. [Effects of electromagnetic radiation on health and immune function of operators].

    Science.gov (United States)

    Li, Yan-zhong; Chen, Shao-hua; Zhao, Ke-fu; Gui, Yun; Fang, Si-xin; Xu, Ying; Ma, Zi-jian

    2013-08-01

    To investigate the effects of electromagnetic radiation on the physiological indices and immune function of operators. The general conditions and electromagnetic radiation awareness rate of 205 operators under electromagnetic radiation were evaluated using a self-designed questionnaire. Physical examination, electrocardiography, and routine urine test were performed in these operators. Peripheral blood was collected from the operators under electromagnetic radiation for blood cell counting and biochemical testing, and their peripheral blood lymphocytes were cultured for determination of chromosomal aberrant frequency and micronucleus frequency. The data from these operators (exposure group) were compared with those of 95 ordinary individuals (control group). The chief complaint of giddiness, tiredness, dizziness, and amnesia showed significant differences between the exposure group and control group (P electromagnetic radiation damage was significantly higher in the exposure group than in the control group. The difference in bradycardia was significant between the two groups (P Electromagnetic radiation may lead to the changes in physiological indices, genetic effects, and immune function and affect the health and immune function in operators. The adverse effects are increased as the working years increase. So it is important to strengthen occupational protection of operators under electromagnetic radiation.

  10. Peripheral neuropathy in a diabetic child treated with linezolid for multidrug-resistant tuberculosis: a case report and review of the literature.

    Science.gov (United States)

    Swaminathan, Aravind; du Cros, Philipp; Seddon, James A; Mirgayosieva, Shamsiya; Asladdin, Rajabov; Dusmatova, Zulfiya

    2017-06-12

    Extensively drug-resistant (XDR) tuberculosis (TB) and multidrug resistant (MDR)-TB with additional resistance to injectable agents or fluoroquinolones are challenging to treat due to lack of available, effective drugs. Linezolid is one of the few drugs that has shown promise in treating these conditions. Long-term linezolid use is associated with toxicities such as peripheral and optic neuropathies. Diabetes mellitus (DM), especially when uncontrolled, can also result in peripheral neuropathy. The global burden of DM is increasing, and DM has been associated with a three-fold increased risk of developing TB disease. TB and DM can be a challenging combination to treat. DM can inhibit the host immune response to tuberculosis infection; and TB and some anti-TB drugs can worsen glycaemic control. A child experiencing neuropathy that is a possible complication of both DM and linezolid used to treat TB has not been reported previously. We report peripheral neuropathy in a 15-year-old boy with type 1 DM, diagnosed with MDR-TB and additional resistance to injectable TB medications. The boy was treated with a linezolid-based regimen, but after 8 months developed peripheral neuropathy. It was unclear whether the neuropathy was caused by the DM or the linezolid therapy. He had clinical improvement following cessation of linezolid and was declared cured following 21 months of treatment. Following completion of treatment, nerve conduction studies demonstrated significant improvement in neuropathy. To the best of our knowledge, this is the first case of peripheral neuropathy reported in a diabetic child on long-term linezolid therapy for tuberculosis. This case study underlines the importance of stringent follow-up for side effects of linezolid, especially when associated with co-morbidity such as DM that increases the chances of adverse effects. The presence of both DM and TB should alert a physician to strive for optimal glycaemic control to minimize the risk of

  11. A neuro-immune model of Myalgic Encephalomyelitis/Chronic fatigue syndrome.

    Science.gov (United States)

    Morris, Gerwyn; Maes, Michael

    2013-12-01

    This paper proposes a neuro-immune model for Myalgic Encephalomyelitis/Chronic fatigue syndrome (ME/CFS). A wide range of immunological and neurological abnormalities have been reported in people suffering from ME/CFS. They include abnormalities in proinflammatory cytokines, raised production of nuclear factor-κB, mitochondrial dysfunctions, autoimmune responses, autonomic disturbances and brain pathology. Raised levels of oxidative and nitrosative stress (O&NS), together with reduced levels of antioxidants are indicative of an immuno-inflammatory pathology. A number of different pathogens have been reported either as triggering or maintaining factors. Our model proposes that initial infection and immune activation caused by a number of possible pathogens leads to a state of chronic peripheral immune activation driven by activated O&NS pathways that lead to progressive damage of self epitopes even when the initial infection has been cleared. Subsequent activation of autoreactive T cells conspiring with O&NS pathways cause further damage and provoke chronic activation of immuno-inflammatory pathways. The subsequent upregulation of proinflammatory compounds may activate microglia via the vagus nerve. Elevated proinflammatory cytokines together with raised O&NS conspire to produce mitochondrial damage. The subsequent ATP deficit together with inflammation and O&NS are responsible for the landmark symptoms of ME/CFS, including post-exertional malaise. Raised levels of O&NS subsequently cause progressive elevation of autoimmune activity facilitated by molecular mimicry, bystander activation or epitope spreading. These processes provoke central nervous system (CNS) activation in an attempt to restore immune homeostatsis. This model proposes that the antagonistic activities of the CNS response to peripheral inflammation, O&NS and chronic immune activation are responsible for the remitting-relapsing nature of ME/CFS. Leads for future research are suggested based on this

  12. Studies on herd-immunity and primary versus secondary infection of VHSV in challenge and vaccination trials with rainbow trout

    DEFF Research Database (Denmark)

    Lorenzen, Ellen; Kjær, Torben Egil; Lorenzen, Niels

    as well as selective breeding, i.e. the more non-susceptible individuals in a population, the lower the risk of disease among susceptible individuals. Thus as part of a recent field trial with a VHS-DNA-vaccine vaccinated as well as naïve fish from a Danish fish farm were brought to the laboratory......Abstract for Scofda meeting 4-5.11.09 Studies on herd-immunity effect and primary versus secondary infection of VHSV by Ellen Lorenzen, Torben Eigil Kjær & Niels Lorenzen, National Veterinary Laboratory, Århus The phenomenon of “herd-immunity” is one of the basal principles behind vaccination...... at a size of 24g to be subjected to an experimental challenge with VHSV. The setup included 7 aquaria with 100 fish in each: 2 aquaria with 100 vaccinated fish (+VHS-challenge), 2 aquaria with 100 naïve fish (+ VHS-challenge), 2 aquaria with 50 vaccinated + 50 naïve fish (+VHS-challenge), and 1 aquarium...

  13. Replicating rather than nonreplicating adenovirus-human immunodeficiency virus recombinant vaccines are better at eliciting potent cellular immunity and priming high-titer antibodies.

    Science.gov (United States)

    Peng, Bo; Wang, Liqun Rejean; Gómez-Román, Victor Raúl; Davis-Warren, Alberta; Montefiori, David C; Kalyanaraman, V S; Venzon, David; Zhao, Jun; Kan, Elaine; Rowell, Thomas J; Murthy, Krishna K; Srivastava, Indresh; Barnett, Susan W; Robert-Guroff, Marjorie

    2005-08-01

    A major challenge in combating the human immunodeficiency virus (HIV) epidemic is the development of vaccines capable of inducing potent, persistent cellular immunity and broadly reactive neutralizing antibody responses to HIV type 1 (HIV-1). We report here the results of a preclinical trial using the chimpanzee model to investigate a combination vaccine strategy involving sequential priming immunizations with different serotypes of adenovirus (Ad)/HIV-1(MN)env/rev recombinants and boosting with an HIV envelope subunit protein, oligomeric HIV(SF162) gp140deltaV2. The immunogenicities of replicating and nonreplicating Ad/HIV-1(MN)env/rev recombinants were compared. Replicating Ad/HIV recombinants were better at eliciting HIV-specific cellular immune responses and better at priming humoral immunity against HIV than nonreplicating Ad-HIV recombinants carrying the same gene insert. Enhanced cellular immunity was manifested by a greater frequency of HIV envelope-specific gamma interferon-secreting peripheral blood lymphocytes and better priming of T-cell proliferative responses. Enhanced humoral immunity was seen in higher anti-envelope binding and neutralizing antibody titers and better induction of antibody-dependent cellular cytotoxicity. More animals primed with replicating Ad recombinants mounted neutralizing antibodies against heterologous R5 viruses after one or two booster immunizations with the mismatched oligomeric HIV-1(SF162) gp140deltaV2 protein. These results support continued development of the replicating Ad-HIV recombinant vaccine approach and suggest that the use of replicating vectors for other vaccines may prove fruitful.

  14. Peripheral neuropathy in HIV: an analysis of evidence-based approaches.

    Science.gov (United States)

    Nicholas, Patrice K; Corless, Inge B; Evans, Linda A

    2014-01-01

    Peripheral neuropathy is a common and vexing symptom for people living with HIV infection (PLWH). Neuropathy occurs in several different syndromes and is identified in the literature as distal sensory polyneuropathy or distal sensory peripheral neuropathy. More recently, the HIV literature has focused on the syndrome as painful HIV-associated sensory neuropathy, addressing the symptom rather than the underlying pathophysiology. Assessment of neuropathy in PLWH is critical and must be incorporated into nursing practice for each visit. Neuropathy has been attributed to the direct effects of HIV, exposure to antiretroviral medications (particularly the nucleoside reverse transcriptase inhibitors), advanced immune suppression, and comorbid tuberculosis infection and exposure to antituberculosis medications. Evidence supports the importance of addressing neuropathy in PLWH with pharmacologic treatment regimens and complementary/alternative approaches. This paper examines the pathophysiology, evidence, and approaches to managing peripheral neuropathy. A case study has been included to illustrate a patient's experience with neuropathy symptoms. Copyright © 2014 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

  15. Targeting Cannabinoid Signaling in the Immune System: “High”-ly Exciting Questions, Possibilities, and Challenges

    Directory of Open Access Journals (Sweden)

    Attila Oláh

    2017-11-01

    Full Text Available It is well known that certain active ingredients of the plants of Cannabis genus, i.e., the “phytocannabinoids” [pCBs; e.g., (−-trans-Δ9-tetrahydrocannabinol (THC, (−-cannabidiol, etc.] can influence a wide array of biological processes, and the human body is able to produce endogenous analogs of these substances [“endocannabinoids” (eCB, e.g., arachidonoylethanolamine (anandamide, AEA, 2-arachidonoylglycerol (2-AG, etc.]. These ligands, together with multiple receptors (e.g., CB1 and CB2 cannabinoid receptors, etc., and a complex enzyme and transporter apparatus involved in the synthesis and degradation of the ligands constitute the endocannabinoid system (ECS, a recently emerging regulator of several physiological processes. The ECS is widely expressed in the human body, including several members of the innate and adaptive immune system, where eCBs, as well as several pCBs were shown to deeply influence immune functions thereby regulating inflammation, autoimmunity, antitumor, as well as antipathogen immune responses, etc. Based on this knowledge, many in vitro and in vivo studies aimed at exploiting the putative therapeutic potential of cannabinoid signaling in inflammation-accompanied diseases (e.g., multiple sclerosis or in organ transplantation, and to dissect the complex immunological effects of medical and “recreational” marijuana consumption. Thus, the objective of the current article is (i to summarize the most recent findings of the field; (ii to highlight the putative therapeutic potential of targeting cannabinoid signaling; (iii to identify open questions and key challenges; and (iv to suggest promising future directions for cannabinoid-based drug development.

  16. ANCA-associated pauci-immune glomerulonephritis in a patient with bacterial endocarditis: a challenging clinical dilemma.

    Science.gov (United States)

    Cervi, Andrea; Kelly, Dylan; Alexopoulou, Iakovina; Khalidi, Nader

    2017-01-01

    We report the case of a 59-year-old man with chronic hepatitis B and C infection presenting with acute kidney injury and enterococcus faecalis-infective endocarditis (IE). An elevated proteinase-3 (PR3)-ANCA and pauci-immune glomerulonephritis (GN) on renal biopsy were discovered, corresponding to ANCA-mediated GN. We conducted a literature review to assess the role of ANCA in IE and treatment implications. On systematic review of the literature, we found five previous cases whereby IE caused by streptococcus and bartonella species were related to ANCA vasculitis-associated GN. Most reports of IE-related GN are mediated by immune complex deposition and resolve following microbial clearance. Of the 5 cases of ANCA GN in the setting of IE, all had markedly elevated levels of PR3-ANCA with either a subacute or chronic course of infection. Patients were treated with a combination of steroids and cyclophosphamide (2/5), steroids and antibiotics alone (1/5), or with valvular replacement (2/5). Renal function was recovered in 4/5 patients. Infection is a major etiologic player in the formation of ANCA; however, the role of PR3-ANCA in IE remains unclear. Kidney biopsy is essential in differentiating IE-related GN due to infection and immune complex deposition versus ANCA-associated vasculitis. A paucity of reports on the development of GN in IE-associated ANCA vasculitis exists, highlighting the rarity of our case and lack of clear therapeutic strategies in a patient with active infection requiring immunosuppression. In this case, the patient's chronic hepatitis B and C coinfection presented a unique challenge.

  17. Antibody responses to tetanus toxoid and Haemophilus influenzae type b conjugate vaccines following autologous peripheral blood stem cell transplantation (PBSCT).

    Science.gov (United States)

    Chan, C Y; Molrine, D C; Antin, J H; Wheeler, C; Guinan, E C; Weinstein, H J; Phillips, N R; McGarigle, C; Harvey, S; Schnipper, C; Ambrosino, D M

    1997-07-01

    Accelerated granulocyte and platelet recovery following peripheral blood stem cell transplantation (PBSCT) are well documented. We hypothesize that functional immunity may also be enhanced in PBSCT and performed a phase II trial of immunizations in patients with lymphoma undergoing autologous transplantation with peripheral blood stem cells or bone marrow. Seventeen BMT and 10 PBSCT recipients were immunized at 3, 6, 12, and 24-months post-transplantation with Haemophilus influenzae type b (HIB)-conjugate and tetanus toxoid (TT) vaccines. IgG anti-HIB and anti-TT antibody concentrations were measured and compared between the two groups. Geometric mean IgG anti-HIB antibody concentrations were significantly higher for PBSCT recipients compared to BMT recipients at 24 months post-transplantation (11.3 micrograms/ml vs 0.93 microgram/ml, P = 0.051) and following the 24 month immunization (66.2 micrograms/ml vs 1.30 micrograms/ml, P = 0.006). Similar results were noted for IgG anti-TT antibody with significantly higher geometric mean antibody concentrations in the PBSCT group at 24 months post-transplantation (182 micrograms/ml vs 21.6 micrograms/ml, P = 0.039). Protective levels of total anti-HIB antibody were achieved earlier in PBSCT recipients compared with those of BMT recipients. PBSCT recipients had higher antigen-specific antibody concentrations following HIB and TT immunizations. These results suggest enhanced recovery of humoral immunity in PBSCT recipients and earlier protection against HIB with immunization.

  18. Systemic antibodies administered by passive immunization prevent generalization of the infection by foot-and-mouth disease virus in cattle after oronasal challenge.

    Science.gov (United States)

    Barrionuevo, Florencia; Di Giacomo, Sebastián; Bucafusco, Danilo; Ayude, Andrea; Schammas, Juan; Miraglia, M Cruz; Capozzo, Alejandra; Borca, Manuel V; Perez-Filgueira, Mariano

    2018-05-01

    The role of passively transferred sera in the protection against aerogenous foot-and-mouth disease (FMD) virus infection in cattle was evaluated using vaccine-induced immune serum preparations obtained at 7 and 26 days post-vaccination (dpv). We showed that circulating antibodies were sufficient to prevent disease generalization after oronasal infection in animals passively transferred with 26-dpv serum but not with the 7-dpv serum. Conversely, conventional FMD vaccination provided clinical protection at 7 dpv, promoting fast and robust antibody responses upon challenge and even though antibody titers were similar to those found in animals passively immunized with 7-dpv serum. These results demonstrate that presence of antigen-specific antibodies is critical to prevent the dissemination of the virus within the animal. Conventional FMD vaccination additionally promoted the deployment of rapid, high titer and isotype-switched antibody responses at systemic and mucosal levels after infection, thus conferring protection even in the presence of low pre-challenge antibody titers. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Immune Mechanisms in Myelodysplastic Syndrome

    DEFF Research Database (Denmark)

    Glenthøj, Andreas; Ørskov, Andreas Due; Hansen, Jakob Werner

    2016-01-01

    diseases are common in patients with MDS, fueling hypotheses of common etiological mechanisms. Both innate and adaptive immune pathways are overly active in the hematopoietic niche of MDS. Although supportive care, growth factors, and hypomethylating agents are the mainstay of MDS treatment, some patients......-especially younger low-risk patients with HLA-DR15 tissue type-demonstrate impressive response rates after immunosuppressive therapy. This is in contrast to higher-risk MDS patients, where several immune activating treatments, such as immune checkpoint inhibitors, are in the pipeline. Thus, the dual role of immune...... mechanisms in MDS is challenging, and rigorous translational studies are needed to establish the value of immune manipulation as a treatment of MDS....

  20. Immune sensitization against epidermal antigens in polymorphous light eruption

    International Nuclear Information System (INIS)

    Gonzalez-Amaro, R.; Baranda, L.; Salazar-Gonzalez, J.F.; Abud-Mendoza, C.; Moncada, B.

    1991-01-01

    To get further insight into the pathogenesis of polymorphous light eruption, we studied nine patients with polymorphous light eruption and six healthy persons. Two skin biopsy specimens were obtained from each person, one from previously ultraviolet light-irradiated skin and another one from unirradiated skin. An epidermal cell suspension, skin homogenate, or both were prepared from each specimen. Autologous cultures were made with peripheral blood mononuclear cells combined with irradiated or unirradiated skin homogenate and peripheral blood mononuclear cells combined with irradiated or unirradiated epidermal cell suspension. Cell proliferation was assessed by 3H-thymidine incorporation assay. The response of peripheral blood mononuclear cells to unirradiated epidermal cells or unirradiated skin homogenate was similar in both patients and controls. However, peripheral blood mononuclear cells from patients with polymorphous light eruption showed a significantly increased proliferative response to both irradiated epidermal cells and irradiated skin homogenate. Our results indicate that ultraviolet light increases the stimulatory capability of polymorphous light eruption epidermal cells in a unidirectional mixed culture with autologous peripheral blood mononuclear cells. This suggests that an immune sensitization against autologous ultraviolet light-modified skin antigens occurs in polymorphous light eruption

  1. Vaccines and immunization

    African Journals Online (AJOL)

    Prof Ezechukwu

    vaccines for malaria and HIV infection. Despite the ... decades, effective vaccines against the major causes of ... challenge antibodies, specific helper and effector T lymphocytes ... materials to produced immunity to a disease. It was originally ...

  2. Immunization with DNA plasmids coding for crimean-congo hemorrhagic fever virus capsid and envelope proteins and/or virus-like particles induces protection and survival in challenged mice

    DEFF Research Database (Denmark)

    Hinkula, Jorma; Devignot, Stéphanie; Åkerström, Sara

    2017-01-01

    , there was no correlation with the neutralizing antibody titers alone, which were higher in the tc-VLP-vaccinated mice. However, the animals with a lower neutralizing titer, but a dominant cell-mediated Th1 response and a balanced Th2 response, resisted the CCHFV challenge. Moreover, we found that in challenged mice...... with a Th1 response (immunized by DNA/DNA and boosted by tc-VLPs), the immune response changed to Th2 at day 9 postchallenge. In addition, we were able to identify new linear B-cell epitope regions that are highly conserved between CCHFV strains. Altogether, our results suggest that a predominantly Th1-type...

  3. Adaptive immunity alters distinct host feeding pathways during nematode induced inflammation, a novel mechanism in parasite expulsion.

    Directory of Open Access Journals (Sweden)

    John J Worthington

    2013-01-01

    Full Text Available Gastrointestinal infection is often associated with hypophagia and weight loss; however, the precise mechanisms governing these responses remain poorly defined. Furthermore, the possibility that alterations in feeding during infection may be beneficial to the host requires further study. We used the nematode Trichinella spiralis, which transiently inhabits the small intestine before migrating to skeletal muscle, as a biphasic model of infection to determine the cellular and molecular pathways controlling feeding during enteric and peripheral inflammation. Through the infection of genetically modified mice lacking cholecystokinin, Tumor necrosis factor α receptors and T and B-cells, we observed a biphasic hypophagic response to infection resulting from two separate immune-driven mechanisms. The enteroendocrine I-cell derived hormone cholecystokinin is an essential mediator of initial hypophagia and is induced by CD4+ T-cells during enteritis. In contrast, the second hypophagic response is extra-intestinal and due to the anorectic effects of TNFα during peripheral infection of the muscle. Moreover, via maintaining naive levels of the adipose secreted hormone leptin throughout infection we demonstrate a novel feedback loop in the immunoendocrine axis. Immune driven I-cell hyperplasia and resultant weight loss leads to a reduction in the inflammatory adipokine leptin, which in turn heightens protective immunity during infection. These results characterize specific immune mediated mechanisms which reduce feeding during intestinal or peripheral inflammation. Importantly, the molecular mediators of each phase are entirely separate. The data also introduce the first evidence that I-cell hyperplasia is an adaptively driven immune response that directly impinges on the outcome to infection.

  4. Immunotherapy and Immune Evasion in Prostate Cancer

    International Nuclear Information System (INIS)

    Thakur, Archana; Vaishampayan, Ulka; Lum, Lawrence G.

    2013-01-01

    Metastatic prostate cancer remains to this day a terminal disease. Prostatectomy and radiotherapy are effective for organ-confined diseases, but treatment for locally advanced and metastatic cancer remains challenging. Although advanced prostate cancers treated with androgen deprivation therapy achieves debulking of disease, responses are transient with subsequent development of castration-resistant and metastatic disease. Since prostate cancer is typically a slowly progressing disease, use of immune-based therapies offers an advantage to target advanced tumors and to induce antitumor immunity. This review will discuss the clinical merits of various vaccines and immunotherapies in castrate resistant prostate cancer and challenges to this evolving field of immune-based therapies

  5. Immunotherapy and Immune Evasion in Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Thakur, Archana, E-mail: thakur@karmanos.org; Vaishampayan, Ulka [Department of Oncology, Wayne State University, Detroit, MI 48201 (United States); Lum, Lawrence G., E-mail: thakur@karmanos.org [Department of Oncology, Wayne State University, Detroit, MI 48201 (United States); Department of Medicine, Wayne State University, Detroit, MI 48201 (United States); Department of Immunology and Microbiology, Wayne State University, Detroit, MI 48201 (United States)

    2013-05-24

    Metastatic prostate cancer remains to this day a terminal disease. Prostatectomy and radiotherapy are effective for organ-confined diseases, but treatment for locally advanced and metastatic cancer remains challenging. Although advanced prostate cancers treated with androgen deprivation therapy achieves debulking of disease, responses are transient with subsequent development of castration-resistant and metastatic disease. Since prostate cancer is typically a slowly progressing disease, use of immune-based therapies offers an advantage to target advanced tumors and to induce antitumor immunity. This review will discuss the clinical merits of various vaccines and immunotherapies in castrate resistant prostate cancer and challenges to this evolving field of immune-based therapies.

  6. Immune-modulatory effects of syncytiotrophoblast extracellular vesicles in pregnancy and preeclampsia

    NARCIS (Netherlands)

    Göhner, Claudia; Plösch, Torsten; Faas, Marijke M

    2017-01-01

    Unique immunologic adaptations exist to successfully establish and maintain pregnancy and to avoid an immune attack against the semi allogenic fetus. These adaptations occur both locally at the maternofetal interface and in the peripheral circulation and affect the innate as well as the adaptive

  7. Elimination of self-reactive CD8+, but not CD4+, T cells by a peripheral immune mechanism

    International Nuclear Information System (INIS)

    Rammensee, H.G.; Huegin, D.

    1990-01-01

    Unirradiated (BALB/c X B6)F1 recipients of lymphocytes from either parent or (B6 X DBA/2)F2 recipients of DBA/2 parental lymphocytes specifically remove the function of donor-derived F1-reactive CTL from the spleen, since such cells could not be recovered 1 week after injection. However, donor-derived CTL specific for third-party antigens, as well as donor-derived F1-reactive CD4+ T cells could be recovered. In contrast, CTL in spleens from recipients sublethally irradiated prior to injections consisted predominantly of F1-reactive CTL in all strain combinations tested. Athymic BALB/c nude mice grafted with fetal thymus of B6 develop a T cell compartment tolerant of BALB/c and B6, like (BALB/c X B6)F1 animals. However, unlike the F1 mice, the thymus-grafted nude mice were not able to eliminate B6-reactive lymphocytes after injection of normal BALB/c spleen cells. Our data indicate the existence of a peripheral immune mechanism capable of selectively eliminating self-reactive CD8+ CTL, but not CD4+, T cells. This mechanism requires self antigen expressed on radiosensitive cells. The presence of T cells tolerant to self antigen by thymic negative selection is not sufficient and perhaps not required. Most likely, this mechanism is involved in the relative resistance to lethal GVHR mediated by parental CD8+ T cells in parent-into-F1 situations

  8. Effects of γ-rays on Th1 and Th2 immune function of mice

    International Nuclear Information System (INIS)

    Jin Wei; Cui Yufang; An Xiaoxia; Xu Han; Dong Bo; Liu Xiaolan; Luo Qingliang

    2007-01-01

    Objective: To observe the effects of 6 Gy whole body γ-irradiation on immune function of Th1 and Th2 in mouse, and to investigate the cellular and molecular mechanism of immune system injury induced by irradiation. Methods: Surface marker and intracellular cytokines of lymphocytes were stained with fluorescence-labeled monoclonal antibodies, then the changes of lymphocyte subpopulations, especially the Th1 and Th2 in mouse peripheral blood and spleen were analyzed by flow cytometry. Results: (1) 1 d after 6 Gy y- irradiation, lymphocytic subsets of CD 19 + and CD 8 + in spleen decreased apparently and the percentages of them were only 30% and 41% of control groups respectively (P 19 + and 14 d for CD 8 + respectively, however, up to 21 d post-irradiation they still did not return to control level. (2) Th1 subpopulations in mouse peripheral blood and spleen were significantly reduced at 1 d after irradiation and were only 2.6% and 7.6% of control groups (P 4 + / CD 8 + were significantly increased at 1 d post-irradiation in mouse spleen because of swift reduction of CD 8 + cells. Interestingly, either in peripheral blood or in spleen in irradiated mice, the ratio of Th1/Th2 were evidently raised because of the decrement of Th1 cells, exhibited obviously a phenomenon of predominant immune response of Th2 cells. Conclusions: It is suggested that the depression of mouse immune function induced by 6 Gy γ-irradiation might be caused by changes of CD 4 + /CD 8 + ratio, especially the imbalance of Th1/Th2 function subpopulations. It is shown that the imbalance of Th1/Th2 function subpopulations plays an important role in radiation-induced immune injury, thus providing a better insight into the molecular mechanism and new strategies for prevent and treatment measures of immune injury by irradiation. (authors)

  9. Immune response to allergens in sheep sensitized to house dust mite

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    Velden Joanne

    2008-10-01

    Full Text Available Abstract Background House dust mite (HDM allergens are a major cause of allergic asthma. Most studies using animal models of allergic asthma have used rodents sensitized with the 'un-natural' allergen ovalbumin. It has only recently been recognized that the use of animal models based on HDM provide a more relevant insight into the allergen-induced mechanisms that underpin human allergic disease. We have previously described a sheep model of human allergic asthma that uses Dermatophagoides pteronyssinus HDM. The present study extends our understanding of the immune effects of HDM and the allergens Der p 1 and Der p 2 in the sheep model of asthma. Methods Peripheral blood sera from non-sensitized (control sheep and sheep sensitized to HDM was collected to determine immunoglobulin (Ig reactivities to HDM, Der p 1 and Der p 2 by ELISA. Bronchoalveolar lavage (BAL fluid collected following allergen challenge was also assessed for the presence of HDM-specific antibodies. To examine the cellular immune response to HDM allergens, T cell proliferation and cutaneous responses were assessed in sensitized and control sheep. Results Strong HDM- and Der p 1-specific IgE, IgG1, IgG2 and IgA serum responses were observed in sensitized sheep, while detectable levels of HDM-specific IgG1 and IgA were seen in BAL fluid of allergen-challenged lungs. In contrast, minimal antibody reactivity was observed to Der p 2. Marked T cell proliferation and late phase cutaneous responses, accompanied by the recruitment of eosinophils, indicates the induction of a cellular and delayed-type hypersensitivity (DTH type II response by HDM and Der p 1 allergen, but not Der p 2. Conclusion This work characterizes the humoral and cellular immune effects of HDM extract and its major constituent allergens in sheep sensitized to HDM. The effects of allergen in HDM-sensitized sheep were detectable both locally and systemically, and probably mediated via enzymatic and immune actions of the

  10. Effects of Dietary Additives and Early Feeding on Performance, Gut Development and Immune Status of Broiler Chickens Challenged with

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    Z. Ao

    2012-04-01

    Full Text Available The effects of dietary additives and holding time on resistance and resilience of broiler chickens to Clostridium perfringens challenge were investigated by offering four dietary treatments. These were a negative control (basal, a positive control (Zn-bacitracin and two dietary additives, mannanoligosaccharides (MOS, and acidifier. Two holding times included (a immediate access to feed and water post hatch (FED and (b access to both feed and water 48 h post hatch (HELD. Chicks fed Zn-bacitracin had no intestinal lesions attributed to necrotic enteritis (NE, whereas chicks fed both MOS or acidifier showed signs of NE related lesions. All dietary treatments were effective in reducing the numbers of C. perfringens in the ileum post challenge. The FED chicks had heavier body weight and numerically lower mortality. The FED chicks also showed stronger immune responses to NE challenge, showing enhanced (p<0.05 proliferation of T-cells. Early feeding of the MOS supplemented diet increased (p<0.05 IL-6 production. The relative bursa weight of the FED chicks was heavier at d 21 (p<0.05. All the additives increased the relative spleen weight of the HELD chicks at d 14 (p<0.05. The FED chicks had increased villus height and reduced crypt depth, and hence an increased villus/crypt ratio, especially in the jejunum at d 14 (p<0.05. The same was true for the HELD chicks given dietary additives (p<0.05. It may be concluded that the chicks with early access to dietary additives showed enhanced immune response and gut development, under C. perfringens challenge. The findings of this study shed light on managerial and nutritional strategies that could be used to prevent NE in the broiler industry without the use of in-feed antibiotics.

  11. Measuring Cellular Immunity to Influenza: Methods of Detection, Applications and Challenges

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    Lynda Coughlan

    2015-04-01

    Full Text Available Influenza A virus is a respiratory pathogen which causes both seasonal epidemics and occasional pandemics; infection continues to be a significant cause of mortality worldwide. Current influenza vaccines principally stimulate humoral immune responses that are largely directed towards the variant surface antigens of influenza. Vaccination can result in an effective, albeit strain-specific antibody response and there is a need for vaccines that can provide superior, long-lasting immunity to influenza. Vaccination approaches targeting conserved viral antigens have the potential to provide broadly cross-reactive, heterosubtypic immunity to diverse influenza viruses. However, the field lacks consensus on the correlates of protection for cellular immunity in reducing severe influenza infection, transmission or disease outcome. Furthermore, unlike serological methods such as the standardized haemagglutination inhibition assay, there remains a large degree of variation in both the types of assays and method of reporting cellular outputs. T-cell directed immunity has long been known to play a role in ameliorating the severity and/or duration of influenza infection, but the precise phenotype, magnitude and longevity of the requisite protective response is unclear. In order to progress the development of universal influenza vaccines, it is critical to standardize assays across sites to facilitate direct comparisons between clinical trials.

  12. Multiple Roles of Myd88 in the Immune Response to the Plague F1-V Vaccine and in Protection against an Aerosol Challenge of Yersinia pestis CO92 in Mice

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    Jennifer L. Dankmeyer

    2014-01-01

    Full Text Available The current candidate vaccine against Yersinia pestis infection consists of two subunit proteins: the capsule protein or F1 protein and the low calcium response V protein or V-antigen. Little is known of the recognition of the vaccine by the host’s innate immune system and how it affects the acquired immune response to the vaccine. Thus, we vaccinated Toll-like receptor (Tlr 2, 4, and 2/4-double deficient, as well as signal adaptor protein Myd88-deficient mice. We found that Tlr4 and Myd88 appeared to be required for an optimal immune response to the F1-V vaccine but not Tlr2 when compared to wild-type mice. However, there was a difference between the requirement for Tlr4 and MyD88 in vaccinated animals. When F1-V vaccinated Tlr4 mutant (lipopolysaccharide tolerant and Myd88-deficient mice were challenged by aerosol with Y. pestis CO92, all but one Tlr4 mutant mice survived the challenge, but no vaccinated Myd88-deficient mice survived the challenge. Spleens from these latter nonsurviving mice showed that Y. pestis was not cleared from the infected mice. Our results suggest that MyD88 appears to be important for both an optimal immune response to F1-V and in protection against a lethal challenge of Y. pestis CO92 in F1-V vaccinated mice.

  13. Serum Antibodies Protect against Intraperitoneal Challenge with Enterotoxigenic Escherichia coli

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    Xinghong Yang

    2011-01-01

    Full Text Available To assess whether anticolonization factor antigen I (CFA/I fimbriae antibodies (Abs from enterotoxigenic Escherichia coli (ETEC can protect against various routes of challenge, BALB/c mice were immunized with a live attenuated Salmonella vaccine vector expressing CFA/I fimbriae. Vaccinated mice elicited elevated systemic IgG and mucosal IgA Abs, unlike mice immunized with the empty Salmonella vector. Mice were challenged with wild-type ETEC by the oral, intranasal (i.n., and intraperitoneal (i.p. routes. Naïve mice did not succumb to oral challenge, but did to i.n. challenge, as did immunized mice; however, vaccinated mice were protected against i.p. ETEC challenge. Two intramuscular (i.m. immunizations with CFA/I fimbriae without adjuvant conferred 100% protection against i.p. ETEC challenge, while a single 30 μg dose conferred 88% protection. Bactericidal assays showed that ETEC is highly sensitive to anti-CFA/I sera. These results suggest that parenteral immunization with purified CFA/I fimbriae can induce protective Abs and may represent an alternative method to elicit protective Abs for passive immunity to ETEC.

  14. Antisporozoite antibodies in mice immunized with irradiation-attenuated Plasmodium berghei sporozoites

    International Nuclear Information System (INIS)

    Hansen, R.; Silva, S.de; Strickland, G.T.

    1979-01-01

    Sera from NMRI/NIH mice were tested for the presence of IgM and IgG anti-sporozoite antibodies using the indirect fluorescent antibody test (IFAT). Both IgM and IgG antibody titres were related to the number of immunizations with irradiation-attenuated Plasmodium berghei sporozoites, and protection from challenge with subsequent non-attenuated sporozoites correlated with the pre-challenge antibody titre. Sera taken five days following challenge showed marked reductions in antibody titres, except for the group receiving the maximum (four) immunizations. Groups immunized with frozen sporozoites or mosquito tissue antigen developed neither antibodies to sporozoites nor protective immunity; nor did animals infected with parasitized blood. However, sera from mice immunized four times with attenuated sporozoites demonstrated IFA titres to blood-stage antigens. The results showed that both IgM and IgG anti-sporozoite antibodies could be detected in mice immunized with attenuated-sporozoites by IFAT, and that the antibody titres correlated with protective immunity. Cross reaction with blood-stage antigens occurred, but the test should still prove useful. (author)

  15. Gene Expression Differences in Peripheral Blood of Parkinson's Disease Patients with Distinct Progression Profiles.

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    Raquel Pinho

    Full Text Available The prognosis of neurodegenerative disorders is clinically challenging due to the inexistence of established biomarkers for predicting disease progression. Here, we performed an exploratory cross-sectional, case-control study aimed at determining whether gene expression differences in peripheral blood may be used as a signature of Parkinson's disease (PD progression, thereby shedding light into potential molecular mechanisms underlying disease development. We compared transcriptional profiles in the blood from 34 PD patients who developed postural instability within ten years with those of 33 patients who did not develop postural instability within this time frame. Our study identified >200 differentially expressed genes between the two groups. The expression of several of the genes identified was previously found deregulated in animal models of PD and in PD patients. Relevant genes were selected for validation by real-time PCR in a subset of patients. The genes validated were linked to nucleic acid metabolism, mitochondria, immune response and intracellular-transport. Interestingly, we also found deregulation of these genes in a dopaminergic cell model of PD, a simple paradigm that can now be used to further dissect the role of these molecular players on dopaminergic cell loss. Altogether, our study provides preliminary evidence that expression changes in specific groups of genes and pathways, detected in peripheral blood samples, may be correlated with differential PD progression. Our exploratory study suggests that peripheral gene expression profiling may prove valuable for assisting in prediction of PD prognosis, and identifies novel culprits possibly involved in dopaminergic cell death. Given the exploratory nature of our study, further investigations using independent, well-characterized cohorts will be essential in order to validate our candidates as predictors of PD prognosis and to definitively confirm the value of gene expression

  16. Urbanization and the Resulting Peripheralization in Solo Raya, Indonesia

    Science.gov (United States)

    Pradoto, W.; Mardiansjah, F. H.; Manullang, O. R.; Putra, A. A.

    2018-02-01

    Dynamic urbanization in Solo Raya, a local term for Surakarta Metropolitan, amongst rapid regional based-urbanization in Indonesia, shows the unbalance pattern of growth. A number of Surakarta City’s peripherals become the newly growing area which is characterized by a well-facilitated region, while the former urbanized areas next to the city center present the declining process. Different socioeconomic development triggers a unique mosaic of socio-spatial pattern, on which the phenomena of peripheralization could be investigated. Urban investment that boosted by the political will of both the national and local government has led to a shift in demographic condition. A relatively massive in-migration has been attracted to the peripheral and creates the new landscape of urban-rural society. Complex dynamic of metropolitan growth and the resulting peripheralization reminds that socio-spatial pattern calls the challenges for managing the rapid change of land use and space use. The pattern of urbanization that differs upon the surrounding areas of Surakarta City would be interesting to be explored. This paper will discuss the conceptual framework of peripheral urbanization and the methodological approach. It is actually the part of ongoing research on peripheralisation in Solo Raya.

