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Sample records for anti-cd4 immunity insights

  1. Protection of xenografts by a combination of immunoisolation and a single dose of anti-CD4 antibody.

    Science.gov (United States)

    Mckenzie, A W; Georgiou, H M; Zhan, Y; Brady, J L; Lew, A M

    2001-01-01

    Immunoisolation is the separation of transplanted cells from cells of the immune system using a semipermeable membrane. Using one such immunoisolation capsule-the TheraCyte device-we have assessed the survival of encapsulated xenogeneic tissue in vivo as well as the contribution of CD4+ve T cells to encapsulated xenograft rejection. The foreign body reaction to the TheraCyte capsule in vivo was assessed by transplanting empty capsules into normal mice. These capsules elicit a foreign body response by the host animal. Encapsulated CHO, NIT-1, and PK-15 cells were placed in culture and in immunodeficient mice to investigate their growth characteristics in the TheraCyte device. These cell lines survive both in culture and in immunodeficient SCID mice. Xenogeneic PK cells were also transplanted into normal C57BL/6 mice. These cells do not survive in normal mice despite the absence of direct contact between infiltrating and encapsulated cells. In addition, the survival of encapsulated cells in mice treated with a single dose of anti-CD4 antibody was examined. This was assessed using two systems: 1) histological analysis of capsule sections; 2) a quantitative luciferase reporter system using PK cells transfected to express luciferase. In both cases, anti-CD4 antibody contributed to prolonged encapsulated xenogeneic cell survival. Encapsulated xenogeneic cells survive in immunodeficient mice but not normal mice. Treatment of normal mice with anti-CD4 antibody results in prolonged survival of xenogeneic cells that can be measured using a luciferase reporter system. These results highlight the contribution of CD4+ve T cells to encapsulated xenograft rejection.

  2. Minimal contribution of cell-bound antibodies to the immunoscintigraphy of inflamed joints with 99mTc-anti-CD4 monoclonal antibodies

    International Nuclear Information System (INIS)

    Kinne, R.W.; Palombo-Kinne, E.; Wolski, A.; Wolf, F.; Emmrich, F.; Becker, W.

    2002-01-01

    Aim: The cellular joint infiltrate in rheumatoid arthritis patients is rich in CD4-positive T-helper lymphocytes and macrophages, rendering anti-CD4 monoclonal antibodies (mAbs) suitable for specific immunoscintigraphy of human/experimental arthritis. Following intravenous injection, however, mAbs are present both in the free form and bound to CD4-positive, circulating monocytes and T-cells. Thus, the present study aimed at analyzing the relative contribution of the free and the cell-bound component to the imaging of inflamed joints in experimental adjuvant arthritis (AA). Methods: AA rat pertioneal macrophages or lymph node T-cells were incubated in vitro with saturating amounts of 99mTc-anti-CD4 mAb (W3/25) and injected i.v. into rats with AA. Results: In vitro release of 99m Tc-anti-CD4 mAb from the cells was limited (on average 1.57%/h for macrophages and 0.84%/h for T-cells). Following i.v. injection, whole body/joints scans and tissue measurements showed only negligible accumulation of radioactivity in inflamed ankle joints (tissue: 0.22 and 0.34% of the injected activity, respectively), whereas the radioactivity was concentrated in liver (tissue: 79% and 71%, respectively), kidney, and urinary bladder. Unlike macrophages, however, anti-CD4 mAb-coated T-cells significantly accumulated in lymphoid organs, the inflamed synovial membrane of the ankle joints, as well as in elbow and knee joints. Conclusion: While the overall contribution of cell-bound mAbs to the imaging of arthritic joints with anti-CD4 mAbs is minimal, differential accumulation of macrophages and T-cells in lymphoid organs and the inflamed synovial membrane indicates preferential migration patterns of these 2 cell populations in arthritic rats. Although only validated for 99m Tc-anti-CD4 mAbs, extrapolation of the results to other anticellular mAbs with similar affinity for their antigen may be possible. (orig.) [de

  3. ImmunoPET Imaging of Murine CD4+ T Cells Using Anti-CD4 Cys-Diabody: Effects of Protein Dose on T Cell Function and Imaging.

    Science.gov (United States)

    Freise, Amanda C; Zettlitz, Kirstin A; Salazar, Felix B; Lu, Xiang; Tavaré, Richard; Wu, Anna M

    2017-08-01

    preclinical disease models. Future approaches to minimizing biological effects may include the creation of monovalent fragments or selecting anti-CD4 antibodies which target alternative epitopes.

  4. Immune and stress responses in oysters with insights on adaptation.

    Science.gov (United States)

    Guo, Ximing; He, Yan; Zhang, Linlin; Lelong, Christophe; Jouaux, Aude

    2015-09-01

    Oysters are representative bivalve molluscs that are widely distributed in world oceans. As successful colonizers of estuaries and intertidal zones, oysters are remarkably resilient against harsh environmental conditions including wide fluctuations in temperature and salinity as well as prolonged air exposure. Oysters have no adaptive immunity but can thrive in microbe-rich estuaries as filter-feeders. These unique adaptations make oysters interesting models to study the evolution of host-defense systems. Recent advances in genomic studies including sequencing of the oyster genome have provided insights into oyster's immune and stress responses underlying their amazing resilience. Studies show that the oyster genomes are highly polymorphic and complex, which may be key to their resilience. The oyster genome has a large gene repertoire that is enriched for immune and stress response genes. Thousands of genes are involved in oyster's immune and stress responses, through complex interactions, with many gene families expanded showing high sequence, structural and functional diversity. The high diversity of immune receptors and effectors may provide oysters with enhanced specificity in immune recognition and response to cope with diverse pathogens in the absence of adaptive immunity. Some members of expanded immune gene families have diverged to function at different temperatures and salinities or assumed new roles in abiotic stress response. Most canonical innate immunity pathways are conserved in oysters and supported by a large number of diverse and often novel genes. The great diversity in immune and stress response genes exhibited by expanded gene families as well as high sequence and structural polymorphisms may be central to oyster's adaptation to highly stressful and widely changing environments. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. New insights into innate immune control of systemic candidiasis

    Science.gov (United States)

    Lionakis, Michail S.

    2014-01-01

    Systemic infection caused by Candida species is the fourth leading cause of nosocomial bloodstream infection in modern hospitals and carries high morbidity and mortality despite antifungal therapy. A recent surge of immunological studies in the mouse models of systemic candidiasis and the parallel discovery and phenotypic characterization of inherited genetic disorders in antifungal immune factors that are associated with enhanced susceptibility or resistance to the infection have provided new insights into the cellular and molecular basis of protective innate immune responses against Candida. In this review, the new developments in our understanding of how the mammalian immune system responds to systemic Candida challenge are synthesized and important future research directions are highlighted. PMID:25023483

  6. The multitasking organ: recent insights into skin immune function.

    Science.gov (United States)

    Di Meglio, Paola; Perera, Gayathri K; Nestle, Frank O

    2011-12-23

    The skin provides the first line defense of the human body against injury and infection. By integrating recent findings in cutaneous immunology with fundamental concepts of skin biology, we portray the skin as a multitasking organ ensuring body homeostasis. Crosstalk between the skin and its microbial environment is also highlighted as influencing the response to injury, infection, and autoimmunity. The importance of the skin immune network is emphasized by the identification of several skin-resident cell subsets, each with its unique functions. Lessons learned from targeted therapy in inflammatory skin conditions, such as psoriasis, provide further insights into skin immune function. Finally, we look at the skin as an interacting network of immune signaling pathways exemplified by the development of a disease interactome for psoriasis. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Epigenetic modulation of host: new insights into immune evasion by ...

    Indian Academy of Sciences (India)

    Viruses have evolved with their hosts, which include all living species. This has been partly responsible for the development of highly advanced immune systems in the hosts. However, viruses too have evolved ways to regulate and evade the host's immune defence. In addition to mutational mechanisms that viruses employ ...

  8. Probiotic bacteria and the immune system: mechanistic insights and therapeutic implications

    NARCIS (Netherlands)

    Mariman, R.

    2013-01-01

    This thesis aimed to provide insight into the role of microbiota-host interactions in the regulation of mucosal and systemic immunity in the context of IBD. Regulation of microbiota composition (e.g. by probiotics and prebiotics) offers the possibility to modulate immune responses and contribute to

  9. Recent Advances in Type-2-Cell-Mediated Immunity: Insights from Helminth Infection.

    Science.gov (United States)

    Harris, Nicola L; Loke, P'ng

    2017-12-19

    Type-2-cell-mediated immune responses play a critical role in mediating both host-resistance and disease-tolerance mechanisms during helminth infections. Recently, type 2 cell responses have emerged as major regulators of tissue repair and metabolic homeostasis even under steady-state conditions. In this review, we consider how studies of helminth infection have contributed toward our expanding cellular and molecular understanding of type-2-cell-mediated immunity, as well as new areas such as the microbiome. By studying how these successful parasites form chronic infections without overt pathology, we are gaining additional insights into allergic and inflammatory diseases, as well as normal physiology. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Immunization

    Science.gov (United States)

    ... a lot worse. Some are even life-threatening. Immunization shots, or vaccinations, are essential. They protect against ... B, polio, tetanus, diphtheria, and pertussis (whooping cough). Immunizations are important for adults as well as children. ...

  11. A role for CD4+ but not CD8+ T cells in immunity to Schistosoma mansoni induced by 20 krad-irradiated and Ro 11-3128-terminated infections

    International Nuclear Information System (INIS)

    Vignali, D.A.A.; Bickle, Q.D.; Taylor, M.G.; Crocker, P.; Cobbold, S.; Waldmann, H

    1989-01-01

    The role of CD4 + (L3/T4 + ) and CD8 + (Lyt-2 + ) T cells in immunity to Schistosoma mansoni induced by 20 krad-irradiated and Ro 11-terminated infections in mice was investigated directly by in vivo depletion of these subsets with cytotoxic rat monoclonal antibodies (mAb). Effective physical depletion was demonstrated by flow cytometric analysis and immunohistochemical staining. Functional depletion of helper activity following anti-CD4 treatment was indicated by an abrogation of concanavalin A(Con A)-induced colony-stimulating factor (CSF) release, while anti-CD8 treatment had no effect in these assays. Pre-existing S. mansoni-specific antibody levels were unaffected by anti-CD4 and anti-CD8 treatment. In vivo depletion of CD4 + T cells resulted in a dramatic reduction in immunity induced by one (up to 100%) and two (up to 70%) vaccinations with 20 krad-irradiated cercariae and also of resistance induced by Ro 11-attenuated infections (up to 100%). Depletion of CD8 + T cells had no effect on resistance induced by any of the vaccination protocols investigated. A correlation was observed between resistance and T cell-induced, macrophage-mediated killing of schistosomula in vitro, both of which were abrogated following anti-CD4 treatment but were unaffected by CD8 + T-cell depletion. The possible role of CD4 + T cells in vivo and the implications for vaccine development are discussed. (author)

  12. Innate Immunity Evasion by Enteroviruses: Insights into Virus-Host Interaction

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    Xiaobo Lei

    2016-01-01

    Full Text Available Enterovirus genus includes multiple important human pathogens, such as poliovirus, coxsackievirus, enterovirus (EV A71, EV-D68 and rhinovirus. Infection with EVs can cause numerous clinical conditions including poliomyelitis, meningitis and encephalitis, hand-foot-and-mouth disease, acute flaccid paralysis, diarrhea, myocarditis and respiratory illness. EVs, which are positive-sense single-stranded RNA viruses, trigger activation of the host antiviral innate immune responses through pathogen recognition receptors such as retinoic acid-inducible gene (RIG-I-likeand Toll-like receptors. In turn, EVs have developed sophisticated strategies to evade host antiviral responses. In this review, we discuss the interplay between the host innate immune responses and EV infection, with a primary focus on host immune detection and protection against EV infection and viral strategies to evade these antiviral immune responses.

  13. Gene expression profiling provides insights into the immune mechanism of Plutella xylostella midgut to microbial infection.

    Science.gov (United States)

    Lin, Junhan; Xia, Xiaofeng; Yu, Xiao-Qiang; Shen, Jinhong; Li, Yong; Lin, Hailan; Tang, Shanshan; Vasseur, Liette; You, Minsheng

    2018-03-20

    Insect gut immunity plays a key role in defense against microorganism infection. The knowledge of insect gut immunity has been obtained mostly from Drosophila melanogaster. Little is known about gut immunity in the diamondback moth, Plutella xylostella (L.), a pest destroying cruciferous crops worldwide. In this study, expressions of the immune-related genes in the midgut of P. xylostella orally infected with Staphylococcus aureus, Escherichia coli and Pichia pastoris were profiled by RNA-seq and qRT-PCR approaches. The results revealed that the Toll, IMD, JNK and JAK-STAT pathways and possibly the prophenoloxidase activation system in P. xylostella could be activated by oral infections, and moricins, gloverins and lysozyme2 might act as important effectors against microorganisms. Subsequent knock-down of IMD showed that this gene was involved in regulating the expression of down-stream genes in the IMD pathway. Our work indicates that the Toll, IMD, JNK and JAK-STAT pathways may synergistically modulate immune responses in the P. xylostella midgut, implying a complex and diverse immune system in the midgut of insects. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Visualizing the Immune System: Providing Key Insights into HIV/SIV Infections

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    Jacob D. Estes

    2018-03-01

    Full Text Available Immunological inductive tissues, such as secondary lymphoid organs, are composed of distinct anatomical microenvironments for the generation of immune responses to pathogens and immunogens. These microenvironments are characterized by the compartmentalization of highly specialized immune and stromal cell populations, as well as the presence of a complex network of soluble factors and chemokines that direct the intra-tissue trafficking of naïve and effector cell populations. Imaging platforms have provided critical contextual information regarding the molecular and cellular interactions that orchestrate the spatial microanatomy of relevant cells and the development of immune responses against pathogens. Particularly in HIV/SIV disease, imaging technologies are of great importance in the investigation of the local interplay between the virus and host cells, with respect to understanding viral dynamics and persistence, immune responses (i.e., adaptive and innate inflammatory responses, tissue structure and pathologies, and changes to the surrounding milieu and function of immune cells. Merging imaging platforms with other cutting-edge technologies could lead to novel findings regarding the phenotype, function, and molecular signatures of particular immune cell targets, further promoting the development of new antiviral treatments and vaccination strategies.

  15. Feminizing Wolbachia: a transcriptomics approach with insights on the immune response genes in Armadillidium vulgare

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    Chevalier Frédéric

    2012-01-01

    Full Text Available Abstract Background Wolbachia are vertically transmitted bacteria known to be the most widespread endosymbiont in arthropods. They induce various alterations of the reproduction of their host, including feminization of genetic males in isopod crustaceans. In the pill bug Armadillidium vulgare, the presence of Wolbachia is also associated with detrimental effects on host fertility and lifespan. Deleterious effects have been demonstrated on hemocyte density, phenoloxidase activity, and natural hemolymph septicemia, suggesting that infected individuals could have defective immune capacities. Since nothing is known about the molecular mechanisms involved in Wolbachia-A. vulgare interactions and its secondary immunocompetence modulation, we developed a transcriptomics strategy and compared A. vulgare gene expression between Wolbachia-infected animals (i.e., “symbiotic” animals and uninfected ones (i.e., “asymbiotic” animals as well as between animals challenged or not challenged by a pathogenic bacteria. Results Since very little genetic data is available on A. vulgare, we produced several EST libraries and generated a total of 28 606 ESTs. Analyses of these ESTs revealed that immune processes were over-represented in most experimental conditions (responses to a symbiont and to a pathogen. Considering canonical crustacean immune pathways, these genes encode antimicrobial peptides or are involved in pathogen recognition, detoxification, and autophagy. By RT-qPCR, we demonstrated a general trend towards gene under-expression in symbiotic whole animals and ovaries whereas the same gene set tends to be over-expressed in symbiotic immune tissues. Conclusion This study allowed us to generate the first reference transcriptome ever obtained in the Isopoda group and to identify genes involved in the major known crustacean immune pathways encompassing cellular and humoral responses. Expression of immune-related genes revealed a modulation of host

  16. Protumor Activities of the Immune Response: Insights in the Mechanisms of Immunological Shift, Oncotraining, and Oncopromotion

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    G. K. Chimal-Ramírez

    2013-01-01

    Full Text Available Experimental and clinical studies indicate that cells of the innate and adaptive immune system have both anti- and pro-tumor activities. This dual role of the immune system has led to a conceptual shift in the role of the immune system’s regulation of cancer, in which immune-tumor cell interactions are understood as a dynamic process that comprises at least five phases: immunosurveillance, immunoselection, immunoescape, oncotraining, and oncopromotion. The tumor microenvironment shifts immune cells to perform functions more in tune with the tumor needs (oncotraining; these functions are related to chronic inflammation and tissue remodeling activities. Among them are increased proliferation and survival, increased angiogenesis and vessel permeability, protease secretion, acquisition of migratory mesenchymal characteristics, and self-renewal properties that altogether promote tumor growth and metastasis (oncopromotion. Important populations in all these pro-tumor processes are M2 macrophages, N2 neutrophils, regulatory T cells, and myeloid derived suppressor cells; the main effectors molecules are CSF-1, IL-6, metalloproteases, VEGF, PGE-2, TGF-β, and IL-10. Cancer prognosis correlates with densities and concentrations of protumoral populations and molecules, providing ideal targets for the intelligent design of directed preventive or anticancer therapies.

  17. New Insights into the Role of the Immune Microenvironment in Breast Carcinoma

    Science.gov (United States)

    de la Cruz-Merino, Luis; Barco-Sánchez, Antonio; Henao Carrasco, Fernando; Nogales Fernández, Esteban; Vallejo Benítez, Ana; Brugal Molina, Javier; Martínez Peinado, Antonio; Grueso López, Ana; Ruiz Borrego, Manuel; Codes Manuel de Villena, Manuel; Sánchez-Margalet, Víctor; Nieto-García, Adoración; Alba Conejo, Emilio; Casares Lagar, Noelia; Ibáñez Martínez, José

    2013-01-01

    Recently, immune edition has been recognized as a new hallmark of cancer. In this respect, some clinical trials in breast cancer have reported imppressive outcomes related to laboratory immune findings, especially in the neoadjuvant and metastatic setting. Infiltration by tumor infiltrating lymphocytes (TIL) and their subtypes, tumor-associated macrophages (TAM) and myeloid-derived suppressive cells (MDSC) seem bona fide prognostic and even predictive biomarkers, that will eventually be incorporated into diagnostic and therapeutic algorithms of breast cancer. In addition, the complex interaction of costimulatory and coinhibitory molecules on the immune synapse and the different signals that they may exert represent another exciting field to explore. In this review we try to summarize and elucidate these new concepts and knowledge from a translational perspective focusing on breast cancer, paying special attention to those aspects that might have more significance in clinical practice and could be useful to design successful therapeutic strategies in the future. PMID:23861693

  18. Transcriptome Analysis of the Sydney Rock Oyster, Saccostrea glomerata: Insights into Molluscan Immunity.

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    Nicole G Ertl

    Full Text Available Oysters have important ecological functions in their natural environment, acting as global carbon sinks and improving water quality by removing excess nutrients from the water column. During their life-time oysters are exposed to a variety of pathogens that can cause severe mortality in a range of oyster species. Environmental stressors encountered in their habitat can increase the susceptibility of oysters to these pathogens and in general have been shown to impact on oyster immunity, making immune parameters expressed in these marine animals an important research topic.Paired-end Illumina high throughput sequencing of six S. glomerata tissues exposed to different environmental stressors resulted in a total of 484,121,702 paired-end reads. When reads and assembled transcripts were compared to the C. gigas genome, an overall low level of similarity at the nucleotide level, but a relatively high similarity at the protein level was observed. Examination of the tissue expression pattern showed that some transcripts coding for cathepsins, heat shock proteins and antioxidant proteins were exclusively expressed in the haemolymph of S. glomerata, suggesting a role in innate immunity. Furthermore, analysis of the S. glomerata ORFs showed a wide range of genes potentially involved in innate immunity, from pattern recognition receptors, components of the Toll-like signalling and apoptosis pathways to a complex antioxidant defence mechanism.This is the first large scale RNA-Seq study carried out in S. glomerata, showing the complex network of innate immune components that exist in this species. The results confirmed that many of the innate immune system components observed in mammals are also conserved in oysters; however, some, such as the TLR adaptors MAL, TRIF and TRAM are either missing or have been modified significantly. The components identified in this study could help explain the oysters' natural resilience against pathogenic microorganisms

  19. Filovirus pathogenesis and immune evasion: insights from Ebola virus and Marburg virus

    Energy Technology Data Exchange (ETDEWEB)

    Messaoudi, Ilhem; Amarasinghe, Gaya K.; Basler, Christopher F.

    2015-10-06

    Ebola viruses and Marburg viruses, members of the filovirus family, are zoonotic pathogens that cause severe disease in people, as highlighted by the latest Ebola virus epidemic in West Africa. Filovirus disease is characterized by uncontrolled virus replication and the activation of host responses that contribute to pathogenesis. Underlying these phenomena is the potent suppression of host innate antiviral responses, particularly the type I interferon response, by viral proteins, which allows high levels of viral replication. In this Review, we describe the mechanisms used by filoviruses to block host innate immunity and discuss the links between immune evasion and filovirus pathogenesis.

  20. Insights into the immune manipulation mechanisms of pollen allergens by protein domain profiling.

    Science.gov (United States)

    Patel, Seema; Rani, Aruna; Goyal, Arun

    2017-10-01

    Plant pollens are airborne allergens, as their inhalation causes immune activation, leading to rhinitis, conjunctivitis, sinusitis and oral allergy syndrome. A myriad of pollen proteins belonging to profilin, expansin, polygalacturonase, glucan endoglucosidase, pectin esterase, and lipid transfer protein class have been identified. In the present in silico study, the protein domains of fifteen pollen sequences were extracted from the UniProt database and submitted to the interactive web tool SMART (Simple Modular Architecture Research Tool), for finding the protein domain profiles. Analysis of the data based on custom-made scripts revealed the conservation of pathogenic domains such as OmpH, PROF, PreSET, Bet_v_1, Cpl-7 and GAS2. Further, the retention of critical domains like CHASE2, Galanin, Dak2, DALR_1, HAMP, PWI, EFh, Excalibur, CT, PbH1, HELICc, and Kelch in pollen proteins, much like cockroach allergens and lethal viruses (such as HIV, HCV, Ebola, Dengue and Zika) was observed. Based on the shared motifs in proteins of taxonomicall-ydispersed organisms, it can be hypothesized that allergens and pathogens manipulate the human immune system in a similar manner. Allergens, being inanimate, cannot replicate in human body, and are neutralized by immune system. But, when the allergens are unremitting, the immune system becomes persistently hyper-sensitized, creating an inflammatory milieu. This study is expected to contribute to the understanding of pollen allergenicity and pathogenicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. In-silico insights on the prognostic potential of immune cell infiltration patterns in the breast lobular epithelium

    Science.gov (United States)

    Alfonso, J. C. L.; Schaadt, N. S.; Schönmeyer, R.; Brieu, N.; Forestier, G.; Wemmert, C.; Feuerhake, F.; Hatzikirou, H.

    2016-09-01

    Scattered inflammatory cells are commonly observed in mammary gland tissue, most likely in response to normal cell turnover by proliferation and apoptosis, or as part of immunosurveillance. In contrast, lymphocytic lobulitis (LLO) is a recurrent inflammation pattern, characterized by lymphoid cells infiltrating lobular structures, that has been associated with increased familial breast cancer risk and immune responses to clinically manifest cancer. The mechanisms and pathogenic implications related to the inflammatory microenvironment in breast tissue are still poorly understood. Currently, the definition of inflammation is mainly descriptive, not allowing a clear distinction of LLO from physiological immunological responses and its role in oncogenesis remains unclear. To gain insights into the prognostic potential of inflammation, we developed an agent-based model of immune and epithelial cell interactions in breast lobular epithelium. Physiological parameters were calibrated from breast tissue samples of women who underwent reduction mammoplasty due to orthopedic or cosmetic reasons. The model allowed to investigate the impact of menstrual cycle length and hormone status on inflammatory responses to cell turnover in the breast tissue. Our findings suggested that the immunological context, defined by the immune cell density, functional orientation and spatial distribution, contains prognostic information previously not captured by conventional diagnostic approaches.

  2. Insight into the mechanisms regulating immune homeostasis in health and disease.

    Science.gov (United States)

    Sirisinha, Stitaya

    2011-03-01

    Innate and adaptive immune systems consist of cells and molecules that work together in concert to fight against microbial infection and maintain homeostasis. Hosts encounter microbes / exogenous pathogen-associated molecular patterns (PAMPs) and endogenous damage-associated molecular patterns (DAMPs) all the time and they must have proper mechanisms to counteract the danger such that appropriate responses (e.g., degree of inflammation and types of mediators induced) can be mounted in different scenarios. Increasing numbers of endogenous danger signals of host origin are being identified including, for example, uric acid and cholesterol crystals, high mobility group box1 (HMGB1) protein, oxidized LDL, vesicans, heat shock proteins (HSPs) and self DNA. Many of these endogenous ligands have been shown to be associated with inflammation-related diseases like atherosclerosis, gout and type 2 diabetes. Several DAMPs appear to have the ability to interact with more than one receptor. We are now beginning to understand how the immune system can distinguish infection from endogenous ligands elaborated following cellular insults and tissue damage. Appropriate responses to maintain the homeostatic state in health and disease depend largely on the recognition and response to these stimuli by germline encoded pattern-recognition receptors (PRRs) present on both immune and non-immune cells. These receptors are, for example, Toll-like receptors (TLRs), C-type lectin receptors (CLRs) and cytosolic receptors (e.g., RLRs, NLRs and some intracellular DNA sensors). Atypical PRR "danger" receptors, like the receptor for advanced glycation end products (RAGE) and their ligands have been identified. A proper response to maintain homeostasis relies on specific negative regulators and regulatory pathways to dampen its response to tissue injury while maintaining the capacity to eliminate infection and induce proper tissue repair. Moreover, some PRRs (e.g., TLR2,TLR4 and NLRP3) and atypical

  3. Mechanistic insights into the role of C-type lectin receptor/CARD9 signaling in human antifungal immunity

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    Rebecca A. Drummond

    2016-04-01

    Full Text Available Human CARD9 deficiency is an autosomal recessive primary immunodeficiency disorder caused by biallelic mutations in the gene CARD9, which encodes a signaling protein that is found downstream of many C-type lectin receptors (CLRs. CLRs encompass a large family of innate recognition receptors, expressed predominantly by myeloid and epithelial cells, which bind fungal carbohydrates and initiate antifungal immune responses. Accordingly, human CARD9 deficiency is associated with the spontaneous development of persistent and severe fungal infections that primarily localize to the skin and subcutaneous tissue, mucosal surfaces and/or central nervous system (CNS. In the last few years, more than 15 missense and nonsense CARD9 mutations have been reported which associate with the development of a wide spectrum of fungal infections caused by a variety of fungal organisms. The mechanisms by which CARD9 provides organ-specific protection against these fungal infections are now emerging. In this review, we summarize recent immunological and clinical advances that have provided significant mechanistic insights into the pathogenesis of human CARD9 deficiency. We also discuss how genetic mutations in CARD9-coupled receptors (Dectin-1, Dectin-2 and CARD9-binding partners (MALT1, BCL10 affect human antifungal immunity relative to CARD9 deficiency, and we highlight major understudied research questions which merit future investigation.

  4. Malaria immunity in man and mosquito: insights into unsolved mysteries of a deadly infectious disease

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    Crompton, Peter D.; Moebius, Jacqueline; Portugal, Silvia; Waisberg, Michael; Hart, Geoffrey; Garver, Lindsey S.; Miller, Louis H.; Barillas, Carolina; Pierce, Susan K.

    2014-01-01

    Malaria is a mosquito-borne disease caused by parasites of the obligate intracellular Apicomplexa family, the most deadly of which, Plasmodium falciparum, prevails in Africa. Malaria imposes a huge health burden on the world’s most vulnerable populations, claiming the lives of nearly a million children and pregnant women each year in Africa alone. Although there is keen interest in eradicating malaria, we do not yet have the necessary tools to meet this challenge, including an effective malaria vaccine and adequate vector control strategies. Here we review what is known about the mechanisms at play in immune resistance to malaria in both the human and mosquito hosts at each step in the parasite’s complex life cycle with a view towards developing the tools that will contribute to the prevention of disease and death and ultimately the goal of malaria eradication. In so doing we hope to inspire immunologists to participate in defeating this devastating disease. PMID:24655294

  5. A possible role for the immune system in adult neurogenesis: new insights from an invertebrate model.

    Science.gov (United States)

    Harzsch, Steffen; von Bohlen Und Halbach, Oliver

    2016-04-01

    Persistent neurogenesis in the adult brain of both vertebrates and invertebrates was previously considered to be driven by self-renewing neuronal stem cells of ectodermal origin. Recent findings in an invertebrate model challenge this view and instead provide evidence for a recruitment of neuronal precursors from a non-neuronal source. In the brain of adult crayfish, a neurogenic niche was identified that contributes progeny to the adult central olfactory pathway. The niche may function in attracting cells from the hemolymph and transforming them into cells with a neuronal fate. This finding implies that the first-generation neuronal precursors located in the crayfish neurogenic niche are not self-renewing. Evidence is summarized in support of a critical re-evaluation of long-term self-renewal of mammalian neuronal stem cells. Latest findings suggest that a tight link between the immune system and the system driving adult neurogenesis may not only exist in the crayfish but also in mammals. Copyright © 2015 Elsevier GmbH. All rights reserved.

  6. Novel insight into neutrophil immune responses by dry mass determination of Candida albicans morphotypes.

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    Ava Hosseinzadeh

    Full Text Available The common fungal pathogen Candida albicans has the ability to grow as a yeast or as a hypha and can alternate between these morphotypes. The overall biomass of both morphotypes increases with growth. However, only yeasts, but not hyphae, exist as discrete cellular entities. Multiplicity of infection (MOI is a useful parameter to determine the initial inoculum of yeasts for in vitro infection assays. Since the amount of hyphae is difficult to quantify, comparable starting conditions in such assays cannot be determined accurately for yeasts and hyphae using MOI. To circumvent this problem, we have established a set of correlation coefficients to convert fungal metabolic activity and optical density to dry mass. Using these correlations, we were able to accurately compare ROS production and IL-8 release by polymorphonuclear neutrophils upon infection with equal dry mass amounts of yeast and hyphal morphotypes. Neutrophil responses depended on the initial form of infection, irrespective of C. albicans wild-type yeasts transforming to hyphal growth during the assay. Infection with a high mass of live C. albicans yeasts resulted in lower neutrophil ROS and this decrease stems from efficient ROS detoxification by C. albicans without directly affecting the phagocyte ROS machinery. Moreover, we show that dead C. albicans induces significantly less ROS and IL-8 release than live fungi, but thimerosal-killed C. albicans were still able to detoxify neutrophil ROS. Thus, the dry mass approach presented in this study reveals neutrophil responses to different amounts and morphotypes of C. albicans and serves as a template for studies that aim to identify morphotype-specific responses in a variety of immune cells.

  7. Shifting of Immune Responsiveness to House Dust Mite by Influenza A Infection: Genomic Insights

    KAUST Repository

    Al-Garawi, A.

    2011-12-14

    Respiratory viral infections have been associated with an increased incidence of allergic asthma. However, the mechanisms by which respiratory infections facilitate allergic airway disease are incompletely understood.We previously showed that exposure to a low dose of house dust mite (HDM) resulted in enhanced HDM-mediated allergic airway inflammation, and, importantly, marked airway hyperreactivity only when allergen exposure occurred during an acute influenza A infection. In this study, we evaluated the impact of concurrent influenza infection and allergen exposure at the genomic level, using whole-genome micro-array. Our data showed that, in contrast to exposure to a low dose of HDM, influenza A infection led to a dramatic increase in gene expression, particularly of TLRs, C-type lectin receptors, several complement components, as well as FcεR1. Additionally, we observed increased expression of a number of genes encoding chemokines and cytokines associated with the recruitment of proinflammatory cells. Moreover, HDM exposure in the context of an influenza A infection resulted in the induction of unique genes, including calgranulin A (S100a8), an endogenous damage-associated molecular pattern and TLR4 agonist. In addition, we observed significantly increased expression of serum amyloid A (Saa3) and serine protease inhibitor 3n (Serpina3n). This study showed that influenza infection markedly increased the expression of multiple gene classes capable of sensing allergens and amplifying the ensuing immune-inflammatory response. We propose that influenza A infection primes the lung environment in such a way as to lower the threshold of allergen responsiveness, thus facilitating the emergence of a clinically significant allergic phenotype. Copyright © 2012 by The American Association of Immunologists, Inc.

  8. Insight on the impacts of free amino acids and their metabolites on the immune system from a perspective of inborn errors of amino acid metabolism.

    Science.gov (United States)

    Pakula, Malgorzata M; Maier, Thorsten J; Vorup-Jensen, Thomas

    2017-06-01

    Amino acids (AAs) support a broad range of functions in living organisms, including several that affect the immune system. The functions of the immune system are affected when free AAs are depleted or in excess because of external factors, such as starvation, or because of genetic factors, such as inborn errors of metabolism. Areas covered: In this review, we discuss the current insights into how free AAs affect immune responses. When possible, we make comparisons to known disease states resulting from inborn errors of metabolism, in which changed levels of AAs or AA metabolites provide insight into the impact of AAs on the human immune system in vivo. We also explore the literature describing how changes in AA levels might provide pharmaceutical targets for safe immunomodulatory treatment. Expert opinion: The impact of free AAs on the immune system is a neglected topic in most immunology textbooks. That neglect is undeserved, because free AAs have both direct and indirect effects on the immune system. Consistent choices of pre-clinical models and better strategies for creating formulations are required to gain clinical impact.

  9. Insights into the mechanisms of protective immunity against Cryptococcus neoformans infection using a mouse model of pulmonary cryptococcosis.

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    Karen L Wozniak

    2009-09-01

    Full Text Available Cryptococcus neoformans is an opportunistic fungal pathogen that causes life-threatening pneumonia and meningoencephalitis in immune compromised individuals. Previous studies have shown that immunization of BALB/c mice with an IFN-gamma-producing C. neoformans strain, H99gamma, results in complete protection against a second pulmonary challenge with an otherwise lethal cryptococcal strain. The current study evaluated local anamnestic cell-mediated immune responses against pulmonary cryptococcosis in mice immunized with C. neoformans strain H99gamma compared to mice immunized with heat-killed C. neoformans (HKC.n.. Mice immunized with C. neoformans strain H99gamma had significantly reduced pulmonary fungal burden post-secondary challenge compared to mice immunized with HKC.n. Protection against pulmonary cryptococcosis was associated with increased pulmonary granulomatous formation and leukocyte infiltration followed by a rapid resolution of pulmonary inflammation, which protected the lungs from severe allergic bronchopulmonary mycosis (ABPM-pathology that developed in the lungs of mice immunized with HKC.n. Pulmonary challenge of interleukin (IL-4 receptor, IL-12p40, IL-12p35, IFN-gamma, T cell and B cell deficient mice with C. neoformans strain H99gamma demonstrated a requirement for Th1-type T cell-mediated immunity, but not B cell-mediated immunity, for the induction of H99gamma-mediated protective immune responses against pulmonary C. neoformans infection. CD4(+ T cells, CD11c(+ cells, and Gr-1(+ cells were increased in both proportion and absolute number in protected mice. In addition, significantly increased production of Th1-type/pro-inflammatory cytokines and chemokines, and conversely, reduced Th2-type cytokine production was observed in the lungs of protected mice. Interestingly, protection was not associated with increased production of cytokines IFN-gamma or TNF-alpha in lungs of protected mice. In conclusion, immunization with C

  10. Anti-CD4 therapy for AIDS suggested by mathematical models

    NARCIS (Netherlands)

    Boer, R.J. de; Boucher, C.A.B.

    1996-01-01

    HIV-1 infection typically involves a long clinical latency stage during which CD4 counts decline slowly. For the later part of the clinical latency stage it was found recently that this is a highly dynamic phase characterized by rapid turnover rates. Clinical latency can therefore be considered as a

  11. Insights into pathogenic events of HIV-associated Kaposi sarcoma and immune reconstitution syndrome related Kaposi sarcoma

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    Lemmer Johan

    2008-01-01

    Full Text Available Abstract A decrease in the incidence of human immune deficiency virus-associated Kaposi sarcoma (HIV-KS and regression of some established HIV-KS lesions is evident after the introduction of highly active anti-retroviral treatment (HAART, and is attributed to generalized immune restoration, to the reconstitution of human herpesvirus (HHV-8 specific cellular immune responses, and to the decrease in HIV Tat protein and HHV-8 loads following HAART. However, a small subset of HIV-seropositive subjects with a low CD4+ T cell count at the time of introduction of HAART, may develop HIV-KS as immune reconstitution inflammatory syndrome (IRIS within 8 weeks thereafter.

  12. Transcriptional profiling provides insights into metronomic cyclophosphamide-activated, innate immune-dependent regression of brain tumor xenografts

    International Nuclear Information System (INIS)

    Doloff, Joshua C; Waxman, David J

    2015-01-01

    Cyclophosphamide treatment on a six-day repeating metronomic schedule induces a dramatic, innate immune cell-dependent regression of implanted gliomas. However, little is known about the underlying mechanisms whereby metronomic cyclophosphamide induces innate immune cell mobilization and recruitment, or about the role of DNA damage and cell stress response pathways in eliciting the immune responses linked to tumor regression. Untreated and metronomic cyclophosphamide-treated human U251 glioblastoma xenografts were analyzed on human microarrays at two treatment time points to identify responsive tumor cell-specific factors and their upstream regulators. Mouse microarray analysis across two glioma models (human U251, rat 9L) was used to identify host factors and gene networks that contribute to the observed immune and tumor regression responses. Metronomic cyclophosphamide increased expression of tumor cell-derived DNA damage, cell stress, and cell death genes, which may facilitate innate immune activation. Increased expression of many host (mouse) immune networks was also seen in both tumor models, including complement components, toll-like receptors, interferons, and cytolysis pathways. Key upstream regulators activated by metronomic cyclophosphamide include members of the interferon, toll-like receptor, inflammatory response, and PPAR signaling pathways, whose activation may contribute to anti-tumor immunity. Many upstream regulators inhibited by metronomic cyclophosphamide, including hypoxia-inducible factors and MAP kinases, have glioma-promoting activity; their inhibition may contribute to the therapeutic effectiveness of the six-day repeating metronomic cyclophosphamide schedule. Large numbers of responsive cytokines, chemokines and immune regulatory genes linked to innate immune cell recruitment and tumor regression were identified, as were several immunosuppressive factors that may contribute to the observed escape of some tumors from metronomic CPA

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

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    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

  14. Small non-coding RNAs: new insights in modulation of host immune response by intracellular bacterial pathogens

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    Waqas Ahmed

    2016-10-01

    Full Text Available Pathogenic bacteria possess intricate regulatory networks that temporally control the production of virulence factors, and enable the bacteria to survive and proliferate within host cell. Small non-coding RNAs (sRNAs have been identified as important regulators of gene expression in diverse biological contexts. Recent research has shown bacterial sRNAs involved in growth and development, cell proliferation, differentiation, metabolism, cell signaling and immune response through regulating protein–protein interactions or via their ability to base pair with RNA and DNA. In this review, we provide a brief overview of mechanism of action employed by immune-related sRNAs, their known functions in immunity, and how they can be integrated into regulatory circuits that govern virulence, which will facilitates to understand pathogenesis and the development of novel, more effective therapeutic approaches to treat infections caused by intracellular bacterial pathogens.

  15. New insights into enterocin CRL35: mechanism of action and immunity revealed by heterologous expression in Escherichia coli.

    Science.gov (United States)

    Barraza, Daniela E; Ríos Colombo, Natalia S; Galván, Adriana E; Acuña, Leonardo; Minahk, Carlos J; Bellomio, Augusto; Chalón, Miriam C

    2017-09-01

    The role of the class IIa bacteriocin membrane receptor protein remains unclear, and the following two different mechanisms have been proposed: the bacteriocin could interact with the receptor changing it to an open conformation or the receptor might act as an anchor allowing subsequent bacteriocin insertion and membrane disruption. Bacteriocin-producing cells synthesize an immunity protein that forms an inactive bacteriocin-receptor-immunity complex. To better understand the molecular mechanism of enterocin CRL35, the peptide was expressed as the suicidal probe EtpM-enterocin CRL35 in Escherichia coli, a naturally insensitive microorganism since it does not express the receptor. When the bacteriocin is anchored to the periplasmic face of the plasma membrane through the bitopic membrane protein, EtpM , E. coli cells depolarize and die. Moreover, co-expression of the immunity protein prevents the deleterious effect of EtpM-enterocin CRL35. The binding and anchoring of the bacteriocin to the membrane has demonstrated to be a sufficient condition for its membrane insertion. The final step of membrane disruption by EtpM-enterocin CRL35 is independent from the receptor, which means that the mannose PTS might not be involved in the pore structure. In addition, the immunity protein can protect even in the absence of the receptor. © 2017 John Wiley & Sons Ltd.

  16. Hypothyroidism in Cancer Patients on Immune Checkpoint Inhibitors with anti-PD1 Agents: Insights on Underlying Mechanisms.

    Science.gov (United States)

    Alhusseini, M; Samantray, J

    2017-04-01

    Background: Immune therapy using monoclonal antibodies against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death 1 receptor (PD-1) for various cancers have been reported to cause thyroid dysfunction. Little is known, however, about the underlying pathogenic mechanisms and the course of hypothyroidism that subsequently develops. In this report, we use the change in thyroglobulin and thyroid antibody levels in patients on immune therapy who develop hypothyroidism to better understand its pathogenesis as well as examine the status of hypothyroidism in the long term. Methods: We report a case series of 10 patients who developed hypothyroidism after initiation of immune therapy (either anti-PD-1 alone or in combination with anti-CTLA-4). Available thyroid antibodies including anti-thyroglobulin (anti-Tg), anti-thyroid peroxidase (anti-TPO), and thyroid stimulating immunoglobulin (TSI) were noted during the initial thyroiditis phase as well as the hypothyroid phase. Persistence or remission of hypothyroidism was noted at 6 months. Summary: During the thyroiditis phase, 50% of the patients had elevated Tg titers, 40% had elevated anti-Tg, and 40% had elevated TSI. All of these titers decreased during the hypothyroid phase. Permanent hypothyroidism was noted in 80% of the cases. Conclusion: Hypothyroidism following initiation of immune therapy has immunologic and non-immunologic mediated mechanisms and is likely to be persistent. © Georg Thieme Verlag KG Stuttgart · New York.

  17. Ancient duplications and functional divergence in the interferon regulatory factors of vertebrates provide insights into the evolution of vertebrate immune systems.

    Science.gov (United States)

    Du, Kang; Zhong, Zaixuan; Fang, Chengchi; Dai, Wei; Shen, Yanjun; Gan, Xiaoni; He, Shunping

    2018-04-01

    Interferon regulatory factors (IRFs) were first discovered as transcription factors that regulate the transcription of human interferon (IFN)-β. Increasing evidence shows that they might be important players involved in Adaptive immune system (AIS) evolution. Although numbers of IRFs have been identified in chordates, the evolutionary history and functional diversity of this gene family during the early evolution of vertebrates have remained obscure. Using IRF HMM profile and HMMER searches, we identified 148 IRFs in 11 vertebrates and 4 protochordates. For them, we reconstructed the phylogenetic relationships, determined the synteny conservation, investigated the profile of natural selection, and analyzed the expression patterns in four "living fossil" vertebrates: lamprey, elephant shark, coelacanth and bichir. The results from phylogeny and synteny analysis imply that vertebrate IRFs evolved from three predecessors, instead of four as suggested in a previous study, as results from an ancient duplication followed by special expansions and lost during the vertebrate evolution. The profile of natural selection and expression reveals functional dynamics during the process. Together, they suggest that the 2nd whole-genome duplication (2WGD) provided raw materials for innovation in the IRF family, and that the birth of type-I IFN might be an important factor inducing the establishment of IRF-mediated immune networks. As a member involved in the AIS evolution, IRF provide insights into the process and mechanism involved in the complexity and novelties of vertebrate immune systems. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Insight into Genotype-Phenotype Associations through eQTL Mapping in Multiple Cell Types in Health and Immune-Mediated Disease.

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    James E Peters

    2016-03-01

    Full Text Available Genome-wide association studies (GWAS have transformed our understanding of the genetics of complex traits such as autoimmune diseases, but how risk variants contribute to pathogenesis remains largely unknown. Identifying genetic variants that affect gene expression (expression quantitative trait loci, or eQTLs is crucial to addressing this. eQTLs vary between tissues and following in vitro cellular activation, but have not been examined in the context of human inflammatory diseases. We performed eQTL mapping in five primary immune cell types from patients with active inflammatory bowel disease (n = 91, anti-neutrophil cytoplasmic antibody-associated vasculitis (n = 46 and healthy controls (n = 43, revealing eQTLs present only in the context of active inflammatory disease. Moreover, we show that following treatment a proportion of these eQTLs disappear. Through joint analysis of expression data from multiple cell types, we reveal that previous estimates of eQTL immune cell-type specificity are likely to have been exaggerated. Finally, by analysing gene expression data from multiple cell types, we find eQTLs not previously identified by database mining at 34 inflammatory bowel disease-associated loci. In summary, this parallel eQTL analysis in multiple leucocyte subsets from patients with active disease provides new insights into the genetic basis of immune-mediated diseases.

  19. Glia and immune cell signaling in bipolar disorder: insights from neuropharmacology and molecular imaging to clinical application.

    Science.gov (United States)

    Watkins, C C; Sawa, A; Pomper, M G

    2014-01-21

    Bipolar disorder (BD) is a debilitating mental illness characterized by severe fluctuations in mood, sleep, energy and executive functioning. Pharmacological studies of selective serotonin reuptake inhibitors and the monoamine system have helped us to clinically understand bipolar depression. Mood stabilizers such as lithium and valproic acid, the first-line treatments for bipolar mania and depression, inhibit glycogen synthase kinase-3 beta (GSK-3β) and regulate the Wnt pathway. Recent investigations suggest that microglia, the resident immune cells of the brain, provide a physiological link between the serotonin system and the GSK-3β/Wnt pathway through neuroinflammation. We review the pharmacological, translational and brain imaging studies that support a role for microglia in regulating neurotransmitter synthesis and immune cell activation. These investigations provide a model for microglia involvement in the pathophysiology and phenotype of BD that may translate into improved therapies.

  20. Transcriptomic and proteomic insights into innate immunity and adaptations to a symbiotic lifestyle in the gutless marine worm Olavius algarvensis.

    Science.gov (United States)

    Wippler, Juliane; Kleiner, Manuel; Lott, Christian; Gruhl, Alexander; Abraham, Paul E; Giannone, Richard J; Young, Jacque C; Hettich, Robert L; Dubilier, Nicole

    2016-11-21

    The gutless marine worm Olavius algarvensis has a completely reduced digestive and excretory system, and lives in an obligate nutritional symbiosis with bacterial symbionts. While considerable knowledge has been gained of the symbionts, the host has remained largely unstudied. Here, we generated transcriptomes and proteomes of O. algarvensis to better understand how this annelid worm gains nutrition from its symbionts, how it adapted physiologically to a symbiotic lifestyle, and how its innate immune system recognizes and responds to its symbiotic microbiota. Key adaptations to the symbiosis include (i) the expression of gut-specific digestive enzymes despite the absence of a gut, most likely for the digestion of symbionts in the host's epidermal cells; (ii) a modified hemoglobin that may bind hydrogen sulfide produced by two of the worm's symbionts; and (iii) the expression of a very abundant protein for oxygen storage, hemerythrin, that could provide oxygen to the symbionts and the host under anoxic conditions. Additionally, we identified a large repertoire of proteins involved in interactions between the worm's innate immune system and its symbiotic microbiota, such as peptidoglycan recognition proteins, lectins, fibrinogen-related proteins, Toll and scavenger receptors, and antimicrobial proteins. We show how this worm, over the course of evolutionary time, has modified widely-used proteins and changed their expression patterns in adaptation to its symbiotic lifestyle and describe expressed components of the innate immune system in a marine oligochaete. Our results provide further support for the recent realization that animals have evolved within the context of their associations with microbes and that their adaptive responses to symbiotic microbiota have led to biological innovations.

  1. Effects of wheat germ agglutinin on human gastrointestinal epithelium: Insights from an experimental model of immune/epithelial cell interaction

    International Nuclear Information System (INIS)

    Pellegrina, Chiara Dalla; Perbellini, Omar; Scupoli, Maria Teresa; Tomelleri, Carlo; Zanetti, Chiara; Zoccatelli, Gianni; Fusi, Marina; Peruffo, Angelo; Rizzi, Corrado; Chignola, Roberto

    2009-01-01

    Wheat germ agglutinin (WGA) is a plant protein that binds specifically to sugars expressed, among many others, by human gastrointestinal epithelial and immune cells. WGA is a toxic compound and an anti-nutritional factor, but recent works have shown that it may have potential as an anti-tumor drug and as a carrier for oral drugs. To quantitate the toxicity threshold for WGA on normal epithelial cells we previously investigated the effects of the lectin on differentiated Caco2 cells, and showed that in the micromolar range of concentrations WGA could alter the integrity of the epithelium layer and increase its permeability to both mannitol and dextran. WGA was shown to be uptaken by Caco2 cells and only ∼ 0.1% molecules were observed to cross the epithelium layer by transcytosis. Here we show that at nanomolar concentrations WGA is unexpectedly bioactive on immune cells. The supernatants of WGA-stimulated peripheral blood mononuclear cells (PBMC) can alter the integrity of the epithelium layer when administered to the basolateral side of differentiated Caco2 cells and the effects can be partially inhibited by monoclonal antibodies against IL1, IL6 and IL8. At nanomolar concentrations WGA stimulates the synthesis of pro-inflammatory cytokines and thus the biological activity of WGA should be reconsidered by taking into account the effects of WGA on the immune system at the gastrointestinal interface. These results shed new light onto the molecular mechanisms underlying the onset of gastrointestinal disorders observed in vivo upon dietary intake of wheat-based foods.

  2. Genetic Associations in Acquired Immune-Mediated Bone Marrow Failure Syndromes: Insights in Aplastic Anemia and Chronic Idiopathic Neutropenia

    Science.gov (United States)

    Mavroudi, Irene; Papadaki, Helen A.