  17. Evidence of functional cell-mediated immune responses to nontypeable Haemophilus influenzae in otitis-prone children

    Science.gov (United States)

    Seppanen, Elke; Tan, Dino; Corscadden, Karli J.; Currie, Andrew J.; Richmond, Peter C.; Thornton, Ruth B.

    2018-01-01

    Otitis media (OM) remains a common paediatric disease, despite advances in vaccinology. Susceptibility to recurrent acute OM (rAOM) has been postulated to involve defective cell-mediated immune responses to common otopathogenic bacteria. We compared the composition of peripheral blood mononuclear cells (PBMC) from 20 children with a history of rAOM (otitis-prone) and 20 healthy non-otitis-prone controls, and assessed innate and cell-mediated immune responses to the major otopathogen nontypeable Haemophilus influenzae (NTHi). NTHi was a potent stimulator of inflammatory cytokine secretion from PBMC within 4 hours, with no difference in cytokine levels produced between PBMC from cases or controls. In the absence of antigen stimulation, otitis-prone children had more circulating Natural Killer (NK) cells (potitis-prone and non-otitis-prone children (potitis-prone children are functional and respond to NTHi. CD8+ T cells and NK cells from both cases and controls produced IFNγ in response to polyclonal stimulus (Staphylococcal enterotoxin B; SEB), with more IFNγ+ CD8+ T cells present in cases than controls (pOtitis-prone children had more circulating IFNγ-producing NK cells (potitis-prone children mounted innate and T cell-mediated responses to NTHi challenge that were comparable to healthy children. These data provide evidence that otitis-prone children do not have impaired functional cell mediated immunity. PMID:29621281

  18. Brain and Peripheral Atypical Inflammatory Mediators Potentiate Neuroinflammation and Neurodegeneration.

    Science.gov (United States)

    Kempuraj, Duraisamy; Thangavel, Ramasamy; Selvakumar, Govindhasamy P; Zaheer, Smita; Ahmed, Mohammad E; Raikwar, Sudhanshu P; Zahoor, Haris; Saeed, Daniyal; Natteru, Prashant A; Iyer, Shankar; Zaheer, Asgar

    2017-01-01

    Neuroinflammatory response is primarily a protective mechanism in the brain. However, excessive and chronic inflammatory responses can lead to deleterious effects involving immune cells, brain cells and signaling molecules. Neuroinflammation induces and accelerates pathogenesis of Parkinson's disease (PD), Alzheimer's disease (AD) and Multiple sclerosis (MS). Neuroinflammatory pathways are indicated as novel therapeutic targets for these diseases. Mast cells are immune cells of hematopoietic origin that regulate inflammation and upon activation release many proinflammatory mediators in systemic and central nervous system (CNS) inflammatory conditions. In addition, inflammatory mediators released from activated glial cells induce neurodegeneration in the brain. Systemic inflammation-derived proinflammatory cytokines/chemokines and other factors cause a breach in the blood brain-barrier (BBB) thereby allowing for the entry of immune/inflammatory cells including mast cell progenitors, mast cells and proinflammatory cytokines and chemokines into the brain. These peripheral-derived factors and intrinsically generated cytokines/chemokines, α-synuclein, corticotropin-releasing hormone (CRH), substance P (SP), beta amyloid 1-42 (Aβ1-42) peptide and amyloid precursor proteins can activate glial cells, T-cells and mast cells in the brain can induce additional release of inflammatory and neurotoxic molecules contributing to chronic neuroinflammation and neuronal death. The glia maturation factor (GMF), a proinflammatory protein discovered in our laboratory released from glia, activates mast cells to release inflammatory cytokines and chemokines. Chronic increase in the proinflammatory mediators induces neurotoxic Aβ and plaque formation in AD brains and neurodegeneration in PD brains. Glial cells, mast cells and T-cells can reactivate each other in neuroinflammatory conditions in the brain and augment neuroinflammation. Further, inflammatory mediators from the brain can

  19. Oral warfarin affects peripheral blood leukocyte IL-6 and TNFα production in rats.

    Science.gov (United States)

    Popov, Aleksandra; Belij, Sandra; Subota, Vesna; Zolotarevski, Lidija; Mirkov, Ivana; Kataranovski, Dragan; Kataranovski, Milena

    2013-01-01

    Warfarin is a Vitamin K (VK) antagonist that affects Vitamin K-dependent (VKD) processes, including blood coagulation, as well as processes unrelated to hemostasis such as bone growth, calcification, and growth of some cell types. In addition, warfarin exerts influence on some non-VKD-related activities, including anti-tumor and immunomodulating activity. With respect to the latter, both immune stimulating and suppressive effects have been noted in different experimental systems. To explore the in vivo immunomodulatory potential of warfarin on one type of activity (i.e., cytokine production) in two different immune cell populations (i.e., mononuclear or polymorphonuclear cells), effects of subchronic oral warfarin intake in rats on pro-inflammatory cytokine (i.e., TNFα, IL-6) production by peripheral blood mononuclear and polymorphonuclear cells (granulocytes) was examined. Differential effects of warfarin intake on TNFα and IL-6 were noted, depending on the type of peripheral blood leukocytes and on the cytokine examined. Specifically, a lack of effect on TNFα and a priming of IL-6 production by mononuclear cells along with a decrease in TNFα and a lack of effect on IL-6 in polymorphonuclear cells were seen in warfarin-exposed hosts. The cell- and cytokine-dependent effects from subchronic oral warfarin intake on peripheral blood leukocytes demonstrated in this study could, possibly, differentially affect reactions mediated by these cells. Ultimately, the observed effects in rats might have implications for those humans who are on long-term/prolonged warfarin therapy.

  20. Mucosal Immunity and Protective Efficacy of Intranasal Inactivated Influenza Vaccine Is Improved by Chitosan Nanoparticle Delivery in Pigs

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    Santosh Dhakal

    2018-05-01

    Full Text Available Annually, swine influenza A virus (SwIAV causes severe economic loss to swine industry. Currently used inactivated SwIAV vaccines administered by intramuscular injection provide homologous protection, but limited heterologous protection against constantly evolving field viruses, attributable to the induction of inadequate levels of mucosal IgA and cellular immune responses in the respiratory tract. A novel vaccine delivery platform using mucoadhesive chitosan nanoparticles (CNPs administered through intranasal (IN route has the potential to elicit strong mucosal and systemic immune responses in pigs. In this study, we evaluated the immune responses and cross-protective efficacy of IN chitosan encapsulated inactivated SwIAV vaccine in pigs. Killed SwIAV H1N2 (δ-lineage antigens (KAg were encapsulated in chitosan polymer-based nanoparticles (CNPs-KAg. The candidate vaccine was administered twice IN as mist to nursery pigs. Vaccinates and controls were then challenged with a zoonotic and virulent heterologous SwIAV H1N1 (γ-lineage. Pigs vaccinated with CNPs-KAg exhibited an enhanced IgG serum antibody and mucosal secretory IgA antibody responses in nasal swabs, bronchoalveolar lavage (BAL fluids, and lung lysates that were reactive against homologous (H1N2, heterologous (H1N1, and heterosubtypic (H3N2 influenza A virus strains. Prior to challenge, an increased frequency of cytotoxic T lymphocytes, antigen-specific lymphocyte proliferation, and recall IFN-γ secretion by restimulated peripheral blood mononuclear cells in CNPs-KAg compared to control KAg vaccinates were observed. In CNPs-KAg vaccinated pigs challenged with heterologous virus reduced severity of macroscopic and microscopic influenza-associated pulmonary lesions were observed. Importantly, the infectious SwIAV titers in nasal swabs [days post-challenge (DPC 4] and BAL fluid (DPC 6 were significantly (p < 0.05 reduced in CNPs-KAg vaccinates but not in KAg vaccinates when compared

  1. Mucosal Immunity and Protective Efficacy of Intranasal Inactivated Influenza Vaccine Is Improved by Chitosan Nanoparticle Delivery in Pigs.

    Science.gov (United States)

    Dhakal, Santosh; Renu, Sankar; Ghimire, Shristi; Shaan Lakshmanappa, Yashavanth; Hogshead, Bradley T; Feliciano-Ruiz, Ninoshkaly; Lu, Fangjia; HogenEsch, Harm; Krakowka, Steven; Lee, Chang Won; Renukaradhya, Gourapura J

    2018-01-01

    Annually, swine influenza A virus (SwIAV) causes severe economic loss to swine industry. Currently used inactivated SwIAV vaccines administered by intramuscular injection provide homologous protection, but limited heterologous protection against constantly evolving field viruses, attributable to the induction of inadequate levels of mucosal IgA and cellular immune responses in the respiratory tract. A novel vaccine delivery platform using mucoadhesive chitosan nanoparticles (CNPs) administered through intranasal (IN) route has the potential to elicit strong mucosal and systemic immune responses in pigs. In this study, we evaluated the immune responses and cross-protective efficacy of IN chitosan encapsulated inactivated SwIAV vaccine in pigs. Killed SwIAV H1N2 (δ-lineage) antigens (KAg) were encapsulated in chitosan polymer-based nanoparticles (CNPs-KAg). The candidate vaccine was administered twice IN as mist to nursery pigs. Vaccinates and controls were then challenged with a zoonotic and virulent heterologous SwIAV H1N1 (γ-lineage). Pigs vaccinated with CNPs-KAg exhibited an enhanced IgG serum antibody and mucosal secretory IgA antibody responses in nasal swabs, bronchoalveolar lavage (BAL) fluids, and lung lysates that were reactive against homologous (H1N2), heterologous (H1N1), and heterosubtypic (H3N2) influenza A virus strains. Prior to challenge, an increased frequency of cytotoxic T lymphocytes, antigen-specific lymphocyte proliferation, and recall IFN-γ secretion by restimulated peripheral blood mononuclear cells in CNPs-KAg compared to control KAg vaccinates were observed. In CNPs-KAg vaccinated pigs challenged with heterologous virus reduced severity of macroscopic and microscopic influenza-associated pulmonary lesions were observed. Importantly, the infectious SwIAV titers in nasal swabs [days post-challenge (DPC) 4] and BAL fluid (DPC 6) were significantly ( p  influenza nanovaccine may be an ideal candidate vaccine for use in pigs, and pig is a

  2. Approaches Mediating Oxytocin Regulation of the Immune System.

    Science.gov (United States)

    Li, Tong; Wang, Ping; Wang, Stephani C; Wang, Yu-Feng

    2016-01-01

    The hypothalamic neuroendocrine system is mainly composed of the neural structures regulating hormone secretion from the pituitary gland and has been considered as the higher regulatory center of the immune system. Recently, the hypothalamo-neurohypophysial system (HNS) emerged as an important component of neuroendocrine-immune network, wherein the oxytocin (OT)-secreting system (OSS) plays an essential role. The OSS, consisting of OT neurons in the supraoptic nucleus, paraventricular nucleus, their several accessory nuclei and associated structures, can integrate neural, endocrine, metabolic, and immune information and plays a pivotal role in the development and functions of the immune system. The OSS can promote the development of thymus and bone marrow, perform immune surveillance, strengthen immune defense, and maintain immune homeostasis. Correspondingly, OT can inhibit inflammation, exert antibiotic-like effect, promote wound healing and regeneration, and suppress stress-associated immune disorders. In this process, the OSS can release OT to act on immune system directly by activating OT receptors or through modulating activities of other hypothalamic-pituitary-immune axes and autonomic nervous system indirectly. However, our understandings of the role of the OSS in neuroendocrine regulation of immune system are largely incomplete, particularly its relationship with other hypothalamic-pituitary-immune axes and the vasopressin-secreting system that coexists with the OSS in the HNS. In addition, it remains unclear about the relationship between the OSS and peripherally produced OT in immune regulation, particularly intrathymic OT that is known to elicit central immunological self-tolerance of T-cells to hypophysial hormones. In this work, we provide a brief review of current knowledge of the features of OSS regulation of the immune system and of potential approaches that mediate OSS coordination of the activities of entire neuroendocrine-immune network.

  3. Dissecting interferon-induced transcriptional programs in human peripheral blood cells.

    Directory of Open Access Journals (Sweden)

    Simon J Waddell

    2010-03-01

    Full Text Available Interferons are key modulators of the immune system, and are central to the control of many diseases. The response of immune cells to stimuli in complex populations is the product of direct and indirect effects, and of homotypic and heterotypic cell interactions. Dissecting the global transcriptional profiles of immune cell populations may provide insights into this regulatory interplay. The host transcriptional response may also be useful in discriminating between disease states, and in understanding pathophysiology. The transcriptional programs of cell populations in health therefore provide a paradigm for deconvoluting disease-associated gene expression profiles.We used human cDNA microarrays to (1 compare the gene expression programs in human peripheral blood mononuclear cells (PBMCs elicited by 6 major mediators of the immune response: interferons alpha, beta, omega and gamma, IL12 and TNFalpha; and (2 characterize the transcriptional responses of purified immune cell populations (CD4+ and CD8+ T cells, B cells, NK cells and monocytes to IFNgamma stimulation. We defined a highly stereotyped response to type I interferons, while responses to IFNgamma and IL12 were largely restricted to a subset of type I interferon-inducible genes. TNFalpha stimulation resulted in a distinct pattern of gene expression. Cell type-specific transcriptional programs were identified, highlighting the pronounced response of monocytes to IFNgamma, and emergent properties associated with IFN-mediated activation of mixed cell populations. This information provides a detailed view of cellular activation by immune mediators, and contributes an interpretive framework for the definition of host immune responses in a variety of disease settings.

  4. Social cues trigger differential immune investment strategies in a non-social insect, Tenebrio molitor.

    Science.gov (United States)

    Gallagher, Joe D; Siva-Jothy, Michael T; Evison, Sophie E F

    2018-02-01

    Social immunization (SI) is a horizontal transfer of immunity that protects naive hosts against infection following exposure to infected nestmates. While mainly documented in eusocial insects, non-social species also share similar ecological features which favour the development of group-level immunity. Here, we investigate SI in Tenebrio molitor by pairing naive females with a pathogen-challenged conspecific for 72 h before measuring a series of immune and fitness traits. We found no evidence for SI, as beetles who cohabited with a live pathogen-challenged conspecific were not better protected against bacterial challenge. However, exposure to a heat-killed-bacteria-challenged conspecific appeared to increase pathogen tolerance, which manifested in differential fitness investment. Our results together suggest that T. molitor do respond to immune-related cues in the social environment, despite not showing a classic immunization response as predicted. © 2018 The Author(s).

  5. Altered Immune Regulation in Type 1 Diabetes

    Science.gov (United States)

    Zóka, András; Műzes, Györgyi; Somogyi, Anikó; Varga, Tímea; Szémán, Barbara; Al-Aissa, Zahra; Hadarits, Orsolya; Firneisz, Gábor

    2013-01-01

    Research in genetics and immunology was going on separate strands for a long time. Type 1 diabetes mellitus might not be characterized with a single pathogenetic factor. It develops when a susceptible individual is exposed to potential triggers in a given sequence and timeframe that eventually disarranges the fine-tuned immune mechanisms that keep autoimmunity under control in health. Genomewide association studies have helped to understand the congenital susceptibility, and hand-in-hand with the immunological research novel paths of immune dysregulation were described in central tolerance, apoptotic pathways, or peripheral tolerance mediated by regulatory T-cells. Epigenetic factors are contributing to the immune dysregulation. The interplay between genetic susceptibility and potential triggers is likely to play a role at a very early age and gradually results in the loss of balanced autotolerance and subsequently in the development of the clinical disease. Genetic susceptibility, the impaired elimination of apoptotic β-cell remnants, altered immune regulatory functions, and environmental factors such as viral infections determine the outcome. Autoreactivity might exist under physiologic conditions and when the integrity of the complex regulatory process is damaged the disease might develop. We summarized the immune regulatory mechanisms that might have a crucial role in disease pathology and development. PMID:24285974

  6. Altered Immune Regulation in Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    András Zóka

    2013-01-01

    Full Text Available Research in genetics and immunology was going on separate strands for a long time. Type 1 diabetes mellitus might not be characterized with a single pathogenetic factor. It develops when a susceptible individual is exposed to potential triggers in a given sequence and timeframe that eventually disarranges the fine-tuned immune mechanisms that keep autoimmunity under control in health. Genomewide association studies have helped to understand the congenital susceptibility, and hand-in-hand with the immunological research novel paths of immune dysregulation were described in central tolerance, apoptotic pathways, or peripheral tolerance mediated by regulatory T-cells. Epigenetic factors are contributing to the immune dysregulation. The interplay between genetic susceptibility and potential triggers is likely to play a role at a very early age and gradually results in the loss of balanced autotolerance and subsequently in the development of the clinical disease. Genetic susceptibility, the impaired elimination of apoptotic β-cell remnants, altered immune regulatory functions, and environmental factors such as viral infections determine the outcome. Autoreactivity might exist under physiologic conditions and when the integrity of the complex regulatory process is damaged the disease might develop. We summarized the immune regulatory mechanisms that might have a crucial role in disease pathology and development.

  7. Modulation of immunity in young-adult and aged squirrel, Funambulus pennanti by melatonin and p-chlorophenylalanine

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    Singh Rajesh

    2009-04-01

    Full Text Available Abstract Background Our interest was to find out whether pineal gland and their by melatonin act as modulator of immunosenescence. Parachlorophenylalanine (PCPA – a β adrenergic blocker, is known to perform chemical pinealectomy (Px by suppressing indirectly the substrate 5-hydroxytryptamine (5-HT for melatonin synthesis and thereby melatonin itself. The role of PCPA, alone and in combination with melatonin was recorded in immunomodulation and free radical load in spleen of young adult and aged seasonal breeder Indian palm squirrel Funambulus pennanti. Results Aged squirrel presented reduced immune parameters (i.e. total leukocyte count (TLC, Lymphocytes Count (LC, % stimulation ratio of splenocytes (% SR against T cell mitogen concanavalin A (Con A, delayed type hypersensitivity (DTH to oxazolone when compared to young adult group. Melatonin administration (25 μg/100 g body mass/day significantly increased the immune parameters in aged more than the young adult squirrel while PCPA administration (4.5 mg/100 g body mass/day reduced all the immune parameters more significantly in young than aged. Combination of PCPA and melatonin significantly increased the immune parameters to the normal control level of both the age groups. TBARS level was significantly high in aged than the young group. PCPA treatment increased TBARS level of young and aged squirrels both while melatonin treatment decreased it even than the controls. Nighttime peripheral melatonin level was low in control aged group than the young group. Melatonin injection at evening hours significantly increased the peripheral level of nighttime melatonin, while combined injection of PCPA and melatonin brought it to control level in both aged and young adult squirrels. Conclusion PCPA suppressed immune status more in aged than in adult by reducing melatonin level as it did chemical Px. Melatonin level decreased in control aged squirrels and so there was a decrease in immune parameters

  8. The Effects of Serotonin in Immune Cells

    OpenAIRE

    Herr, Nadine; Bode, Christoph; Duerschmied, Daniel

    2017-01-01

    Serotonin [5-hydroxytryptamine (5-HT)] plays an important role in many organs as a peripheral hormone. Most of the body’s serotonin is circulating in the bloodstream, transported by blood platelets and is released upon activation. The functions of serotonin are mediated by members of the 7 known mammalian serotonin receptor subtype classes (15 known subtypes), the serotonin transporter (SERT), and by covalent binding of serotonin to different effector proteins. Almost all immune cells express...

  9. The influence of recovery and training phases on body composition, peripheral vascular function and immune system of professional soccer players.

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    Simon Reinke

    Full Text Available Professional soccer players have a lengthy playing season, throughout which high levels of physical stress are maintained. The following recuperation period, before starting the next pre-season training phase, is generally considered short but sufficient to allow a decrease in these stress levels and therefore a reduction in the propensity for injury or musculoskeletal tissue damage. We hypothesised that these physical extremes influence the body composition, blood flow, and endothelial/immune function, but that the recuperation may be insufficient to allow a reduction of tissue stress damage. Ten professional football players were examined at the end of the playing season, at the end of the season intermission, and after the next pre-season endurance training. Peripheral blood flow and body composition were assessed using venous occlusion plethysmography and DEXA scanning respectively. In addition, selected inflammatory and immune parameters were analysed from blood samples. Following the recuperation period a significant decrease of lean body mass from 74.4+/-4.2 kg to 72.2+/-3.9 kg was observed, but an increase of fat mass from 10.3+/-5.6 kg to 11.1+/-5.4 kg, almost completely reversed the changes seen in the pre-season training phase. Remarkably, both resting and post-ischemic blood flow (7.3+/-3.4 and 26.0+/-6.3 ml/100 ml/min respectively, were strongly reduced during the playing and training stress phases, but both parameters increased to normal levels (9.0+/-2.7 and 33.9+/-7.6 ml/100 ml/min during the season intermission. Recovery was also characterized by rising levels of serum creatinine, granulocytes count, total IL-8, serum nitrate, ferritin, and bilirubin. These data suggest a compensated hypo-perfusion of muscle during the playing season, followed by an intramuscular ischemia/reperfusion syndrome during the recovery phase that is associated with muscle protein turnover and inflammatory endothelial reaction, as demonstrated by i

  10. Vaccine-Mediated Mechanisms Controlling Replication of Francisella tularensis in Human Peripheral Blood Mononuclear Cells Using a Co-culture System

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    Kjell Eneslätt

    2018-02-01

    Full Text Available Cell-mediated immunity (CMI is normally required for efficient protection against intracellular infections, however, identification of correlates is challenging and they are generally lacking. Francisella tularensis is a highly virulent, facultative intracellular bacterium and CMI is critically required for protection against the pathogen, but how this is effectuated in humans is poorly understood. To understand the protective mechanisms, we established an in vitro co-culture assay to identify how control of infection of F. tularensis is accomplished by human cells and hypothesized that the model will mimic in vivo immune mechanisms. Non-adherent peripheral blood mononuclear cells (PBMCs were expanded with antigen and added to cultures with adherent PBMC infected with the human vaccine strain, LVS, or the highly virulent SCHU S4 strain. Intracellular numbers of F. tularensis was followed for 72 h and secreted and intracellular cytokines were analyzed. Addition of PBMC expanded from naïve individuals, i.e., those with no record of immunization to F. tularensis, generally resulted in little or no control of intracellular bacterial growth, whereas addition of PBMC from a majority of F. tularensis-immune individuals executed static and sometimes cidal effects on intracellular bacteria. Regardless of infecting strain, statistical differences between the two groups were significant, P < 0.05. Secretion of 11 cytokines was analyzed after 72 h of infection and significant differences with regard to secretion of IFN-γ, TNF, and MIP-1β was observed between immune and naïve individuals for LVS-infected cultures. Also, in LVS-infected cultures, CD4 T cells from vaccinees, but not CD8 T cells, showed significantly higher expression of IFN-γ, MIP-1β, TNF, and CD107a than cells from naïve individuals. The co-culture system appears to identify correlates of immunity that are relevant for the understanding of mechanisms of the protective host immunity to

  11. Transdermal influenza immunization with vaccine-coated microneedle arrays.

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    Dimitrios G Koutsonanos

    Full Text Available Influenza is a contagious disease caused by a pathogenic virus, with outbreaks all over the world and thousands of hospitalizations and deaths every year. Due to virus antigenic drift and short-lived immune responses, annual vaccination is required. However, vaccine coverage is incomplete, and improvement in immunization is needed. The objective of this study is to investigate a novel method for transdermal delivery using metal microneedle arrays (MN coated with inactivated influenza virus to determine whether this route is a simpler and safer approach than the conventional immunization, capable to induce robust immune responses and confer protection against lethal virus challenge.Inactivated A/Aichi/2/68 (H3N2 influenza virus was coated on metal microneedle arrays and applied to mice as a vaccine in the caudal dorsal skin area. Substantial antibody titers with hemagglutination inhibition activity were detected in sera collected two and four weeks after a single vaccine dose. Challenge studies in mice with 5 x LD(50 of mouse adapted Aichi virus demonstrated complete protection. Microneedle vaccination induced a broad spectrum of immune responses including CD4+ and CD8+ responses in the spleen and draining lymph node, a high frequency of antigen-secreting cells in the lung and induction of virus-specific memory B-cells. In addition, the use of MN showed a dose-sparing effect and a strong Th2 bias when compared to an intramuscular (IM reference immunization.The present results show that delivery of inactivated influenza virus through the skin using metal microneedle arrays induced strong humoral and cellular immune responses capable of conferring protection against virus challenge as efficiently as intramuscular immunization, which is the standard vaccination route. In view of the convenience of delivery and the potential for self-administration, vaccine-coated metal microneedles may provide a novel and highly effective immunization method.

  12. Effects of source and level of energy on the immune competence and response to an Infectious Bovine Rhinotracheitis Virus (IBRV) challenge in cattle

    Science.gov (United States)

    Objectives were to evaluate how dietary energy level and source affect immune competence and response to a viral challenge in cattle. Forty-eight crossbred beef steers were stratified by BW within 2 periods and randomized to 1 of 3 dietary treatments (8 steers/treatment within period). Treatments we...

  13. Pregnancy induces transcriptional activation of the peripheral innate immune system and increases oxidative DNA damage among healthy third trimester pregnant women.

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    Xinyin Jiang

    Full Text Available BACKGROUND: Pregnancy induces physiological adaptations that may involve, or contribute to, alterations in the genomic landscape. Pregnancy also increases the nutritional demand for choline, an essential nutrient that can modulate epigenomic and transcriptomic readouts secondary to its role as a methyl donor. Nevertheless, the interplay between human pregnancy, choline and the human genome is largely unexplored. METHODOLOGY/PRINCIPAL FINDINGS: As part of a controlled feeding study, we assessed the influence of pregnancy and choline intake on maternal genomic markers. Healthy third trimester pregnant (n = 26, wk 26-29 gestation and nonpregnant (n = 21 women were randomized to choline intakes of 480 mg/day, approximating the Adequate Intake level, or 930 mg/day for 12-weeks. Blood leukocytes were acquired at study week 0 and study week 12 for microarray, DNA damage and global DNA/histone methylation measurements. A main effect of pregnancy that was independent of choline intake was detected on several of the maternal leukocyte genomic markers. Compared to nonpregnant women, third trimester pregnant women exhibited higher (P<0.05 transcript abundance of defense response genes associated with the innate immune system including pattern recognition molecules, neutrophil granule proteins and oxidases, complement proteins, cytokines and chemokines. Pregnant women also exhibited higher (P<0.001 levels of DNA damage in blood leukocytes, a genomic marker of oxidative stress. No effect of choline intake was detected on the maternal leukocyte genomic markers with the exception of histone 3 lysine 4 di-methylation which was lower among pregnant women in the 930 versus 480 mg/d choline intake group. CONCLUSIONS: Pregnancy induces transcriptional activation of the peripheral innate immune system and increases oxidative DNA damage among healthy third trimester pregnant women.

  14. Crop immunity against viruses: outcomes and future challenges

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    Valerie eNicaise

    2014-11-01

    Full Text Available Viruses cause epidemics on all major cultures of agronomic importance, representing a serious threat to global food security. As strict intracellular pathogens, they cannot be controlled chemically and prophylactic measures consist mainly in the destruction of infected plants and excessive pesticide applications to limit the population of vector organisms. A powerful alternative frequently employed in agriculture relies on the use of crop genetic resistances, approach that depends on mechanisms governing plant-virus interactions. Hence, knowledge related to the molecular bases of viral infections and crop resistances is key to face viral attacks in fields. Over the past 80 years, great advances have been made on our understanding of plant immunity against viruses. Although most of the known natural resistance genes have long been dominant R genes (encoding NBS-LRR proteins, a vast number of crop recessive resistance genes were cloned in the last decade, emphasizing another evolutive strategy to block viruses. In addition, the discovery of RNA interference pathways highlighted a very efficient antiviral system targeting the infectious agent at the nucleic acid level. Insidiously, plant viruses evolve and often acquire the ability to overcome the resistances employed by breeders. The development of efficient and durable resistances able to withstand the extreme genetic plasticity of viruses therefore represents a major challenge for the coming years. This review aims at describing some of the most devastating diseases caused by viruses on crops and summarizes current knowledge about plant-virus interactions, focusing on resistance mechanisms that prevent or limit viral infection in plants. In addition, I will discuss the current outcomes of the actions employed to control viral diseases in fields and the future investigations that need to be undertaken to develop sustainable broad-spectrum crop resistances against viruses.

  15. Immunization with Pre-Erythrocytic Antigen CelTOS from Plasmodium falciparum Elicits Cross-Species Protection against Heterologous Challenge with Plasmodium berghei

    Science.gov (United States)

    2010-08-01

    or the early liver-stages of the mammalian life cycle . One of these antigens is the cell-traversal protein for ookinetes and sporozoites (CelTOS...Immunization with Pre-Erythrocytic Antigen CelTOS from Plasmodium falciparum Elicits Cross-Species Protection against Heterologous Challenge with... Plasmodium berghei Elke S. Bergmann-Leitner1*, Ryan M. Mease1, Patricia De La Vega1, Tatyana Savranskaya2, Mark Polhemus1, Christian Ockenhouse1, Evelina

  16. Studies on the transfer of protective immunity with lymphoid cells from mice immune to malaria sporozoites

    International Nuclear Information System (INIS)

    Verhave, J.P.; Strickland, G.T.; Jaffe, H.A.; Ahmed, A.

    1978-01-01

    In an effort to understand the mechanisms involved in the protective immunity to malarial sporozoites, an A/J mouse/Plasmodium berghei model was studied. Protective immunity could consistently be adoptively transferred only by using sublethal irradiation of recipients (500 R); a spleen equivalent (100 x 10 6 ) of donor cells from immune syngeneic mice; and a small booster immunization (1 x 10 4 ) of recipients with irradiation-attenuated sporozoites. Recipient animals treated in this manner were protected from lethal challenge with 1 x 10 4 nonattenuated sporozoites. Immune and nonimmune serum and spleen cells from nonimmune animals did not protect recipient mice. Fewer immune spleen cells (50 x 10 6 ) protected some recipients. In vitro treatment of immune spleen cells with anti-theta sera and complement abolished their ability to transfer protection. This preliminary study suggests that protective sporozoite immunity can be transferred with cells, and that it is T cell dependent

  17. DNA immunization with fusion of CTLA-4 to hepatitis B virus (HBV core protein enhanced Th2 type responses and cleared HBV with an accelerated kinetic.

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    Ying Yin

    Full Text Available BACKGROUND: Typically, DNA immunization via the intramuscular route induces specific, Th1-dominant immune responses. However, plasmids expressing viral proteins fused to cytotoxic T lymphocyte antigen 4 (CTLA-4 primed Th2-biased responses and were able to induced effective protection against viral challenge in the woodchuck model. Thus, we addressed the question in the mouse model how the Th1/Th2 bias of primed immune responses by a DNA vaccine influences hepatitis B virus (HBV clearance. PRINCIPAL FINDINGS: Plasmids expressing HBV core protein (HBcAg or HBV e antigen and HBcAg fused to the extracellular domain of CTLA-4 (pCTLA-4-HBc, CD27, and full length CD40L were constructed. Immunizations of these DNA plasmids induced HBcAg-specific antibody and cytotoxic T-cell responses in mice, but with different characteristics regarding the titers and subtypes of specific antibodies and intensity of T-cell responses. The plasmid pHBc expressing HBcAg induced an IgG2a-dominant response while immunizations of pCTLA-4-HBc induced a balanced IgG1/IgG2a response. To assess the protective values of the immune responses of different characteristics, mice were pre-immunized with pCTLA-4-HBc and pHBc, and challenged by hydrodynamic injection (HI of pAAV/HBV1.2. HBV surface antigen (HBsAg and DNA in peripheral blood and HBcAg in liver tissue were cleared with significantly accelerated kinetics in both groups. The clearance of HBsAg was completed within 16 days in immunized mice while more than 50% of the control mice are still positive for HBsAg on day 22. Stronger HBcAg-specific T-cell responses were primed by pHBc correlating with a more rapid decline of HBcAg expression in liver tissue, while anti-HBs antibody response developed rapidly in the mice immunized with pCTLA-4-HBc, indicating that the Th1/Th2 bias of vaccine-primed immune responses influences the mode of viral clearance. CONCLUSION: Viral clearance could be efficiently achieved by Th1/Th2-balanced

  18. Effect of pulmonary irradiation from inhaled 90Y on immunity to Listeria monocytogenes in mice

    International Nuclear Information System (INIS)

    Sanchez, A.; Lundgren, D.L.; McClellan, R.O.

    1976-01-01

    The immunological response of mice subjected to irradiation from particles deposited in the lungs and challenged with Listeria monocytogenes was investigated. Mice, exposed by inhalation to 90 Y (a beta-emitting radionuclide) in relatively insoluble fused aluminosilicate particles, were immunized with L. monocytogenes either before or after exposure. Two additional groups of mice were either immunized or irradiated only. A group of control mice received no irradiation or immunization. The beta radiation dose absorbed by the lungs of each mouse at time of challenge averaged 10,000 rads. Fourteen days after immunization, all mice were challenged with 2 LD 50 doses of L. monocytogenes via the respiratory route. Survival of all immunized mice either with or without exposure to 90 Y varied from 90 to 100% as compared to 10 to 20% for the mice irradiated only and for control mice through 14 days after challenge. Pulmonary clearance of inhaled L. monocytogenes during the first 4 hr after challenge was suppressed in the mice irradiated only but not in those immunized only, or in the immunized and irradiated groups, and control mice. There appeared to be a suppression of proliferation of L. monocytogenes in lungs and spleen in the immunized groups 72 hr after challenge, whereas the lungs and spleens of the mice irradiated only and the control mice had extensive bacterial invasion. It was concluded that the 10,000 rads of beta radiation absorbed by the lungs did not suppress the immune mechanisms of the immunized mice

  19. Protective immunity by oral immunization with heat-killed Shigella strains in a guinea pig colitis model.

    Science.gov (United States)

    Barman, Soumik; Koley, Hemanta; Ramamurthy, Thandavarayan; Chakrabarti, Manoj Kumar; Shinoda, Sumio; Nair, Gopinath Balakrish; Takeda, Yoshifumi

    2013-11-01

    The protective efficacy of and immune response to heat-killed cells of monovalent and hexavalent mixtures of six serogroups/serotypes of Shigella strains (Shigella dysenteriae 1, Shigella flexneri 2a, S. flexneri 3a, S. flexneri 6, Shigella boydii 4, and Shigella sonnei) were examined in a guinea pig colitis model. A monovalent or hexavalent mixture containing 1 × 10(7) of each serogroup/serotype of heat-killed Shigella cells was administered orally on Days 0, 7, 14 and 21. On Day 28, the immunized animals were challenged rectally with 1 × 10(9) live virulent cells of each of the six Shigella serogroups/serotypes. In all immunized groups, significant levels of protection were observed after these challenges. The serum titers of IgG and IgA against the lipopolysaccharide of each of the six Shigella serogroups/serotypes increased exponential during the course of immunization. High IgA titers against the lipopolysaccharide of each of the six Shigella serogroups/serotypes were also observed in intestinal lavage fluid from all immunized animals. These data indicate that a hexavalent mixture of heat-killed cells of the six Shigella serogroups/serotypes studied would be a possible broad-spectrum candidate vaccine against shigellosis. © 2013 The Societies and Wiley Publishing Asia Pty Ltd.

  20. Immunization with Paracoccidioides brasiliensis radioattenuated yeast cells induces Th1 immune response in Balb/C mice

    Energy Technology Data Exchange (ETDEWEB)

    Martins, Estefania M.N.; Andrade, Antero S.R. [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN-CNEN/MG), Belo Horizonte, MG (Brazil)], e-mail: estefaniabio@yahoo.com.br, e-mail: antero@cdtn.br; Resende, Maria Aparecida de [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Microbiologia], e-mail: maresend@mono.icb.ufmg.br; Reis, Bernardo S.; Goes, Alfredo M. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Bioquimica e Imunologia], e-mail: goes@mono.icb.ufmg.br, e-mail: brsgarbi@mono.icb.ufmg.br

    2009-07-01

    Paracoccidioides brasiliensis is the agent of paracoccidioidomycosis, the most prevalent mycosis in Latin America. To date, there is no effective vaccine. In our laboratory yeast cells of P. brasiliensis were attenuated by gamma irradiation. We defined an absorbed dose in which the pathogen loses the reproductive ability, while retaining the morphology, the synthesis and secretion of proteins and the oxidative metabolism. The immunization with these cells was able to confer protection in BALB/c mice. The aim of the present work was evaluate the immune response pathway activated in mice immunized with P. brasiliensis radioattenuated yeast cells. The protector effect was evaluated in BALB/c mice groups immunized once or twice, respectively. Each group was divided in three sub groups that were challenge 30, 45 or 60 days after the immunization. These groups were called G1A, G1B and G1C in the group immunized once and G2A, G2B and G2C in the group immunized twice. Recovery of CFUs and cytokines determination (IFN - {gamma}, IL - 10 and IL IV 4) were performed three months post challenge. Quantitative RT-PCR was the method of choice used to quantify the expression of cytokines. The sera were collected weekly to evaluate the IgG antibody titers and the IgG1 and IgG2a pattern in the course of infection. A significant reduction in CFUs recovery was verified 90 days post challenge in mice submitted to one immunization: 73.0%, 96.0% and 76.3% for sub-groups G1A, G1B and G1C, respectively. In the group submitted to two immunizations, a remarkable increase in the protection was obtained. No CFUs was recovered from sub-groups G2B and G2C and very few CFUs (reduction of 98.6%) were recovered from the lungs of sub group G2A. In mice submitted to one immunization, Th1 and Th2 cytokines were simultaneously produced. In the group submitted to two immunizations, levels of IL-10 and IL-4 were very low, while IFN-{gamma} production was maintained indicating that a Th1 pattern was

  1. Immunization with Paracoccidioides brasiliensis radioattenuated yeast cells induces Th1 immune response in Balb/C mice

    International Nuclear Information System (INIS)

    Martins, Estefania M.N.; Andrade, Antero S.R.; Resende, Maria Aparecida de; Reis, Bernardo S.; Goes, Alfredo M.