    2012-01-01

    Increasing interest on the field of autoimmune diseases has unveiled a plethora of genetic factors that predispose to these diseases. However, in immune-mediated bone marrow failure syndromes, such as acquired aplastic anemia and chronic idiopathic neutropenia, in which the pathophysiology results from a myelosuppressive bone marrow microenvironment mainly due to the presence of activated T lymphocytes, leading to the accelerated apoptotic death of the hematopoietic stem and progenitor cells, such genetic associations have been very limited. Various alleles and haplotypes of human leucocyte antigen (HLA) molecules have been implicated in the predisposition of developing the above diseases, as well as polymorphisms of inhibitory cytokines such as interferon-γ, tumor necrosis factor-α, and transforming growth factor-β1 along with polymorphisms on molecules of the immune system including the T-bet transcription factor and signal transducers and activators of transcription. In some cases, specific polymorphisms have been implicated in the outcome of treatment on those patients. PMID:22956967

  3. Urinary tract infection: recent insight into the evolutionary arms race between uropathogenic Escherichia coli and our immune system.

    Science.gov (United States)

    Schwab, Sebastian; Jobin, Katarzyna; Kurts, Christian

    2017-12-01

    Urinary tract infections (UTIs) are among the most common bacterial infections worldwide. Humans evolved various immune-dependent and independent defense mechanisms, while pathogens evolved multiple virulence factors to fight back. This article summarizes recent findings regarding the arms race between hosts and pathogens in UTIs. It was recently reported that macrophage subsets regulate neutrophil-mediated defense in primary UTIs but seem to subvert adaptive immunity upon re-infection. Moreover, some bacterial strains can survive inside macrophages, leading to recurrent infections. Inflammasome activation results in infected host cell death and pathogen release, facilitating the removal of intracellular bacteria. As a counteraction, some bacteria evolved mechanisms to disrupt inflammasome activation. Mucosal-associated invariant T cells are further effectors that can lyse infected epithelial cells and release intracellular bacteria. Once released, the bacteria are phagocytosed by neutrophils. However, some bacteria can inhibit neutrophil migration and deprive neutrophils of nutrients. Furthermore, the complement system, considered generally bactericidal, is exploited by the bacteria for cellular invasion. Another weapon against UTI is antimicrobial peptides, e.g. ribonuclease 7, but its production is inhibited by certain bacterial strains. Thus the arms race in UTI is ongoing, and knowing the enemy's methods can help in developing new drugs to win the race. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  4. Structural Insights into Immune Recognition of the Severe Acute Respiratory Syndrome Coronavirus S Protein Receptor Binding Domain

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    Pak, J.; Sharon, C; Satkunarajah, M; Thierry, C; Cameron, C; Kelvin, D; Seetharaman, J; Cochrane, A; Plummer, F; et. al.

    2009-01-01

    The spike (S) protein of the severe acute respiratory syndrome coronavirus (SARS-CoV) is responsible for host cell attachment and fusion of the viral and host cell membranes. Within S the receptor binding domain (RBD) mediates the interaction with angiotensin-converting enzyme 2 (ACE2), the SARS-CoV host cell receptor. Both S and the RBD are highly immunogenic and both have been found to elicit neutralizing antibodies. Reported here is the X-ray crystal structure of the RBD in complex with the Fab of a neutralizing mouse monoclonal antibody, F26G19, elicited by immunization with chemically inactivated SARS-CoV. The RBD-F26G19 Fab complex represents the first example of the structural characterization of an antibody elicited by an immune response to SARS-CoV or any fragment of it. The structure reveals that the RBD surface recognized by F26G19 overlaps significantly with the surface recognized by ACE2 and, as such, suggests that F26G19 likely neutralizes SARS-CoV by blocking the virus-host cell interaction.

  5. Correlation of proteome-wide changes with social immunity behaviors provides insight into resistance to the parasitic mite, Varroa destructor, in the honey bee (Apis mellifera).

    Science.gov (United States)

    Parker, Robert; Guarna, M Marta; Melathopoulos, Andony P; Moon, Kyung-Mee; White, Rick; Huxter, Elizabeth; Pernal, Stephen F; Foster, Leonard J

    2012-06-29

    Disease is a major factor driving the evolution of many organisms. In honey bees, selection for social behavioral responses is the primary adaptive process facilitating disease resistance. One such process, hygienic behavior, enables bees to resist multiple diseases, including the damaging parasitic mite Varroa destructor. The genetic elements and biochemical factors that drive the expression of these adaptations are currently unknown. Proteomics provides a tool to identify proteins that control behavioral processes, and these proteins can be used as biomarkers to aid identification of disease tolerant colonies. We sampled a large cohort of commercial queen lineages, recording overall mite infestation, hygiene, and the specific hygienic response to V. destructor. We performed proteome-wide correlation analyses in larval integument and adult antennae, identifying several proteins highly predictive of behavior and reduced hive infestation. In the larva, response to wounding was identified as a key adaptive process leading to reduced infestation, and chitin biosynthesis and immune responses appear to represent important disease resistant adaptations. The speed of hygienic behavior may be underpinned by changes in the antenna proteome, and chemosensory and neurological processes could also provide specificity for detection of V. destructor in antennae. Our results provide, for the first time, some insight into how complex behavioural adaptations manifest in the proteome of honey bees. The most important biochemical correlations provide clues as to the underlying molecular mechanisms of social and innate immunity of honey bees. Such changes are indicative of potential divergence in processes controlling the hive-worker maturation.

  6. The natural history of varicella zoster virus infection in Norway: Further insights on exogenous boosting and progressive immunity to herpes zoster.

    Directory of Open Access Journals (Sweden)

    Luigi Marangi

    Full Text Available We use age-structured models for VZV transmission and reactivation to reconstruct the natural history of VZV in Norway based on available pre-vaccination serological data, contact matrices, and herpes zoster incidence data. Depending on the hypotheses on contact and transmission patterns, the basic reproduction number of varicella in Norway ranges between 3.7 and 5.0, implying a vaccine coverage between 73 and 80% to effectively interrupt transmission with a 100% vaccine efficacy against infection. The varicella force of infection peaks during early childhood (3-5 yrs and shows a prolonged phase of higher risk during the childbearing period, though quantitative variations can occur depending on contact patterns. By expressing the magnitude of exogenous boosting as a proportion of the force of infection, it is shown that reactivation is well described by a progressive immunity mechanism sustained by a large, though possibly below 100%, degree of exogenous boosting, in agreement with findings from other Nordic countries, implying large reproduction numbers of boosting. Moreover, magnitudes of exogenous boosting below 40% are robustly disconfirmed by data. These results bring further insight on the magnitude of immunity boosting and its relationship with reactivation.

  7. The transcriptome of Trichuris suis--first molecular insights into a parasite with curative properties for key immune diseases of humans.

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    Cinzia Cantacessi

    Full Text Available Iatrogenic infection of humans with Trichuris suis (a parasitic nematode of swine is being evaluated or promoted as a biological, curative treatment of immune diseases, such as inflammatory bowel disease (IBD and ulcerative colitis, in humans. Although it is understood that short-term T. suis infection in people with such diseases usually induces a modified Th2-immune response, nothing is known about the molecules in the parasite that induce this response.As a first step toward filling the gaps in our knowledge of the molecular biology of T. suis, we characterised the transcriptome of the adult stage of this nematode employing next-generation sequencing and bioinformatic techniques. A total of ∼65,000,000 reads were generated and assembled into ∼20,000 contiguous sequences ( = contigs; ∼17,000 peptides were predicted and classified based on homology searches, protein motifs and gene ontology and biological pathway mapping.These analyses provided interesting insights into a number of molecular groups, particularly predicted excreted/secreted molecules (n = 1,288, likely to be involved in the parasite-host interactions, and also various molecules (n = 120 linked to chemokine, T-cell receptor and TGF-β signalling as well as leukocyte transendothelial migration and natural killer cell-mediated cytotoxicity, which are likely to be immuno-regulatory or -modulatory in the infected host. This information provides a conceptual framework within which to test the immunobiological basis for the curative effect of T. suis infection in humans against some immune diseases. Importantly, the T. suis transcriptome characterised herein provides a curated resource for detailed studies of the immuno-molecular biology of this parasite, and will underpin future genomic and proteomic explorations.

  8. Insight into bacterial virulence mechanisms against host immune response via the Yersinia pestis-human protein-protein interaction network.

    Science.gov (United States)

    Yang, Huiying; Ke, Yuehua; Wang, Jian; Tan, Yafang; Myeni, Sebenzile K; Li, Dong; Shi, Qinghai; Yan, Yanfeng; Chen, Hui; Guo, Zhaobiao; Yuan, Yanzhi; Yang, Xiaoming; Yang, Ruifu; Du, Zongmin

    2011-11-01

    A Yersinia pestis-human protein interaction network is reported here to improve our understanding of its pathogenesis. Up to 204 interactions between 66 Y. pestis bait proteins and 109 human proteins were identified by yeast two-hybrid assay and then combined with 23 previously published interactions to construct a protein-protein interaction network. Topological analysis of the interaction network revealed that human proteins targeted by Y. pestis were significantly enriched in the proteins that are central in the human protein-protein interaction network. Analysis of this network showed that signaling pathways important for host immune responses were preferentially targeted by Y. pestis, including the pathways involved in focal adhesion, regulation of cytoskeleton, leukocyte transendoepithelial migration, and Toll-like receptor (TLR) and mitogen-activated protein kinase (MAPK) signaling. Cellular pathways targeted by Y. pestis are highly relevant to its pathogenesis. Interactions with host proteins involved in focal adhesion and cytoskeketon regulation pathways could account for resistance of Y. pestis to phagocytosis. Interference with TLR and MAPK signaling pathways by Y. pestis reflects common characteristics of pathogen-host interaction that bacterial pathogens have evolved to evade host innate immune response by interacting with proteins in those signaling pathways. Interestingly, a large portion of human proteins interacting with Y. pestis (16/109) also interacted with viral proteins (Epstein-Barr virus [EBV] and hepatitis C virus [HCV]), suggesting that viral and bacterial pathogens attack common cellular functions to facilitate infections. In addition, we identified vasodilator-stimulated phosphoprotein (VASP) as a novel interaction partner of YpkA and showed that YpkA could inhibit in vitro actin assembly mediated by VASP.

  9. RNA-seq analysis of early enteromyxosis in turbot (Scophthalmus maximus): new insights into parasite invasion and immune evasion strategies.

    Science.gov (United States)

    Ronza, Paolo; Robledo, Diego; Bermúdez, Roberto; Losada, Ana Paula; Pardo, Belén G; Sitjà-Bobadilla, Ariadna; Quiroga, María Isabel; Martínez, Paulino

    2016-07-01

    Enteromyxum scophthalmi, an intestinal myxozoan parasite, is the causative agent of a threatening disease for turbot (Scophthalmus maximus, L.) aquaculture. The colonisation of the digestive tract by this parasite leads to a cachectic syndrome associated with high morbidity and mortality rates. This myxosporidiosis has a long pre-patent period and the first detectable clinical and histopathological changes are subtle. The pathogenic mechanisms acting in the early stages of infection are still far from being fully understood. Further information on the host-parasite interaction is needed to assist in finding efficient preventive and therapeutic measures. Here, a RNA-seq-based transcriptome analysis of head kidney, spleen and pyloric caeca from experimentally-infected and control turbot was performed. Only infected fish with early signs of infection, determined by histopathology and immunohistochemical detection of E. scophthalmi, were selected. The RNA-seq analysis revealed, as expected, less intense transcriptomic changes than those previously found during later stages of the disease. Several genes involved in IFN-related pathways were up-regulated in the three organs, suggesting that the IFN-mediated immune response plays a main role in this phase of the disease. Interestingly, an opposite expression pattern had been found in a previous study on severely infected turbot. In addition, possible strategies for immune system evasion were suggested by the down-regulation of different genes encoding complement components and acute phase proteins. At the site of infection (pyloric caeca), modulation of genes related to different structural proteins was detected and the expression profile indicated the inhibition of cell proliferation and differentiation. These transcriptomic changes provide indications regarding the mechanisms of parasite attachment to and invasion of the host. The current results contribute to a better knowledge of the events that characterise the early

  10. Non-classical mechanisms of transcriptional regulation by the vitamin D receptor: insights into calcium homeostasis, immune system regulation and cancer chemoprevention.

    Science.gov (United States)

    Dimitrov, Vassil; Salehi-Tabar, Reyhaneh; An, Beum-Soo; White, John H

    2014-10-01

    Hormonal 1,25-dihydroxyvitamin D [1,25(OH)2D] signals through the nuclear vitamin D receptor (VDR), a ligand-regulated transcription factor. Gene expression profiling studies have revealed that 1,25(OH)2D signaling through the VDR can lead to activation or repression of target gene transcription in roughly equal proportions. Classically, transcriptional regulation by the VDR, similar to other nuclear receptors, has been characterized by its capacity to recognize high affinity cognate vitamin D response elements (VDREs), located in the regulatory regions of target genes. Several biochemical studies revealed that the VDRE-bound receptor recruits a series of coregulatory proteins, leading to transactivation of adjacent target genes. However, genome-wide and other analyses of VDR binding have revealed that a subset of VDR binding sites does not contain VDREs, and that VDREs are not associated with transcriptionally repressed VDR target genes. Work over the last ∼20 years and in particular recent findings have revealed a diverse array of mechanisms by which VDR can form complexes with several other classes of transcriptional activators, leading to repression of gene transcription. Moreover, these efforts have led to several insights into the molecular basis for the physiological regulation of calcium homeostasis, immune system function and cancer chemoprevention by 1,25(OH)2D/VDR signaling. This article is part of a Special Issue entitled '16th Vitamin D Workshop'. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. The role of CD4+ T cells in cell-mediated immunity to LCMV: studies in MHC class I and class II deficient mice

    DEFF Research Database (Denmark)

    Christensen, Jan Pravsgaard; Marker, O; Thomsen, Allan Randrup

    1994-01-01

    Parameters of the virus-specific T-cell response were analysed in order to dissect the contribution of CD4+ and CD8+ T cells to cell-mediated immunity to lymphocytic choriomeningitis virus. In MHC class II deficient mice, initial T-cell responsiveness was not impaired, but virus clearance...... was delayed, and virus-specific Td activity declined more rapidly. Furthermore, class I restricted Tc memory appeared to be impaired in these mice. To directly evaluate the role of CD4+ cells in virus clearance and T-cell mediated inflammation, MHC class I deficient mice were also studied. No virus...... exudate. This low-grade response was associated with some degree of virus control as organ titres were lower in these animals than in matched T-cell deficient nu/nu mice or class I deficient mice treated with anti-CD4 monoclonal antibody. This confirms that CD4+ cells are not needed to induce a virus...

  12. Predictive validity and immune cell involvement in the pathogenesis of piroxicam-accelerated colitis in interleukin-10 knockout mice.

    Science.gov (United States)

    Holgersen, Kristine; Kvist, Peter Helding; Hansen, Axel Kornerup; Holm, Thomas Lindebo

    2014-07-01

    Piroxicam administration is a method for induction of enterocolitis in interleukin-10 knockout (IL-10 k.o.) mice. The piroxicam-accelerated colitis (PAC) IL-10 k.o. model combines a dysregulated immune response against the gut microbiota with a decreased mucosal integrity. The predictive validity and pathogenic mechanisms of the model have not been thoroughly investigated. In this study, IL-10 k.o. mice received piroxicam in the chow, and model qualification was performed by examining the efficacy of prophylactic anti-IL-12/23p40 monoclonal antibody (mAb), anti-TNFα mAb, cyclosporine A (CsA) and oral prednisolone treatment. To evaluate cell involvement in the disease pathogenesis, specific cell subsets were depleted by treatment with anti-CD4 mAb, anti-CD8 mAb or clodronate-encapsulated liposomes. T cell receptor co-stimulation was blocked by CTLA4-Ig. Cytokine profiling ELISAs and calprotectin immunohistochemistry were performed on colon tissue. Treatments with anti-IL-12/23p40 mAb and CsA prevented disease in PAC IL-10 k.o. mice and reduced IFNγ, IL-17A, MPO and calprotectin levels in colon. Anti-TNFα mAb treatment caused amelioration of selected clinical parameters. No effect of prednisolone was detected. Depletion of CD8(+) cells tended to increase mortality, whereas treatment with anti-CD4 mAb or CTLA4-Ig had no significant effect on disease development. Clodronate liposome treatment induced a loss of body weight; nevertheless macrophage depletion was associated with a significant reduction in colonic pathology. In conclusion, reference drugs with known efficacy in severe inflammatory bowel disease were efficacious in the PAC IL-10 k.o. model. Our data indicate that in this model macrophages are a main driver of colitis, whereas CD4(+) cells are not. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. DMPD: Toll-like receptors: from the discovery of NFkappaB to new insights intotranscriptional regulations in innate immunity. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16930560 Toll-like receptors: from the discovery of NFkappaB to new insights intotr...2-13. Epub 2006 Aug 22. (.png) (.svg) (.html) (.csml) Show Toll-like receptors: from the discovery of NFkapp...6930560 Title Toll-like receptors: from the discovery of NFkappaB to new insights intotranscriptional regula

  14. Novel insights in preventing Gram-negative bacterial infection in cirrhotic patients: review on the effects of GM-CSF in maintaining homeostasis of the immune system.

    Science.gov (United States)

    Xu, Dong; Zhao, Manzhi; Song, Yuhu; Song, Jianxin; Huang, Yuancheng; Wang, Junshuai

    2015-01-01

    Cirrhotic patients with dysfunctional and/or low numbers of leukocytes are often infected with bacteria, especially Gram-negative bacteria, which is characterized by producing lipopolysaccharide (LPS). Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine that influences the production, maturation, function, and survival of various immune cells. In this paper, we reviewed not only Toll-like receptors 4 (TLR4) signaling pathway and its immunological effect, but also the specific stimulating function and autocrine performance of GM-CSF on hematopoietic cells, as well as the recent discovery of innate response activator-B cells in protection against microbial sepsis and the direct LPS-TLR4 signaling on hematopoiesis. Thus we concluded that GM-CSF might play important roles in preventing Gram-negative bacterial infections in cirrhotic patients through maintaining immune system functions and homeostasis.

  15. Genome wide transcriptome profiling of a murine acute melioidosis model reveals new insights into how Burkholderia pseudomallei overcomes host innate immunity

    Directory of Open Access Journals (Sweden)

    Nathan Sheila

    2010-11-01

    Full Text Available Abstract Background At present, very little is known about how Burkholderia pseudomallei (B. pseudomallei interacts with its host to elicit melioidosis symptoms. We established a murine acute-phase melioidosis model and used DNA microarray technology to investigate the global host/pathogen interaction. We compared the transcriptome of infected liver and spleen with uninfected tissues over an infection period of 42 hr to identify genes whose expression is altered in response to an acute infection. Results Viable B. pseudomallei cells were consistently detected in the blood, liver and spleen during the 42 hr course of infection. Microarray analysis of the liver and spleen over this time course demonstrated that genes involved in immune response, stress response, cell cycle regulation, proteasomal degradation, cellular metabolism and signal transduction pathways were differentially regulated. Up regulation of toll-like receptor 2 (TLR2 gene expression suggested that a TLR2-mediated signalling pathway is responsible for recognition and initiation of an inflammatory response to the acute B. pseudomallei infection. Most of the highly elevated inflammatory genes are a cohort of "core host immune response" genes commonly seen in general inflammation infections. Concomitant to this initial inflammatory response, we observed an increase in transcripts associated with cell-death, caspase activation and peptidoglysis that ultimately promote tissue injury in the host. The complement system responsible for restoring host cellular homeostasis and eliminating intracellular bacteria was activated only after 24 hr post-infection. However, at this time point, diverse host nutrient metabolic and cellular pathways including glycolysis, fatty acid metabolism and tricarboxylic acid (TCA cycle were repressed. Conclusions This detailed picture of the host transcriptional response during acute melioidosis highlights a broad range of innate immune mechanisms that are

  16. Introduction of OX40 ligand into lymphoma cells elicits anti-lymphoma immunity in vivo.

    Science.gov (United States)

    Kaneko, Hitomi; Hori, Toshiyuki; Yanagita, Soshi; Kadowaki, Norimitsu; Uchiyama, Takashi

    2005-03-01

    OX40, a member of the TNF receptor superfamily, and its ligand (OX40L) play crucial roles in induction and maintenance of integrated T cell immune response. Engagement of OX40L delivers a costimulatory signal to T cells. In this study, we investigated whether inoculation of OX40L-transfected EL4, a murine T cell lymphoma cell line, could induce anti-lymphoma immunity in mice. Female C57BL/6 mice were inoculated with 1 x 10(5) cells of parental EL4, OX40L-transfected EL4 (EL4-OX40L), or mock control vector-transfected EL4 (EL4-mock), and then the tumor size, overall survival, CTL activity of spleen cells, and the immunohistochemistry were compared. While both parental EL4 and EL4-mock grew rapidly, EL4-OX40L was rejected or grew slower than parental EL4 or EL4-mock. Pretreatment of mice with either anti-CD4 or anti-CD8 mAb accelerated the growth of EL4-OX40L, suggesting that both CD4+ and CD8+ T cells were involved in anti-lymphoma immunity. The immunohistochemical study revealed the infiltration of CD8+ T cells into the tumor of EL4-OX40L. In vitro CTL assay demonstrated that spleen cells of mice that had rejected EL4-OX40L had significant cytotoxic activity against parental EL4. The gene transfer of OX40L into lymphoma cells is an eligible and efficient modality to induce anti-lymphoma immunity.

  17. The expression of inflammatory cytokines, TAM tyrosine kinase receptors and their ligands is upregulated in venous leg ulcer patients: a novel insight into chronic wound immunity.

    Science.gov (United States)

    Filkor, Kata; Németh, Tibor; Nagy, István; Kondorosi, Éva; Urbán, Edit; Kemény, Lajos; Szolnoky, Győző

    2016-08-01

    The systemic host defence mechanisms, especially innate immunity, in venous leg ulcer patients are poorly investigated. The aim of the current study was to measure Candida albicans killing activity and gene expressions of pro- and anti-inflammatory cytokines and innate immune response regulators, TAM receptors and ligands of peripheral blood mononuclear cells separated from 69 venous leg ulcer patients and 42 control probands. Leg ulcer patients were stratified into responder and non-responder groups on the basis of wound healing properties. No statistical differences were found in Candida killing among controls, responders and non-responders. Circulating blood mononuclear cells of patients overexpress pro-inflammatory (IL-1α, TNFα, CXCL-8) and anti-inflammatory (IL-10) cytokines as well as TAM receptors (Tyro, Axl, MerTK) and their ligands Gas6 and Protein S compared with those of control individuals. IL-1α is notably overexpressed in venous leg ulcer treatment non-responders; in contrast, Axl gene expression is robustly stronger among responders. These markers may be considered as candidates for the prediction of treatment response among venous leg ulcer patients. © 2015 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  18. New insights into non-conventional epitopes as T cell targets: The missing link for breaking immune tolerance in autoimmune disease?

    Science.gov (United States)

    Harbige, James; Eichmann, Martin; Peakman, Mark

    2017-11-01

    The mechanism by which immune tolerance is breached in autoimmune disease is poorly understood. One possibility is that post-translational modification of self-antigens leads to peripheral recognition of neo-epitopes against which central and peripheral tolerance is inadequate. Accumulating evidence points to multiple mechanisms through which non-germline encoded sequences can give rise to these non-conventional epitopes which in turn engage the immune system as T cell targets. In particular, where these modifications alter the rules of epitope engagement with MHC molecules, such non-conventional epitopes offer a persuasive explanation for associations between specific HLA alleles and autoimmune diseases. In this review article, we discuss current understanding of mechanisms through which non-conventional epitopes may be generated, focusing on several recently described pathways that can transpose germline-encoded sequences. We contextualise these discoveries around type 1 diabetes, the prototypic organ-specific autoimmune disease in which specific HLA-DQ molecules confer high risk. Non-conventional epitopes have the potential to act as tolerance breakers or disease drivers in type 1 diabetes, prompting a timely re-evaluation of models of a etiopathogenesis. Future studies are required to elucidate the disease-relevance of a range of potential non-germline epitopes and their relationship to the natural peptide repertoire. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Insights into the multifunctional role of natural killer enhancing factor-A (NKEF-A/Prx1) in big-belly seahorse (Hippocampus abdominalis): DNA protection, insulin reduction, H2O2 scavenging, and immune modulation activity.

    Science.gov (United States)

    Godahewa, G I; Perera, N C N; Lee, Jehee

    2018-02-05

    Natural killer enhancing factor A (NKEF-A), also known as peroxiredoxin 1 (Prx1), is a well-known antioxidant involved in innate immunity. Although NKEF-A/Prx1 has been studied in different fish species, the present study broadens the knowledge of NKEF-A gene in terms of molecular structure, function, and immune responses in fish species. Hippocampus abdominalis NKEF-A (HaNKEF-A) cDNA encoded a putative protein of 198 amino acids containing a thioredoxin_2 domain, VCP motifs, and three conserved cysteine residues including peroxidatic and resolving cysteines. Amino acid sequence comparison and phylogenetic breakdown showed the higher sequence identity and closer evolutionary position of HaNKEF-A to those of other fish counterparts. A recombinant protein of HaNKEF-A was shown to i) protect supercoiled DNA against mixed catalyzed oxidation, ii) reduce insulin disulfide bonds, and iii) scavenge extracellular H 2 O 2 . Results of in vitro assays demonstrated the concentration dependent antioxidant function of recombinant HaNKEF-A. In addition, qPCR assessments revealed that the HaNKEF-A transcripts were constitutively expressed in fourteen tissues with the highest expression in liver. As an innate immune response, HaNKEF-A transcripts were up-regulated in liver post injection of LPS, Edwardsiella tarda, Streptococcus iniae, and polyinosinic-polycytidylic acid. Thus, HaNKEF-A can safeguards big-belly seahorse from oxidative damage and pathogenic infections. This study provides insight into the functions of NKEF-A/Prx1 in fish species. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Neural circuitry and immunity

    Science.gov (United States)

    Pavlov, Valentin A.; Tracey, Kevin J.

    2015-01-01

    Research during the last decade has significantly advanced our understanding of the molecular mechanisms at the interface between the nervous system and the immune system. Insight into bidirectional neuroimmune communication has characterized the nervous system as an important partner of the immune system in the regulation of inflammation. Neuronal pathways, including the vagus nerve-based inflammatory reflex are physiological regulators of immune function and inflammation. In parallel, neuronal function is altered in conditions characterized by immune dysregulation and inflammation. Here, we review these regulatory mechanisms and describe the neural circuitry modulating immunity. Understanding these mechanisms reveals possibilities to use targeted neuromodulation as a therapeutic approach for inflammatory and autoimmune disorders. These findings and current clinical exploration of neuromodulation in the treatment of inflammatory diseases defines the emerging field of Bioelectronic Medicine. PMID:26512000

  1. New Insights into the Mechanisms of Chinese Herbal Products on Diabetes: A Focus on the “Bacteria-Mucosal Immunity-Inflammation-Diabetes” Axis

    Directory of Open Access Journals (Sweden)

    Zezheng Gao

    2017-01-01

    Full Text Available Diabetes, especially type 2, has been rapidly increasing all over the world. Although many drugs have been developed and used to treat diabetes, side effects and long-term efficacy are of great challenge. Therefore, natural health product and dietary supplements have been of increasing interest alternatively. In this regard, Chinese herbs and herbal products have been considered a rich resource of product development. Although increasing evidence has been produced from various scientific studies, the mechanisms of action are lacking. Here, we have proposed that many herbal monomers and formulae improve glucose homeostasis and diabetes through the BMID axis; B represents gut microbiota, M means mucosal immunity, I represents inflammation, and D represents diabetes. Chinese herbs have been traditionally used to treat diabetes, with minimal side and toxic effects. Here, we reviewed monomers such as berberine, ginsenoside, M. charantia extract, and curcumin and herbal formulae such as Gegen Qinlian Decoction, Danggui Liuhuang Decoction, and Huanglian Wendan Decoction. This review was intended to provide new perspectives and strategies for future diabetes research and product.

  2. A novel C-type lysozyme from Mytilus galloprovincialis: insight into innate immunity and molecular evolution of invertebrate C-type lysozymes.

    Directory of Open Access Journals (Sweden)

    Qing Wang

    Full Text Available A c-type lysozyme (named as MgCLYZ gene was cloned from the mussel Mytilus galloprovincialis. Blast analysis indicated that MgCLYZ was a salivary c-type lysozyme which was mainly found in insects. The nucleotide sequence of MgCLYZ was predicted to encode a polypeptide of 154 amino acid residues with the signal peptide comprising the first 24 residues. The deduced mature peptide of MgCLYZ was of a calculated molecular weight of 14.4 kD and a theoretical isoelectric point (pI of 8.08. Evolution analysis suggested that bivalve branch of the invertebrate c-type lysozymes phylogeny tree underwent positive selection during evolution. By quantitative real-time RT-PCR (qRT-PCR analysis, MgCLYZ transcript was widely detected in all examined tissues and responded sensitively to bacterial challenge in hemocytes and hepatopancreas. The optimal temperature and pH of recombinant MgCLYZ (rMgCLYZ were 20°C and 4, respectively. The rMgCLYZ displayed lytic activities against Gram-positive bacteria including Micrococcus luteus and Staphyloccocus aureus, and Gram-negative bacteria including Vibrio anguillarum, Enterobacter cloacae, Pseudomonas putida, Proteus mirabilis and Bacillus aquimaris. These results suggest that MgCLYZ perhaps play an important role in innate immunity of M. galloprovincialis, and invertebrate c-type lysozymes might be under positive selection in a species-specific manner during evolution for undergoing adaptation to different environment and diverse pathogens.

  3. Similarities and differences between helminth parasites and cancer cell lines in shaping human monocytes: Insights into parallel mechanisms of immune evasion.

    Directory of Open Access Journals (Sweden)

    Prakash Babu Narasimhan

    2018-04-01

    Full Text Available A number of features at the host-parasite interface are reminiscent of those that are also observed at the host-tumor interface. Both cancer cells and parasites establish a tissue microenvironment that allows for immune evasion and may reflect functional alterations of various innate cells. Here, we investigated how the phenotype and function of human monocytes is altered by exposure to cancer cell lines and if these functional and phenotypic alterations parallel those induced by exposure to helminth parasites. Thus, human monocytes were exposed to three different cancer cell lines (breast, ovarian, or glioblastoma or to live microfilariae (mf of Brugia malayi-a causative agent of lymphatic filariasis. After 2 days of co-culture, monocytes exposed to cancer cell lines showed markedly upregulated expression of M1-associated (TNF-α, IL-1β, M2-associated (CCL13, CD206, Mreg-associated (IL-10, TGF-β, and angiogenesis associated (MMP9, VEGF genes. Similar to cancer cell lines, but less dramatically, mf altered the mRNA expression of IL-1β, CCL13, TGM2 and MMP9. When surface expression of the inhibitory ligands PDL1 and PDL2 was assessed, monocytes exposed to both cancer cell lines and to live mf significantly upregulated PDL1 and PDL2 expression. In contrast to exposure to mf, exposure to cancer cell lines increased the phagocytic ability of monocytes and reduced their ability to induce T cell proliferation and to expand Granzyme A+ CD8+ T cells. Our data suggest that despite the fact that helminth parasites and cancer cell lines are extraordinarily disparate, they share the ability to alter the phenotype of human monocytes.

  4. Similarities and differences between helminth parasites and cancer cell lines in shaping human monocytes: Insights into parallel mechanisms of immune evasion.

    Science.gov (United States)

    Narasimhan, Prakash Babu; Akabas, Leor; Tariq, Sameha; Huda, Naureen; Bennuru, Sasisekhar; Sabzevari, Helen; Hofmeister, Robert; Nutman, Thomas B; Tolouei Semnani, Roshanak

    2018-04-01

    A number of features at the host-parasite interface are reminiscent of those that are also observed at the host-tumor interface. Both cancer cells and parasites establish a tissue microenvironment that allows for immune evasion and may reflect functional alterations of various innate cells. Here, we investigated how the phenotype and function of human monocytes is altered by exposure to cancer cell lines and if these functional and phenotypic alterations parallel those induced by exposure to helminth parasites. Thus, human monocytes were exposed to three different cancer cell lines (breast, ovarian, or glioblastoma) or to live microfilariae (mf) of Brugia malayi-a causative agent of lymphatic filariasis. After 2 days of co-culture, monocytes exposed to cancer cell lines showed markedly upregulated expression of M1-associated (TNF-α, IL-1β), M2-associated (CCL13, CD206), Mreg-associated (IL-10, TGF-β), and angiogenesis associated (MMP9, VEGF) genes. Similar to cancer cell lines, but less dramatically, mf altered the mRNA expression of IL-1β, CCL13, TGM2 and MMP9. When surface expression of the inhibitory ligands PDL1 and PDL2 was assessed, monocytes exposed to both cancer cell lines and to live mf significantly upregulated PDL1 and PDL2 expression. In contrast to exposure to mf, exposure to cancer cell lines increased the phagocytic ability of monocytes and reduced their ability to induce T cell proliferation and to expand Granzyme A+ CD8+ T cells. Our data suggest that despite the fact that helminth parasites and cancer cell lines are extraordinarily disparate, they share the ability to alter the phenotype of human monocytes.

  5. Carbon dioxide-dependent regulation of NF-κB family members RelB and p100 gives molecular insight into CO2-dependent immune regulation.

    Science.gov (United States)

    Keogh, Ciara E; Scholz, Carsten C; Rodriguez, Javier; Selfridge, Andrew C; von Kriegsheim, Alexander; Cummins, Eoin P

    2017-07-07

    CO 2 is a physiological gas normally produced in the body during aerobic respiration. Hypercapnia (elevated blood pCO 2 >≈50 mm Hg) is a feature of several lung pathologies, e.g. chronic obstructive pulmonary disease. Hypercapnia is associated with increased susceptibility to bacterial infections and suppression of inflammatory signaling. The NF-κB pathway has been implicated in these effects; however, the molecular mechanisms underpinning cellular sensitivity of the NF-κB pathway to CO 2 are not fully elucidated. Here, we identify several novel CO 2 -dependent changes in the NF-κB pathway. NF-κB family members p100 and RelB translocate to the nucleus in response to CO 2 A cohort of RelB protein-protein interactions ( e.g. with Raf-1 and IκBα) are altered by CO 2 exposure, although others are maintained ( e.g. with p100). RelB is processed by CO 2 in a manner dependent on a key C-terminal domain located in its transactivation domain. Loss of the RelB transactivation domain alters NF-κB-dependent transcriptional activity, and loss of p100 alters sensitivity of RelB to CO 2 Thus, we provide molecular insight into the CO 2 sensitivity of the NF-κB pathway and implicate altered RelB/p100-dependent signaling in the CO 2 -dependent regulation of inflammatory signaling. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Altered Cellular Metabolism Drives Trained Immunity.

    Science.gov (United States)

    Sohrabi, Yahya; Godfrey, Rinesh; Findeisen, Hannes M

    2018-04-04

    Exposing innate immune cells to an initial insult induces a long-term proinflammatory response due to metabolic and epigenetic alterations which encompass an emerging new concept called trained immunity. Recent studies provide novel insights into mechanisms centered on metabolic reprogramming which induce innate immune memory in hematopoietic stem cells and monocytes. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Childhood Immunization

    Science.gov (United States)

    ... lowest levels in history, thanks to years of immunization. Children must get at least some vaccines before ... child provide protection for many years, adults need immunizations too. Centers for Disease Control and Prevention

  8. Immunizations - diabetes

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000331.htm Immunizations - diabetes To use the sharing features on this page, please enable JavaScript. Immunizations (vaccines or vaccinations) help protect you from some ...

  9. Immunization Coverage

    Science.gov (United States)

    ... room/fact-sheets/detail/immunization-coverage","@context":"http://schema.org","@type":"Article"}; العربية 中文 français русский español ... Plan Global Health Observatory (GHO) data - Immunization More information on vaccines and immunization News 1 in 10 ...

  10. Immunizing Children

    Directory of Open Access Journals (Sweden)

    Geraldine Jody Macdonald

    2014-11-01

    Full Text Available This article addresses the complex contexts within which Canadian health professionals engage in immunizing children and focuses on the Canadian practice guidelines and current scientific evidence that direct Canadian health professional competencies. The article begins by presenting two current global vaccine initiatives and links these to immunization in Canada. A selected literature review identifies current best immunization practices. With the purpose of promoting quality improvement, three key Canadian immunization competencies for health professional are highlighted: communication with parents, including those who are experiencing vaccine hesitancy; administration of immunizing agents; and documentation of immunizations. Health professionals are encouraged to reflect on immunization competencies and ensure evidence-based practices underpin vaccine delivery in their primary care settings.

  11. Altering the balance between immune activation versus regulation in the skin to promote CD8+ T-cell activity within epithelial cancers

    DEFF Research Database (Denmark)

    Bridge, Jennifer A.; Overgaard, Nana Haahr; Steptoe, Raymond

    . The expression, in a mouse model (“E7”), of the HPV16 E7 gene in keratinocytes under the control of the K14 promoter, leads to a local immune suppressive environment, as evidenced by the lack of graft rejection when E7 skin grafts are placed on WT recipient mice. Furthermore, well healed (>30 days) E7 skin...... did not reject. As in the WT mice however, rejection could be induced through the coadministration of an anti-CD4 antibody. The data suggest that the removal of a CD4+, non T-reg cell, leads to CD8+ T-cell activity in the skin as evidenced by E7 skin graft destruction....... grafts are not rejected when mice are immunised with E7 peptide in combination with Quil A- or CASAC-based adjuvants. This is despite a substantial increase in E7 peptide/H-2Db pentamer staining in the blood, and marked killing of E7-peptide expressing TC-1 cells when injected i.v., confirming that CD8 T...

  12. Corneal rat-to-mouse xenotransplantation and the effects of anti-CD4 or anti-CD8 treatment on cytokine and nitric oxide production

    Czech Academy of Sciences Publication Activity Database

    Pindjáková, Jana; Vítová, Andrea; Krulová, Magdalena; Zajícová, Alena; Filipec, M.; Holáň, Vladimír

    2005-01-01

    Roč. 18, č. 7 (2005), s. 854-862 ISSN 0934-0874 R&D Projects: GA MZd(CZ) NR7816; GA MZd(CZ) NI7531; GA ČR GP310/02/D162; GA ČR(CZ) GD310/03/H147; GA MŠk(CZ) ME 300; GA AV ČR KSK5020115 Institutional research plan: CEZ:AV0Z5052915 Keywords : corneal xenotransplantation * cytokines * nitric oxide Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.797, year: 2005

  13. Preparation of anti-CD4 monoclonal antibody-conjugated magnetic poly(glycidyl methacrylate) particles and their application on CD4+ lymphocyte separation.

    Science.gov (United States)

    Pimpha, Nuttaporn; Chaleawlert-umpon, Saowaluk; Chruewkamlow, Nuttapol; Kasinrerk, Watchara

    2011-03-15

    Novel immunomagnetic particles have been prepared for separation of CD4(+) lymphocytes. The magnetic nanoparticles with a diameter of approximately 5-6 nm were first synthesized by co-precipitation from ferrous and ferric iron solutions and subsequently encapsulated with poly(glycidyl methacrylate) (PGMA) by precipitation polymerization. Monoclonal antibody specific to CD4 molecules expressed on CD4(+) lymphocytes was conjugated to the surface of magnetic PGMA particles through covalent bonding between epoxide functional groups on the particle surface and primary amine groups of the antibodies. The generated immunomagnetic particles have successfully separated CD4(+) lymphocytes from whole blood with over 95% purity. The results indicated that these particles can be employed for cell separation and provide a strong potential to be applied in various biomedical applications including diagnosis, and monitoring of human diseases. Copyright © 2010 Elsevier B.V. All rights reserved.

  14. Immune regulation and CNS autoimmune disease

    DEFF Research Database (Denmark)

    Antel, J P; Owens, T

    1999-01-01

    The central nervous system is a demonstrated target of both clinical and experimental immune mediated disorders. Immune regulatory mechanisms operative at the levels of the systemic immune system, the blood brain barrier, and within the CNS parenchyma are important determinants of the intensity...... and duration of the tissue directed injury. Convergence of research, involving direct manipulation of specific cells and molecular mediators in animal models and in vitro analysis of human immune and neural cells and tissues, is providing increasing insight into the role of these immune regulatory functions...

  15. Immune System

    Science.gov (United States)

    A properly functioning immune system is essential to good health. It defends the body against infectious agents and in some cases tumor cells. Individuals with immune deficiencies resulting from genetic defects, diseases (e.g., AIDS, leukemia), or drug therapies are more suscepti...

  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. Innate immunity

    African Journals Online (AJOL)

    Ronnie Anderson is Director of the Medical Research Council Unit for Inflammation and Immunity. ... field have included macrophage, T cell, cytokine and cytokine activated killer cell interactions .... monocytes, mast cells, lymphocytes, eccrine.

  18. Childhood immunization

    Science.gov (United States)

    Romain, Sandra; Schillaci, Michael A.

    2009-01-01

    ABSTRACT OBJECTIVE To examine childhood immunization levels relative to the number of family physicians, pediatricians, and public health nurses in Ontario. DESIGN Retrospective comparative analysis of publicly available data on immunization coverage levels and the relative number of family physicians, pediatricians, and public health nurses. SETTING Ontario. PARTICIPANTS Seven-year-old children, family physicians, pediatricians, and public health nurses in Ontario. MAIN OUTCOME MEASURES The association between immunization coverage levels and the relative number of family physicians, pediatricians, and public health nurses. RESULTS We found correlations between immunization coverage levels and the relative number (ie, per 1000 Ontario residents) of family physicians (ρ = 0.60) and pediatricians (ρ = 0.70) and a lower correlation with the relative number of public health nurses (ρ = 0.40), although none of these correlations was significant. A comparison of temporal trends illustrated that variation in the relative number of family physicians and pediatricians in Ontario was associated with similar variation in immunization coverage levels. CONCLUSION Increasing the number of family physicians and pediatricians might help to boost access to immunizations and perhaps other components of cost-saving childhood preventive care. PMID:19910599

  19. 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

  20. 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.

  1. Life span, testis damage and immune cell populations of spleen in C57BL mice with neutron irradiation by lying flat pose

    Energy Technology Data Exchange (ETDEWEB)

    Chun, Ki Jung; kim, Myung Sup; Kyung, Yoo Bo [KAERI, Taejon (Korea)

    2003-10-01

    This study deals with the biological effects of black mouse (C57BL) irradiated with neutron irradiation by using Boron Neutron Capture Therapy facility in HANARO reactor. These include mortality, body wt., hair color, testis volume, sperm count and immune cell populations in mouse spleen after 80 days later by thermal neutron irradiation. Six week old C57BL male mice were irradiated with neutron irradiation for 1 hr or 2 hrs (flux : 1.036739E +09). These irradiat ion doses estimated 15Gy and 30Gy, respectively. Survival days and hair color in mice was checked. On day 80 after irradiation, testis were taken for volume and sperm count. Also spleen was taken for FACS and spleen cells were isolatd and discarded RBC by treating with lysising solution. These cells were placed on ice and immunofluorescence staining was performed. Phycoerythrin (PE )-anti-CD3e, fluorescein isothiocyanate (FITC)-anti-CD4, and FITC-anti-CD8 were added, then the immunostaining cells were incubated on ice for 40 min. The resulting cells were washed with a PBS buffer 3 times and analyzed using a Flow cytometer. All experimental animals survived over 90 days but in case of 30 Gy neutron irradiation, black mice hair were changed white color on the center of the back. Neutron irradiation of black mice show similar in damage of spleen immune cells by subpopulation of T helper and T cytotoxic cells compared to the control non - irradiated group. These results show that treatment of neutron irradiation without boron compounds for 2 hrs in mice can survive over 90 days with hair color change from black to white. Damaged spleen cells recover after long time by irradiation but testis volume and no. of sperm are not recover compared to the normal group in response to neutron irradiation.

  2. Life span, testis damage and immune cell populations of spleen in C57BL mice with neutron irradiation by lying flat pose

    International Nuclear Information System (INIS)

    Chun, Ki Jung; kim, Myung Sup; Kyung, Yoo Bo

    2003-01-01

    This study deals with the biological effects of black mouse (C57BL) irradiated with neutron irradiation by using Boron Neutron Capture Therapy facility in HANARO reactor. These include mortality, body wt., hair color, testis volume, sperm count and immune cell populations in mouse spleen after 80 days later by thermal neutron irradiation. Six week old C57BL male mice were irradiated with neutron irradiation for 1 hr or 2 hrs (flux : 1.036739E +09). These irradiat ion doses estimated 15Gy and 30Gy, respectively. Survival days and hair color in mice was checked. On day 80 after irradiation, testis were taken for volume and sperm count. Also spleen was taken for FACS and spleen cells were isolatd and discarded RBC by treating with lysising solution. These cells were placed on ice and immunofluorescence staining was performed. Phycoerythrin (PE )-anti-CD3e, fluorescein isothiocyanate (FITC)-anti-CD4, and FITC-anti-CD8 were added, then the immunostaining cells were incubated on ice for 40 min. The resulting cells were washed with a PBS buffer 3 times and analyzed using a Flow cytometer. All experimental animals survived over 90 days but in case of 30 Gy neutron irradiation, black mice hair were changed white color on the center of the back. Neutron irradiation of black mice show similar in damage of spleen immune cells by subpopulation of T helper and T cytotoxic cells compared to the control non - irradiated group. These results show that treatment of neutron irradiation without boron compounds for 2 hrs in mice can survive over 90 days with hair color change from black to white. Damaged spleen cells recover after long time by irradiation but testis volume and no. of sperm are not recover compared to the normal group in response to neutron irradiation

  3. [The role of the innate immune system in atopic dermatitis].

    Science.gov (United States)

    Volz, T; Kaesler, S; Skabytska, Y; Biedermann, T

    2015-02-01

    The mechanisms how the innate immune system detects microbes and mounts a rapid immune response have been more and more elucidated in the past years. Subsequently it has been shown that innate immunity also shapes adaptive immune responses and determines their quality that can be either inflammatory or tolerogenic. As atopic dermatitis is characterized by disturbances of innate and adaptive immune responses, colonization with pathogens and defects in skin barrier function, insight into mechanisms of innate immunity has helped to understand the vicious circle of ongoing skin inflammation seen in atopic dermatitis patients. Elucidating general mechanisms of the innate immune system and its functions in atopic dermatitis paves the way for developing new therapies. Especially the novel insights into the human microbiome and potential functional consequences make the innate immune system a very fundamental and promising target. As a result atopic dermatitis manifestations can be attenuated or even resolved. These currently developed strategies will be introduced in the current review.

  4. Immune System

    Science.gov (United States)

    ... of the Immune System Print en español El sistema inmunitario Whether you're stomping through the showers ... of Use Notice of Nondiscrimination Visit the Nemours Web site. Note: All information on TeensHealth® is for ...

  5. Immunizing Adults

    Centers for Disease Control (CDC) Podcasts

    Vaccines aren’t just for kids; adults also need to get immunized. Overall, far too many people 19 years and older aren’t getting the vaccines they need and remain unprotected. In this podcast, Dr. Walter Williams discuss the importance of adults being fully vaccinated.

  6. Africa Insight

    African Journals Online (AJOL)

    Africa Insight is a quarterly, peer-reviewed journal of the Africa Institute of South Africa. It is accredited by the South African National Department of Higher Education and Training (DHET) and is indexed in the International Bibliography of Social Science (IBSS). It is a multi-disciplinary journal primarily focusing on African ...

  7. Vaccines (immunizations) - overview

    Science.gov (United States)

    Vaccinations; Immunizations; Immunize; Vaccine shots; Prevention - vaccine ... of the vaccine. VACCINE SCHEDULE The recommended vaccination (immunization) schedule is updated every 12 months by the ...

  8. Novel intravaginal nanomedicine for the targeted delivery of saquinavir to CD4+ immune cells

    Directory of Open Access Journals (Sweden)

    Yang S

    2013-08-01

    Full Text Available Sidi Yang,1,2 Yufei Chen,1,2 Kaien Gu,1,2 Alicia Dash,1,2 Casey L Sayre,1 Neal M Davies,1 Emmanuel A Ho1,2 1Faculty of Pharmacy, 2Laboratory for Drug Delivery and Biomaterials, University of Manitoba, Winnipeg, MB, Canada Abstract: The goal of this study was to develop and characterize an intravaginal nanomedicine for the active targeted delivery of saquinavir (SQV to CD4+ immune cells as a potential strategy to prevent or reduce HIV infection. The nanomedicine was formulated into a vaginal gel to provide ease in self-administration and to enhance retention within the vaginal tract. SQV-encapsulated nanoparticles (SQV-NPs were prepared from poly(lactic-co-glycolic acid(PLGA and conjugated to antihuman anti-CD4 antibody. Antibody-conjugated SQV-NPs (Ab-SQV-NPs had an encapsulation efficiency (EE% of 74.4% ± 3.7% and an antibody conjugation efficiency (ACE% of 80.95% ± 1.10%. Over 50% of total loaded SQV was released from NPs over 3 days. NPs were rapidly taken up by Sup-T1 cells, with more than a twofold increase in the intracellular levels of SQV when delivered by Ab-SQV-NPs in comparison to controls 1 hour post-treatment. No cytotoxicity was observed when vaginal epithelial cells were treated for 24 hours with drug-free Ab-NPs (1,000 µg/mL, 1% HEC placebo gel (200 mg/mL, or 1% HEC gel loaded with drug-free Ab-NPs (5 mg NPs/g gel, 200 mg/mL of gel mixture. Overall, we described an intravaginal nanomedicine that is nontoxic and can specifically deliver SQV into CD4+ immune cells. This platform may demonstrate potential utility in its application as postexposure prophylaxis for the treatment or reduction of HIV infection, but further studies are required. Keywords: nanoparticles, saquinavir, antibody conjugation, intravaginal gel, HIV/AIDS, microbicide

  9. Bioinformatics functional analysis of let-7a, miR-34a, and miR-199a/b reveals novel insights into immune system pathways and cancer hallmarks for hepatocellular carcinoma.

    Science.gov (United States)

    Soliman, Bangly; Salem, Ahmed; Ghazy, Mohamed; Abu-Shahba, Nourhan; El Hefnawi, Mahmoud

    2018-05-01

    Let-7a, miR-34a, and miR-199 a/b have gained a great attention as master regulators for cellular processes. In particular, these three micro-RNAs act as potential onco-suppressors for hepatocellular carcinoma. Bioinformatics can reveal the functionality of these micro-RNAs through target prediction and functional annotation analysis. In the current study, in silico analysis using innovative servers (miRror Suite, DAVID, miRGator V3.0, GeneTrail) has demonstrated the combinatorial and the individual target genes of these micro-RNAs and further explored their roles in hepatocellular carcinoma progression. There were 87 common target messenger RNAs (p ≤ 0.05) that were predicted to be regulated by the three micro-RNAs using miRror 2.0 target prediction tool. In addition, the functional enrichment analysis of these targets that was performed by DAVID functional annotation and REACTOME tools revealed two major immune-related pathways, eight hepatocellular carcinoma hallmarks-linked pathways, and two pathways that mediate interconnected processes between immune system and hepatocellular carcinoma hallmarks. Moreover, protein-protein interaction network for the predicted common targets was obtained by using STRING database. The individual analysis of target genes and pathways for the three micro-RNAs of interest using miRGator V3.0 and GeneTrail servers revealed some novel predicted target oncogenes such as SOX4, which we validated experimentally, in addition to some regulated pathways of immune system and hepatocarcinogenesis such as insulin signaling pathway and adipocytokine signaling pathway. In general, our results demonstrate that let-7a, miR-34a, and miR-199 a/b have novel interactions in different immune system pathways and major hepatocellular carcinoma hallmarks. Thus, our findings shed more light on the roles of these miRNAs as cancer silencers.

  10. Adult Immunization

    Directory of Open Access Journals (Sweden)

    Omer Coskun

    2008-04-01

    Full Text Available Despite the many advances in modern medicine, each year thousands of people in the world die from diseases that are easily prevented by safe and effective vaccines. Few measures in preventive medicine are of such proven value and as easy to implement as routine immunization against infectious diseases. Prevention of infection by immunization is a lifelong process. There are a number of vaccines that all adults (¡I18 years require. There are also other vaccines that need to be tailored to meet individual variations in risk resulting from occupation, foreign travel, underlying illness, lifestyle and age. In this study, we tried to review this important subject. [TAF Prev Med Bull 2008; 7(2.000: 159-166

  11. Immunizations for Preterm Babies

    Science.gov (United States)

    ... Issues Health Issues Health Issues Conditions Injuries & Emergencies Vaccine Preventable Diseases ... Children > Safety & Prevention > Immunizations > Immunizations For Preterm Babies Safety & ...

  12. Weakened Immune Systems

    Science.gov (United States)

    ... Issues Health Issues Health Issues Conditions Injuries & Emergencies Vaccine Preventable Diseases ... Children > Safety & Prevention > Immunizations > Weakened Immune Systems Safety & Prevention ...

  13. Immunizations: Active vs. Passive

    Science.gov (United States)

    ... Issues Health Issues Health Issues Conditions Injuries & Emergencies Vaccine Preventable Diseases ... Children > Safety & Prevention > Immunizations > Immunizations: Active vs. Passive Safety & ...

  14. Insights into the Impact of CD8+ Immune Modulation on Human Immunodeficiency Virus Evolutionary Dynamics in Distinct Anatomical Compartments by Using Simian Immunodeficiency Virus-Infected Macaque Models of AIDS Progression.

    Science.gov (United States)

    Rife Magalis, Brittany; Nolan, David J; Autissier, Patrick; Burdo, Tricia H; Williams, Kenneth C; Salemi, Marco

    2017-12-01

    A thorough understanding of the role of human immunodeficiency virus (HIV) intrahost evolution in AIDS pathogenesis has been limited by the need for longitudinally sampled viral sequences from the vast target space within the host, which are often difficult to obtain from human subjects. CD8 + lymphocyte-depleted macaques infected with simian immunodeficiency virus (SIV) provide an increasingly utilized model of pathogenesis due to clinical manifestations similar to those for HIV-1 infection and AIDS progression, as well as a characteristic rapid disease onset. Comparison of this model with SIV-infected non-CD8 + lymphocyte-depleted macaques also provides a unique opportunity to investigate the role of CD8 + cells in viral evolution and population dynamics throughout the duration of infection. Using several different phylogenetic methods, we analyzed viral gp120 sequences obtained from extensive longitudinal sampling of multiple tissues and enriched leukocyte populations from SIVmac251-infected macaques with or without CD8 + lymphocyte depletion. SIV evolutionary and selection patterns in non-CD8 + lymphocyte-depleted animals were characterized by sequential population turnover and continual viral adaptation, a scenario readily comparable to intrahost evolutionary patterns during human HIV infection in the absence of antiretroviral therapy. Alternatively, animals that were depleted of CD8 + lymphocytes exhibited greater variation in population dynamics among tissues and cell populations over the course of infection. Our findings highlight the major role for CD8 + lymphocytes in prolonging disease progression through continual control of SIV subpopulations from various anatomical compartments and the potential for greater independent viral evolutionary behavior among these compartments in response to immune modulation. IMPORTANCE Although developments in combined antiretroviral therapy (cART) strategies have successfully prolonged the time to AIDS onset in HIV-1

  15. Integrated Circuit Immunity

    Science.gov (United States)

    Sketoe, J. G.; Clark, Anthony

    2000-01-01

    This paper presents a DOD E3 program overview on integrated circuit immunity. The topics include: 1) EMI Immunity Testing; 2) Threshold Definition; 3) Bias Tee Function; 4) Bias Tee Calibration Set-Up; 5) EDM Test Figure; 6) EMI Immunity Levels; 7) NAND vs. and Gate Immunity; 8) TTL vs. LS Immunity Levels; 9) TP vs. OC Immunity Levels; 10) 7805 Volt Reg Immunity; and 11) Seventies Chip Set. This paper is presented in viewgraph form.

  16. Immune System Quiz

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español Quiz: Immune System KidsHealth / For Kids / Quiz: Immune System Print How much do you know about your immune system? Find out by taking this quiz! About Us ...

  17. Immunization Schedules for Adults

    Science.gov (United States)

    ... ACIP Vaccination Recommendations Why Immunize? Vaccines: The Basics Immunization Schedule for Adults (19 Years of Age and ... diseases that can be prevented by vaccines . 2018 Immunization Schedule Recommended Vaccinations for Adults by Age and ...

  18. Immunizations and African Americans

    Science.gov (United States)

    ... Data > Minority Population Profiles > Black/African American > Immunizations Immunizations and African Americans African American adults are less ... 19 to 35 months had comparable rates of immunization. African American women are as likely to have ...

  19. Instant Childhood Immunization Schedule

    Science.gov (United States)

    ... Recommendations Why Immunize? Vaccines: The Basics Instant Childhood Immunization Schedule Recommend on Facebook Tweet Share Compartir Get ... date. See Disclaimer for additional details. Based on Immunization Schedule for Children 0 through 6 Years of ...

  20. T cell immunity

    OpenAIRE

    Emel Bülbül Başkan

    2013-01-01

    Since birth, our immune system is constantly bombarded with self-antigens and foreign pathogens. To stay healthy, complex immune strategies have evolved in our immune system to maintain self-tolerance and to defend against foreign pathogens. Effector T cells are the key players in steering the immune responses to execute immune functions. While effector T cells were initially identified to be immune promoting, recent studies unraveled negative regulatory functions of effector T cells...

  1. Immunization Action Coalition

    Science.gov (United States)

    ... IAC | Contact | A-Z Index | Donate | Shop | SUBSCRIBE Immunization Action Coalition Favorites ACIP Recommendations Package Inserts Additional Immunization Resources Photos Adult Vaccination Screening Checklists Ask the ...

  2. Antitumor Immunity Is Controlled by Tetraspanin Proteins

    Directory of Open Access Journals (Sweden)

    Fleur Schaper

    2018-05-01

    Full Text Available Antitumor immunity is shaped by the different types of immune cells that are present in the tumor microenvironment (TME. In particular, environmental signals (for instance, soluble factors or cell–cell contact transmitted through the plasma membrane determine whether immune cells are activated or inhibited. Tetraspanin proteins are emerging as central building blocks of the plasma membrane by their capacity to cluster immune receptors, enzymes, and signaling molecules into the tetraspanin web. Whereas some tetraspanins (CD81, CD151, CD9 are widely and broadly expressed, others (CD53, CD37, Tssc6 have an expression pattern restricted to hematopoietic cells. Studies using genetic mouse models have identified important immunological functions of these tetraspanins on different leukocyte subsets, and as such, may be involved in the immune response against tumors. While multiple studies have been performed with regards to deciphering the function of tetraspanins on cancer cells, the effect of tetraspanins on immune cells in the antitumor response remains understudied. In this review, we will focus on tetraspanins expressed by immune cells and discuss their potential role in antitumor immunity. New insights in tetraspanin function in the TME and possible prognostic and therapeutic roles of tetraspanins will be discussed.

  3. Our Immune System

    Science.gov (United States)

    Our Immune System A story for children with primary immunodeficiency diseases Written by Sara LeBien IMMUNE DEFICIENCY FOUNDATION A note ... who are immune deficient to better understand their immune system. What is a “ B-cell, ” a “ T-cell, ” ...

  4. Cross-protective immunity to Leishmania amazonensis is mediated by CD4+ and CD8+-epitopes of Leishmania donovani Nucleoside Hydrolase terminal domains

    Directory of Open Access Journals (Sweden)

    Dirlei eNico

    2014-05-01

    Full Text Available The Nucleoside hydrolase of Leishmania donovani (NH36 is a phylogenetic marker of high homology among Leishmania parasites. In mice and dog vaccination NH36 induces a CD4+ T cell-driven protective response against Leishmania chagasi infection directed against its C-terminal domain (F3. The C-terminal and N-terminal domain vaccines also decreased the footpad lesion caused by Leishmania amazonensis. We studied the basis of the crossed immune response using recombinant generated peptides covering the whole NH36 sequence and saponin for mice prophylaxis against L. amazonensis. The F1 (amino acids 1-103 and F3 peptide (amino acids 199-314 vaccines enhanced the IgG and IgG2a anti-NH36 antibodies to similar levels. The F3 vaccine induced the strongest DTH response, the highest proportions of NH36-specific CD4+ and CD8+ T cells after challenge and the highest expression of IFN-γ and TNF-α. The F1 vaccine, on the other hand, induced a weaker but significant DTH response and a mild enhancement of IFN-γ and TNF-α levels. The in vivo depletion with anti-CD4 or CD8 monoclonal antibodies disclosed that cross-protection against L. amazonensis infection was mediated by a CD4+ T cell response directed against the C-terminal domain (75% of reduction of the size of footpad lesion followed by a CD8+ T cell response against the N-terminal domain of NH36 (57% of reduction of footpad lesions. Both vaccines were capable of inducing long-term cross-immunity. The amino acid sequence of NH36 showed 93% identity to the sequence of the NH A34480 of L. amazonensis which also showed the presence of completely conserved predicted epitopes for CD4+ and CD8+ T cells in F1 domain, and of CD4+ epitopes differing in a single amino acid, in F1 and F3 domains. The identification of the C-terminal and N-terminal domains as the targets of the immune response to NH36 in the model of L. amazonesis infection represents a basis for the rationale development of a bivalent vaccine

  5. Metabolic immune restraints: implications for anticancer vaccines.

    Science.gov (United States)

    Mocellin, Simone

    2010-01-01

    Metabolic immune restraints belong to a highly complex network of molecular mechanisms underlying the failure of naturally occurring and therapeutically induced immune responses against cancer. In the light of the disappointing results yielded so far with anticancer vaccines in the clinical setting, the dissection of the cascade of molecular events leading to tumor immune escape appears the most promising way to develop more effective immunotherapeutic strategies. Here we review the significant advances recently made in the understanding of the tumor-specific metabolic features that contribute to keep malignant cells from being recognized and destroyed by immune effectors. These mechanistic insights are fostering the development of rationally designed therapeutics aimed to revert the immunosuppressive circuits and thus to enhance the effectiveness of anticancer vaccines.

  6. The immune system, adaptation, and machine learning

    Science.gov (United States)

    Farmer, J. Doyne; Packard, Norman H.; Perelson, Alan S.

    1986-10-01

    The immune system is capable of learning, memory, and pattern recognition. By employing genetic operators on a time scale fast enough to observe experimentally, the immune system is able to recognize novel shapes without preprogramming. Here we describe a dynamical model for the immune system that is based on the network hypothesis of Jerne, and is simple enough to simulate on a computer. This model has a strong similarity to an approach to learning and artificial intelligence introduced by Holland, called the classifier system. We demonstrate that simple versions of the classifier system can be cast as a nonlinear dynamical system, and explore the analogy between the immune and classifier systems in detail. Through this comparison we hope to gain insight into the way they perform specific tasks, and to suggest new approaches that might be of value in learning systems.

  7. Immune barriers of Ebola virus infection.

    Science.gov (United States)

    McElroy, Anita K; Mühlberger, Elke; Muñoz-Fontela, César

    2018-02-01

    Since its initial emergence in 1976 in northern Democratic Republic of Congo (DRC), Ebola virus (EBOV) has been a global health concern due to its virulence in humans, the mystery surrounding the identity of its host reservoir and the unpredictable nature of Ebola virus disease (EVD) outbreaks. Early after the first clinical descriptions of a disease resembling a 'septic-shock-like syndrome', with coagulation abnormalities and multi-system organ failure, researchers began to evaluate the role of the host immune response in EVD pathophysiology. In this review, we summarize how data gathered during the last 40 years in the laboratory as well as in the field have provided insight into EBOV immunity. From molecular mechanisms involved in EBOV recognition in infected cells, to antigen processing and adaptive immune responses, we discuss current knowledge on the main immune barriers of infection as well as outstanding research questions. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. [Evasion of anti-infectious immunity by Brucella - A review].

    Science.gov (United States)

    Quan, Wurong; Yang, Yongjie

    2016-05-04

    Brucellosis, caused by Brucella species, is a worldwide zoonosis. As facultative intracellular pathogens, Brucella possess non-classical virulence factor, but its virulence is very powerful and can elicit chronic infections of both animals and humans. Evasion of host anti-infectious immunity is a prerequisite for chronic infections, this ability appears increasingly crucial for Brucella virulence. As successful pathogens, Brucella can escape or suppress innate immunity and modulate adaptive immunity to establish long lasting infections in host cells. In this review, we address the molecular mechanisms of Brucella to evade anti-infectious immunity. This will shed new insights on Brucella virulence and will, potentially, open new prophylactic avenues.

  9. Skin innate immune system

    Directory of Open Access Journals (Sweden)

    Berna Aksoy

    2013-06-01

    Full Text Available All multicellular organisms protect themselves from external universe and microorganisms by innate immune sytem that is constitutively present. Skin innate immune system has several different components composed of epithelial barriers, humoral factors and cellular part. In this review information about skin innate immune system and its components are presented to the reader. Innate immunity, which wasn’t adequately interested in previously, is proven to provide a powerfull early protection system, control many infections before the acquired immunity starts and directs acquired immunity to develop optimally

  10. Eosinophils in mucosal immune responses

    Science.gov (United States)

    Travers, J; Rothenberg, M E

    2015-01-01

    Eosinophils, multifunctional cells that contribute to both innate and adaptive immunity, are involved in the initiation, propagation and resolution of immune responses, including tissue repair. They achieve this multifunctionality by expression of a diverse set of activation receptors, including those that directly recognize pathogens and opsonized targets, and by their ability to store and release preformed cytotoxic mediators that participate in host defense, to produce a variety of de novo pleotropic mediators and cytokines and to interact directly and indirectly with diverse cell types, including adaptive and innate immunocytes and structural cells. Herein, we review the basic biology of eosinophils and then focus on new emerging concepts about their role in mucosal immune homeostasis, particularly maintenance of intestinal IgA. We review emerging data about their development and regulation and describe new concepts concerning mucosal eosinophilic diseases. We describe recently developed therapeutic strategies to modify eosinophil levels and function and provide collective insight about the beneficial and detrimental functions of these enigmatic cells. PMID:25807184

  11. Imbalanced immune homeostasis in immune thrombocytopenia.

    Science.gov (United States)

    Yazdanbakhsh, Karina

    2016-04-01

    Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder resulting from low platelet counts caused by inadequate production as well as increased destruction by autoimmune mechanisms. As with other autoimmune disorders, chronic ITP is characterized by perturbations of immune homeostasis with hyperactivated effector cells as well as defective regulatory arm of the adaptive immune system, which will be reviewed here. Interestingly, some ITP treatments are associated with restoring the regulatory imbalance, although it remains unclear whether the immune system is redirected to a state of tolerance once treatment is discontinued. Understanding the mechanisms that result in breakdown of immune homeostasis in ITP will help to identify novel pathways for restoring tolerance and inhibiting effector cell responses. This information can then be translated into developing therapies for averting autoimmunity not only in ITP but also many autoimmune disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Immune System (For Parents)

    Science.gov (United States)

    ... of the Immune System Print en español El sistema inmunitario The immune system, which is made up ... of Use Notice of Nondiscrimination Visit the Nemours Web site. Note: All information on KidsHealth® is for ...

  13. Immunity by equilibrium.

    Science.gov (United States)

    Eberl, Gérard

    2016-08-01

    The classical model of immunity posits that the immune system reacts to pathogens and injury and restores homeostasis. Indeed, a century of research has uncovered the means and mechanisms by which the immune system recognizes danger and regulates its own activity. However, this classical model does not fully explain complex phenomena, such as tolerance, allergy, the increased prevalence of inflammatory pathologies in industrialized nations and immunity to multiple infections. In this Essay, I propose a model of immunity that is based on equilibrium, in which the healthy immune system is always active and in a state of dynamic equilibrium between antagonistic types of response. This equilibrium is regulated both by the internal milieu and by the microbial environment. As a result, alteration of the internal milieu or microbial environment leads to immune disequilibrium, which determines tolerance, protective immunity and inflammatory pathology.

  14. Immunity's ancient arms

    OpenAIRE

    Litman, Gary W.; Cannon, John P.

    2009-01-01

    Diverse receptors on two types of cell mediate adaptive immunity in jawed vertebrates. In the lamprey, a jawless vertebrate, immunity is likewise compartmentalized but the molecular mechanics are very different.

  15. [Immune system and tumors].

    Science.gov (United States)

    Terme, Magali; Tanchot, Corinne

    2017-02-01

    Despite having been much debated, it is now well established that the immune system plays an essential role in the fight against cancer. In this article, we will highlight the implication of the immune system in the control of tumor growth and describe the major components of the immune system involved in the antitumoral immune response. The immune system, while exerting pressure on tumor cells, also will play a pro-tumoral role by sculpting the immunogenicity of tumors cells as they develop. Finally, we will illustrate the numerous mechanisms of immune suppression that take place within the tumoral microenvironment which allow tumor cells to escape control from the immune system. The increasingly precise knowledge of the brakes to an effective antitumor immune response allows the development of immunotherapy strategies more and more innovating and promising of hope. Copyright © 2016. Published by Elsevier Masson SAS.

  16. Immune System and Disorders

    Science.gov (United States)

    Your immune system is a complex network of cells, tissues, and organs that work together to defend against germs. It ... t, to find and destroy them. If your immune system cannot do its job, the results can be ...

  17. Aging changes in immunity

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/004008.htm Aging changes in immunity To use the sharing features ... cells and antibodies that destroy these harmful substances. AGING CHANGES AND THEIR EFFECTS ON THE IMMUNE SYSTEM ...

  18. Immunizations for adult women.

    Science.gov (United States)

    Faubion, Stephanie S; Larkin, Lisa C

    2016-12-01

    Immunizations protect individual persons and contribute to public health by reducing morbidity and mortality associated with common infectious diseases. In this Practice Pearl, we review guidelines for adult immunizations and recent and potential changes in vaccines.

  19. Immune system simulation online

    DEFF Research Database (Denmark)

    Rapin, Nicolas; Lund, Ole; Castiglione, Filippo

    2011-01-01

    MOTIVATION: The recognition of antigenic peptides is a major event of an immune response. In current mesoscopic-scale simulators of the immune system, this crucial step has been modeled in a very approximated way. RESULTS: We have equipped an agent-based model of the immune system with immuno...

  20. The Immune System Game

    Science.gov (United States)

    Work, Kirsten A.; Gibbs, Melissa A.; Friedman, Erich J.

    2015-01-01

    We describe a card game that helps introductory biology students understand the basics of the immune response to pathogens. Students simulate the steps of the immune response with cards that represent the pathogens and the cells and molecules mobilized by the immune system. In the process, they learn the similarities and differences between the…

  1. Plant innate immunity

    Indian Academy of Sciences (India)

    Plants are invaded by an array of pathogens of which only a few succeed in causing disease. The attack by others is countered by a sophisticated immune system possessed by the plants. The plant immune system is broadly divided into two, viz. microbial-associated molecular-patterns-triggered immunity (MTI) and ...

  2. Induction of antitumor immunity through xenoplacental immunization

    Directory of Open Access Journals (Sweden)

    Agadjanyan Michael G

    2006-05-01

    Full Text Available Abstract Historically cancer vaccines have yielded suboptimal clinical results. We have developed a novel strategy for eliciting antitumor immunity based upon homology between neoplastic tissue and the developing placenta. Placenta formation shares several key processes with neoplasia, namely: angiogenesis, activation of matrix metalloproteases, and active suppression of immune function. Immune responses against xenoantigens are well known to break self-tolerance. Utilizing xenogeneic placental protein extracts as a vaccine, we have successfully induced anti-tumor immunity against B16 melanoma in C57/BL6 mice, whereas control xenogeneic extracts and B16 tumor extracts where ineffective, or actually promoted tumor growth, respectively. Furthermore, dendritic cells were able to prime tumor immunity when pulsed with the placental xenoantigens. While vaccination-induced tumor regression was abolished in mice depleted of CD4 T cells, both CD4 and CD8 cells were needed to adoptively transfer immunity to naïve mice. Supporting the role of CD8 cells in controlling tumor growth are findings that only freshly isolated CD8 cells from immunized mice were capable of inducing tumor cell caspases-3 activation ex vivo. These data suggest feasibility of using xenogeneic placental preparations as a multivalent vaccine potently targeting not just tumor antigens, but processes that are essential for tumor maintenance of malignant potential.

  3. Epigenetic modulation of host: new insights into immune evasion

    Indian Academy of Sciences (India)

    MADHU

    regulation of gene expression is intrinsically active inside the host and is involved in regulating gene expression and .... self from non-self, helps the packaging of the viral DNA ..... with DNA as genetic material, and having the potential to.

  4. Cytokine regulation of immune tolerance

    OpenAIRE

    Wu, Jie; Xie, Aini; Chen, Wenhao

    2014-01-01

    The immune system provides defenses against invading pathogens while maintaining immune tolerance to self-antigens. This immune homeostasis is harmonized by the direct interactions between immune cells and the cytokine environment in which immune cells develop and function. Herein, we discuss three non-redundant paradigms by which cytokines maintain or break immune tolerance. We firstly describe how anti-inflammatory cytokines exert direct inhibitory effects on immune cells to enforce immune ...

  5. Kidney and innate immunity.

    Science.gov (United States)

    Wang, Ying-Hui; Zhang, Yu-Gen

    2017-03-01

    Innate immune system is an important modulator of the inflammatory response during infection and tissue injury/repair. The kidney as a vital organ with high energy demand plays a key role in regulating the disease related metabolic process. Increasing research interest has focused on the immune pathogenesis of many kidney diseases. However, innate immune cells such as dendritic cells, macrophages, NK cells and a few innate lymphocytes, as well as the complement system are essential for renal immune homeostasis and ensure a coordinated balance between tissue injury and regeneration. The innate immune response provides the first line of host defense initiated by several classes of pattern recognition receptors (PRRs), such as membrane-bound Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), together with inflammasomes responsible for early innate immune response. Although the innate immune system is well studied, the research on the detailed relationship between innate immunity and kidney is still very limited. In this review, we will focus on the innate immune sensing system in renal immune homeostasis, as well as the corresponding pathogenesis of many kidney diseases. The pivotal roles of innate immunity in renal injury and regeneration with special emphasis on kidney disease related immunoregulatory mechanism are also discussed. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  6. Alternative Immune Systems

    Directory of Open Access Journals (Sweden)

    Luis Fernando Cadavid Gutierrez

    2011-09-01

    Full Text Available The immune system in animals is a complex network of molecules, cells and tissues that coordinately maintain the physiological and genetic integrity of the organism. Traditionally, two classes of immunity have been considered, the innate immunity and the adaptive immunity. The former is ancestral, with limited variability and low discrimination. The latter is highly variable, specific and limited to jawed vertebrates. Adaptive immunity is based on antigen receptors that rearrange somatically to generate a nearly unlimited diversity of molecules. Likely, this mechanism of somatic recombination arose as a consequence of a horizontal transfer of transposons and transposases from bacterial genomes in the ancestor of jawed vertebrates. The recent discovery in jawless vertebrates and invertebrates of alternative adaptive immune mechanisms, suggests during evolution different animal groups have found alternative solutions to the problem of immune recognition.

  7. Inflammation, Immunity, and Vaccines for Helicobacter pylori Infection

    DEFF Research Database (Denmark)

    Walduck, Anna; Andersen, Leif P; Raghavan, Sukanya

    2015-01-01

    studies that contribute with new insights in the host response to H. pylori infection. Also, the adaptive immune response to H. pylori and particularly the role of IL-22 have been addressed in some studies. These advances may improve vaccine development where new strategies have been published. Two major...... studies analyzed H. pylori genomes of 39 worldwide strains and looked at the protein profiles. In addition, multi-epitope vaccines for therapeutic use have been investigated. Studies on different adjuvants and delivery systems have also given us new insights. This review presents articles from the last...... year that reveal detailed insight into immunity and regulation of inflammation, the contribution of immune cells to the development of gastric cancer, and understanding mechanisms of vaccine-induced protection....

  8. Role of the immune system in pancreatic cancer progression and immune modulating treatment strategies.

    Science.gov (United States)

    Sideras, K; Braat, H; Kwekkeboom, J; van Eijck, C H; Peppelenbosch, M P; Sleijfer, S; Bruno, M

    2014-05-01

    Traditional chemotherapeutics have largely failed to date to produce significant improvements in pancreatic cancer survival. One of the reasons for the resilience of pancreatic cancer towards intensive treatment is that the cancer is capable of high jacking the immune system: during disease progression the immune system is converted from a system that attacks tumor cells into a support structure for the cancer, exerting trophic actions on the cancer cells. This turn-around of immune system action is achieved through mobilization and activation of regulatory T cells, myeloid derived suppressor cells, tumor-associated macrophages and fibroblasts, all of which suppress CD8 T cells and NK cells. This immune suppression occurs both through the expression of tolerance-inducing cell surface molecules, such as PD-L1, as well as through the production of "tolerogenic" cytokines, such as IL-10 and TGF-β. Based on the accumulating insight into the importance of the immune system for the outcome of pancreatic cancer patients multiple new immunotherapeutic approaches against pancreatic cancer are being currently tested in clinical trials. In this review we give an overview of both the immune escaping mechanisms of pancreatic cancer as well as the new immune related therapeutic strategies currently being tested in pancreatic cancer clinical trials. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Measuring polio immunity to plan immunization activities.

    Science.gov (United States)

    Voorman, Arend; Lyons, Hil M

    2016-11-21

    The Global Polio Eradication Initiative is closer than ever to achieving a polio-free world. Immunization activities must still be carried out in non-endemic countries to maintain population immunity at levels which will stop poliovirus from spreading if it is re-introduced from still-infected areas. In areas where there is no active transmission of poliovirus, programs must rely on surrogate indicators of population immunity to determine the appropriate immunization activities, typically caregiver-reported vaccination history obtained from non-polio acute flaccid paralysis patients identified through polio surveillance. We used regression models to examine the relationship between polio vaccination campaigns and caregiver-reported polio vaccination history. We find that in many countries, vaccination campaigns have a surprisingly weak impact on these commonly used indicators. We conclude that alternative criteria and data, such as routine immunization indicators from vaccination records or household surveys, should be considered for planning polio vaccination campaigns, and that validation of such surrogate indicators is necessary if they are to be used as the basis for program planning and risk assessment. We recommend that the GPEI and similar organizations consider or continue devoting additional resources to rigorously study population immunity and campaign effectiveness in at-risk countries. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Proofs that Develop Insight

    Science.gov (United States)

    Weber, Keith

    2010-01-01

    Many mathematics educators have noted that mathematicians do not only read proofs to gain conviction but also to obtain insight. The goal of this article is to discuss what this insight is from mathematicians' perspective. Based on interviews with nine research-active mathematicians, two sources of insight are discussed. The first is reading a…

  11. Exosomes and their roles in immune regulation and cancer.

    Science.gov (United States)

    Greening, David W; Gopal, Shashi K; Xu, Rong; Simpson, Richard J; Chen, Weisan

    2015-04-01

    Exosomes, a subset of extracellular vesicles (EVs), function as a mode of intercellular communication and molecular transfer. Exosomes facilitate the direct extracellular transfer of proteins, lipids, and miRNA/mRNA/DNAs between cells in vitro and in vivo. The immunological activities of exosomes affect immunoregulation mechanisms including modulating antigen presentation, immune activation, immune suppression, immune surveillance, and intercellular communication. Besides immune cells, cancer cells secrete immunologically active exosomes that influence both physiological and pathological processes. The observation that exosomes isolated from immune cells such as dendritic cells (DCs) modulate the immune response has enforced the way these membranous vesicles are being considered as potential immunotherapeutic reagents. Indeed, tumour- and immune cell-derived exosomes have been shown to carry tumour antigens and promote immunity, leading to eradication of established tumours by CD8(+) T cells and CD4(+) T cells, as well as directly suppressing tumour growth and resistance to malignant tumour development. Further understanding of these areas of exosome biology, and especially of molecular mechanisms involved in immune cell targeting, interaction and manipulation, is likely to provide significant insights into immunorecognition and therapeutic intervention. Here, we review the emerging roles of exosomes in immune regulation and the therapeutic potential in cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Origins of adaptive immunity.

    Science.gov (United States)

    Liongue, Clifford; John, Liza B; Ward, Alister

    2011-01-01

    Adaptive immunity, involving distinctive antibody- and cell-mediated responses to specific antigens based on "memory" of previous exposure, is a hallmark of higher vertebrates. It has been argued that adaptive immunity arose rapidly, as articulated in the "big bang theory" surrounding its origins, which stresses the importance of coincident whole-genome duplications. Through a close examination of the key molecules and molecular processes underpinning adaptive immunity, this review suggests a less-extreme model, in which adaptive immunity emerged as part of longer evolutionary journey. Clearly, whole-genome duplications provided additional raw genetic materials that were vital to the emergence of adaptive immunity, but a variety of other genetic events were also required to generate some of the key molecules, whereas others were preexisting and simply co-opted into adaptive immunity.

  13. Novel Insights Into Causes of Scleroderma Offer Potential New Treatment Strategies

    Science.gov (United States)

    ... Spotlight on Research Novel Insights Into Causes of Scleroderma Offer Potential New Treatment Strategies By Kirstie Saltsman, Ph.D. | December 15, 2013 In scleroderma, immune cells invade the skin, but the role ...

  14. Introduction to the role of the immune system in melanoma.

    Science.gov (United States)

    Margolin, Kim

    2014-06-01

    The concept of immunosurveillance of cancer has been widely accepted for many years, but only recently have the precise mechanisms of tumor-host immune interactions been revealed. Inflammatory and immune reactions play a role in melanomagenesis, and may contribute to the eradication of tumor as well as potentiating its growth and proliferation. Studies of the role of tumor-immune system interactions are providing insights into the pathogenesis and opportunities for highly effective therapeutic strategies. Some patients, even with advanced disease, are now cured with immunotherapy, and increasing numbers of such cures are likely in future. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Friends and foes of tuberculosis: modulation of protective immunity.

    Science.gov (United States)

    Brighenti, Susanna; Joosten, Simone A

    2018-05-27

    Protective immunity in tuberculosis (TB) is subject of debate in the TB research community, as this is key to fully understand TB pathogenesis and to develop new promising tools for TB diagnosis and prognosis as well as a more efficient TB vaccine. IFN-γ producing CD4 + T cells are key in TB control, but may not be sufficient to provide protection. Additional subsets have been identified that contribute to protection such as multifunctional and cytolytic T cell subsets, including classical and non-classical T cells as well as novel innate immune cell subsets resulting from trained immunity. However, to define protective immune responses against TB, the complexity of balancing TB immunity also has to be considered. In this review, insights in effector cell immunity and how this is modulated by regulatory cells, associated comorbidities and the host microbiome is discussed. We systematically map how different suppressive immune cell subsets may affect effector cell responses at the local site of infection. We also dissect how common co-morbidities such as HIV, helminthes and diabetes may bias protective TB immunity towards pathogenic and regulatory responses. Finally, also the composition and diversity of the microbiome in the lung and gut could affect host TB immunity. Understanding these various aspects of the immunological balance in the human host is fundamental to prevent TB infection and disease. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  16. Stress Hyperglycemia, Insulin Treatment, and Innate Immune Cells

    Directory of Open Access Journals (Sweden)

    Fangming Xiu

    2014-01-01

    Full Text Available Hyperglycemia (HG and insulin resistance are the hallmarks of a profoundly altered metabolism in critical illness resulting from the release of cortisol, catecholamines, and cytokines, as well as glucagon and growth hormone. Recent studies have proposed a fundamental role of the immune system towards the development of insulin resistance in traumatic patients. A comprehensive review of published literatures on the effects of hyperglycemia and insulin on innate immunity in critical illness was conducted. This review explored the interaction between the innate immune system and trauma-induced hypermetabolism, while providing greater insight into unraveling the relationship between innate immune cells and hyperglycemia. Critical illness substantially disturbs glucose metabolism resulting in a state of hyperglycemia. Alterations in glucose and insulin regulation affect the immune function of cellular components comprising the innate immunity system. Innate immune system dysfunction via hyperglycemia is associated with a higher morbidity and mortality in critical illness. Along with others, we hypothesize that reduction in morbidity and mortality observed in patients receiving insulin treatment is partially due to its effect on the attenuation of the immune response. However, there still remains substantial controversy regarding moderate versus intensive insulin treatment. Future studies need to determine the integrated effects of HG and insulin on the regulation of innate immunity in order to provide more effective insulin treatment regimen for these patients.

  17. 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

  18. Ethics of Immunization

    NARCIS (Netherlands)

    Verweij, M.F.; Quah, S.R.; Cockerham, W.C.

    2017-01-01

    Collective immunization can be highly effective in protecting societies against infectious diseases, but policy decisions about both the character and the content of immunization policies require ethical justification. This article offers an overview of ethical aspects that should be taken into

  19. Immunity and skin cancer

    International Nuclear Information System (INIS)

    Smith, E.B.; Brysk, M.M.

    1981-01-01

    Observations in humans and animal studies support the theory that immunologic surveillance plays an important role in limiting the development of skin malignancies. These immune responses undergo progressive diminution with age. In addition, other factors, such as bereavement, poor nutrition, and acute and chronic exposure to ultraviolet light, can further diminish immune mechanisms

  20. Immunizations. Position Statement. Revised

    Science.gov (United States)

    Bobo, Nichole; Garrett, Jennifer; Teskey, Carmen; Duncan, Kay; Strasser, Kathy; Burrows-Mezu, Alicia L.

    2015-01-01

    It is the position of the National Association of School Nurses (NASN) that immunizations are essential to primary prevention of disease from infancy through adulthood. Promotion of immunizations by the registered professional school nurse (hereinafter referred to as school nurse) is central to the public health focus of school nursing practice…

  1. Disparity in childhood immunizations

    NARCIS (Netherlands)

    Lemstra, Mark; Neudorf, Cory; Opondo, Johnmark; Toye, Jennifer; Kurji, Ayisha; Kunst, Anton; Tournier, Ceal

    2007-01-01

    BACKGROUND: Incomplete immunization coverage is common in low-income families and Aboriginal children in Canada. OBJECTIVE: To determine whether child immunization coverage rates at two years of age were lower in low-income neighbourhoods of Saskatoon, Saskatchewan. METHODS: Parents who were and

  2. Immune dysfunction in periparturient dairy cows: Insight into pharmacologic and dietary immune treatments

    Science.gov (United States)

    With a $40.5 billion Gross Domestic Value for milk produced in the U.S. during 2013, the dairy industry was the third largest sector of the 2013 U.S. animal agriculture economic engine. The value of milk produced in 2013 represented 24% of the total value of animal agriculture production; this figu...

  3. In Search of Insight.

    Science.gov (United States)

    Kaplan, Craig A.; Simon, Herbert A.

    1990-01-01

    Attaining the insight needed to solve the Mutilated Checkerboard problem, which requires discovery of an effective problem representation (EPR), is described. Performance on insight problems can be predicted from the availability of generators and constraints in the search for an EPR. Data for 23 undergraduates were analyzed. (TJH)

  4. 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...

  5. Periodontitis: from microbial immune subversion to systemic inflammation

    Science.gov (United States)

    Hajishengallis, George

    2014-01-01

    Periodontitis is a dysbiotic inflammatory disease with an adverse impact on systemic health. Recent studies have provided insights into the emergence and persistence of dysbiotic oral microbial communities, which can mediate inflammatory pathology at local as well as distant sites. This Review discusses mechanisms of microbial immune subversion that tip the balance from homeostasis to disease in oral or extraoral sites. PMID:25534621

  6. Crucial role of antibodies to pertactin in Bordetella pertussis immunity

    NARCIS (Netherlands)

    Hellwig, SMM; Rodriguez, ME; Berbers, GAM; de Winkel, JGJV; Mooi, FR

    2003-01-01

    Pertussis, a serious infectious disease of the respiratory tract caused by Bordetella pertussis, is reemerging in vaccinated populations. Efforts to curtail this disease are hampered by limited insight into the basis of protective immunity. Opsonophagocytosis was recently found to play a central

  7. Rebuilding immunity with Remune.

    Science.gov (United States)

    Whitfield, L

    1998-01-01

    Remune, an immune response therapy composed of inactivated HIV, is designed to enhance the immune system's ability to recognize and kill HIV proteins. Developed by Dr. Jonas Salk, researchers hope Remune's actions can alter the course of HIV infection and slow disease progression. Remune has gained Food and Drug Administration (FDA) approval to enter the critical Phase III trial stage. Two clinical trials are tracking Remune's immunogenicity (ability to provoke an immune response), its immunogenicity relative to dose level, and its effect on viral load. An ongoing trial, approved in February of 1996, enrolled 2,500 patients at 74 sites. The manufacturer, Immune Response Corporation (IRC), announced earlier this year that treatment with Remune induces an immune response to HIV that cross-reacts with different strains of the virus. This immune response is crucial for developing an effective worldwide treatment. Remune decreases levels of tumor necrosis factor alpha (TNF-a). IRC recently began a Phase I clinical trial in Great Britain that combines Remune with a protease inhibitor, two antiviral nucleoside analogues, and Interleukin-2. The trial is designed to determine the role that the drug may play in restoring immune response.

  8. National Network for Immunization Information

    Science.gov (United States)

    ... American College of Obstetricians and Gynecologists . © Copyright National Network for Immunization Information. The information contained in the National Network for Immunization Information Web site should not be ...

  9. Immunity: Insect Immune Memory Goes Viral.

    Science.gov (United States)

    Ligoxygakis, Petros

    2017-11-20

    Adaptive memory in insect immunity has been controversial. In this issue, Andino and co-workers propose that acquisition of viral sequences in the host genome gives rise to anti-sense, anti-viral piRNAs. Such sequences can be regarded as both a genomic archive of past infections and as an armour of potential heritable memory. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Regulatory immune cells and functions in autoimmunity and transplantation immunology.

    Science.gov (United States)

    Papp, Gabor; Boros, Peter; Nakken, Britt; Szodoray, Peter; Zeher, Margit

    2017-05-01

    In physiological circumstances, various tolerogenic mechanisms support the protection of self-structures during immune responses. However, quantitative and/or qualitative changes in regulatory immune cells and mediators can evoke auto-reactive immune responses, and upon susceptible genetic background, along with the presence of other concomitant etiological factors, autoimmune disease may develop. In transplant immunology, tolerogenic mechanisms are also critical, since the balance between of alloantigen-reactive effector cells and the regulatory immune cells will ultimately determine whether a graft is accepted or rejected. Better understanding of the immunological tolerance and the potential modulations of immune regulatory processes are crucial for developing effective therapies in autoimmune diseases as well as in organ transplantation. In this review, we focus on the novel insights regarding the impaired immune regulation and other relevant factors contributing to the development of auto-reactive and graft-reactive immune responses in autoimmune diseases and transplant rejection, respectively. We also address some promising approaches for modification of immune-regulatory processes and tolerogenic mechanisms in autoimmunity and solid organ transplantation, which may be beneficial in future therapeutic strategies. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Fish innate immunity against intestinal helminths.

    Science.gov (United States)

    Dezfuli, B S; Bosi, G; DePasquale, J A; Manera, M; Giari, L

    2016-03-01

    Most individual fish in farmed and wild populations are infected with parasites. Upon dissection of fish, helminths from gut are often easily visible. Enteric helminths include several species of digeneans, cestodes, acanthocephalans and nematodes. Some insights into biology, morphology and histopathological effects of the main fish enteric helminths taxa will be described here. The immune system of fish, as that of other vertebrates, can be subdivided into specific and aspecific types, which in vivo act in concert with each other and indeed are interdependent in many ways. Beyond the small number of well-described models that exist, research focusing on innate immunity in fish against parasitic infections is lacking. Enteric helminths frequently cause inflammation of the digestive tract, resulting in a series of chemical and morphological changes in the affected tissues and inducing leukocyte migration to the site of infection. This review provides an overview on the aspecific defence mechanisms of fish intestine against helminths. Emphasis will be placed on the immune cellular response involving mast cells, neutrophils, macrophages, rodlet cells and mucous cells against enteric helminths. Given the relative importance of innate immunity in fish, and the magnitude of economic loss in aquaculture as a consequence of disease, this area deserves considerable attention and support. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. HIV and Immunizations

    Science.gov (United States)

    ... AIDS Drugs Clinical Trials Apps skip to content HIV Treatment Home Understanding HIV/AIDS Fact Sheets HIV ... 4 p.m. ET) Send us an email HIV and Immunizations Last Reviewed: February 6, 2018 Key ...

  13. Immunity to parasitic infection

    National Research Council Canada - National Science Library

    Lamb, Tracey J

    2012-01-01

    .... Often endemic in developing countries many parasitic diseases are neglected in terms of research funding and much remains to be understood about parasites and the interactions they have with the immune system...

  14. Exercise and immunity

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/007165.htm Exercise and immunity To use the sharing features on ... take a daily walk or follow a simple exercise routine a few times a week. Exercise helps ...

  15. Adults Need Immunizations, Too!

    Centers for Disease Control (CDC) Podcasts

    In this podcast, Dr. Andrew Kroger from CDC’s National Center for Immunization and Respiratory Diseases discusses simple, safe, and effective ways adults can help protect themselves, their family, and their community from serious and deadly diseases.

  16. [Exosomes and Immune Cells].

    Science.gov (United States)

    Seo, Naohiro

    2017-05-01

    In addition to the cytokines and cytotoxic granules, exosomes have been known as the intercellular communicator and cytotoxic missile of immune cells for the past decade. It has been well known that mature dendritic cell(DC)-derived exosomes participate in the T cell and natural killer(NK)cell activation, while immature DCs secrete tolerogenic exosomes for regulatory T(Treg)cell generation. Treg cell-derived EVs act as a suppressor against pathogenic type-1 T helper(Th1)cell responses. CD8+ T cells produce tumoricidal exosomes for preventing tumor invasion and metastasis transiently after T cell receptor(TCR)-mediated stimulation. Thus, immune cells produce functional exosomes in the activation state- and/or differentiation stage-dependent manner. In this review, the role of immune cell-derived exosomes will be introduced, focusing mainly on immune reaction against tumor.

  17. Immune responses to metastases

    International Nuclear Information System (INIS)

    Herberman, R.B.; Wiltrout, R.H.; Gorelik, E.

    1987-01-01

    The authors present the changes in the immune system in tumor-bearing hosts that may influence the development of progression of metastases. Included are mononuclear cell infiltration of metastases; alterations in natural resistance mediated by natural killer cells and macrophages; development of specific immunity mediated by T-lymphocytes or antibodies; modulation of tumor-associated antigen expression; and the down-regulation of the immune response to the tumor by several suppressor mechanisms; the augmentation of the immune response and its potential for therapeutic application; includes the prophylaxis of metastases formation by NK cells; the therapy of metastases by augmentation NK-, macrophage-, or T-lymphocyte-mediated responses by biological response modifiers; and the transfer of anticancer activity by cytoxic T-lymphocytes or immunoconjugates of monoclonal antibodies with specificity for tumors

  18. Immunity of international organizations

    CERN Document Server

    Schrijver, Nico

    2015-01-01

    Immunity rules are part and parcel of the law of international organizations. It has long been accepted that international organizations and their staff need to enjoy immunity from the jurisdiction of national courts. However, it is the application of these rules in practice that increasingly causes controversy. Claims against international organizations are brought before national courts by those who allegedly suffer from their activities. These can be both natural and legal persons such as companies. National courts, in particular lower courts, have often been less willing to recognize the immunity of the organization concerned than the organization s founding fathers. Likewise, public opinion and legal writings frequently criticize international organizations for invoking their immunity and for the lack of adequate means of redress for claimants. It is against this background that an international conference was organized at Leiden University in June 2013. A number of highly qualified academics and practit...

  19. 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 ...

  20. Zinc Signals and Immunity.

    Science.gov (United States)

    Maywald, Martina; Wessels, Inga; Rink, Lothar

    2017-10-24

    Zinc homeostasis is crucial for an adequate function of the immune system. Zinc deficiency as well as zinc excess result in severe disturbances in immune cell numbers and activities, which can result in increased susceptibility to infections and development of especially inflammatory diseases. This review focuses on the role of zinc in regulating intracellular signaling pathways in innate as well as adaptive immune cells. Main underlying molecular mechanisms and targets affected by altered zinc homeostasis, including kinases, caspases, phosphatases, and phosphodiesterases, will be highlighted in this article. In addition, the interplay of zinc homeostasis and the redox metabolism in affecting intracellular signaling will be emphasized. Key signaling pathways will be described in detail for the different cell types of the immune system. In this, effects of fast zinc flux, taking place within a few seconds to minutes will be distinguish from slower types of zinc signals, also designated as "zinc waves", and late homeostatic zinc signals regarding prolonged changes in intracellular zinc.

  1. Immunization in pregnancy.

    Science.gov (United States)

    Gruslin, Andrée; Steben, Marc; Halperin, Scott; Money, Deborah M; Yudin, Mark H

    2009-11-01

    To review the evidence and provide recommendations on immunization in pregnancy. Outcomes evaluated include effectiveness of immunization, risks and benefits for mother and fetus. The Medline and Cochrane databases were searched for articles published up to June 2008 on the topic of immunization in pregnancy. The evidence obtained was reviewed and evaluated by the Infectious Diseases Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) under the leadership of the principal authors, and recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care. Implementation of the recommendations in this guideline should result in more appropriate immunization of pregnant and breastfeeding women, decreased risk of contraindicated immunization, and better disease prevention. The quality of evidence reported in this document has been assessed using the evaluation of evidence criteria in the Report of the Canadian Task Force on Preventive Health Care (Table 1). (1) All women of childbearing age should be evaluated for the possibility of pregnancy before immunization. (III-A). (2) Health care providers should obtain a relevant immunization history from all women accessing prenatal care. (III-A). (3) In general, live and/or live-attenuated virus vaccines should not be administered during pregnancy, as there is a, largely theoretical, risk to the fetus. (II-3B). (4) Women who have inadvertently received immunization with live or live-attenuated vaccines during pregnancy should not be counselled to terminate the pregnancy because of a teratogenic risk. (II-2A). (5) Non-pregnant women immunized with a live or live-attenuated vaccine should be counselled to delay pregnancy for at least four weeks. (III-B). (6) Inactivated viral vaccines, bacterial vaccines, and toxoids can be used safely in pregnancy. (II-1A). (7) Women who are breastfeeding can still be immunized (passive-active immunization, live or killed

  2. Immunization alters body odor.

    Science.gov (United States)

    Kimball, Bruce A; Opiekun, Maryanne; Yamazaki, Kunio; Beauchamp, Gary K

    2014-04-10

    Infections have been shown to alter body odor. Because immune activation accompanies both infection and immunization, we tested the hypothesis that classical immunization might similarly result in the alteration of body odors detectable by trained biosensor mice. Using a Y-maze, we trained biosensor mice to distinguish between urine odors from rabies-vaccinated (RV) and unvaccinated control mice. RV-trained mice generalized this training to mice immunized with the equine West Nile virus (WNV) vaccine compared with urine of corresponding controls. These results suggest that there are similarities between body odors of mice immunized with these two vaccines. This conclusion was reinforced when mice could not be trained to directly discriminate between urine odors of RV- versus WNV-treated mice. Next, we trained biosensor mice to discriminate the urine odors of mice treated with lipopolysaccharide (LPS; a general elicitor of innate immunological responses) from the urine of control mice. These LPS-trained biosensors could distinguish between the odors of LPS-treated mouse urine and RV-treated mouse urine. Finally, biosensor mice trained to distinguish between the odors of RV-treated mouse urine and control mouse urine did not generalize this training to discriminate between the odors of LPS-treated mouse urine and control mouse urine. From these experiments, we conclude that: (1) immunization alters urine odor in similar ways for RV and WNV immunizations; and (2) immune activation with LPS also alters urine odor but in ways different from those of RV and WNV. Published by Elsevier Inc.

  3. Adults Need Immunizations, Too!

    Centers for Disease Control (CDC) Podcasts

    2012-03-19

    In this podcast, Dr. Andrew Kroger from CDC’s National Center for Immunization and Respiratory Diseases discusses simple, safe, and effective ways adults can help protect themselves, their family, and their community from serious and deadly diseases.  Created: 3/19/2012 by National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 3/19/2012.