    2009-01-01

    Paracoccidioides brasiliensis is the agent of paracoccidioidomycosis, the most prevalent mycosis in Latin America. To date, there is no effective vaccine. In our laboratory yeast cells of P. brasiliensis were attenuated by gamma irradiation. We defined an absorbed dose in which the pathogen loses the reproductive ability, while retaining the morphology, the synthesis and secretion of proteins and the oxidative metabolism. The immunization with these cells was able to confer protection in BALB/c mice. The aim of the present work was evaluate the immune response pathway activated in mice immunized with P. brasiliensis radioattenuated yeast cells. The protector effect was evaluated in BALB/c mice groups immunized once or twice, respectively. Each group was divided in three sub groups that were challenge 30, 45 or 60 days after the immunization. These groups were called G1A, G1B and G1C in the group immunized once and G2A, G2B and G2C in the group immunized twice. Recovery of CFUs and cytokines determination (IFN - γ, IL - 10 and IL IV 4) were performed three months post challenge. Quantitative RT-PCR was the method of choice used to quantify the expression of cytokines. The sera were collected weekly to evaluate the IgG antibody titers and the IgG1 and IgG2a pattern in the course of infection. A significant reduction in CFUs recovery was verified 90 days post challenge in mice submitted to one immunization: 73.0%, 96.0% and 76.3% for sub-groups G1A, G1B and G1C, respectively. In the group submitted to two immunizations, a remarkable increase in the protection was obtained. No CFUs was recovered from sub-groups G2B and G2C and very few CFUs (reduction of 98.6%) were recovered from the lungs of sub group G2A. In mice submitted to one immunization, Th1 and Th2 cytokines were simultaneously produced. In the group submitted to two immunizations, levels of IL-10 and IL-4 were very low, while IFN-γ production was maintained indicating that a Th1 pattern was dominant. For

  2. Neonatal Vaccination: Challenges and Intervention Strategies.

    Science.gov (United States)

    Morris, Matthew C; Surendran, Naveen

    2016-01-01

    While vaccines have been tremendously successful in reducing the incidence of serious infectious diseases, newborns remain particularly vulnerable in the first few months of their life to life-threatening infections. A number of challenges exist to neonatal vaccination. However, recent advances in the understanding of neonatal immunology offer insights to overcome many of those challenges. This review will present an overview of the features of neonatal immunity which make vaccination difficult, survey the mechanisms of action of available vaccine adjuvants with respect to the unique features of neonatal immunity, and propose a possible mechanism contributing to the inability of neonates to generate protective immune responses to vaccines. We surveyed recent published findings on the challenges to neonatal vaccination and possible intervention strategies including the use of novel vaccine adjuvants to develop efficacious neonatal vaccines. Challenges in the vaccination of neonates include interference from maternal antibody and excessive skewing towards Th2 immunity, which can be counteracted by the use of proper adjuvants. Synergistic stimulation of multiple Toll-like receptors by incorporating well-defined agonist-adjuvant combinations to vaccines is a promising strategy to ensure a protective vaccine response in neonates. © 2016 S. Karger AG, Basel.

  3. Improved survival in rhesus macaques immunized with modified vaccinia virus Ankara recombinants expressing simian immunodeficiency virus envelope correlates with reduction in memory CD4+ T-cell loss and higher titers of neutralizing antibody.

    Science.gov (United States)

    Ourmanov, Ilnour; Kuwata, Takeo; Goeken, Robert; Goldstein, Simoy; Iyengar, Ranjani; Buckler-White, Alicia; Lafont, Bernard; Hirsch, Vanessa M

    2009-06-01

    Previous studies demonstrated that immunization of macaques with simian immunodeficiency virus (SIV) Gag-Pol and Env recombinants of the attenuated poxvirus modified vaccinia virus Ankara (MVA) provided protection from high viremia and AIDS following challenge with a pathogenic strain of SIV. Although all animals became infected, plasma viremia was significantly reduced in animals that received the MVA-SIV recombinant vaccines compared with animals that received nonrecombinant MVA. Most importantly, the reduction in viremia resulted in a significant increase in median and cumulative survival. Continued analysis of these animals over the subsequent 9 years has shown that they maintain a survival advantage, although all but two of the macaques have progressed to AIDS. Importantly, improved survival correlated with preservation of memory CD4(+) T cells in the peripheral blood. The greatest survival advantage was observed in macaques immunized with regimens containing SIV Env, and the titer of neutralizing antibodies to the challenge virus prior to or shortly following challenge correlated with preservation of CD4(+) T cells. These data are consistent with a role for neutralizing antibodies in nonsterilizing protection from high viremia and associated memory CD4(+) T-cell loss.

  4. Effect of Xiao Chaihu Tang combined with intravenous chemotherapy on tumor markers and immune function in patients with advanced breast cancer

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    Jian-Ping Zhong

    2017-05-01

    Full Text Available Objective: To study the effect of Xiao Chaihu Tang combined with intravenous chemotherapy on tumor markers and immune function in patients with advanced breast cancer. Methods: 76 patients with advanced breast cancer treated in our hospital between May 2012 and November 2015 were collected and divided into the combined treatment group (n=34 who accepted Xiao Chaihu Tang combined with intravenous chemotherapy and the control group (n=42 who accepted intravenous chemotherapy alone according to different treatment, and the treatment cycle was 3 months for both groups. Before treatment and 3 months after treatment, ELISA method was used to detect serum levels of broad-spectrum tumor markers and breast cancerspecific tumor markers; flow cytometer was used to detect cellular immune function index levels, and turbidimetric immunoassay was used to detect humoral immune function index levels in peripheral blood. Results: Before treatment, differences in serum tumor marker levels as well as cellular immunity and humoral immunity index levels in peripheral blood were not statistically significant between two groups of patients (P>0.05; after 3 months of treatment, broad-spectrum tumor markers carcinoembryonic antigen (CEA, carbohydrate antigen 153 (CA153 and carbohydrate antigen 125 (CA125 levels in serum of combined treatment group were lower than those of control group, and breast cancer-specific tumor markers insulin-like growth factor-1 (IGF-1, midkine (MK, soluble E-cadherin (sEC and thymidine kinase 1 (TK1 levels were lower than those of control group (P<0.05; CD3+ and CD4+ T lymphocyte levels as well as CD4+/CD8+ ratio in peripheral blood of combined treatment group were higher than those of control group while CD8+ T lymphocyte level was lower than that of control group, and immunoglobulin G (IgG, immunoglobulin A (IgA and immunoglobulin M (IgM levels in peripheral blood were higher than those of control group (P<0.05. Conclusions: Xiao Chaihu Tang

  5. Transcriptome Analysis and Discovery of Genes Involved in Immune Pathways from Coelomocytes of Sea Cucumber (Apostichopus japonicus) after Vibrio splendidus Challenge.

    Science.gov (United States)

    Gao, Qiong; Liao, Meijie; Wang, Yingeng; Li, Bin; Zhang, Zheng; Rong, Xiaojun; Chen, Guiping; Wang, Lan

    2015-07-17

    Vibrio splendidus is identified as one of the major pathogenic factors for the skin ulceration syndrome in sea cucumber (Apostichopus japonicus), which has vastly limited the development of the sea cucumber culture industry. In order to screen the immune genes involving Vibrio splendidus challenge in sea cucumber and explore the molecular mechanism of this process, the related transcriptome and gene expression profiling of resistant and susceptible biotypes of sea cucumber with Vibrio splendidus challenge were collected for analysis. A total of 319,455,942 trimmed reads were obtained, which were assembled into 186,658 contigs. After that, 89,891 representative contigs (without isoform) were clustered. The analysis of the gene expression profiling identified 358 differentially expression genes (DEGs) in the bacterial-resistant group, and 102 DEGs in the bacterial-susceptible group, compared with that in control group. According to the reported references and annotation information from BLAST, GO and KEGG, 30 putative bacterial-resistant genes and 19 putative bacterial-susceptible genes were identified from DEGs. The qRT-PCR results were consistent with the RNA-Seq results. Furthermore, many DGEs were involved in immune signaling related pathways, such as Endocytosis, Lysosome, MAPK, Chemokine and the ERBB signaling pathway.

  6. Feto-maternal immune regulation by TIM-3/galectin-9 pathway and PD-1 molecule in mice at day 14.5 of pregnancy

    DEFF Research Database (Denmark)

    Meggyes, Matyas; Lajko, Adrienn; Palkovics, Tamas

    2015-01-01

    INTRODUCTION: Immunoregulation implies the activation of negative pathways leading to the modulation of specific immune responses. Co-inhibitory receptors (such as PD-1 and TIM-3) represent possible tools for this purpose. PD-1 and TIM-3 have been demonstrated to be present on immune cells...... suggesting general involvement in immunosuppression such as fetomaternal tolerance. The aim of our study was to investigate the expression pattern of PD-1, TIM-3, and its ligand Gal-9 on different immune cell subsets in the peripheral blood and at the fetomaternal interface in pregnant mice. METHODS: TIM-3...... and PD-1 expression by peripheral and decidual immune cells from pregnant BALB-c mice in 2 weeks of gestational age were measures by flow cytometry. Placental galectin-9 expression was determined by immunohistochemically and RT-PCR. RESULTS: Gal-9 was found to be present in the spongiotrophoblast layer...

  7. Contributions of immune responses to developmental resistance in Lymantria dispar challenged with baculovirus

    Science.gov (United States)

    James McNeil; Diana Cox-Foster; James Slavicek; Kelli. Hoover

    2010-01-01

    How the innate immune system functions to defend insects from viruses is an emerging field of study. We examined the impact of melanized encapsulation, a component of innate immunity that integrates both cellular and humoral immune responses, on the success of the baculovirus Lymantria dispar multiple nucleocapsid nucleopolyhedrovirus (LdMNPV) in its...

  8. Sympathetic neural modulation of the immune system

    International Nuclear Information System (INIS)

    Madden, K.S.

    1989-01-01

    One route by which the central nervous system communicates with lymphoid organs in the periphery is through the sympathetic nervous system (SNS). To study SNS regulation of immune activity in vivo, selective removal of peripheral noradrenergic nerve fibers was achieved by administration of the neurotoxic drug, 6-hydroxydopamine (6-OHDA), to adult mice. To assess SNS influence on lymphocyte proliferation in vitro, uptake of 125 iododeoxyuridine ( 125 IUdR), a DNA precursor, was measured following 6-OHDA treatment. Sympathectomy prior to epicutaneous immunization with TNCB did not alter draining lymph nodes (LN) cell proliferation, whereas 6-OHDA treatment before footpad immunization with KLH reduced DNA synthesis in popliteal LN by 50%. In mice which were not deliberately immunized, sympathectomy stimulated 125 IUdR uptake inguinal and axillary LN, spleen, and bone marrow. In vitro, these LN and spleen cells exhibited decreased proliferation responses to the T cell mitogen, concanavalin A (Con A), whereas lipopolysaccharide (LPS)-stimulated IgG secretion was enhanced. Studies examining 51 Cr-labeled lymphocyte trafficking to LN suggested that altered cell migration may play a part in sympathectomy-induced changes in LN cell function

  9. Peripheral nerve regeneration with conduits: use of vein tubes

    OpenAIRE

    Sabongi, Rodrigo Guerra; Fernandes, Marcela; dos Santos, Jo?o Baptista Gomes

    2015-01-01

    Treatment of peripheral nerve injuries remains a challenge to modern medicine due to the complexity of the neurobiological nerve regenerating process. There is a greater challenge when the transected nerve ends are not amenable to primary end-to-end tensionless neurorraphy. When facing a segmental nerve defect, great effort has been made to develop an alternative to the autologous nerve graft in order to circumvent morbidity at donor site, such as neuroma formation, scarring and permanent los...

  10. Sculpting humoral immunity through dengue vaccination to enhance protective immunity

    Directory of Open Access Journals (Sweden)

    Wayne eCrill

    2012-11-01

    Full Text Available Dengue viruses (DENV are the most important mosquito transmitted viral pathogens infecting humans. DENV infection produces a spectrum of disease, most commonly causing a self-limiting flu-like illness known as dengue fever; yet with increased frequency, manifesting as life-threatening dengue hemorrhagic fever (DHF. Waning cross-protective immunity from any of the four dengue serotypes may enhance subsequent infection with another heterologous serotype to increase the probability of DHF. Decades of effort to develop dengue vaccines are reaching the finishing line with multiple candidates in clinical trials. Nevertheless, concerns remain that imbalanced immunity, due to the prolonged prime-boost schedules currently used in clinical trials, could leave some vaccinees temporarily unprotected or with increased susceptibility to enhanced disease. Here we develop a DENV serotype 1 (DENV-1 DNA vaccine with the immunodominant cross-reactive B cell epitopes associated with immune enhancement removed. We compare wild-type (WT with this cross-reactivity reduced (CRR vaccine and demonstrate that both vaccines are equally protective against lethal homologous DENV-1 challenge. Under conditions mimicking natural exposure prior to acquiring protective immunity, WT vaccinated mice enhanced a normally sub-lethal heterologous DENV-2 infection resulting in DHF-like disease and 95% mortality in AG129 mice. However, CRR vaccinated mice exhibited redirected serotype-specific and protective immunity, and significantly reduced morbidity and mortality not differing from naïve mice. Thus, we demonstrate in an in vivo DENV disease model, that non-protective vaccine-induced immunity can prime vaccinees for enhanced DHF-like disease and that CRR DNA immunization significantly reduces this potential vaccine safety concern. The sculpting of immune memory by the modified vaccine and resulting redirection of humoral immunity provide insight into DENV vaccine induced immune

  11. Group 3 Innate Lymphoid Cells: Communications Hubs of the Intestinal Immune System.

    Science.gov (United States)

    Withers, David R; Hepworth, Matthew R

    2017-01-01

    The maintenance of mammalian health requires the generation of appropriate immune responses against a broad range of environmental and microbial challenges, which are continually encountered at barrier tissue sites including the skin, lung, and gastrointestinal tract. Dysregulated barrier immune responses result in inflammation, both locally and systemically in peripheral organs. Group 3 innate lymphoid cells (ILC3) are constitutively present at barrier sites and appear to be highly specialized in their ability to sense a range of environmental and host-derived signals. Under homeostatic conditions, ILC3 respond to local cues to maintain tissue homeostasis and restrict inflammatory responses. In contrast, perturbations in the tissue microenvironment resulting from disease, infection, or tissue damage can drive dysregulated pro-inflammatory ILC3 responses and contribute to immunopathology. The tone of the ILC3 response is dictated by a balance of "exogenous" signals, such as dietary metabolites and commensal microbes, and "endogenous" host-derived signals from stromal cells, immune cells, and the nervous system. ILC3 must therefore have the capacity to simultaneously integrate a wide array of complex and dynamic inputs in order to regulate barrier function and tissue health. In this review, we discuss the concept of ILC3 as a "communications hub" in the intestinal tract and associated lymphoid tissues and address the variety of signals, derived from multiple biological systems, which are interpreted by ILC3 to modulate the release of downstream effector molecules and regulate cell-cell crosstalk. Successful integration of environmental cues by ILC3 and downstream propagation to the broader immune system is required to maintain a tolerogenic and anti-inflammatory tone and reinforce barrier function, whereas dysregulation of ILC3 responses can contribute to the onset or progression of clinically relevant chronic inflammatory diseases.

  12. Group 3 Innate Lymphoid Cells: Communications Hubs of the Intestinal Immune System

    Directory of Open Access Journals (Sweden)

    David R. Withers

    2017-10-01

    Full Text Available The maintenance of mammalian health requires the generation of appropriate immune responses against a broad range of environmental and microbial challenges, which are continually encountered at barrier tissue sites including the skin, lung, and gastrointestinal tract. Dysregulated barrier immune responses result in inflammation, both locally and systemically in peripheral organs. Group 3 innate lymphoid cells (ILC3 are constitutively present at barrier sites and appear to be highly specialized in their ability to sense a range of environmental and host-derived signals. Under homeostatic conditions, ILC3 respond to local cues to maintain tissue homeostasis and restrict inflammatory responses. In contrast, perturbations in the tissue microenvironment resulting from disease, infection, or tissue damage can drive dysregulated pro-inflammatory ILC3 responses and contribute to immunopathology. The tone of the ILC3 response is dictated by a balance of “exogenous” signals, such as dietary metabolites and commensal microbes, and “endogenous” host-derived signals from stromal cells, immune cells, and the nervous system. ILC3 must therefore have the capacity to simultaneously integrate a wide array of complex and dynamic inputs in order to regulate barrier function and tissue health. In this review, we discuss the concept of ILC3 as a “communications hub” in the intestinal tract and associated lymphoid tissues and address the variety of signals, derived from multiple biological systems, which are interpreted by ILC3 to modulate the release of downstream effector molecules and regulate cell–cell crosstalk. Successful integration of environmental cues by ILC3 and downstream propagation to the broader immune system is required to maintain a tolerogenic and anti-inflammatory tone and reinforce barrier function, whereas dysregulation of ILC3 responses can contribute to the onset or progression of clinically relevant chronic inflammatory diseases.

  13. Group 3 Innate Lymphoid Cells: Communications Hubs of the Intestinal Immune System

    Science.gov (United States)

    Withers, David R.; Hepworth, Matthew R.

    2017-01-01

    The maintenance of mammalian health requires the generation of appropriate immune responses against a broad range of environmental and microbial challenges, which are continually encountered at barrier tissue sites including the skin, lung, and gastrointestinal tract. Dysregulated barrier immune responses result in inflammation, both locally and systemically in peripheral organs. Group 3 innate lymphoid cells (ILC3) are constitutively present at barrier sites and appear to be highly specialized in their ability to sense a range of environmental and host-derived signals. Under homeostatic conditions, ILC3 respond to local cues to maintain tissue homeostasis and restrict inflammatory responses. In contrast, perturbations in the tissue microenvironment resulting from disease, infection, or tissue damage can drive dysregulated pro-inflammatory ILC3 responses and contribute to immunopathology. The tone of the ILC3 response is dictated by a balance of “exogenous” signals, such as dietary metabolites and commensal microbes, and “endogenous” host-derived signals from stromal cells, immune cells, and the nervous system. ILC3 must therefore have the capacity to simultaneously integrate a wide array of complex and dynamic inputs in order to regulate barrier function and tissue health. In this review, we discuss the concept of ILC3 as a “communications hub” in the intestinal tract and associated lymphoid tissues and address the variety of signals, derived from multiple biological systems, which are interpreted by ILC3 to modulate the release of downstream effector molecules and regulate cell–cell crosstalk. Successful integration of environmental cues by ILC3 and downstream propagation to the broader immune system is required to maintain a tolerogenic and anti-inflammatory tone and reinforce barrier function, whereas dysregulation of ILC3 responses can contribute to the onset or progression of clinically relevant chronic inflammatory diseases. PMID:29085366

  14. Intracellular Bacterial Infections: A Challenge for Developing Cellular Mediated Immunity Vaccines for Farmed Fish

    Directory of Open Access Journals (Sweden)

    Hetron Mweemba Munang’andu

    2018-04-01

    Full Text Available Aquaculture is one of the most rapidly expanding farming systems in the world. Its rapid expansion has brought with it several pathogens infecting different fish species. As a result, there has been a corresponding expansion in vaccine development to cope with the increasing number of infectious diseases in aquaculture. The success of vaccine development for bacterial diseases in aquaculture is largely attributed to empirical vaccine designs based on inactivation of whole cell (WCI bacteria vaccines. However, an upcoming challenge in vaccine design is the increase of intracellular bacterial pathogens that are not responsive to WCI vaccines. Intracellular bacterial vaccines evoke cellular mediated immune (CMI responses that “kill” and eliminate infected cells, unlike WCI vaccines that induce humoral immune responses whose protective mechanism is neutralization of extracellular replicating pathogens by antibodies. In this synopsis, I provide an overview of the intracellular bacterial pathogens infecting different fish species in aquaculture, outlining their mechanisms of invasion, replication, and survival intracellularly based on existing data. I also bring into perspective the current state of CMI understanding in fish together with its potential application in vaccine development. Further, I highlight the immunological pitfalls that have derailed our ability to produce protective vaccines against intracellular pathogens for finfish. Overall, the synopsis put forth herein advocates for a shift in vaccine design to include CMI-based vaccines against intracellular pathogens currently adversely affecting the aquaculture industry.

  15. Detection of Bartonella henselae DNA in clinical samples including peripheral blood of immune competent and immune compromised patients by three nested amplifications

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    Karina Hatamoto Kawasato

    2013-02-01

    Full Text Available Bacteria of the genus Bartonella are emerging pathogens detected in lymph node biopsies and aspirates probably caused by increased concentration of bacteria. Twenty-three samples of 18 patients with clinical, laboratory and/or epidemiological data suggesting bartonellosis were subjected to three nested amplifications targeting a fragment of the 60-kDa heat shock protein (HSP, the internal transcribed spacer 16S-23S rRNA (ITS and the cell division (FtsZ of Bartonella henselae, in order to improve detection in clinical samples. In the first amplification 01, 04 and 05 samples, were positive by HSP (4.3%, FtsZ (17.4% and ITS (21.7%, respectively. After the second round six positive samples were identified by nested-HSP (26%, eight by nested-ITS (34.8% and 18 by nested-FtsZ (78.2%, corresponding to 10 peripheral blood samples, five lymph node biopsies, two skin biopsies and one lymph node aspirate. The nested-FtsZ was more sensitive than nested-HSP and nested-ITS (p < 0.0001, enabling the detection of Bartonella henselae DNA in 15 of 18 patients (83.3%. In this study, three nested-PCR that should be specific for Bartonella henselae amplification were developed, but only the nested-FtsZ did not amplify DNA from Bartonella quintana. We conclude that nested amplifications increased detection of B. henselae DNA, and that the nested-FtsZ was the most sensitive and the only specific to B. henselae in different biological samples. As all samples detected by nested-HSP and nested-ITS, were also by nested-FtsZ, we infer that in our series infections were caused by Bartonella henselae. The high number of positive blood samples draws attention to the use of this biological material in the investigation of bartonellosis, regardless of the immune status of patients. This fact is important in the case of critically ill patients and young children to avoid more invasive procedures such as lymph nodes biopsies and aspirates.

  16. Peripheral arterial disease and revascularization of the diabetic foot.

    Science.gov (United States)

    Forsythe, R O; Brownrigg, J; Hinchliffe, R J

    2015-05-01

    Diabetes is a complex disease with many serious potential sequelae, including large vessel arterial disease and microvascular dysfunction. Peripheral arterial disease is a common large vessel complication of diabetes, implicated in the development of tissue loss in up to half of patients with diabetic foot ulceration. In addition to peripheral arterial disease, functional changes in the microcirculation also contribute to the development of a diabetic foot ulcer, along with other factors such as infection, oedema and abnormal biomechanical loading. Peripheral arterial disease typically affects the distal vessels, resulting in multi-level occlusions and diffuse disease, which often necessitates challenging distal revascularisation surgery or angioplasty in order to improve blood flow. However, technically successful revascularisation does not always result in wound healing. The confounding effects of microvascular dysfunction must be recognised--treatment of a patient with a diabetic foot ulcer and peripheral arterial disease should address this complex interplay of pathophysiological changes. In the case of non-revascularisable peripheral arterial disease or poor response to conventional treatment, alternative approaches such as cell-based treatment, hyperbaric oxygen therapy and the use of vasodilators may appear attractive, however more robust evidence is required to justify these novel approaches. © 2014 John Wiley & Sons Ltd.

  17. Detailing profiles of Lawsonia intracellularis specific lymphocytes in the immune response to a challenge inoculation after oral vaccination or primary inoculation with virulent bacteria

    DEFF Research Database (Denmark)

    Riber, Ulla; Hvass, Henriette Cordes; Heegaard, Peter M. H.

    2012-01-01

    Vaccination against the intracellular porcine enteric pathogen Lawsonia intracellularis remains a challenge as the commercially available vaccine does not provide full protection. In an experimental challenge study, the Enterisol® Ileitis attenuated live vaccine against Lawsonia intracellularis did...... not induce measurable primary humoral or cell-mediated immune responses, nor was it able to reduce faecal shedding of bacteria from eight vaccinated pigs compared to seven age-matched naïve challenge-control pigs. Vaccinated pigs did, however, respond to vaccination with an acute phase protein response...

  18. Effects of dietary source and intake of energy on immune competence and the response to an infectious bovine rhinotracheitis virus (IBRV) challenge in cattle

    Science.gov (United States)

    Objectives were to evaluate how dietary energy intake and source affect immune competence and response to an infectious bovine rhinotracheitis virus (IBRV) challenge in cattle. Forty-eight crossbred beef steers were stratified by body weight within 2 periods and randomized to 1 of 3 dietary treatmen...

  19. Effect of enrofloxacin on Haemophilus parasuis infection, disease and immune response.

    Science.gov (United States)

    Macedo, Nubia; Cheeran, Maxim C J; Rovira, Albert; Holtcamp, Andrew; Torremorell, Montserrat

    2017-02-01

    Haemophilus parasuis, the causative agent of Glasser's disease, is a pathogen that colonizes the upper respiratory tract (URT) of pigs, invades the bloodstream and causes polyserositis. Because antimicrobials are highly effective against H. parasuis, we hypothesized that they could have a detrimental effect on the establishment of an immune response if given at the time of URT colonization. In this study, we characterized clinical outcomes and antibody and IFN-γ responses to H. parasuis in pigs treated with enrofloxacin before or after low dose inoculation with a pathogenic H. parasuis strain. Pigs that were only inoculated with the agent (EXP group) and pigs that were treated with enrofloxacin and then inoculated (ABT/EXP group) developed signs of disease starting at 4days post inoculation (DPI), presented a significant increase in serum IgG and were protected against a subsequent homologous challenge. In contrast, pigs treated with antibiotic after inoculation (EXP/ABT group) neither showed signs of disease nor seroconverted (IgG) after low dose inoculation. EXP/ABT pigs as well as naïve control pigs [enrofloxacin only (ABT) and challenge only (CHA)] were susceptible to challenge. Variable levels of antibodies in bronchioalveolar fluid and IFN-γ in peripheral blood mononuclear cells were observed after H. parasuis inoculation, but were not associated with protection. In summary, only pigs treated before low dose H. parasuis inoculation seroconverted and were protected against subsequent challenge. Results from this study can help determine timing of antimicrobial use and contribute to our current understanding of judicious antibiotic use. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Induction of mucosal immune responses and protection of cattle against direct-contact challenge by intranasal delivery with foot-and-mouth disease virus antigen mediated by nanoparticles

    Directory of Open Access Journals (Sweden)

    Pan L

    2014-12-01

    Full Text Available Li Pan,1,2 Zhongwang Zhang,1,2 Jianliang Lv,1,2 Peng Zhou,1,2 Wenfa Hu,1,2 Yuzhen Fang,1,2 Haotai Chen,1,2 Xinsheng Liu,1,2 Junjun Shao,1,2 Furong Zhao,1,2 Yaozhong Ding,1,2 Tong Lin,1,2 Huiyun Chang,1,2 Jie Zhang,1,2 Yongguang Zhang,1,2 Yonglu Wang1,2 1State Key Laboratory of Veterinary Etiological Biology, National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS, Lanzhou, Gansu, People’s Republic of China; 2Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, People’s Republic of China Abstract: The aim of this study was to enhance specific mucosal, systemic, and cell-mediated immunity and to induce earlier onset of protection against direct-contact challenge in cattle by intranasal delivery of a nanoparticle-based nasal vaccine against type A foot-and-mouth disease (FMD. In this study, two kinds of nanoparticle-based nasal vaccines against type A FMD were designed: (1 chitosan-coated poly(lactic-co-glycolic acid (PLGA loaded with plasmid DNA (Chi-PLGA-DNA and (2 chitosan-trehalose and inactivated foot-and-mouth disease virus (FMDV (Chi-Tre-Inactivated. Cattle were immunized by an intranasal route with nanoparticles and then challenged for 48 hours by direct contact with two infected donor cattle per pen. Donors were inoculated intradermally in the tongue 48 hours before challenge, with 0.2 mL cattle-passaged FMDV. Serological and mucosal antibody responses were evaluated, and virus excretion and the number of contact infections were quantified. FMDV-specific secretory immunoglobulin (IgA (sIgA antibodies in nasal washes were initially detected at 4 days postvaccination (dpv with two kinds of nanoparticles. The highest levels of sIgA expression were observed in nasal washes, at 10 dpv, from animals with Chi-PLGA-DNA nanoparticles, followed by animals immunized once by intranasal route with

  1. Registry Assessment of Peripheral Interventional Devices (RAPID) - Registry Assessment of Peripheral Interventional Devices Core Data Elements.

    Science.gov (United States)

    Jones, W Schuyler; Krucoff, Mitchell W; Morales, Pablo; Wilgus, Rebecca W; Heath, Anne H; Williams, Mary F; Tcheng, James E; Marinac-Dabic, J Danica; Malone, Misti L; Reed, Terrie L; Fukaya, Rie; Lookstein, Robert; Handa, Nobuhiro; Aronow, Herbert D; Bertges, Daniel J; Jaff, Michael R; Tsai, Thomas T; Smale, Joshua A; Zaugg, Margo J; Thatcher, Robert J; Cronenwett, Jack L; Nc, Durham; Md, Silver Spring; Japan, Tokyo; Ny, New York; Ri, Providence; Vt, Burlington; Mass, Newton; Colo, Denver; Ariz, Tempe; Calif, Santa Clara; Minn, Minneapolis; Nh, Lebanon

    2018-01-25

    The current state of evaluating patients with peripheral artery disease and more specifically of evaluating medical devices used for peripheral vascular intervention (PVI) remains challenging because of the heterogeneity of the disease process, the multiple physician specialties that perform PVI, the multitude of devices available to treat peripheral artery disease, and the lack of consensus about the best treatment approaches. Because PVI core data elements are not standardized across clinical care, clinical trials, and registries, aggregation of data across different data sources and physician specialties is currently not feasible.Methods and Results:Under the auspices of the U.S. Food and Drug Administration's Medical Device Epidemiology Network initiative-and its PASSION (Predictable and Sustainable Implementation of the National Registries) program, in conjunction with other efforts to align clinical data standards-the Registry Assessment of Peripheral Interventional Devices (RAPID) workgroup was convened. RAPID is a collaborative, multidisciplinary effort to develop a consensus lexicon and to promote interoperability across clinical care, clinical trials, and national and international registries of PVI. The current manuscript presents the initial work from RAPID to standardize clinical data elements and definitions, to establish a framework within electronic health records and health information technology procedural reporting systems, and to implement an informatics-based approach to promote the conduct of pragmatic clinical trials and registry efforts in PVI. Ultimately, we hope this work will facilitate and improve device evaluation and surveillance for patients, clinicians, health outcomes researchers, industry, policymakers, and regulators.

  2. Intranasal delivery of cationic PLGA nano/microparticles-loaded FMDV DNA vaccine encoding IL-6 elicited protective immunity against FMDV challenge.

    Directory of Open Access Journals (Sweden)

    Gang Wang

    Full Text Available Mucosal vaccination has been demonstrated to be an effective means of eliciting protective immunity against aerosol infections of foot and mouth disease virus (FMDV and various approaches have been used to improve mucosal response to this pathogen. In this study, cationic PLGA (poly(lactide-co-glycolide nano/microparticles were used as an intranasal delivery vehicle as a means administering FMDV DNA vaccine encoding the FMDV capsid protein and the bovine IL-6 gene as a means of enhancing mucosal and systemic immune responses in animals. Three eukaryotic expression plasmids with or without bovine IL-6 gene (pc-P12A3C, pc-IL2AP12A3C and pc-P12AIL3C were generated. The two latter plasmids were designed with the IL-6 gene located either before or between the P12A and 3C genes, respectively, as a means of determining if the location of the IL-6 gene affected capsid assembly and the subsequent immune response. Guinea pigs and rats were intranasally vaccinated with the respective chitosan-coated PLGA nano/microparticles-loaded FMDV DNA vaccine formulations. Animals immunized with pc-P12AIL3C (followed by animals vaccinated with pc-P12A3C and pc-IL2AP12A3C developed the highest levels of antigen-specific serum IgG and IgA antibody responses and the highest levels of sIgA (secretory IgA present in mucosal tissues. However, the highest levels of neutralizing antibodies were generated in pc-IL2AP12A3C-immunized animals (followed by pc-P12AIL3C- and then in pc-P12A3C-immunized animals. pc-IL2AP12A3C-immunized animals also developed stronger cell mediated immune responses (followed by pc-P12AIL3C- and pc-P12A3C-immunized animals as evidenced by antigen-specific T-cell proliferation and expression levels of IFN-γ by both CD4+ and CD8+ splenic T cells. The percentage of animals protected against FMDV challenge following immunizations with pc-IL2AP12A3C, pc-P12AIL3C or pc-P12A3C were 3/5, 1/5 and 0/5, respectively. These data suggested that intranasal delivery

  3. Diverse Roles of Inhibitor of Differentiation 2 in Adaptive Immunity

    Directory of Open Access Journals (Sweden)

    Lucille Rankin

    2011-01-01

    Full Text Available The helix-loop-helix (HLH transcription factor inhibitor of DNA binding 2 (Id2 has been implicated as a regulator of hematopoiesis and embryonic development. While its role in early lymphopoiesis has been well characterized, new roles in adaptive immune responses have recently been uncovered opening exciting new directions for investigation. In the innate immune system, Id2 is required for the development of mature natural killer (NK cells, lymphoid tissue-inducer (LTi cells, and the recently identified interleukin (IL-22 secreting nonconventional innate lymphocytes found in the gut. In addition, Id2 has been implicated in the development of specific dendritic cell (DC subsets, decisions determining the formation of αβ and γδ T-cell development, NK T-cell behaviour, and in the maintenance of effector and memory CD8+ T cells in peripheral tissues. Here, we review the current understanding of the role of Id2 in lymphopoiesis and in the development of the adaptive immune response required for maintaining immune homeostasis and immune protection.

  4. Characterization of γδ regulatory T cells from peripheral blood in patients with multiple myeloma

    International Nuclear Information System (INIS)

    Ma, Yongyong; Lei, Huyi; Tan, Jie; Xuan, Li; Wu, Xiuli; Liu, Qifa

    2016-01-01

    γδ regulatory T cells are able to inhibit the activation and function of T cells involved in antigen-specific immune responses. This study aimed to investigate the potential role of γδ regulatory T cells in inhibiting anti-tumor immune responses in patients diagnosed as multiple myeloma (MM). We measured the levels of γδ T cells, the distribution and clonally amplified TCR Vγ and VδT cells in peripheral blood of healthy donors, patients recently diagnosed with MM, and MM patients in remission cohorts. In addition, we evaluated the ability of γδ regulatory T cells to inhibit the proliferation of CD4+CD25- T cells and detected the expression of immunoregulatory-associated molecules. We found that the levels of γδ regulatory T cells from the peripheral blood in patients of MM were significantly higher than those in healthy donors. Comparison of γδT regulatory cells function in MM and healthy donors showed similarly inhibitory effects on the proliferation of T cells. Additionally, TLR8 expression level increased significantly in MM patients compared to healthy donors, while the expression levels of Foxp3, CD25, CTLA4, GITR, GATA3 and Tbet in MM patients and healthy donors showed no significant difference. Taken together, our study reveals the potential role of γδ regulatory T cells in inhibiting anti-tumor immune responses in MM patients.

  5. The role of immune mechanisms in Tourette syndrome.

    Science.gov (United States)

    Martino, Davide; Zis, Panagiotis; Buttiglione, Maura

    2015-08-18

    Tourette syndrome (TS) is a childhood-onset tic disorder associated with abnormal development of brain networks involved in the sensory and motor processing. An involvement of immune mechanisms in its pathophysiology has been proposed. Animal models based on active immunization with bacterial or viral mimics, direct injection of cytokines or patients' serum anti-neuronal antibodies, and transgenic approaches replicated stereotyped behaviors observed in human TS. A crucial role of microglia in the neural-immune crosstalk within TS and related disorders has been proposed by animal models and confirmed by recent post mortem studies. With analogy to autism, genetic and early life environmental factors could foster the involvement of immune mechanisms to the abnormal developmental trajectories postulated in TS, as well as lead to systemic immune dysregulation in this condition. Clinical studies demonstrate an association between TS and immune responses to pathogens like group A Streptococcus (GAS), although their role as risk-modifiers is still undefined. Overactivity of immune responses at a systemic level is suggested by clinical studies exploring cytokine and immunoglobulin levels, immune cell subpopulations, and gene expression profiling of peripheral lymphocytes. The involvement of autoantibodies, on the other hand, remains uncertain and warrants more work using live cell-based approaches. Overall, a body of evidence supports the hypothesis that disease mechanisms in TS, like other neurodevelopmental illnesses (e.g. autism), may involve dysfunctional neural-immune cross-talk, ultimately leading to altered maturation of brain pathways controlling different behavioral domains and, possibly, differences in organising immune and stress responses. This article is part of a Special Issue entitled SI: Neuroimmunology in Health And Disease. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Exercise and the Regulation of Immune Functions.