  4. Immune dysfunction in cirrhosis

    Science.gov (United States)

    Sipeki, Nora; Antal-Szalmas, Peter; Lakatos, Peter L; Papp, Maria

    2014-01-01

    Innate and adaptive immune dysfunction, also referred to as cirrhosis-associated immune dysfunction syndrome, is a major component of cirrhosis, and plays a pivotal role in the pathogenesis of both the acute and chronic worsening of liver function. During the evolution of the disease, acute decompensation events associated with organ failure(s), so-called acute-on chronic liver failure, and chronic decompensation with progression of liver fibrosis and also development of disease specific complications, comprise distinct clinical entities with different immunopathology mechanisms. Enhanced bacterial translocation associated with systemic endotoxemia and increased occurrence of systemic bacterial infections have substantial impacts on both clinical situations. Acute and chronic exposure to bacteria and/or their products, however, can result in variable clinical consequences. The immune status of patients is not constant during the illness; consequently, alterations of the balance between pro- and anti-inflammatory processes result in very different dynamic courses. In this review we give a detailed overview of acquired immune dysfunction and its consequences for cirrhosis. We demonstrate the substantial influence of inherited innate immune dysfunction on acute and chronic inflammatory processes in cirrhosis caused by the pre-existing acquired immune dysfunction with limited compensatory mechanisms. Moreover, we highlight the current facts and future perspectives of how the assessment of immune dysfunction can assist clinicians in everyday practical decision-making when establishing treatment and care strategies for the patients with end-stage liver disease. Early and efficient recognition of inappropriate performance of the immune system is essential for overcoming complications, delaying progression and reducing mortality. PMID:24627592

  5. Immunity to Fish Rhabdoviruses

    OpenAIRE

    Purcell, Maureen K.; Laing, Kerry J.; Winton, James R.

    2012-01-01

    Members of the family Rhabdoviridae are single-stranded RNA viruses and globally important pathogens of wild and cultured fish and thus relatively well studied in their respective hosts or other model systems. Here, we review the protective immune mechanisms that fish mount in response to rhabdovirus infections. Teleost fish possess the principal components of innate and adaptive immunity found in other vertebrates. Neutralizing antibodies are critical for long-term protection from fish rhabd...

  6. The role of selenium in inflammation and immunity: from molecular mechanisms to therapeutic opportunities.

    Science.gov (United States)

    Huang, Zhi; Rose, Aaron H; Hoffmann, Peter R

    2012-04-01

    Dietary selenium (]Se), mainly through its incorporation into selenoproteins, plays an important role in inflammation and immunity. Adequate levels of Se are important for initiating immunity, but they are also involved in regulating excessive immune responses and chronic inflammation. Evidence has emerged regarding roles for individual selenoproteins in regulating inflammation and immunity, and this has provided important insight into mechanisms by which Se influences these processes. Se deficiency has long been recognized to negatively impact immune cells during activation, differentiation, and proliferation. This is related to increased oxidative stress, but additional functions such as protein folding and calcium flux may also be impaired in immune cells under Se deficient conditions. Supplementing diets with above-adequate levels of Se can also impinge on immune cell function, with some types of inflammation and immunity particularly affected and sexually dimorphic effects of Se levels in some cases. In this comprehensive article, the roles of Se and individual selenoproteins in regulating immune cell signaling and function are discussed. Particular emphasis is given to how Se and selenoproteins are linked to redox signaling, oxidative burst, calcium flux, and the subsequent effector functions of immune cells. Data obtained from cell culture and animal models are reviewed and compared with those involving human physiology and pathophysiology, including the effects of Se levels on inflammatory or immune-related diseases including anti-viral immunity, autoimmunity, sepsis, allergic asthma, and chronic inflammatory disorders. Finally, the benefits and potential adverse effects of intervention with Se supplementation for various inflammatory or immune disorders are discussed.

  7. Immune mediated liver failure.

    Science.gov (United States)

    Wang, Xiaojing; Ning, Qin

    2014-01-01

    Liver failure is a clinical syndrome of various etiologies, manifesting as jaundice, encephalopathy, coagulopathy and circulatory dysfunction, which result in subsequent multiorgan failure. Clinically, liver failure is classified into four categories: acute, subacute, acute-on-chronic and chronic liver failure. Massive hepatocyte death is considered to be the core event in the development of liver failure, which occurs when the extent of hepatocyte death is beyond the liver regenerative capacity. Direct damage and immune-mediated liver injury are two major factors involved in this process. Increasing evidence has suggested the essential role of immune-mediated liver injury in the pathogenesis of liver failure. Here, we review the evolved concepts concerning the mechanisms of immune-mediated liver injury in liver failure from human and animal studies. Both innate and adaptive immunity, especially the interaction of various immune cells and molecules as well as death receptor signaling system are discussed. In addition, we highlight the concept of "immune coagulation", which has been shown to be related to the disease progression and liver injury exacerbation in HBV related acute-on-chronic liver failure.

  8. Mammalian Gut Immunity

    Science.gov (United States)

    Chassaing, Benoit; Kumar, Manish; Baker, Mark T.; Singh, Vishal; Vijay-Kumar, Matam

    2016-01-01

    The mammalian intestinal tract is the largest immune organ in the body and comprises cells from non-hemopoietic (epithelia, Paneth cells, goblet cells) and hemopoietic (macrophages, dendritic cells, T-cells) origin, and is also a dwelling for trillions of microbes collectively known as the microbiota. The homeostasis of this large microbial biomass is prerequisite to maintain host health by maximizing beneficial symbiotic relationships and minimizing the risks of living in such close proximity. Both microbiota and host immune system communicate with each other to mutually maintain homeostasis in what could be called a “love–hate relationship.” Further, the host innate and adaptive immune arms of the immune system cooperate and compensate each other to maintain the equilibrium of a highly complex gut ecosystem in a stable and stringent fashion. Any imbalance due to innate or adaptive immune deficiency or aberrant immune response may lead to dysbiosis and low-grade to robust gut inflammation, finally resulting in metabolic diseases. PMID:25163502

  9. Immune system handling time may alter the outcome of competition between pathogens and the immune system.

    Science.gov (United States)

    Greenspoon, Philip B; Banton, Sydney; Mideo, Nicole

    2018-06-14

    Predators may be limited in their ability to kill prey (i.e., have type II or III functional responses), an insight that has had far-reaching consequences in the ecological literature. With few exceptions, however, this possibility has not been extended to the behaviour of immune cells, which kill pathogens much as predators kill their prey. Rather, models of the within-host environment have tended to tacitly assume that immune cells have an unlimited ability to target and kill pathogens (i.e., a type I functional response). Here we explore the effects of changing this assumption on infection outcomes (i.e., pathogen loads). We incorporate immune cell handling time into an ecological model of the within-host environment that considers both the predatory nature of the pathogen-immune cell interaction as well as competition between immune cells and pathogens for host resources. Unless pathogens can preempt immune cells for host resources, adding an immune cell handling time increases equilibrium pathogen load. We find that the shape of the relationship between energy intake and pathogen load can change: with a type I functional response, pathogen load is maximised at intermediate inputs, while for a type II or III functional response, pathogen load is solely increasing. With a type II functional response, pathogen load can fluctuate rather than settling to an equilibrium, a phenomenon unobserved with type I or III functional responses. Our work adds to a growing literature highlighting the role of resource availability in host-parasite interactions. Implications of our results for adaptive anorexia are discussed. Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. Mathematical and Computational Modeling for Tumor Virotherapy with Mediated Immunity.

    Science.gov (United States)

    Timalsina, Asim; Tian, Jianjun Paul; Wang, Jin

    2017-08-01

    We propose a new mathematical modeling framework based on partial differential equations to study tumor virotherapy with mediated immunity. The model incorporates both innate and adaptive immune responses and represents the complex interaction among tumor cells, oncolytic viruses, and immune systems on a domain with a moving boundary. Using carefully designed computational methods, we conduct extensive numerical simulation to the model. The results allow us to examine tumor development under a wide range of settings and provide insight into several important aspects of the virotherapy, including the dependence of the efficacy on a few key parameters and the delay in the adaptive immunity. Our findings also suggest possible ways to improve the virotherapy for tumor treatment.

  11. Stromal infrastructure of the lymph node and coordination of immunity.

    Science.gov (United States)

    Chang, Jonathan E; Turley, Shannon J

    2015-01-01

    The initiation of adaptive immune responses depends upon the careful maneuvering of lymphocytes and antigen into and within strategically placed lymph nodes (LNs). Non-hematopoietic stromal cells form the cellular infrastructure that directs this process. Once regarded as merely structural features of lymphoid tissues, these cells are now appreciated as essential regulators of immune cell trafficking, fluid flow, and LN homeostasis. Recent advances in the identification and in vivo targeting of specific stromal populations have resulted in striking new insights to the function of stromal cells and reveal a level of complexity previously unrealized. We discuss here recent discoveries that highlight the pivotal role that stromal cells play in orchestrating immune cell homeostasis and adaptive immunity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. DNA Tumor Virus Regulation of Host DNA Methylation and Its Implications for Immune Evasion and Oncogenesis.

    Science.gov (United States)

    Kuss-Duerkop, Sharon K; Westrich, Joseph A; Pyeon, Dohun

    2018-02-13

    Viruses have evolved various mechanisms to evade host immunity and ensure efficient viral replication and persistence. Several DNA tumor viruses modulate host DNA methyltransferases for epigenetic dysregulation of immune-related gene expression in host cells. The host immune responses suppressed by virus-induced aberrant DNA methylation are also frequently involved in antitumor immune responses. Here, we describe viral mechanisms and virus-host interactions by which DNA tumor viruses regulate host DNA methylation to evade antiviral immunity, which may contribute to the generation of an immunosuppressive microenvironment during cancer development. Recent trials of immunotherapies have shown promising results to treat multiple cancers; however, a significant number of non-responders necessitate identifying additional targets for cancer immunotherapies. Thus, understanding immune evasion mechanisms of cancer-causing viruses may provide great insights for reversing immune suppression to prevent and treat associated cancers.

  13. DNA Tumor Virus Regulation of Host DNA Methylation and Its Implications for Immune Evasion and Oncogenesis

    Directory of Open Access Journals (Sweden)

    Sharon K. Kuss-Duerkop

    2018-02-01

    Full Text Available Viruses have evolved various mechanisms to evade host immunity and ensure efficient viral replication and persistence. Several DNA tumor viruses modulate host DNA methyltransferases for epigenetic dysregulation of immune-related gene expression in host cells. The host immune responses suppressed by virus-induced aberrant DNA methylation are also frequently involved in antitumor immune responses. Here, we describe viral mechanisms and virus–host interactions by which DNA tumor viruses regulate host DNA methylation to evade antiviral immunity, which may contribute to the generation of an immunosuppressive microenvironment during cancer development. Recent trials of immunotherapies have shown promising results to treat multiple cancers; however, a significant number of non-responders necessitate identifying additional targets for cancer immunotherapies. Thus, understanding immune evasion mechanisms of cancer-causing viruses may provide great insights for reversing immune suppression to prevent and treat associated cancers.

  14. U.S. Immunization program adult immunization activities and resources

    Science.gov (United States)

    Woods, LaDora O.; Bridges, Carolyn B.; Graitcer, Samuel B.; Lamont, Brock

    2016-01-01

    ABSTRACT Adults are recommended to receive vaccines based on their age, medical conditions, prior vaccinations, occupation and lifestyle. However, adult immunization coverage is low in the United States and lags substantially below Healthy People 2020 goals. To assess activities and resources designated for adult immunization programs by state and local health department immunization programs in the United States, we analyzed 2012 and 2013 data from the Centers for Disease Control and Prevention's (CDC) Program Annual Reports and Progress Assessments (PAPA) survey of CDC-funded immunization programs. Fifty-six of 64 funded US immunization programs' responses were included in the analysis. Eighty-two percent of (n = 46) programs reported having a designated adult immunization coordinator in 2012 and 73% (n = 41) in 2013. Of the 46 coordinators reported in 2012, 30% (n = 14) spent more than 50% of their time on adult immunization activities, and only 24% (n = 10) of the 41 adult coordinators in 2013 spent more than 50% of their time on adult immunization activities. In 2012, 23% (n = 13) of the 56 programs had a separate immunization coalition for adults and 68% (n = 38) included adult issues in their overall immunization program coalition. In 2013, 25% (n = 14) had a separate adult immunization coalition while 57% (n = 32) incorporated adult immunizations into their overall immunization program coalition. The results indicate substantial variation across the US in public health infrastructure to support adult immunizations. Continued assessment of adult immunization resources and activities will be important in improving adult immunization coverage levels though program support. With many programs having limited resources dedicated to improving adult immunization rates in the in US, efforts by the health departments to collaborate with providers and other partners in their jurisdictions to increase awareness, increase the use of proven strategies to improve

  15. Functional Insights from Structural Genomics

    Energy Technology Data Exchange (ETDEWEB)

    Forouhar,F.; Kuzin, A.; Seetharaman, J.; Lee, I.; Zhou, W.; Abashidze, M.; Chen, Y.; Montelione, G.; Tong, L.; et al

    2007-01-01

    Structural genomics efforts have produced structural information, either directly or by modeling, for thousands of proteins over the past few years. While many of these proteins have known functions, a large percentage of them have not been characterized at the functional level. The structural information has provided valuable functional insights on some of these proteins, through careful structural analyses, serendipity, and structure-guided functional screening. Some of the success stories based on structures solved at the Northeast Structural Genomics Consortium (NESG) are reported here. These include a novel methyl salicylate esterase with important role in plant innate immunity, a novel RNA methyltransferase (H. influenzae yggJ (HI0303)), a novel spermidine/spermine N-acetyltransferase (B. subtilis PaiA), a novel methyltransferase or AdoMet binding protein (A. fulgidus AF{_}0241), an ATP:cob(I)alamin adenosyltransferase (B. subtilis YvqK), a novel carboxysome pore (E. coli EutN), a proline racemase homolog with a disrupted active site (B. melitensis BME11586), an FMN-dependent enzyme (S. pneumoniae SP{_}1951), and a 12-stranded {beta}-barrel with a novel fold (V. parahaemolyticus VPA1032).

  16. Filoviral Immune Evasion Mechanisms

    Directory of Open Access Journals (Sweden)

    Christopher F. Basler

    2011-09-01

    Full Text Available The Filoviridae family of viruses, which includes the genera Ebolavirus (EBOV and Marburgvirus (MARV, causes severe and often times lethal hemorrhagic fever in humans. Filoviral infections are associated with ineffective innate antiviral responses as a result of virally encoded immune antagonists, which render the host incapable of mounting effective innate or adaptive immune responses. The Type I interferon (IFN response is critical for establishing an antiviral state in the host cell and subsequent activation of the adaptive immune responses. Several filoviral encoded components target Type I IFN responses, and this innate immune suppression is important for viral replication and pathogenesis. For example, EBOV VP35 inhibits the phosphorylation of IRF-3/7 by the TBK-1/IKKε kinases in addition to sequestering viral RNA from detection by RIG-I like receptors. MARV VP40 inhibits STAT1/2 phosphorylation by inhibiting the JAK family kinases. EBOV VP24 inhibits nuclear translocation of activated STAT1 by karyopherin-α. The examples also represent distinct mechanisms utilized by filoviral proteins in order to counter immune responses, which results in limited IFN-α/β production and downstream signaling.

  17. 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.

  18. Immunity to fish rhabdoviruses

    Science.gov (United States)

    Purcell, Maureen K.; Laing, Kerry J.; Winton, James R.

    2012-01-01

    Members of the family Rhabdoviridae are single-stranded RNA viruses and globally important pathogens of wild and cultured fish and thus relatively well studied in their respective hosts or other model systems. Here, we review the protective immune mechanisms that fish mount in response to rhabdovirus infections. Teleost fish possess the principal components of innate and adaptive immunity found in other vertebrates. Neutralizing antibodies are critical for long-term protection from fish rhabdoviruses, but several studies also indicate a role for cell-mediated immunity. Survival of acute rhabdoviral infection is also dependent on innate immunity, particularly the interferon (IFN) system that is rapidly induced in response to infection. Paradoxically, rhabdoviruses are sensitive to the effects of IFN but virulent rhabdoviruses can continue to replicate owing to the abilities of the matrix (M) protein to mediate host-cell shutoff and the non-virion (NV) protein to subvert programmed cell death and suppress functional IFN. While many basic features of the fish immune response to rhabdovirus infections are becoming better understood, much less is known about how factors in the environment affect the ecology of rhabdovirus infections in natural populations of aquatic animals.

  19. Immunity to fish rhabdoviruses.

    Science.gov (United States)

    Purcell, Maureen K; Laing, Kerry J; Winton, James R

    2012-01-01

    Members of the family Rhabdoviridae are single-stranded RNA viruses and globally important pathogens of wild and cultured fish and thus relatively well studied in their respective hosts or other model systems. Here, we review the protective immune mechanisms that fish mount in response to rhabdovirus infections. Teleost fish possess the principal components of innate and adaptive immunity found in other vertebrates. Neutralizing antibodies are critical for long-term protection from fish rhabdoviruses, but several studies also indicate a role for cell-mediated immunity. Survival of acute rhabdoviral infection is also dependent on innate immunity, particularly the interferon (IFN) system that is rapidly induced in response to infection. Paradoxically, rhabdoviruses are sensitive to the effects of IFN but virulent rhabdoviruses can continue to replicate owing to the abilities of the matrix (M) protein to mediate host-cell shutoff and the non‑virion (NV) protein to subvert programmed cell death and suppress functional IFN. While many basic features of the fish immune response to rhabdovirus infections are becoming better understood, much less is known about how factors in the environment affect the ecology of rhabdovirus infections in natural populations of aquatic animals.

  20. Immunity to Fish Rhabdoviruses

    Directory of Open Access Journals (Sweden)

    Maureen K. Purcell

    2012-01-01

    Full Text Available Members of the family Rhabdoviridae are single-stranded RNA viruses and globally important pathogens of wild and cultured fish and thus relatively well studied in their respective hosts or other model systems. Here, we review the protective immune mechanisms that fish mount in response to rhabdovirus infections. Teleost fish possess the principal components of innate and adaptive immunity found in other vertebrates. Neutralizing antibodies are critical for long-term protection from fish rhabdoviruses, but several studies also indicate a role for cell-mediated immunity. Survival of acute rhabdoviral infection is also dependent on innate immunity, particularly the interferon (IFN system that is rapidly induced in response to infection. Paradoxically, rhabdoviruses are sensitive to the effects of IFN but virulent rhabdoviruses can continue to replicate owing to the abilities of the matrix (M protein to mediate host-cell shutoff and the non‑virion (NV protein to subvert programmed cell death and suppress functional IFN. While many basic features of the fish immune response to rhabdovirus infections are becoming better understood, much less is known about how factors in the environment affect the ecology of rhabdovirus infections in natural populations of aquatic animals.

  1. The dynamics of naturally acquired immunity to Plasmodium falciparum infection.

    Directory of Open Access Journals (Sweden)

    Mykola Pinkevych

    Full Text Available Severe malaria occurs predominantly in young children and immunity to clinical disease is associated with cumulative exposure in holoendemic settings. The relative contribution of immunity against various stages of the parasite life cycle that results in controlling infection and limiting disease is not well understood. Here we analyse the dynamics of Plasmodium falciparum malaria infection after treatment in a cohort of 197 healthy study participants of different ages in order to model naturally acquired immunity. We find that both delayed time-to-infection and reductions in asymptomatic parasitaemias in older age groups can be explained by immunity that reduces the growth of blood stage as opposed to liver stage parasites. We found that this mechanism would require at least two components - a rapidly acting strain-specific component, as well as a slowly acquired cross-reactive or general immunity to all strains. Analysis and modelling of malaria infection dynamics and naturally acquired immunity with age provides important insights into what mechanisms of immune control may be harnessed by malaria vaccine strategists.

  2. A review of the immune molecules in the sea cucumber.

    Science.gov (United States)

    Xue, Zhuang; Li, Hui; Wang, Xiuli; Li, Xia; Liu, Yang; Sun, Jing; Liu, Cenjie

    2015-05-01

    It is very important to identify and characterize the immune-related genes that respond to pathogens. Until recently, only some of the immune-related genes in sea cucumbers had been characterized. Their expression patterns after pathogen challenges have been analyzed via expressed sequence tag libraries, microarray studies and proteomic approaches. These genes include lectins, antimicrobial peptides, lysozyme, enzymes, clotting protein, pattern recognition proteins, Toll receptors, complement C3 and other humoral factors that might participate in the innate immune system of sea cucumbers. Although the participation of some of these immune molecules in the sea cucumber's innate immune defense against invading pathogens has been demonstrated, the functions of many of the molecules remain unclear. This review focuses on the discovery and functional characterization of the immune-related molecules from the sea cucumber for the first time and provides new insights into the immune mechanisms of the sea cucumber, which opens new possibilities for developing drugs for novel anti-bacterial and antiviral applications in fisheries. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. The immortality of humoral immunity.

    Science.gov (United States)

    Elgueta, Raul; de Vries, Victor C; Noelle, Randolph J

    2010-07-01

    Decades of high-titered antibody are sustained due to the persistence of memory B cells and long-lived plasma cells (PCs). The differentiation of each of these subsets is antigen- and T-cell driven and is dependent on signals acquired and integrated during the germinal center response. Inherent in the primary immune response must be the delivery of signals to B cells to create these populations, which have virtual immortality. Differences in biology and chemotactic behavior disperse memory B cells and long-lived PCs to a spectrum of anatomic sites. Each subset must rely on survival factors that can support their longevity. This review focuses on the generation of each of these subsets, their survival, and renewal, which must occur to sustain serological memory. In this context, we discuss the role of antigen, bystander inflammation, and cellular niches. The contribution of BAFF (B-cell activating factor belonging to the tumor necrosis factor family) and APRIL (a proliferation-inducing ligand) to the persistence of memory B cells and PCs are also detailed. Insights that have been provided over the past few years in the regulation of long-lived B-cell responses will have profound impact on vaccine development, the treatment of pre-sensitized patients for organ transplantation, and therapeutic interventions in both antibody- and T-cell-mediated autoimmunity.

  4. Quercetin, Inflammation and Immunity

    Directory of Open Access Journals (Sweden)

    Yao Li

    2016-03-01

    Full Text Available In vitro and some animal models have shown that quercetin, a polyphenol derived from plants, has a wide range of biological actions including anti-carcinogenic, anti-inflammatory and antiviral activities; as well as attenuating lipid peroxidation, platelet aggregation and capillary permeability. This review focuses on the physicochemical properties, dietary sources, absorption, bioavailability and metabolism of quercetin, especially main effects of quercetin on inflammation and immune function. According to the results obtained both in vitro and in vivo, good perspectives have been opened for quercetin. Nevertheless, further studies are needed to better characterize the mechanisms of action underlying the beneficial effects of quercetin on inflammation and immunity.

  5. Pentraxins and immunity

    Directory of Open Access Journals (Sweden)

    Priya Nagar

    2014-01-01

    Full Text Available Pentraxin-3 (PTX3 is a multifactorial protein involved in immunity and inflammation, which is rapidly produced and released by several cell types in response to inflammatory signals. It may be suggested that PTX3 is related to periodontal tissue inflammation. Its salivary concentrations may have a diagnostic potential. Pentraxin-3 (PTX3 is an ancient family of multifactorial proteins involved in immunity and inflammation. They are rapidly produced and released by various types of cells when there are indications of inflammation. PTX3 is related to inflammation in the periodontal tissue and it can be suggested that salivary concentrations may be used for diagnosing the same.

  6. Mucosal immunity to poliovirus.

    Science.gov (United States)

    Ogra, Pearay L; Okayasu, Hiromasa; Czerkinsky, Cecil; Sutter, Roland W

    2011-10-01

    The Global Polio Eradication Initiative (GPEI) currently based on use of oral poliovirus vaccine (OPV) has identified suboptimal immunogenicity of this vaccine as a major impediment to eradication, with a failure to induce protection against paralytic poliomyelitis in certain population segments in some parts of the world. The Mucosal Immunity and Poliovirus Vaccines: Impact on Wild Poliovirus Infection, Transmission and Vaccine Failure conference was organized to obtain a better understanding of the current status of global control of poliomyelitis and identify approaches to improve the immune responsiveness and effectiveness of the orally administered poliovirus vaccines in order to accelerate the global eradication of paralytic poliomyelitis.

  7. Training and natural immunity

    DEFF Research Database (Denmark)

    Pedersen, Bente Klarlund; Helge, Jørn Wulff; Richter, Erik

    2000-01-01

    these subjects were used to eliminate day-to-day variation in the immunological tests. Independently of diet, training increased the percentage of CD3-CD16+ CD56+ natural killer (NK) cells from [mean (SEM)] 14 (1) % to 20 (3) % (P = 0.05), whereas the NK-cell activity, either unstimulated or stimulated...... influence natural immunity, and suggest that ingestion of a fat-rich diet during training is detrimental to the immune system compared to the effect of a carbohydrate-rich diet....

  8. Vaccines and Immunization Practice.

    Science.gov (United States)

    Hogue, Michael D; Meador, Anna E

    2016-03-01

    Vaccines are among most cost-effective public health strategies. Despite effective vaccines for many bacterial and viral illnesses, tens of thousands of adults and hundreds of children die each year in the United States from vaccine-preventable diseases. Underutilization of vaccines requires rethinking the approach to incorporating vaccines into practice. Arguably, immunizations could be a part all health care encounters. Shared responsibility is paramount if deaths are to be reduced. This article reviews the available vaccines in the US market, as well as practice recommendations of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Dreaming and insight

    Science.gov (United States)

    Edwards, Christopher L.; Ruby, Perrine M.; Malinowski, Josie E.; Bennett, Paul D.; Blagrove, Mark T.

    2013-01-01

    This paper addresses claims that dreams can be a source of personal insight. Whereas there has been anecdotal backing for such claims, there is now tangential support from findings of the facilitative effect of sleep on cognitive insight, and of REM sleep in particular on emotional memory consolidation. Furthermore, the presence in dreams of metaphorical representations of waking life indicates the possibility of novel insight as an emergent feature of such metaphorical mappings. In order to assess whether personal insight can occur as a result of the consideration of dream content, 11 dream group discussion sessions were conducted which followed the Ullman Dream Appreciation technique, one session for each of 11 participants (10 females, 1 male; mean age = 19.2 years). Self-ratings of deepened self-perception and personal gains from participation in the group sessions showed that the Ullman technique is an effective procedure for establishing connections between dream content and recent waking life experiences, although wake life sources were found for only 14% of dream report text. The mean Exploration-Insight score on the Gains from Dream Interpretation questionnaire was very high and comparable to outcomes from the well-established Hill (1996) therapist-led dream interpretation method. This score was associated between-subjects with pre-group positive Attitude Toward Dreams (ATD). The need to distinguish “aha” experiences as a result of discovering a waking life source for part of a dream, from “aha” experiences of personal insight as a result of considering dream content, is discussed. Difficulties are described in designing a control condition to which the dream report condition can be compared. PMID:24550849

  10. Immune System and Kidney Transplantation.

    Science.gov (United States)

    Shrestha, Badri Man

    2017-01-01

    The immune system recognises a transplanted kidney as foreign body and mounts immune response through cellular and humoral mechanisms leading to acute or chronic rejection, which ultimately results in graft loss. Over the last five decades, there have been significant advances in the understanding of the immune responses to transplanted organs in both experimental and clinical transplant settings. Modulation of the immune response by using immunosuppressive agents has led to successful outcomes after kidney transplantation. The paper provides an overview of the general organisation and function of human immune system, immune response to kidney transplantation, and the current practice of immunosuppressive therapy in kidney transplantation in the United Kingdom.

  11. OpenGL Insights

    CERN Document Server

    Cozzi, Patrick

    2012-01-01

    Get Real-World Insight from Experienced Professionals in the OpenGL Community With OpenGL, OpenGL ES, and WebGL, real-time rendering is becoming available everywhere, from AAA games to mobile phones to web pages. Assembling contributions from experienced developers, vendors, researchers, and educators, OpenGL Insights presents real-world techniques for intermediate and advanced OpenGL, OpenGL ES, and WebGL developers. Go Beyond the Basics The book thoroughly covers a range of topics, including OpenGL 4.2 and recent extensions. It explains how to optimize for mobile devices, explores the design

  12. World energy insight 2011

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2011-11-15

    The World Energy Insight 2011 is the official publication of the World Energy Council. It includes interviews, articles and case studies from a distinguished panel of World Energy Council Officers, CEOs, government ministers, academics and opinion formers from all areas of the energy sector and provides perspectives from around the globe. Government, industry and NGO's offer both policy and technology perspectives. The insights within this publication add to the work that WEC is doing to provide the forum for energy leaders, along with the on-going WEC studies and programmes on Energy Policies, 2050 Energy Scenarios, Energy Resources & Technologies, Energy for Urban Innovation, Rules Of Energy Trade and Global Energy Access.

  13. Variant-specific immunity to Plasmodium berghei in pregnant mice

    DEFF Research Database (Denmark)

    Megnekou, Rosette; Hviid, Lars; Staalsoe, Trine

    2009-01-01

    for recrudescence-type IEs are related to the protection of pregnant mice from maternal anemia, low birth weight, and decreased litter size. We conclude that the model replicates many of the key parasitological and immunological features of PAM, although the P. berghei genome does not encode proteins homologous...... to the P. falciparum erythrocyte membrane protein 1 adhesins, which are of key importance in P. falciparum malaria. The study of P. berghei malaria in pregnant, immune mice can be used to gain significant new insights regarding malaria pathogenesis and immunity in general and regarding PAM in particular....

  14. Neuroendocrine-immune interaction

    NARCIS (Netherlands)

    Kemenade, van Lidy; Cohen, Nicholas; Chadzinska, Magdalena

    2017-01-01

    It has now become accepted that the immune system and neuroendocrine system form an integrated part of our physiology. Immunological defense mechanisms act in concert with physiological processes like growth and reproduction, energy intake and metabolism, as well as neuronal development. Not only

  15. Amyloid and immune homeostasis.

    Science.gov (United States)

    Wang, Ying-Hui; Zhang, Yu-Gen

    2018-03-01

    Extracellular amyloid deposition defines a range of amyloidosis and amyloid-related disease. Addition to primary and secondary amyloidosis, amyloid-related disease can be observed in different tissue/organ that sharing the common pathogenesis based on the formation of amyloid deposition. Currently, both Alzheimer's disease and type 2 diabetes can be diagnosed with certainly only based on the autopsy results, by which amyloidosis of the associative tissue/organ is observed. Intriguingly, since it demonstrated that amyloid deposits trigger inflammatory reaction through the activation of cascaded immune response, wherein several lines of evidence implies a protective role of amyloid in preventing autoimmunity. Furthermore, attempts for preventing amyloid formation and/or removing amyloid deposits from the brain have caused meningoencephalitis and consequent deaths among the subjects. Hence, it is important to note that amyloid positively participates in maintaining immune homeostasis and contributes to irreversible inflammatory response. In this review, we will focus on the interactive relationship between amyloid and the immune system, discussing the potential functional roles of amyloid in immune tolerance and homeostasis. Copyright © 2017 Elsevier GmbH. All rights reserved.

  16. Lymphoma: Immune Evasion Strategies

    International Nuclear Information System (INIS)

    Upadhyay, Ranjan; Hammerich, Linda; Peng, Paul; Brown, Brian; Merad, Miriam; Brody, Joshua D.

    2015-01-01

    While the cellular origin of lymphoma is often characterized by chromosomal translocations and other genetic aberrations, its growth and development into a malignant neoplasm is highly dependent upon its ability to escape natural host defenses. Neoplastic cells interact with a variety of non-malignant cells in the tumor milieu to create an immunosuppressive microenvironment. The resulting functional impairment and dysregulation of tumor-associated immune cells not only allows for passive growth of the malignancy but may even provide active growth signals upon which the tumor subsequently becomes dependent. In the past decade, the success of immune checkpoint blockade and adoptive cell transfer for relapsed or refractory lymphomas has validated immunotherapy as a possible treatment cornerstone. Here, we review the mechanisms by which lymphomas have been found to evade and even reprogram the immune system, including alterations in surface molecules, recruitment of immunosuppressive subpopulations, and secretion of anti-inflammatory factors. A fundamental understanding of the immune evasion strategies utilized by lymphomas may lead to better prognostic markers and guide the development of targeted interventions that are both safer and more effective than current standards of care

  17. Lymphoma: Immune Evasion Strategies

    Energy Technology Data Exchange (ETDEWEB)

    Upadhyay, Ranjan; Hammerich, Linda; Peng, Paul [Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Brown, Brian [Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Merad, Miriam [Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Brody, Joshua D., E-mail: joshua.brody@mssm.edu [Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States)

    2015-04-30

    While the cellular origin of lymphoma is often characterized by chromosomal translocations and other genetic aberrations, its growth and development into a malignant neoplasm is highly dependent upon its ability to escape natural host defenses. Neoplastic cells interact with a variety of non-malignant cells in the tumor milieu to create an immunosuppressive microenvironment. The resulting functional impairment and dysregulation of tumor-associated immune cells not only allows for passive growth of the malignancy but may even provide active growth signals upon which the tumor subsequently becomes dependent. In the past decade, the success of immune checkpoint blockade and adoptive cell transfer for relapsed or refractory lymphomas has validated immunotherapy as a possible treatment cornerstone. Here, we review the mechanisms by which lymphomas have been found to evade and even reprogram the immune system, including alterations in surface molecules, recruitment of immunosuppressive subpopulations, and secretion of anti-inflammatory factors. A fundamental understanding of the immune evasion strategies utilized by lymphomas may lead to better prognostic markers and guide the development of targeted interventions that are both safer and more effective than current standards of care.

  18. Fully immunized child

    DEFF Research Database (Denmark)

    Mutua, Martin Kavao; Kimani-Murage, Elizabeth; Ngomi, Nicholas

    2016-01-01

    Background: More efforts have been put in place to increase full immunization coverage rates in the last decade. Little is known about the levels and consequences of delaying or vaccinating children in different schedules. Vaccine effectiveness depends on the timing of its administration, and it ...

  19. Tick Innate Immunity.

    Czech Academy of Sciences Publication Activity Database

    Kopáček, Petr; Hajdušek, Ondřej; Burešová, Veronika; Daffre, S.

    2010-01-01

    Roč. 708, - (2010), 137-162 ISSN 0065-2598 R&D Projects: GA ČR GAP506/10/2136; GA MŠk(CZ) LC06009 Institutional research plan: CEZ:AV0Z60220518 Keywords : tick * pathogen transmission * innate immunity Subject RIV: EC - Immunology Impact factor: 1.379, year: 2010

  20. Global China Insights

    NARCIS (Netherlands)

    Segers, Rien; Fischer, Ingrid

    Journal in which the Groningen Confucius Institute (GCI) shares different perspectives on China and provides insights into China from as many different aspects as possible. GCI aims to provide a full view of real China to the readers as well as featuring international and comprehensive perspectives,

  1. Global China Insights

    NARCIS (Netherlands)

    Segers, Rien; Havinga, Marieke; Fischer, Ingrid

    2013-01-01

    Journal in which the Groningen Confucius Institute (GCI) shares different perspectives on China and provides insights into China from as many different aspects as possible. GCI aims to provide a full view of real China to the readers as well as featuring international and comprehensive perspectives,

  2. Africa Insight: Submissions

    African Journals Online (AJOL)

    Author Guidelines. Africa Insight is a quarterly, peer-reviewed journal of the Africa Institute of South Africa (AISA). It is accredited by the Department of Higher ... Abstract: All articles should be accompanied by an abstract of between 100 and 125 words stating the main research problem, major findings and conclusion(s).

  3. [Poor insight and psychosis].

    Science.gov (United States)

    Giotakos, O

    2017-01-01

    A variety of phenomena might be considered as reflecting impaired insight in psychosis, like failure to recognize signs, symptoms or disease, failure to derive appropriate cognitive representations, despite recognition of the disease, and misattribution of the source or cause of the disease. The unawareness of tardive dyskinesia symptoms in schizophrenic patients points that self-awareness deficits in schizophrenia may be domain specific. Poor insight is an independent phenomenological and a prevalent feature in psychotic disorders in general, and in schizophrenia in particular, but we don't know yet if delusions in schizophrenia are the result of an entirely normal attempt to account for abnormal perceptual experiences or a product of abnormal experience but of normal reasoning. The theoretical approaches regarding impaired insight include the disturbed perceptual input, the impaired linkage between thought and emotion and the breakdown of the process of self-monitoring and error checking. The inability to distinguish between internally and externally generated mental events has been described by the metarepresentation theory. This theory includes the awareness of ones' goals, which leads to disorders of willed action, the awareness of intention, which leads to movement disorders, and the awareness of intentions of others, which leads to paranoid delusions. The theory of metarepresentation implies mainly output mechanisms, like the frontal cortex, while the input mechanism implies posterior brain systems, including the parietal lobe. There are many similarities between the disturbances of awareness seen in schizophrenia and those seen as a result of known neurological impairment. Neuropsychological models of impaired insight typically attribute the disturbance to any of a variety of core deficits in the processing of information. In this respect, lack of insight is on conceptual par with alogia, apraxia or aphasia in reflecting disturbed cognitive processing. In

  4. Frequently Asked Questions about Immunizations

    Science.gov (United States)

    ... will be too late for the vaccine to work. The best time to immunize kids is when they're healthy. Can immunizations cause a bad reaction in my child? The most common reactions to vaccines are minor ...

  5. Technique Selectively Represses Immune System

    Science.gov (United States)

    ... Research Matters December 3, 2012 Technique Selectively Represses Immune System Myelin (green) encases and protects nerve fibers (brown). A new technique prevents the immune system from attacking myelin in a mouse model of ...

  6. Differential Gender Effects in the Relationship between Perceived Immune Functioning and Autistic Traits.

    Science.gov (United States)

    Mackus, Marlou; Kruijff, Deborah de; Otten, Leila S; Kraneveld, Aletta D; Garssen, Johan; Verster, Joris C

    2017-04-12

    Altered immune functioning has been demonstrated in individuals with autism spectrum disorder (ASD). The current study explores the relationship between perceived immune functioning and experiencing ASD traits in healthy young adults. N = 410 students from Utrecht University completed a survey on immune functioning and autistic traits. In addition to a 1-item perceived immune functioning rating, the Immune Function Questionnaire (IFQ) was completed to assess perceived immune functioning. The Dutch translation of the Autism-Spectrum Quotient (AQ) was completed to examine variation in autistic traits, including the domains "social insights and behavior", "difficulties with change", "communication", "phantasy and imagination", and "detail orientation". The 1-item perceived immune functioning score did not significantly correlate with the total AQ score. However, a significant negative correlation was found between perceived immune functioning and the AQ subscale "difficulties with change" (r = -0.119, p = 0.019). In women, 1-item perceived immune functioning correlated significantly with the AQ subscales "difficulties with change" (r = -0.149, p = 0.029) and "communication" (r = -0.145, p = 0.032). In men, none of the AQ subscales significantly correlated with 1-item perceived immune functioning. In conclusion, a modest relationship between perceived immune functioning and several autistic traits was found.

  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. Vitamin E, immunity, and infection

    Science.gov (United States)

    A normally functioning immune system is critical for the body to fight and eliminate invading pathogens from the environment. On the other hand, the immune system also protects the body from internal risks such as neoplasia growing within and autoimmune responses that attack self. The immune system ...

  9. A systems model for immune cell interactions unravels the mechanism of inflammation in human skin.

    Science.gov (United States)

    Valeyev, Najl V; Hundhausen, Christian; Umezawa, Yoshinori; Kotov, Nikolay V; Williams, Gareth; Clop, Alex; Ainali, Crysanthi; Ouzounis, Christos; Tsoka, Sophia; Nestle, Frank O

    2010-12-02

    Inflammation is characterized by altered cytokine levels produced by cell populations in a highly interdependent manner. To elucidate the mechanism of an inflammatory reaction, we have developed a mathematical model for immune cell interactions via the specific, dose-dependent cytokine production rates of cell populations. The model describes the criteria required for normal and pathological immune system responses and suggests that alterations in the cytokine production rates can lead to various stable levels which manifest themselves in different disease phenotypes. The model predicts that pairs of interacting immune cell populations can maintain homeostatic and elevated extracellular cytokine concentration levels, enabling them to operate as an immune system switch. The concept described here is developed in the context of psoriasis, an immune-mediated disease, but it can also offer mechanistic insights into other inflammatory pathologies as it explains how interactions between immune cell populations can lead to disease phenotypes.

  10. The genetic architecture of the human immune system: a bioresource for autoimmunity and disease pathogenesis.

    Science.gov (United States)

    Roederer, Mario; Quaye, Lydia; Mangino, Massimo; Beddall, Margaret H; Mahnke, Yolanda; Chattopadhyay, Pratip; Tosi, Isabella; Napolitano, Luca; Terranova Barberio, Manuela; Menni, Cristina; Villanova, Federica; Di Meglio, Paola; Spector, Tim D; Nestle, Frank O

    2015-04-09

    Despite recent discoveries of genetic variants associated with autoimmunity and infection, genetic control of the human immune system during homeostasis is poorly understood. We undertook a comprehensive immunophenotyping approach, analyzing 78,000 immune traits in 669 female twins. From the top 151 heritable traits (up to 96% heritable), we used replicated GWAS to obtain 297 SNP associations at 11 genetic loci, explaining up to 36% of the variation of 19 traits. We found multiple associations with canonical traits of all major immune cell subsets and uncovered insights into genetic control for regulatory T cells. This data set also revealed traits associated with loci known to confer autoimmune susceptibility, providing mechanistic hypotheses linking immune traits with the etiology of disease. Our data establish a bioresource that links genetic control elements associated with normal immune traits to common autoimmune and infectious diseases, providing a shortcut to identifying potential mechanisms of immune-related diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. A systems model for immune cell interactions unravels the mechanism of inflammation in human skin.

    Directory of Open Access Journals (Sweden)

    Najl V Valeyev

    2010-12-01

    Full Text Available Inflammation is characterized by altered cytokine levels produced by cell populations in a highly interdependent manner. To elucidate the mechanism of an inflammatory reaction, we have developed a mathematical model for immune cell interactions via the specific, dose-dependent cytokine production rates of cell populations. The model describes the criteria required for normal and pathological immune system responses and suggests that alterations in the cytokine production rates can lead to various stable levels which manifest themselves in different disease phenotypes. The model predicts that pairs of interacting immune cell populations can maintain homeostatic and elevated extracellular cytokine concentration levels, enabling them to operate as an immune system switch. The concept described here is developed in the context of psoriasis, an immune-mediated disease, but it can also offer mechanistic insights into other inflammatory pathologies as it explains how interactions between immune cell populations can lead to disease phenotypes.

  12. Suppressive influences in the immune response to cancer.

    Science.gov (United States)

    Bronte, Vincenzo; Mocellin, Simone

    2009-01-01

    Although much evidence has been gathered demonstrating that immune effectors can play a significant role in controlling tumor growth under natural conditions or in response to therapeutic manipulation, it is clear that malignant cells do evade immune surveillance in most cases. Considering that anticancer active specific immunotherapy seems to have reached a plateau of results and that currently no vaccination regimen is indicated as a standard anticancer therapy, the dissection of the molecular events underlying tumor immune escape is the necessary condition to make anticancer vaccines a therapeutic weapon effective enough to be implemented in the routine clinical setting. Recent years have witnessed significant advances in our understanding of the molecular mechanisms underlying tumor immune escape. These mechanistic insights are fostering the development of rationally designed therapeutics aimed to revert the immunosuppressive circuits that undermine an effective antitumor immune response. In this review, the best characterized mechanisms that allow cancer cells to evade immune surveillance are overviewed and the most debated controversies constellating this complex field are highlighted.

  13. The vagal innervation of the gut and immune homeostasis.

    Science.gov (United States)

    Matteoli, Gianluca; Boeckxstaens, Guy E

    2013-08-01

    The central nervous system interacts dynamically with the immune system to modulate inflammation through humoral and neural pathways. Recently, in animal models of sepsis, the vagus nerve (VN) has been proposed to play a crucial role in the regulation of the immune response, also referred to as the cholinergic anti-inflammatory pathway. The VN, through release of acetylcholine, dampens immune cell activation by interacting with α-7 nicotinic acetylcholine receptors. Recent evidence suggests that the vagal innervation of the gastrointestinal tract also plays a major role controlling intestinal immune activation. Indeed, VN electrical stimulation potently reduces intestinal inflammation restoring intestinal homeostasis, whereas vagotomy has the reverse effect. In this review, we will discuss the current understanding concerning the mechanisms and effects involved in the cholinergic anti-inflammatory pathway in the gastrointestinal tract. Deeper investigation on this counter-regulatory neuroimmune mechanism will provide new insights in the cross-talk between the nervous and immune system leading to the identification of new therapeutic targets to treat intestinal immune disease.

  14. Immunity to tumour antigens.

    Science.gov (United States)

    Li, Geng; Ali, Selman A; McArdle, Stephanie E B; Mian, Shahid; Ahmad, Murrium; Miles, Amanda; Rees, Robert C

    2005-01-01

    During the last decade, a large number of human tumour antigens have been identified. These antigens are classified as tumour-specific shared antigens, tissue-specific differentiation antigens, overexpressed antigens, tumour antigens resulting from mutations, viral antigens and fusion proteins. Antigens recognised by effectors of immune system are potential targets for antigen-specific cancer immunotherapy. However, most tumour antigens are self-proteins and are generally of low immunogenicity and the immune response elicited towards these tumour antigens is not always effective. Strategies to induce and enhance the tumour antigen-specific response are needed. This review will summarise the approaches to discovery of tumour antigens, the current status of tumour antigens, and their potential application to cancer treatment.

  15. Agency privileges and immunities

    International Nuclear Information System (INIS)

    1969-01-01

    Switzerland has become the thirty-fifth Member State to be a party to the Agreement on the Privileges and Immunities of the International Atomic Energy Agency. Its Resident Representative, Ambassador Alfred Eschler, deposited his Government's instrument of acceptance on 16 September. This is the fourth such instrument to be deposited with the Agency since the beginning of this year, the others being Ecuador on 16 April, Niger on 17 June and Vietnam on 31 July. (author)

  16. Immune disorders in anorexia

    OpenAIRE

    SŁOTWIŃSKA, SYLWIA MAŁGORZATA; SŁOTWIŃSKI, ROBERT

    2017-01-01

    Anorexia nervosa is a disease involving eating disorders. It mainly affects young people, especially teenage women. The disease is often latent and occurs in many sub-clinical and partial forms. Approximately from 0.3% to 1% of the population suffers from anorexia. It has been shown that patients with anorexia develop neurotransmitter-related disorders, leading to uncontrolled changes in the immune and endocrine systems. Interactions between cytokines, neuropeptides, and neurotransmitters pla...

  17. Ebola and Immune System

    OpenAIRE

    KOMENAN, Alexis

    2016-01-01

    Ebola hemorrhagic fever is a formidable disease whose surges always result in a high number of victims in sub-Saharan Africa. There is no official treatment against the virus, which makes the task of containment extremely delicate. However, the existence of survivors to the virus demonstrates curable nature of the disease and suggests the existence of favorable factors of immunity. The author examines these factors and their challenges and perspectives in the cure of the disease.

  18. Immune disorders in anorexia

    Directory of Open Access Journals (Sweden)

    Sylwia Małgorzata Słotwińska

    2017-10-01

    Full Text Available Anorexia nervosa is a disease involving eating disorders. It mainly affects young people, especially teenage women. The disease is often latent and occurs in many sub-clinical and partial forms. Approximately from 0.3% to 1% of the population suffers from anorexia. It has been shown that patients with anorexia develop neurotransmitter-related disorders, leading to uncontrolled changes in the immune and endocrine systems. Interactions between cytokines, neuropeptides, and neurotransmitters play an important role in disease development. Significant malnutrition induces disorders and alterations in T-cell populations. The cellular response in patients with anorexia nervosa has been shown to be normal, although opinions on this issue are controversial. Laboratory studies on neutrophils in anorexia patients showed decreased adhesion and reduced bactericidal and cell activities. Despite such unfavourable results, patients with anorexia are resistant to infections, which are very rare in this group. Glutamine improves the performance of the human immune system. The administration of glutamine to anorexia patients, as a supplement to parenteral nutrition, has resulted in significant improvements in immune system parameters. The results of previous studies on the causes and risk factors in the development of anorexia nervosa are still ambiguous. One can hope that the differences and similarities between patients with anorexia nervosa and those with other forms of protein-calorie malnutrition may be helpful in determining the relationship between nutritional status and body defences and susceptibility to infection, and can help to broaden the knowledge about the aetiopathogenesis of anorexia nervosa.

  19. Immune disorders in anorexia.

    Science.gov (United States)

    Słotwińska, Sylwia Małgorzata; Słotwiński, Robert

    2017-01-01

    Anorexia nervosa is a disease involving eating disorders. It mainly affects young people, especially teenage women. The disease is often latent and occurs in many sub-clinical and partial forms. Approximately from 0.3% to 1% of the population suffers from anorexia. It has been shown that patients with anorexia develop neurotransmitter-related disorders, leading to uncontrolled changes in the immune and endocrine systems. Interactions between cytokines, neuropeptides, and neurotransmitters play an important role in disease development. Significant malnutrition induces disorders and alterations in T-cell populations. The cellular response in patients with anorexia nervosa has been shown to be normal, although opinions on this issue are controversial. Laboratory studies on neutrophils in anorexia patients showed decreased adhesion and reduced bactericidal and cell activities. Despite such unfavourable results, patients with anorexia are resistant to infections, which are very rare in this group. Glutamine improves the performance of the human immune system. The administration of glutamine to anorexia patients, as a supplement to parenteral nutrition, has resulted in significant improvements in immune system parameters. The results of previous studies on the causes and risk factors in the development of anorexia nervosa are still ambiguous. One can hope that the differences and similarities between patients with anorexia nervosa and those with other forms of protein-calorie malnutrition may be helpful in determining the relationship between nutritional status and body defences and susceptibility to infection, and can help to broaden the knowledge about the aetiopathogenesis of anorexia nervosa.

  20. Hyperthermia, immunity and metastases

    International Nuclear Information System (INIS)

    Lopatin, V.F.