    Science.gov (United States)

    Simpson, Richard J; Kunz, Hawley; Agha, Nadia; Graff, Rachel

    2015-01-01

    Exercise has a profound effect on the normal functioning of the immune system. It is generally accepted that prolonged periods of intensive exercise training can depress immunity, while regular moderate intensity exercise is beneficial. Single bouts of exercise evoke a striking leukocytosis and a redistribution of effector cells between the blood compartment and the lymphoid and peripheral tissues, a response that is mediated by increased hemodynamics and the release of catecholamines and glucocorticoids following the activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis. Single bouts of prolonged exercise may impair T-cell, NK-cell, and neutrophil function, alter the Type I and Type II cytokine balance, and blunt immune responses to primary and recall antigens in vivo. Elite athletes frequently report symptoms associated with upper respiratory tract infections (URTI) during periods of heavy training and competition that may be due to alterations in mucosal immunity, particularly reductions in secretory immunoglobulin A. In contrast, single bouts of moderate intensity exercise are "immuno-enhancing" and have been used to effectively increase vaccine responses in "at-risk" patients. Improvements in immunity due to regular exercise of moderate intensity may be due to reductions in inflammation, maintenance of thymic mass, alterations in the composition of "older" and "younger" immune cells, enhanced immunosurveillance, and/or the amelioration of psychological stress. Indeed, exercise is a powerful behavioral intervention that has the potential to improve immune and health outcomes in the elderly, the obese, and patients living with cancer and chronic viral infections such as HIV. © 2015 Elsevier Inc. All rights reserved.

  7. The Immune System in Irritable Bowel Syndrome

    Science.gov (United States)

    Cremon, Cesare; Carini, Giovanni; Bellacosa, Lara; Zecchi, Lisa; De Giorgio, Roberto; Corinaldesi, Roberto; Stanghellini, Vincenzo

    2011-01-01

    The potential relevance of systemic and gastrointestinal immune activation in the pathophysiology and symptom generation in the irritable bowel syndrome (IBS) is supported by a number of observations. Infectious gastroenteritis is the strongest risk factor for the development of IBS and increased rates of IBS-like symptoms have been detected in patients with inflammatory bowel disease in remission or in celiac disease patients on a gluten free diet. The number of T cells and mast cells in the small and large intestine of patients with IBS is increased in a large proportion of patients with IBS over healthy controls. Mediators released by immune cells and likely from other non-immune competent cells impact on the function of enteric and sensory afferent nerves as well as on epithelial tight junctions controlling mucosal barrier of recipient animals, isolated human gut tissues or cell culture systems. Antibodies against microbiota antigens (bacterial flagellin), and increased levels of cytokines have been detected systemically in the peripheral blood advocating the existence of abnormal host-microbial interactions and systemic immune responses. Nonetheless, there is wide overlap of data obtained in healthy controls; in addition, the subsets of patients showing immune activation have yet to be clearly identified. Gender, age, geographic differences, genetic predisposition, diet and differences in the intestinal microbiota likely play a role and further research has to be done to clarify their relevance as potential mechanisms in the described immune system dysregulation. Immune activation has stimulated interest for the potential identification of biomarkers useful for clinical and research purposes and the development of novel therapeutic approaches. PMID:22148103

  8. Registry Assessment of Peripheral Interventional Devices (RAPID): Registry assessment of peripheral interventional devices core data elements.

    Science.gov (United States)

    Jones, W Schuyler; Krucoff, Mitchell W; Morales, Pablo; Wilgus, Rebecca W; Heath, Anne H; Williams, Mary F; Tcheng, James E; Marinac-Dabic, J Danica; Malone, Misti L; Reed, Terrie L; Fukaya, Rie; Lookstein, Robert A; Handa, Nobuhiro; Aronow, Herbert D; Bertges, Daniel J; Jaff, Michael R; Tsai, Thomas T; Smale, Joshua A; Zaugg, Margo J; Thatcher, Robert J; Cronenwett, Jack L

    2018-02-01

    The current state of evaluating patients with peripheral artery disease and more specifically of evaluating medical devices used for peripheral vascular intervention (PVI) remains challenging because of the heterogeneity of the disease process, the multiple physician specialties that perform PVI, the multitude of devices available to treat peripheral artery disease, and the lack of consensus about the best treatment approaches. Because PVI core data elements are not standardized across clinical care, clinical trials, and registries, aggregation of data across different data sources and physician specialties is currently not feasible. Under the auspices of the U.S. Food and Drug Administration's Medical Device Epidemiology Network initiative-and its PASSION (Predictable and Sustainable Implementation of the National Registries) program, in conjunction with other efforts to align clinical data standards-the Registry Assessment of Peripheral Interventional Devices (RAPID) workgroup was convened. RAPID is a collaborative, multidisciplinary effort to develop a consensus lexicon and to promote interoperability across clinical care, clinical trials, and national and international registries of PVI. The current manuscript presents the initial work from RAPID to standardize clinical data elements and definitions, to establish a framework within electronic health records and health information technology procedural reporting systems, and to implement an informatics-based approach to promote the conduct of pragmatic clinical trials and registry efforts in PVI. Ultimately, we hope this work will facilitate and improve device evaluation and surveillance for patients, clinicians, health outcomes researchers, industry, policymakers, and regulators. Copyright © 2017 Society for Vascular Surgery. All rights reserved.

  9. Sex-specific consequences of an induced immune response on reproduction in a moth.

    Science.gov (United States)

    Barthel, Andrea; Staudacher, Heike; Schmaltz, Antje; Heckel, David G; Groot, Astrid T

    2015-12-16

    Immune response induction benefits insects in combatting infection by pathogens. However, organisms have a limited amount of resources available and face the dilemma of partitioning resources between immunity and other life-history traits. Since males and females differ in their life histories, sex-specific resource investment strategies to achieve an optimal immune response following an infection can be expected. We investigated immune response induction of females and males of Heliothis virescens in response to the entomopathogenic bacterium Serratia entomophila, and its effects on mating success and the female sexual signal. We found that females had higher expression levels of immune-related genes after bacterial challenge than males. However, males maintained a higher baseline expression of immune-related genes than females. The increased investment in immunity of female moths was negatively correlated with mating success and the female sexual signal. Male mating success was unaffected by bacterial challenge. Our results show that the sexes differed in their investment strategies: females invested in immune defense after a bacterial challenge, indicating facultative immune deployment, whereas males had higher baseline immunity than females, indicating immune maintenance. Interestingly, these differences in investment were reflected in the mate choice assays. As female moths are the sexual signallers, females need to invest resources in their attractiveness. However, female moths appeared to invest in immunity at the cost of reproductive effort.

  10. Country Immunization Information System Assessments - Kenya, 2015 and Ghana, 2016.

    Science.gov (United States)

    Scott, Colleen; Clarke, Kristie E N; Grevendonk, Jan; Dolan, Samantha B; Ahmed, Hussein Osman; Kamau, Peter; Ademba, Peter Aswani; Osadebe, Lynda; Bonsu, George; Opare, Joseph; Diamenu, Stanley; Amenuvegbe, Gregory; Quaye, Pamela; Osei-Sarpong, Fred; Abotsi, Francis; Ankrah, Joseph Dwomor; MacNeil, Adam

    2017-11-10

    The collection, analysis, and use of data to measure and improve immunization program performance are priorities for the World Health Organization (WHO), global partners, and national immunization programs (NIPs). High quality data are essential for evidence-based decision-making to support successful NIPs. Consistent recording and reporting practices, optimal access to and use of health information systems, and rigorous interpretation and use of data for decision-making are characteristics of high-quality immunization information systems. In 2015 and 2016, immunization information system assessments (IISAs) were conducted in Kenya and Ghana using a new WHO and CDC assessment methodology designed to identify root causes of immunization data quality problems and facilitate development of plans for improvement. Data quality challenges common to both countries included low confidence in facility-level target population data (Kenya = 50%, Ghana = 53%) and poor data concordance between child registers and facility tally sheets (Kenya = 0%, Ghana = 3%). In Kenya, systemic challenges included limited supportive supervision and lack of resources to access electronic reporting systems; in Ghana, challenges included a poorly defined subdistrict administrative level. Data quality improvement plans (DQIPs) based on assessment findings are being implemented in both countries. IISAs can help countries identify and address root causes of poor immunization data to provide a stronger evidence base for future investments in immunization programs.

  11. Comparison of the Functional microRNA Expression in Immune Cell Subsets of Neonates and Adults

    Science.gov (United States)

    Yu, Hong-Ren; Hsu, Te-Yao; Huang, Hsin-Chun; Kuo, Ho-Chang; Li, Sung-Chou; Yang, Kuender D.; Hsieh, Kai-Sheng

    2016-01-01

    Diversity of biological molecules in newborn and adult immune cells contributes to differences in cell function and atopic properties. Micro RNAs (miRNAs) are reported to involve in the regulation of immune system. Therefore, determining the miRNA expression profile of leukocyte subpopulations is important for understanding immune system regulation. In order to explore the unique miRNA profiling that contribute to altered immune in neonates, we comprehensively analyzed the functional miRNA signatures of eight leukocyte subsets (polymorphonuclear cells, monocytes, CD4+ T cells, CD8+ T cells, natural killer cells, B cells, plasmacytoid dendritic cells, and myeloid dendritic cells) from both neonatal and adult umbilical cord and peripheral blood samples, respectively. We observed distinct miRNA profiles between adult and neonatal blood leukocyte subsets, including unique miRNA signatures for each cell lineage. Leukocyte miRNA signatures were altered after stimulation. Adult peripheral leukocytes had higher let-7b-5p expression levels compared to neonatal cord leukocytes across multiple subsets, irrespective of stimulation. Transfecting neonatal monocytes with a let-7b-5p mimic resulted in a reduction of LPS-induced interleukin (IL)-6 and TNF-α production, while transfection of a let-7b-5p inhibitor into adult monocytes enhanced IL-6 and TNF-α production. With this functional approach, we provide intact differential miRNA expression profiling of specific immune cell subsets between neonates and adults. These studies serve as a basis to further understand the altered immune response observed in neonates and advance the development of therapeutic strategies. PMID:28066425

  12. Comparison of the functional microRNA expression in immune cell subsets of neonates and adults

    Directory of Open Access Journals (Sweden)

    Hong-Ren Yu

    2016-12-01

    Full Text Available Diversity of biological molecules in newborn and adult immune cells contributes to differences in cell function and atopic properties. Micro RNAs (miRNAs are reported involve in the regulation of immune system. Therefore, determining the miRNA expression profile of leukocyte sub-populations is important for understanding immune system regulation. In order to explore the unique microRNA profiling that contribute to altered immune in neonates, we comprehensively analyzed the functional miRNA signatures of eight leukocyte subsets (polymorphonuclear cells, monocytes, CD4+ T cells, CD8+ T cells, natural killer cells, B cells, plasmacytoid dendritic cells (pDCs, and myeloid dendritic cells (mDCs from both neonatal and adult umbilical cord and peripheral blood samples, respectively. We observed distinct miRNA profiles between adult and neonatal blood leukocyte subsets, including unique miRNA signatures for each cell lineage. Leukocyte miRNA signatures were altered after stimulation. Adult peripheral leukocytes had higher let-7b-5p expression levels compared to neonatal cord leukocytes across multiple subsets, irrespective of stimulation. Transfecting neonatal monocytes with a let-7b-5p mimic resulted in a reduction of LPS-induced IL-6 and TNF-alpha production, while transfection of a let-7b-5p inhibitor into adult monocytes enhanced IL-6 and TNF-alpha production. With this functional approach, we provide intact differential microRNA expression profiling of specific immune cell subsets between neonates and adults. These studies serve as a basis to further understand the altered immune response observed in neonates and advance the development of therapeutic strategies.

  13. [Oral diseases in auto-immune polyendocrine syndrome type 1].

    Science.gov (United States)

    Proust-Lemoine, Emmanuelle; Guyot, Sylvie

    2017-09-01

    Auto-immune polyendocrine syndrome type 1 (APS1) also called Auto-immune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED) is a rare monogenic childhood-onset auto-immune disease. This autosomal recessive disorder is caused by mutations in the auto-immune regulator (AIRE) gene, and leads to autoimmunity targeting peripheral tissues. There is a wide variability in clinical phenotypes in patients with APSI, with auto-immune endocrine and non-endocrine disorders, and chronic mucocutaneous candidiasis. These patients suffer from oral diseases such as dental enamel hypoplasia and candidiasis. Both are frequently described, and in recent series, enamel hypoplasia and candidiasis are even the most frequent components of APS1 together with hypoparathyroidism. Both often occur during childhood (before 5 years old for canrdidiasis, and before 15 years old for enamel hypoplasia). Oral candidiasis is recurrent all life long, could become resistant to azole antifungal after years of treatment, and be carcinogenic, leading to severe oral squamous cell carcinoma. Oral components of APS1 should be diagnosed and rigorously treated. Dental enamel hypoplasia and/or recurrent oral candidiasis in association with auto-immune diseases in a young child should prompt APS1 diagnosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  14. Arginine and vitamin E improve the immune response after a Salmonella challenge in broiler chicks.

    Science.gov (United States)

    Liu, X; Byrd, J A; Farnell, M; Ruiz-Feria, C A

    2014-04-01

    Two experiments were conducted to evaluate the effects of Arg, vitamin E (VE), and mannanoligosaccharide (MOS) on the immune response and clearance of Salmonella in broiler chickens. In each experiment, 1-d-old chicks (n = 160) were randomly distributed into 4 groups: antibiotic-free diet (negative control, CTL-), antibiotic-supplemented diet (positive control, CTL+), antibiotic free-diet plus Arg and VE (AVE), or antibiotic-free diet plus Arg, VE, and MOS (AVM). Birds were orally challenged with 10(6) cfu of a novobiocyn and nalidixic acid-resistant Salmonella enterica serovar Typhimurium strain at d 7 (experiment 1) or at d 3 (experiment 2). Heterophil- (HOB) and monocyte- (MOB) oxidative burst and lymphocyte proliferation (LPR), antibody titers, and Salmonella content in the ceca were measured at several intervals postinfection (PI). In experiment 1, both AVM and AVE decreased HOB compared with the controls 5 and 9 d PI, but increased LPR 9 d PI. In the same experiment, birds fed the AVE diet had higher MOB than birds fed CTL+ or the AVM diet at 7 d PI, whereas 9 d PI birds fed the AVM diet had the highest MOB. In experiment 2, birds fed the AVE diet had higher MOB, HOB, and LPR than birds in the other treatments 7 and 14 d PI, except at 7 d PI, when MOB was not different among treatments. Birds fed the AVM diet had the highest IgA antibody titer, and a higher IgM antibody titer than the CTL+ birds. In experiment 1, Salmonella Typhimurium content in the ceca was lower in birds fed the AVM diet compared with birds fed the CTL- diet 3 d PI, but later on (10 and 17 d PI), and in experiment 2 (7, 14, and 21 d PI), Salmonella Typhimurium concentrations were not different among treatments. Thus, Arg and VE improved immune response after a Salmonella Typhimurium challenge in young chicks, and although they did not reduce Salmonella Typhimurium concentrations in the ceca, they may improve bacterial resistance against other pathogens in commercial growing conditions.

  15. Peripheral and central immune cell reservoirs in tissues from asymptomatic cats chronically infected with feline immunodeficiency virus

    Science.gov (United States)

    Sparger, E. E.; Pitt, K. A.

    2017-01-01

    Feline immunodeficiency virus (FIV) infection in cats results in life-long viral persistence and progressive immunopathology. We have previously described a cohort of experimentally infected cats demonstrating a progressive decline of peripheral blood CD4+ T-cell over six years in the face of apparent peripheral viral latency. More recently we reported findings from this same cohort that revealed popliteal lymph node tissue as sites for ongoing viral replication suggesting that tissue reservoirs are important in FIV immunopathogenesis during the late asymptomatic phase of infection. Results reported herein characterize important tissue reservoirs of active viral replication during the late asymptomatic phase by examining biopsied specimens of spleen, mesenteric lymph node (MLN), and intestine from FIV-infected and uninfected control cats. Peripheral blood collected coincident with harvest of tissues demonstrated severe CD4+ T-cell depletion, undetectable plasma viral gag RNA and rarely detectable peripheral blood mononuclear cell (PBMC)-associated viral RNA (vRNA) by real-time PCR. However, vRNA was detectable in all three tissue sites from three of four FIV-infected cats despite the absence of detectable vRNA in plasma. A novel in situ hybridization assay identified B cell lymphoid follicular domains as microanatomical foci of ongoing FIV replication. Additionally, we demonstrated that CD4+ leukocyte depletion in tissues, and CD4+ and CD21+ leukocytes as important cellular reservoirs of ongoing replication. These findings revealed that tissue reservoirs support foci of ongoing viral replication, in spite of highly restricted viral replication in blood. Lentiviral eradication strategies will need address tissue viral reservoirs. PMID:28384338

  16. Peripheral and central immune cell reservoirs in tissues from asymptomatic cats chronically infected with feline immunodeficiency virus.

    Directory of Open Access Journals (Sweden)

    C D Eckstrand

    Full Text Available Feline immunodeficiency virus (FIV infection in cats results in life-long viral persistence and progressive immunopathology. We have previously described a cohort of experimentally infected cats demonstrating a progressive decline of peripheral blood CD4+ T-cell over six years in the face of apparent peripheral viral latency. More recently we reported findings from this same cohort that revealed popliteal lymph node tissue as sites for ongoing viral replication suggesting that tissue reservoirs are important in FIV immunopathogenesis during the late asymptomatic phase of infection. Results reported herein characterize important tissue reservoirs of active viral replication during the late asymptomatic phase by examining biopsied specimens of spleen, mesenteric lymph node (MLN, and intestine from FIV-infected and uninfected control cats. Peripheral blood collected coincident with harvest of tissues demonstrated severe CD4+ T-cell depletion, undetectable plasma viral gag RNA and rarely detectable peripheral blood mononuclear cell (PBMC-associated viral RNA (vRNA by real-time PCR. However, vRNA was detectable in all three tissue sites from three of four FIV-infected cats despite the absence of detectable vRNA in plasma. A novel in situ hybridization assay identified B cell lymphoid follicular domains as microanatomical foci of ongoing FIV replication. Additionally, we demonstrated that CD4+ leukocyte depletion in tissues, and CD4+ and CD21+ leukocytes as important cellular reservoirs of ongoing replication. These findings revealed that tissue reservoirs support foci of ongoing viral replication, in spite of highly restricted viral replication in blood. Lentiviral eradication strategies will need address tissue viral reservoirs.

  17. Peripheral and central immune cell reservoirs in tissues from asymptomatic cats chronically infected with feline immunodeficiency virus.

    Science.gov (United States)

    Eckstrand, C D; Sparger, E E; Pitt, K A; Murphy, B G

    2017-01-01

    Feline immunodeficiency virus (FIV) infection in cats results in life-long viral persistence and progressive immunopathology. We have previously described a cohort of experimentally infected cats demonstrating a progressive decline of peripheral blood CD4+ T-cell over six years in the face of apparent peripheral viral latency. More recently we reported findings from this same cohort that revealed popliteal lymph node tissue as sites for ongoing viral replication suggesting that tissue reservoirs are important in FIV immunopathogenesis during the late asymptomatic phase of infection. Results reported herein characterize important tissue reservoirs of active viral replication during the late asymptomatic phase by examining biopsied specimens of spleen, mesenteric lymph node (MLN), and intestine from FIV-infected and uninfected control cats. Peripheral blood collected coincident with harvest of tissues demonstrated severe CD4+ T-cell depletion, undetectable plasma viral gag RNA and rarely detectable peripheral blood mononuclear cell (PBMC)-associated viral RNA (vRNA) by real-time PCR. However, vRNA was detectable in all three tissue sites from three of four FIV-infected cats despite the absence of detectable vRNA in plasma. A novel in situ hybridization assay identified B cell lymphoid follicular domains as microanatomical foci of ongoing FIV replication. Additionally, we demonstrated that CD4+ leukocyte depletion in tissues, and CD4+ and CD21+ leukocytes as important cellular reservoirs of ongoing replication. These findings revealed that tissue reservoirs support foci of ongoing viral replication, in spite of highly restricted viral replication in blood. Lentiviral eradication strategies will need address tissue viral reservoirs.

  18. Omega 3 (peripheral type benzodiazepine binding) site distribution in the rat immune system: an autoradiographic study with the photoaffinity ligand [3H]PK 14105

    International Nuclear Information System (INIS)

    Benavides, J.; Dubois, A.; Dennis, T.; Hamel, E.; Scatton, B.

    1989-01-01

    The anatomical distribution of omega 3 (peripheral type benzodiazepine binding) sites in the immune system organs of the rat has been studied autoradiographically at both macroscopic and microscopic levels of resolution using either reversible or irreversible (UV irradiation) labeling with [ 3 H]PK 14105. In thymus sections, [ 3 H]PK 14105 labeled with high affinity (Kd, derived from saturation experiments = 10.8 nM) a single population of sites which possessed the pharmacological characteristics of omega 3 sites. In the thymus gland, higher omega 3 site densities were detected in the cortex than in the medulla; in these subregions, silver grains were associated to small (10-18 microns diameter) cells. In the spleen, omega 3 sites were more abundant in the white than in the red pulp. In the white pulp, silver grains were denser in the marginal zone than in the vicinity of the central artery and labeling was, as in the thymus, associated to small cytoplasm-poor cells. In the red pulp, omega 3 site associated silver grains were observed mainly in the Bilroth cords. In the lymph nodes, the medullary region showed a higher labeling than the surrounding follicles and paracortex. A significant accumulation of silver grains was observed in the lymph node medullary cords. In the intestine, Peyer patches were particularly enriched in omega 3 sites (especially in the periphery of the follicles). The distribution of omega 3 sites in the immune system organs suggests a preferential labeling of cells of T and monocytic lineages. This is consistent with the proposed immunoregulatory properties of some omega 3 site ligands

  19. Primary pulmonary immunity to a soluble antigen in the dog

    International Nuclear Information System (INIS)

    Weissman, D.N.; Bice, D.E.; Muggenburg, B.A.; Schuyler, M.R.

    1988-01-01

    In order to study primary lung immunity to soluble antigen, Beagle dogs underwent trans-bronchoscopic instillation of 10 mg keyhole limpet hemocyanin (KLH) into the right cardiac lobe and saline into the left cardiac lobe. Over the next 3 wk, specific immune responses were monitored in blood and bronchoalveolar lavage (BAL) fluids obtained from immunized and control lung lobes. Primary lung immunization of dogs with KLH resulted in easily measurable specific IgG, IgM, and IgA responses in blood and bronchoalveolar lavage fluids. Important class differences were noted to exist for these responses. Levels of specific IgG and IgA in BAL remained elevated at 21 days after immunization, while BAL-specific IgM levels fell to control values by 12 days after immunization. In unimmunized lung lobes, specific antibody levels in BAL and production of specific antibody by bronchoalveolar lavage cells was far greater for IgG than for IgM or IgA. Finally, despite easily detectable specific IgA in serum and BAL fluid, production of specific IgA by peripheral blood mononuclear cells or bronchoalveolar lavage cells after primary lung immunization with KLH could not be demonstrated, suggesting that specific IgA was produced by a compartment of cells poorly sampled in blood and BAL. (author)

  20. Primary pulmonary immunity to a soluble antigen in the dog

    Energy Technology Data Exchange (ETDEWEB)

    Weissman, D N; Bice, D E; Muggenburg, B A; Schuyler, M R

    1988-12-01

    In order to study primary lung immunity to soluble antigen, Beagle dogs underwent trans-bronchoscopic instillation of 10 mg keyhole limpet hemocyanin (KLH) into the right cardiac lobe and saline into the left cardiac lobe. Over the next 3 wk, specific immune responses were monitored in blood and bronchoalveolar lavage (BAL) fluids obtained from immunized and control lung lobes. Primary lung immunization of dogs with KLH resulted in easily measurable specific IgG, IgM, and IgA responses in blood and bronchoalveolar lavage fluids. Important class differences were noted to exist for these responses. Levels of specific IgG and IgA in BAL remained elevated at 21 days after immunization, while BAL-specific IgM levels fell to control values by 12 days after immunization. In unimmunized lung lobes, specific antibody levels in BAL and production of specific antibody by bronchoalveolar lavage cells was far greater for IgG than for IgM or IgA. Finally, despite easily detectable specific IgA in serum and BAL fluid, production of specific IgA by peripheral blood mononuclear cells or bronchoalveolar lavage cells after primary lung immunization with KLH could not be demonstrated, suggesting that specific IgA was produced by a compartment of cells poorly sampled in blood and BAL. (author)

  1. Peripheral blood monocyte subsets predict antiviral response in chronic hepatitis C.

    Science.gov (United States)

    Rodríguez-Muñoz, Y; Martín-Vílchez, S; López-Rodríguez, R; Hernández-Bartolomé, A; Trapero-Marugán, M; Borque, M J; Moreno-Otero, R; Sanz-Cameno, P

    2011-10-01

    Hepatitis C virus infection evolves into chronic progressive liver disease in a significant percentage of patients. Monocytes constitute a diverse group of myeloid cells that mediate innate and adaptive immune response. In addition to proinflammatory CD16+ monocytes, a Tie-2+ subgroup - Tie-2 expressing monocytes (TEMs) - that has robust proangiogenic potential has been recently defined. To study the heterogeneity of peripheral blood monocytes in chronic hepatitis C (CHC) patients and to examine their proposed pathophysiological roles on disease progression and response to antiviral therapy. We studied CD16+ and Tie-2+ peripheral monocyte subpopulations in 21 healthy subjects and 39 CHC patients in various stages of disease and responses to antiviral treatment using flow cytometry. Expression profiles of proangiogenic and tissue remodelling factors in monocyte supernatants were measured using ELISA and protein arrays. Intrahepatic expression of CD14, CD31 and Tie-2 was analysed using immunofluorescence. Increases of certain peripheral monocyte subsets were observed in the blood of CHC patients, wherein those cells with proinflammatory (CD16+) or proangiogenic (TEMs) potential expanded (P TEMs were significantly increased in nonresponders, particularly those with lower CD16 expression. In addition, many angiogenic factors were differentially expressed by peripheral monocytes from control or CHC patients, such as angiopoietin-1 and angiogenin (P TEMs were distinguished within portal infiltrates of CHC patients. These findings suggest for the first time the relevance of peripheral monocytes phenotypes for the achievement of response to treatment. Hence, the study of monocyte subset regulation might effect improved CHC prognoses and adjuvant therapies. © 2011 Blackwell Publishing Ltd.

  2. Natural immunity factors in Polish mixed breed rabbits.

    Science.gov (United States)

    Tokarz-Deptuła, B; Niedźwiedzka-Rystwej, P; Adamiak, M; Hukowska-Szematowicz, B; Trzeciak-Ryczek, A; Deptuła, W

    2015-01-01

    Mixed-breed rabbits in Poland are widely used for diagnostic and scientific research and as utility animals, therefore there is a need to know their immunological status, as well as their haematological status. In this study natural immunity factors were analyzed in Polish mixed-breed rabbits and Polish mixed-breed rabbits with addition of blood of meet-breed, considering the impact of sex and season of the year (spring, summer, autumn, winter) using measurement of non-specific cellular and humoral immunity parameters in peripheral blood. The study has revealed that there is a variety between the two commonly used mixed-breed types of rabbits, especially when sex and season is concerned, which is crucial for using these animals in experiments.

  3. Gamma-irradiated scrub typhus immunogens: development of cell-mediated immunity after vaccination of inbred mice

    International Nuclear Information System (INIS)

    Jerrells, T.R.; Palmer, B.A.; Osterman, J.V.

    1983-01-01

    Mice immunized with three injections of gamma-irradiated Karp strain of Rickettsia tsutsugamushi were evaluated for the presence of cell-mediated immunity by using delayed-type hypersensitivity, antigen-induced lymphocyte proliferation, and antigen-induced lymphokine production. These animals also were evaluated for levels of circulating antibody after immunization as well as for the presence of rickettsemia after intraperitoneal challenge with viable Karp rickettsiae. After immunization with irradiated Karp rickettsiae, a demonstrable cell-mediated immunity was present as evidenced by delayed-type hypersensitivity responsiveness, lymphocyte proliferation, and production of migration inhibition factor and interferon by immune spleen lymphocytes. Also, a reduction in circulating rickettsiae was seen in mice immunized with irradiated rickettsiae after challenge with 1,000 50% mouse lethal doses of viable, homologous rickettsiae. All responses except antibody titer and reduction of rickettsemia were similar to the responses noted in mice immunized with viable organisms. Antibody levels were lower in mice immunized with irradiated rickettsiae than in mice immunized with viable rickettsiae. Furthermore, mice that were immunized with viable rickettsiae demonstrated markedly lower levels of rickettsemia after intraperitoneal challenge compared with either mice immunized with irradiated rickettsiae or nonimmunized mice

  4. Heat shock protein 10 (Hsp10) in immune-related diseases: one coin, two sides

    Science.gov (United States)

    Jia, Haibo; Halilou, Amadou I.; Hu, Liang; Cai, Wenqian; Liu, Jing; Huang, Bo

    2011-01-01

    Heat shock protein 10 (Hsp10) in eukaryotes, originally identified as a mitochondrial chaperone, now is also known to be present in cytosol, cell surface, extracellular space and peripheral blood. Functionally besides participating in mitochondrial protein folding in association with Hsp60, Hsp10 appears to be related to pregnancy, cancer and autoimmune inhibition. Hsp10 can be released to peripheral blood at very early time point of pregnancy and given another name called early pregnancy factor (EPF), which seems to play a critical role in developing a pregnant niche. In malignant disorders, Hsp10 is usually abnormally expressed in the cytosol of malignant cells and further released to extracellular space, resulting in tumor-promoting effect from various aspects. Furthermore, distinct from other heat shock protein members, whose soluble form is recognized as danger signal by immune cells and triggers immune responses, Hsp10 after release, however, is designed to be an inhibitory signal by limiting immune response. This review discusses how Hsp10 participates in various physiological and pathological processes from basic protein molecule folding to pregnancy, cancer and autoimmune diseases, and emphasizes how important the location is for the function exertion of a molecule. PMID:21969171

  5. Systematic review of mucosal immunity induced by oral and inactivated poliovirus vaccines against virus shedding following oral poliovirus challenge.

    Directory of Open Access Journals (Sweden)

    Thomas R Hird

    Full Text Available Inactivated poliovirus vaccine (IPV may be used in mass vaccination campaigns during the final stages of polio eradication. It is also likely to be adopted by many countries following the coordinated global cessation of vaccination with oral poliovirus vaccine (OPV after eradication. The success of IPV in the control of poliomyelitis outbreaks will depend on the degree of nasopharyngeal and intestinal mucosal immunity induced against poliovirus infection. We performed a systematic review of studies published through May 2011 that recorded the prevalence of poliovirus shedding in stool samples or nasopharyngeal secretions collected 5-30 days after a "challenge" dose of OPV. Studies were combined in a meta-analysis of the odds of shedding among children vaccinated according to IPV, OPV, and combination schedules. We identified 31 studies of shedding in stool and four in nasopharyngeal samples that met the inclusion criteria. Individuals vaccinated with OPV were protected against infection and shedding of poliovirus in stool samples collected after challenge compared with unvaccinated individuals (summary odds ratio [OR] for shedding 0.13 (95% confidence interval [CI] 0.08-0.24. In contrast, IPV provided no protection against shedding compared with unvaccinated individuals (summary OR 0.81 [95% CI 0.59-1.11] or when given in addition to OPV, compared with individuals given OPV alone (summary OR 1.14 [95% CI 0.82-1.58]. There were insufficient studies of nasopharyngeal shedding to draw a conclusion. IPV does not induce sufficient intestinal mucosal immunity to reduce the prevalence of fecal poliovirus shedding after challenge, although there was some evidence that it can reduce the quantity of virus shed. The impact of IPV on poliovirus transmission in countries where fecal-oral spread is common is unknown but is likely to be limited compared with OPV.

  6. Protection of Broiler Chicks Housed with Immunized Cohorts Against Infection with Eimeria maxima and E. acervulina.

    Science.gov (United States)

    Fetterer, Raymond H; Barfield, Ruth C; Jenkins, Mark C

    2015-03-01

    The use of live oocyst vaccines is becoming increasingly important in the control of avian coccidiosis in broilers. Knowledge of the mechanisms employed when chicks uptake oocysts and become immune is important for optimizing delivery of live vaccines. The current study tests the hypothesis that chicks not initially immunized may ingest oocysts by contact with litter containing oocysts shed by immunized cohorts. In Experiment 1, day-old broiler chicks were housed in pens containing clean litter. In Trial 1, 100% of chicks in some pens were immunized with 2.5 X 10(3) Eimeria acervulina oocysts while in other pens only 75% of chicks were immunized and remaining cohorts within the pens were not immunized. Other pens contained chicks that served as nonimmunized nonchallenged controls or nonimmunized challenged controls (NIC). On day 21, birds were given a homologous challenge of 6 X 10(5) oocysts. A second identical trial was conducted, except birds were immunized with 500 Eimeria maxima oocysts and were challenged with 3 X 10(3) E. maxima oocysts. In Experiment 2, 100% of chicks in some pens were immunized with 500 E. acervulina oocysts while in other pens either 75% or 50% of the birds were immunized. On day 14, birds were challenged with 1 X 10(6) oocysts. Trial 2 was identical to Trial 1 except that birds were immunized with 100 E. maxima oocysts and challenged with 1 X 10(6) oocysts. For all experiments weight gain, feed conversion ratio (FCR), plasma carotenoids, and litter oocyst counts were measured. In Experiment 1, the level of protection in groups containing 25% nonimmunized cohorts, as measured by weight gain, carotenoid level, FCR, and oocyst litter counts, was identical to groups containing 100% immunized chicks. In Experiment 2, pens where 50% or 75% of birds were immunized with either E. maxima or E. acervulina were not well protected from decreases in weight gain and plasma carotenoids nor from increases in litter oocyst counts following a challenge

  7. Porcine endogenous retroviral nucleic acid in peripheral tissues is associated with migration of porcine cells post islet transplant.

    Science.gov (United States)

    Binette, Tanya M; Seeberger, Karen L; Lyon, James G; Rajotte, Ray V; Korbutt, Gregory S

    2004-07-01

    Porcine islets represent an alternative source of insulin-producing tissue, however, porcine endogenous retrovirus (PERV) remains a concern. In this study, SCID mice were transplanted with nonencapsulated (non-EC), microencapsulated (EC) or macroencapsulated (in a TheraCyte trade mark device) neonatal porcine islets (NPIs), and peripheral tissues were screened for presence of viral DNA and mRNA. To understand the role of an intact immune system in PERV incidence, mice with established NPI grafts were reconstituted with splenocytes. Peripheral tissues were screened for PERV and porcine DNA using PCR. Tissues with positive DNA were analyzed for PERV mRNA using RT-PCR. No significant difference was observed between non-EC and EC transplants regarding presence of PERV or porcine-specific DNA or mRNA. In reconstituted animals, little PERV or porcine DNA, and no PERV mRNA was detected. No PERV or porcine-specific DNA was observed in animals implanted with a TheraCyte trade mark device. In conclusion, an intact immune system significantly lowered the presence of PERV. Microencapsulation of islets did not alter PERV presence, however, macroencapsulation in the TheraCyte device did. Lower PERV incidence coincided with lower porcine DNA in peripheral tissues, linking the presence of PERV to migration of porcine cells.

  8. RESTOP: Retaining External Peripheral State in Intermittently-Powered Sensor Systems.

    Science.gov (United States)

    Rodriguez Arreola, Alberto; Balsamo, Domenico; Merrett, Geoff V; Weddell, Alex S

    2018-01-10

    Energy harvesting sensor systems typically incorporate energy buffers (e.g., rechargeable batteries and supercapacitors) to accommodate fluctuations in supply. However, the presence of these elements limits the miniaturization of devices. In recent years, researchers have proposed a new paradigm, transient computing, where systems operate directly from the energy harvesting source and allow computation to span across power cycles, without adding energy buffers. Various transient computing approaches have addressed the challenge of power intermittency by retaining the processor's state using non-volatile memory. However, no generic approach has yet been proposed to retain the state of peripherals external to the processing element. This paper proposes RESTOP, flexible middleware which retains the state of multiple external peripherals that are connected to a computing element (i.e., a microcontroller) through protocols such as SPI or I 2 C. RESTOP acts as an interface between the main application and the peripheral, which keeps a record, at run-time, of the transmitted data in order to restore peripheral configuration after a power interruption. RESTOP is practically implemented and validated using three digitally interfaced peripherals, successfully restoring their configuration after power interruptions, imposing a maximum time overhead of 15% when configuring a peripheral. However, this represents an overhead of only 0.82% during complete execution of our typical sensing application, which is substantially lower than existing approaches.

  9. Oral immunization of mice with gamma-irradiated Brucella neotomae induces protection against intraperitoneal and intranasal challenge with virulent B. abortus 2308.

    Science.gov (United States)

    Dabral, Neha; Martha-Moreno-Lafont; Sriranganathan, Nammalwar; Vemulapalli, Ramesh

    2014-01-01

    Brucella spp. are Gram-negative, facultative intracellular coccobacilli that cause one of the most frequently encountered zoonosis worldwide. Humans naturally acquire infection through consumption of contaminated dairy and meat products and through direct exposure to aborted animal tissues and fluids. No vaccine against brucellosis is available for use in humans. In this study, we tested the ability of orally inoculated gamma-irradiated B. neotomae and B. abortus RB51 in a prime-boost immunization approach to induce antigen-specific humoral and cell mediated immunity and protection against challenge with virulent B. abortus 2308. Heterologous prime-boost vaccination with B. abortus RB51 and B. neotomae and homologous prime-boost vaccination of mice with B. neotomae led to the production of serum and mucosal antibodies specific to the smooth LPS. The elicited serum antibodies included the isotypes of IgM, IgG1, IgG2a, IgG2b and IgG3. All oral vaccination regimens induced antigen-specific CD4(+) and CD8(+) T cells capable of secreting IFN-γ and TNF-α. Upon intra-peritoneal challenge, mice vaccinated with B. neotomae showed the highest level of resistance against virulent B. abortus 2308 colonization in spleen and liver. Experiments with different doses of B. neotomae showed that all tested doses of 10(9), 10(10) and 10(11) CFU-equivalent conferred significant protection against the intra-peritoneal challenge. However, a dose of 10(11) CFU-equivalent of B. neotomae was required for affording protection against intranasal challenge as shown by the reduced bacterial colonization in spleens and lungs. Taken together, these results demonstrate the feasibility of using gamma-irradiated B. neotomae as an effective and safe oral vaccine to induce protection against respiratory and systemic infections with virulent Brucella.

  10. Immunization of Mastomys coucha with Brugia malayi recombinant trehalose-6-phosphate phosphatase results in significant protection against homologous challenge infection.

    Directory of Open Access Journals (Sweden)

    Susheela Kushwaha

    Full Text Available Development of a vaccine to prevent or reduce parasite development in lymphatic filariasis would be a complementary approach to existing chemotherapeutic tools. Trehalose-6-phosphate phosphatase of Brugia malayi (Bm-TPP represents an attractive vaccine target due to its absence in mammals, prevalence in the major life stages of the parasite and immunoreactivity with human bancroftian antibodies, especially from endemic normal subjects. We have recently reported on the cloning, expression, purification and biochemical characterization of this vital enzyme of B. malayi. In the present study, immunoprophylactic evaluation of Bm-TPP was carried out against B. malayi larval challenge in a susceptible host Mastomys coucha and the protective ability of the recombinant protein was evaluated by observing the adverse effects on microfilarial density and adult worm establishment. Immunization caused 78.4% decrease in microfilaremia and 71.04% reduction in the adult worm establishment along with sterilization of 70.06% of the recovered live females. The recombinant protein elicited a mixed Th1/Th2 type of protective immune response as evidenced by the generation of both pro- and anti-inflammatory cytokines IL-2, IFN-γ, TNF-α, IL-4 and an increased production of antibody isotypes IgG1, IgG2a, IgG2b and IgA. Thus immunization with Bm-TPP conferred considerable protection against B. malayi establishment by engendering a long-lasting effective immune response and therefore emerges as a potential vaccine candidate against lymphatic filariasis (LF.

  11. Difference in effect of single immunosuppressive agents (cyclophosphamide, CCNU, 5-FU) on peripheral blood immune cell parameters and central nervous system immunoglobulin synthesis rate in patients with multiple sclerosis.

    Science.gov (United States)

    Shih, W W; Baumhefner, R W; Tourtellotte, W W; Haskell, C M; Korn, E L; Fahey, J L

    1983-01-01

    Cyclophosphamide (CY), 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) and 5-fluorouracil (5-FU) were given in single course schedules to chronic progressive multiple sclerosis (MS) patients clinically stable for 6 months. The following peripheral immune cellular parameters were measured before, during and after each drug administration: white blood count (WBC), polymorphonuclear count (PMN), lymphocyte count, percentage of T cells, T cell response to phytohaemagglutinin (PHA), percentage of B cells, percentage of cells bearing receptors for the Fc portion of immunoglobulin (% FcR cells), killer (K) cell activity defined by antibody-dependent cellular cytotoxicity (ADCC), and natural killer (NK) cell activity. Central nervous system (CNS) immunoglobulin G (IgG) synthesis was also measured. The patients were followed carefully by both quantitative and qualitative methods for any change in their neurologic condition. Selective reduction in NK activity was observed with CY and 5-FU while no significant alteration was seen in %FcR cells and K activity. CY differed from 5-FU in reducing lymphocyte count and B cell percentage while 5-FU decreased the percentage of T cells. CCNU, but not the other drugs, reduced T cell proliferative response to PHA. In addition, CCNU, which is known to penetrate well into the nervous system, caused a modest reduction in CNS IgG synthesis, while 5-FU had an uncertain effect. Clinically the patients were unchanged or continued to progress in their disability. The results suggest an independence of the CNS immune from the systemic immune system in MS in response to many immunosuppressive drugs. PMID:6603303

  12. Cooperative Effects of Corticosteroids and Catecholamines upon Immune Deviation of the Type-1/Type-2 Cytokine Balance in Favor of Type-2 Expression in Human Peripheral Blood Mononuclear Cells

    Science.gov (United States)

    Salicru, A. N.; Sams, Clarence F.; Marshall, G. D.

    2007-01-01

    A growing number of studies show strong associations between stress and altered immune function. In vivo studies of chronic and acute stress have demonstrated that cognitive stressors are strongly correlated with high levels of catecholamines (CT) and corticosteroids (CS). Although both CS and CT individually can inhibit the production of T-helper 1 (TH1, type-1 like) cytokines and simultaneously promote the production of T-helper 2 (TH2, type-2 like) cytokines in antigen-specific and mitogen stimulated human leukocyte cultures in vitro, little attention has been focused on the effects of combination CT and CS in immune responses that may be more physiologically relevant. We therefore investigated the combined effects of in vitro CT and CS upon the type-1/type-2 cytokine balance of human peripheral blood mononuclear cells (PBMC) as a model to study the immunomodulatory effects of superimposed acute and chronic stress. Results demonstrated a significant decrease in type-1 cytokine production (IFN-gamma) and a significant increase in type-2 cytokine production (IL-4, IL-10) in our CS+CT incubated cultures when compared to either CT or CS agents alone. Furthermore, variable enhancement of type-1/type-2 immune deviation occurred depending upon when the CT was added. The data suggest that CS can increase the sensitivity of PBMC to the immunomodulatory effects of CT and establishes an in vitro model to study the combined effects of in vivo type-1/type-2 cytokine alterations observed in acute and chronic stress.

  13. Immune cells in Chernobyl radiation workers exposed to low-dose irradiation

    International Nuclear Information System (INIS)

    Bazyka, D.; Chumak, A.; Byelyaeva, N.; Gulaya, N.; Margytich, V.; Thevenon, C.; Guichardant, M.; Lagarde, M.

    2002-01-01

    the aim of this work was to study immune response parameters in Chernobyl emergency and recovery operation radiation workers and nuclear industry workers exposed under professional limits. The monohydroxylated fatty acid content in peripheral blood mononuclear cell of radiation workers compared to unexposed control at the 12-th year after Chernobyl NPP accident was studied too

  14. Stronger T-Cell Alloreactivity and Diminished Suppressive Capacity of Peripheral Regulatory T Cells in Infertile Women Undergoing In Vitro Fertilization

    NARCIS (Netherlands)

    Lashley, Lisa E. E. L. O.; van der Keur, Carin; van Beelen, Els; Schaap, Rowena; van der Westerlaken, Lucette A. J.; Scherjon, Sicco A.; Claas, Frans H. J.

    ProblemIncreasing evidence suggests modulation of the maternal immune response to be essential for successful pregnancy. We studied the immunophenotypic profile and function of peripheral blood T lymphocytes in infertile women undergoing in vitro fertilization (IVF) and fertile control population.

  15. Immune memory in invertebrates.

    Science.gov (United States)

    Milutinović, Barbara; Kurtz, Joachim

    2016-08-01

    Evidence for innate immune memory (or 'priming') in invertebrates has been accumulating over the last years. We here provide an in-depth review of the current state of evidence for immune memory in invertebrates, and in particular take a phylogenetic viewpoint. Invertebrates are a very heterogeneous group of animals and accordingly, evidence for the phenomenon of immune memory as well as the hypothesized molecular underpinnings differ largely for the diverse invertebrate taxa. The majority of research currently focuses on Arthropods, while evidence from many other groups of invertebrates is fragmentary or even lacking. We here concentrate on immune memory that is induced by pathogenic challenges, but also extent our view to a non-pathogenic context, i.e. allograft rejection, which can also show forms of memory and can inform us about general principles of specific self-nonself recognition. We discuss definitions of immune memory and a number of relevant aspects such as the type of antigens used, the route of exposure, and the kinetics of reactions following priming. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Insect parents improve the anti-parasitic and anti-bacterial defence of their offspring by priming the expression of immune-relevant genes.

    Science.gov (United States)

    Trauer-Kizilelma, Ute; Hilker, Monika

    2015-09-01

    Insect parents that experienced an immune challenge are known to prepare (prime) the immune activity of their offspring for improved defence. This phenomenon has intensively been studied by analysing especially immunity-related proteins. However, it is unknown how transgenerational immune priming affects transcript levels of immune-relevant genes of the offspring upon an actual threat. Here, we investigated how an immune challenge of Manduca sexta parents affects the expression of immune-related genes in their eggs that are attacked by parasitoids. Furthermore, we addressed the question whether the transgenerational immune priming of expression of genes in the eggs is still traceable in adult offspring. Our study revealed that a parental immune challenge did not affect the expression of immune-related genes in unparasitised eggs. However, immune-related genes in parasitised eggs of immune-challenged parents were upregulated to a higher level than those in parasitised eggs of unchallenged parents. Hence, this transgenerational immune priming of the eggs was detected only "on demand", i.e. upon parasitoid attack. The priming effects were also traceable in adult female progeny of immune-challenged parents which showed higher transcript levels of several immune-related genes in their ovaries than non-primed progeny. Some of the primed genes showed enhanced expression even when the progeny was left unchallenged, whereas other genes were upregulated to a greater extent in primed female progeny than non-primed ones only when the progeny itself was immune-challenged. Thus, the detection of transgenerational immune priming strongly depends on the analysed genes and the presence or absence of an actual threat for the offspring. We suggest that M. sexta eggs laid by immune-challenged parents "afford" to upregulate the transcription of immunity-related genes only upon attack, because they have the chance to be endowed by parentally directly transferred protective proteins

  17. ROUTINE IMMUNIZATION IN INDIA: A PERSPECTIVE

    Directory of Open Access Journals (Sweden)

    G Taneja

    2013-08-01

    Full Text Available The Universal Immunization Programme is possibly the longest and one of the biggest public health intervention measures undertaken in India. To improve immunization coverage in the country various initiatives have been undertaken since the inception of the programme in 1985; key inputs being strengthening and expanding the cold chain system, establishing a network of outreach immunization sites, alternate vaccine delivery model, capacity building of health functionaries and medical officers and intensified polio control measures. Introduction of new and underutilized vaccines, drafting of the national vaccine policy, tracking of beneficiaries through the Maternal and Child Tracking system are some of the recent developments. However in spite of more than 25 years since inception the programme is still adversely impacted by challenges across key thematic areas of programme management, cold chain and vaccine management, recording and reporting and injection safety. To further strengthen and improve service delivery 2012-13 has been declared as the “Year of Intensification of Routine Immunization” with the objective of improving immunization coverage rates across poor performing districts and states so as to attain Global Immunization Vision and Strategy goals of 90% coverage at national and more than 80% coverage at district level. Key activities planned during the year include sustained advocacy at all levels, improved communication and social mobilization, robust and regular program reviews, comprehensive microplanning, strengthening cold chain and vaccine logistics system, special catch up rounds through immunization weeks, piloting the teeka express, improved surveillance systems, strengthened partnerships and operational research activities. The current review pertains to the existing scenario of Universal Immunization Program in the country with impetus on the existing challenges, progress achieved till date as a result of various

  18. Transcriptome Analysis and Discovery of Genes Involved in Immune Pathways from Coelomocytes of Sea Cucumber (Apostichopus japonicus after Vibrio splendidus Challenge

    Directory of Open Access Journals (Sweden)

    Qiong Gao

    2015-07-01

    Full Text Available Vibrio splendidus is identified as one of the major pathogenic factors for the skin ulceration syndrome in sea cucumber (Apostichopus japonicus, which has vastly limited the development of the sea cucumber culture industry. In order to screen the immune genes involving Vibrio splendidus challenge in sea cucumber and explore the molecular mechanism of this process, the related transcriptome and gene expression profiling of resistant and susceptible biotypes of sea cucumber with Vibrio splendidus challenge were collected for analysis. A total of 319,455,942 trimmed reads were obtained, which were assembled into 186,658 contigs. After that, 89,891 representative contigs (without isoform were clustered. The analysis of the gene expression profiling identified 358 differentially expression genes (DEGs in the bacterial-resistant group, and 102 DEGs in the bacterial-susceptible group, compared with that in control group. According to the reported references and annotation information from BLAST, GO and KEGG, 30 putative bacterial-resistant genes and 19 putative bacterial-susceptible genes were identified from DEGs. The qRT-PCR results were consistent with the RNA-Seq results. Furthermore, many DGEs were involved in immune signaling related pathways, such as Endocytosis, Lysosome, MAPK, Chemokine and the ERBB signaling pathway.

  19. The immunomodulatory effects of shark cartilage on the mouse and human immune system

    Directory of Open Access Journals (Sweden)

    ali Sheikhian

    2007-01-01

    Materials and methods: In an experimental study, the effects of different doses of shark cartilage on humoral (antibody titer immune response against sheep red blood cells (SRBC, were measured in mouse. In addition, we evaluated the modulatory effects of the shark cartilage on the natural killer (NK activity of the peritoneal cells of mouse against a tumor cell line called K562, according to the standard methods. The proliferative response of the human peripheral blood mononuclear cells was measured under the influence of shark cartilage. Results: Pure shark cartilage enhanced antibody response against SRBC in vivo. The hemagglutination titer which was 1/147 in the control group (injected with hen cartilage, increased to 1/1355 in the test group. The optimal dose was 100 mg/ml. both type of cartilage had blastogenic effect on peripheral blood mononuclear cells (the blastogenic index was 6.7 and 4.9 for impure shark cartilage and hen cartilage, respectively. NK activity was inhibited completely by pure shark cartilage (the amount of the killing activity of the effector peritoneal cells for the control and test groups against target cells was 25.9% and 5.5% respectively. Conclusion: Shark cartilage has a potent immunomodulatory effect on the specific immune mechanisms and some inhibitory effects on the innate immune mechanisms such as NC activity. Since the specific immunity has a more pivotal role against tumor formation, shark cartilage can be used as a cancer immunotherapeutic.

  20. Using network properties to evaluate targeted immunization algorithms

    Directory of Open Access Journals (Sweden)

    Bita Shams

    2014-09-01

    Full Text Available Immunization of complex network with minimal or limited budget is a challenging issue for research community. In spite of much literature in network immunization, no comprehensive research has been conducted for evaluation and comparison of immunization algorithms. In this paper, we propose an evaluation framework for immunization algorithms regarding available amount of vaccination resources, goal of immunization program, and time complexity. The evaluation framework is designed based on network topological metrics which is extensible to all epidemic spreading model. Exploiting evaluation framework on well-known targeted immunization algorithms shows that in general, immunization based on PageRank centrality outperforms other targeting strategies in various types of networks, whereas, closeness and eigenvector centrality exhibit the worst case performance.

  1. Abdominal pain in Irritable Bowel Syndrome: a review of putative psychological, neural and neuro-immune mechanisms.

    Science.gov (United States)

    Elsenbruch, Sigrid

    2011-03-01

    Chronic abdominal pain is a common symptom of great clinical significance in several areas of medicine. In many cases no organic cause can be established resulting in the classification as functional gastrointestinal disorder. Irritable Bowel Syndrome (IBS) is the most common of these conditions and is considered an important public health problem because it can be disabling and constitutes a major social and economic burden given the lack of effective treatments. IBS aetiology is most likely multi-factorial involving biological, psychological and social factors. Visceral hyperalgesia (or hypersensitivity) and visceral hypervigilance, which could be mediated by peripheral, spinal, and/or central pathways, constitute key concepts in current research on pathophysiological mechanisms of visceral hyperalgesia. The role of central nervous system mechanisms along the "brain-gut axis" is increasingly appreciated, owing to accumulating evidence from brain imaging studies that neural processing of visceral stimuli is altered in IBS together with long-standing knowledge regarding the contribution of stress and negative emotions to symptom frequency and severity. At the same time, there is also growing evidence suggesting that peripheral immune mechanisms and disturbed neuro-immune communication could play a role in the pathophysiology of visceral hyperalgesia. This review presents recent advances in research on the pathophysiology of visceral hyperalgesia in IBS, with a focus on the role of stress and anxiety in central and peripheral response to visceral pain stimuli. Together, these findings support that in addition to lower pain thresholds displayed by a significant proportion of patients, the evaluation of pain appears to be altered in IBS. This may be attributable to affective disturbances, negative emotions in anticipation of or during visceral stimulation, and altered pain-related expectations and learning processes. Disturbed "top-down" emotional and cognitive pain

  2. Age-dependent trade-offs between immunity and male, but not female, reproduction.

    Science.gov (United States)

    McNamara, Kathryn B; van Lieshout, Emile; Jones, Therésa M; Simmons, Leigh W

    2013-01-01

    Immune function is costly and must be traded off against other life-history traits, such as gamete production. Studies of immune trade-offs typically focus on adult individuals, yet the juvenile stage can be a highly protracted period when reproductive resources are acquired and immune challenges are ubiquitous. Trade-offs during development are likely to be important, yet no studies have considered changes in adult responses to immune challenges imposed at different stages of juvenile development. By manipulating the timing of a bacterial immune challenge to the larvae of the cotton bollworm moth, we examined potential trade-offs between investment into immunity at different stages of juvenile development (early or late) and subsequent adult reproductive investment into sperm or egg production. Our data reveal an age-dependent trade-off between juvenile immune function and adult male reproductive investment. Activation of the immune response during late development resulted in a reduced allocation of resources to eupyrene (fertilizing) sperm production. Immune activation from the injection procedure itself (irrespective of whether individuals were injected with an immune elicitor or a control solution) also caused reproductive trade-offs; males injected early in development produced fewer apyrene (nonfertilizing) sperm. Contrary to many other studies, our study demonstrates these immune trade-offs under ad libitum nutritional conditions. No trade-offs were observed between female immune activation and adult reproductive investment. We suggest the differences in trade-offs observed between male sperm types and the absence of reproductive trade-offs in females may be the result of ontogenetic differences in gamete production in this species. Our data reveal developmental windows when trade-offs between immune function and gametic investment are made, and highlight the importance of considering multiple developmental periods when making inferences regarding the

  3. Systemic and Terminal Ileum Mucosal Immunity Elicited by Oral Immunization With the Ty21a Typhoid Vaccine in HumansSummary

    Directory of Open Access Journals (Sweden)

    Jayaum S. Booth

    2017-11-01

    Full Text Available Background & Aims: Systemic cellular immunity elicited by the Ty21a oral typhoid vaccine has been extensively characterized. However, very limited data are available in humans regarding mucosal immunity at the site of infection (terminal ileum [TI]. Here we investigated the host immunity elicited by Ty21a immunization on terminal ileum–lamina propria mononuclear cells (LPMC and peripheral blood in volunteers undergoing routine colonoscopy. Methods: We characterized LPMC-T memory (TM subsets and assessed Salmonella enterica serovar Typhi (S Typhi–specific responses by multichromatic flow cytometry. Results: No differences were observed in cell yields and phenotypes in LPMC CD8+-TM subsets following Ty21a immunization. However, Ty21a immunization elicited LPMC CD8+ T cells exhibiting significant S Typhi–specific responses (interferon-γ, tumor necrosis factor-α, interleukin-17A, and/or CD107a in all major TM subsets (T-effector/memory [TEM], T-central/memory, and TEM-CD45RA+, although each TM subset exhibited unique characteristics. We also investigated whether Ty21a immunization elicited S Typhi–specific multifunctional effectors in LPMC CD8+ TEM. We observed that LPMC CD8+ TEM responses were mostly multifunctional, except for those cells exhibiting the characteristics associated with cytotoxic responses. Finally, we compared mucosal with systemic responses and made the important observation that LPMC CD8+ S Typhi–specific responses were unique and distinct from their systemic counterparts. Conclusions: This study provides the first demonstration of S Typhi–specific responses in the human terminal ileum mucosa and provides novel insights into the generation of mucosal immune responses following oral Ty21a immunization. Keywords: Lamina Propria Mononuclear Cells, Multifunctional T Cells, CD8+-T Memory Cells, Typhoid, Vaccines

  4. Assessment of immune surveillance among inhabitants of high natural background radiation areas in Ramsar-Iran

    International Nuclear Information System (INIS)

    Sileh, Sajad Borzouei; Monfared, Ali Shabestani; Mostafazade, Amrollah; Abedian, Said

    2010-01-01

    In this study by Multi-parameter flow cytometry, immunologic analyze is performed on peripheral blood, NK cells, most effective cells in innate immune and the proportion of TCD8/TCD4 cells that is effective in cellular immune system will be determined. Lysosomal-associated membrane protein-1 (LAMP-1 or CD107a) is used as a functional marker for the identification of natural killer cell activity. Immune surveillance and immune system role in tumoral defense in Ramsar inhabitants will be determined. Radiation dose rate in Talesh mahalle is very high and was many times greater than Chaparsar (another region in Ramsar). Immune surveillance and immune system role in tumoral defense in Talesh mahalle inhabitants will be compared to Chaparsar inhabitants. If this doesn't have significant difference, we should think about some other aspects such as free radical scavengers that will study later

  5. Immune Mechanisms in Myelodysplastic Syndrome

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    Andreas Glenthøj

    2016-06-01

    Full Text Available Myelodysplastic syndrome (MDS is a spectrum of diseases, characterized by debilitating cytopenias and a propensity of developing acute myeloid leukemia. Comprehensive sequencing efforts have revealed a range of mutations characteristic, but not specific, of MDS. Epidemiologically, autoimmune diseases are common in patients with MDS, fueling hypotheses of common etiological mechanisms. Both innate and adaptive immune pathways are overly active in the hematopoietic niche of MDS. Although supportive care, growth factors, and hypomethylating agents are the mainstay of MDS treatment, some patients—especially younger low-risk patients with HLA-DR15 tissue type—demonstrate impressive response rates after immunosuppressive therapy. This is in contrast to higher-risk MDS patients, where several immune activating treatments, such as immune checkpoint inhibitors, are in the pipeline. Thus, the dual role of immune mechanisms in MDS is challenging, and rigorous translational studies are needed to establish the value of immune manipulation as a treatment of MDS.

  6. Attrition of schistosomes in an irradiation-attenuated cercarial immunization model of Schistosoma mansoni

    International Nuclear Information System (INIS)

    Stek, M. Jr.; Dean, D.A.; Clark, S.S.

    1981-01-01

    The attrition of Schistosoma mansoni challenge worms was studied in irradiation-attenuated cercaria-immunized mice as a function of site and time. The peak recovery of schistosomula from the lungs of immunized mice was delayed 2 days in comparison with non-immunized controls. The difference between the peak recoveries of control and immunized mice accounted for about half of the final attrition observed at the 7-week adult worm stge. Hepatic-mesenteric vein worm recoveries obtained 10 to 42 days after challenge were reduced in most cases at least as much as the 49-day counts. Somewhat higher reductions were observed at 14 to 28 days than at 49 days, confirming the evidence of delayed migration obtained at the lung phase. These findings, coupled with histologic observations, indicate that at least half of the worm elimination attributable to immunization occurs 8 or more days after the challenge infection

  7. No protection in chickens immunized by the oral or intra-muscular immunization route with Ascaridia galli soluble antigen

    DEFF Research Database (Denmark)

    Andersen, Janne Pleidrup; Norup, Liselotte R.; Dalgaard, Tina S.

    2013-01-01

    In chickens, the nematode Ascaridia galli is found with prevalences of up to 100% causing economic losses to farmers. No avian nematode vaccines have yet been developed and detailed knowledge about the chicken immune response towards A. galli is therefore of great importance. The objective...... of this study was to evaluate the induction of protective immune responses to A. galli soluble antigen by different immunization routes. Chickens were immunized with a crude extract of A. galli via an oral or intra-muscular route using cholera toxin B subunit as adjuvant and subsequently challenged with A...... immunization had an effect on both Th1 and Th2 cytokines in caecal tonsils and Meckel's diverticulum. Thus both humoral and cellular immune responses are inducible by soluble A. galli antigen, but in this study no protection against the parasite was achieved....

  8. Injectable systems and implantable conduits for peripheral nerve repair

    International Nuclear Information System (INIS)

    Lin, Yen-Chih; Marra, Kacey G

    2012-01-01

    Acute sensory problems following peripheral nerve injury include pain and loss of sensation. Approximately 360 000 people in the United States suffer from upper extremity paralytic syndromes every year. Restoration of sufficient functional recovery after long-gap peripheral nerve damage remains a clinical challenge. Potential nerve repair therapies have increased in the past decade as the field of tissue engineering expands. The following review describes the use of biomaterials in nerve tissue engineering. Namely, the use of both synthetic and natural biomaterials, including non-degradable and degradable nerve grafts, is addressed. The enhancement of axonal regeneration can be achieved by further modification of the nerve guides. These approaches include injectable hydrogel fillers, controlled drug delivery systems, and cell incorporation. Hydrogels are a class of liquid–gel biomaterials with high water content. Injectable and gelling hydrogels can serve as growth factor delivery vehicles and cell carriers for tissue engineering applications. While natural hydrogels and polymers are suitable for short gap nerve repair, the use of polymers for relatively long gaps remains a clinical challenge. (paper)

  9. Comparison of metabolic, hematological, and peripheral blood leukocyte cytokine profiles of dairy cows and heifers during the periparturient period.

    Science.gov (United States)

    Jonsson, N N; Fortes, M R S; Piper, E K; Vankan, D M; de Cisneros, J Prada J; Wittek, T

    2013-04-01

    The periparturient period presents major physiological challenges for the dairy cow. It is a period that is affected by metabolic stressors, major changes in endocrine status, and altered immune function, which together result in an increased risk of disease. Immunological, hematological, and metabolic profiles from the periparturient period of heifers (primipara) were compared with those of cows (pluripara) to test the hypothesis that at the time of calving they have qualitatively different peripheral blood profiles. Blood samples were collected from 22 Holstein-Friesian animals on 3 occasions: approximately 2 wk before calving, within 24h after calving, and approximately 2 wk after calving. Quantitative PCR was used to measure the expression of a selected set of cytokines and receptors by peripheral blood leukocytes. Additional analyses included hemoglobin concentration, red cell, platelet and white cell counts (total and differentiated), and clinical diagnostic biochemical profiles. Total leukocyte counts, neutrophils, and lymphocytes were higher in heifers than cows before calving and within 24h after calving. Alkaline phosphatase was consistently higher in heifers than cows and several significant differences were observed between the 2 groups with regards to cytokine and cytokine-receptor mRNA expression. The results warrant further investigation from the perspective of identifying risk factors for metabolic and parturient disease in dairy cattle. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  10. Immunization of pigs against infection with Schistosoma japonicum using ultraviolet-attenuated cercariae

    International Nuclear Information System (INIS)

    Shi, Y.-E.; Jiang, C.-F.; Han, J.-J.; Li, Y.-L.

    1993-01-01

    Since pigs are important in the zoonotic transmission of schistosomiasis japonica in China, a veterinary vaccine might contribute to the control of the disease in humans. Pigs were immunized with three doses each of 10 000 cercariae of Schistosoma japonicum attenuated with ultraviolet light (400 μWatt.min/cm 2 ). The experiment was performed with portable irradiation equipment in a rural area of the Hubei Province (P.R. China). A challenge infection of 1000 untreated cercariae was given 2.5 or 6 months after the last immunization, and age-matched naive pigs were challenged as a control. Immunized pigs developed about 90% resistance against the challenge. The liver egg load of these animals was reduced by over 90%. Less than 0.01% of the immunizing cercariae developed to adult parasites and the vaccination had no apparent adverse influence on the pig's health. (Author)

  11. Effect of thoracoscopic esophagus cancer surgery on postoperative incision pain as well as non-specific and specific immune response

    Directory of Open Access Journals (Sweden)

    Jin-Long Wu1

    2017-04-01

    Full Text Available Objective: To explore the effect of thoracoscopic esophagus cancer surgery on postoperative incision pain as well as non-specific and specific immune response. Methods: 56 patients with esophageal cancer who accepted surgical treatment in our hospital between March 2011 and February 2016 were collected, the operation methods and related laboratory tests were reviewed, and then they were divided into the thoracoscope group (n=27 who accepted thoracoscopic surgery and the open surgery group (n=29 who accepted traditional thoracotomy. Before operation and 1 d after operation, immune scatter turbidimetry was used to detect serum levels of pain mediators, and flow cytometer was used to detect the levels of nonspecific immune indexes and specific immune indexes. Results: Before operation, the differences in serum pain mediators as well as nonspecific immune response and specific immune response indexes were not statistically significant between two groups of patients (P>0.05. 1 d after operation, serum pain mediators 5-HT, K+ and NE levels of thoracoscope group were lower than those of open surgery group (P<0.05; nonspecific immune response indexes NK cell as well as C3 and C4 levels in peripheral blood of thoracoscope group were significantly higher than those of open surgery group (P<0.05; specific immune response indexes CD4+, CD4+/CD8+, IgA and IgG levels in peripheral blood of thoracoscope group were significantly higher than those of open surgery group (P<0.05. Conclusion: Thoracoscopic esophagus cancer surgery causes less damage, has lighter inhibition on the immune response system, and is an ideal operation method for patients with early middle esophagus cancer.

  12. Granulomatosis with Polyangiitis Presenting as Pauci-Immune Crescentic Glomerulonephritis in Pregnancy

    Directory of Open Access Journals (Sweden)

    Ryan Kunjal

    2016-01-01

    Full Text Available Antineutrophil cytoplasmic antibody (ANCA associated vasculitis rarely affects females of reproductive age. A 28-year-old African American woman presented at 8 weeks of gestation with intractable vomiting attributed to hyperemesis gravidarum. She was found to have acute kidney injury that was unresponsive to vigorous fluid resuscitation and urine sediment examination was suggestive of an underlying glomerulonephritis. Serum c-ANCA and PR3 were elevated and there was no peripheral eosinophilia. During her course she also developed one episode of small volume hemoptysis with right upper lobe infiltrates on CT Chest. There were no cutaneous manifestations of vasculitis or upper respiratory symptoms. Renal biopsy revealed a pauci-immune crescentic glomerulonephritis (PICGN. The diagnosis was consistent with granulomatosis with polyangiitis (GPA. Management initially comprised teratogen sparing agents; steroids, intravenous immunoglobulin; and plasma exchange. The response was suboptimal and she became dependent on daily renal replacement therapy. Ultimately the pregnancy was terminated allowing for traditional treatment approaches with dramatic effect. This is the first case of GPA presenting as PICGN in pregnancy and highlights the challenges of its management.

  13. Granulomatosis with Polyangiitis Presenting as Pauci-Immune Crescentic Glomerulonephritis in Pregnancy.

    Science.gov (United States)

    Kunjal, Ryan; Makary, Raafat; Poenariu, Andreea

    2016-01-01

    Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis rarely affects females of reproductive age. A 28-year-old African American woman presented at 8 weeks of gestation with intractable vomiting attributed to hyperemesis gravidarum. She was found to have acute kidney injury that was unresponsive to vigorous fluid resuscitation and urine sediment examination was suggestive of an underlying glomerulonephritis. Serum c-ANCA and PR3 were elevated and there was no peripheral eosinophilia. During her course she also developed one episode of small volume hemoptysis with right upper lobe infiltrates on CT Chest. There were no cutaneous manifestations of vasculitis or upper respiratory symptoms. Renal biopsy revealed a pauci-immune crescentic glomerulonephritis (PICGN). The diagnosis was consistent with granulomatosis with polyangiitis (GPA). Management initially comprised teratogen sparing agents; steroids, intravenous immunoglobulin; and plasma exchange. The response was suboptimal and she became dependent on daily renal replacement therapy. Ultimately the pregnancy was terminated allowing for traditional treatment approaches with dramatic effect. This is the first case of GPA presenting as PICGN in pregnancy and highlights the challenges of its management.

  14. Aberrant Pregnancy Adaptations in the Peripheral Immune Response in Type 1 Diabetes: A Rat Model.

    Directory of Open Access Journals (Sweden)

    Bart Groen

    Full Text Available Despite tight glycemic control, pregnancy complication rate in type 1 diabetes patients is higher than in normal pregnancy. Other etiological factors may be responsible for the development of adverse pregnancy outcome. Acceptance of the semi-allogeneic fetus is accompanied by adaptations in the maternal immune-response. Maladaptations of the immune-response has been shown to contribute to pregnancy complications. We hypothesized that type 1 diabetes, as an autoimmune disease, may be associated with maladaptations of the immune-response to pregnancy, possibly resulting in pregnancy complications.We studied pregnancy outcome and pregnancy-induced immunological adaptations in a normoglycemic rat-model of type 1 diabetes, i.e. biobreeding diabetes-prone rats (BBDP; 5 non-pregnant rats, 7 pregnant day 10 rats and 6 pregnant day 18 rats , versus non-diabetic control rats (i.e. congenic non-diabetic biobreeding diabetes-resistant (BBDR; 6 non-pregnant rats, 6 pregnant day 10 rats and 6 pregnant day 18 rats and Wistar-rats (6 non-pregnant, 6 pregnant day 10 rats and 5 pregnant day 18 rats.We observed reduced litter size, lower fetal weight of viable fetuses and increased numbers of resorptions versus control rats. These complications are accompanied by various differences in the immune-response between BBDP and control rats in both pregnant and non-pregnant animals. The immune-response in non-pregnant BBDP-rats was characterized by decreased percentages of lymphocytes, increased percentages of effector T-cells, regulatory T-cells and natural killer cells, an increased Th1/Th2-ratio and activated monocytes versus Wistar and BBDR-rats. Furthermore, pregnancy-induced adaptations in BBDP-rats coincided with an increased Th1/Th2-ratio, a decreased mean fluorescence intensity CD161a/NKR-P1b ratio and no further activation of monocytes versus non-diabetic control rats.This study suggests that even in the face of strict normoglycemia, pregnancy complications

  15. Nitrated alpha-synuclein immunity accelerates degeneration of nigral dopaminergic neurons.

    Directory of Open Access Journals (Sweden)

    Eric J Benner

    2008-01-01

    Full Text Available The neuropathology of Parkinson's disease (PD includes loss of dopaminergic neurons in the substantia nigra, nitrated alpha-synuclein (N-alpha-Syn enriched intraneuronal inclusions or Lewy bodies and neuroinflammation. While the contribution of innate microglial inflammatory activities to disease are known, evidence for how adaptive immune mechanisms may affect the course of PD remains obscure. We reasoned that PD-associated oxidative protein modifications create novel antigenic epitopes capable of peripheral adaptive T cell responses that could affect nigrostriatal degeneration.Nitrotyrosine (NT-modified alpha-Syn was detected readily in cervical lymph nodes (CLN from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP intoxicated mice. Antigen-presenting cells within the CLN showed increased surface expression of major histocompatibility complex class II, initiating the molecular machinery necessary for efficient antigen presentation. MPTP-treated mice produced antibodies to native and nitrated alpha-Syn. Mice immunized with the NT-modified C-terminal tail fragment of alpha-Syn, but not native protein, generated robust T cell proliferative and pro-inflammatory secretory responses specific only for the modified antigen. T cells generated against the nitrated epitope do not respond to the unmodified protein. Mice deficient in T and B lymphocytes were resistant to MPTP-induced neurodegeneration. Transfer of T cells from mice immunized with N-alpha-Syn led to a robust neuroinflammatory response with accelerated dopaminergic cell loss.These data show that NT modifications within alpha-Syn, can bypass or break immunological tolerance and activate peripheral leukocytes in draining lymphoid tissue. A novel mechanism for disease is made in that NT modifications in alpha-Syn induce adaptive immune responses that exacerbate PD pathobiology. These results have implications for both the pathogenesis and treatment of this disabling neurodegenerative disease.

  16. Immune monitoring using mRNA-transfected dendritic cells

    DEFF Research Database (Denmark)

    Borch, Troels Holz; Svane, Inge Marie; Met, Özcan

    2016-01-01

    Dendritic cells are known to be the most potent antigen presenting cell in the immune system and are used as cellular adjuvants in therapeutic anticancer vaccines using various tumor-associated antigens or their derivatives. One way of loading antigen into the dendritic cells is by m......RNA electroporation, ensuring presentation of antigen through major histocompatibility complex I and potentially activating T cells, enabling them to kill the tumor cells. Despite extensive research in the field, only one dendritic cell-based vaccine has been approved. There is therefore a great need to elucidate...... and understand the immunological impact of dendritic cell vaccination in order to improve clinical benefit. In this chapter, we describe a method for performing immune monitoring using peripheral blood mononuclear cells and autologous dendritic cells transfected with tumor-associated antigen-encoding mRNA....

  17. Immune complexes stimulate CCR7-dependent dendritic cell migration to lymph nodes

    Science.gov (United States)

    Clatworthy, Menna R.; Aronin, Caren E. Petrie; Mathews, Rebeccah J.; Morgan, Nicole; Smith, Kenneth G.C.; Germain, Ronald N.