    1983-01-01

    The analysis of literature data concerning local hyperthermia effects shows that temperatures over 41-42 deg C (in the whole tumor volume), causing tumor growth inhibition and cell injury, can change antigenic nature of a malignant tissue. The tumor injured by thermal effect is able probably the full length of time of injured tissue resorption to maintain at a sufficiently high level antitumoral immunity and lay obstacles to emergence of metastases or even cause regression of those tumoral foci which have not been exposed to direct effect of the injuring agent. The facts of tumoral foci regression take place also upon radiation effect which is associated as well with participation of immune mechanisms. In.experiments with animals an essential increase of immunogenic character of malignant cells exposed to ionizing radiation effect has been observed. It follows that radiation injury of tumoral tissue as well as thermal one is able to stimulate antitumoral immunity and reduce the probability of emergence of metastases. But in case of radiotherapy immunosuppression effect of ionizing radiation (at the expense of inhibition of proliferation and death of immunocompetent cells) can essentially overlap immunostimulating effect related to the changes in antigenic character of tumoral cells

  1. Linear ubiquitination in immunity.

    Science.gov (United States)

    Shimizu, Yutaka; Taraborrelli, Lucia; Walczak, Henning

    2015-07-01

    Linear ubiquitination is a post-translational protein modification recently discovered to be crucial for innate and adaptive immune signaling. The function of linear ubiquitin chains is regulated at multiple levels: generation, recognition, and removal. These chains are generated by the linear ubiquitin chain assembly complex (LUBAC), the only known ubiquitin E3 capable of forming the linear ubiquitin linkage de novo. LUBAC is not only relevant for activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) in various signaling pathways, but importantly, it also regulates cell death downstream of immune receptors capable of inducing this response. Recognition of the linear ubiquitin linkage is specifically mediated by certain ubiquitin receptors, which is crucial for translation into the intended signaling outputs. LUBAC deficiency results in attenuated gene activation and increased cell death, causing pathologic conditions in both, mice, and humans. Removal of ubiquitin chains is mediated by deubiquitinases (DUBs). Two of them, OTULIN and CYLD, are constitutively associated with LUBAC. Here, we review the current knowledge on linear ubiquitination in immune signaling pathways and the biochemical mechanisms as to how linear polyubiquitin exerts its functions distinctly from those of other ubiquitin linkage types. © 2015 The Authors. Immunological Reviews Published by John Wiley & Sons Ltd.

  2. World energy insight 2011

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2011-11-15

    The World Energy Insight 2011 is the official publication of the World Energy Council. It includes interviews, articles and case studies from a distinguished panel of World Energy Council Officers, CEOs, government ministers, academics and opinion formers from all areas of the energy sector and provides perspectives from around the globe. Government, industry and NGO's offer both policy and technology perspectives. The insights within this publication add to the work that WEC is doing to provide the forum for energy leaders, along with the on-going WEC studies and programmes on Energy Policies, 2050 Energy Scenarios, Energy Resources & Technologies, Energy for Urban Innovation, Rules Of Energy Trade and Global Energy Access.

  3. The politics of insight

    OpenAIRE

    Salvi, Carola; Cristofori, Irene; Grafman, Jordan; Beeman, Mark

    2016-01-01

    Previous studies showed that liberals and conservatives differ in cognitive style. Liberals are more flexible, and tolerant of complexity and novelty, whereas conservatives are more rigid, are more resistant to change, and prefer clear answers. We administered a set of compound remote associate problems, a task extensively used to differentiate problem-solving styles (via insight or analysis). Using this task, several researches have proven that self-reports, which differentiate between insig...

  4. HPC Insights, Fall 2011

    Science.gov (United States)

    2011-01-01

    Power 6 ( Davinci ) systems. We have also made use of the Air Force Research Laboratory DSRC Altix (Hawk) and the Engineer Research and Development...the design and development of high performance gas turbine combustion systems both as a pretest analysis tool to predict static and dynamic...application while gaining insight into MATLAB’s value as an engineering tool . I would like to thank the MHPCC and the Akamai Workforce Initiative

  5. The politics of insight.

    Science.gov (United States)

    Salvi, Carola; Cristofori, Irene; Grafman, Jordan; Beeman, Mark

    2016-01-01

    Previous studies showed that liberals and conservatives differ in cognitive style. Liberals are more flexible, and tolerant of complexity and novelty, whereas conservatives are more rigid, are more resistant to change, and prefer clear answers. We administered a set of compound remote associate problems, a task extensively used to differentiate problem-solving styles (via insight or analysis). Using this task, several researches have proven that self-reports, which differentiate between insight and analytic problem-solving, are reliable and are associated with two different neural circuits. In our research we found that participants self-identifying with distinct political orientations demonstrated differences in problem-solving strategy. Liberals solved significantly more problems via insight instead of in a step-by-step analytic fashion. Our findings extend previous observations that self-identified political orientations reflect differences in cognitive styles. More specifically, we show that type of political orientation is associated with problem-solving strategy. The data converge with previous neurobehavioural and cognitive studies indicating a link between cognitive style and the psychological mechanisms that mediate political beliefs.

  6. The politics of insight

    Science.gov (United States)

    Salvi, Carola; Cristofori, Irene; Grafman, Jordan; Beeman, Mark

    2016-01-01

    Previous studies showed that liberals and conservatives differ in cognitive style. Liberals are more flexible, and tolerant of complexity and novelty, whereas conservatives are more rigid, are more resistant to change, and prefer clear answers. We administered a set of compound remote associate problems, a task extensively used to differentiate problem-solving styles (via insight or analysis). Using this task, several researches have proven that self-reports, which differentiate between insight and analytic problem-solving, are reliable and are associated with two different neural circuits. In our research we found that participants self-identifying with distinct political orientations demonstrated differences in problem-solving strategy. Liberals solved significantly more problems via insight instead of in a step-by-step analytic fashion. Our findings extend previous observations that self-identified political orientations reflect differences in cognitive styles. More specifically, we show that type of political orientation is associated with problem-solving strategy. The data converge with previous neurobehavioural and cognitive studies indicating a link between cognitive style and the psychological mechanisms that mediate political beliefs. PMID:26810954

  7. Neuroimmune interaction and the regulation of intestinal immune homeostasis.

    Science.gov (United States)

    Verheijden, Simon; Boeckxstaens, Guy E

    2018-01-01

    Many essential gastrointestinal functions, including motility, secretion, and blood flow, are regulated by the autonomic nervous system (ANS), both through intrinsic enteric neurons and extrinsic (sympathetic and parasympathetic) innervation. Recently identified neuroimmune mechanisms, in particular the interplay between enteric neurons and muscularis macrophages, are now considered to be essential for fine-tuning peristalsis. These findings shed new light on how intestinal immune cells can support enteric nervous function. In addition, both intrinsic and extrinsic neural mechanisms control intestinal immune homeostasis in different layers of the intestine, mainly by affecting macrophage activation through neurotransmitter release. In this mini-review, we discuss recent insights on immunomodulation by intrinsic enteric neurons and extrinsic innervation, with a particular focus on intestinal macrophages. In addition, we discuss the relevance of these novel mechanisms for intestinal immune homeostasis in physiological and pathological conditions, mainly focusing on motility disorders (gastroparesis and postoperative ileus) and inflammatory disorders (colitis).

  8. Super-enhancers: Asset management in immune cell genomes.

    Science.gov (United States)

    Witte, Steven; O'Shea, John J; Vahedi, Golnaz

    2015-09-01

    Super-enhancers (SEs) are regions of the genome consisting of clusters of regulatory elements bound with very high amounts of transcription factors, and this architecture appears to be the hallmark of genes and noncoding RNAs linked with cell identity. Recent studies have identified SEs in CD4(+) T cells and have further linked these regions to single nucleotide polymorphisms (SNPs) associated with immune-mediated disorders, pointing to an important role for these structures in the T cell differentiation and function. Here we review the features that define SEs, and discuss their function within the broader understanding of the mechanisms that define immune cell identity and function. We propose that SEs present crucial regulatory hubs, coordinating intrinsic and extrinsic differentiation signals, and argue that delineating these regions will provide important insight into the factors and mechanisms that define immune cell identity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Boosting innate immunity to sustainably control diseases in crops.

    Science.gov (United States)

    Nicaise, Valerie

    2017-10-01

    Viruses cause epidemics in all major crops, threatening global food security. The development of efficient and durable resistance able to withstand viral attacks represents a major challenge for agronomy, and relies greatly on the understanding of the molecular dialogue between viral pathogens and their hosts. Research over the last decades provided substantial advances in the field of plant-virus interactions. Remarkably, the advent of studies of plant innate immunity has recently offered new strategies exploitable in the field. This review summarizes the recent breakthroughs that define the mechanisms underlying antiviral innate immunity in plants, and emphasizes the importance of integrating that knowledge into crop improvement actions, particularly by exploiting the insights related to immune receptors. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Adaptation in the innate immune system and heterologous innate immunity.

    Science.gov (United States)

    Martin, Stefan F

    2014-11-01

    The innate immune system recognizes deviation from homeostasis caused by infectious or non-infectious assaults. The threshold for its activation seems to be established by a calibration process that includes sensing of microbial molecular patterns from commensal bacteria and of endogenous signals. It is becoming increasingly clear that adaptive features, a hallmark of the adaptive immune system, can also be identified in the innate immune system. Such adaptations can result in the manifestation of a primed state of immune and tissue cells with a decreased activation threshold. This keeps the system poised to react quickly. Moreover, the fact that the innate immune system recognizes a wide variety of danger signals via pattern recognition receptors that often activate the same signaling pathways allows for heterologous innate immune stimulation. This implies that, for example, the innate immune response to an infection can be modified by co-infections or other innate stimuli. This "design feature" of the innate immune system has many implications for our understanding of individual susceptibility to diseases or responsiveness to therapies and vaccinations. In this article, adaptive features of the innate immune system as well as heterologous innate immunity and their implications are discussed.

  11. Impact of pharmacists providing immunizations on adolescent influenza immunization.

    Science.gov (United States)

    Robison, Steve G

    2016-01-01

    To determine if the Oregon law change in 2011 to allow pharmacists to immunize adolescents 11 to 17 years of age increased influenza immunizations or changed existing immunization venues. With the use of Oregon's ALERT Immunization Information System (IIS), 2 measures of impact were developed. First, the change in adolescent age 11-17 influenza immunizations before (2007-2010) and after (2011-2014) the pharmacy law change was evaluated against a reference cohort (aged 7-10) not affected by the law. Community pharmacies were also compared with other types of influenza immunization sites within one of the study influenza seasons (2013-2014). From 2007 to 2014, adolescent influenza immunizations at community pharmacies increased from 36 to 6372 per year. After the 2011 pharmacy law change, adolescents aged 11 to 17 were more likely to receive an influenza immunization compared with the reference population (odds ratio, 1.21; 95% CI, 1.19-1.22). Analysis of the 2013-2014 influenza season suggests that community pharmacies immunized a different population of adolescents than other providers. The 2011 change in Oregon law allowed pharmacists to increase the total of influenza immunizations given to adolescents. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  12. What are System Dynamics Insights?

    OpenAIRE

    Stave, K.; Zimmermann, N. S.; Kim, H.

    2016-01-01

    This paper explores the concept of system dynamics insights. In our field, the term “insight” is generally understood to mean dynamic insight, that is, a deep understanding about the relationship between structure and behavior. We argue this is only one aspect of the range of insights possible from system dynamics activities, and describe a broader range of potential system dynamics insights. We also propose an initial framework for discussion that relates different types of system dynamics a...

  13. The identification of immune genes in the milk transcriptome of the Tasmanian devil (Sarcophilus harrisii

    Directory of Open Access Journals (Sweden)

    Rehana V. Hewavisenti

    2016-01-01

    Full Text Available Tasmanian devil (Sarcophilus harrisii pouch young, like other marsupials, are born underdeveloped and immunologically naïve, and are unable to mount an adaptive immune response. The mother’s milk provides nutrients for growth and development as well as providing passive immunity. To better understand immune response in this endangered species, we set out to characterise the genes involved in passive immunity by sequencing and annotating the transcriptome of a devil milk sample collected during mid-lactation. At mid-lactation we expect the young to have heightened immune responses, as they have emerged from the pouch, encountering new pathogens. A total of 233,660 transcripts were identified, including approximately 17,827 unique protein-coding genes and 846 immune genes. The most highly expressed transcripts were dominated by milk protein genes such as those encoding early lactation protein, late lactation proteins, α-lactalbumin, α-casein and β-casein. There were numerous highly expressed immune genes including lysozyme, whey acidic protein, ferritin and major histocompatibility complex I and II. Genes encoding immunoglobulins, antimicrobial peptides, chemokines and immune cell receptors were also identified. The array of immune genes identified in this study reflects the importance of the milk in providing immune protection to Tasmanian devil young and provides the first insight into Tasmanian devil milk.

  14. Conservation of a Unique Mechanism of Immune Evasion across the Lyssavirus Genus

    Science.gov (United States)

    Wiltzer, L.; Larrous, F.; Oksayan, S.; Ito, N.; Marsh, G. A.; Wang, L. F.; Blondel, D.; Bourhy, H.; Jans, D. A.

    2012-01-01

    The evasion of host innate immunity by Rabies virus, the prototype of the genus Lyssavirus, depends on a unique mechanism of selective targeting of interferon-activated STAT proteins by the viral phosphoprotein (P-protein). However, the immune evasion strategies of other lyssaviruses, including several lethal human pathogens, are unresolved. Here, we show that this mechanism is conserved between the most distantly related members of the genus, providing important insights into the pathogenesis and potential therapeutic targeting of lyssaviruses. PMID:22740405

  15. Conservation of a unique mechanism of immune evasion across the Lyssavirus genus.

    Science.gov (United States)

    Wiltzer, L; Larrous, F; Oksayan, S; Ito, N; Marsh, G A; Wang, L F; Blondel, D; Bourhy, H; Jans, D A; Moseley, G W

    2012-09-01

    The evasion of host innate immunity by Rabies virus, the prototype of the genus Lyssavirus, depends on a unique mechanism of selective targeting of interferon-activated STAT proteins by the viral phosphoprotein (P-protein). However, the immune evasion strategies of other lyssaviruses, including several lethal human pathogens, are unresolved. Here, we show that this mechanism is conserved between the most distantly related members of the genus, providing important insights into the pathogenesis and potential therapeutic targeting of lyssaviruses.

  16. Pseudoachondroplasia with immune deficiency

    International Nuclear Information System (INIS)

    Kultursay, N.; Taneli, B.; Cavusoglu, A.

    1988-01-01

    A 5-year old boy was admitted to the hospital with failure to thrive since he was 2 years old, with weakness in his legs and a waddling gait. He has normal mental development. His parents are normal phenotypically and are unrelated. In analysing his pedigree only a grandfather is described to have waddling gait. He has a normal craniofacial appearance but a disproportionate body with normal trunk and short extremities with height below the 3rd percentile. The diagnosis of pseudoachondroplasia was made on clinical, radiological and laboratory findings. He also had immune deficiency characterised by low T-lymphocyte populations and a low level of serum immunoglobulin A. (orig.)

  17. 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....

  18. Impact of the Gut Microbiota on Intestinal Immunity Mediated by Tryptophan Metabolism

    Science.gov (United States)

    Gao, Jing; Xu, Kang; Liu, Hongnan; Liu, Gang; Bai, Miaomiao; Peng, Can; Li, Tiejun; Yin, Yulong

    2018-01-01

    The gut microbiota influences the health of the host, especially with regard to gut immune homeostasis and the intestinal immune response. In addition to serving as a nutrient enhancer, L-tryptophan (Trp) plays crucial roles in the balance between intestinal immune tolerance and gut microbiota maintenance. Recent discoveries have underscored that changes in the microbiota modulate the host immune system by modulating Trp metabolism. Moreover, Trp, endogenous Trp metabolites (kynurenines, serotonin, and melatonin), and bacterial Trp metabolites (indole, indolic acid, skatole, and tryptamine) have profound effects on gut microbial composition, microbial metabolism, the host's immune system, the host-microbiome interface, and host immune system–intestinal microbiota interactions. The aryl hydrocarbon receptor (AhR) mediates the regulation of intestinal immunity by Trp metabolites (as ligands of AhR), which is beneficial for immune homeostasis. Among Trp metabolites, AhR ligands consist of endogenous metabolites, including kynurenine, kynurenic acid, xanthurenic acid, and cinnabarinic acid, and bacterial metabolites, including indole, indole propionic acid, indole acetic acid, skatole, and tryptamine. Additional factors, such as aging, stress, probiotics, and diseases (spondyloarthritis, irritable bowel syndrome, inflammatory bowel disease, colorectal cancer), which are associated with variability in Trp metabolism, can influence Trp–microbiome–immune system interactions in the gut and also play roles in regulating gut immunity. This review clarifies how the gut microbiota regulates Trp metabolism and identifies the underlying molecular mechanisms of these interactions. Increased mechanistic insight into how the microbiota modulates the intestinal immune system through Trp metabolism may allow for the identification of innovative microbiota-based diagnostics, as well as appropriate nutritional supplementation of Trp to prevent or alleviate intestinal inflammation

  19. Scavenger receptors in homeostasis and immunity.

    Science.gov (United States)

    Canton, Johnathan; Neculai, Dante; Grinstein, Sergio

    2013-09-01

    Scavenger receptors were originally identified by their ability to recognize and to remove modified lipoproteins; however, it is now appreciated that they carry out a striking range of functions, including pathogen clearance, lipid transport, the transport of cargo within the cell and even functioning as taste receptors. The large repertoire of ligands recognized by scavenger receptors and their broad range of functions are not only due to the wide range of receptors that constitute this family but also to their ability to partner with various co-receptors. The ability of individual scavenger receptors to associate with different co-receptors makes their responsiveness extremely versatile. This Review highlights recent insights into the structural features that determine the function of scavenger receptors and the emerging role that these receptors have in immune responses, notably in macrophage polarization and in the pathogenesis of diseases such as atherosclerosis and Alzheimer's disease.

  20. Immune Aspects of Female Infertility

    Directory of Open Access Journals (Sweden)

    Andrea Brazdova

    2016-05-01

    Full Text Available Immune infertility, in terms of reproductive failure, has become a serious health issue involving approximately 1 out of 5 couples at reproductive age. Semen that is defined as a complex fluid containing sperm, cellular vesicles and other cells and components, could sensitize the female genital tract. The immune rejection of male semen in the female reproductive tract is explained as the failure of natural tolerance leading to local and/or systemic immune response. Present active immune mechanism may induce high levels of anti-seminal/sperm antibodies. It has already been proven that iso-immunization is associated with infertility. Comprehensive studies with regards to the identification of antibody-targets and the determination of specific antibody class contribute to the development of effective immuno-therapy and, on the other hand, potential immuno-contraception, and then of course to complex patient diagnosis. This review summarizes the aspects of female immune infertility.

  1. Immune interactions in endometriosis

    Science.gov (United States)

    Herington, Jennifer L; Bruner-Tran, Kaylon L; Lucas, John A; Osteen, Kevin G

    2011-01-01

    Endometriosis is a common, complex gynecologic disorder characterized by the presence of endometrial glands and stroma at extrauterine (ectopic) sites. In women who develop this disease, alterations in specific biological processes involving both the endocrine and immune systems have been observed, which may explain the survival and growth of displaced endometrial tissue in affected women. In the past decade, a considerable amount of research has implicated a role for alterations in progesterone action at both eutopic and ectopic sites of endometrial growth which may contribute to the excessive inflammation associated with progression of endometriosis; however, it remains unclear whether these anomalies induce the condition or are simply a consequence of the disease process. In this article, we summarize current knowledge of alterations within the immune system of endometriosis patients and discuss how endometrial cells from women with this disease not only have the capacity to escape immunosurveillance, but also use inflammatory mechanisms to promote their growth within the peritoneal cavity. Finally, we discuss evidence that exposure to an environmental endocrine disruptor, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin, can mediate the development of an endometrial phenotype that exhibits both reduced progesterone responsiveness and hypersensitivity to proinflammatory stimuli mimicking the endometriosis phenotype. Future studies in women with endometriosis should consider whether a heightened inflammatory response within the peritoneal microenvironment contributes to the development and persistence of this disease. PMID:21895474

  2. Skin Immunization Obviates Alcohol-Related Immune Dysfunction

    Directory of Open Access Journals (Sweden)

    Rhonda M. Brand

    2015-11-01

    Full Text Available Alcoholics suffer from immune dysfunction that can impede vaccine efficacy. If ethanol (EtOH-induced immune impairment is in part a result of direct exposure of immune cells to EtOH, then reduced levels of exposure could result in less immune dysfunction. As alcohol ingestion results in lower alcohol levels in skin than blood, we hypothesized that the skin immune network may be relatively preserved, enabling skin-targeted immunizations to obviate the immune inhibitory effects of alcohol consumption on conventional vaccines. We employed the two most common chronic EtOH mouse feeding models, the liver-damaging Lieber-DeCarli (LD and liver-sparing Meadows-Cook (MC diets, to examine the roles of EtOH and/or EtOH-induced liver dysfunction on alcohol related immunosuppression. Pair-fed mice were immunized against the model antigen ovalbumin (OVA by DNA immunization or against flu by administering the protein-based influenza vaccine either systemically (IV, IM, directly to liver (hydrodynamic, or cutaneously (biolistic, ID. We measured resulting tissue EtOH levels, liver stress, regulatory T cell (Treg, and myeloid-derived suppressor cell (MDSC populations. We compared immune responsiveness by measuring delayed-type hypersensitivity (DTH, antigen-specific cytotoxic T lymphocyte (CTL, and antibody induction as a function of delivery route and feeding model. We found that, as expected, and independent of the feeding model, EtOH ingestion inhibits DTH, CTL lysis, and antigen-specific total IgG induced by traditional systemic vaccines. On the other hand, skin-targeted vaccines were equally immunogenic in alcohol-exposed and non-exposed subjects, suggesting that cutaneous immunization may result in more efficacious vaccination in alcohol-ingesting subjects.

  3. Immune Evasion, Immunopathology and the Regulation of the Immune System

    Directory of Open Access Journals (Sweden)

    Bruno Faivre

    2013-02-01

    Full Text Available Costs and benefits of the immune response have attracted considerable attention in the last years among evolutionary biologists. Given the cost of parasitism, natural selection should favor individuals with the most effective immune defenses. Nevertheless, there exists huge variation in the expression of immune effectors among individuals. To explain this apparent paradox, it has been suggested that an over-reactive immune system might be too costly, both in terms of metabolic resources and risks of immune-mediated diseases, setting a limit to the investment into immune defenses. Here, we argue that this view neglects one important aspect of the interaction: the role played by evolving pathogens. We suggest that taking into account the co-evolutionary interactions between the host immune system and the parasitic strategies to overcome the immune response might provide a better picture of the selective pressures that shape the evolution of immune functioning. Integrating parasitic strategies of host exploitation can also contribute to understand the seemingly contradictory results that infection can enhance, but also protect from, autoimmune diseases. In the last decades, the incidence of autoimmune disorders has dramatically increased in wealthy countries of the northern hemisphere with a concomitant decrease of most parasitic infections. Experimental work on model organisms has shown that this pattern may be due to the protective role of certain parasites (i.e., helminths that rely on the immunosuppression of hosts for their persistence. Interestingly, although parasite-induced immunosuppression can protect against autoimmunity, it can obviously favor the spread of other infections. Therefore, we need to think about the evolution of the immune system using a multidimensional trade-off involving immunoprotection, immunopathology and the parasitic strategies to escape the immune response.

  4. Persistent hepatitis virus infection and immune homeostasis

    OpenAIRE

    ZHOU Yun

    2014-01-01

    Homeostasis between the host and viruses is naturally maintained. On the one hand, the immune system activates the immune response to kill or eliminate viruses; on the other hand, the immune system controls the immune response to maintain immune homeostasis. The cause of persistent infections with hepatitis viruses such as HBV and HCV is that viral molecules damage the immune system of the host and their variants escape immune clearance. Long-term coexistence of the host and viruses is the pr...

  5. Immune responses of ducks infected with duck Tembusu virus

    Directory of Open Access Journals (Sweden)

    Ning eLi

    2015-05-01

    Full Text Available Duck Tembusu virus (DTMUV can cause serious disease in ducks, characterized by reduced egg production. Although the virus has been isolated and detection methods developed, the host immune responses to DTMUV infection are unclear. Therefore, we systematically examined the expression of immune-related genes and the viral distribution in DTMUV-infected ducks, using quantitative real-time PCR. Our results show that DTMUV replicates quickly in many tissues early in infection, with the highest viral titers in the spleen 1 day after infection. Rig-1, Mda5, and Tlr3 are involved in the host immune response to DTMUV, and the expression of proinflammatory cytokines (Il-1β, -2, -6, Cxcl8 and antiviral proteins (Mx, Oas, etc. are also upregulated early in infection. The expression of Il-6 increased most significantly in the tissues tested. The upregulation of Mhc-I was observed in the brain and spleen, but the expression of Mhc-II was upregulated in the brain and downregulated in the spleen. The expression of the interferons was also upregulated to different degrees in the spleen but that of the brain was various. Our study suggests that DTMUV replicates rapidly in various tissues and that the host immune responses are activated early in infection. However, the overexpression of cytokines may damage the host. These results extend our understanding of the immune responses of ducks to DTMUV infection, and provide insight into the pathogenesis of DTMUV attributable to host factors.

  6. Oral immune therapy: targeting the systemic immune system via the gut immune system for the treatment of inflammatory bowel disease.

    Science.gov (United States)

    Ilan, Yaron

    2016-01-01

    Inflammatory bowel diseases (IBD) are associated with an altered systemic immune response leading to inflammation-mediated damage to the gut and other organs. Oral immune therapy is a method of systemic immune modulation via alteration of the gut immune system. It uses the inherit ability of the innate system of the gut to redirect the systemic innate and adaptive immune responses. Oral immune therapy is an attractive clinical approach to treat autoimmune and inflammatory disorders. It can induce immune modulation without immune suppression, has minimal toxicity and is easily administered. Targeting the systemic immune system via the gut immune system can serve as an attractive novel therapeutic method for IBD. This review summarizes the current data and discusses several examples of oral immune therapeutic methods for using the gut immune system to generate signals to reset systemic immunity as a treatment for IBD.

  7. Evolutionary perspectives on innate immunity from the study of Caenorhabditis elegans.

    Science.gov (United States)

    Kim, Dennis H; Ausubel, Frederick M

    2005-02-01

    Genetic and functional genomic approaches have begun to define the molecular determinants of pathogen resistance in Caenorhabditis elegans. Conserved signal transduction components are required for pathogen resistance, including a Toll/IL-1 receptor domain adaptor protein that functions upstream of a conserved p38 MAP kinase pathway. We suggest that this pathway is an ancestral innate immune signaling pathway present in the common ancestor of nematodes, arthropods and vertebrates, which is likely to predate the involvement of canonical Toll signaling pathways in innate immunity. We anticipate that the study of pathogen resistance in C. elegans will continue to provide evolutionary and mechanistic insights into the signal transduction and physiology of innate immunity.

  8. Immunization Information System and Informatics to Promote Immunizations: Perspective From Minnesota Immunization Information Connection.

    Science.gov (United States)

    Muscoplat, Miriam Halstead; Rajamani, Sripriya

    2017-01-01

    The vision for management of immunization information is availability of real-time consolidated data and services for all ages, to clinical, public health, and other stakeholders. This is being executed through Immunization Information Systems (IISs), which are population-based and confidential computerized systems present in most US states and territories. Immunization Information Systems offer many functionalities, such as immunization assessment reports, client follow-up, reminder/recall feature, vaccine management tools, state-supplied vaccine ordering, comprehensive immunization history, clinical decision support/vaccine forecasting and recommendations, data processing, and data exchange. This perspective article will present various informatics tools in an IIS, in the context of the Minnesota Immunization Information Connection.

  9. The Major Players in Adaptive Immunity-Cell-mediated Immunity

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 14; Issue 6. The Major Players in Adaptive Immunity - Cell-mediated Immunity. Asma Ahmed Banishree Saha Anand Patwardhan Shwetha Shivaprasad Dipankar Nandi. General Article Volume 14 Issue 6 June 2009 pp 610-621 ...

  10. Partial immunity in murine by immunization with a toxoplasmic DNA ...

    African Journals Online (AJOL)

    arsenal

    2012-06-12

    Jun 12, 2012 ... vaccine can be effective in partial protection against this parasite. In this study ... that mice immunized by pcROP1 with or without alum produced high Th1 immune response compared .... antigen-specific antibodies, 96-well costar plates were coated .... vaccines against some protozoa, for example, malaria,.

  11. The Immune Response of Maternally Immune Chicks to Vaccination ...

    African Journals Online (AJOL)

    The Immune Response of Maternally Immune Chicks to Vaccination with Newcastle Disease Virus. ... G A El-Tayeb, M Y El-Ttegani, I E Hajer, M A Mohammed ... This study was conducted to determine the persistence of maternally derived antibodies (MDA) to Newcastle disease virus (NDV) in newly hatched chicks and the ...

  12. Insight in seasonal affective disorder.

    Science.gov (United States)

    Ghaemi, S N; Sachs, G S; Baldassano, C F; Truman, C J

    1997-01-01

    Lack of insight complicates the evaluation and treatment of patients with psychotic and affective disorders. No studies of insight in seasonal affective disorder (SAD) have been reported. Thirty patients with SAD diagnosed by the Structured Clinical Interview for DSM-III-R but no other axis I conditions were treated short-term with light-therapy. Insight was measured with the Scale to Assess Unawareness of Mental Disorder (SUMD) as modified by the authors to assess the self-report of insight into depressive symptoms. Increasing scores (1 to 5) indicated increasing unawareness of illness (i.e., less insight). SAD patients displayed a moderate amount of insight when depressed (mean SUMD score, 2.5). When recovered, they showed no significant change in insight into past depressive symptoms (mean SUMD score, 2.8). Greater insight into current depressive symptoms correlated with more depressive symptoms on the Hamilton Rating Scale for Depression score ([HRSD] r = .35, P depressive symptoms that does not change after recovery, a result in agreement with studies of insight in psychosis and mania. Further, in SAD, increased severity of illness may be associated with increased insight into depressive symptoms, consistent with the hypothesis of depressive realism.

  13. Immune reactivities against gums.

    Science.gov (United States)

    Vojdani, Aristo; Vojdani, Charlene

    2015-01-01

    Different kinds of gums from various sources enjoy an extremely broad range of commercial and industrial use, from food and pharmaceuticals to printing and adhesives. Although generally recognized as safe by the US Food and Drug Administration (FDA), gums have a history of association with sensitive or allergic reactions. In addition, studies have shown that gums have a structural, molecular similarity to a number of common foods. A possibility exists for cross-reactivity. Due to the widespread use of gums in almost every aspect of modern life, the overall goal of the current investigation was to determine the degree of immune reactivity to various gum antigens in the sera of individuals representing the general population. The study was a randomized, controlled trial. 288 sera purchased from a commercial source. The sera was screened for immunoglobulin G (IgG) and immunoglobulin E (IgE) antibodies against extracts of mastic gum, carrageenan, xantham gum, guar gum, gum tragacanth, locust bean gum, and β-glucan, using indirect enzyme-linked immunosorbent assay (ELISA) testing. For each gum antigen, inhibition testing was performed on the 4 sera that showed the highest IgG and IgE immune reactivity against the different gums used in the study. Inhibition testing on these same sera for sesame albumin, lentil, corn, rice, pineapple, peanut, pea protein, shrimp, or kidney bean was used to determine the cross-reactivity of these foods with the gum. Of the 288 samples, 4.2%-27% of the specimens showed a significant elevation in IgG antibodies against various gums. Only 4 of 288, or 1.4%, showed a simultaneous elevation of the IgG antibody against all 7 gum extracts. For the IgE antibody, 15.6%-29.1% of the specimens showed an elevation against the various gums. A significant percentage of the specimens, 12.8%, simultaneously produced IgE antibodies against all 7 tested extracts. Overall, the percentage of elevation in IgE antibodies against different gum extracts, with

  14. The Distinctive Sensitivity to Microgravity of Immune Cell Subpopulations

    Science.gov (United States)

    Chen, Hui; Luo, Haiying; Liu, Jing; Wang, Peng; Dong, Dandan; Shang, Peng; Zhao, Yong

    2015-11-01

    Immune dysfunction in astronauts is well documented after spaceflights. Microgravity is one of the key factors directly suppressing the function of immune system. However, it is unclear which subpopulations of immune cells including innate and adaptive immune cells are more sensitive to microgravity We herein investigated the direct effects of modeled microgravity (MMg) on different immune cells in vitro. Mouse splenocytes, thymocytes and bone marrow cells were exposed to MMg for 16 hrs. The survival and the phenotypes of different subsets of immune cells including CD4+T cells, CD8+T cells, CD4+Foxp3+ regulatory T cells (Treg), B cells, monocytes/macrophages, dendritic cells (DCs), natural killer cells (NK) were determined by flow cytometry. After splenocytes were cultured under MMg for 16h, the cell frequency and total numbers of monocytes, macrophages and CD4+Foxp3+T cells were significantly decreased more than 70 %. MMg significantly decreased the cell numbers of CD8+ T cells, B cells and neutrophils in splenocytes. The cell numbers of CD4+T cells and NK cells were unchanged significantly when splenocytes were cultured under MMg compared with controls. However, MMg significantly increased the ratio of mature neutrophils to immature neutrophils in bone marrow and the cell number of DCs in splenocytes. Based on the cell survival ability, monocytes, macrophages and CD4+Foxp3+Treg cells are most sensitive to microgravity; CD4+T cells and NK cells are resistant to microgravity; CD8+T cells and neutrophils are impacted by short term microgravity exposure. Microgravity promoted the maturation of neutrophils and development of DCs in vitro. The present studies offered new insights on the direct effects of MMg on the survival and homeostasis of immune cell subsets.

  15. 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

  16. 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.

  17. Effects of BRAF mutations and BRAF inhibition on immune responses to melanoma

    Science.gov (United States)

    Ilieva, Kristina M.; Correa, Isabel; Josephs, Debra H.; Karagiannis, Panagiotis; Egbuniwe, Isioma U.; Cafferkey, Michiala J.; Spicer, James F.; Harries, Mark; Nestle, Frank O.; Lacy, Katie E.; Karagiannis, Sophia N.

    2014-01-01

    Malignant melanoma is associated with poor clinical prognosis; however, novel molecular and immune therapies are now improving patient outcomes. Almost 50% of melanomas harbor targetable activating mutations of BRAF which promote RAS-RAF-MEK-ERK pathway activation and melanoma proliferation. Recent evidence also indicates that melanomas bearing mutant BRAF may also have altered immune responses, suggesting additional avenues for treatment of this patient group. The small molecule inhibitors selective for mutant BRAF induce significant but short-lived clinical responses in a proportion of patients, but also lead to immune stimulatory bystander events, which then subside with the emergence of resistance to inhibition. Simultaneous BRAF and MEK inhibition, and especially combination of BRAF inhibitors with new immunotherapies such as checkpoint blockade antibodies, may further enhance immune activation, or counteract immunosuppressive signals. Pre-clinical evaluation and ongoing clinical trials should provide novel insights into the role of immunity in the therapy of BRAF-mutant melanoma. PMID:25385327

  18. Insights on STEM Careers

    Energy Technology Data Exchange (ETDEWEB)

    Wendelberger, Joanne Roth [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2014-11-05

    This presentation will provide career advice for individuals seeking to go beyond just having a job to building a successful career in the areas of Science, Technology, Engineering, and Mathematics. Careful planning can be used to turn a job into a springboard for professional advancement and personal satisfaction. Topics to be addressed include setting priorities, understanding career ladders, making tough choices, overcoming stereotypes and assumptions by others, networking, developing a professional identify, and balancing a career with family and other personal responsibilities. Insights on the transition from individual technical work to leadership will also be provided. The author will draw upon experiences gained in academic, industrial, and government laboratory settings, as well as extensive professional service and community involvement.

  19. Osho - Insights on sex.

    Science.gov (United States)

    Nagaraj, Anil Kumar Mysore

    2013-01-01

    Sex is a mysterious phenomenon, which has puzzled even great sages. Human beings have researched and mastered the biology of sex. But that is not all. Sex needs to be understood from the spiritual perspective too. The vision of Osho is an enlightening experience in this regard. Out of the thousands of lectures, five lectures on sex made Osho most notorious. Born into a Jain family of Madhya Pradesh, Rajneesh, who later wanted himself to be called Osho, is a great master. He has spoken volumes on a wide range of topics ranging from sex to super-consciousness. His contributions in the area of sex are based on the principles of "Tantra" which has its origin from Buddhism. This article focuses on his life and insights on sex, which if understood properly, can be a stepping stone for enlightenment.

  20. Outsourcing/Offshoring Insights

    DEFF Research Database (Denmark)

    Tate, Wendy; Bals, Lydia

    2017-01-01

    Findings: Both the geographical and governance dimensions are part of the rightshoring decision which is an important conceptual foundation for this special issue, as it invited insightful pieces on all of these phenomena (e.g. outsourcing, insourcing, offshoring, reshoring), acknowledging...... for future research out of the six papers are summarized in Table III. There is ample opportunity to further shed light on these suggestions as well as to cover parts of the “rightshoring” framework presented, that remain less covered here (e.g. insourcing and/or reshoring). Practical implications: The array...... of potential “rightshoring” options fosters clarity about the phenomena studied and their implications. The main practical implications of the six papers are summarized in Table II. Originality/value: The overall conceptual framework highlights the positioning of the final papers included into the special...

  1. Microscale Immune Studies Laboratory.

    Energy Technology Data Exchange (ETDEWEB)

    Poschet, Jens Fredrich; Carroll-Portillo, Amanda; Wu, Meiye; Manginell, Ronald Paul; Herr, Amy Elizabeth; Martino, Anthony A.; Perroud, Thomas D.; Branda, Catherine; Srivastava, Nimisha; Sinclair, Michael B.; Moorman, Matthew Wallace; Apblett, Christopher Alan; Sale, Kenneth L.; James, Conrad D.; Carles, Elizabeth L.; Lidke, Diane S. (University of New Mexico, Albuquerque, NM); Van Benthem, Mark Hilary; Rebeil, Roberto; Kaiser, Julie; Seaman, William (University of California, San Francisco, CA); Rempe, Susan; Brozik, Susan Marie; Jones, Howland D. T.; Gemperline, Paul (East Carolina University, Greenville, NC); Throckmorton, Daniel J.; Misra, Milind; Murton, Jaclyn K.; Carson, Bryan D.; Zhang, Zhaoduo; Plimpton, Steven James; Renzi, Ronald F.; Lane, Todd W.; Ndiaye-Dulac, Elsa; Singh, Anup K.; Haaland, David Michael; Faulon, Jean-Loup Michel; Davis, Ryan W.; Ricken, James Bryce; Branda, Steven S.; Patel, Kamlesh D.; Joo, Jaewook; Kubiak, Glenn D.; Brennan, James S.; Martin, Shawn Bryan; Brasier, Allan (University of Texas Mecial Branch, Galveston, TX)

    2009-01-01

    The overarching goal is to develop novel technologies to elucidate molecular mechanisms of the innate immune response in host cells to pathogens such as bacteria and viruses including the mechanisms used by pathogens to subvert/suppress/obfuscate the immune response to cause their harmful effects. Innate immunity is our first line of defense against a pathogenic bacteria or virus. A comprehensive 'system-level' understanding of innate immunity pathways such as toll-like receptor (TLR) pathways is the key to deciphering mechanisms of pathogenesis and can lead to improvements in early diagnosis or developing improved therapeutics. Current methods for studying signaling focus on measurements of a limited number of components in a pathway and hence, fail to provide a systems-level understanding. We have developed a systems biology approach to decipher TLR4 pathways in macrophage cell lines in response to exposure to pathogenic bacteria and their lipopolysaccharide (LPS). Our approach integrates biological reagents, a microfluidic cell handling and analysis platform, high-resolution imaging and computational modeling to provide spatially- and temporally-resolved measurement of TLR-network components. The Integrated microfluidic platform is capable of imaging single cells to obtain dynamic translocation data as well as high-throughput acquisition of quantitative protein expression and phosphorylation information of selected cell populations. The platform consists of multiple modules such as single-cell array, cell sorter, and phosphoflow chip to provide confocal imaging, cell sorting, flow cytomtery and phosphorylation assays. The single-cell array module contains fluidic constrictions designed to trap and hold single host cells. Up to 100 single cells can be trapped and monitored for hours, enabling detailed statistically-significant measurements. The module was used to analyze translocation behavior of transcription factor NF-kB in macrophages upon activation

  2. Modeling rejection immunity

    Directory of Open Access Journals (Sweden)

    Gaetano Andrea De

    2012-05-01

    Full Text Available Abstract Background Transplantation is often the only way to treat a number of diseases leading to organ failure. To overcome rejection towards the transplanted organ (graft, immunosuppression therapies are used, which have considerable side-effects and expose patients to opportunistic infections. The development of a model to complement the physician’s experience in specifying therapeutic regimens is therefore desirable. The present work proposes an Ordinary Differential Equations model accounting for immune cell proliferation in response to the sudden entry of graft antigens, through different activation mechanisms. The model considers the effect of a single immunosuppressive medication (e.g. cyclosporine, subject to first-order linear kinetics and acting by modifying, in a saturable concentration-dependent fashion, the proliferation coefficient. The latter has been determined experimentally. All other model parameter values have been set so as to reproduce reported state variable time-courses, and to maintain consistency with one another and with the experimentally derived proliferation coefficient. Results The proposed model substantially simplifies the chain of events potentially leading to organ rejection. It is however able to simulate quantitatively the time course of graft-related antigen and competent immunoreactive cell populations, showing the long-term alternative outcomes of rejection, tolerance or tolerance at a reduced functional tissue mass. In particular, the model shows that it may be difficult to attain tolerance at full tissue mass with acceptably low doses of a single immunosuppressant, in accord with clinical experience. Conclusions The introduced model is mathematically consistent with known physiology and can reproduce variations in immune status and allograft survival after transplantation. The model can be adapted to represent different therapeutic schemes and may offer useful indications for the optimization of

  3. Cholinergic signalling in gut immunity

    NARCIS (Netherlands)

    Dhawan, Shobhit; Cailotto, Cathy; Harthoorn, Lucien F.; de Jonge, Wouter J.

    2012-01-01

    The gut immune system shares many signalling molecules and receptors with the autonomic nervous system. A good example is the vagal neurotransmitter acetylcholine (ACh), for which many immune cell types express cholinergic receptors (AChR). In the last decade the vagal nerve has emerged as an

  4. Alcohol, aging, and innate immunity.

    Science.gov (United States)

    Boule, Lisbeth A; Kovacs, Elizabeth J

    2017-07-01

    The global population is aging: in 2010, 8% of the population was older than 65 y, and that is expected to double to 16% by 2050. With advanced age comes a heightened prevalence of chronic diseases. Moreover, elderly humans fair worse after acute diseases, namely infection, leading to higher rates of infection-mediated mortality. Advanced age alters many aspects of both the innate and adaptive immune systems, leading to impaired responses to primary infection and poor development of immunologic memory. An often overlooked, yet increasingly common, behavior in older individuals is alcohol consumption. In fact, it has been estimated that >40% of older adults consume alcohol, and evidence reveals that >10% of this group is drinking more than the recommended limit by the National Institute on Alcohol Abuse and Alcoholism. Alcohol consumption, at any level, alters host immune responses, including changes in the number, phenotype, and function of innate and adaptive immune cells. Thus, understanding the effect of alcohol ingestion on the immune system of older individuals, who are already less capable of combating infection, merits further study. However, there is currently almost nothing known about how drinking alters innate immunity in older subjects, despite innate immune cells being critical for host defense, resolution of inflammation, and maintenance of immune homeostasis. Here, we review the effects of aging and alcohol consumption on innate immune cells independently and highlight the few studies that have examined the effects of alcohol ingestion in aged individuals. © Society for Leukocyte Biology.

  5. Insights into business student's book

    CERN Document Server

    Lannon, Michael; Trappe, Tonya

    1993-01-01

    With Challenging reading and listening texts from a range of authentic business sources, New Insights into Business will really engage your students. The thorough language and vocabulary syllabus together with the strong focus on business skills development gives students everything they need to function effectively in the workplace. New Insights into Business is a self-contained course and is also an ideal follow-on to First Insights into Business.

  6. Insight in schizophrenia: a review.

    Science.gov (United States)

    Dam, Jesper

    2006-01-01

    The issue of insight in schizophrenia must be assumed to be one of the most important aspects of the clinical examination. Comprehensive studies have shown that between 50% and 80% of all patients suffering from schizophrenia do not believe that they have a disorder. In recent years, poor insight in schizophrenia has been the subject of increasing interest, as manifested in a number of studies discussed in the present review. Some of these studies focus on insight correlated to various parameters such as psychopathology, neuropsychology, clinical relevance and compliance. Other studies refer to more theoretical implications, among these the issue of defining the concept of insight: whether insight can be seen as a "primary" phenomenon in schizophrenia, and whether insight may be graduated, dimensioned or increased. Several authors have developed rating scales in an attempt to obtain a measure for the degree or dimension of insight. Here, the range of parameters employed gives an excellent impression of the complexity of the concept of insight. In the concluding discussion, a phenomenological aspect is brought in, in an attempt to place the concept of insight in relation to disturbances of the self in schizophrenia and to primary symptoms in schizophrenia, amongst these autism.

  7. VACCINES AND IMMUNIZATION: WORLD SITUATION

    Directory of Open Access Journals (Sweden)

    G.H. Brundtland

    2007-01-01

    Full Text Available The last issue of the report «vaccines and immunization: world situation» stresses considerable success in immunization at the global level since the mid 90 s — completely total eradication of poliomyelitis across the world, as well as the drastic reduction of the new measles and tetanus cases among mothers and newborns in some poor countries. The report also briefly describes the progress in the development and implementation of the new life saving vaccines, which may save millions of lives annually. The authors have explained some of the reasons, why the global community should invest in immunization, as well as the perspectives for the use of vaccines and immunization in future.Key words: vaccine, immunization, children.

  8. Immune Mechanisms in Myelodysplastic Syndrome

    Directory of Open Access Journals (Sweden)

    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.

  9. [Stress and auto-immunity].

    Science.gov (United States)

    Delévaux, I; Chamoux, A; Aumaître, O

    2013-08-01

    The etiology of auto-immune disorders is multifactorial. Stress is probably a participating factor. Indeed, a high proportion of patients with auto-immune diseases report uncommon stress before disease onset or disease flare. The biological consequences of stress are increasingly well understood. Glucocorticoids and catecholamines released by hypothalamic-pituitary-adrenal axis during stress will alter the balance Th1/Th2 and the balance Th17/Treg. Stress impairs cellular immunity, decreases immune tolerance and stimulates humoral immunity exposing individuals to autoimmune disease among others. The treatment for autoimmune disease should include stress management. Copyright © 2012 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  10. 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....

  11. Melatonin: Buffering the Immune System

    Directory of Open Access Journals (Sweden)

    Juan M. Guerrero

    2013-04-01

    Full Text Available Melatonin modulates a wide range of physiological functions with pleiotropic effects on the immune system. Despite the large number of reports implicating melatonin as an immunomodulatory compound, it still remains unclear how melatonin regulates immunity. While some authors argue that melatonin is an immunostimulant, many studies have also described anti-inflammatory properties. The data reviewed in this paper support the idea of melatonin as an immune buffer, acting as a stimulant under basal or immunosuppressive conditions or as an anti-inflammatory compound in the presence of exacerbated immune responses, such as acute inflammation. The clinical relevance of the multiple functions of melatonin under different immune conditions, such as infection, autoimmunity, vaccination and immunosenescence, is also reviewed.

  12. Melatonin: Buffering the Immune System

    Science.gov (United States)

    Carrillo-Vico, Antonio; Lardone, Patricia J.; Álvarez-Sánchez, Nuria; Rodríguez-Rodríguez, Ana; Guerrero, Juan M.

    2013-01-01

    Melatonin modulates a wide range of physiological functions with pleiotropic effects on the immune system. Despite the large number of reports implicating melatonin as an immunomodulatory compound, it still remains unclear how melatonin regulates immunity. While some authors argue that melatonin is an immunostimulant, many studies have also described anti-inflammatory properties. The data reviewed in this paper support the idea of melatonin as an immune buffer, acting as a stimulant under basal or immunosuppressive conditions or as an anti-inflammatory compound in the presence of exacerbated immune responses, such as acute inflammation. The clinical relevance of the multiple functions of melatonin under different immune conditions, such as infection, autoimmunity, vaccination and immunosenescence, is also reviewed. PMID:23609496

  13. 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.

  14. Student pharmacists' perceptions of immunizations.

    Science.gov (United States)

    Kubli, Kara; McBane, Sarah; Hirsch, Jan D; Lorentz, Sarah

    2017-05-01

    The primary aim of this study was to explore changes in knowledge level, perceived importance and apprehension of immunizations by first year pharmacy students pre- vs. post-immunization education and training. First year pharmacy students at the University of California San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences (UC San Diego SSPPS) completed a pre- and post-immunization training course questionnaire. Knowledge base and perceived importance level of immunizations including hepatitis B, influenza, measles, mumps, rubella (MMR), varicella, tetanus, diphtheria, pertussis (Tdap), meningococcal and human papilloma virus (HPV) were assessed. In addition, apprehension of needle administration and fears regarding safety and efficacy were evaluated. Of 120 students, 85 (71%) completed pre- and post-course questionnaires for this study. Mean knowledge test scores increased from 56% pre-course to 83% post-course. Pre-course, 73% of participants considered immunizations as very important in preventing future disease outbreaks. Post-course, this percentage climbed to 94%. Prior to taking the course, 52% of students were apprehensive about administering injections; however, after completing the course this percentage declined to 33%. The majority of students who had been fearful prior to the course retained their fears of receiving needle injections. The proportion of students believing immunizations should be a personal choice, not mandatory, did not significantly change from pre-course (49%) to post-course (44%). The UC San Diego SSPPS immunization course increased student knowledge of immunization facts and the perceived importance of immunizations. However, a substantial portion of students retained apprehension about administering and receiving needle injections and the proportion believing immunizations should be a personal choice, almost half, did not change appreciably. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Immune oncology, immune responsiveness and the theory of everything.

    Science.gov (United States)

    Turan, Tolga; Kannan, Deepti; Patel, Maulik; Matthew Barnes, J; Tanlimco, Sonia G; Lu, Rongze; Halliwill, Kyle; Kongpachith, Sarah; Kline, Douglas E; Hendrickx, Wouter; Cesano, Alessandra; Butterfield, Lisa H; Kaufman, Howard L; Hudson, Thomas J; Bedognetti, Davide; Marincola, Francesco; Samayoa, Josue

    2018-06-05

    Anti-cancer immunotherapy is encountering its own checkpoint. Responses are dramatic and long lasting but occur in a subset of tumors and are largely dependent upon the pre-existing immune contexture of individual cancers. Available data suggest that three landscapes best define the cancer microenvironment: immune-active, immune-deserted and immune-excluded. This trichotomy is observable across most solid tumors (although the frequency of each landscape varies depending on tumor tissue of origin) and is associated with cancer prognosis and response to checkpoint inhibitor therapy (CIT). Various gene signatures (e.g. Immunological Constant of Rejection - ICR and Tumor Inflammation Signature - TIS) that delineate these landscapes have been described by different groups. In an effort to explain the mechanisms of cancer immune responsiveness or resistance to CIT, several models have been proposed that are loosely associated with the three landscapes. Here, we propose a strategy to integrate compelling data from various paradigms into a "Theory of Everything". Founded upon this unified theory, we also propose the creation of a task force led by the Society for Immunotherapy of Cancer (SITC) aimed at systematically addressing salient questions relevant to cancer immune responsiveness and immune evasion. This multidisciplinary effort will encompass aspects of genetics, tumor cell biology, and immunology that are pertinent to the understanding of this multifaceted problem.

  16. Molecular Mechanisms Underlying β-Adrenergic Receptor-Mediated Cross-Talk between Sympathetic Neurons and Immune Cells

    Directory of Open Access Journals (Sweden)

    Dianne Lorton

    2015-03-01

    Full Text Available Cross-talk between the sympathetic nervous system (SNS and immune system is vital for health and well-being. Infection, tissue injury and inflammation raise firing rates of sympathetic nerves, increasing their release of norepinephrine (NE in lymphoid organs and tissues. NE stimulation of β2-adrenergic receptors (ARs in immune cells activates the cAMP-protein kinase A (PKA intracellular signaling pathway, a pathway that interfaces with other signaling pathways that regulate proliferation, differentiation, maturation and effector functions in immune cells. Immune–SNS cross-talk is required to maintain homeostasis under normal conditions, to develop an immune response of appropriate magnitude after injury or immune challenge, and subsequently restore homeostasis. Typically, β2-AR-induced cAMP is immunosuppressive. However, many studies report actions of β2-AR stimulation in immune cells that are inconsistent with typical cAMP–PKA signal transduction. Research during the last decade in non-immune organs, has unveiled novel alternative signaling mechanisms induced by β2-AR activation, such as a signaling switch from cAMP–PKA to mitogen-activated protein kinase (MAPK pathways. If alternative signaling occurs in immune cells, it may explain inconsistent findings of sympathetic regulation of immune function. Here, we review β2-AR signaling, assess the available evidence for alternative signaling in immune cells, and provide insight into the circumstances necessary for “signal switching” in immune cells.

  17. Immunization Schedules for Infants and Children

    Science.gov (United States)

    ... ACIP Vaccination Recommendations Why Immunize? Vaccines: The Basics Immunization Schedule for Infants and Children (Birth through 6 ... any questions please talk to your doctor. 2018 Immunization Schedule Recommended Vaccinations for Infants and Children Schedule ...

  18. Immunizations and Asians and Pacific Islanders

    Science.gov (United States)

    ... and Data > Minority Population Profiles > Asian American > Immunizations Immunizations and Asians and Pacific Islanders Asian/Pacific Islander ... 35 months reached the Healthy People goal for immunizations for hepatitis B, MMR (measles-mumps-rubella), polio ...

  19. Play the Immune System Defender Game

    Science.gov (United States)

    ... Questionnaire The Immune System Play the Immune System Game About the game Granulocytes, macrophages and dendritic cells are immune cells ... last will in Paris. Play the Blood Typing Game Try to save some patients and learn about ...

  20. Insights into PRA methodologies

    International Nuclear Information System (INIS)

    Gallagher, D.; Lofgren, E.; Atefi, B.; Liner, R.; Blond, R.; Amico, P.

    1984-08-01

    Probabilistic Risk Assessments (PRAs) for six nuclear power plants were examined to gain insight into how the choice of analytical methods can affect the results of PRAs. The PRA sreflectope considered was limited to internally initiated accidents sequences through core melt. For twenty methodological topic areas, a baseline or minimal methodology was specified. The choice of methods for each topic in the six PRAs was characterized in terms of the incremental level of effort above the baseline. A higher level of effort generally reflects a higher level of detail or a higher degree of sophistication in the analytical approach to a particular topic area. The impact on results was measured in terms of how additional effort beyond the baseline level changed the relative importance and ordering of dominant accident sequences compared to what would have been observed had methods corresponding to the baseline level of effort been employed. This measure of impact is a more useful indicator of how methods affect perceptions of plant vulnerabilities than changes in core melt frequency would be. However, the change in core melt frequency was used as a secondary measure of impact for nine topics where availability of information permitted. Results are presented primarily in the form of effort-impact matrices for each of the twenty topic areas. A suggested effort-impact profile for future PRAs is presented

  1. Grigor Narekatsi's astronomical insights

    Science.gov (United States)

    Poghosyan, Samvel

    2015-07-01

    What stand out in the solid system of Gr. Narekatsi's naturalistic views are his astronomical insights on the material nature of light, its high speed and the Sun being composed of "material air". Especially surprising and fascinating are his views on stars and their clusters. What astronomers, including great Armenian academician V. Ambartsumian (scattering of stellar associations), would understand and prove with much difficulty thousand years later, Narekatsi predicted in the 10th century: "Stars appear and disappear untimely", "You who gather and scatter the speechless constellations, like a flock of sheep". Gr. Narekatsti's reformative views were manifested in all the spheres of the 10th century social life; he is a reformer of church life, great language constructor, innovator in literature and music, freethinker in philosophy and science. His ideology is the reflection of the 10th century Armenian Renaissance. During the 9th-10th centuries, great masses of Armenians, forced to migrate to the Balkans, took with them and spread reformative ideas. The forefather of the western science, which originated in the period of Reformation, is considered to be the great philosopher Nicholas of Cusa. The study of Gr. Narekatsti's logic and naturalistic views enables us to claim that Gr. Narekatsti is the great grandfather of European science.

  2. O insight em psiquiatria

    Directory of Open Access Journals (Sweden)

    Ana Margarida P. Cardoso

    2008-12-01

    Full Text Available O sinal de que algo está a acontecer contribui para que o paciente reconheça que alguma coisa de estranho se está a passar consigo. Este reconhecimento faz com que o sujeito possa desempenhar uma função activa e seja um elemento colaborante do seu processo de recuperação. Cada doença apresenta, contudo, diferentes sintomas, uma vez que cada doença psiquiátrica consiste em diferentes perturbações com diversos efeitos sobre o funcionamento mental. Desta maneira, o fenómeno do insight que é registado em cada doença é diferente e expressa-se sob diferentes formas, não somente devido às manifestações clínicas da doença mas também devido às características individuais do sujeito.

  3. Constitutive innate immunity is a component of the pace-of-life syndrome in tropical birds

    NARCIS (Netherlands)

    Tieleman, BI; Williams, JB; Ricklefs, RE; Klasing, KC; Williams, Joseph B.; Ricklefs, Robert E.; Klasing, Kirk C.

    2005-01-01

    We studied the relationship between one component of immune function and basal metabolic rate (BMR), an indicator of the 'pace-of-life syndrome', among 12 tropical bird species and among individuals of the tropical house wren (Troglodytes aedon), to gain insights into functional connections between

  4. Dynamics of immune system vulnerabilities

    Science.gov (United States)

    Stromberg, Sean P.

    The adaptive immune system can be viewed as a complex system, which adapts, over time, to reflect the history of infections experienced by the organism. Understanding its operation requires viewing it in terms of tradeoffs under constraints and evolutionary history. It typically displays "robust, yet fragile" behavior, meaning common tasks are robust to small changes but novel threats or changes in environment can have dire consequences. In this dissertation we use mechanistic models to study several biological processes: the immune response, the homeostasis of cells in the lymphatic system, and the process that normally prevents autoreactive cells from entering the lymphatic system. Using these models we then study the effects of these processes interacting. We show that the mechanisms that regulate the numbers of cells in the immune system, in conjunction with the immune response, can act to suppress autoreactive cells from proliferating, thus showing quantitatively how pathogenic infections can suppress autoimmune disease. We also show that over long periods of time this same effect can thin the repertoire of cells that defend against novel threats, leading to an age correlated vulnerability. This vulnerability is shown to be a consequence of system dynamics, not due to degradation of immune system components with age. Finally, modeling a specific tolerance mechanism that normally prevents autoimmune disease, in conjunction with models of the immune response and homeostasis we look at the consequences of the immune system mistakenly incorporating pathogenic molecules into its tolerizing mechanisms. The signature of this dynamic matches closely that of the dengue virus system.

  5. Immune regulation by microbiome metabolites.

    Science.gov (United States)

    Kim, Chang H

    2018-03-22

    Commensal microbes and the host immune system have been co-evolved for mutual regulation. Microbes regulate the host immune system, in part, by producing metabolites. A mounting body of evidence indicates that diverse microbial metabolites profoundly regulate the immune system via host receptors and other target molecules. Immune cells express metabolite-specific receptors such as P2X 7 , GPR41, GPR43, GPR109A, aryl hydrocarbon receptor precursor (AhR), pregnane X receptor (PXR), farnesoid X receptor (FXR), TGR5 and other molecular targets. Microbial metabolites and their receptors form an extensive array of signals to respond to changes in nutrition, health and immunological status. As a consequence, microbial metabolite signals contribute to nutrient harvest from diet, and regulate host metabolism and the immune system. Importantly, microbial metabolites bidirectionally function to promote both tolerance and immunity to effectively fight infection without developing inflammatory diseases. In pathogenic conditions, adverse effects of microbial metabolites have been observed as well. Key immune-regulatory functions of the metabolites, generated from carbohydrates, proteins and bile acids, are reviewed in this article. © 2018 John Wiley & Sons Ltd.

  6. Cognitive insight: A systematic review.

    Science.gov (United States)

    Van Camp, L S C; Sabbe, B G C; Oldenburg, J F E

    2017-07-01

    Cognitive insight is the ability to re-evaluate thoughts and beliefs in order to make thoughtful conclusions. It differs from clinical insight, as it focuses on more general metacognitive processes. Therefore, it could be relevant to diverse disorders and non-clinical subjects. There is a growing body of research on cognitive insight in individuals with and without psychosis. This review has summarised the current state of the art regarding this topic. We conclude that while cognitive insight in its current form seems valid for use in individuals with psychosis, it is less so for individuals without psychosis. Additionally, higher cognitive insight not always leads to better psychological functioning. For instance, higher levels of self-reflection are often associated with depressive mood. We therefore recommend the sub-components of cognitive insight to be studied separately. Also, it is unclear what position cognitive insight takes within the spectrum of metacognitive processes and how it relates to other self-related concepts that have been defined previously in literature. Combining future and past research on cognitive insight and its analogue concepts will help in the formation of a uniform definition that fits all subjects discussed here. Copyright © 2017. Published by Elsevier Ltd.

  7. Hyperons: Insights into baryon structures

    International Nuclear Information System (INIS)

    Lach, J.

    1991-08-01

    The baryon octet is composed mainly of hyperons. Modern high energy hyperon beams provide a tool for the study of hyperon static properties and interactions. Experiments with these beams have provided new insights into hyperon rare decays, magnetic moments, and interactions. These experiments provide us with insights into the strong, weak, and electromagnetic structure of the baryons. 65 refs., 45 figs., 5 tabs

  8. 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.

  9. 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.

  10. Leptin as immune mediator: Interaction between neuroendocrine and immune system.

    Science.gov (United States)

    Procaccini, Claudio; La Rocca, Claudia; Carbone, Fortunata; De Rosa, Veronica; Galgani, Mario; Matarese, Giuseppe

    2017-01-01

    Leptin is an adipocyte-derived hormone/cytokine that links nutritional status with neuroendocrine and immune functions. Initially described as an anti-obesity hormone, leptin has subsequently been shown to exert pleiotropic effects, being also able to influence haematopoiesis, thermogenesis, reproduction, angiogenesis, and more importantly immune homeostasis. As a cytokine, leptin can affect both innate and adaptive immunity, by inducing a pro-inflammatory response and thus playing a key role in the regulation of the pathogenesis of several autoimmune/inflammatory diseases. In this review, we discuss the most recent advances on the role of leptin as immune-modulator in mammals and we also provide an overview on its main functions in non-mammalian vertebrates. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. immune response can measuring immunity to hiv during ...

    African Journals Online (AJOL)

    2005-11-01

    Nov 1, 2005 ... inhibitors (PIs), have resulted in significant suppression of viral replication. ... thymus, with the potential for immune reconstitution when ..... HIV-exposed but uninfected Gambian women [published erratum appears in. Nat Med ...

  12. Curating the innate immunity interactome.

    LENUS (Irish Health Repository)

    Lynn, David J

    2010-01-01

    The innate immune response is the first line of defence against invading pathogens and is regulated by complex signalling and transcriptional networks. Systems biology approaches promise to shed new light on the regulation of innate immunity through the analysis and modelling of these networks. A key initial step in this process is the contextual cataloguing of the components of this system and the molecular interactions that comprise these networks. InnateDB (http:\\/\\/www.innatedb.com) is a molecular interaction and pathway database developed to facilitate systems-level analyses of innate immunity.

  13. Spirochetal Lipoproteins and Immune Evasion

    Science.gov (United States)

    Christodoulides, Alexei; Boyadjian, Ani; Kelesidis, Theodoros

    2017-01-01

    Spirochetes are a major threat to public health. However, the exact pathogenesis of spirochetal diseases remains unclear. Spirochetes express lipoproteins that often determine the cross talk between the host and spirochetes. Lipoproteins are pro-inflammatory, modulatory of immune responses, and enable the spirochetes to evade the immune system. In this article, we review the modulatory effects of spirochetal lipoproteins related to immune evasion. Understanding lipoprotein-induced immunomodulation will aid in elucidating innate pathogenesis processes and subsequent adaptive mechanisms potentially relevant to spirochetal disease vaccine development and treatment. PMID:28424696

  14. The Entomopathogenic Fungi Isaria fumosorosea Plays a Vital Role in Suppressing the Immune System of Plutella xylostella: RNA-Seq and DGE Analysis of Immunity-Related Genes.

    Science.gov (United States)

    Xu, Jin; Xu, Xiaoxia; Shakeel, Muhammad; Li, Shuzhong; Wang, Shuang; Zhou, Xianqiang; Yu, Jialin; Xu, Xiaojing; Yu, Xiaoqiang; Jin, Fengliang

    2017-01-01

    Most, if not all, entomopathogenic fungi have been used as alternative control agents to decrease the insect resistance and harmful effects of the insecticides on the environment. Among them, Isaria fumosorosea has also shown great potential to control different insect pests. In the present study, we explored the immune response of P. xylostella to the infection of I. fumosorosea at different time points by using RNA-Sequencing and differential gene expression technology at the genomic level. To gain insight into the host-pathogen interaction at the genomic level, five libraries of P. xylostella larvae at 12, 18, 24, and 36 h post-infection and a control were constructed. In total, 161 immunity-related genes were identified and grouped into four categories; immune recognition families, toll and Imd pathway, melanization, and antimicrobial peptides (AMPs). The results of differentially expressed immunity-related genes depicted that 15, 13, 53, and 14 up-regulated and 38, 51, 56, and 49 were down-regulated in P. xylostella at 12, 18, 24, and 36 h post-treatment, respectively. RNA-Seq results of immunity-related genes revealed that the expression of AMPs was reduced after treatment with I. fumosorosea . To validate RNA-Seq results by RT-qPCR, 22 immunity-related genes were randomly selected. In conclusion, our results demonstrate that I. fumosorosea has the potential to suppress the immune response of P. xylostella and can become a potential biopesticide for controlling P. xylostella .

  15. The Entomopathogenic Fungi Isaria fumosorosea Plays a Vital Role in Suppressing the Immune System of Plutella xylostella: RNA-Seq and DGE Analysis of Immunity-Related Genes

    Directory of Open Access Journals (Sweden)

    Jin Xu

    2017-07-01

    Full Text Available Most, if not all, entomopathogenic fungi have been used as alternative control agents to decrease the insect resistance and harmful effects of the insecticides on the environment. Among them, Isaria fumosorosea has also shown great potential to control different insect pests. In the present study, we explored the immune response of P. xylostella to the infection of I. fumosorosea at different time points by using RNA-Sequencing and differential gene expression technology at the genomic level. To gain insight into the host-pathogen interaction at the genomic level, five libraries of P. xylostella larvae at 12, 18, 24, and 36 h post-infection and a control were constructed. In total, 161 immunity-related genes were identified and grouped into four categories; immune recognition families, toll and Imd pathway, melanization, and antimicrobial peptides (AMPs. The results of differentially expressed immunity-related genes depicted that 15, 13, 53, and 14 up-regulated and 38, 51, 56, and 49 were down-regulated in P. xylostella at 12, 18, 24, and 36 h post-treatment, respectively. RNA-Seq results of immunity-related genes revealed that the expression of AMPs was reduced after treatment with I. fumosorosea. To validate RNA-Seq results by RT-qPCR, 22 immunity-related genes were randomly selected. In conclusion, our results demonstrate that I. fumosorosea has the potential to suppress the immune response of P. xylostella and can become a potential biopesticide for controlling P. xylostella.

  16. Immunizations challenge healthcare personnel and affects immunization rates.

    Science.gov (United States)

    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. Human embryo immune escape mechanisms rediscovered by the tumor.

    Science.gov (United States)

    Ridolfi, Laura; Petrini, Massimiliano; Fiammenghi, Laura; Riccobon, Angela; Ridolfi, Ruggero

    2009-01-01

    Towards the end of the 1990s, the two opposing theories on immunosurveillance and immunostimulation were extensively studied by researchers in an attempt to understand the complex mechanisms that regulate the relation between tumors and the host's immune system. Both theories probably have elements that would help us to comprehend how the host can induce anti-tumor clinical responses through stimulation of the immune system and which could also give us a deeper insight into the mechanisms of tumor immunosuppression. The model that most resembles the behavior of tumor cells in terms of growth, infiltration and suppression of the immune system of the environment in which they live is undoubtedly that of the embryonic cell. The fetus behaves like an allogenic transplant within the mother's body, using every means it has to escape from and defend itself against the mother's immune system. The majority of these mechanisms are the same as those found in tumor cells: antigenic loss, lack of expression of classic HLA-I molecules, production of immunosuppressive cytokines, induction of lack of expression of co-stimulatory molecules in antigen presenting cells, and induction of apoptosis in infiltrating lymphocytes, with activation of a type Th2 regulatory lymphocyte response. A careful and comparative study of key mechanisms capable of triggering tolerance or cytotoxicity in both embryonic and tumor cells could prove immensely valuable in designing new strategies for anti-tumor immunotherapy.

  18. Immunity to intestinal pathogens: lessons learned from Salmonella

    Science.gov (United States)

    McSorley, Stephen J.

    2014-01-01

    Summary Salmonella are a common source of food or water-borne infection and cause a wide range of clinical disease in human and animal hosts. Salmonella are relatively easy to culture and manipulate in a laboratory setting, and the infection of laboratory animals induces robust innate and adaptive immune responses. Thus, immunologists have frequently turned to Salmonella infection models to expand understanding of immunity to intestinal pathogens. In this review, I summarize current knowledge of innate and adaptive immunity to Salmonella and highlight features of this response that have emerged from recent studies. These include the heterogeneity of the antigen-specific T-cell response to intestinal infection, the prominence of microbial mechanisms to impede T and B-cell responses, and the contribution of non-cognate pathways for elicitation of T-cell effector functions. Together, these different issues challenge an overly simplistic view of host-pathogen interaction during mucosal infection but also allow deeper insight into the real-world dynamic of protective immunity to intestinal pathogens. PMID:24942689

  19. Aggravating Impact of Nanoparticles on Immune-Mediated Pulmonary Inflammation

    Directory of Open Access Journals (Sweden)

    Ken-Ichiro Inoue

    2011-01-01

    Full Text Available Although the adverse health effects of nanoparticles have been proposed and are being clarified, their aggravating effects on pre-existing pathological conditions have not been fully investigated. In this review, we provide insights into the immunotoxicity of both airborne and engineered nanoparticles as an exacerbating factor on hypersusceptible subjects, especially those with immune-mediated pulmonary inflammation, using our in vivo experimental model. First, we exhibit the effects of nanoparticles on pulmonary inflammation induced by bacterial endotoxin (lipopolysaccharide: LPS as a disease model in innate immunity, and demonstrate that nanoparticles instilled through both an intratracheal tube and an inhalation system can exacerbate the lung inflammation. Second, we introduce the effects of nanoparticles on allergic pulmonary inflammation as a disease model in adaptive immunity, and show that repetitive pulmonary exposure to nanoparticles has aggravating effects on allergic inflammation, including adjuvant effects on Th2-milieu. Third, we show that very small nanoparticle exposure exacerbates emphysematous pulmonary inflammation, which is concomitant with enhanced lung expression of proinflammatory molecules (including those that are innate immunity related. Taken together, nanoparticle exposure may synergistically facilitate pathological pulmonary inflammation via both innate and adaptive immunological impairment.

  20. Controlling Cytomegalovirus: Helping the Immune System Take the Lead

    Directory of Open Access Journals (Sweden)

    Patrick J. Hanley

    2014-05-01

    Full Text Available Cytomegalovirus, of the Herpesviridae family, has evolved alongside humans for thousands of years with an intricate balance of latency, immune evasion, and transmission. While upwards of 70% of humans have evidence of CMV infection, the majority of healthy people show little to no clinical symptoms of primary infection and CMV disease is rarely observed during persistent infection in immunocompetent hosts. Despite the fact that the majority of infected individuals are asymptomatic, immunologically, CMV hijacks the immune system by infecting and remaining latent in antigen-presenting cells that occasionally reactivate subclinically and present antigen to T cells, eventually causing the inflation of CMV-specific T cells until they can compromise up to 10% of the entire T cell repertoire. Because of this impact on the immune system, as well as its importance in fields such as stem cell and organ transplant, the relationship between CMV and the immune response has been studied in depth. Here we provide a review of many of these studies and insights into how CMV-specific T cells are currently being used therapeutically.

  1. 2012 National Immunization Survey Data

    Science.gov (United States)

    ... Tweet Share Compartir This website is archived for historical purposes and is no longer being maintained or ... 12, 2013: Content on this page kept for historical reasons. National Immunization Survey (NIS) – Children (19-35 ...

  2. Pregnancy immunology: decidual immune cells.

    Science.gov (United States)

    Sanguansermsri, Donruedee; Pongcharoen, Sutatip

    2008-01-01

    Human pregnancy is a complex process. Placental development depends on the function of secretory molecules produced by placental trophoblast cells as well as by maternal uterine immune cells within the decidua. These decidual immune cells are T cells, natural killer cells, macrophages and dendritic cells. The interactions between the trophoblast cells and the maternal immune cells have an impact on the outcome of the pregnancy. Knowledge about the phenotypes and functions of the maternal immune cells in normal and pathological pregnancies including recurrent spontaneous abortions, preeclampsia and hydatidiform moles may improve our understanding of the immunobiology of the normal pregnancy as a whole and may provide approaches for improving the treatment of pathological pregnancies.

  3. Pauci-immune necrotizing glomerulonephritis

    NARCIS (Netherlands)

    Rutgers, Abraham; Sanders, Jan S F; Stegeman, Coen A; Kallenberg, Cees G M

    Pauci-immune necrotizing glomerulonephritis is the most frequent cause of rapidly progressive glomerulonephritis and, in most cases, is associated with antineutrophil cytoplasmic antibodies (ANCA). It is either the renal manifestation of Wegener's granulomatosis, microscopic polyangiitis of

  4. Arkansas community pharmacists' opinions on providing immunizations.

    Science.gov (United States)

    Pace, Anne C; Flowers, Schwanda K; Hastings, Jan K

    2010-10-01

    To determine community pharmacists' attitudes and knowledge on providing immunizations including perceived barriers to immunizing. The study also examined the percentage of Arkansas pharmacists providing immunizations and the utilization of student pharmacists. Survey. Arkansas community pharmacies from February to March 2009. Community pharmacists. Mailed survey. Perceived barriers to providing immunizations, pharmacists' attitudes regarding immunizations, number of immunization-certified pharmacists, immunization administration rates within the last year, and senior student pharmacists utilization. A total of 350 surveys were mailed, and 129 were returned. In all, 79% of the respondents believed administering immunizations has advanced or significantly advanced the profession. Being certified and attitude toward providing immunizations were correlated; 37% of the respondents held certification to immunize, of which 77% reported immunizing within the last year. Commonly reported barriers included time (76%) followed by reimbursement and legal liability. Only half the respondents realized fourth year student pharmacists could immunize and only 33% of certified pharmacists utilized student pharmacists to immunize. Pharmacists perceive many barriers to providing immunizations. Training student pharmacists to give immunizations may not result in them providing immunizations upon graduation. Additional education on overcoming potential barriers and using senior student pharmacists to administer immunizations is needed.

  5. Threshold for extinction and survival in stochastic tumor immune system

    Science.gov (United States)

    Li, Dongxi; Cheng, Fangjuan

    2017-10-01

    This paper mainly investigates the stochastic character of tumor growth and extinction in the presence of immune response of a host organism. Firstly, the mathematical model describing the interaction and competition between the tumor cells and immune system is established based on the Michaelis-Menten enzyme kinetics. Then, the threshold conditions for extinction, weak persistence and stochastic persistence of tumor cells are derived by the rigorous theoretical proofs. Finally, stochastic simulation are taken to substantiate and illustrate the conclusion we have derived. The modeling results will be beneficial to understand to concept of immunoediting, and develop the cancer immunotherapy. Besides, our simple theoretical model can help to obtain new insight into the complexity of tumor growth.

  6. Dual oxidase in mucosal immunity and host-microbe homeostasis.

    Science.gov (United States)

    Bae, Yun Soo; Choi, Myoung Kwon; Lee, Won-Jae

    2010-07-01

    Mucosal epithelia are in direct contact with microbes, which range from beneficial symbionts to pathogens. Accordingly, hosts must have a conflicting strategy to combat pathogens efficiently while tolerating symbionts. Recent progress has revealed that dual oxidase (DUOX) plays a key role in mucosal immunity in organisms that range from flies to humans. Information from the genetic model of Drosophila has advanced our understanding of the regulatory mechanism of DUOX and its role in mucosal immunity. Further investigations of DUOX regulation in response to symbiotic or non-symbiotic bacteria and the in vivo consequences in host physiology will give a novel insight into the microbe-controlling system of the mucosa. Copyright 2010 Elsevier Ltd. All rights reserved.

  7. Innate Immunity and Breast Milk.

    Science.gov (United States)

    Cacho, Nicole Theresa; Lawrence, Robert M

    2017-01-01

    Human milk is a dynamic source of nutrients and bioactive factors; unique in providing for the human infant's optimal growth and development. The growing infant's immune system has a number of developmental immune deficiencies placing the infant at increased risk of infection. This review focuses on how human milk directly contributes to the infant's innate immunity. Remarkable new findings clarify the multifunctional nature of human milk bioactive components. New research techniques have expanded our understanding of the potential for human milk's effect on the infant that will never be possible with milk formulas. Human milk microbiome directly shapes the infant's intestinal microbiome, while the human milk oligosaccharides drive the growth of these microbes within the gut. New techniques such as genomics, metabolomics, proteomics, and glycomics are being used to describe this symbiotic relationship. An expanded role for antimicrobial proteins/peptides within human milk in innate immune protection is described. The unique milieu of enhanced immune protection with diminished inflammation results from a complex interaction of anti-inflammatory and antioxidative factors provided by human milk to the intestine. New data support the concept of mucosal-associated lymphoid tissue and its contribution to the cellular content of human milk. Human milk stem cells (hMSCs) have recently been discovered. Their direct role in the infant for repair and regeneration is being investigated. The existence of these hMSCs could prove to be an easily harvested source of multilineage stem cells for the study of cancer and tissue regeneration. As the infant's gastrointestinal tract and immune system develop, there is a comparable transition in human milk over time to provide fewer immune factors and more calories and nutrients for growth. Each of these new findings opens the door to future studies of human milk and its effect on the innate immune system and the developing infant.

  8. Innate Immunity and Breast Milk

    Directory of Open Access Journals (Sweden)

    Nicole Theresa Cacho

    2017-05-01

    Full Text Available Human milk is a dynamic source of nutrients and bioactive factors; unique in providing for the human infant’s optimal growth and development. The growing infant’s immune system has a number of developmental immune deficiencies placing the infant at increased risk of infection. This review focuses on how human milk directly contributes to the infant’s innate immunity. Remarkable new findings clarify the multifunctional nature of human milk bioactive components. New research techniques have expanded our understanding of the potential for human milk’s effect on the infant that will never be possible with milk formulas. Human milk microbiome directly shapes the infant’s intestinal microbiome, while the human milk oligosaccharides drive the growth of these microbes within the gut. New techniques such as genomics, metabolomics, proteomics, and glycomics are being used to describe this symbiotic relationship. An expanded role for antimicrobial proteins/peptides within human milk in innate immune protection is described. The unique milieu of enhanced immune protection with diminished inflammation results from a complex interaction of anti-inflammatory and antioxidative factors provided by human milk to the intestine. New data support the concept of mucosal-associated lymphoid tissue and its contribution to the cellular content of human milk. Human milk stem cells (hMSCs have recently been discovered. Their direct role in the infant for repair and regeneration is being investigated. The existence of these hMSCs could prove to be an easily harvested source of multilineage stem cells for the study of cancer and tissue regeneration. As the infant’s gastrointestinal tract and immune system develop, there is a comparable transition in human milk over time to provide fewer immune factors and more calories and nutrients for growth. Each of these new findings opens the door to future studies of human milk and its effect on the innate immune system

  9. Gut immunity in Lepidopteran insects.

    Science.gov (United States)

    Wu, Kai; Yang, Bing; Huang, Wuren; Dobens, Leonard; Song, Hongsheng; Ling, Erjun

    2016-11-01

    Lepidopteran insects constitute one of the largest fractions of animals on earth, but are considered pests in their relationship with man. Key to the success of this order of insects is its ability to digest food and absorb nutrition, which takes place in the midgut. Because environmental microorganisms can easily enter Lepidopteran guts during feeding, the innate immune response guards against pathogenic bacteria, virus and microsporidia that can be devoured with food. Gut immune responses are complicated by both resident gut microbiota and the surrounding peritrophic membrane and are distinct from immune responses in the body cavity, which depend on the function of the fat body and hemocytes. Due to their relevance to agricultural production, studies of Lepidopteran insect midgut and immunity are receiving more attention, and here we summarize gut structures and functions, and discuss how these confer immunity against different microorganisms. It is expected that increased knowledge of Lepidopteran gut immunity may be utilized for pest biological control in the future. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Universal immunity to influenza must outwit immune evasion

    Directory of Open Access Journals (Sweden)

    Sergio Manuel Quinones-Parra

    2014-06-01

    Full Text Available Although an influenza vaccine has been available for 70 years, influenza virus still causes seasonal epidemics and worldwide pandemics. Currently available vaccines elicit strain-specific antibody responses to the surface haemagglutinin (HA and neuraminidase (NA proteins, but these can be ineffective against serologically-distinct viral variants and novel subtypes. Thus, there is a need for cross-protective or universal influenza vaccines to overcome the necessity for annual immunisation against seasonal influenza and to provide immunity to reduce the severity of infection with pandemic or outbreak viruses. It is well established that natural influenza infection can provide cross-reactive immunity that can reduce the impact of infection with distinct influenza type A strains and subtypes, including H1N1, H3N2, H2N2, H5N1 and H7N9. The key to generating universal influenza immunity via vaccination is to target functionally-conserved regions of the virus, which include epitopes on the internal proteins for cross-reactive T cell immunity or on the HA stem for broadly reactive antibody responses. In the wake of the 2009 H1N1 pandemic, broadly neutralizing antibodies have been characterized and isolated from convalescent and vaccinated individuals, inspiring development of new vaccination techniques to elicit such responses. Induction of influenza-specific T cell responses through vaccination has also been examined in clinical trials. Strong evidence is available from human and animal models of influenza to show that established influenza-specific T cell memory can reduce viral shedding and symptom severity. However, the published evidence also shows that CD8+ T cells can efficiently select immune escape mutants early after influenza virus infection. Here, we discuss universal immunity to influenza viruses mediated by both cross-reactive T cells and antibodies, the mechanisms of immune evasion in influenza, and how to counteract commonly occurring

  11. Immunization coverage among Hispanic ancestry, 2003 National Immunization Survey.

    Science.gov (United States)

    Darling, Natalie J; Barker, Lawrence E; Shefer, Abigail M; Chu, Susan Y

    2005-12-01

    The Hispanic population is increasing and heterogeneous (Hispanic refers to persons of Spanish, Hispanic, or Latino descent). The objective was to examine immunization rates among Hispanic ancestry for the 4:3:1:3:3 series (> or = 4 doses diphtheria, tetanus toxoids, and pertussis vaccine; > or = 3 doses poliovirus vaccine; > or = 1 doses measles-containing vaccine; > or = 3 doses Haemophilus influenzae type b vaccine; and > or = 3 doses hepatitis B vaccine). The National Immunization Survey measures immunization coverage among 19- to 35-month-old U.S. children. Coverage was compared from combined 2001-2003 data among Hispanics and non-Hispanic whites using t-tests, and among Hispanic ancestry using a chi-square test. Hispanics were categorized as Mexican, Mexican American, Central American, South American, Puerto Rican, Cuban, Spanish Caribbean (primarily Dominican Republic), other, and multiple ancestry. Children of Hispanic ancestry increased from 21% in 1999 to 25% in 2003. These Hispanic children were less well immunized than non-Hispanic whites (77.0%, +/-2.1% [95% confidence interval] compared to 82.5%, +/-1.1% (95% CI) > in 2003). Immunization coverage did not vary significantly among Hispanics of varying ancestries (p=0.26); however, there was substantial geographic variability. In some areas, immunization coverage among Hispanics was significantly higher than non-Hispanic whites. Hispanic children were less well immunized than non-Hispanic whites; however, coverage varied notably by geographic area. Although a chi-square test found no significant differences in coverage among Hispanic ancestries, the range of coverage, 79.2%, +/-5.1% for Cuban Americans to 72.1%, +/-2.4% for Mexican descent, may suggest a need for improved and more localized monitoring among Hispanic communities.

  12. Parental insightfulness: retrospect and prospect.

    Science.gov (United States)

    Koren-Karie, Nina; Oppenheim, David

    2018-06-01

    We open this introductory paper to the special issue with the theoretical and clinical roots of the insightfulness concept. Next, the Insightfulness Assessment (IA) is presented, followed by a review of key empirical findings supporting the IA. The central points in the papers in this special issue are reviewed next. These include the use of the IA with parents of children ranging in age from infancy to adolescence, its applicability outside the parent-child relationship (e.g. insightfulness toward a close friend), its use with high-risk mothers, and the usefulness of insightfulness both as a continuous and a categorical measure. The clinical applications of the IA are discussed, and we close with future directions for IA research.

  13. Franchise Business Model: Theoretical Insights

    OpenAIRE

    Levickaitė, Rasa; Reimeris, Ramojus

    2010-01-01

    The article is based on literature review, theoretical insights, and deals with the topic of franchise business model. The objective of the paper is to analyse peculiarities of franchise business model and its developing conditions in Lithuania. The aim of the paper is to make an overview on franchise business model and its environment in Lithuanian business context. The overview is based on international and local theoretical insights. In terms of practical meaning, this article should be re...

  14. The Future Prospects of Immune Therapy in Gastric and Esophageal Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Walid L. Shaib

    2016-11-01

    Full Text Available The prognosis of esophageal cancers is poor and novel approaches are urgently needed. Despite improvements in outcomes with transtuzumab and ramucirumab, these improvements added an average of only 2 to 3 months with a median overall survival reported to be around 1 year. Comprehensive genomic sequencing has defined some molecular alterations with potential targets, but the majority of patients still do not benefit from druggable targets. Breakthroughs in immune checkpoint blockade have provided new therapeutic options in many cancers. Programmed death ligand 1 (PDL1 overexpression, a possible biomarker predicting response to immune checkpoint inhibitors, approaches forty percent in esophageal and gastric cancers. Translational and molecular studies have shown that esophageal cancers are possible candidate malignancies for immune checkpoint inhibition. In this review, we plan to highlight the mechanisms, preclinical, and early clinical data that provide insight on the role of immune therapeutics in esophageal cancers.

  15. Silencing the alarms: innate immune antagonism by rotavirus NSP1 and VP3

    Science.gov (United States)

    Morelli, Marco; Ogden, Kristen M.; Patton, John T.

    2016-01-01

    The innate immune response involves a broad array of pathogen sensors that stimulate the production of interferons (IFN) to induce an antiviral state. Rotavirus, a significant cause of childhood gastroenteritis and a member of the Reoviridae family of segmented, double-stranded RNA viruses, encodes at least two direct antagonists of host innate immunity: NSP1 and VP3. NSP1, a putative E3 ubiquitin ligase, mediates the degradation of cellular factors involved in both IFN induction and downstream signaling. VP3, the viral capping enzyme, utilizes a 2H-phosphodiesterase domain to prevent activation of the cellular oligoadenylate synthase (OAS)-RNase L pathway. Computational, molecular, and biochemical studies have provided key insights into the structural and mechanistic basis of innate immune antagonism by NSP1 and VP3 of group A rotaviruses (RVA). Future studies with non-RVA isolates will be essential to understand how other RV species evade host innate immune responses. PMID:25724417

  16. Immune defense of wild-caught Norway rats is characterized by increased levels of basal activity but reduced capability to respond to further immune stimulation.

    Science.gov (United States)

    Mirkov, Ivana; Popov Aleksandrov, Aleksandra; Subota, Vesna; Kataranovski, Dragan; Kataranovski, Milena

    2018-03-01

    Studies of wild animals' immunity often use comparison with laboratory-raised individuals. Using such an approach, various data were obtained concerning wild Norway rat's immunity. Lower or higher potential of immune system cells to respond to activation stimuli were shown, because of analysis of disparate parameters and/ or small number of analyzed individuals. Inconsistent differences between laboratory and wild rats were shown too, owing to great response variability in wild rats. We hypothesized that wild rats will express more intense immune activity compared to their laboratory counterparts which live in a less demanding environment. To test this, we analyzed the circulating levels of inflammatory cytokine interleukin-6 (IL-6), a mediator which has a central role in host immune defense. In addition, we examined the activity of the central immune organ, the spleen, including cell proliferation and production of pro-inflammatory cytokines interferon-γ (IFN-γ) and interleukin-17 (IL-17), which are major effectors of cellular adaptive immune response. In order to obtain reasonable insight into the immunity of wild Norway rats, analysis was conducted on a much larger number of individuals compared to other studies. Higher levels of plasma IL-6, higher spleen mass, cellularity and basal IFN-γ production concomitantly with lower basal production of anti-inflammatory cytokine interleukin-10 (IL-10) revealed more intense immune activity in the wild compared to laboratory rats. However, lower responsiveness of their spleen cells' proinflammatory cytokine production to concanavalin A (ConA) stimulation, along with preserved capacity of IL-10 response, might be perceived as an indication of wild rats' reduced capability to cope with incoming environmental stimuli, but also as a means to limit tissue damage. © 2017 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

  17. 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

  18. Artificial Immune Networks: Models and Applications

    Directory of Open Access Journals (Sweden)

    Xian Shen

    2008-06-01

    Full Text Available Artificial Immune Systems (AIS, which is inspired by the nature immune system, has been applied for solving complex computational problems in classification, pattern rec- ognition, and optimization. In this paper, the theory of the natural immune system is first briefly introduced. Next, we compare some well-known AIS and their applications. Several representative artificial immune networks models are also dis- cussed. Moreover, we demonstrate the applications of artificial immune networks in various engineering fields.

  19. SOME ISSUES OF DIAGNOSTICS IN IMMUNE PATHOLOGY

    Directory of Open Access Journals (Sweden)

    I. A. Tousankina

    2010-01-01

    Full Text Available Present lecture contains an author's opinion concerning diagnostic issues in immunopathology, including primary and secondary immune deficiencies, immune-dependent states that are based on immunopathological syndromes. Original formulations are suggested for some key categories of clinical immunology, physical, instrumental and laboratory diagnostics of immune deficiencies and immune-dependent diseases. The results of original long-term observations, as well as data on Sverdlovsk Regional Register of primary immune deficiencies are presented in the work.

  20. 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

  1. Immunization delivery in British Columbia

    Science.gov (United States)

    Omura, John; Buxton, Jane; Kaczorowski, Janusz; Catterson, Jason; Li, Jane; Derban, Andrea; Hasselback, Paul; Machin, Shelagh; Linekin, Michelle; Morgana, Tamsin; O’Briain, Barra; Scheifele, David; Dawar, Meena

    2014-01-01

    Abstract Objective To explore the experiences of family physicians and pediatricians delivering immunizations, including perceived barriers and supports. Design Qualitative study using focus groups. Setting Ten cities throughout British Columbia. Participants A total of 46 family physicians or general practitioners, 10 pediatricians, and 2 residents. Methods A semistructured dialogue guide was used by a trained facilitator to explore participants’ experiences and views related to immunization delivery in British Columbia. Verbatim transcriptions were independently coded by 2 researchers. Key themes were analyzed and identified in an iterative manner using interpretive description. Main findings Physicians highly valued vaccine delivery. Factors facilitating physician-delivered immunizations included strong beliefs in the value of vaccines and having adequate information. Identified barriers included the large time commitment and insufficient communication about program changes, new vaccines, and the adult immunization program in general. Some physicians reported good relationships with local public health, while others reported the opposite experience, and this varied by geographic location. Conclusion These findings suggest that physicians are supportive of delivering vaccines. However, there are opportunities to improve the sustainability of physician-delivered immunizations. While compensation schemes remain under the purview of the provincial governments, local public health authorities can address the information needs of physicians. PMID:24627403

  2. Age-dependent changes in innate immune phenotype and function in rhesus macaques (Macaca mulatta

    Directory of Open Access Journals (Sweden)

    Mark Asquith

    2012-06-01

    Full Text Available Aged individuals are more susceptible to infections due to a general decline in immune function broadly referred to as immune senescence. While age-related changes in the adaptive immune system are well documented, aging of the innate immune system remains less well understood, particularly in nonhuman primates. A more robust understanding of age-related changes in innate immune function would provide mechanistic insight into the increased susceptibility of the elderly to infection. Rhesus macaques have proved a critical translational model for aging research, and present a unique opportunity to dissect age-dependent modulation of the innate immune system. We examined age-related changes in: (i innate immune cell frequencies; (ii expression of pattern recognition receptors (PRRs and innate signaling molecules; (iii cytokine responses of monocytes and dendritic cells (DC following stimulation with PRR agonists; and (iv plasma cytokine levels in this model. We found marked changes in both the phenotype and function of innate immune cells. This included an age-associated increased frequency of myeloid DC (mDC. Moreover, we found toll-like receptor (TLR agonists lipopolysaccharide (TLR4, fibroblast stimulating ligand-1 (TLR2/6, and ODN2006 (TLR7/9 induced reduced cytokine responses in aged mDC. Interestingly, with the exception of the monocyte-derived TNFα response to LPS, which increased with age, TNFα, IL-6, and IFNα responses declined with age. We also found that TLR4, TLR5, and innate negative regulator, sterile alpha and TIR motif containing protein (SARM, were all expressed at lower levels in young animals. By contrast, absent in melanoma 2 and retinoic acid-inducible gene I expression was lowest in aged animals. Together, these observations indicate that several parameters of innate immunity are significantly modulated by age and contribute to differential immune function in aged macaques.

  3. Babies Galore; or recent findings and future perspectives of pregnancy cohorts with a focus on immunity.

    Science.gov (United States)

    Hartwig, Isabel; Diemert, Anke; Tolosa, Eva; Hecher, Kurt; Arck, Petra

    2015-04-01

    Population-based pregnancy cohorts recruiting women before or at the moment of childbirth allow a longitudinal follow-up on children's health later in life. Important findings arising from pregnancy cohorts are discussed in the present review. These insights have led to revised guidelines on how to minimize disease risks in children, e.g., in the context of chronic immune diseases including allergies and asthma. Moreover, insights from pregnancy cohorts also unveiled a collateral effect of pregnancy on maternal immunity, mirrored by an ameliorated course of certain autoimmune diseases, but also an increased risk of infection with influenza A virus. Future pregnancy cohort studies are still required to close gaps in knowledge on how parameters involved in the developmental origin of health or poor immunity observed in children later in life are operational. We discuss here features that should be covered by future pregnancy cohort studies. Expected insights from such studies will then lay the foundation for biomarker discovery and offer opportunities for interventions to ameliorate adverse immune responses in humans. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Therapeutics targeting tumor immune escape: towards the development of new generation anticancer vaccines.

    Science.gov (United States)

    Mocellin, Simone; Nitti, Donato

    2008-05-01

    Despite the evidence that immune effectors can play a significant role in controlling tumor growth under natural conditions or in response to therapeutic manipulation, it is clear that malignant cells evade immune surveillance in most cases. Considering that anticancer vaccination has reached a plateau of results and currently no vaccination regimen is indicated as a standard anticancer therapy, the dissection of the molecular events underlying tumor immune escape is the necessary condition to make anticancer vaccines a therapeutic weapon effective enough to be implemented in the routine clinical setting. Recent years have witnessed significant advances in our understanding of the molecular mechanisms underlying tumor immune escape. These mechanistic insights are fostering the development of rationally designed therapeutics aimed at reverting the immunosuppressive circuits that undermine an effective antitumor immune response. In this review, the best characterized mechanisms that allow cancer cells to evade immune surveillance are overviewed and the most debated controversies constellating this complex field are highlighted. In addition, the latest therapeutic strategies devised to overcome tumor immune escape are described, with special regard to those entering clinical phase investigation. Copyright (c) 2007 Wiley-Periodicals, Inc.

  5. Dscam1 in Pancrustacean Immunity: Current Status and a Look to the Future

    Directory of Open Access Journals (Sweden)

    Sophie A. O. Armitage

    2017-06-01

    Full Text Available The Down syndrome cell adhesion molecule 1 (Dscam1 gene is an extraordinary example of diversity: by combining alternatively spliced exons, thousands of isoforms can be produced from just one gene. So far, such diversity in this gene has only been found in insects and crustaceans, and its essential part in neural wiring has been well-characterized for Drosophila melanogaster. Ten years ago evidence from D. melanogaster showed that the Dscam1 gene is involved in insect immune defense and work on Anopheles gambiae indicated that it is a hypervariable immune receptor. These exciting findings showed that via processes of somatic diversification insects have the possibility to produce unexpected immune molecule diversity, and it was hypothesized that Dscam1 could provide the mechanistic underpinnings of specific immune responses. Since these first publications the quest to understand the function of this gene has uncovered fascinating insights from insects and crustaceans. However, we are still far from a complete understanding of how Dscam1 functions in relation to parasites and pathogens and its full relevance for the immune system. In this Hypothesis and Theory article, we first briefly introduce Dscam1 and what we know so far about how it might function in immunity. By focusing on seven questions, we then share our sometimes contrasting thoughts on what the evidence tells us so far, what essential experiments remain to be done, and the future prospects, with the aim to provide a multiangled view on what this fascinating gene has to do with immune defense.

  6. The role of CD103+ Dendritic cells in the intestinal mucosal immune system.

    Directory of Open Access Journals (Sweden)

    Darren Thomas Ruane

    2011-07-01

    Full Text Available While dendritic cells (DC are central to the induction and regulation of adaptive immunity, these cells are very heterogenous and specific subsets can be characterized based on the expression of cell surface markers and functional properties. Intestinal CD103+ DCs are the subject of particular interest due to their role in regulating mucosal immunity. Since the epithelial surfaces are constantly exposed to a high antigenic load, tight regulation of innate and adaptive intestinal immune responses is vital as intestinal inflammation can have detrimental consequences for the host. Strategically positioned within the lamina propria, CD103+ DCs play an important role in maintaining intestinal immune homeostasis. These cells are required for the induction of tolerogenic immune responses and imprinting gut homing phenotypic changes on antigen-specific T cells. Recent insights into their development and regulatory properties have revealed additional immunoregulatory roles and further highlighted their importance for intestinal immunity. In this review we discuss the nature of the intestinal CD103+ DC population and the emerging roles of these cells in the regulation of mucosal immunity.

  7. Cancer-Targeted Oncolytic Adenoviruses for Modulation of the Immune System.

    Science.gov (United States)

    Cerullo, Vincenzo; Capasso, Cristian; Vaha-Koskela, Markus; Hemminki, Otto; Hemminki, Akseli

    2018-01-01

    Adenovirus is one of the most commonly used vectors for gene therapy and it is the first approved virus-derived drug for treatment of cancer. As an oncolytic agent, it can induce lysis of infected cells, but it can also engage the immune system, promoting activation and maturation of antigen- presenting cells (APCs). In essence, oncolysis combined with the associated immunostimulatory actions result in a "personalized in situ vaccine" for each patient. In order to take full advantage of these features, we should try to understand how adenovirus interacts with the immune system, what are the receptors involved in triggering subsequent signals and which kind of responses they elicit. Tackling these questions will give us further insight in how to manipulate adenovirus-mediated immune responses for enhancement of anti-tumor efficacy. In this review, we first highlight how oncolytic adenovirus interacts with the innate immune system and its receptors such as Toll-like receptors, nucleotide-binding and oligomerization domain (NOD)- like receptors and other immune sensors. Then we describe the effect of these interactions on the adaptive immune system and its cells, especially B and T lymphocytes. Finally, we summarize the most significant preclinical and clinical results in the field of gene therapy where researchers have engineered adenovirus to manipulate the host immune system by expressing cytokines and signalingmediators. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Immune function in arctic mammals

    DEFF Research Database (Denmark)

    Desforges, Jean-Pierre; Jasperse, Lindsay; Jensen, Trine Hammer

    2018-01-01

    Natural killer (NK) cells are a vital part of the rapid and non-specific immune defense against invading pathogens and tumor cells. This study evaluated NK cell-like activity by flow cytometry for the first time in three ecologically and culturally important Arctic mammal species: polar bear (Ursus...... the effector:target cell ratio increased. Comparing NK activity between fresh and cryopreserved mouse lymphocytes revealed little to no difference in function, highlighting the applicability of cryopreserving cells in field studies. The evaluation of this important innate immune function in Arctic mammals can...... contribute to future population health assessments, especially as pollution-induced suppression of immune function may increase infectious disease susceptibility....