    2014-01-01

    Antibodies are critical for defence against a variety of microbes but may also be pathogenic in some autoimmune diseases. Many effector functions of antibody are mediated by Fcγ receptors (FcγRs), which are found on most immune cells, including dendritic cells (DCs). DCs are important antigen presenting cells and play a central role in inducing antigen-specific tolerance or immunity1,2. Following antigen acquisition in peripheral tissues, DCs migrate to draining lymph nodes via lymphatics to present antigen to T cells. In this study we demonstrate that FcγR engagement by IgG immune complexes (IC) stimulates DC migration from peripheral tissues to the paracortex of draining lymph nodes. In vitro, IC-stimulated murine and human DCs showed enhanced directional migration in a CCL19 gradient and increased CCR7 expression. Using intravital two-photon microscopy, we observed that local administration of IC resulted in dermal DC mobilisation. We confirmed that dermal DC migration to lymph nodes was CCR7-dependent and increased in the absence of the inhibitory receptor, FcγRIIb. These observations have relevance to autoimmunity, because autoantibody-containing serum from mice and humans with SLE also increased dermal DC migration to lymph nodes in vivo, suggesting that this process may occur in lupus, potentially driving the inappropriate localisation of autoantigen-bearing DCs. PMID:25384086

  18. The Mucosal Immune System and Its Regulation by Autophagy.

    Science.gov (United States)

    Kabat, Agnieszka M; Pott, Johanna; Maloy, Kevin J

    2016-01-01

    The gastrointestinal tract presents a unique challenge to the mucosal immune system, which has to constantly monitor the vast surface for the presence of pathogens, while at the same time maintaining tolerance to beneficial or innocuous antigens. In the intestinal mucosa, specialized innate and adaptive immune components participate in directing appropriate immune responses toward these diverse challenges. Recent studies provide compelling evidence that the process of autophagy influences several aspects of mucosal immune responses. Initially described as a "self-eating" survival pathway that enables nutrient recycling during starvation, autophagy has now been connected to multiple cellular responses, including several aspects of immunity. Initial links between autophagy and host immunity came from the observations that autophagy can target intracellular bacteria for degradation. However, subsequent studies indicated that autophagy plays a much broader role in immune responses, as it can impact antigen processing, thymic selection, lymphocyte homeostasis, and the regulation of immunoglobulin and cytokine secretion. In this review, we provide a comprehensive overview of mucosal immune cells and discuss how autophagy influences many aspects of their physiology and function. We focus on cell type-specific roles of autophagy in the gut, with a particular emphasis on the effects of autophagy on the intestinal T cell compartment. We also provide a perspective on how manipulation of autophagy may potentially be used to treat mucosal inflammatory disorders.

  19. Bovine response to lipoarabinomannan vaccination and challenge with Mycobacterium paratuberculosis.

    Science.gov (United States)

    Jolly, Ana; Morsella, Claudia; Bass, Laura; Fiorentino, María Andrea; Paolicchi, Fernando Alberto; Mundo, Silvia Leonor

    2013-01-01

    This study aimed to evaluate the immune response in bovines following immunization with a mycobaterial Lipoarabinomannan extract (LAMe) and the effect of Map challenge. LAMe vaccine induced specific antibody levels that diminished after the challenge and affected Map excretion at least for 100 days thereafter.

  20. Serotonin induces peripheral antinociception via the opioidergic system.

    Science.gov (United States)

    Diniz, Danielle Aguiar; Petrocchi, Júlia Alvarenga; Navarro, Larissa Caldeira; Souza, Tâmara Cristina; Castor, Marina Gomes Miranda E; Duarte, Igor Dimitri Gama; Romero, Thiago Roberto Lima

    2018-01-01

    Studies conducted since 1969 have shown that the release of serotonin (5-HT) in the dorsal horn of the spinal cord contributes to opioid analgesia. In the present study, the participation of the opioidergic system in antinociceptive effect serotonin at the peripheral level was examined. The paw pressure test was used with mice (Swiss, males from 35 g) which had increased pain sensitivity by intraplantar injection of PGE 2 (2 μg). Serotonin (250 ng), administered locally to the right paw of animals, produces antinociception in this model. The selective antagonists for mu, delta and kappa opioid receptors, clocinnamox clocinnamox (40 μg), naltrindole (60 μg) and nor-binaltorfimina (200 μg), respectively, inhibited the antinociceptive effect induced by serotonin. Additionally, bestatin (400 μg), an inhibitor of enkephalinases that degrade peptides opioids, enhanced the antinociceptive effect induced by serotonin (low dose of 62.5 ng). These results suggest that serotonin possibly induce peripheral antinociception through the release of endogenous opioid peptides, possible from immune cells or keratinocytes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  1. [Impact of thymic function in age-related immune deterioration].

    Science.gov (United States)

    Ferrando-Martínez, Sara; de la Fuente, Mónica; Guerrero, Juan Miguel; Leal, Manuel; Muñoz-Fernández, M Ángeles

    2013-01-01

    Age-related biological deterioration also includes immune system deterioration and, in consequence, a rise in the incidence and prevalence of infections and cancers, as well as low responses to vaccination strategies. Out of all immune cell subsets, T-lymphocytes seem to be involved in most of the age-related defects. Since T-lymphocytes mature during their passage through the thymus, and the thymus shows an age-related process of atrophy, thymic regression has been proposed as the triggering event of this immune deterioration in elderly people. Historically, it has been accepted that the young thymus sets the T-lymphocyte repertoire during the childhood, whereupon atrophy begins until the elderly thymus is a non-functional evolutionary trace. However, a rising body of knowledge points toward the thymus functioning during adulthood. In the elderly, higher thymic function is associated with a younger immune system, while thymic function failure is associated with all-cause mortality. Therefore, any new strategy focused on the improvement of the elderly quality of life, especially those trying to influence the immune system, should take into account, together with peripheral homeostasis, thymus function as a key element in slowing down age-related decline. Copyright © 2012 SEGG. Published by Elsevier Espana. All rights reserved.

  2. The risk for behavioural deficits is determined by the maternal immune response to prenatal immune challenge in a neurodevelopmental model.

    Science.gov (United States)

    Missault, S; Van den Eynde, K; Vanden Berghe, W; Fransen, E; Weeren, A; Timmermans, J P; Kumar-Singh, S; Dedeurwaerdere, S

    2014-11-01

    Schizophrenia is a highly disabling psychiatric disorder with a proposed neurodevelopmental basis. One mechanism through which genetic and environmental risk factors might act is by triggering persistent brain inflammation, as evidenced by long-lasting neuro-immunological disturbances in patients. Our goal was to investigate whether microglia activation is a neurobiological correlate to the altered behaviour in the maternal immune activation (MIA) model, a well-validated animal model with relevance to schizophrenia. A recent observation in the MIA model is the differential maternal body weight response to the immune stimulus, correlated with a different behavioural outcome in the offspring. Although it is generally assumed that the differences in maternal weight response reflect differences in cytokine response, this has not been investigated so far. Our aim was to investigate whether (i) the maternal weight response to MIA reflects differences in the maternal cytokine response, (ii) the differential behavioural phenotype of the offspring extends to depressive symptoms such as anhedonia and (iii) there are changes in chronic microglia activation dependent on the behavioural phenotype. Based on a dose-response study, MIA was induced in pregnant rats by injecting 4mg/kg Poly I:C at gestational day 15. Serum samples were collected to assess the amount of TNF-α in the maternal blood following MIA. MIA offspring were divided into weight loss (WL; n=14) and weight gain (WG; n=10) groups, depending on the maternal body weight response to Poly I:C. Adult offspring were behaviourally phenotyped for prepulse inhibition, locomotor activity with and without amphetamine and MK-801 challenge, and sucrose preference. Finally, microglia activation was scored on CD11b- and Iba1-immunohistochemically stained sections. Pregnant dams that lost weight following MIA showed increased levels of TNF-α compared to controls, unlike dams that gained weight following MIA. Poly I:C WL

  3. Effects of Resveratrol and Essential Oils on Growth Performance, Immunity, Digestibility and Fecal Microbial Shedding in Challenged Piglets

    Directory of Open Access Journals (Sweden)

    S. T. Ahmed

    2013-05-01

    Full Text Available A study was conducted to evaluate the effects of resveratrol and essential oils from medicinal plants on the growth performance, immunity, digestibility, and fecal microbial shedding of weaned piglets. A total of 48 weaned piglets (8 kg initial weight, 28-d-old were randomly allotted to four dietary treatments with 3 replications of 4 piglets each. The dietary treatments were NC (negative control; basal diet, PC (positive control; basal diet+0.002% apramycin, T1 (basal diet+0.2% resveratrol, and T2 (basal diet+0.0125% essential oil blend. All piglets were orally challenged with 5 ml culture fluid containing 2.3×108 cfu/ml of Escherichia coli KCTC 2571 and 5.9×108 cfu/ml Salmonella enterica serover Typhimurium. The PC group (p0.05. Serum IgG level was increased in the T1 group, whereas TNF-α levels was reduced in the supplemented groups compared to control (p<0.05. The PC diet improved the dry matter (DM digestibility, whereas PC and T2 diets improved nitrogen (N digestibility compared to NC and T1 diets (p<0.05. Fecal Salmonella and E. coli counts were reduced in all treatment groups compared to control (p<0.05. Fecal Lactobacillus spp. count was increased in the T2 group compared to others (p<0.05. Dietary treatments had no significant effect on fecal Bacillus spp. count throughout the entire experimental period. Based on these results, resveratrol showed strong potential as antibiotic alternatives for reversing the adverse effects of weaning stress on growth performance, immunity and microbial environment in E. coli and Salmonella-challenged piglets.

  4. Neonatal infection produces significant changes in immune function with no associated learning deficits in juvenile rats.

    Science.gov (United States)

    Osborne, Brittany F; Caulfield, Jasmine I; Solomotis, Samantha A; Schwarz, Jaclyn M

    2017-10-01

    The current experiments examined the impact of early-life immune activation and a subsequent mild immune challenge with lipopolysaccharide (LPS; 25µg/kg) on hippocampal-dependent learning, proinflammatory cytokine expression in the brain, and peripheral immune function in juvenile male and female rats at P24, an age when hippocampal-dependent learning and memory first emerges. Our results indicate that neonatal infection did not produce learning deficits in the hippocampal-dependent context pre-exposure facilitation effect paradigm in juvenile males and females, contrary to what has been observed in adults. Neonatal infection produced an increase in baseline IL-1β expression in the hippocampus (HP) and medial prefrontal cortex (mPFC) of juvenile rats. Furthermore, neonatally infected rats showed exaggerated IL-1β expression in the HP following LPS treatment as juveniles; and juvenile females, but not males, showed exaggerated IL-1β expression in the mPFC following LPS treatment. Neonatal infection attenuated the production of IL-6 expression following LPS treatment in both the brain and the spleen, and neonatal infection decreased the numbers of circulating white blood cells in juvenile males and females, an effect that was further exacerbated by subsequent LPS treatment. Together, our data indicate that the consequences of neonatal infection are detectable even early in juvenile development, though we found no concomitant hippocampal-dependent learning deficits at this young age. These findings underscore the need to consider age and associated on-going neurodevelopmental processes as important factors contributing to the emergence of cognitive and behavioral disorders linked to early-life immune activation. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1221-1236, 2017. © 2017 Wiley Periodicals, Inc.

  5. Menstrual blood closely resembles the uterine immune micro-environment and is clearly distinct from peripheral blood

    NARCIS (Netherlands)

    Molen, R.G. van der; Schutten, J.H.; Cranenbroek, B. van; Meer, M. ter; Donckers, J.; Scholten, R.R.; Heijden, O.W.H. van der; Spaanderman, M.E.A.; Joosten, I.

    2014-01-01

    STUDY QUESTION: Is menstrual blood a suitable source of endometrial derived lymphocytes? SUMMARY ANSWER: Mononuclear cells isolated from menstrual samples (menstrual blood mononuclear cells (MMC)) are clearly distinct from peripheral blood mononuclear cells (PBMC) and show a strong resemblance with

  6. Transfer of immunity by transfer of bone marrow cells: T-cell dependency

    International Nuclear Information System (INIS)

    Marusic, M.

    1978-01-01

    Thymectomized, lethally irradiated mice reconstituted with normal bone marrow cells succumbed when challenged ip with rat Yoshida ascites sarcoma (YAS) cells 40 days after irradiation and reconstitution. In contrast, thymectomized irradiated mice reconstituted with bone marrow cells from YAS-immune donors rejected the subsequent tumor challenge. Pretreatment of the bone marrow cells from immune donors with anti-Thy 1.2 antiserum and complement completely abolished the transfer of anti-YAS resistance. Bone marrow cells from donors thymectomized 2 months before immunization enabled almost all recipients to reject YAS, but bone marrow cells from donors thymectomized 8 months before immunization protected only 50 percent of the recipients. Further analysis showed that mice thymectomized 8 months before immunization failed to generate anti-YAS antibody response, whereas the antibody response of mice thymectomized 2 months before immunization did not differ from that of non-thymectomized age-matched control mice. The data suggest that the immune reaction of mice against xenogeneic YAS requires long-lived T 2 lymphocytes

  7. The kinetics of early T and B cell immune recovery after bone marrow transplantation in RAG-2-deficient SCID patients.

    Directory of Open Access Journals (Sweden)

    Atar Lev

    Full Text Available The kinetics of T and B cell immune recovery after bone marrow transplantation (BMT is affected by many pre- and post-transplant factors. Because of the profoundly depleted baseline T and B cell immunity in recombination activating gene 2 (RAG-2-deficient severe combined immunodeficiency (SCID patients, some of these factors are eliminated, and the immune recovery after BMT can then be clearly assessed. This process was followed in ten SCID patients in parallel to their associated transplant-related complications. Early peripheral presence of T and B cells was observed in 8 and 4 patients, respectively. The latter correlated with pre-transplant conditioning therapy. Cells from these patients carried mainly signal joint DNA episomes, indicative of newly derived B and T cells. They were present before the normalization of the T cell receptor (TCR and the B cell receptor (BCR repertoire. Early presentation of the ordered TCR gene rearrangements after BMT occurred simultaneously, but this pattern was heterogeneous over time, suggesting different and individual thymic recovery processes. Our findings early after transplant could suggest the long-term patients' clinical outcome. Early peripheral presence of newly produced B and T lymphocytes from their production and maturation sites after BMT suggests donor stem cell origin rather than peripheral expansion, and is indicative of successful outcome. Peripheral detection of TCR excision circles and kappa-deleting recombination excision circles in RAG-2-deficient SCID post-BMT are early markers of T and B cell reconstitution, and can be used to monitor outcome and tailor specific therapy for patients undergoing BMT.

  8. Pretransplant Immune- and Apoptosis-Related Gene Expression Is Associated with Kidney Allograft Function

    Directory of Open Access Journals (Sweden)

    Dorota Kamińska

    2016-01-01

    Full Text Available Renal transplant candidates present immune dysregulation, caused by chronic uremia. The aim of the study was to investigate whether pretransplant peripheral blood gene expression of immune factors affects clinical outcome of renal allograft recipients. Methods. In a prospective study, we analyzed pretransplant peripheral blood gene expression in87 renal transplant candidates with real-time PCR on custom-designed low density arrays (TaqMan. Results. Immediate posttransplant graft function (14-day GFR was influenced negatively by TGFB1 (P=0.039 and positively by IL-2 gene expression (P=0.040. Pretransplant blood mRNA expression of apoptosis-related genes (CASP3, FAS, and IL-18 and Th1-derived cytokine gene IFNG correlated positively with short- (6-month GFR CASP3: P=0.027, FAS: P=0.021, and IFNG: P=0.029 and long-term graft function (24-month GFR CASP3: P=0.003, FAS: P=0.033, IL-18: P=0.044, and IFNG: P=0.04. Conclusion. Lowered pretransplant Th1-derived cytokine and apoptosis-related gene expressions were a hallmark of subsequent worse kidney function but not of acute rejection rate. The pretransplant IFNG and CASP3 and FAS and IL-18 genes’ expression in the recipients’ peripheral blood is the possible candidate for novel biomarker of short- and long-term allograft function.

  9. Comparison of subcutaneous versus intranasal immunization of male koalas (Phascolarctos cinereus) for induction of mucosal and systemic immunity against Chlamydia pecorum.

    Science.gov (United States)

    Waugh, Courtney A; Timms, Peter; Andrew, Dean; Rawlinson, Galit; Brumm, Jacqui; Nilsson, Karen; Beagley, Kenneth W

    2015-02-11

    Chlamydia pecorum infections are debilitating in the koala, contributing significantly to morbidity and mortality, with current antibiotic treatments having minimal success and adversely affecting gut microflora. This, combined with the sometimes-asymptomatic nature of the infection, suggests that an efficacious anti-chlamydial vaccine is required to control chlamydial infections in the koala. To date vaccination studies have focused primarily on female koalas, however, given the physiological differences between male and female reproductive tracts, we tested the efficacy of a vaccine in 12 captive male koalas. We evaluated the potential of both subcutaneous and intranasal vaccine delivery to elicit mucosal immunity in male koalas. Our results showed that both intranasal and subcutaneous delivery of a vaccine consisting of C. pecorum major outer membrane protein (MOMP) and the adjuvant immunostimulating complex (ISC) induced significant immune responses in male koalas. Subcutaneous immunization elicited stronger cell-mediated responses in peripheral blood lymphocytes (PBL), and greater plasma antibody levels whereas the intranasal immunization elicited stronger humoral responses in urogenital tract (UGT) secretions. This is the first time a Chlamydia vaccine has been tested in the male koala and the first assessment of a mucosal vaccination route in this species. Our results suggest that vaccination of male koalas can elicit mucosal immunity and could contribute to the long-term survivability of wild populations of the koala. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Immune thrombocytopenia associated with malaria: a case report.

    Science.gov (United States)

    Miloudi, Mouhcine; Sbaai, Mohammed; Fatihi, Jamal

    2017-10-01

    The association of immune thrombocytopenic with malaria is a rare event. We describ the case of a young soldier who, after returning from Central Africa, presented a fever associated with petechial purpura and gingivorrhagia, hemogram showed deep thrombocytopenia and macrocytic normochrome anemia, thick peripheral blood smears confirmed the diagnosis of Plasmodium falciparum malaria, the patient was treated with quinine, but deep thrombocytopenia and hemorrhagic manifestations persisted, the patient then underwent corticosteroid therapy, with favorable evolution and progressive normalization of platelets.

  11. Aged Garlic Extract Modifies Human Immunity.

    Science.gov (United States)

    Percival, Susan S

    2016-02-01

    Garlic contains numerous compounds that have the potential to influence immunity. Immune cells, especially innate immune cells, are responsible for the inflammation necessary to kill pathogens. Two innate lymphocytes, γδ-T and natural killer (NK) cells, appear to be susceptible to diet modification. The purpose of this review was to summarize the influence of aged garlic extract (AGE) on the immune system. The author's laboratory is interested in AGE's effects on cell proliferation and activation and inflammation and to learn whether those changes might affect the occurrence and severity of colds and flu. Healthy human participants (n = 120), between 21 and 50 y of age, were recruited for a randomized, double-blind, placebo-controlled parallel-intervention study to consume 2.56 g AGE/d or placebo supplements for 90 d during the cold and flu season. Peripheral blood mononuclear cells were isolated before and after consumption, and γδ-T and NK cell function was assessed by flow cytometry. The effect on cold and flu symptoms was determined by using daily diary records of self-reported illnesses. After 45 d of AGE consumption, γδ-T and NK cells proliferated better and were more activated than cells from the placebo group. After 90 d, although the number of illnesses was not significantly different, the AGE group showed reduced cold and flu severity, with a reduction in the number of symptoms, the number of days participants functioned suboptimally, and the number of work/school days missed. These results suggest that AGE supplementation may enhance immune cell function and may be partly responsible for the reduced severity of colds and flu reported. The results also suggest that the immune system functions well with AGE supplementation, perhaps with less accompanying inflammation. This trial was registered at clinicaltrials.gov as NCT01390116. © 2016 American Society for Nutrition.

  12. Mechanisms of diabetic autoimmunity: I--the inductive interface between islets and the immune system at onset of inflammation.

    Science.gov (United States)

    Askenasy, Nadir

    2016-04-01

    The mechanisms of autoimmune reactivity onset in type 1 diabetes (T1D) remain elusive despite extensive experimentation and discussion. We reconsider several key aspects of the early stages of autoimmunity at four levels: islets, pancreatic lymph nodes, thymic function and peripheral immune homeostasis. Antigen presentation is the islets and has the capacity to provoke immune sensitization, either in the process of physiological neonatal β cell apoptosis or as a consequence of cytolytic activity of self-reactive thymocytes that escaped negative regulation. Diabetogenic effectors are efficiently expanded in both the islets and the lymph nodes under conditions of empty lymphoid niches during a period of time coinciding with a synchronized wave of β cell apoptosis surrounding weaning. A major drive of effector cell activation and expansion is inherent peripheral lymphopenia characteristic of neonates, though it remains unclear when is autoimmunity triggered in subjects displaying hyperglycemia in late adolescence. Our analysis suggests that T1D evolves through coordinated activity of multiple physiological mechanisms of stimulation within specific characteristics of the neonate immune system.

  13. Protective immune responses during prepatency in goat kids experimentally infected with Eimeria ninakohlyakimovae.

    Science.gov (United States)

    Matos, L; Muñoz, M C; Molina, J M; Rodríguez, F; Perez, D; Lopez, A; Ferrer, O; Hermosilla, C; Taubert, A; Ruiz, A

    2017-08-15

    During the first schizogony, the goat coccidia Eimeria ninakohlyakimovae develops macroschizonts in lacteal duct endothelial cells, whose rupture leads to severe ileal damage and clinical signs during the prepatent period. The immune response elicited against early stages of the parasite development still requires to be investigated. In the present study we have evaluated immune reactions in goat kids primary- and challenged-infected with Eimeria ninakohlyakimovae, and sacrificed during prepatency (7days after challenge). The oocyst output during the primary infection, body weight and clinical condition of all the animals were examined and, at the end of the experiment, all the goat kids were euthanized and subjected to necropsy. Samples were taken from different sections of the ileum, colon and mesenteric lymph nodes (MLN) of primary- and challenged E. ninakohlyakimovae-infected animals. Intestinal leukocyte subpopulations were characterized in E. ninakohlyakimovae-infected mucosa and counts of lymphocytes, eosinophils, polymorphonuclear neutrophils (PMN), globular leukocytes and mast cells were recorded. Additionally, gene expression of caprine IL-2, IL-4, IL-10 and INFγ of ileal, colonic and MLN tissues were performed, as well as the immunohistochemical characterization of immune cells. The E. ninakohlyakimovae primary infection resulted in moderate to severe enteritis with different degrees of diarrhoea and was accompanied by high OPG counts and an increase of most immune cells analyzed when compared to uninfected control animals. Furthermore, eosinophil-, lymphocyte-, globular leukocyte- and mast cell-counts were significantly higher in the challenge group compared to the primary infected animals, whilst the opposite was true for PMN counts. The challenge infection was also associated with moderate increased levels of local mucosal IgA. Interestingly, the number of immature schizonts found at the ileal mucosa was statistically higher in the challenge infected

  14. Lol p I-specific IgE and IgG synthesis by peripheral blood mononuclear cells from atopic subjects in SCID mice.

    Science.gov (United States)

    Gagnon, R; Boutin, Y; Hébert, J

    1995-06-01

    The development of an animal model representative of the in vivo situation of human atopic diseases is always of interest for a better understanding of IgE production and regulation. Along these lines, mice with severe combined immunodeficiency (SCID mice) engrafted with lymphocytes from atopic subjects might be a suitable model for such studies. This study aims to analyze the production of Lol p I-specific IgE and IgG antibodies in SCID mice after transplantation of human peripheral blood mononuclear cells from atopic patients sensitive to grass pollens and from nonatopic donors. Peripheral blood mononuclear cells were transplanted into SCID mice, which were then challenged with Lol p I, and antibody responses (IgG and IgE) were analyzed over a 6-week period. Total IgG antibody was measured in each mouse serum after transplantation. Also, most mice (regardless of whether donors were atopic) that were challenged with Lol p I produced specific IgG antibody. Total IgE antibody production was observed only in mice grafted with cells from atopic patients. Lol p I-specific IgE antibodies were also produced after immunization with Lol p I. Although IgG antibody/response tended to plateau, the IgE antibody response increased until it peaked and declined thereafter. Interferon-gamma was detected in sera from mice producing IgE antibody, which supports a possible role of interferon-gamma in the decrease of IgE response. This study suggests that the SCID mouse model could represent an interesting approach to studying specific, total IgG and IgE antibody production, and ultimately their regulation.

  15. Dietary Animal Plasma Proteins Improve the Intestinal Immune Response in Senescent Mice.

    Science.gov (United States)

    Miró, Lluïsa; Garcia-Just, Alba; Amat, Concepció; Polo, Javier; Moretó, Miquel; Pérez-Bosque, Anna

    2017-12-11

    Increased life expectancy has promoted research on healthy aging. Aging is accompanied by increased non-specific immune activation (inflammaging) which favors the appearance of several disorders. Here, we study whether dietary supplementation with spray-dried animal plasma (SDP), which has been shown to reduce the activation of gut-associated lymphoid tissue (GALT) in rodents challenged by S. aureus enterotoxin B (SEB), and can also prevent the effects of aging on immune system homeostasis. We first characterized GALT in a mouse model of accelerated senescence (SAMP8) at different ages (compared to mice resistant to accelerated senescence; SAMR1). Second, we analyzed the SDP effects on GALT response to an SEB challenge in SAMP8 mice. In GALT characterization, aging increased the cell number and the percentage of activated Th lymphocytes in mesenteric lymph nodes and Peyer's patches (all, p < 0.05), as well as the expression of IL-6 and TNF-α in intestinal mucosa (both, p < 0.05). With respect to GALT response to the SEB challenge, young mice showed increased expression of intestinal IL-6 and TNF-α, as well as lymphocyte recruitment and activation (all, p < 0.05). However, the immune response of senescent mice to the SEB challenge was weak, since SEB did not change cell recruitment or the percentage of activated Th lymphocytes. Mice supplemented with SDP showed improved capacity to respond to the SEB challenge, similar to the response of the young mice. These results indicate that senescent mice have an impaired mucosal immune response characterized by unspecific GALT activation and a weak specific immune response. SDP supplementation reduces non-specific basal immune activation, allowing for the generation of specific responses.

  16. Quality and Timing of Stressors Differentially Impact on Brain Plasticity and Neuroendocrine-Immune Function in Mice

    Directory of Open Access Journals (Sweden)

    Sara Capoccia

    2013-01-01

    Full Text Available A growing body of evidence suggests that psychological stress is a major risk factor for psychiatric disorders. The basic mechanisms are still under investigation but involve changes in neuroendocrine-immune interactions, ultimately affecting brain plasticity. In this study we characterized central and peripheral effects of different stressors, applied for different time lengths, in adult male C57BL/6J mice. We compared the effects of repeated (7 versus 21 days restraint stress (RS and chronic disruption of social hierarchy (SS on neuroendocrine (corticosterone and immune function (cytokines and splenic apoptosis and on a marker of brain plasticity (brain-derived neurotrophic factor, BDNF . Neuroendocrine activation did not differ between SS and control subjects; by contrast, the RS group showed a strong neuroendocrine response characterized by a specific time-dependent profile. Immune function and hippocampal BDNF levels were inversely related to hypothalamic-pituitary-adrenal axis activation. These data show a fine modulation of the crosstalk between central and peripheral pathways of adaptation and plasticity and suggest that the length of stress exposure is crucial to determine its final outcome on health or disease.

  17. T Cell-Mediated Immunity towards Yellow Fever Virus and Useful Animal Models.

    Science.gov (United States)

    Watson, Alan M; Klimstra, William B

    2017-04-11

    The 17D line of yellow fever virus vaccines is among the most effective vaccines ever created. The humoral and cellular immunity elicited by 17D has been well characterized in humans. Neutralizing antibodies have long been known to provide protection against challenge with a wild-type virus. However, a well characterized T cell immune response that is robust, long-lived and polyfunctional is also elicited by 17D. It remains unclear whether this arm of immunity is protective following challenge with a wild-type virus. Here we introduce the 17D line of yellow fever virus vaccines, describe the current state of knowledge regarding the immunity directed towards the vaccines in humans and conclude with a discussion of animal models that are useful for evaluating T cell-mediated immune protection to yellow fever virus.

  18. Vasculitic peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Mona Amini

    2014-02-01

    Full Text Available Primary systemic vasculitis in pre-capillary arteries is associated with peripheral neuropathy. In some types of systematic vasculitis about 60 % of patients have peripheral nervous system (PNS involvement. In vasculitic peripheral neuropathies (VPN a necrotizing and inflammatory process leads to narrowing of vasa nervorum lumen and eventually the appearance of ischemic lesions in peripheral nerves. Some features might be suggestive of VPN, like: axonal nerve degeneration, wallerian-like degeneration, and diameter irregularity of nerve. Peripheral nervous system (PNS destruction during systemic vasculitides should be considered, due to its frequency and early occurrence in vasculitis progression. The first line treatment of non systematic VPNs is corticosteroid agents, but these drugs might worsen the VPNs or systemic vasculitis.

  19. In vitro effects of ATG-Fresenius on immune cell adhesion.

    Science.gov (United States)

    Kanzler, I; Seitz-Merwald, I; Schleger, S; Kaczmarek, I; Kur, F; Beiras-Fernandez, A

    2013-06-01

    ATG-Fresenius, a purified rabbit polyclonal anti-human T-lymphocyte immunoglobulin is used for induction immunosuppression as well as prevention and treatment of acute rejection episodes among patients receiving solid organ transplants. The aim of this study was to investigate the in vitro activity of ATG-Fresenius upon immune cell adhesion, which may explain its activity to mitigate ischemia-reperfusion injury. Human vascular endothelial cells (HUVEC) and peripheral blood mononuclear cells (PBMCs) isolated from umbilical vein or peripheral blood were incubated 20 to 24 hours before analysis. HUVEC were incubated with 10 and 100 μg/mL ATG-Fresenius or reference polyclonal rabbit immunoglobulin G. Analysis of immune cell adhesion to endothelial cells was studied in cocultures of PBMCs and adherent HUVEC. Endothelial cell expression of adhesion molecules CD62E and CD54 was determined by flow cytometry. The numbers of T-, B- and natural killer cells attached to HUVEC were also determined by flow cytometry. Groups were compared using one-way analysis of variance. We showed that ATG-Fresenius binds to endothelial cells particularly activated ones expressing increased levels of E-selectin and ICAM-1. The increased binding of ATG-Fresenius to activated endothelial cells was consistent with its known binding to Intercellular Adhesion Molecule 1 (ICAM-1) and selectins. We also showed that ATG-Fresenius inhibited adhesion of prestimulated immune cells to activated endothelium. We demonstrated dose-dependent binding of ATG-Fresenius to activated endothelial cells. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Limited immune surveillance in lymphoid tissue by cytolytic CD4+ T cells during health and HIV disease

    Science.gov (United States)

    McLane, Laura M.; Steblyanko, Maria; Anikeeva, Nadia; Ablanedo-Terrazas, Yuria; Demers, Korey; Eller, Michael A.; Streeck, Hendrik; Jansson, Marianne; Sönnerborg, Anders; Canaday, David H.; Naji, Ali; Wherry, E. John; Robb, Merlin L.; Reyes-Teran, Gustavo; Sykulev, Yuri; Betts, Michael R.

    2018-01-01

    CD4+ T cells subsets have a wide range of important helper and regulatory functions in the immune system. Several studies have specifically suggested that circulating effector CD4+ T cells may play a direct role in control of HIV replication through cytolytic activity or autocrine β-chemokine production. However, it remains unclear whether effector CD4+ T cells expressing cytolytic molecules and β-chemokines are present within lymph nodes (LNs), a major site of HIV replication. Here, we report that expression of β-chemokines and cytolytic molecules are enriched within a CD4+ T cell population with high levels of the T-box transcription factors T-bet and eomesodermin (Eomes). This effector population is predominately found in peripheral blood and is limited in LNs regardless of HIV infection or treatment status. As a result, CD4+ T cells generally lack effector functions in LNs, including cytolytic capacity and IFNγ and β-chemokine expression, even in HIV elite controllers and during acute/early HIV infection. While we do find the presence of degranulating CD4+ T cells in LNs, these cells do not bear functional or transcriptional effector T cell properties and are inherently poor to form stable immunological synapses compared to their peripheral blood counterparts. We demonstrate that CD4+ T cell cytolytic function, phenotype, and programming in the peripheral blood is dissociated from those characteristics found in lymphoid tissues. Together, these data challenge our current models based on blood and suggest spatially and temporally dissociated mechanisms of viral control in lymphoid tissues. PMID:29652923

  1. Bovine response to lipoarabinomannan vaccination and challenge with Mycobacterium paratuberculosis

    Directory of Open Access Journals (Sweden)

    Ana Jolly

    2013-01-01

    Full Text Available This study aimed to evaluate the immune response in bovines following immunization with a mycobaterial Lipoarabinomannan extract (LAMe and the effect of Map challenge. LAMe vaccine induced specific antibody levels that diminished after the challenge and affected Map excretion at least for 100 days thereafter.

  2. Immunization with avian metapneumovirus harboring chicken Fc induces higher immune responses.

    Science.gov (United States)

    Paudel, Sarita; Easwaran, Maheswaran; Jang, Hyun; Jung, Ho-Kyoung; Kim, Joo-Hun; Shin, Hyun-Jin

    2016-07-15

    In this study, we evaluated the immune responses of avian metapneumovirus harboring chicken Fc molecule. Stable Vero cells expressing chicken Fc chimera on its surface (Vero-cFc) were established, and we confirmed that aMPV grown in Vero-cFc incorporated host derived chimera Fc into the aMPV virions. Immunization of chicken with aMPV-cFc induced higher level of antibodies and inflammatory cytokines; (Interferon (IFN)-γ and Interleukin (IL)-1β) compared to those of aMPV. The increased levels of antibodies and inflammatory cytokines in chicken immunized with aMPV-cFc were statistically significantly (p<0.05) to that of aMPV and control. The aMPV-cFc group also generated the highest neutralizing antibody response. After challenges, chickens immunized with aMPV-cFc showed much less pathological signs in nasal turbinates and trachea so that we could confirm aMPV-cFc induced higher protection than that of aMPV. The greater ability of aMPV harboring chicken Fc to that of aMPV presented it as a possible vaccine candidate. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Alternative adaptive immunity in invertebrates

    DEFF Research Database (Denmark)

    Kurtz, Joachim; Armitage, Sophie Alice Octavia

    2006-01-01

    Vertebrate adaptive immunity is characterized by challenge-specific long-term protection. This specific memory is achieved through the vast diversity of somatically rearranged immunological receptors such as antibodies. Whether or not invertebrates are capable of a comparable phenotypic plasticity...

  4. Increasing Hematopoietic Stem Cell Yield to Develop Mice with Human Immune Systems

    Directory of Open Access Journals (Sweden)

    Juan-Carlos Biancotti

    2013-01-01

    Full Text Available Hematopoietic stem cells (HSCs are unique in their capacity to give rise to all mature cells of the immune system. For years, HSC transplantation has been used for treatment of genetic and neoplastic diseases of the hematopoietic and immune systems. The sourcing of HSCs from human umbilical cord blood has salient advantages over isolation from mobilized peripheral blood. However, poor sample yield has prompted development of methodologies to expand HSCs ex vivo. Cytokines, trophic factors, and small molecules have been variously used to promote survival and proliferation of HSCs in culture, whilst strategies to lower the concentration of inhibitors in the culture media have recently been applied to promote HSC expansion. In this paper, we outline strategies to expand HSCs in vitro, and to improve engraftment and reconstitution of human immune systems in immunocompromised mice. To the extent that these “humanized” mice are representative of the endogenous human immune system, they will be invaluable tools for both basic science and translational medicine.

  5. Transcriptome profiling analysis on whole bodies of microbial challenged Eriocheir sinensis larvae for immune gene identification and SNP development.

    Directory of Open Access Journals (Sweden)

    Zhaoxia Cui

    Full Text Available To study crab immunogenetics of individuals, newly hatched Eriocheir sinensis larvae were stimulated with a mixture of three pathogen strains (Gram-positive bacteria Micrococcus luteus, Gram-negative bacteria Vibrio alginolyticus and fungi Pichia pastoris; 10(8 cfu·mL(-1. A total of 44,767,566 Illumina clean reads corresponding to 4.52 Gb nucleotides were generated and assembled into 100,252 unigenes (average length: 1,042 bp; range: 201-19,357 bp. 17,097 (26.09% of 65,535 non-redundant unigenes were annotated in NCBI non-redundant protein (Nr database. Moreover, 23,188 (35.38% unigenes were assigned to three Gene Ontology (GO categories, 15,071 (23.00% to twenty-six Clusters of orthologous Groups (COG and 8,574 (13.08% to six Kyoto Encyclopedia of Genes and Genomes (KEGG pathways, respectively. Numerous genes were further identified to be associated with multiple immune pathways, including Toll, immune deficiency (IMD, janus kinase (JAK-signal transducers and activators of transcription (STAT and mitogen-activated protein kinase (MAPK pathways. Some of them, such as tumor necrosis factor receptor associated factor 6 (TRAF6, fibroblast growth factor (FGF, protein-tyrosine phosphatase (PTP, JNK-interacting protein 1 (JIP1, were first identified in E. sinensis. TRAF6 was even first discovered in crabs. Additionally, 49,555 single nucleotide polymorphisms (SNPs were developed from over 13,309 unigenes. This is the first transcriptome report of whole bodies of E. sinensis larvae after immune challenge. Data generated here not only provide detail information to identify novel genes in genome reference-free E. sinensis, but also facilitate our understanding on host immunity and defense mechanism of the crab at whole transcriptome level.

  6. The placental immune milieu is characterized by a Th2- and anti-inflammatory transcription profile, regardless of maternal allergy, and associates with neonatal immunity.

    Science.gov (United States)

    Abelius, Martina S; Janefjord, Camilla; Ernerudh, Jan; Berg, Göran; Matthiesen, Leif; Duchén, Karel; Nilsson, Lennart J; Jenmalm, Maria C

    2015-05-01

    How maternal allergy affects the systemic and local immunological environment during pregnancy and the immune development of the offspring is unclear. Expression of 40 genes was quantified by PCR arrays in placenta, peripheral blood mononuclear cells (PBMC), and cord blood mononuclear cells (CBMC) from 7 allergic and 12 non-allergic women and their offspring. Placental gene expression was dominated by a Th2-/anti-inflammatory profile, irrespectively of maternal allergy, as compared to gene expression in PBMC. p35 expression in placenta correlated with fetal Tbx21 (ρ = -0.88, P pregnancy was partly associated with the offspring's gene expression, possibly indicating that the immunological milieu is important for fetal immune development. Maternal allergy was not associated with an enhanced Th2 immunity in placenta or PBMC, while a marked prenatal Th2 skewing, shown as increased CCL22 mRNA expression, might contribute to postnatal allergy development. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Vaccine-mediated immune responses to experimental pulmonary Cryptococcus gattii infection in mice.

    Directory of Open Access Journals (Sweden)

    Ashok K Chaturvedi

    Full Text Available Cryptococcus gattii is a fungal pathogen that can cause life-threatening respiratory and disseminated infections in immune-competent and immune-suppressed individuals. Currently, there are no standardized vaccines against cryptococcosis in humans, underlying an urgent need for effective therapies and/or vaccines. In this study, we evaluated the efficacy of intranasal immunization with C. gattii cell wall associated (CW and/or cytoplasmic (CP protein preparations to induce protection against experimental pulmonary C. gattii infection in mice. BALB/c mice immunized with C. gattii CW and/or CP protein preparations exhibited a significant reduction in pulmonary fungal burden and prolonged survival following pulmonary challenge with C. gattii. Protection was associated with significantly increased pro-inflammatory and Th1-type cytokine recall responses, in vitro and increased C. gattii-specific antibody production in immunized mice challenged with C. gattii. A number of immunodominant proteins were identified following immunoblot analysis of C. gattii CW and CP protein preparations using sera from immunized mice. Immunization with a combined CW and CP protein preparation resulted in an early increase in pulmonary T cell infiltrates following challenge with C. gattii. Overall, our studies show that C. gattii CW and CP protein preparations contain antigens that may be included in a subunit vaccine to induce prolonged protection against pulmonary C. gattii infection.

  8. Immunity to sporozoite-induced malaria infection in mice. I. The effect of immunization of T and B cell-deficient mice

    International Nuclear Information System (INIS)

    Chen, D.H.; Tigelaar, R.E.; Weinbaum, F.I.

    1977-01-01

    The cellular basis of immunity to sporozoites was investigated by examining the effect of immunization of T and B cell-deficient C57BL/6N x BALB/c AnN F 1 (BLCF 1 ) mice compared to immunocompetent controls. Immunization of T cell-deficient (ATX-BM-ATS) BLCF 1 mice with x-irradiated sporozoites did not result in the generation of protective immunity. The same immunization protocols protected all immunocompetent controls. In contrast, B cell-deficient (μ-suppressed) BLCF 1 mice were protected by immunization in the majority of cases. The absence of detectable serum circumsporozoite precipitins or sporozoite neutralizing activity in the μ-suppressed mice that resisted a sporozoite challenge suggests a minor role for these humoral factors in protection. These data demonstrate a preeminent role for T cells in the induction of protective immunity in BLCF 1 mice against a P. berghei sporozoite infection

  9. Optical cuff for optogenetic control of the peripheral nervous system

    Science.gov (United States)

    Michoud, Frédéric; Sottas, Loïc; Browne, Liam E.; Asboth, Léonie; Latremoliere, Alban; Sakuma, Miyuki; Courtine, Grégoire; Woolf, Clifford J.; Lacour, Stéphanie P.

    2018-02-01

    Objective. Nerves in the peripheral nervous system (PNS) contain axons with specific motor, somatosensory and autonomic functions. Optogenetics offers an efficient approach to selectively activate axons within the nerve. However, the heterogeneous nature of nerves and their tortuous route through the body create a challenging environment to reliably implant a light delivery interface. Approach. Here, we propose an optical peripheral nerve interface—an optocuff—, so that optogenetic modulation of peripheral nerves become possible in freely behaving mice. Main results. Using this optocuff, we demonstrate orderly recruitment of motor units with epineural optical stimulation of genetically targeted sciatic nerve axons, both in anaesthetized and in awake, freely behaving animals. Behavioural experiments and histology show the optocuff does not damage the nerve thus is suitable for long-term experiments. Significance. These results suggest that the soft optocuff might be a straightforward and efficient tool to support more extensive study of the PNS using optogenetics.

  10. Protection against avian metapneumovirus subtype C in turkeys immunized via the respiratory tract with inactivated virus.

    Science.gov (United States)

    Cha, Ra Mi; Khatri, Mahesh; Sharma, Jagdev M

    2011-01-10

    Avian metapneumovirus subtype C (aMPV/C) causes a severe upper respiratory tract (URT) infection in turkeys. Turkeys were inoculated oculonasally with inactivated aMPV/C adjuvanted with synthetic double-stranded RNA polyriboinosinic polyribocytidylic acid (Poly IC). Immunized turkeys had elevated numbers of mucosal IgA+ cells in the URT and increased levels of virus-specific IgG and IgA in the lachrymal fluid and IgG in the serum. After 7 or 21 days post immunization, turkeys were challenged oculonasally with pathogenic aMPV/C. Immunized groups were protected against respiratory lesions induced by the challenge virus. Further, the viral copy number of the challenge virus in the URT were significantly lower in the immunized turkeys than in the unimmunized turkeys (P<0.05). These results showed that inactivated aMPV/C administered by the respiratory route induced protective immunity against pathogenic virus challenge. Copyright © 2010 Elsevier Ltd. All rights reserved.

  11. Earthworm's immunity in the nanomaterial world: new room, future challenges

    DEFF Research Database (Denmark)

    Hayashi, Yuya; Engelmann, Péter

    2013-01-01

    of the immune responses to nanoparticles with references to other invertebrate species and vertebrate counterparts. We discuss the significant contribution of amoebocytes as nanoparticle scavengers and suggest a possibility of studying inter-cellular communications in coelomocytes. Implications from the leading...

  12. Antarctic isolation: immune and viral studies

    Science.gov (United States)

    Tingate, T. R.; Lugg, D. J.; Muller, H. K.; Stowe, R. P.; Pierson, D. L.

    1997-01-01

    Stressful environmental conditions are a major determinant of immune reactivity. This effect is pronounced in Australian National Antarctic Research Expedition populations exposed to prolonged periods of isolation in the Antarctic. Alterations of T cell function, including depression of cutaneous delayed-type hypersensitivity responses and a peak 48.9% reduction of T cell proliferation to the mitogen phytohaemagglutinin, were documented during a 9-month period of isolation. T cell dysfunction was mediated by changes within the peripheral blood mononuclear cell compartment, including a paradoxical atypical monocytosis associated with altered production of inflammatory cytokines. There was a striking reduction in the production by peripheral blood mononuclear cells of the predominant pro-inflammatory monokine TNF-alpha and changes were also detected in the production of IL-1, IL-2, IL-6, IL-1ra and IL-10. Prolonged Antarctic isolation is also associated with altered latent herpesvirus homeostasis, including increased herpesvirus shedding and expansion of the polyclonal latent Epstein-Barr virus-infected B cell population. These findings have important long-term health implications.

  13. Carbohydrate Mimetic Peptides Augment Carbohydrate-Reactive Immune Responses in the Absence of Immune Pathology

    International Nuclear Information System (INIS)

    Hennings, Leah; Artaud, Cecile; Jousheghany, Fariba; Monzavi-Karbassi, Behjatolah; Pashov, Anastas; Kieber-Emmons, Thomas

    2011-01-01

    Among the most challenging of clinical targets for cancer immunotherapy are Tumor Associated Carbohydrate Antigens (TACAs). To augment immune responses to TACA we are developing carbohydrate mimetic peptides (CMPs) that are sufficiently potent to activate broad-spectrum anti-tumor reactivity. However, the activation of immune responses against terminal mono- and disaccharide constituents of TACA raises concerns regarding the balance between “tumor destruction” and “tissue damage”, as mono- and disaccharides are also expressed on normal tissue. To support the development of CMPs for clinical trial testing, we demonstrate in preclinical safety assessment studies in mice that vaccination with CMPs can enhance responses to TACAs without mediating tissue damage to normal cells expressing TACA. BALB/c mice were immunized with CMPs that mimic TACAs reactive with Griffonia simplicifolia lectin 1 (GS-I), and tissue reactivity of serum antibodies were compared with the tissue staining profile of GS-I. Tissues from CMP immunized mice were analyzed using hematoxylin and eosin stain, and Luxol-fast blue staining for myelination. Western blots of membranes from murine mammary 4T1 cells, syngeneic with BALB/c mice, were also compared using GS-I, immunized serum antibodies, and naive serum antibodies. CMP immunization enhanced glycan reactivities with no evidence of pathological autoimmunity in any immunized mice demonstrating that tissue damage is not an inevitable consequence of TACA reactive responses

  14. Carbohydrate Mimetic Peptides Augment Carbohydrate-Reactive Immune Responses in the Absence of Immune Pathology

    Energy Technology Data Exchange (ETDEWEB)

    Hennings, Leah; Artaud, Cecile; Jousheghany, Fariba; Monzavi-Karbassi, Behjatolah; Pashov, Anastas; Kieber-Emmons, Thomas, E-mail: tke@uams.edu [Winthrop P. Rockefeller Cancer Institute and Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States)

    2011-11-11

    Among the most challenging of clinical targets for cancer immunotherapy are Tumor Associated Carbohydrate Antigens (TACAs). To augment immune responses to TACA we are developing carbohydrate mimetic peptides (CMPs) that are sufficiently potent to activate broad-spectrum anti-tumor reactivity. However, the activation of immune responses against terminal mono- and disaccharide constituents of TACA raises concerns regarding the balance between “tumor destruction” and “tissue damage”, as mono- and disaccharides are also expressed on normal tissue. To support the development of CMPs for clinical trial testing, we demonstrate in preclinical safety assessment studies in mice that vaccination with CMPs can enhance responses to TACAs without mediating tissue damage to normal cells expressing TACA. BALB/c mice were immunized with CMPs that mimic TACAs reactive with Griffonia simplicifolia lectin 1 (GS-I), and tissue reactivity of serum antibodies were compared with the tissue staining profile of GS-I. Tissues from CMP immunized mice were analyzed using hematoxylin and eosin stain, and Luxol-fast blue staining for myelination. Western blots of membranes from murine mammary 4T1 cells, syngeneic with BALB/c mice, were also compared using GS-I, immunized serum antibodies, and naive serum antibodies. CMP immunization enhanced glycan reactivities with no evidence of pathological autoimmunity in any immunized mice demonstrating that tissue damage is not an inevitable consequence of TACA reactive responses.

  15. Genotype I of Japanese Encephalitis Virus Virus-like Particles Elicit Sterilizing Immunity against Genotype I and III Viral Challenge in Swine.

    Science.gov (United States)

    Fan, Yi-Chin; Chen, Jo-Mei; Lin, Jen-Wei; Chen, Yi-Ying; Wu, Guan-Hong; Su, Kuan-Hsuan; Chiou, Ming-Tang; Wu, Shang-Rung; Yin, Ji-Hang; Liao, Jiunn-Wang; Chang, Gwong-Jen J; Chiou, Shyan-Song

    2018-05-10

    Swine are a critical amplifying host involved in human Japanese encephalitis (JE) outbreaks. Cross-genotypic immunogenicity and sterile protection are important for the current genotype III (GIII) virus-derived vaccines in swine, especially now that emerging genotype I (GI) JE virus (JEV) has replaced GIII virus as the dominant strain. Herein, we aimed to develop a system to generate GI JEV virus-like particles (VLPs) and evaluate the immunogenicity and protection of the GI vaccine candidate in mice and specific pathogen-free swine. A CHO-heparan sulfate-deficient (CHO-HS(-)) cell clone, named 51-10 clone, stably expressing GI-JEV VLP was selected and continually secreted GI VLPs without signs of cell fusion. 51-10 VLPs formed a homogeneously empty-particle morphology and exhibited similar antigenic activity as GI virus. GI VLP-immunized mice showed balanced cross-neutralizing antibody titers against GI to GIV viruses (50% focus-reduction micro-neutralization assay titers 71 to 240) as well as potent protection against GI or GIII virus infection. GI VLP-immunized swine challenged with GI or GIII viruses showed no fever, viremia, or viral RNA in tonsils, lymph nodes, and brains as compared with phosphate buffered saline-immunized swine. We thus conclude GI VLPs can provide sterile protection against GI and GIII viruses in swine.

  16. Imaging findings and therapeutic alternatives for peripheral vascular malformations

    International Nuclear Information System (INIS)

    Monsignore, Lucas Moretti; Nakiri, Guilherme Seizem; Santos, Daniela dos; Abud, Thiago Giansante; Abud, Daniel Giansante

    2010-01-01

    Peripheral vascular malformations represent a spectrum of lesions that appear through the lifetime and can be found in the whole body. Such lesions are uncommon and are frequently confounded with infantile hemangioma, a common benign neoplastic lesion. In the presence of such lesions, the correlation between the clinical and radiological findings is extremely important to achieve a correct diagnosis, which will guide the best therapeutic approach. The most recent classifications for peripheral vascular malformations are based on the blood flow (low or high) and on the main vascular components (arterial, capillary, lymphatic or venous). Peripheral vascular malformations represent a diagnostic and therapeutic challenge, and complementary methods such as computed tomography, Doppler ultrasonography and magnetic resonance imaging, in association with clinical findings can provide information regarding blood flow characteristics and lesions extent. Arteriography and venography confirm the diagnosis, evaluate the lesions extent and guide the therapeutic decision making. Generally, low flow vascular malformations are percutaneously treated with sclerosing agents injection, while in high flow lesions the approach is endovascular, with permanent liquid or solid embolization agents. (author)

  17. Phenotypic, ultra-structural, and functional characterization of bovine peripheral blood dendritic cell subsets.

    Directory of Open Access Journals (Sweden)

    Janet J Sei

    Full Text Available Dendritic cells (DC are multi-functional cells that bridge the gap between innate and adaptive immune systems. In bovine, significant information is lacking on the precise identity and role of peripheral blood DC subsets. In this study, we identify and characterize bovine peripheral blood DC subsets directly ex vivo, without further in vitro manipulation. Multi-color flow cytometric analysis revealed that three DC subsets could be identified. Bovine plasmacytoid DC were phenotypically identified by a unique pattern of cell surface protein expression including CD4, exhibited an extensive endoplasmic reticulum and Golgi apparatus, efficiently internalized and degraded exogenous antigen, and were the only peripheral blood cells specialized in the production of type I IFN following activation with Toll-like receptor (TLR agonists. Conventional DC were identified by expression of a different pattern of cell surface proteins including CD11c, MHC class II, and CD80, among others, the display of extensive dendritic protrusions on their plasma membrane, expression of very high levels of MHC class II and co-stimulatory molecules, efficient internalization and degradation of exogenous antigen, and ready production of detectable levels of TNF-alpha in response to TLR activation. Our investigations also revealed a third novel DC subset that may be a precursor of conventional DC that were MHC class II+ and CD11c-. These cells exhibited a smooth plasma membrane with a rounded nucleus, produced TNF-alpha in response to TLR-activation (albeit lower than CD11c+ DC, and were the least efficient in internalization/degradation of exogenous antigen. These studies define three bovine blood DC subsets with distinct phenotypic and functional characteristics which can be analyzed during immune responses to pathogens and vaccinations of cattle.

  18. Immune mechanisms in Ehrlich ascites tumor growth in mice

    International Nuclear Information System (INIS)

    Marusic, M.

    1979-01-01

    Normal mice immunised with irradiated Ehrlich ascites tumor (EAT) cells rejected EAT challenge given 2 weeks later but T-cell-deficient thymectomised lethally irradiated, and bone-marrow-reconstituted (TIR) mice succumbed. However, when TIR mice were injected i.v. with thymus, lymph node, or spleen cells from normalsyngetic donors immediately following i.p. injection of irradiated EAT cells, they rejected the subsequent tumor challenge. This induction of immunity in TIR mice was shown to be T-cell dependent. Spleen cells from EAT- bearing mice given immediately after irradiated tumor cells were also able to promote rejection of EAT challenge in TIR mice. Spleen cells from EAT-immune mice inhibited EAT growth when admixed with tumor cells prior to i.p. injection into normal recipients, but had no effect on progressive tumor growth when given i.v. immediately after i.p. tumor injection. Immune serum inhibited i.p. EAT growth when given either i.p. or i.v. Whereas inhibition of EAT growth by admixed spleen cells was shown to be T-cell independent. The data indicate that T lymphocytes are required only in the induction phase of the immune reponse of mice against EAT, while the efferent phase of the response is accomplished by serum antibodies, perhaps through an interaction with host macrophages. (author)

  19. Impact of carbon nanotubes and graphene on immune cells

    Science.gov (United States)

    2014-01-01

    It has been recently proposed that nanomaterials, alone or in concert with their specific biomolecular conjugates, can be used to directly modulate the immune system, therefore offering a new tool for the enhancement of immune-based therapies against infectious disease and cancer. Here, we revised the publications on the impact of functionalized carbon nanotubes (f-CNTs), graphene and carbon nanohorns on immune cells. Whereas f-CNTs are the nanomaterial most widely investigated, we noticed a progressive increase of studies focusing on graphene in the last couple of years. The majority of the works (56%) have been carried out on macrophages, following by lymphocytes (30% of the studies). In the case of lymphocytes, T cells were the most investigated (22%) followed by monocytes and dendritic cells (7%), mixed cell populations (peripheral blood mononuclear cells, 6%), and B and natural killer (NK) cells (1%). Most of the studies focused on toxicity and biocompatibility, while mechanistic insights on the effect of carbon nanotubes on immune cells are generally lacking. Only very recently high-throughput gene-expression analyses have shed new lights on unrecognized effects of carbon nanomaterials on the immune system. These investigations have demonstrated that some f-CNTs can directly elicitate specific inflammatory pathways. The interaction of graphene with the immune system is still at a very early stage of investigation. This comprehensive state of the art on biocompatible f-CNTs and graphene on immune cells provides a useful compass to guide future researches on immunological applications of carbon nanomaterials in medicine. PMID:24885781

  20. Impact of carbon nanotubes and graphene on immune cells.

    Science.gov (United States)

    Orecchioni, Marco; Bedognetti, Davide; Sgarrella, Francesco; Marincola, Francesco M; Bianco, Alberto; Delogu, Lucia Gemma

    2014-05-21

    It has been recently proposed that nanomaterials, alone or in concert with their specific biomolecular conjugates, can be used to directly modulate the immune system, therefore offering a new tool for the enhancement of immune-based therapies against infectious disease and cancer. Here, we revised the publications on the impact of functionalized carbon nanotubes (f-CNTs), graphene and carbon nanohorns on immune cells. Whereas f-CNTs are the nanomaterial most widely investigated, we noticed a progressive increase of studies focusing on graphene in the last couple of years. The majority of the works (56%) have been carried out on macrophages, following by lymphocytes (30% of the studies). In the case of lymphocytes, T cells were the most investigated (22%) followed by monocytes and dendritic cells (7%), mixed cell populations (peripheral blood mononuclear cells, 6%), and B and natural killer (NK) cells (1%). Most of the studies focused on toxicity and biocompatibility, while mechanistic insights on the effect of carbon nanotubes on immune cells are generally lacking. Only very recently high-throughput gene-expression analyses have shed new lights on unrecognized effects of carbon nanomaterials on the immune system. These investigations have demonstrated that some f-CNTs can directly elicitate specific inflammatory pathways. The interaction of graphene with the immune system is still at a very early stage of investigation. This comprehensive state of the art on biocompatible f-CNTs and graphene on immune cells provides a useful compass to guide future researches on immunological applications of carbon nanomaterials in medicine.

  1. Regulation of peripheral inflammation by spinal p38 MAP kinase in rats.

    Directory of Open Access Journals (Sweden)

    David L Boyle

    2006-09-01

    Full Text Available Somatic afferent input to the spinal cord from a peripheral inflammatory site can modulate the peripheral response. However, the intracellular signaling mechanisms in the spinal cord that regulate this linkage have not been defined. Previous studies suggest spinal cord p38 mitogen-activated protein (MAP kinase and cytokines participate in nociceptive behavior. We therefore determined whether these pathways also regulate peripheral inflammation in rat adjuvant arthritis, which is a model of rheumatoid arthritis.Selective blockade of spinal cord p38 MAP kinase by administering the p38 inhibitor SB203580 via intrathecal (IT catheters in rats with adjuvant arthritis markedly suppressed paw swelling, inhibited synovial inflammation, and decreased radiographic evidence of joint destruction. The same dose of SB203580 delivered systemically had no effect, indicating that the effect was mediated by local concentrations in the neural compartment. Evaluation of articular gene expression by quantitative real-time PCR showed that spinal p38 inhibition markedly decreased synovial interleukin-1 and -6 and matrix metalloproteinase (MMP3 gene expression. Activation of p38 required tumor necrosis factor alpha (TNFalpha in the nervous system because IT etanercept (a TNF inhibitor given during adjuvant arthritis blocked spinal p38 phosphorylation and reduced clinical signs of adjuvant arthritis.These data suggest that peripheral inflammation is sensed by the central nervous system (CNS, which subsequently activates stress-induced kinases in the spinal cord via a TNFalpha-dependent mechanism. Intracellular p38 MAP kinase signaling processes this information and profoundly modulates somatic inflammatory responses. Characterization of this mechanism could have clinical and basic research implications by supporting development of new treatments for arthritis and clarifying how the CNS regulates peripheral immune responses.

  2. Decreased Numbers of CD57+CD3- Cells Identify Potential Innate Immune Differences in Patients with Autism Spectrum Disorder.

    Science.gov (United States)

    Siniscalco, Dario; Mijatovic, Tatjana; Bosmans, Eugene; Cirillo, Alessandra; Kruzliak, Peter; Lombardi, Vincent C; De Meirleir, Kenny; Antonucci, Nicola

    2016-01-01

    Autism spectrum disorders (ASD) are complex, and severe heterogeneous neurodevelopmental pathologies with accepted but complex immune system abnormalities. Additional knowledge regarding potential immune dysfunctions may provide a greater understanding of this malady. The aim of this study was to evaluate the CD57(+)CD3(-) mature lymphocyte subpopulation of natural killer cells as a marker of immune dysfunction in ASD. Three-color flow cytometry-based analysis of fresh peripheral blood samples from children with autism was utilized to measure CD57(+)CD3(-) lymphocytes. A reduction of CD57(+)CD3(-) lymphocyte count was recorded in a significant number of patients with autism. We demonstrated that the number of peripheral CD57(+)CD3(-) cells in children with autism often falls below the clinically accepted normal range. This implies that a defect in the counter-regulatory functions necessary for balancing pro-inflammatory cytokines exists, thus opening the way to chronic inflammatory conditions associated with ASD. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  3. Maternal immunization increases nestling energy expenditure, immune function, and fledging success in a passerine bird

    Directory of Open Access Journals (Sweden)

    Gary Burness

    2018-04-01

    Full Text Available Female birds transfer maternally derived antibodies (matAb to their nestlings, via the egg yolk. These antibodies are thought to provide passive protection, and allow nestlings to avoid the costs associated with mounting an innate immune response. To test whether there is an energetic benefit to nestlings from receiving matAb, we challenged adult female tree swallows (Tachycineta bicolor prior to clutch initiation with either lipopolysaccharide (LPS or saline (Control. Following hatching, one half of each female's nestlings were immunized on day 8 post-hatch with LPS or saline, and the 4-h post-immunization nestling metabolic rate (MR was measured. There was no difference in either LPS-reactive antibodies or total Ig levels between offspring of immunized and non-immunized mothers on day 6 or 14 post-hatch, possibly reflecting a relatively short half-life of matAbs in altricial birds. Additionally, we found no evidence that nestlings from LPS-immunized mothers could avoid the growth suppression that may result from activation of an inflammatory response. Unexpectedly, we found that control nestlings from LPS mothers had higher resting MR than control nestlings of control mothers. We attribute the increased MR to the costs associated with a general non-specific enhancement of immune function in nestlings from LPS-immunized mothers. Consistent with enhanced immune function, nestlings of immunized mothers had a more robust inflammatory response to phytohaemagglutinin and higher fledging success. Our results suggest that maternal antigen exposure pre-laying can result in increased fitness for both mothers and offspring, depending on food availability.

  4. ZFAT plays critical roles in peripheral T cell homeostasis and its T cell receptor-mediated response

    International Nuclear Information System (INIS)

    Doi, Keiko; Fujimoto, Takahiro; Okamura, Tadashi; Ogawa, Masahiro; Tanaka, Yoko; Mototani, Yasumasa; Goto, Motohito; Ota, Takeharu; Matsuzaki, Hiroshi; Kuroki, Masahide; Tsunoda, Toshiyuki; Sasazuki, Takehiko; Shirasawa, Senji

    2012-01-01

    Highlights: ► We generated Cd4-Cre-mediated T cell-specific Zfat-deficient mice. ► Zfat-deficiency leads to reduction in the number of the peripheral T cells. ► Impaired T cell receptor-mediated response in Zfat-deficient peripheral T cells. ► Decreased expression of IL-7Rα, IL-2Rα and IL-2 in Zfat-deficient peripheral T cells. ► Zfat plays critical roles in peripheral T cell homeostasis. -- Abstract: ZFAT, originally identified as a candidate susceptibility gene for autoimmune thyroid disease, has been reported to be involved in apoptosis, development and primitive hematopoiesis. Zfat is highly expressed in T- and B-cells in the lymphoid tissues, however, its physiological function in the immune system remains totally unknown. Here, we generated the T cell-specific Zfat-deficient mice and demonstrated that Zfat-deficiency leads to a remarkable reduction in the number of the peripheral T cells. Intriguingly, a reduced expression of IL-7Rα and the impaired responsiveness to IL-7 for the survival were observed in the Zfat-deficient T cells. Furthermore, a severe defect in proliferation and increased apoptosis in the Zfat-deficient T cells following T cell receptor (TCR) stimulation was observed with a reduced IL-2Rα expression as well as a reduced IL-2 production. Thus, our findings reveal that Zfat is a critical regulator in peripheral T cell homeostasis and its TCR-mediated response.

  5. T Cell-Mediated Immunity towards Yellow Fever Virus and Useful Animal Models

    Science.gov (United States)

    Watson, Alan M.; Klimstra, William B.

    2017-01-01

    The 17D line of yellow fever virus vaccines is among the most effective vaccines ever created. The humoral and cellular immunity elicited by 17D has been well characterized in humans. Neutralizing antibodies have long been known to provide protection against challenge with a wild-type virus. However, a well characterized T cell immune response that is robust, long-lived and polyfunctional is also elicited by 17D. It remains unclear whether this arm of immunity is protective following challenge with a wild-type virus. Here we introduce the 17D line of yellow fever virus vaccines, describe the current state of knowledge regarding the immunity directed towards the vaccines in humans and conclude with a discussion of animal models that are useful for evaluating T cell-mediated immune protection to yellow fever virus. PMID:28398253

  6. Peripherally Generated Foxp3+ Regulatory T Cells Mediate the Immunomodulatory Effects of IVIg in Allergic Airways Disease.

    Science.gov (United States)

    Massoud, Amir H; Kaufman, Gabriel N; Xue, Di; Béland, Marianne; Dembele, Marieme; Piccirillo, Ciriaco A; Mourad, Walid; Mazer, Bruce D

    2017-04-01

    IVIg is widely used as an immunomodulatory therapy. We have recently demonstrated that IVIg protects against airway hyperresponsiveness (AHR) and inflammation in mouse models of allergic airways disease (AAD), associated with induction of Foxp3 + regulatory T cells (Treg). Using mice carrying a DTR/EGFP transgene under the control of the Foxp3 promoter (DEREG mice), we demonstrate in this study that IVIg generates a de novo population of peripheral Treg (pTreg) in the absence of endogenous Treg. IVIg-generated pTreg were sufficient for inhibition of OVA-induced AHR in an Ag-driven murine model of AAD. In the absence of endogenous Treg, IVIg failed to confer protection against AHR and airway inflammation. Adoptive transfer of purified IVIg-generated pTreg prior to Ag challenge effectively prevented airway inflammation and AHR in an Ag-specific manner. Microarray gene expression profiling of IVIg-generated pTreg revealed upregulation of genes associated with cell cycle, chromatin, cytoskeleton/motility, immunity, and apoptosis. These data demonstrate the importance of Treg in regulating AAD and show that IVIg-generated pTreg are necessary and sufficient for inhibition of allergen-induced AAD. The ability of IVIg to generate pure populations of highly Ag-specific pTreg represents a new avenue to study pTreg, the cross-talk between humoral and cellular immunity, and regulation of the inflammatory response to Ags. Copyright © 2017 by The American Association of Immunologists, Inc.

  7. Proliferation induced by Plasmodium falciparum antigen and interleukin-2 production by lymphocytes isolated from malaria-immune individuals

    DEFF Research Database (Denmark)

    Theander, T G; Bygbjerg, I C; Jepsen, S

    1986-01-01

    Affinity-purified Plasmodium falciparum soluble antigens (SPAg) isolated from in vitro cultures of the parasite were shown to be relatively free of nonspecific polyclonal activators. To determine the presence of lymphocytes with specificity against SPAg in the peripheral blood of malaria-immune i......Affinity-purified Plasmodium falciparum soluble antigens (SPAg) isolated from in vitro cultures of the parasite were shown to be relatively free of nonspecific polyclonal activators. To determine the presence of lymphocytes with specificity against SPAg in the peripheral blood of malaria...

  8. Dietary Animal Plasma Proteins Improve the Intestinal Immune Response in Senescent Mice

    Directory of Open Access Journals (Sweden)

    Lluïsa Miró

    2017-12-01

    Full Text Available Increased life expectancy has promoted research on healthy aging. Aging is accompanied by increased non-specific immune activation (inflammaging which favors the appearance of several disorders. Here, we study whether dietary supplementation with spray-dried animal plasma (SDP, which has been shown to reduce the activation of gut-associated lymphoid tissue (GALT in rodents challenged by S. aureus enterotoxin B (SEB, and can also prevent the effects of aging on immune system homeostasis. We first characterized GALT in a mouse model of accelerated senescence (SAMP8 at different ages (compared to mice resistant to accelerated senescence; SAMR1. Second, we analyzed the SDP effects on GALT response to an SEB challenge in SAMP8 mice. In GALT characterization, aging increased the cell number and the percentage of activated Th lymphocytes in mesenteric lymph nodes and Peyer’s patches (all, p < 0.05, as well as the expression of IL-6 and TNF-α in intestinal mucosa (both, p < 0.05. With respect to GALT response to the SEB challenge, young mice showed increased expression of intestinal IL-6 and TNF-α, as well as lymphocyte recruitment and activation (all, p < 0.05. However, the immune response of senescent mice to the SEB challenge was weak, since SEB did not change cell recruitment or the percentage of activated Th lymphocytes. Mice supplemented with SDP showed improved capacity to respond to the SEB challenge, similar to the response of the young mice. These results indicate that senescent mice have an impaired mucosal immune response characterized by unspecific GALT activation and a weak specific immune response. SDP supplementation reduces non-specific basal immune activation, allowing for the generation of specific responses.

  9. Immune response of flounder (Paralichthys olivaceus) was associated with the concentration of inactivated Edwardsiella tarda and immersion time.

    Science.gov (United States)

    Du, Yang; Tang, Xiaoqian; Sheng, Xiuzhen; Xing, Jing; Zhan, Wenbin

    2015-09-15

    In the optimization of immersion strategy, vaccine concentration and immersion time are two key factors needed to be considered, which largely determined the immune efficacy. In this work, the healthy flounder were vaccinated in formalin-killed Edwardsiella tarda at four concentrations (10(6), 10(7), 10(8), 10(9) CFU ml(-1)) for three immersion times (30, 60, 90 min), respectively. At the 6th week post vaccination, the flounders were challenged with live E. tarda, and the relative percent survival (RPS) of flounder in 10(9)-30, 10(8)-60, 10(8)-90 and 10(7)-90 min groups were 70%, 78%, 74% and 65%, respectively, which were much higher than the other vaccination groups. Meanwhile, the sIg(+) cells in the leucocytes of peripheral blood (PBL), spleen (SL), head kidney (HKL) were monitored by flow cytometry, and the specific sera and mucosal antibodies were measured by indirect ELISA for 6 weeks. The results showed that the proportions of sIg(+) cells in PBL, SL and HKL of vaccinated fish were significantly higher than the untreated fish since the 2nd week (P0.05). These results demonstrated that the higher RPS was closely associated with stronger immune response, and immersion with formalin-inactivated E. tarda under 10(8) CFU ml(-1) for 60 min induced the highest immune response of flounder against E. tarda bacterin, which might be applied for the control of edwardsiellosis in flounder. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Expression features of follicular helper T cells in peripheral blood in patients with chronic hepatitis B

    Directory of Open Access Journals (Sweden)

    WANG Yan

    2018-01-01

    Full Text Available Objective To investigate the expression features of follicular helper T (Tfh cells in peripheral blood in patients with chronic hepatitis B (CHB. Methods A total of 53 CHB patients who were admitted to Department of Hepatology in Hospital of Traditional Chinese Medicine Affiliated to Xinjiang Medical University from March 2016 to March 2017 were enrolled. Fasting venous blood samples were collected in the morning, and flow cytometry was used to measure Tfh and its subsets in peripheral blood. A total of 48 healthy individuals were enrolled as controls. The independent samples t-test was used for comparison of normally distributed continuous data between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the LSD-t test was used for further comparison between any two groups. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between multiple groups. The chi-square test or Fisher′s exact test was used for comparison of categorical data between groups. A Pearson correlation analysis was performed to investigate correlation. Results The CHB group had significant higher percentages of CD4+ ICOS+, CD4+ CXCR5+, and CD4+ ICOS+ CXCR5+ Tfh cells than the control group (Z=-4.319, P<0.001; t=3.742, P<0.001; t=15.948, P<0.001. There were no significant differences in the percentages of CD4+ ICOS+, CD4+ CXCR5+, and CD4+ ICOS+ CXCR5+ Tfh cells between the CHB patients with different immune stages, i.e., low-level replication, immune tolerance, and immune clearance (all P>0.05. CD4+ ICOS+ CXCR5+ was not correlated with HBsAg quantitation or HBV DNA. Conclusion Tfh cells are involved in the immune response mediated by hepatitis B virus, and they exert an anti-HBV effect by regulating humoral immune response.

  11. Tumors of peripheral nerves; Tumoren der peripheren Nerven

    Energy Technology Data Exchange (ETDEWEB)

    Ho, Michael [Universitaetsklinikum Zuerich, Institut fuer Diagnostische Radiologie, Zuerich (Switzerland); Lutz, Amelie M. [Stanford University School of Medicine, Department of Radiology, Stanford, CA (United States)

    2017-03-15

    Differentiation between malignant and benign tumors of peripheral nerves in the early stages is challenging; however, due to the unfavorable prognosis of malignant tumors early identification is required. To show the possibilities for detection, differential diagnosis and clinical management of peripheral nerve tumors by imaging appearance in magnetic resonance (MR) neurography. Review of current literature available in PubMed and MEDLINE, supplemented by the authors' own observations in clinical practice. Although not pathognomonic, several imaging features have been reported for a differentiation between distinct peripheral nerve tumors. The use of MR neurography enables detection and initial differential diagnosis in tumors of peripheral nerves. Furthermore, it plays an important role in clinical follow-up, targeted biopsy and surgical planning. (orig.) [German] Die Unterscheidung zwischen malignen und benignen Tumoren der peripheren Nerven ist im initialen Stadium schwierig. Die Frueherkennung der malignen Tumoren ist aufgrund ihrer unguenstigen Prognose jedoch wichtig. Moeglichkeiten der MR-Neurographie zur Detektion, Artdiagnostik und klinischem Management von Tumoren der peripheren Nerven anhand bildmorphologischer Charakteristika. Zusammenschau der Studienlage mittels PubMed- bzw. MEDLINE-Recherche. Zusaetzlich Darlegung teils unveroeffentlichter Erkenntnisse aus der eigenen klinischen Beobachtung. Wenn auch nicht pathognomonisch, existieren verschiedene Bildgebungszeichen zur moeglichen Unterscheidung verschiedener Tumoren der peripheren Nerven. Die MR-Neurographie ist ein geeignetes bildgebendes Verfahren zur Detektion und ersten Differenzialdiagnose von Tumoren der peripheren Nerven. Zudem kommt ihr besondere Bedeutung bei der Verlaufskontrolle, der gezielten Biopsie und der operativen Planung zu. (orig.)

  12. Flow cytometric analysis of peripheral blood and tumor-infiltrating regulatory T cells in dogs with oral malignant melanoma.