  9. Immune response to H pylori

    Science.gov (United States)

    Suarez, Giovanni; Reyes, Victor E; Beswick, Ellen J

    2006-01-01

    The gastric mucosa separates the underlying tissue from the vast array of antigens that traffic through the stomach lumen. While the extreme pH of this environment is essential in aiding the activation of enzymes and food digestion, it also renders the gastric epithelium free from bacterial colonization, with the exception of one important human pathogen, H pylori. This bacterium has developed mechanisms to survive the harsh environment of the stomach, actively move through the mucosal layer, attach to the epithelium, evade immune responses, and achieve persistent colonization. While a hallmark of this infection is a marked inflammatory response with the infiltration of various immune cells into the infected gastric mucosa, the host immune response is unable to clear the infection and may actually contribute to the associated pathogenesis. Here, we review the host responses involved during infection with H pylori and how they are influenced by this bacterium. PMID:17007009

  10. Innate Immune Responses in Leprosy

    Science.gov (United States)

    Pinheiro, Roberta Olmo; Schmitz, Veronica; Silva, Bruno Jorge de Andrade; Dias, André Alves; de Souza, Beatriz Junqueira; de Mattos Barbosa, Mayara Garcia; de Almeida Esquenazi, Danuza; Pessolani, Maria Cristina Vidal; Sarno, Euzenir Nunes

    2018-01-01

    Leprosy is an infectious disease that may present different clinical forms depending on host immune response to Mycobacterium leprae. Several studies have clarified the role of various T cell populations in leprosy; however, recent evidences suggest that local innate immune mechanisms are key determinants in driving the disease to its different clinical manifestations. Leprosy is an ideal model to study the immunoregulatory role of innate immune molecules and its interaction with nervous system, which can affect homeostasis and contribute to the development of inflammatory episodes during the course of the disease. Macrophages, dendritic cells, neutrophils, and keratinocytes are the major cell populations studied and the comprehension of the complex networking created by cytokine release, lipid and iron metabolism, as well as antimicrobial effector pathways might provide data that will help in the development of new strategies for leprosy management. PMID:29643852

  11. Immune tolerance in radiation chimeras

    International Nuclear Information System (INIS)

    Awaya, Kazuhiko; Kuniki, Hiromichi; Neki, Miyuki

    1978-01-01

    Establishment of immune tolerance in radiation chimeras and the mechanism of maintaining it were discussed from certain points. Semiallogeneic radiation chimeras are mostly of long-living, and the hematopoietic organ of this individual consists mainly of the cells derived from the marrow donor, i. e., F 1 -type cells. F 1 -type lymphocytes can distinguish parental strain cells from themselves. In these chimeras, a F 1 -skin graft maintains to be fresh as long as the host is alive, showing immune tolerance effective through its life. In establishment and maintenance of this immune tolerance, the suppressing mechanism of host-type or F 1 -type seems to be involved. The allogeneic radiation chimera has very poor long-survival rate compared with that of the semiallogeneic radiation chimera. To raise this survival rate, efforts are now being made from the immunological point of view. (Ueda, J.)

  12. Chromatin Remodeling and Plant Immunity.

    Science.gov (United States)

    Chen, W; Zhu, Q; Liu, Y; Zhang, Q

    Chromatin remodeling, an important facet of the regulation of gene expression in eukaryotes, is performed by two major types of multisubunit complexes, covalent histone- or DNA-modifying complexes, and ATP-dependent chromosome remodeling complexes. Snf2 family DNA-dependent ATPases constitute the catalytic subunits of ATP-dependent chromosome remodeling complexes, which accounts for energy supply during chromatin remodeling. Increasing evidence indicates a critical role of chromatin remodeling in the establishment of long-lasting, even transgenerational immune memory in plants, which is supported by the findings that DNA methylation, histone deacetylation, and histone methylation can prime the promoters of immune-related genes required for disease defense. So what are the links between Snf2-mediated ATP-dependent chromosome remodeling and plant immunity, and what mechanisms might support its involvement in disease resistance? © 2017 Elsevier Inc. All rights reserved.

  13. Innate Immunity against Leishmania Infections

    Science.gov (United States)

    Gurung, Prajwal; Kanneganti, Thirumala-Devi

    2015-01-01

    Leishmaniasis is a major health problem that affects more than 300 million people throughout the world. The morbidity associated with the disease causes serious economic burden in Leishmania endemic regions. Despite the morbidity and economic burden associated with Leishmaniasis, this disease rarely gets noticed and is still categorized under neglected tropical diseases. The lack of research combined with the ability of Leishmania to evade immune recognition has rendered our efforts to design therapeutic treatments or vaccines challenging. Herein, we review the literature on Leishmania from innate immune perspective and discuss potential problems as well as solutions and future directions that could aid in identifying novel therapeutic targets to eliminate this parasite. PMID:26249747

  14. Immune epitope database analysis resource

    DEFF Research Database (Denmark)

    Kim, Yohan; Ponomarenko, Julia; Zhu, Zhanyang

    2012-01-01

    The immune epitope database analysis resource (IEDB-AR: http://tools.iedb.org) is a collection of tools for prediction and analysis of molecular targets of T- and B-cell immune responses (i.e. epitopes). Since its last publication in the NAR webserver issue in 2008, a new generation of peptide......, and the homology mapping tool was updated to enable mapping of discontinuous epitopes onto 3D structures. Furthermore, to serve a wider range of users, the number of ways in which IEDB-AR can be accessed has been expanded. Specifically, the predictive tools can be programmatically accessed using a web interface...

  15. Innate immunity in the pathogenesis of psoriasis.

    LENUS (Irish Health Repository)

    Sweeney, Cheryl M

    2011-12-01

    Psoriasis is a common, immune-mediated inflammatory skin disorder. T helper(h)1 and Th17 lymphocytes contribute to the pathogenesis of psoriasis through the release of inflammatory cytokines that promote further recruitment of immune cells, keratinocyte proliferation and sustained inflammation. The innate immune system is the first line of defence against infection and plays a crucial role in the initiation of the adaptive immune response. The presence of innate immune cells and their products in psoriatic skin plaques suggests a role for innate immunity in this disease. In addition, the innate immune system can direct the development of pathogenic Th cells in psoriasis. In this article, we will summarise the role of the innate immune system in psoriasis with particular emphasis on the role of cytokines, signalling pathways and cells of the innate immune system.

  16. Season of birth shapes neonatal immune function

    DEFF Research Database (Denmark)

    Thysen, Anna Hammerich; Rasmussen, Morten Arendt; Kreiner-Møller, Eskil

    2016-01-01

    Birth season has been reported to be a risk factor for several immune-mediated diseases. We hypothesized that this association is mediated by differential changes in neonatal immune phenotype and function with birth season. We sought to investigate the influence of season of birth on cord blood...... immune cell subsets and inflammatory mediators in neonatal airways. Cord blood was phenotyped for 26 different immune cell subsets, and at 1 month of age, 20 cytokines and chemokines were quantified in airway mucosal lining fluid. Multivariate partial least squares discriminant analyses were applied...... to determine whether certain immune profiles dominate by birth season, and correlations between individual cord blood immune cells and early airway immune mediators were defined. We found a birth season-related fluctuation in neonatal immune cell subsets and in early-life airway mucosal immune function...

  17. Immune regulation by pericytes: modulating innate and adaptive immunity

    DEFF Research Database (Denmark)

    Navarro, Rocio; Compte, Marta; Álvarez-Vallina, Luis

    2016-01-01

    Pericytes (PC) are mural cells that surround endothelial cells (EC) in small blood vessels. PC have traditionally been endowed with structural functions, being essential for vessel maturation and stabilization. However, accumulating evidence suggest that PC also display immune properties. They ca...

  18. Mathematical modeling provides kinetic details of the human immune response to vaccination

    Directory of Open Access Journals (Sweden)

    Dustin eLe

    2015-01-01

    Full Text Available With major advances in experimental techniques to track antigen-specific immune responses many basic questions on the kinetics of virus-specific immunity in humans remain unanswered. To gain insights into kinetics of T and B cell responses in human volunteers we combine mathematical models and experimental data from recent studies employing vaccines against yellow fever and smallpox. Yellow fever virus-specific CD8 T cell population expanded slowly with the average doubling time of 2 days peaking 2.5 weeks post immunization. Interestingly, we found that the peak of the yellow fever-specific CD8 T cell response is determined by the rate of T cell proliferation and not by the precursor frequency of antigen-specific cells as has been suggested in several studies in mice. We also found that while the frequency of virus-specific T cells increases slowly, the slow increase can still accurately explain clearance of yellow fever virus in the blood. Our additional mathematical model describes well the kinetics of virus-specific antibody-secreting cell and antibody response to vaccinia virus in vaccinated individuals suggesting that most of antibodies in 3 months post immunization are derived from the population of circulating antibody-secreting cells. Taken together, our analysis provides novel insights into mechanisms by which live vaccines induce immunity to viral infections and highlight challenges of applying methods of mathematical modeling to the current, state-of-the-art yet limited immunological data.

  19. Mathematical modeling provides kinetic details of the human immune response to vaccination.

    Science.gov (United States)

    Le, Dustin; Miller, Joseph D; Ganusov, Vitaly V

    2014-01-01

    With major advances in experimental techniques to track antigen-specific immune responses many basic questions on the kinetics of virus-specific immunity in humans remain unanswered. To gain insights into kinetics of T and B cell responses in human volunteers we combined mathematical models and experimental data from recent studies employing vaccines against yellow fever and smallpox. Yellow fever virus-specific CD8 T cell population expanded slowly with the average doubling time of 2 days peaking 2.5 weeks post immunization. Interestingly, we found that the peak of the yellow fever-specific CD8 T cell response was determined by the rate of T cell proliferation and not by the precursor frequency of antigen-specific cells as has been suggested in several studies in mice. We also found that while the frequency of virus-specific T cells increased slowly, the slow increase could still accurately explain clearance of yellow fever virus in the blood. Our additional mathematical model described well the kinetics of virus-specific antibody-secreting cell and antibody response to vaccinia virus in vaccinated individuals suggesting that most of antibodies in 3 months post immunization were derived from the population of circulating antibody-secreting cells. Taken together, our analysis provided novel insights into mechanisms by which live vaccines induce immunity to viral infections and highlighted challenges of applying methods of mathematical modeling to the current, state-of-the-art yet limited immunological data.

  20. The Concordance of Parent and Child Immunization.

    Science.gov (United States)

    Robison, Steve G; Osborn, Andrew W

    2017-05-01

    A substantial body of work has related survey-based parental vaccine hesitancy to noncompliant childhood immunization. However little attention has been paid to the connection between parents' own immunization behavior and the immunizations their children receive. Using the Oregon ALERT Immunization Information System, we identified adult caregiver-child pairs for children between 9 months and 17 years of age. The likelihood of adult-child concordance of influenza immunization per influenza season from 2010-2011 through 2014-2015 was assessed. The utility of adult immunization as a predictor was also assessed for other, noninfluenza recommended immunizations for children and adolescents. A total of 450 687 matched adult caregiver-child pairs were included in the study. The children of immunizing adults were 2.77 times more likely to also be immunized for seasonal influenza across all seasons (95% confidence interval, 2.74-2.79), with similar results applying within each season. Adult immunization status was also significantly associated with the likelihood of children and adolescents getting other noninfluenza immunizations, such as the human papillomavirus vaccine (HPV). When adults improved their own behavior from nonimmunizing to immunizing across influenza seasons, their children if not immunized in the previous season were 5.44 times (95% confidence interval, 5.35-5.53) more likely to become immunized for influenza. Children's likelihood of following immunization recommendations is associated with the immunization behavior of their parents. Encouraging parental immunization is a potential tool for increasing children's immunization rates. Copyright © 2017 by the American Academy of Pediatrics.

  1. Entomopathogenic Fungi: New Insights into Host-Pathogen Interactions.

    Science.gov (United States)

    Butt, T M; Coates, C J; Dubovskiy, I M; Ratcliffe, N A

    2016-01-01

    Although many insects successfully live in dangerous environments exposed to diverse communities of microbes, they are often exploited and killed by specialist pathogens. Studies of host-pathogen interactions (HPI) provide valuable insights into the dynamics of the highly aggressive coevolutionary arms race between entomopathogenic fungi (EPF) and their arthropod hosts. The host defenses are designed to exclude the pathogen or mitigate the damage inflicted while the pathogen responds with immune evasion and utilization of host resources. EPF neutralize their immediate surroundings on the insect integument and benefit from the physiochemical properties of the cuticle and its compounds that exclude competing microbes. EPF also exhibit adaptations aimed at minimizing trauma that can be deleterious to both host and pathogen (eg, melanization of hemolymph), form narrow penetration pegs that alleviate host dehydration and produce blastospores that lack immunogenic sugars/enzymes but facilitate rapid assimilation of hemolymph nutrients. In response, insects deploy an extensive armory of hemocytes and macromolecules, such as lectins and phenoloxidase, that repel, immobilize, and kill EPF. New evidence suggests that immune bioactives work synergistically (eg, lysozyme with antimicrobial peptides) to combat infections. Some proteins, including transferrin and apolipophorin III, also demonstrate multifunctional properties, participating in metabolism, homeostasis, and pathogen recognition. This review discusses the molecular intricacies of these HPI, highlighting the interplay between immunity, stress management, and metabolism. Increased knowledge in this area could enhance the efficacy of EPF, ensuring their future in integrated pest management programs. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. 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

  3. Understanding Insight in the Context of Q

    Science.gov (United States)

    Coghlan, David

    2012-01-01

    In Revans' learning formula, L = P + Q, Q represents "questioning insight", by which Revans means that insight comes out of the process of questioning programmed knowledge (P) in the light of experience. We typically focus on the content of an insight rather than on the act of insight. Drawing primarily on the work of Bernard Lonergan this paper…

  4. Approaching the Distinction between Intuition and Insight.

    Science.gov (United States)

    Zhang, Zhonglu; Lei, Yi; Li, Hong

    2016-01-01

    Intuition and insight share similar cognitive and neural basis. Though, there are still some essential differences between the two. Here in this short review, we discriminated between intuition, and insight in two aspects. First, intuition, and insight are toward different aspects of information processing. Whereas intuition involves judgment about "yes or no," insight is related to "what" is the solution. Second, tacit knowledge play different roles in between intuition and insight. On the one hand, tacit knowledge is conducive to intuitive judgment. On the other hand, tacit knowledge may first impede but later facilitate insight occurrence. Furthermore, we share theoretical, and methodological views on how to access the distinction between intuition and insight.

  5. Hormonal signaling in plant immunity

    NARCIS (Netherlands)

    Caarls, L.

    2016-01-01

    Insect hervivores and pathogens are a major problem in agriculture and therefore, control of these pests and diseases is essential. For this, understanding the plant immune response can be instrumental. The plant hormones salicylic acid (SA) and jasmonic acid (JA) play an essential role in defense

  6. 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...

  7. The Immune Landscape of Cancer

    NARCIS (Netherlands)

    Thorsson, Vésteinn; Gibbs, David L.; Brown, Scott D.; Wolf, Denise; Bortone, Dante S.; Ou Yang, Tai Hsien; Porta-Pardo, Eduard; Gao, Galen F.; Plaisier, Christopher L.; Eddy, James A.; Ziv, Elad; Culhane, Aedin C.; Paull, Evan O.; Sivakumar, I. K.Ashok; Gentles, Andrew J.; Malhotra, Raunaq; Farshidfar, Farshad; Colaprico, Antonio; Parker, Joel S.; Mose, Lisle E.; Vo, Nam Sy; Liu, Jianfang; Liu, Yuexin; Rader, Janet; Dhankani, Varsha; Reynolds, Sheila M.; Bowlby, Reanne; Califano, Andrea; Cherniack, Andrew D.; Anastassiou, Dimitris; Bedognetti, Davide; Rao, Arvind; Chen, Ken; Krasnitz, Alexander; Hu, Hai; Malta, Tathiane M.; Noushmehr, Houtan; Pedamallu, Chandra Sekhar; Bullman, Susan; Ojesina, Akinyemi I.; Lamb, Andrew; Zhou, Wanding; Shen, Hui; Choueiri, Toni K.; Weinstein, John N.; Guinney, Justin; Saltz, Joel; Holt, Robert; Rabkin, Charles E.; Caesar-Johnson, Samantha J.; Demchok, John A.; Felau, Ina; Kasapi, Melpomeni; Ferguson, Martin L.; Hutter, Carolyn M.; Sofia, Heidi J.; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C.; Zhang, Jiashan (Julia); Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Cho, Juok; DeFreitas, Timothy; Frazer, Scott; Gehlenborg, Nils; Getz, Gad; Heiman, David I.; Kim, Jaegil; Lawrence, Michael S.; Lin, Pei; Meier, Sam; Noble, Michael S.; Saksena, Gordon; Voet, Doug; Zhang, Hailei; Bernard, Brady; Chambwe, Nyasha; Dhankani, Varsha; Knijnenburg, Theo; Kramer, Roger; Leinonen, Kalle; Liu, Yuexin; Miller, Michael; Reynolds, Sheila; Shmulevich, Ilya; Thorsson, Vesteinn; Zhang, Wei; Akbani, Rehan; Broom, Bradley M.; Hegde, Apurva M.; Ju, Zhenlin; Kanchi, Rupa S.; Korkut, Anil; Li, Jun; Liang, Han; Ling, Shiyun; Liu, Wenbin; Lu, Yiling; Mills, Gordon B.; Ng, Kwok Shing; Rao, Arvind; Ryan, Michael; Wang, Jing; Weinstein, John N.; Zhang, Jiexin; Abeshouse, Adam; Armenia, Joshua; Chakravarty, Debyani; Chatila, Walid K.; de Bruijn, Ino; Gao, Jianjiong; Gross, Benjamin E.; Heins, Zachary J.; Kundra, Ritika; La, Konnor; Ladanyi, Marc; Luna, Augustin; Nissan, Moriah G.; Ochoa, Angelica; Phillips, Sarah M.; Reznik, Ed; Sanchez-Vega, Francisco; Sander, Chris; Schultz, Nikolaus; Sheridan, Robert; Sumer, S. Onur; Sun, Yichao; Taylor, Barry S.; Wang, Jioajiao; Zhang, Hongxin; Anur, Pavana; Peto, Myron; Spellman, Paul; Benz, Christopher; Stuart, Joshua M.; Wong, Christopher K.; Yau, Christina; Hayes, D. Neil; Parker, Joel S.; Wilkerson, Matthew D.; Ally, Adrian; Balasundaram, Miruna; Bowlby, Reanne; Brooks, Denise; Carlsen, Rebecca; Chuah, Eric; Dhalla, Noreen; Holt, Robert; Jones, Steven J.M.; Kasaian, Katayoon; Lee, Darlene; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Mungall, Karen; Robertson, A. Gordon; Sadeghi, Sara; Schein, Jacqueline E.; Sipahimalani, Payal; Tam, Angela; Thiessen, Nina; Tse, Kane; Wong, Tina; Berger, Ashton C.; Beroukhim, Rameen; Cherniack, Andrew D.; Cibulskis, Carrie; Gabriel, Stacey B.; Gao, Galen F.; Ha, Gavin; Meyerson, Matthew; Schumacher, Steven E.; Shih, Juliann; Kucherlapati, Melanie H.; Kucherlapati, Raju S.; Baylin, Stephen; Cope, Leslie; Danilova, Ludmila; Bootwalla, Moiz S.; Lai, Phillip H.; Maglinte, Dennis T.; Van Den Berg, David J.; Weisenberger, Daniel J.; Auman, J. Todd; Balu, Saianand; Bodenheimer, Tom; Fan, Cheng; Hoadley, Katherine A.; Hoyle, Alan P.; Jefferys, Stuart R.; Jones, Corbin D.; Meng, Shaowu; Mieczkowski, Piotr A.; Mose, Lisle E.; Perou, Amy H.; Perou, Charles M.; Roach, Jeffrey; Shi, Yan; Simons, Janae V.; Skelly, Tara; Soloway, Matthew G.; Tan, Donghui; Veluvolu, Umadevi; Fan, Huihui; Hinoue, Toshinori; Laird, Peter W.; Shen, Hui; Zhou, Wanding; Bellair, Michelle; Chang, Kyle; Covington, Kyle; Creighton, Chad J.; Dinh, Huyen; Doddapaneni, Harsha Vardhan; Donehower, Lawrence A.; Drummond, Jennifer; Gibbs, Richard A.; Glenn, Robert; Hale, Walker; Han, Yi; Hu, Jianhong; Korchina, Viktoriya; Lee, Sandra; Lewis, Lora; Li, Wei; Liu, Xiuping; Morgan, Margaret; Morton, Donna; Muzny, Donna; Santibanez, Jireh; Sheth, Margi; Shinbrot, Eve; Wang, Linghua; Wang, Min; Wheeler, David A.; Xi, Liu; Zhao, Fengmei; Hess, Julian; Appelbaum, Elizabeth L.; Bailey, Matthew; Cordes, Matthew G.; Ding, Li; Fronick, Catrina C.; Fulton, Lucinda A.; Fulton, Robert S.; Kandoth, Cyriac; Mardis, Elaine R.; McLellan, Michael D.; Miller, Christopher A.; Schmidt, Heather K.; Wilson, Richard K.; Crain, Daniel; Curley, Erin; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph; Penny, Robert; Shelton, Candace; Shelton, Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Bowen, Jay; Gastier-Foster, Julie M.; Gerken, Mark; Leraas, Kristen M.; Lichtenberg, Tara M.; Ramirez, Nilsa C.; Wise, Lisa; Zmuda, Erik; Corcoran, Niall; Costello, Tony; Hovens, Christopher; Carvalho, Andre L.; de Carvalho, Ana C.; Fregnani, José H.; Longatto-Filho, Adhemar; Reis, Rui M.; Scapulatempo-Neto, Cristovam; Silveira, Henrique C.S.; Vidal, Daniel O.; Burnette, Andrew; Eschbacher, Jennifer; Hermes, Beth; Noss, Ardene; Singh, Rosy; Anderson, Matthew L.; Castro, Patricia D.; Ittmann, Michael; Huntsman, David; Kohl, Bernard; Le, Xuan; Thorp, Richard; Andry, Chris; Duffy, Elizabeth R.; Lyadov, Vladimir; Paklina, Oxana; Setdikova, Galiya; Shabunin, Alexey; Tavobilov, Mikhail; McPherson, Christopher; Warnick, Ronald; Berkowitz, Ross; Cramer, Daniel; Feltmate, Colleen; Horowitz, Neil; Kibel, Adam; Muto, Michael; Raut, Chandrajit P.; Malykh, Andrei; Barnholtz-Sloan, Jill S.; Barrett, Wendi; Devine, Karen; Fulop, Jordonna; Ostrom, Quinn T.; Shimmel, Kristen; Wolinsky, Yingli; Sloan, Andrew E.; De Rose, Agostino; Giuliante, Felice; Goodman, Marc; Karlan, Beth Y.; Hagedorn, Curt H.; Eckman, John; Harr, Jodi; Myers, Jerome; Tucker, Kelinda; Zach, Leigh Anne; Deyarmin, Brenda; Hu, Hai; Kvecher, Leonid; Larson, Caroline; Mural, Richard J.; Somiari, Stella; Vicha, Ales; Zelinka, Tomas; Bennett, Joseph; Iacocca, Mary; Rabeno, Brenda; Swanson, Patricia; Latour, Mathieu; Lacombe, Louis; Têtu, Bernard; Bergeron, Alain; McGraw, Mary; Staugaitis, Susan M.; Chabot, John; Hibshoosh, Hanina; Sepulveda, Antonia; Su, Tao; Wang, Timothy; Potapova, Olga; Voronina, Olga; Desjardins, Laurence; Mariani, Odette; Roman-Roman, Sergio; Sastre, Xavier; Stern, Marc Henri; Cheng, Feixiong; Signoretti, Sabina; Berchuck, Andrew; Bigner, Darell; Lipp, Eric; Marks, Jeffrey; McCall, Shannon; McLendon, Roger; Secord, Angeles; Sharp, Alexis; Behera, Madhusmita; Brat, Daniel J.; Chen, Amy; Delman, Keith; Force, Seth; Khuri, Fadlo; Magliocca, Kelly; Maithel, Shishir; Olson, Jeffrey J.; Owonikoko, Taofeek; Pickens, Alan; Ramalingam, Suresh; Shin, Dong M.; Sica, Gabriel; Van Meir, Erwin G.; Zhang, Hongzheng; Eijckenboom, Wil; Gillis, Ad; Korpershoek, Esther; Looijenga, Leendert; Oosterhuis, Wolter; Stoop, Hans; van Kessel, Kim E.; Zwarthoff, Ellen C.; Calatozzolo, Chiara; Cuppini, Lucia; Cuzzubbo, Stefania; DiMeco, Francesco; Finocchiaro, Gaetano; Mattei, Luca; Perin, Alessandro; Pollo, Bianca; Chen, Chu; Houck, John; Lohavanichbutr, Pawadee; Hartmann, Arndt; Stoehr, Christine; Stoehr, Robert; Taubert, Helge; Wach, Sven; Wullich, Bernd; Kycler, Witold; Murawa, Dawid; Wiznerowicz, Maciej; Chung, Ki; Edenfield, W. Jeffrey; Martin, Julie; Baudin, Eric; Bubley, Glenn; Bueno, Raphael; De Rienzo, Assunta; Richards, William G.; Kalkanis, Steven; Mikkelsen, Tom; Noushmehr, Houtan; Scarpace, Lisa; Girard, Nicolas; Aymerich, Marta; Campo, Elias; Giné, Eva; Guillermo, Armando López; Van Bang, Nguyen; Hanh, Phan Thi; Phu, Bui Duc; Tang, Yufang; Colman, Howard; Evason, Kimberley; Dottino, Peter R.; Martignetti, John A.; Gabra, Hani; Juhl, Hartmut; Akeredolu, Teniola; Stepa, Serghei; Hoon, Dave; Ahn, Keunsoo; Kang, Koo Jeong; Beuschlein, Felix; Breggia, Anne; Birrer, Michael; Bell, Debra; Borad, Mitesh; Bryce, Alan H.; Castle, Erik; Chandan, Vishal; Cheville, John; Copland, John A.; Farnell, Michael; Flotte, Thomas; Giama, Nasra; Ho, Thai; Kendrick, Michael; Kocher, Jean Pierre; Kopp, Karla; Moser, Catherine; Nagorney, David; O'Brien, Daniel; O'Neill, Brian Patrick; Patel, Tushar; Petersen, Gloria; Que, Florencia; Rivera, Michael; Roberts, Lewis; Smallridge, Robert; Smyrk, Thomas; Stanton, Melissa; Thompson, R. Houston; Torbenson, Michael; Yang, Ju Dong; Zhang, Lizhi; Brimo, Fadi; Ajani, Jaffer A.; Gonzalez, Ana Maria Angulo; Behrens, Carmen; Bondaruk, Jolanta; Broaddus, Russell; Czerniak, Bogdan; Esmaeli, Bita; Fujimoto, Junya; Gershenwald, Jeffrey; Guo, Charles; Lazar, Alexander J.; Logothetis, Christopher; Meric-Bernstam, Funda; Moran, Cesar; Ramondetta, Lois; Rice, David; Sood, Anil; Tamboli, Pheroze; Thompson, Timothy; Troncoso, Patricia; Tsao, Anne; Wistuba, Ignacio; Carter, Candace; Haydu, Lauren; Hersey, Peter; Jakrot, Valerie; Kakavand, Hojabr; Kefford, Richard; Lee, Kenneth; Long, Georgina; Mann, Graham; Quinn, Michael; Saw, Robyn; Scolyer, Richard; Shannon, Kerwin; Spillane, Andrew; Stretch, onathan; Synott, Maria; Thompson, John; Wilmott, James; Al-Ahmadie, Hikmat; Chan, Timothy A.; Ghossein, Ronald; Gopalan, Anuradha; Levine, Douglas A.; Reuter, Victor; Singer, Samuel; Singh, Bhuvanesh; Tien, Nguyen Viet; Broudy, Thomas; Mirsaidi, Cyrus; Nair, Praveen; Drwiega, Paul; Miller, Judy; Smith, Jennifer; Zaren, Howard; Park, Joong Won; Hung, Nguyen Phi; Kebebew, Electron; Linehan, W. Marston; Metwalli, Adam R.; Pacak, Karel; Pinto, Peter A.; Schiffman, Mark; Schmidt, Laura S.; Vocke, Cathy D.; Wentzensen, Nicolas; Worrell, Robert; Yang, Hannah; Moncrieff, Marc; Goparaju, Chandra; Melamed, Jonathan; Pass, Harvey; Botnariuc, Natalia; Caraman, Irina; Cernat, Mircea; Chemencedji, Inga; Clipca, Adrian; Doruc, Serghei; Gorincioi, Ghenadie; Mura, Sergiu; Pirtac, Maria; Stancul, Irina; Tcaciuc, Diana; Albert, Monique; Alexopoulou, Iakovina; Arnaout, Angel; Bartlett, John; Engel, Jay; Gilbert, Sebastien; Parfitt, Jeremy; Sekhon, Harman; Thomas, George; Rassl, Doris M.; Rintoul, Robert C.; Bifulco, Carlo; Tamakawa, Raina; Urba, Walter; Hayward, Nicholas; Timmers, Henri; Antenucci, Anna; Facciolo, Francesco; Grazi, Gianluca; Marino, Mirella; Merola, Roberta; de Krijger, Ronald; Gimenez-Roqueplo, Anne Paule; Piché, Alain; Chevalier, Simone; McKercher, Ginette; Birsoy, Kivanc; Barnett, Gene; Brewer, Cathy; Farver, Carol; Naska, Theresa; Pennell, Nathan A.; Raymond, Daniel; Schilero, Cathy; Smolenski, Kathy; Williams, Felicia; Morrison, Carl; Borgia, Jeffrey A.; Liptay, Michael J.; Pool, Mark; Seder, Christopher W.; Junker, Kerstin; Omberg, Larsson; Dinkin, Mikhail; Manikhas, George; Alvaro, Domenico; Bragazzi, Maria Consiglia; Cardinale, Vincenzo; Carpino, Guido; Gaudio, Eugenio; Chesla, David; Cottingham, Sandra; Dubina, Michael; Moiseenko, Fedor; Dhanasekaran, Renumathy; Becker, Karl Friedrich; Janssen, Klaus Peter; Slotta-Huspenina, Julia; Abdel-Rahman, Mohamed H.; Aziz, Dina; Bell, Sue; Cebulla, Colleen M.; Davis, Amy; Duell, Rebecca; Elder, J. Bradley; Hilty, Joe; Kumar, Bahavna; Lang, James; Lehman, Norman L.; Mandt, Randy; Nguyen, Phuong; Pilarski, Robert; Rai, Karan; Schoenfield, Lynn; Senecal, Kelly; Wakely, Paul; Hansen, Paul; Lechan, Ronald; Powers, James; Tischler, Arthur; Grizzle, William E.; Sexton, Katherine C.; Kastl, Alison; Henderson, Joel; Porten, Sima; Waldmann, Jens; Fassnacht, Martin; Asa, Sylvia L.; Schadendorf, Dirk; Couce, Marta; Graefen, Markus; Huland, Hartwig; Sauter, Guido; Schlomm, Thorsten; Simon, Ronald; Tennstedt, Pierre; Olabode, Oluwole; Nelson, Mark; Bathe, Oliver; Carroll, Peter R.; Chan, June M.; Disaia, Philip; Glenn, Pat; Kelley, Robin K.; Landen, Charles N.; Phillips, Joanna; Prados, Michael; Simko, Jeffry; Smith-McCune, Karen; VandenBerg, Scott; Roggin, Kevin; Fehrenbach, Ashley; Kendler, Ady; Sifri, Suzanne; Steele, Ruth; Jimeno, Antonio; Carey, Francis; Forgie, Ian; Mannelli, Massimo; Carney, Michael; Hernandez, Brenda; Campos, Benito; Herold-Mende, Christel; Jungk, Christin; Unterberg, Andreas; von Deimling, Andreas; Bossler, Aaron; Galbraith, Joseph; Jacobus, Laura; Knudson, Michael; Knutson, Tina; Ma, Deqin; Milhem, Mohammed; Sigmund, Rita; Godwin, Andrew K.; Madan, Rashna; Rosenthal, Howard G.; Adebamowo, Clement; Adebamowo, Sally N.; Boussioutas, Alex; Beer, David; Giordano, Thomas; Mes-Masson, Anne Marie; Saad, Fred; Bocklage, Therese; Landrum, Lisa; Mannel, Robert; Moore, Kathleen; Moxley, Katherine; Postier, Russel; Walker, Joan; Zuna, Rosemary; Feldman, Michael; Valdivieso, Federico; Dhir, Rajiv; Luketich, James; Pinero, Edna M.Mora; Quintero-Aguilo, Mario; Carlotti, Carlos Gilberto; Dos Santos, Jose Sebastião; Kemp, Rafael; Sankarankuty, Ajith; Tirapelli, Daniela; Catto, James; Agnew, Kathy; Swisher, Elizabeth; Creaney, Jenette; Robinson, Bruce; Shelley, Carl Simon; Godwin, Eryn M.; Kendall, Sara; Shipman, Cassaundra; Bradford, Carol; Carey, Thomas; Haddad, Andrea; Moyer, Jeffey; Peterson, Lisa; Prince, Mark; Rozek, Laura; Wolf, Gregory; Bowman, Rayleen; Fong, Kwun M.; Yang, Ian; Korst, Robert; Rathmell, W. Kimryn; Fantacone-Campbell, J. Leigh; Hooke, Jeffrey A.; Kovatich, Albert J.; Shriver, Craig D.; DiPersio, John; Drake, Bettina; Govindan, Ramaswamy; Heath, Sharon; Ley, Timothy; Van Tine, Brian; Westervelt, Peter; Rubin, Mark A.; Lee, Jung Il; Aredes, Natália D.; Mariamidze, Armaz; Lazar, Alexander J.; Serody, Jonathan S.; Demicco, Elizabeth G.; Disis, Mary L.; Vincent, Benjamin G.; Shmulevich, llya

    2018-01-01

    We performed an extensive immunogenomic analysis of more than 10,000 tumors comprising 33 diverse cancer types by utilizing data compiled by TCGA. Across cancer types, we identified six immune subtypes—wound healing, IFN-γ dominant, inflammatory, lymphocyte depleted, immunologically quiet, and TGF-β

  8. Immune evasion in ebolavirus infections.

    Science.gov (United States)

    Audet, Jonathan; Kobinger, Gary P

    2015-02-01

    Ebola virus (EBOV) infects humans as well as several animal species. It can lead to a highly lethal disease, with mortality rates approaching 90% in primates. Recent advances have deepened our understanding of how this virus is able to prevent the development of protective immune responses. The EBOV genome encodes eight proteins, four of which were shown to interact with the host in ways that counteract the immune response. The viral protein 35 (VP35) is capable of capping dsRNA and interacts with IRF7 to prevent detection of the virus by immune cells. The main role of the soluble glycoprotein (sGP) is still unclear, but it is capable of subverting the anti-GP1,2 antibody response. The GP1,2 protein has shown anti-tetherin activity and the ability to hide cell-surface proteins. Finally, VP24 interferes with the production of interferons (IFNs) and with IFN signaling in infected cells. Taken together, these data point to extensive adaptation of EBOV to evade the immune system of dead end hosts. While our understanding of the interactions between the human and viral proteins increases, details of those interactions in other hosts remain largely unclear and represent a gap in our knowledge.

  9. The Immune System in Hypertension

    Science.gov (United States)

    Trott, Daniel W.; Harrison, David G.

    2014-01-01

    While hypertension has predominantly been attributed to perturbations of the vasculature, kidney, and central nervous system, research for almost 50 yr has shown that the immune system also contributes to this disease. Inflammatory cells accumulate in the kidneys and vasculature of humans and experimental animals with hypertension and likely…

  10. Recommendations for Institutional Prematriculation Immunizations

    Science.gov (United States)

    Journal of American College Health, 2011

    2011-01-01

    The recommendations presented in this article are provided to colleges and universities to facilitate the implementation of a comprehensive institutional prematriculation immunization policy. Vaccine-preventable diseases continue to occur on American campuses. In response to changing epidemiology and the introduction of new vaccines, the ACHA…

  11. 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...

  12. Innate immunity in the lung regulates the development of asthma.

    Science.gov (United States)

    DeKruyff, Rosemarie H; Yu, Sanhong; Kim, Hye Young; Umetsu, Dale T

    2014-07-01

    The lung, while functioning as a gas exchange organ, encounters a large array of environmental factors, including particulate matter, toxins, reactive oxygen species, chemicals, allergens, and infectious microbes. To rapidly respond to and counteract these elements, a number of innate immune mechanisms have evolved that can lead to lung inflammation and asthma, which is the focus of this review. These innate mechanisms include a role for two incompletely understood cell types, invariant natural killer T (iNKT) cells and innate lymphoid cells (ILCs), which together produce a wide range of cytokines, including interleukin-4 (IL-4), IL-5, IL-13, interferon-γ, IL-17, and IL-22, independently of adaptive immunity and conventional antigens. The specific roles of iNKT cells and ILCs in immunity are still being defined, but both cell types appear to play important roles in the lungs, particularly in asthma. As we gain a better understanding of these innate cell types, we will acquire great insight into the mechanisms by which allergic and non-allergic asthma phenotypes develop. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Alterations in Gut Microbiota and Immunity by Dietary Fat.

    Science.gov (United States)

    Yang, Bo Gie; Hur, Kyu Yeon; Lee, Myung Shik

    2017-11-01

    Gut microbiota play critical physiological roles in energy extraction from the intestine and in the control of systemic immunity, as well as local intestinal immunity. Disturbance of gut microbiota leads to the development of several diseases, such as colitis, inflammatory bowel diseases, metabolic disorders, cancer, etc. From a metabolic point of view, the gut is a large metabolic organ and one of the first to come into contact with dietary fats. Interestingly, excessive dietary fat has been incriminated as a primary culprit of metabolic syndrome and obesity. After intake of high-fat diet or Western diet, extensive changes in gut microbiota have been observed, which may be an underlying cause of alterations in whole body metabolism and nutrient homeostasis. Here, we summarize recent data on changes in the gut microbiota and immunity associated with dietary fat, as well as their relationships with the pathogenesis of metabolic syndrome. These findings may provide insight into the understanding of the complex pathophysiology related to the development of metabolic diseases and offer an opportunity to develop novel candidates for therapeutic agents. © Copyright: Yonsei University College of Medicine 2017.

  14. The most common friend first immunization

    International Nuclear Information System (INIS)

    Nian Fu-Zhong; Hu Cha-Sheng

    2016-01-01

    In this paper, a standard susceptible-infected-recovered-susceptible(SIRS) epidemic model based on the Watts–Strogatz (WS) small-world network model and the Barabsi–Albert (BA) scale-free network model is established, and a new immunization scheme — “the most common friend first immunization” is proposed, in which the most common friend’s node is described as being the first immune on the second layer protection of complex networks. The propagation situations of three different immunization schemes — random immunization, high-risk immunization, and the most common friend first immunization are studied. At the same time, the dynamic behaviors are also studied on the WS small-world and the BA scale-free network. Moreover, the analytic and simulated results indicate that the immune effect of the most common friend first immunization is better than random immunization, but slightly worse than high-risk immunization. However, high-risk immunization still has some limitations. For example, it is difficult to accurately define who a direct neighbor in the life is. Compared with the traditional immunization strategies having some shortcomings, the most common friend first immunization is effective, and it is nicely consistent with the actual situation. (paper)

  15. Insight in psychosis: Metacognitive processes and treatment

    OpenAIRE

    de Vos, Annerieke

    2016-01-01

    Insight is impaired in 50- 80% of the patients with schizophrenia. Annerieke de Vos working at GGZ Drenthe and the University Medical Hospital Groningen, aimed to elucidate which processes underlie impaired insight and tried to improve insight in patients by targeting these processes. On September 21st she will defend her thesis entitled: "Insight in psychosis. Metacognitive processes and treatment.". Patients with impaired insight may fail to recognize that things in life are not going well ...

  16. Transcriptomic immune response of Tenebrio molitor pupae to parasitization by Scleroderma guani.

    Directory of Open Access Journals (Sweden)

    Jia-Ying Zhu

    Full Text Available BACKGROUND: Host and parasitoid interaction is one of the most fascinating relationships of insects, which is currently receiving an increasing interest. Understanding the mechanisms evolved by the parasitoids to evade or suppress the host immune system is important for dissecting this interaction, while it was still poorly known. In order to gain insight into the immune response of Tenebrio molitor to parasitization by Scleroderma guani, the transcriptome of T. molitor pupae was sequenced with focus on immune-related gene, and the non-parasitized and parasitized T. molitor pupae were analyzed by digital gene expression (DGE analysis with special emphasis on parasitoid-induced immune-related genes using Illumina sequencing. METHODOLOGY/PRINCIPAL FINDINGS: In a single run, 264,698 raw reads were obtained. De novo assembly generated 71,514 unigenes with mean length of 424 bp. Of those unigenes, 37,373 (52.26% showed similarity to the known proteins in the NCBI nr database. Via analysis of the transcriptome data in depth, 430 unigenes related to immunity were identified. DGE analysis revealed that parasitization by S. guani had considerable impacts on the transcriptome profile of T. molitor pupae, as indicated by the significant up- or down-regulation of 3,431 parasitism-responsive transcripts. The expression of a total of 74 unigenes involved in immune response of T. molitor was significantly altered after parasitization. CONCLUSIONS/SIGNIFICANCE: obtained T. molitor transcriptome, in addition to establishing a fundamental resource for further research on functional genomics, has allowed the discovery of a large group of immune genes that might provide a meaningful framework to better understand the immune response in this species and other beetles. The DGE profiling data provides comprehensive T. molitor immune gene expression information at the transcriptional level following parasitization, and sheds valuable light on the molecular

  17. Transcriptomic immune response of Tenebrio molitor pupae to parasitization by Scleroderma guani.

    Science.gov (United States)

    Zhu, Jia-Ying; Yang, Pu; Zhang, Zhong; Wu, Guo-Xing; Yang, Bin

    2013-01-01

    Host and parasitoid interaction is one of the most fascinating relationships of insects, which is currently receiving an increasing interest. Understanding the mechanisms evolved by the parasitoids to evade or suppress the host immune system is important for dissecting this interaction, while it was still poorly known. In order to gain insight into the immune response of Tenebrio molitor to parasitization by Scleroderma guani, the transcriptome of T. molitor pupae was sequenced with focus on immune-related gene, and the non-parasitized and parasitized T. molitor pupae were analyzed by digital gene expression (DGE) analysis with special emphasis on parasitoid-induced immune-related genes using Illumina sequencing. In a single run, 264,698 raw reads were obtained. De novo assembly generated 71,514 unigenes with mean length of 424 bp. Of those unigenes, 37,373 (52.26%) showed similarity to the known proteins in the NCBI nr database. Via analysis of the transcriptome data in depth, 430 unigenes related to immunity were identified. DGE analysis revealed that parasitization by S. guani had considerable impacts on the transcriptome profile of T. molitor pupae, as indicated by the significant up- or down-regulation of 3,431 parasitism-responsive transcripts. The expression of a total of 74 unigenes involved in immune response of T. molitor was significantly altered after parasitization. obtained T. molitor transcriptome, in addition to establishing a fundamental resource for further research on functional genomics, has allowed the discovery of a large group of immune genes that might provide a meaningful framework to better understand the immune response in this species and other beetles. The DGE profiling data provides comprehensive T. molitor immune gene expression information at the transcriptional level following parasitization, and sheds valuable light on the molecular understanding of the host-parasitoid interaction.

  18. Transcriptomic Immune Response of Tenebrio molitor Pupae to Parasitization by Scleroderma guani

    Science.gov (United States)

    Zhu, Jia-Ying; Yang, Pu; Zhang, Zhong; Wu, Guo-Xing; Yang, Bin

    2013-01-01

    Background Host and parasitoid interaction is one of the most fascinating relationships of insects, which is currently receiving an increasing interest. Understanding the mechanisms evolved by the parasitoids to evade or suppress the host immune system is important for dissecting this interaction, while it was still poorly known. In order to gain insight into the immune response of Tenebrio molitor to parasitization by Scleroderma guani, the transcriptome of T. molitor pupae was sequenced with focus on immune-related gene, and the non-parasitized and parasitized T. molitor pupae were analyzed by digital gene expression (DGE) analysis with special emphasis on parasitoid-induced immune-related genes using Illumina sequencing. Methodology/Principal Findings In a single run, 264,698 raw reads were obtained. De novo assembly generated 71,514 unigenes with mean length of 424 bp. Of those unigenes, 37,373 (52.26%) showed similarity to the known proteins in the NCBI nr database. Via analysis of the transcriptome data in depth, 430 unigenes related to immunity were identified. DGE analysis revealed that parasitization by S. guani had considerable impacts on the transcriptome profile of T. molitor pupae, as indicated by the significant up- or down-regulation of 3,431 parasitism-responsive transcripts. The expression of a total of 74 unigenes involved in immune response of T. molitor was significantly altered after parasitization. Conclusions/Significance obtained T. molitor transcriptome, in addition to establishing a fundamental resource for further research on functional genomics, has allowed the discovery of a large group of immune genes that might provide a meaningful framework to better understand the immune response in this species and other beetles. The DGE profiling data provides comprehensive T. molitor immune gene expression information at the transcriptional level following parasitization, and sheds valuable light on the molecular understanding of the host

  19. Distinct effects on diversifying selection by two mechanisms of immunity against Streptococcus pneumoniae.

    Directory of Open Access Journals (Sweden)

    Yuan Li

    Full Text Available Antigenic variation to evade host immunity has long been assumed to be a driving force of diversifying selection in pathogens. Colonization by Streptococcus pneumoniae, which is central to the organism's transmission and therefore evolution, is limited by two arms of the immune system: antibody- and T cell- mediated immunity. In particular, the effector activity of CD4(+ T(H17 cell mediated immunity has been shown to act in trans, clearing co-colonizing pneumococci that do not bear the relevant antigen. It is thus unclear whether T(H17 cell immunity allows benefit of antigenic variation and contributes to diversifying selection. Here we show that antigen-specific CD4(+ T(H17 cell immunity almost equally reduces colonization by both an antigen-positive strain and a co-colonized, antigen-negative strain in a mouse model of pneumococcal carriage, thus potentially minimizing the advantage of escape from this type of immunity. Using a proteomic screening approach, we identified a list of candidate human CD4(+ T(H17 cell antigens. Using this list and a previously published list of pneumococcal Antibody antigens, we bioinformatically assessed the signals of diversifying selection among the identified antigens compared to non-antigens. We found that Antibody antigen genes were significantly more likely to be under diversifying selection than the T(H17 cell antigen genes, which were indistinguishable from non-antigens. Within the Antibody antigens, epitopes recognized by human antibodies showed stronger evidence of diversifying selection. Taken together, the data suggest that T(H17 cell-mediated immunity, one form of T cell immunity that is important to limit carriage of antigen-positive pneumococcus, favors little diversifying selection in the targeted antigen. The results could provide new insight into pneumococcal vaccine design.

  20. Ensuring childhood vaccination among slums dwellers under the National Immunization Program in India - Challenges and opportunities.

    Science.gov (United States)

    Singh, Sanjeev; Sahu, Damodar; Agrawal, Ashish; Vashi, Meeta Dhaval

    2018-04-04

    Almost, one third of the world's urban population resides in slums and the number would double by 2030. Slums denotes collection of people from various communities having a meagre income and living in unhygienic conditions thus making themselves most vulnerable for outbreaks of communicable diseases. India contributes substantially to the global disease burden and under-five mortality rates i.e. 20% attributable to vaccine preventable diseases. Immunization plays a crucial role in combating high childhood mortality rates attributable to vaccine preventable diseases across the globe. This systematic review, provides insights on immunization status in slums, identifies various factors influencing it thus, exploring opportunities that may be available to improve vaccination coverage under the National Immunization Program. Taking into account the above aspects, a review of literature was undertaken in various databases that included studies published between 2006 and 2017. In India, ~33% of the urban population lives in slums with suboptimal vaccination coverage ranging from 14% to upto 90%. Few of the important causes for low coverage included socioeconomic factors such as poor community participation, lack of awareness, frequent migration, and loss of daily income. Hence, mere presence of vaccines in the National Immunization Program doesn't do the job, there is a definite unmet need to emphasize upon the importance of immunization among slums dwellers and take necessary steps. For instance, delivering immunization services at the doorstep (e.g. pulse polio program), community-based education, text messaging as reminders and incentivized immunization services are some of the opportunities that can be explored and implemented to improve immunization status in the slums. Thus, in addition to inclusion of more and more vaccines in the National Immunization Program, there is a definite need to focus on people living in high risk areas in order to improve coverage and

  1. Exploiting immune cell metabolic machinery for functional HIV cure and the prevention of inflammaging.

    Science.gov (United States)

    Palmer, Clovis S; Palchaudhuri, Riya; Albargy, Hassan; Abdel-Mohsen, Mohamed; Crowe, Suzanne M

    2018-01-01

    An emerging paradigm in immunology suggests that metabolic reprogramming and immune cell activation and functions are intricately linked. Viral infections, such as HIV infection, as well as cancer force immune cells to undergo major metabolic challenges. Cells must divert energy resources in order to mount an effective immune response. However, the fact that immune cells adopt specific metabolic programs to provide host defense against intracellular pathogens and how this metabolic shift impacts immune cell functions and the natural course of diseases have only recently been appreciated. A clearer insight into how these processes are inter-related will affect our understanding of several fundamental aspects of HIV persistence. Even in patients with long-term use of anti-retroviral therapies, HIV infection persists and continues to cause chronic immune activation and inflammation, ongoing and cumulative damage to multiple organs systems, and a reduction in life expectancy. HIV-associated fundamental changes to the metabolic machinery of the immune system can promote a state of "inflammaging", a chronic, low-grade inflammation with specific immune changes that characterize aging, and can also contribute to the persistence of HIV in its reservoirs. In this commentary, we will bring into focus evolving concepts on how HIV modulates the metabolic machinery of immune cells in order to persist in reservoirs and how metabolic reprogramming facilitates a chronic state of inflammation that underlies the development of age-related comorbidities. We will discuss how immunometabolism is facilitating the changing paradigms in HIV cure research and outline the novel therapeutic opportunities for preventing inflammaging and premature development of age-related conditions in HIV + individuals.

  2. Abundant genetic overlap between blood lipids and immune-mediated diseases indicates shared molecular genetic mechanisms.

    Directory of Open Access Journals (Sweden)

    Ole A Andreassen

    Full Text Available Epidemiological studies suggest a relationship between blood lipids and immune-mediated diseases, but the nature of these associations is not well understood. We used genome-wide association studies (GWAS to investigate shared single nucleotide polymorphisms (SNPs between blood lipids and immune-mediated diseases. We analyzed data from GWAS (n~200,000 individuals, applying new False Discovery Rate (FDR methods, to investigate genetic overlap between blood lipid levels [triglycerides (TG, low density lipoproteins (LDL, high density lipoproteins (HDL] and a selection of archetypal immune-mediated diseases (Crohn's disease, ulcerative colitis, rheumatoid arthritis, type 1 diabetes, celiac disease, psoriasis and sarcoidosis. We found significant polygenic pleiotropy between the blood lipids and all the investigated immune-mediated diseases. We discovered several shared risk loci between the immune-mediated diseases and TG (n = 88, LDL (n = 87 and HDL (n = 52. Three-way analyses differentiated the pattern of pleiotropy among the immune-mediated diseases. The new pleiotropic loci increased the number of functional gene network nodes representing blood lipid loci by 40%. Pathway analyses implicated several novel shared mechanisms for immune pathogenesis and lipid biology, including glycosphingolipid synthesis (e.g. FUT2 and intestinal host-microbe interactions (e.g. ATG16L1. We demonstrate a shared genetic basis for blood lipids and immune-mediated diseases independent of environmental factors. Our findings provide novel mechanistic insights into dyslipidemia and immune-mediated diseases and may have implications for therapeutic trials involving lipid-lowering and anti-inflammatory agents.