    Science.gov (United States)

    Tominaga, Makiko; Horiuchi, Yutaka; Ichikawa, Mika; Yamashita, Masao; Okano, Kumiko; Jikumaru, Yuri; Nariai, Yoko; Kadosawa, Tsuyoshi

    2010-05-01

    It is well known that tumor-infiltrating lymphocytes (TILs) and peripheral blood lymphocytes (PBLs) from patients with advanced-stage cancer have a poor immune response. Regulatory T cells (Tregs), characterized by the expression of a cluster of differentiation 4 and intracellular FoxP3 markers, can inhibit antitumor immunoresponse. In the present study, the prevalence of Tregs in peripheral blood and tumor tissue from dogs with oral malignant melanoma was evaluated by triple-color flow cytometry. The percentage of Tregs in the peripheral blood of the dogs with malignancy was significantly increased compared with healthy control dogs, and the percentage of Tregs within tumors was significantly increased compared with Tregs in peripheral blood of dogs with oral malignant melanoma. This finding suggests that the presence of tumor cells induced either local proliferation or selective migration of Tregs to tumor-infiltrated sites. A better understanding of the underlying mechanisms of Treg regulation in patients with cancer may lead to an effective anticancer immunotherapy against canine malignant melanoma and possibly other tumors.

  13. Costs of mounting an immune response during pregnancy in a lizard.

    Science.gov (United States)

    Meylan, Sandrine; Richard, Murielle; Bauer, Sophie; Haussy, Claudy; Miles, Donald

    2013-01-01

    Immune defenses are of great benefit to hosts, but reducing the impact of infection by mounting an immune response also entails costs. However, the physiological mechanisms that generate the costs of an immune response remain poorly understood. Moreover, the majority of studies investigating the consequences of an immune challenge in vertebrates have been conducted on mammals and birds. The aim of this study is to investigate the physiological costs of mounting an immune response during gestation in an ectothermic species. Indeed, because ectothermic species are unable to internally regulate their body temperature, the apportionment of resources to homeostatic activities in ectothermic species can differ from that in endothermic species. We conducted this study on the common lizard Zootoca vivipara. We investigated the costs of mounting an immune response by injecting females with sheep red blood cells and quantified the consequences to reproductive performance (litter mass and success) and physiological performance (standard metabolic rate, endurance, and phytohemagglutinin response). In addition, we measured basking behavior. Our analyses revealed that mounting an immune response affected litter mass, physiological performance, and basking behavior. Moreover, we demonstrated that the modulation of an immune challenge is impacted by intrinsic factors, such as body size and condition.

  14. Flagella-induced immunity against experimental cholera in adult rabbits.

    Science.gov (United States)

    Yancey, R J; Willis, D L; Berry, L J

    1979-07-01

    The adult rabbit ligated ileal loop model was used to evaluate the prophylactic potential of a crude flagellar (CF) vaccine produced from the classical. Inaba strain CA401. A greater than 1,000-fold increase in the challenge inoculum was required to induce an intestinal fluid response in actively immunized adult rabbits equivalent to that produced in unimmunized animals. Similar protection was afforded against challenge with classical and El Tor biotypes of both Inaba and Ogawa serotypes. Highly virulent 35S-labeled vibrios were inhibited in their ability to associated with the intestinal mucosa of CF-immunized rabbits. The protection conferred by CF immunization was found to be superior to that of a commercial bivalent vaccine and also to that of glutaraldehyde-treated cholera toxoid. The critical immunogenic component of CF appears to be a flagella-derived protein. The immunogenicity of CF was destroyed by heat treatment, and absorption of CF-immune serum with aflagellated mutant vibrios did not diminish its ability to confer a high level of passive protection. The intestinal protection of CF-immunized rabbits was completely reversed by the introduction of both goat anti-rabbit immunoglobulins A and G, but by neither alone.

  15. Prospects, achievements, challenges and opportunities for scaling-up malaria chemoprevention in pregnancy in Tanzania: the perspective of national level officers

    DEFF Research Database (Denmark)

    Mubyazi, Godfrey; Bygbjerg, Ib; Magnussen, Pascal

    2008-01-01

    skills of most HWs and their poor motivation. Other problems were unreliable supply of free SP at private clinics, clean and safe water shortage at many government ANC clinics limiting direct observation treatment and occasionally pregnant women asked to pay for ANC services. Finally, supervision......Objectives: To describe the prospects, achievements, challenges and opportunities for implementing intermittent preventive treatment for malaria in pregnancy (IPTp) in Tanzania in light of national antenatal care (ANC) guidelines and ability of service providers to comply with them. Methods: In...... of peripheral health facilities has been inadequate and national guidelines on district budgeting for health services have been inflexible. IPTp coverage is generally low partly because IPTp is not systematically enforced like programmes on immunization, tuberculosis, leprosy and other infectious diseases...

  16. Identification of myeloid derived suppressor cells in the peripheral blood of tumor bearing dogs

    Directory of Open Access Journals (Sweden)

    Sherger Matthew

    2012-10-01

    Full Text Available Abstract Background Myeloid derived suppressor cells (MDSCs are a recently described population of immune cells that significantly contribute to the immunosuppression seen in cancer patients. MDSCs are one of the most important factors that limit the efficacy of cancer immunotherapy (e.g. cancer vaccines and MDSC levels are increased in cancer in multiple species. Identifying and targeting MDSCs is actively being investigated in the field of human oncology and is increasingly being investigated in veterinary oncology. The treatment of canine cancer not only benefits dogs, but is being used for translational studies evaluating and modifcying candidate therapies for use in humans. Thus, it is necessary to understand the immune alterations seen in canine cancer patients which, to date, have been relatively limited. This study investigates the use of commercially available canine antibodies to detect an immunosuppressive (CD11blow/CADO48low cell population that is increased in the peripheral blood of tumor-bearing dogs. Results Commercially available canine antibodies CD11b and CADO48A were used to evaluate white blood cells from the peripheral blood cells of forty healthy control dogs and forty untreated, tumor-bearing dogs. Tumor-bearing dogs had a statistically significant increase in CD11blow/CADO48Alow cells (7.9% as compared to the control dogs (3.6%. Additionally, sorted CD11blow/CADO48Alow generated in vitro suppressed the proliferation of canine lymphocytes. Conclusions The purpose of this study was aimed at identifying potential canine specific markers for identifying MDSCs in the peripheral blood circulation of dogs. This study demonstrates an increase in a unique CD11blow/CADO48Alow cell population in tumor-bearing dogs. This immunophenotype is consistent with described phenotypes of MDSCs in other species (i.e. mice and utilizes commercially available canine-specific antibodies. Importantly, CD11blow/CADO48Alow from a tumor environment

  17. Peripheral reactions

    International Nuclear Information System (INIS)

    Greiner, D.

    1978-01-01

    Peripheral collisions, that is, collisions involving a small amount of overlap of nuclear matter, are discussed including inclusive interactions, the magnitude of the peripheral cross section, fragmentation, a compilation of experiments and available data, limiting fragmentation, factorization, some models, fragment momentum distributions, and future research directions

  18. Growth versus immunity--a redirection of the cell cycle?

    Science.gov (United States)

    Eichmann, Ruth; Schäfer, Patrick

    2015-08-01

    Diseases caused by plant pathogens significantly reduce growth and yield in agricultural crop production. Raising immunity in crops is therefore a major aim in breeding programs. However, efforts to enhance immunity are challenged by the occurrence of growth inhibition triggered by immunity that can be as detrimental as diseases. In this review, we will propose molecular models to explain the inhibitory growth-immunity crosstalk. We will briefly discuss why the resource reallocation model might not represent the driving force for the observed growth-immunity trade-offs. We suggest a model in which immunity redirects and initiates hormone signalling activities that can impair plant growth by antagonising cell cycle regulation and meristem activities. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. Outer membrane vesicles of Gallibacterium anatis induce protective immunity in egg-laying hens.

    Science.gov (United States)

    Pors, Susanne E; Pedersen, Ida J; Skjerning, Ragnhild Bager; Thøfner, Ida C N; Persson, Gry; Bojesen, Anders M

    2016-11-15

    Gallibacterium anatis causes infections in the reproductive tract of egg-laying hens and induce increased mortality and decreased egg production. New prophylactic measures are needed in order to improve animal welfare and production efficiency. Bacterial outer membrane vesicles (OMVs) have previously shown promising results in protection against infections and we hypothesized that OMVs could serve as an immunogen to protect egg-laying hens against G. anatis. To investigate the immunogenic potential of G. anatis OMVs, two in vivo studies in egg-laying hens were made. The trials assessedthe degree of protection provided by immunization with G. anatis OMV against challenge and the IgY responses in serum after immunization and challenge, respectively. A total of 64 egg-laying hens were included in the trials. OMVs for immunization were produced and purified from a high-producing G. anatis ΔtolR mutant. Challenge was done with G. anatis 12656-12 and evaluated by scoring lesions and bacterial re-isolation rates from peritoneum. Finally, levels of OMV-specific IgY in sera were assayed by ELISA. Immunization with OMVs decreased the lesions scores significantly, while the bacterial re-isolation remained unchanged. Furthermore, a high OMV-specific IgY response was induced by immunization and subsequent challenge of the hens. The results strongly indicate that immunization with G. anatis OMVs provides significant protection against G. anatis challenge and induces specific antibody responses with high titers of OMV-specific IgY in serum. The results therefore show great promise for OMV based vaccines aiming at providing protecting against G. anatis in egg-laying hens. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Condition-Dependent Trade-Off Between Weapon Size and Immunity in Males of the European Earwig.

    Science.gov (United States)

    Körner, Maximilian; Vogelweith, Fanny; Foitzik, Susanne; Meunier, Joël

    2017-08-11

    Investigating the expression of trade-offs between key life-history functions is central to our understanding of how these functions evolved and are maintained. However, detecting trade-offs can be challenging due to variation in resource availability, which masks trade-offs at the population level. Here, we investigated in the European earwig Forficula auricularia whether (1) weapon size trades off with three key immune parameters - hemocyte concentration, phenoloxidase and prophenoloxidase activity - and whether (2) expression and strength of these trade-offs depend on male body condition (body size) and/or change after an immune challenge. Our results partially confirmed condition dependent trade-offs between weapon size and immunity in male earwigs. Specifically, we found that after an immune challenge, weapon size trades off with hemocyte concentrations in low-condition, but not in good-condition males. Contrastingly, weapon size was independent of pre-challenge hemocyte concentration. We also found no trade-off between weapon size and phenoloxidase activity, independent of body condition and immune challenge. Overall, our study reveals that trade-offs with sexual traits may weaken or disappear in good-condition individuals. Given the importance of weapon size for male reproductive success, our results highlight how low-condition individuals may employ alternative life-history investment strategies to cope with resource limitation.

  1. Site requirements and kinetics of immune-dependent elimination of intravascularly administered lung stage schistosomula in mice immunized with highly irradiated cercariae of Schistosoma mansoni

    International Nuclear Information System (INIS)

    Mangold, B.L.; Dean, D.A.; Coulson, P.S.; Wilson, R.A.

    1986-01-01

    Experiments were performed to compare the migration and survival of 75Se-labeled schistosomes, introduced by percutaneous cercarial exposure or by intravascular administration of 7-day-old lung stage schistosomula, in control and irradiated cercaria-immunized mice. Schistosomula were intravascularly introduced into the lungs, systemic organs and liver by injection via the femoral vein (FV), left ventricle (LV), and superior mesenteric vein (SMV), respectively. The fate of challenge larvae was examined by autoradiography of host tissues and by recovery of adult worms. It was found that both normal and immune elimination were site-dependent. In control mice 45%-60% of cercarial penetrants and lung schistosomula injected into the FV and LV were recoverable as adult worms, while a significantly greater number (70%-85%) were recoverable when lung schistosomula were injected into the SMV. In immunized mice, parasites introduced as either cercariae or FV-injected schistosomula were both highly sensitive to immune elimination. LV-injected schistosomula were also sensitive but to a slightly lesser degree. In contrast, schistosomula placed directly in the liver by SMV injection were totally insensitive to immune elimination. It was concluded that elimination of schistosomula in irradiated cercaria-immunized mice occurs in the lungs and/or in the systemic organs, but not in the liver. Also, it was concluded that immune elimination is not a rapid process, since more than 7 days were required after intravascular challenge for the development of demonstrable differences between control and immunized mice

  2. Gamma irradiated antigen extracts improves the immune response and protection in experimental toxoplasmosis

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Andrea da; Galisteo Junior, Andres Jimenez; Andrade Junior, Heitor Franco de, E-mail: andreacosta@usp.br [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil). Instituto de Medicina Tropical; Zorgi, Nahiara Estevez [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil). Instituto de Ciencias Biomedicas; Nascimento, Nanci do [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2015-07-01

    We aimed to use ionizing radiation on soluble extracts of T. gondii tachyzoites (AgTg) and tested the ability of these extracts to induce immunity in BALB/c mice against a challenge. T. gondii RH strain AgTg was irradiated with Co-60 at 0.25 to 4 kGy and were affected after 1 kGy, as evidenced by a progressive high molecular weight protein aggregates and no loss in antigenicity, as detected by immunoblotting, except after 4kGy. BALB/c mice were immunized with biweekly doses of 03 s.c. native or irradiated AgTg without adjuvants; the anti-T.gondii IgG production was detected by ELISA, and higher levels and avidity were detected in mice immunized with 1.5 kGy AgTg compared to controls (p<0.05). Mice immunized with native AgTg exhibited spleen CD19{sup +} B, CD3{sup +}CD4{sup +} or CD3{sup +}CD8{sup +} T cell proliferation levels of 5%, while 1.5 kGy-immunized mice exhibited spleen cell proliferation levels of 12.2%, primarily for CD19{sup +} or CD3{sup +}CD8{sup +} lymphocytes and less evidently for CD3{sup +}CD4{sup +} (8.8%) helper T lymphocytes. All cells from control mice showed little to no proliferation when stimulated with AgTg. These cells secreted more IFN-γ in the 1.5 kGy AgTg-immunized group (p<0.05). BALB/c mice immunized with 1.5 kGy and challenged with different strains of T. gondii were partially protected, as evidenced by survival after RH virulent strain challenge (p<0.0001) but also after ME-49 strain challenge: the brain cyst numbers (p<0.05) and the levels of T. gondii DNA measured by real-time PCR (p<0.05) decreased compared to non-immunized controls. (author)

  3. Gamma irradiated antigen extracts improves the immune response and protection in experimental toxoplasmosis

    International Nuclear Information System (INIS)

    Costa, Andrea da; Galisteo Junior, Andres Jimenez; Andrade Junior, Heitor Franco de

    2015-01-01

    We aimed to use ionizing radiation on soluble extracts of T. gondii tachyzoites (AgTg) and tested the ability of these extracts to induce immunity in BALB/c mice against a challenge. T. gondii RH strain AgTg was irradiated with Co-60 at 0.25 to 4 kGy and were affected after 1 kGy, as evidenced by a progressive high molecular weight protein aggregates and no loss in antigenicity, as detected by immunoblotting, except after 4kGy. BALB/c mice were immunized with biweekly doses of 03 s.c. native or irradiated AgTg without adjuvants; the anti-T.gondii IgG production was detected by ELISA, and higher levels and avidity were detected in mice immunized with 1.5 kGy AgTg compared to controls (p<0.05). Mice immunized with native AgTg exhibited spleen CD19 + B, CD3 + CD4 + or CD3 + CD8 + T cell proliferation levels of 5%, while 1.5 kGy-immunized mice exhibited spleen cell proliferation levels of 12.2%, primarily for CD19 + or CD3 + CD8 + lymphocytes and less evidently for CD3 + CD4 + (8.8%) helper T lymphocytes. All cells from control mice showed little to no proliferation when stimulated with AgTg. These cells secreted more IFN-γ in the 1.5 kGy AgTg-immunized group (p<0.05). BALB/c mice immunized with 1.5 kGy and challenged with different strains of T. gondii were partially protected, as evidenced by survival after RH virulent strain challenge (p<0.0001) but also after ME-49 strain challenge: the brain cyst numbers (p<0.05) and the levels of T. gondii DNA measured by real-time PCR (p<0.05) decreased compared to non-immunized controls. (author)

  4. Inactivated probiotic Bacillus coagulans GBI-30 induces complex immune activating, anti-inflammatory, and regenerative markers in vitro

    OpenAIRE

    Jensen, Gitte S; Cash, Howard A; Farmer, Sean; Keller, David

    2017-01-01

    Gitte S Jensen,1 Howard A Cash,2 Sean Farmer,2 David Keller2 1NIS Labs, Esplanade, Klamath Falls, OR, USA, 2Ganeden Biotech Inc., Landerbrook Drive Suite, Mayfield Heights, OH, USA Objective: The aim of this study was to document the immune activating and anti-inflammatory effects of inactivated probiotic Bacillus coagulans GBI-30, 6086 (Staimune™) cells on human immune cells in vitro.Methods: In vitro cultures of human peripheral blood mononuclear cells (PBMC) from healthy blood do...

  5. Immunity to gastrointestinal nematode infections

    DEFF Research Database (Denmark)

    Sorobetea, D.; Svensson Frej, M.; Grencis, R.

    2018-01-01

    Numerous species of nematodes have evolved to inhabit the gastrointestinal tract of animals and humans, with over a billion of the world's population infected with at least one species. These large multicellular pathogens present a considerable and complex challenge to the host immune system give...

  6. Decreased Cytotoxicity of Peripheral and Peritoneal Natural Killer Cell in Endometriosis.

    Science.gov (United States)

    Jeung, InCheul; Cheon, Keunyoung; Kim, Mee-Ran

    2016-01-01

    Endometriosis causes significant chronic pelvic pain, dysmenorrhea, and infertility and affects 10% of all women. In endometriosis, ectopic endometrium surviving after retrograde menstruation exhibits an abnormal immune response characterized by increased levels of activated macrophages and inflammatory cytokines. Particularly, dysfunctional natural killer (NK) cells play an important role in the pathogenesis of the disease by either facilitating or inhibiting the survival, implantation, and proliferation of endometrial cells. NK cells in the peritoneum and peritoneal fluid exhibit reduced levels of cytotoxicity in women with endometriosis. Several cytokines and inhibitory factors in the serum and peritoneal fluid also dysregulate NK cell cytotoxicity. Additionally, increased numbers of immature peripheral NK cells and induction of NK cell apoptosis are evident in the peritoneal fluid of women with endometriosis. The high rate of endometriosis recurrence after pharmaceutical or surgical treatment, which is associated with dysfunctional NK cells, indicates that new immunomodulatory management strategies are required. A good understanding of immune dysfunction would enable improvement of current treatments for endometriosis.

  7. Decreased Cytotoxicity of Peripheral and Peritoneal Natural Killer Cell in Endometriosis

    Directory of Open Access Journals (Sweden)

    InCheul Jeung

    2016-01-01

    Full Text Available Endometriosis causes significant chronic pelvic pain, dysmenorrhea, and infertility and affects 10% of all women. In endometriosis, ectopic endometrium surviving after retrograde menstruation exhibits an abnormal immune response characterized by increased levels of activated macrophages and inflammatory cytokines. Particularly, dysfunctional natural killer (NK cells play an important role in the pathogenesis of the disease by either facilitating or inhibiting the survival, implantation, and proliferation of endometrial cells. NK cells in the peritoneum and peritoneal fluid exhibit reduced levels of cytotoxicity in women with endometriosis. Several cytokines and inhibitory factors in the serum and peritoneal fluid also dysregulate NK cell cytotoxicity. Additionally, increased numbers of immature peripheral NK cells and induction of NK cell apoptosis are evident in the peritoneal fluid of women with endometriosis. The high rate of endometriosis recurrence after pharmaceutical or surgical treatment, which is associated with dysfunctional NK cells, indicates that new immunomodulatory management strategies are required. A good understanding of immune dysfunction would enable improvement of current treatments for endometriosis.

  8. Children with asthma by school age display aberrant immune responses to pathogenic airway bacteria as infants

    DEFF Research Database (Denmark)

    Larsen, Jeppe Madura; Pedersen, Susanne Brix; Thysen, Anna Hammerich

    2014-01-01

    childhood asthma. We hypothesized that children with asthma have an abnormal immune response to pathogenic bacteria in infancy. ObjectiveWe aimed to assess the bacterial immune response in asymptomatic infants and the association with later development of asthma by age 7 years. MethodsThe Copenhagen...... was assessed based on the pattern of cytokines produced and T-cell activation. ResultsThe immune response to pathogenic bacteria was different in infants with asthma by 7 years of age (P = .0007). In particular, prospective asthmatic subjects had aberrant production of IL-5 (P = .008), IL-13 (P = .057), IL-17...... (P = .001), and IL-10 (P = .028), whereas there were no differences in T-cell activation or peripheral T-cell composition. ConclusionsChildren with asthma by school age exhibited an aberrant immune response to pathogenic bacteria in infancy. We propose that an abnormal immune response to pathogenic...

  9. The choroid plexus response to a repeated peripheral inflammatory stimulus

    Directory of Open Access Journals (Sweden)

    Palha Joana A

    2009-11-01

    Full Text Available Abstract Background Chronic systemic inflammation triggers alterations in the central nervous system that may relate to the underlying inflammatory component reported in neurodegenerative disorders such as multiple sclerosis and Alzheimer's disease. However, it is far from being understood whether and how peripheral inflammation contributes to induce brain inflammatory response in such illnesses. As part of the barriers that separate the blood from the brain, the choroid plexus conveys inflammatory immune signals into the brain, largely through alterations in the composition of the cerebrospinal fluid. Results In the present study we investigated the mouse choroid plexus gene expression profile, using microarray analyses, in response to a repeated inflammatory stimulus induced by the intraperitoneal administration of lipopolysaccharide every two weeks for a period of three months; mice were sacrificed 3 and 15 days after the last lipopolysaccharide injection. The data show that the choroid plexus displays a sustained response to the repeated inflammatory stimuli by altering the expression profile of several genes. From a total of 24,000 probes, 369 are up-regulated and 167 are down-regulated 3 days after the last lipopolysaccharide injection, while at 15 days the number decreases to 98 and 128, respectively. The pathways displaying the most significant changes include those facilitating entry of cells into the cerebrospinal fluid, and those participating in the innate immune response to infection. Conclusion These observations contribute to a better understanding of the brain response to peripheral inflammation and pave the way to study their impact on the progression of several disorders of the central nervous system in which inflammation is known to be implicated.

  10. Anti-diphtheria immunity in Nigerian mothers and their newborns.

    Science.gov (United States)

    Cummings, Henry; Sadoh, Ayebo Evawere; Oviawe, Osawaru; Sadoh, Wilson Ehidiamen

    2014-05-30

    Immunity to diphtheria has been noted to wane with age such that previous studies have shown that a significant proportion of females with characteristics comparable to those of Nigerian women of reproductive age have inadequate levels of immunity to diphtheria. Thus, it is envisaged that Nigerian newborns may inherit inadequate levels of immunity to diphtheria from their mothers. Cord blood and peripheral maternal blood samples were collected from 231 mother-infant pairs at delivery. Anti-diphtheria antibody titres were assayed using Enzyme-linked immunosorbent assay (ELISA) technique. Recruited babies were those born at term with normal birth weight. As much as 29.9% of both mothers and their babies had no protection (antibody titrediphtheria. Ninety (39.0% CI 33%,45%) mothers and 107 (46.3% CI 40%,52%) babies were inadequately protected (antibody titrediphtheria. The difference in the geometric mean antibody titres of mothers and babies was statistically significant (pdiphtheria. Vaccination of parturient women with booster doses of diphtheria toxoid vaccine is recommended. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Emerging nanotechnology approaches in tissue engineering for peripheral nerve regeneration.

    Science.gov (United States)

    Cunha, Carla; Panseri, Silvia; Antonini, Stefania

    2011-02-01

    Effective nerve regeneration and functional recovery subsequent to peripheral nerve injury is still a clinical challenge. Autologous nerve graft transplantation is a feasible treatment in several clinical cases, but it is limited by donor site morbidity and insufficient donor tissue, impairing complete functional recovery. Tissue engineering has introduced innovative approaches to promote and guide peripheral nerve regeneration by using biomimetic conduits creating favorable microenvironments for nervous ingrowth, but despite the development of a plethora of nerve prostheses, few approaches have as yet entered the clinic. Promising strategies using nanotechnology have recently been proposed, such as the use of scaffolds with functionalized cell-binding domains, the use of guidance channels with cell-scale internally oriented fibers, and the possibility of sustained release of neurotrophic factors. This review addresses the fabrication, advantages, drawbacks, and results achieved by the most recent nanotechnology approaches in view of future solutions for peripheral nerve repair. Peripheral nerve repair strategies are very limited despite numerous advances on the field of neurosciences and regenerative medicine. This review discusses nanotechnology based strategies including scaffolds with functionalized cell binding domains, the use of guidance channels, and the potential use of sustained release neurotropic factors. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Improving vaccine registries through mobile technologies: a vision for mobile enhanced Immunization information systems.

    Science.gov (United States)

    Wilson, Kumanan; Atkinson, Katherine M; Deeks, Shelley L; Crowcroft, Natasha S

    2016-01-01

    Immunization registries or information systems are critical to improving the quality and evaluating the ongoing success of immunization programs. However, the completeness of these systems is challenged by a myriad of factors including the fragmentation of vaccine administration, increasing mobility of individuals, new vaccine development, use of multiple products, and increasingly frequent changes in recommendations. Mobile technologies could offer a solution, which mitigates some of these challenges. Engaging individuals to have more control of their own immunization information using their mobile devices could improve the timeliness and accuracy of data in central immunization information systems. Other opportunities presented by mobile technologies that could be exploited to improve immunization information systems include mobile reporting of adverse events following immunization, the capacity to scan 2D barcodes, and enabling bidirectional communication between individuals and public health officials. Challenges to utilizing mobile solutions include ensuring privacy of data, access, and equity concerns, obtaining consent and ensuring adoption of technology at sufficiently high rates. By empowering individuals with their own health information, mobile technologies can also serve as a mechanism to transfer immunization information as individuals cross local, regional, and national borders. Ultimately, mobile enhanced immunization information systems can help realize the goal of the individual, the healthcare provider, and public health officials always having access to the same immunization information. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Parental investment matters for maternal and offspring immune defense in the mouthbrooding cichlid Astatotilapia burtoni.

    Science.gov (United States)

    Keller, Isabel S; Salzburger, Walter; Roth, Olivia

    2017-12-20

    Parental care, while increasing parental fitness through offspring survival, also bears cost to the care-giving parent. Consequentially, trade offs between parental care and other vitally important traits, such as the immune system seem evident. In co-occurring phases of parental care and immunological challenges negative consequences through a resource allocation trade off on both the parental and the offspring conditions can be predicted. While the immune system reflects parental stress conditions, parental immunological investments also boost offspring survival via the transfer of immunological substances (trans-generational immune priming). We investigated this relationship in the mouthbrooding East African cichlid Astotatilapia burtoni. Prior to mating, females were exposed to an immunological activation, while others remained immunologically naïve. Correspondingly, the immunological status of females was either examined directly after reproduction or after mouthbrooding had ceased. Offspring from both groups were exposed to immunological challenges to assess the extent of trans-generational immune priming. As proxy for immune status, cellular immunological activity and gene expression were determined. Both reproducing and mouthbrooding females allocate their resources towards reproduction. While upon reproduction the innate immune system was impeded, mouthbrooding females showed an attenuation of inflammatory components. Juveniles from immune challenged mouthbrooding females showed downregulation of immune and life history candidate genes, implying a limitation of trans-generational plasticity when parents experience stress during the costly reproductive phase. Our results provide evidence that both parental investment via mouthbrooding and the rise of the immunological activity upon an immune challenge are costly traits. If applied simultaneously, not only mothers seem to be impacted in their performance, but also offspring are impeded in their ability to

  14. Immune response to an endotoxin challenge involves multiple immune parameters and is consistent among the annual-cycle stages of a free-living temperate zone bird

    NARCIS (Netherlands)

    Hegemann, Arne; Matson, Kevin D.; Versteegh, Maaike A.; Villegas, Auxiliadora; Tieleman, B. Irene

    Trade-offs between immune function and other physiological and behavioural processes are central in ecoimmunology, but one important problem is how to distinguish a reallocation of resources away from the immune system from a reallocation or redistribution within the immune system. While variation

  15. A cane reduces loss of balance in patients with peripheral neuropathy: results from a challenging unipedal balance test.

    Science.gov (United States)

    Ashton-Miller, J A; Yeh, M W; Richardson, J K; Galloway, T

    1996-05-01

    To test the hypothesis that use of a cane in the nondominant hand during challenging balance tasks would significantly decrease loss of balance in patients with peripheral neuropathy while transferring from bipedal to unipedal stance on an unsteady surface. Nonrandomized control study. Tertiary-care institution. Eight consecutive patients with peripheral neuropathy (PN) and eight age- and gender-matched controls (C) with a mean (SD) age of 65 (8.2) years. Subjects were asked to transfer their weight onto their right foot, despite a rapid +/- 2 degrees or +/- 4 degrees frontal plane tilt of the support surface at 70% of weight transfer, and balance unipedally for at least 3 seconds. The efficacy of their weight transfer was evaluated over 112 consecutive randomized and blocked trials by calculating loss of balance as failure rates (%FR) with and without visual feedback, and with and without use of a cane in the nondominant (left) hand. Results were analyzed using a 2 x 2 x 2 x 2 x 2 repeated-measures analysis of variance (rm-ANOVA) and post hoc t tests. The rm-ANOVA showed that the FR of the PN subjects (47.6% [18.1%]) was significantly higher than C (29.2% [15.2%], p = .036). Removing visual feedback, simulating the dark of night, increased the FR fourfold (p = .000). Use of a cane in the contralateral nondominant hand significantly reduced the FR (p = .000), particularly in the PN group (cane x disease interaction: p = .055). Post hoc t tests showed that with or without visual feedback, the cane reduced the FR of the PN group fourfold and enabled them to perform more reliably than matched controls not using a cane (p = .011). An inversion perturbation resulted in a higher FR than an eversion perturbation (p = .007). The PN group employed larger mean peak cane forces (21.9% BW) than C (13.6% BW) in restoring their balance (p = .000). Use of a cane by PN patients significantly reduced their risk of losing balance on unstable surfaces, especially under low

  16. Influence of 90Sr, adult thymectomy and antilymphocyteglobulin on haematopoietic tissues and peripheral blood leucocytes in CBA mice

    International Nuclear Information System (INIS)

    Bierke, P.

    1986-01-01

    The role or long-time immune suppression in carcinogenesis induced by the long-lived internal emitter 90 Sr, is investigated in an ongoing study. The experimental design is based on the assumption that impaired immune responsiveness, by other means than 90 Sr, might increase the neoplastic response in exposed individuals, and thus reflect a protective function, if existing. Intercomparison is made of the tumour yield in mice exposed to different single doses of 90 Sr and simultaneously subjected or not to long-term immune suppression by adult thymectomy (ATx) and/or antilymphocyteglobulin (ALG) treatment. Information on the general condition and responsiveness of the immune system, in the respective models, during tumour expectancy time, is essential for a conclusive evaluation of the results. To meet theses demands the present paper reports on histopathologic alternations in immune organs and changes in white blood cell counts, induced by the different combinations of 90 Sr, ATx + ALG treatment. The results confirm the prediction, that ATx + ALG is an efficient and, with respect to the purpose of the study, suitable treatment for additive long-term depression of the immune system in 90 Sr irradiated mice, evidenced in particular by increased depletion of monomorphonuclear cells (MNC) in lymphoid organs and peripheral blood. Subsequent reports will deal with functional immune parameters. (orig.)

  17. Peripheral Neuropathy and Agent Orange

    Science.gov (United States)

    ... Enter ZIP code here Enter ZIP code here Peripheral Neuropathy and Agent Orange VA presumes Veterans' early-onset ... 10 percent disabling by VA's rating regulations. About peripheral neuropathy Peripheral neuropathy is a condition of the peripheral ...

  18. Effects of treated sewage effluent on immune function in rainbow trout (Oncorhynchus mykiss)

    Energy Technology Data Exchange (ETDEWEB)

    Hoeger, Birgit [Environmental Toxicology, University of Konstanz, P.O. Box X918, D-78457 Constance (Germany); Heuvel, Michael R. van den [Forest Research, Private Bag 3020, Sala St., Rotorua (New Zealand); Hitzfeld, Bettina C. [Swiss Agency for the Environment, Forests and Landscape (SAEFL), Substances, Soil, Biotechnology Division, Section Substances, 3003 Bern (Switzerland); Dietrich, Daniel R. [Environmental Toxicology, University of Konstanz, P.O. Box X918, D-78457 Constance (Germany)]. E-mail: daniel.dietrich@uni-konstanz.de

    2004-12-20

    In this study, the immune reactions of rainbow trout (Oncorhynchus mykiss) were examined, after exposure to 10, 30 and 70% of tertiary-treated municipal sewage effluent for 27 days. Exposures were conducted concurrently with and without an immune challenge using intraperitoneal injections of inactivated Aeromonas salmonicida salmonicida. Due to the time required to prepare and analyse samples, fish sampling was conducted over two consecutive days. There was no trout mortality for any of the experimental treatments. The exposure to effluent increased in vitro lymphocyte proliferation, decreased circulating lymphocytes and increased degrading erythrocytes in peripheral blood samples. Circulating lymphocytes were only decreased in the sham-injected, but not in the A. salmonicida-injected group. In addition to effluent effects, circulating lymphocytes and lymphocyte proliferation were decreased on day 2 of sampling as compared to day 1. Concentration-dependent degradation of erythrocytes was only observed on day 2 of sampling. Capture and removal of trout on day 1 of sampling presumably caused low-level stress that affected some results on day 2. Oxidative burst, phagocytosis, lysozyme, leucocyte populations other than lymphocytes and A. salmonicida-specific IgM production were not affected by exposure to effluent, and of these parameters, only oxidative burst and total leucocytes showed sampling day effects. From these results it can be observed, that with the exception of oxidative burst, those variables affected by effluent exposure were also significantly changed by the low-level sampling stress imposed by staggered sampling. Elevated liver mixed-function oxygenase activity as measured by 7-ethoxyresorufin-O-deethylase activity, and increased bile polycyclic aromatic hydrocarbon (PAH) metabolites were observed in response to sewage effluent exposure. As both PAHs and stress are known immune suppressors, it is difficult to conclude whether or not changes in immune

  19. Effects of treated sewage effluent on immune function in rainbow trout (Oncorhynchus mykiss)

    International Nuclear Information System (INIS)

    Hoeger, Birgit; Heuvel, Michael R. van den; Hitzfeld, Bettina C.; Dietrich, Daniel R.

    2004-01-01

    In this study, the immune reactions of rainbow trout (Oncorhynchus mykiss) were examined, after exposure to 10, 30 and 70% of tertiary-treated municipal sewage effluent for 27 days. Exposures were conducted concurrently with and without an immune challenge using intraperitoneal injections of inactivated Aeromonas salmonicida salmonicida. Due to the time required to prepare and analyse samples, fish sampling was conducted over two consecutive days. There was no trout mortality for any of the experimental treatments. The exposure to effluent increased in vitro lymphocyte proliferation, decreased circulating lymphocytes and increased degrading erythrocytes in peripheral blood samples. Circulating lymphocytes were only decreased in the sham-injected, but not in the A. salmonicida-injected group. In addition to effluent effects, circulating lymphocytes and lymphocyte proliferation were decreased on day 2 of sampling as compared to day 1. Concentration-dependent degradation of erythrocytes was only observed on day 2 of sampling. Capture and removal of trout on day 1 of sampling presumably caused low-level stress that affected some results on day 2. Oxidative burst, phagocytosis, lysozyme, leucocyte populations other than lymphocytes and A. salmonicida-specific IgM production were not affected by exposure to effluent, and of these parameters, only oxidative burst and total leucocytes showed sampling day effects. From these results it can be observed, that with the exception of oxidative burst, those variables affected by effluent exposure were also significantly changed by the low-level sampling stress imposed by staggered sampling. Elevated liver mixed-function oxygenase activity as measured by 7-ethoxyresorufin-O-deethylase activity, and increased bile polycyclic aromatic hydrocarbon (PAH) metabolites were observed in response to sewage effluent exposure. As both PAHs and stress are known immune suppressors, it is difficult to conclude whether or not changes in immune

  20. The Role of Cryptococcus in the Immune System of Pulmonary Cryptococcosis Patients.

    Directory of Open Access Journals (Sweden)

    Jinlin Wang

    Full Text Available To investigate the role of Cryptococcus in the immune system of immunocompetent patients with pulmonary cryptococcosis (PC by analysing the dynamic changes of patients' immune status before and after antifungal therapy.The level of the serum interferon-γ (IFN-γ and interleukin (IL-2, -4, -10 and -12 was measured before and after 6-months of treatment. Peripheral blood samples were obtained from 30 immunocompetent PC patients and 30 age- and gender-matched healthy controls. Peripheral blood mononuclear cells (PBMCs were isolated and incubated with recombinant human IL-12 (rhIL-12 for 48 h. Then the concentrations of IFN-γ and IL-4 in the supernatant were analysed.Baseline serum IFN-γ level was significantly lower in the PC patients as compared with the control group (P < 0.001. The serum IL-2 and IFN-γ of PC patients were significantly increased after appropriate treatments (P < 0.05 and P < 0.001 when compared to their baseline levels. The productions of IFN-γ in the culture supernatant of PBMCs showed no significant difference between the control and PC patients both before and after antifungal treatments. RhIL-12 is a potent stimulus for IFN-γ production. Culture PBMCs collected from PC patients before treatments had a smaller increase of IFN-γ production in the present of rhIL-12 than the control (P < 0.01; PBMCs from PC patients completing 6-months of treatment showed a comparable increase of IFN-γ production by rhIL-12 stimulation to the control group.In apparently immunocompetent patients with PC, a normalization of serum IFN-γ was achieved after recovery from infection. This suggests that Cryptococcus infection per se can suppress the immune system and its elimination contributes to the reestablishment of an immune equilibrium.