  3. Tumor-altered dendritic cell function: implications for anti-tumor immunity

    Directory of Open Access Journals (Sweden)

    Kristian Michael Hargadon

    2013-07-01

    Full Text Available Dendritic cells are key regulators of both innate and adaptive immunity, and the array of immunoregulatory functions exhibited by these cells is dictated by their differentiation, maturation, and activation status. Although a major role for these cells in the induction of immunity to pathogens has long been appreciated, data accumulated over the last several years has demonstrated that DC are also critical regulators of anti-tumor immune responses. However, despite the potential for stimulation of robust anti-tumor immunity by DC, tumor-altered DC function has been observed in many cancer patients and tumor-bearing animals and is often associated with tumor immune escape. Such dysfunction has significant implications for both the induction of natural anti-tumor immune responses as well as the efficacy of immunotherapeutic strategies that target endogenous DC in situ or that employ exogenous DC as part of anti-cancer immunization maneuvers. In this review, the major types of tumor-altered DC function will be described, with emphasis on recent insights into the mechanistic bases for the inhibition of DC differentiation from hematopoietic precursors, the altered programming of DC precursors to differentiate into myeloid-derived suppressor cells or tumor-associated macrophages, the suppression of DC maturation and activation, and the induction of immunoregulatory DC by tumors, tumor-derived factors, and tumor-associated cells within the milieu of the tumor microenvironment. The impact of these tumor-altered cells on the quality of the overall anti-tumor immune response will also be discussed. Finally, this review will also highlight questions concerning tumor-altered DC function that remain unanswered, and it will address factors that have limited advances in the study of this phenomenon in order to focus future research efforts in the field on identifying strategies for interfering with tumor-associated DC dysfunction and improving DC-mediated anti

  4. Characterization of the effect of Cr(VI) on humoral innate immunity using Drosophila melanogaster.

    Science.gov (United States)

    Pragya, P; Shukla, A K; Murthy, R C; Abdin, M Z; Kar Chowdhuri, D

    2015-11-01

    With the advancement of human race, different anthropogenic activities have heaped the environment with chemicals that can cause alteration in the immune system of exposed organism. As a first line of barrier, the evolutionary conserved innate immunity is crucial for the health of an organism. However, there is paucity of information regarding in vivo assessment of the effect of environmental chemicals on innate immunity. Therefore, we examined the effect of a widely used environmental chemical, Cr(VI), on humoral innate immune response using Drosophila melanogaster. The adverse effect of Cr(VI) on host humoral response was characterized by decreased gene expression of antimicrobial peptides (AMPs) in the exposed organism. Concurrently, a significantly decreased transcription of humoral pathway receptors (Toll and PGRP) and triglyceride level along with inhibition of antioxidant enzyme activities were observed in exposed organism. This in turn weakened the immune response of exposed organism that was manifested by their reduced resistance against bacterial infection. In addition, overexpression of the components of humoral immunity particularly Diptericin benefits Drosophila from Cr(VI)-induced humoral immune-suppressive effect. To our knowledge, this is the first report regarding negative impact of an environmental chemical on humoral innate immune response of Drosophila along with subsequent protection by AMPs, which may provide novel insight into host-chemical interactions. Also, our data validate the utility and sensitivity of Drosophila as a model that could be used for screening the possible risk of environmental chemicals on innate immunity with minimum ethical concern that can be further extrapolated to higher organisms. © 2014 Wiley Periodicals, Inc.

  5. New Insights into Behavioral Finance

    NARCIS (Netherlands)

    G. Baltussen (Guido)

    2008-01-01

    textabstractThis thesis applies insights from psychology and other behavioral sciences to overcome the shortcomings of the traditional finance approach (which assumes that agents and markets are rational) and improves our understanding of financial markets and its participants. More specific, this

  6. Investigating Insight as Sudden Learning

    Science.gov (United States)

    Ash, Ivan K.; Jee, Benjamin D.; Wiley, Jennifer

    2012-01-01

    Gestalt psychologists proposed two distinct learning mechanisms. Associative learning occurs gradually through the repeated co-occurrence of external stimuli or memories. Insight learning occurs suddenly when people discover new relationships within their prior knowledge as a result of reasoning or problem solving processes that re-organize or…

  7. Immunization of Epidemics in Multiplex Networks

    Science.gov (United States)

    Zhao, Dawei; Wang, Lianhai; Li, Shudong; Wang, Zhen; Wang, Lin; Gao, Bo

    2014-01-01

    Up to now, immunization of disease propagation has attracted great attention in both theoretical and experimental researches. However, vast majority of existing achievements are limited to the simple assumption of single layer networked population, which seems obviously inconsistent with recent development of complex network theory: each node could possess multiple roles in different topology connections. Inspired by this fact, we here propose the immunization strategies on multiplex networks, including multiplex node-based random (targeted) immunization and layer node-based random (targeted) immunization. With the theory of generating function, theoretical analysis is developed to calculate the immunization threshold, which is regarded as the most critical index for the effectiveness of addressed immunization strategies. Interestingly, both types of random immunization strategies show more efficiency in controlling disease spreading on multiplex Erdös-Rényi (ER) random networks; while targeted immunization strategies provide better protection on multiplex scale-free (SF) networks. PMID:25401755

  8. Immune Cells in Blood Recognize Tumors

    Science.gov (United States)

    NCI scientists have developed a novel strategy for identifying immune cells circulating in the blood that recognize specific proteins on tumor cells, a finding they believe may have potential implications for immune-based therapies.

  9. Immune System Dysfunction in the Elderly.

    Science.gov (United States)

    Fuentes, Eduardo; Fuentes, Manuel; Alarcón, Marcelo; Palomo, Iván

    2017-01-01

    Human aging is characterized by both physical and physiological frailty that profoundly affects the immune system. In this context aging is associated with declines in adaptive and innate immunity established as immunosenescence. Immunosenescence is a new concept that reflects the age-associated restructuring changes of innate and adaptive immune functions. Thus elderly individuals usually present chronic low-level inflammation, higher infection rates and chronic diseases. A study of alterations in the immune system during aging could provide a potentially useful biomarker for the evaluation of immune senescence treatment. The immune system is the result of the interplay between innate and adaptive immunity, yet the impact of aging on this function is unclear. In this article the function of the immune system during aging is explored.

  10. Unique aspects of the perinatal immune system.

    Science.gov (United States)

    Zhang, Xiaoming; Zhivaki, Dania; Lo-Man, Richard

    2017-08-01

    The early stages of life are associated with increased susceptibility to infection, which is in part due to an ineffective immune system. In the context of infection, the immune system must be stimulated to provide efficient protection while avoiding insufficient or excessive activation. Yet, in early life, age-dependent immune regulation at molecular and cellular levels contributes to a reduced immunological fitness in terms of pathogen clearance and response to vaccines. To enable microbial colonization to be tolerated at birth, epigenetic immune cell programming and early life-specific immune regulatory and effector mechanisms ensure that vital functions and organ development are supported and that tissue damage is avoided. Advancement in our understanding of age-related remodelling of immune networks and the consequent tuning of immune responsiveness will open up new possibilities for immune intervention and vaccine strategies that are designed specifically for early life.

  11. Weakened Immune System and Adult Vaccination

    Science.gov (United States)

    ... Basics Adult Vaccination Resources for Healthcare Professionals Weakened Immune System and Adult Vaccination Recommend on Facebook Tweet Share ... people with health conditions such as a weakened immune system. If you have cancer or other immunocompromising conditions, ...

  12. Immunization of epidemics in multiplex networks.

    Science.gov (United States)

    Zhao, Dawei; Wang, Lianhai; Li, Shudong; Wang, Zhen; Wang, Lin; Gao, Bo

    2014-01-01

    Up to now, immunization of disease propagation has attracted great attention in both theoretical and experimental researches. However, vast majority of existing achievements are limited to the simple assumption of single layer networked population, which seems obviously inconsistent with recent development of complex network theory: each node could possess multiple roles in different topology connections. Inspired by this fact, we here propose the immunization strategies on multiplex networks, including multiplex node-based random (targeted) immunization and layer node-based random (targeted) immunization. With the theory of generating function, theoretical analysis is developed to calculate the immunization threshold, which is regarded as the most critical index for the effectiveness of addressed immunization strategies. Interestingly, both types of random immunization strategies show more efficiency in controlling disease spreading on multiplex Erdös-Rényi (ER) random networks; while targeted immunization strategies provide better protection on multiplex scale-free (SF) networks.

  13. Immunization of epidemics in multiplex networks.

    Directory of Open Access Journals (Sweden)

    Dawei Zhao

    Full Text Available Up to now, immunization of disease propagation has attracted great attention in both theoretical and experimental researches. However, vast majority of existing achievements are limited to the simple assumption of single layer networked population, which seems obviously inconsistent with recent development of complex network theory: each node could possess multiple roles in different topology connections. Inspired by this fact, we here propose the immunization strategies on multiplex networks, including multiplex node-based random (targeted immunization and layer node-based random (targeted immunization. With the theory of generating function, theoretical analysis is developed to calculate the immunization threshold, which is regarded as the most critical index for the effectiveness of addressed immunization strategies. Interestingly, both types of random immunization strategies show more efficiency in controlling disease spreading on multiplex Erdös-Rényi (ER random networks; while targeted immunization strategies provide better protection on multiplex scale-free (SF networks.

  14. Drug-induced immune hemolytic anemia

    Science.gov (United States)

    Immune hemolytic anemia secondary to drugs; Anemia - immune hemolytic - secondary to drugs ... Drugs that can cause this type of hemolytic anemia include: Cephalosporins (a class of antibiotics), most common ...

  15. The inhibitory receptor FcgammaRII reduces joint inflammation and destruction in experimental immune complex-mediated arthritides not only by inhibition of FcgammaRI/III but also by efficient clearance and endocytosis of immune complexes.

    NARCIS (Netherlands)

    Lent, P.L.E.M. van; Nabbe, K.C.A.M.; Boross, P.; Blom, A.B.; Roth, J.; Holthuysen, A.E.M.; Sloetjes, A.W.; Verbeek, S.; Berg, W.B. van den

    2003-01-01

    Studies of FcgammaRII-/- mice identified the inhibitory function of this receptor in joint inflammation and cartilage destruction induced with immune complexes (ICs). To extend our insight in the role of FcgammaRII in arthritis, we explored the role of FcgammaRII in the absence of activating

  16. Cross-talk between the Immune System and Tuberculosis Pathogenesis; a Review with Emphasis on the Immune Based Treatment

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Javan

    2016-11-01

    Full Text Available As a globally major health problem, tuberculosis (TB causes almost two million cases of death annually. Epidemiological studies demonstrate that a third of the world’s individuals is infected with Mycobacterium tuberculosis. Approximately 10% of infected patients with M. tuberculosis develop chronic manifestation as TB. Due to HIV coinfection and emerging the drug-resistant TB, the disease has been increasing and its control has been frustrated in several parts of the world.Current diagnostic techniques and therapeutic tools for TB are not satisfactory. Consequently, it is urgently essential to establish new therapies concerning vaccines, immunotherapeutic agents to provide prosperous attempts for TB controlling. To achieve this goal, it is required to be armed with comprehensive understanding of immunobiology and immunopathogenesis of TB. This would be beneficial in designing new immune-based protections, drug discoveries, personalized medicine by choosing highly-effective immunotherapeutic interventions, identification and development of novel drug candidates. Hopefully, immunotherapies could be advantageous in modulating the immune system in patients with TB, providing efficient control of M. tuberculosis infection perpetuation and, therefore, its pathogenesis. This review herein attempts to describe the function of immune system in response to TB that is of the therapeutical and clinical importance. Moreover, new insights based on therapeutics to resolve TB with immunological orientation will be discussed.

  17. Immune-Neuroendocrine Interactions and Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Luis J. Jara

    2006-01-01

    Full Text Available The relationship between immune-neuroendocrine system is firmly established. The messengers of this connection are hormones, neuropeptides, neurotransmitters and cytokines. The immune-neuroendocrine system have the capacity to synthesize and release these molecules, which, in turn, can stimulate or suppress the activity of immune or neuroendocrine cells by binding to receptors. In fact, hormones, neuropeptides and neurotransmitters participate in innate and adaptive immune response.

  18. SOME ISSUES OF DIAGNOSTICS IN IMMUNE PATHOLOGY

    OpenAIRE

    I. A. Tousankina

    2010-01-01

    Present lecture contains an author's opinion concerning diagnostic issues in immunopathology, including primary and secondary immune deficiencies, immune-dependent states that are based on immunopathological syndromes. Original formulations are suggested for some key categories of clinical immunology, physical, instrumental and laboratory diagnostics of immune deficiencies and immune-dependent diseases. The results of original long-term observations, as well as data on Sverdlovsk Regional Reg...

  19. Immune-escape mutations and stop-codons in HBsAg develop in a large proportion of patients with chronic HBV infection exposed to anti-HBV drugs in Europe

    DEFF Research Database (Denmark)

    Colagrossi, Luna; Hermans, Lucas E; Salpini, Romina

    2018-01-01

    structure of HBV genome, some immune-escape mutations or stop-codons in HBsAg can derive from drug-resistance mutations in RT. This study is aimed at gaining insight in prevalence and characteristics of immune-associated escape mutations, and stop-codons in HBsAg in chronically HBV-infected patients...

  20. Immune Repertoire Characteristics and Dynamics in Cancer

    DEFF Research Database (Denmark)

    Liu, Xiao

    The diversity of T and B cells in terms of their receptors is huge in the invertebrate’s immune system, to provide broad protection against the vast diversity of pathogens. Immune repertoire is defined as the sum of total subtypes that makes the organism’s immune system, either T cell receptor or...

  1. Viral immune evasion: a masterpiece of evolution

    NARCIS (Netherlands)

    Vossen, Mireille T. M.; Westerhout, Ellen M.; Söderberg-Nauclér, Cécilia; Wiertz, Emmanuel J. H. J.

    2002-01-01

    Coexistence of viruses and their hosts imposes an evolutionary pressure on both the virus and the host immune system. On the one hand, the host has developed an immune system able to attack viruses and virally infected cells, whereas on the other hand, viruses have developed an array of immune

  2. Cellular immune responses to respiratory viruses

    NARCIS (Netherlands)

    van Helden, M.J.G.

    2011-01-01

    When a respiratory virus successfully infects the lungs, cascades of immune responses are initiated aimed to remove the pathogen. Immediate non-specific protection is provided by the innate immune system and this reduces the viral load during the first days of infection. The adaptive immune response

  3. Immune System Toxicity and Immunotoxicity Hazard Identification

    Science.gov (United States)

    Exposure to chemicals may alter immune system health, increasing the risk of infections, allergy and autoimmune diseases. The chapter provides a concise overview of the immune system, host factors that affect immune system heal, and the effects that xenobiotic exposure may have ...

  4. 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.

  5. 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…

  6. Immune regulation in gut and cord : opportunities for directing the immune system

    NARCIS (Netherlands)

    de Roock, S.

    2012-01-01

    The gut is an important organ for the immune system. Microbes and immune cells interact directly or via epithelial cells. Both TH17 and Treg cells mature in this environment. The composition of the microbiota has an important influence on the immune homeostasis. Influencing the immune system via the

  7. Histomorphometric evaluation of intestinal cellular immune responses in pigs immunized with live oral F4ac+ non-enterotoxigenic E. coli vaccine against postweaning colibacillosis

    Directory of Open Access Journals (Sweden)

    A. Kovšca Janjatovic

    2010-02-01

    Full Text Available Enterotoxigenic Escherichia coli (ETEC infection is the most common type of porcine postweaning colibacillosis (PWC. Among fimbriae of porcine ETEC strains the best studied family of fimbriae are the members of F4 adhesins, existing in at least three variants: ab, ac, ad. Active immunization against porcine PWC is difficult due to: i ETEC strains are only one of the essential predisposing factors, ii the success of vaccinal antigen uptake depends on the presence of enterocyte receptors for F4 adhesins, iii the intestinal immune system may react with tolerance or hypersensitivity to the same antigens depending on the dose and form of the vaccinal immunogen, and iv kinetics of the specific immune responses may be different in the case of F4 (earlier and the other ETEC adhesins, particularly F18 (later. The aim of this study was to test the effectiveness of a live attenuated F4ac+ non-ETEC vaccine against porcine PWC by analyzing quantitative differences in the small intestinal lymphoid and myeloid cell subsets of immunized (with or without levamisole given as an adjuvant vs control non-immunized pigs. Four week-old pigs were intragastrically immunized with a vaccine candidate F4ac+ non-ETEC strain 2407 at day 0, challenged 7 days later with a virulent F4ac+ strain ETEC 11-800/1/94, euthanatized at day 13 and sampled for immunohistology. Non-immunized pigs received saline at day 0 and were processed as the principals. Immuno-phenotypes of lymphoid and myeloid cell subsets were demonstrated within jejunal and ileal mucosa by immunohistochemical avidin-biotin complex method and corresponding morphometric data were analyzed using software program Lucia G for digital image analyses. Monoclonal antibodies reactive with surface molecules on porcine immune cells such as CD3, CD45RA, CD45RC, CD21 and SWC3 enabled clear insight into distribution patterns and amount of these cells within the gut-associated lymphoid tissues (GALT examined. The numbers of

  8. Nasal delivery of an adenovirus-based vaccine bypasses pre-existing immunity to the vaccine carrier and improves the immune response in mice.

    Directory of Open Access Journals (Sweden)

    Maria A Croyle

    Full Text Available Pre-existing immunity to human adenovirus serotype 5 (Ad5 is common in the general population. Bypassing pre-existing immunity could maximize Ad5 vaccine efficacy. Vaccination by the intramuscular (I.M., nasal (I.N. or oral (P.O. route with Ad5 expressing Ebola Zaire glycoprotein (Ad5-ZGP fully protected naïve mice against lethal challenge with Ebola. In the presence of pre-existing immunity, only mice vaccinated I.N. survived. The frequency of IFN-gamma+ CD8+ T cells was reduced by 80% and by 15% in animals vaccinated by the I.M. and P.O. routes respectively. Neutralizing antibodies could not be detected in serum from either treatment group. Pre-existing immunity did not compromise the frequency of IFN-gamma+ CD8+ T cells (3.9+/-1% naïve vs. 3.6+/-1% pre-existing immunity, PEI nor anti-Ebola neutralizing antibody (NAB, 40+/-10 reciprocal dilution, both groups. The number of INF-gamma+ CD8+ cells detected in bronchioalveolar lavage fluid (BAL after I.N. immunization was not compromised by pre-existing immunity to Ad5 (146+/-14, naïve vs. 120+/-16 SFC/million MNCs, PEI. However, pre-existing immunity reduced NAB levels in BAL by approximately 25% in this group. To improve the immune response after oral vaccination, the Ad5-based vaccine was PEGylated. Mice given the modified vaccine did not survive challenge and had reduced levels of IFN-gamma+ CD8+ T cells 10 days after administration (0.3+/-0.3% PEG vs. 1.7+/-0.5% unmodified. PEGylation did increase NAB levels 2-fold. These results provide some insight about the degree of T and B cell mediated immunity necessary for protection against Ebola virus and suggest that modification of the virus capsid can influence the type of immune response elicited by an Ad5-based vaccine.

  9. Immune-Specific Expression and Estrogenic Regulation of the Four Estrogen Receptor Isoforms in Female Rainbow Trout (Oncorhynchus mykiss

    Directory of Open Access Journals (Sweden)

    Ayako Casanova-Nakayama

    2018-03-01

    Full Text Available Genomic actions of estrogens in vertebrates are exerted via two intracellular estrogen receptor (ER subtypes, ERα and ERβ, which show cell- and tissue-specific expression profiles. Mammalian immune cells express ERs and are responsive to estrogens. More recently, evidence became available that ERs are also present in the immune organs and cells of teleost fish, suggesting that the immunomodulatory function of estrogens has been conserved throughout vertebrate evolution. For a better understanding of the sensitivity and the responsiveness of the fish immune system to estrogens, more insight is needed on the abundance of ERs in the fish immune system, the cellular ratios of the ER subtypes, and their autoregulation by estrogens. Consequently, the aims of the present study were (i to determine the absolute mRNA copy numbers of the four ER isoforms in the immune organs and cells of rainbow trout, Oncorhynchus mykiss, and to compare them to the hepatic ER numbers; (ii to analyse the ER mRNA isoform ratios in the immune system; and, (iii finally, to examine the alterations of immune ER mRNA expression levels in sexually immature trout exposed to 17β-estradiol (E2, as well as the alterations of immune ER mRNA expression levels in sexually mature trout during the reproductive cycle. All four ER isoforms were present in immune organs—head kidney, spleen-and immune cells from head kidney and blood of rainbow trout, but their mRNA levels were substantially lower than in the liver. The ER isoform ratios were tissue- and cell-specific, both within the immune system, but also between the immune system and the liver. Short-term administration of E2 to juvenile female trout altered the ER mRNA levels in the liver, but the ERs of the immune organs and cells were not responsive. Changes of ER gene transcript numbers in immune organs and cells occurred during the reproductive cycle of mature female trout, but the changes in the immune ER profiles differed

  10. GDSL lipases modulate immunity through lipid homeostasis in rice.

    Science.gov (United States)

    Gao, Mingjun; Yin, Xin; Yang, Weibing; Lam, Sin Man; Tong, Xiaohong; Liu, Jiyun; Wang, Xin; Li, Qun; Shui, Guanghou; He, Zuhua

    2017-11-01

    Lipids and lipid metabolites play important roles in plant-microbe interactions. Despite the extensive studies of lipases in lipid homeostasis and seed oil biosynthesis, the involvement of lipases in plant immunity remains largely unknown. In particular, GDSL esterases/lipases, characterized by the conserved GDSL motif, are a subfamily of lipolytic enzymes with broad substrate specificity. Here, we functionally identified two GDSL lipases, OsGLIP1 and OsGLIP2, in rice immune responses. Expression of OsGLIP1 and OsGLIP2 was suppressed by pathogen infection and salicylic acid (SA) treatment. OsGLIP1 was mainly expressed in leaf and leaf sheath, while OsGLIP2 showed high expression in elongating internodes. Biochemical assay demonstrated that OsGLIP1 and OsGLIP2 are functional lipases that could hydrolyze lipid substrates. Simultaneous down-regulation of OsGLIP1 and OsGLIP2 increased plant resistance to both bacterial and fungal pathogens, whereas disease resistance in OsGLIP1 and OsGLIP2 overexpression plants was significantly compromised, suggesting that both genes act as negative regulators of disease resistance. OsGLIP1 and OsGLIP2 proteins mainly localize to lipid droplets and the endoplasmic reticulum (ER) membrane. The proper cellular localization of OsGLIP proteins is indispensable for their functions in immunity. Comprehensive lipid profiling analysis indicated that the alteration of OsGLIP gene expression was associated with substantial changes of the levels of lipid species including monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG). We show that MGDG and DGDG feeding could attenuate disease resistance. Taken together, our study indicates that OsGLIP1 and OsGLIP2 negatively regulate rice defense by modulating lipid metabolism, thus providing new insights into the function of lipids in plant immunity.

  11. Applying insights from biofilm biology to drug development - can a new approach be developed?

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Ciofu, Oana; Molin, Søren

    2013-01-01

    Most of the research on bacterial pathogenesis has focused on acute infections, but much less is known about the pathogenesis of infections caused by bacteria that grow as aggregates in biofilms. These infections tend to be chronic as they resist innate and adaptive immune defence mechanisms...... and pathology, and discuss how a deep insight into the physical and biological characteristics of biofilms can inform therapeutic strategies and molecular targets for the development of anti-biofilm drugs....

  12. Both live and dead Enterococci activate Caenorhabditis elegans host defense via immune and stress pathways.

    Science.gov (United States)

    Yuen, Grace J; Ausubel, Frederick M

    2018-12-31

    The innate immune response of the nematode Caenorhabditis elegans has been extensively studied and a variety of Toll-independent immune response pathways have been identified. Surprisingly little, however, is known about how pathogens activate the C. elegans immune response. Enterococcus faecalis and Enterococcus faecium are closely related enterococcal species that exhibit significantly different levels of virulence in C. elegans infection models. Previous work has shown that activation of the C. elegans immune response by Pseudomonas aeruginosa involves P. aeruginosa-mediated host damage. Through ultrastructural imaging, we report that infection with either E. faecalis or E. faecium causes the worm intestine to become distended with proliferating bacteria in the absence of extensive morphological changes and apparent physical damage. Genetic analysis, whole-genome transcriptional profiling, and multiplexed gene expression analysis demonstrate that both enterococcal species, whether live or dead, induce a rapid and similar transcriptional defense response dependent upon previously described immune signaling pathways. The host response to E. faecium shows a stricter dependence upon stress response signaling pathways than the response to E. faecalis. Unexpectedly, we find that E. faecium is a C. elegans pathogen and that an active wild-type host defense response is required to keep an E. faecium infection at bay. These results provide new insights into the mechanisms underlying the C. elegans immune response to pathogen infection.

  13. Nutritional components regulate the gut immune system and its association with intestinal immune disease development.

    Science.gov (United States)

    Lamichhane, Aayam; Kiyono, Hiroshi; Kunisawa, Jun

    2013-12-01

    The gut is equipped with a unique immune system for maintaining immunological homeostasis, and its functional immune disruption can result in the development of immune diseases such as food allergy and intestinal inflammation. Accumulating evidence has demonstrated that nutritional components play an important role in the regulation of gut immune responses and also in the development of intestinal immune diseases. In this review, we focus on the immunological functions of lipids, vitamins, and nucleotides in the regulation of the intestinal immune system and as potential targets for the control of intestinal immune diseases. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  14. Immunization against Small Ruminant Lentiviruses

    Directory of Open Access Journals (Sweden)

    Beatriz Amorena

    2013-08-01

    Full Text Available Multisystemic disease caused by Small Ruminant Lentiviruses (SRLV in sheep and goats leads to production losses, to the detriment of animal health and welfare. This, together with the lack of treatments, has triggered interest in exploring different strategies of immunization to control the widely spread SRLV infection and, also, to provide a useful model for HIV vaccines. These strategies involve inactivated whole virus, subunit vaccines, DNA encoding viral proteins in the presence or absence of plasmids encoding immunological adjuvants and naturally or artificially attenuated viruses. In this review, we revisit, comprehensively, the immunization strategies against SRLV and analyze this double edged tool individually, as it may contribute to either controlling or enhancing virus replication and/or disease.

  15. Innate immune system and preeclampsia

    Directory of Open Access Journals (Sweden)

    Alejandra ePerez-Sepulveda

    2014-05-01

    Full Text Available Normal pregnancy is considered as a Th2 type immunological state that favors an immune-tolerance environment in order to prevent fetal rejection. PE has been classically described as a Th1/Th2 imbalance; however, the Th1/Th2 paradigm has proven insufficient to fully explain the functional and molecular changes observed during normal/pathological pregnancies. Recent studies have expanded the Th1/Th2 into a Th1⁄Th2⁄Th17 and regulatory T (Treg cells paradigm and where dendritic cells could have a crucial role. Recently, some evidence has emerged supporting the idea that mesenchymal stem cells might be part of the feto-maternal tolerance environment. This review will discuss the involvement of the innate immune system in the establishment of a physiological environment that favors pregnancy and possible alterations related to the development of preeclampsia.

  16. Dynamic expression of leukocyte innate immune genes in whole blood from horses with lipopolysaccharide-induced acute systemic inflammation

    DEFF Research Database (Denmark)

    Vinther, Anne Mette L.; Skovgaard, Kerstin; Heegaard, Peter M. H.

    2015-01-01

    Background: In horses, insights into the innate immune processes in acute systemic inflammation are limited even though these processes may be highly important for future diagnostic and therapeutic advances in high-mortality disease conditions as the systemic inflammatory response syndrome (SIRS......) and sepsis. Therefore, the aim of this study was to investigate the expression of 31 selected blood leukocyte immune genes in an equine model of acute systemic inflammation to identify significantly regulated genes and to describe their expression dynamics during a 24-h experimental period. Systemic...... expressions in blood leukocytes during equine acute LPS-induced systemic inflammation thoroughly characterized a highly regulated and dynamic innate immune response. These results provide new insights into the molecular mechanisms of equine systemic inflammation....

  17. The Immune Landscape of Cancer

    OpenAIRE

    Thorsson, Vésteinn; Gibbs, David L.; Brown, Scott D.; Wolf, Denise; Bortone, Dante S.; Ou Yang, Tai Hsien; Porta-Pardo, Eduard; Gao, Galen F.; Plaisier, Christopher L.; Eddy, James A.; Ziv, Elad; Culhane, Aedin C.; Paull, Evan O.; Sivakumar, I. K.Ashok; Gentles, Andrew J.

    2018-01-01

    We performed an extensive immunogenomic analysis of more than 10,000 tumors comprising 33 diverse cancer types by utilizing data compiled by TCGA. Across cancer types, we identified six immune subtypes—wound healing, IFN-γ dominant, inflammatory, lymphocyte depleted, immunologically quiet, and TGF-β dominant—characterized by differences in macrophage or lymphocyte signatures, Th1:Th2 cell ratio, extent of intratumoral heterogeneity, aneuploidy, extent of neoantigen load, overall cell prolifer...

  18. Immunizations Part II: Shingles Vaccine

    Centers for Disease Control (CDC) Podcasts

    2008-09-24

    This podcast discusses older adults and shingles, as well as the importance of getting the shingles vaccine. It is primarily targeted to public health and aging services professionals.  Created: 9/24/2008 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP) and National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 9/24/2008.

  19. The Epitranscriptome and Innate Immunity.

    Directory of Open Access Journals (Sweden)

    Mary A O'Connell

    2015-12-01

    Full Text Available Our knowledge of the variety and abundances of RNA base modifications is rapidly increasing. Modified bases have critical roles in tRNAs, rRNAs, translation, splicing, RNA interference, and other RNA processes, and are now increasingly detected in all types of transcripts. Can new biological principles associated with this diversity of RNA modifications, particularly in mRNAs and long non-coding RNAs, be identified? This review will explore this question by focusing primarily on adenosine to inosine (A-to-I RNA editing by the adenine deaminase acting on RNA (ADAR enzymes that have been intensively studied for the past 20 years and have a wide range of effects. Over 100 million adenosine to inosine editing sites have been identified in the human transcriptome, mostly in embedded Alu sequences that form potentially innate immune-stimulating dsRNA hairpins in transcripts. Recent research has demonstrated that inosine in the epitranscriptome and ADAR1 protein establish innate immune tolerance for host dsRNA formed by endogenous sequences. Innate immune sensors that detect viral nucleic acids are among the readers of epitranscriptome RNA modifications, though this does preclude a wide range of other modification effects.

  20. The commensal microbiota drives immune homeostasis

    Directory of Open Access Journals (Sweden)

    Marie-Claire eArrieta

    2012-03-01

    Full Text Available For millions of years, microbes have coexisted with eukaryotic cells at the mucosal surfaces of vertebrates in a complex, yet usually harmonious symbiosis. An ever-expanding number of reports describe how eliminating or shifting the intestinal microbiota has profound effects on the development and functionality of the mucosal and systemic immune systems. Here, we examine some of the mechanisms by which bacterial signals affect immune homeostasis. Focusing on the strategies that microbes use to keep our immune system healthy, as opposed to trying to correct the immune imbalances caused by dysbiosis, may prove to be a more astute and efficient way of treating immune-mediated disease.

  1. Diversity and dialogue in immunity to helminths.

    Science.gov (United States)

    Allen, Judith E; Maizels, Rick M

    2011-06-01

    The vertebrate immune system has evolved in concert with a broad range of infectious agents, including ubiquitous helminth (worm) parasites. The constant pressure of helminth infections has been a powerful force in shaping not only how immunity is initiated and maintained, but also how the body self-regulates and controls untoward immune responses to minimize overall harm. In this Review, we discuss recent advances in defining the immune cell types and molecules that are mobilized in response to helminth infection. Finally, we more broadly consider how these immunological players are blended and regulated in order to accommodate persistent infection or to mount a vigorous protective response and achieve sterile immunity.

  2. Mechanisms regulating skin immunity and inflammation.

    Science.gov (United States)

    Pasparakis, Manolis; Haase, Ingo; Nestle, Frank O

    2014-05-01

    Immune responses in the skin are important for host defence against pathogenic microorganisms. However, dysregulated immune reactions can cause chronic inflammatory skin diseases. Extensive crosstalk between the different cellular and microbial components of the skin regulates local immune responses to ensure efficient host defence, to maintain and restore homeostasis, and to prevent chronic disease. In this Review, we discuss recent findings that highlight the complex regulatory networks that control skin immunity, and we provide new paradigms for the mechanisms that regulate skin immune responses in host defence and in chronic inflammation.

  3. Immunity to Fasciola hepatica in the rat

    International Nuclear Information System (INIS)

    Armour, J.; Dargie, J.D.

    1974-01-01

    Experiments were carried out which demonstrated an acquired immunity to Fasciola hapatica in the rat. It was shown that this immunity could be transferred to recipients using either lymphoid cells or serum from infected donor rats. The extent of the protection obtained by cells appeared to be related to the quantity and persistence of the antigenic stimulus in the donor. Likewise, the degree of immunity conferred by immune serum was dependent upon the volume transferred. The significance of these results in relation to the mechanism of immunity to fascioliasis is discussed

  4. 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....

  5. Comparative Analysis of Bat Genomes Provides Insight into the Evolution of Flight and Immunity

    DEFF Research Database (Denmark)

    Zhang, Guojie; Cowled, Christopher; Shi, Zhengli

    2013-01-01

    Bats are the only mammals capable of sustained flight and are notorious reservoir hosts for some of the world's most highly pathogenic viruses, including Nipah, Hendra, Ebola, and severe acute respiratory syndrome (SARS). To identify genetic changes associated with the development of bat-specific......Bats are the only mammals capable of sustained flight and are notorious reservoir hosts for some of the world's most highly pathogenic viruses, including Nipah, Hendra, Ebola, and severe acute respiratory syndrome (SARS). To identify genetic changes associated with the development of bat...

  6. Microglia - insights into immune system structure, function, and reactivity in the central nervous system

    DEFF Research Database (Denmark)

    Wirenfeldt, Martin; Babcock, Alicia A; Vinters, Harry V

    2011-01-01

    Microglia are essential cellular components of a well-functioning central nervous system (CNS). The development and establishment of the microglial population differs from the other major cell populations in the CNS i.e. neurons and macroglia (astrocytes and oligodendrocytes). This different onto...

  7. Shifting of Immune Responsiveness to House Dust Mite by Influenza A Infection: Genomic Insights

    KAUST Repository

    Al-Garawi, A.; Husain, M.; Ilieva, D.; Humbles, A. A.; Kolbeck, R.; Stampfli, M. R.; O'Byrne, P. M.; Coyle, A. J.; Jordana, M.

    2011-01-01

    significantly increased expression of serum amyloid A (Saa3) and serine protease inhibitor 3n (Serpina3n). This study showed that influenza infection markedly increased the expression of multiple gene classes capable of sensing allergens and amplifying

  8. Study Provides Insights into Diagnosis, Treatment of Rare Immune Disease: Autoimmmune Lymphoproliferative Syndrome ...

    Science.gov (United States)

    ... in the blood. While DNT cells are a hallmark of ALPS, scientists do not fully understand their ... higher-than-average risk of developing lymphoma, or cancer of the lymph nodes. In the current study, ...

  9. Characterization of the immune response against Testudinid herpesvirus 3: new insight

    Directory of Open Access Journals (Sweden)

    Marco Tecilla

    2017-05-01

    Full Text Available Testudinid herpesvirus 3 (TeHV3 is one of the most lethal viral agents in tortoises worldwide. Although TeHV3 have been extensively studied, only little information is available about host-pathogen interaction. TeHV3 infections in different species of the genus Testudo correlate with various lesions profiles, disease severity and clinical outcome, suggesting the existence of a complex host-pathogen interaction. This might reflect a possible viral-host coevolution (Origgi, 2012. To study the host-pathogen interaction, we previously screened 5.000 clones from a bacteriophage library obtained from the TeHV3 genomic DNA using Testudo graeca seropositive sera. Of the six detected positive clones, only one was confirmed by F.A.C.S. Selected clone was determined to be a concatamer of different TeHV3 genomic fragments including the partial sequence of TE17, UL15, Major capsid protein (MCP, and Glycoprotein B (gB genes. After complete sequencing of the selected clone, the MCP and the gB were antisenses compared to the phagemid promoter. In order to assess which of the gene fragments among TE17 and UL15 was encoding for the antigenic determinant that was recognized by the anti-TeHV3 tortoise sera, distinct approaches were followed. TE-17 and UL15 fragments were knock out from the original phagemid using the following approaches: a directed-site mutagenesis, b molecular cloning, and c restriction enzymes cloning. All the modified constructs were cloned in two different E. coli cloning vectors (D5α and XL 1-Blue. Transformation of competent cells with the constructs described above did not yield any viable bacteria. Among the different aspects might have influenced transformation success rate, construct size was probably the most relevant (about 9Kb. Furthermore, we could not entirely exclude that genomic DNA editing might have induced mutations in the construct sequence causing toxic effects on the host bacterial cell. Cloning of TE-17 and UL15 gene fragments into different prokaryotic expression vectors is currently under way.

  10. Provider insight on surmounting specialty practice challenges to improve Tdap immunization rates among pregnant women

    Directory of Open Access Journals (Sweden)

    Arpita Mehrotra

    2018-05-01

    Conclusions: Findings indicate while most ob-gyns recognize the benefits of Tdap and recommend vaccination during pregnancy, barriers such as insurance reimbursement and financial concerns for the practice can outweigh the perceived benefits. This resulted in some ob-gyns reporting choosing not to stock and administer the vaccine in their practice. Recommendations to address these concerns include 1 structural support for Tdap vaccine administration in ob-gyns practices; 2 Continuing medical education-equivalent educational interventions that address management techniques, vaccine coding, and other relevant information; and 3 interventions to assist physicians in communicating the importance of Tdap vaccination during pregnancy.

  11. Immunomodulator, immunosuppression of radiation and immune reconstruction

    International Nuclear Information System (INIS)

    Mao Jianping; Fang Jing; Zhou Ying; Cui Yufang; Jiang Zhujun; Du Li; Ma Qiong

    2010-01-01

    There is a refined and complicated regulatory network between immune cells, and between immune cells and secretory factors. The immune system is kept in a homeostasis and equilibrium by positive activation and negative inhibition. In recent years, the mechanisms of immunosuppression in depth for successful allograft transplantation were studied, and many immunosuppressants and immunosuppressive drugs have been developed for clinical use. Most of them are targeting T cell receptors and three kinds of singnal pathways. The receptors of the immunosuppression were either found highly expressed in immune cells after irradiation. To relieve the suppression by regulating the receptors could help the immune reconstruction out of radiation damage. Many new immunoenhancers have been discovered to improve the immune system function for radiation by Toll-like receptors. The search for new immunoenhancers and agents for relieving immunosuppression is of great importance to immune construction for radiation sickness. (authors)

  12. Innate immunity in vertebrates: an overview.

    Science.gov (United States)

    Riera Romo, Mario; Pérez-Martínez, Dayana; Castillo Ferrer, Camila

    2016-06-01

    Innate immunity is a semi-specific and widely distributed form of immunity, which represents the first line of defence against pathogens. This type of immunity is critical to maintain homeostasis and prevent microbe invasion, eliminating a great variety of pathogens and contributing with the activation of the adaptive immune response. The components of innate immunity include physical and chemical barriers, humoral and cell-mediated components, which are present in all jawed vertebrates. The understanding of innate defence mechanisms in non-mammalian vertebrates is the key to comprehend the general picture of vertebrate innate immunity and its evolutionary history. This is also essential for the identification of new molecules with applications in immunopharmacology and immunotherapy. In this review, we describe and discuss the main elements of vertebrate innate immunity, presenting core findings in this field and identifying areas that need further investigation. © 2016 John Wiley & Sons Ltd.

  13. Evaluation of lung immunity in chimpanzees

    International Nuclear Information System (INIS)

    Bice, D.E.; Harris, D.L.; Muggenburg, B.A.; Bowen, J.A.

    1980-01-01

    The effects of inhaled pollutants on the immune defenses in the lung can be studied in several animal species. To assure that the data obtained can be extrapolated to man, it is essential that the development of lung immunity is similar in the experimental animal selected and in humans. Because of the similarity of immune responses in chimpanzees and in humans, the development of immunity in the chimpanzee after lung immunization was evaluated. The results from the chimpanzees were qualitatively the same as those from previous studies in which single lung lobes of dogs were immunized. It was concluded that immunotoxicology data obtained in dogs can be used to estimate the effects of inhaled pollutants on the immune defense mechanism in the human lung

  14. Immune Regulation by Self-Recognition

    DEFF Research Database (Denmark)

    Andersen, Mads Hald

    2015-01-01

    Circulating T cells that specifically target normal self-proteins expressed by regulatory immune cells were first described in patients with cancer, but can also be detected in healthy individuals. The adaptive immune system is distinguished for its ability to differentiate between self......-antigens and foreign antigens. Thus, it was remarkable to discover T cells that apparently lacked tolerance to important self-proteins, eg, IDO, PD-L1, and FoxP3, expressed in regulatory immune cells. The ability of self-reactive T cells to react to and eliminate regulatory immune cells can influence general immune...... reactions. This suggests that they may be involved in immune homeostasis. It is here proposed that these T cells should be termed antiregulatory T cells (anti-Tregs). The role of anti-Tregs in immune-regulatory networks may be diverse. For example, pro-inflammatory self-reactive T cells that react...

  15. Reinforcement Learning Based Artificial Immune Classifier

    Directory of Open Access Journals (Sweden)

    Mehmet Karakose

    2013-01-01

    Full Text Available One of the widely used methods for classification that is a decision-making process is artificial immune systems. Artificial immune systems based on natural immunity system can be successfully applied for classification, optimization, recognition, and learning in real-world problems. In this study, a reinforcement learning based artificial immune classifier is proposed as a new approach. This approach uses reinforcement learning to find better antibody with immune operators. The proposed new approach has many contributions according to other methods in the literature such as effectiveness, less memory cell, high accuracy, speed, and data adaptability. The performance of the proposed approach is demonstrated by simulation and experimental results using real data in Matlab and FPGA. Some benchmark data and remote image data are used for experimental results. The comparative results with supervised/unsupervised based artificial immune system, negative selection classifier, and resource limited artificial immune classifier are given to demonstrate the effectiveness of the proposed new method.

  16. Vaccination, herd behavior, and herd immunity.

    Science.gov (United States)

    Cohen, Matan J; Brezis, Mayer; Block, Colin; Diederich, Adele; Chinitz, David

    2013-11-01

    During the 2009 outbreak of novel influenza AH1N1, insufficient data were available to adequately inform decision makers about benefits and risks of vaccination and disease. We hypothesized that individuals would opt to mimic their peers, having no better decision anchor. We used Game Theory, decision analysis, and transmission models to simulate the impact of subjective risks and preference estimates on vaccination behavior. We asked 95 students to provide estimates of risk and health state valuations with regard to AH1N1 infection, complications, and expectations of vaccine benefits and risks. These estimates were included in a sequential chain of models: a dynamic epidemic model, a decision tree, and a population-level model. Additionally, participants' intentions to vaccinate or not at varying vaccination rates were documented. The model showed that at low vaccination rates, vaccination dominated. When vaccination rates increased above 78%, nonvaccination was the dominant strategy. We found that vaccination intentions did not correspond to the shift in strategy dominance and segregated to 3 types of intentions: regardless of what others do 29/95 (31%) intended to vaccinate while 27/95 (28%) did not; among 39 of 95 (41%) intention was positively associated with putative vaccination rates. Some people conform to the majority's choice, either shifting epidemic dynamics toward herd immunity or, conversely, limiting societal goals. Policy leaders should use models carefully, noting their limitations and theoretical assumptions. Behavior drivers were not explicitly explored in this study, and the discrepant results beg further investigation. Models including real subjective perceptions with empiric or subjective probabilities can provide insight into deviations from expected rational behavior and suggest interventions in order to provide better population outcomes.

  17. Evaluation of Mucosal and Systemic Immune Responses Elicited by GPI-0100-Adjuvanted Influenza Vaccine Delivered by Different Immunization Strategies

    NARCIS (Netherlands)

    Liu, Heng; Patil, Harshad P.; de Vries-Idema, Jacqueline; Wilschut, Jan; Huckriede, Anke

    2013-01-01

    Vaccines for protection against respiratory infections should optimally induce a mucosal immune response in the respiratory tract in addition to a systemic immune response. However, current parenteral immunization modalities generally fail to induce mucosal immunity, while mucosal vaccine delivery

  18. Alveolar macrophages and type I IFN in airway homeostasis and immunity.

    Science.gov (United States)

    Divangahi, Maziar; King, Irah L; Pernet, Erwan

    2015-05-01

    Globally, respiratory infections cause more than 4 million deaths per year, with influenza and tuberculosis (TB) in particular being major causes of mortality and morbidity. Although immune cell activation is critical for killing respiratory pathogens, this response must be tightly regulated to effectively control and eliminate invading microorganisms while minimizing immunopathology and maintaining pulmonary function. The distinct microenvironment of the lung is constantly patrolled by alveolar macrophages (Mφ), which are essential for tissue homeostasis, early pathogen recognition, initiation of the local immune response, and resolution of inflammation. Here, we focus on recent advances that have provided insight into the relation between pulmonary Mφ, type I interferon (IFN) signaling, and the delicate balance between protective and pathological immune responses in the lung. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. The Multibiome: The Intestinal Ecosystem's Influence on Immune Homeostasis, Health, and Disease.

    Science.gov (United States)

    Filyk, Heather A; Osborne, Lisa C

    2016-11-01

    Mammalian evolution has occurred in the presence of mutualistic, commensal, and pathogenic micro- and macro-organisms for millennia. The presence of these organisms during mammalian evolution has allowed for intimate crosstalk between these colonizing species and the host immune system. In this review, we introduce the concept of the 'multibiome' to holistically refer to the biodiverse collection of bacteria, viruses, fungi and multicellular helminthic worms colonizing the mammalian intestine. Furthermore, we discuss new insights into multibiome-host interactions in the context of host-protective immunity and immune-mediated diseases, including inflammatory bowel disease and multiple sclerosis. Finally, we provide reasons to account for the multibiome in experimental design, analysis and in therapeutic applications. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  20. cGAS/STING Pathway in Cancer: Jekyll and Hyde Story of Cancer Immune Response

    Directory of Open Access Journals (Sweden)

    Debojit Bose

    2017-11-01

    Full Text Available The last two decades have witnessed enormous growth in the field of cancer immunity. Mechanistic insights of cancer immunoediting have not only enhanced our understanding but also paved the way to target and/or harness the innate immune system to combat cancer, called cancer immunotherapy. Cyclic GMP-AMP synthase (cGAS/Stimulator of interferon genes(STING pathway has recently emerged as nodal player in cancer immunity and is currently being explored as potential therapeutic target. Although therapeutic activation of this pathway has shown promising anti-tumor effects in vivo, evidence also indicates the role of this pathway in inflammation mediated carcinogenesis. This review highlights our current understanding of cGAS/STING pathway in cancer, its therapeutic targeting and potential alternate approaches to target this pathway. Optimal therapeutic targeting and artificial tunability of this pathway still demand in depth understanding of cGAS/STING pathway regulation and homeostasis.

  1. cGAS/STING Pathway in Cancer: Jekyll and Hyde Story of Cancer Immune Response.

    Science.gov (United States)

    Bose, Debojit

    2017-11-18

    The last two decades have witnessed enormous growth in the field of cancer immunity. Mechanistic insights of cancer immunoediting have not only enhanced our understanding but also paved the way to target and/or harness the innate immune system to combat cancer, called cancer immunotherapy. Cyclic GMP-AMP synthase (cGAS)/Stimulator of interferon genes(STING) pathway has recently emerged as nodal player in cancer immunity and is currently being explored as potential therapeutic target. Although therapeutic activation of this pathway has shown promising anti-tumor effects in vivo, evidence also indicates the role of this pathway in inflammation mediated carcinogenesis. This review highlights our current understanding of cGAS/STING pathway in cancer, its therapeutic targeting and potential alternate approaches to target this pathway. Optimal therapeutic targeting and artificial tunability of this pathway still demand in depth understanding of cGAS/STING pathway regulation and homeostasis.

  2. Sleeping to fuel the immune system: mammalian sleep and resistance to parasites

    Directory of Open Access Journals (Sweden)

    Opp Mark R

    2009-01-01

    Full Text Available Abstract Sleep is an enigma. Why animals forgo eating and reproducing, while potentially increasing their risk of predation remains unknown. Although some may question whether all animals sleep, it is clear that all living organisms possess defenses against attack by pathogens. Immune responses of humans and animals are impaired by sleep loss, and responses to immune challenge include altered sleep. Thus, sleep is hypothesized to be a component of the acute phase response to infection and to function in host defense. Examining phylogenetic relationships among sleep parameters, components of the mammalian immune system and resistance to infection may provide insight into the evolution of sleep and lead to a greater appreciation for the role of sleep in host defense.

  3. Immunizations

    Science.gov (United States)

    ... vaccine leaves a person unprotected and still at risk for getting a disease. Other vaccinations require a booster shot every few years to ... who get diseases like mumps may be at risk for side effects of the illness, such ... children). Vaccinations are about protecting you in the future, not ...

  4. Location of tumor affects local and distant immune cell type and number.

    Science.gov (United States)

    Hensel, Jonathan A; Khattar, Vinayak; Ashton, Reading; Lee, Carnellia; Siegal, Gene P; Ponnazhagan, Selvarangan

    2017-03-01

    Tumors comprise heterogeneous populations of cells, including immune infiltrates that polarize during growth and metastasis. Our preclinical studies on breast cancer (BCa) identified functional differences in myeloid-derived suppressor cells based on tumor microenvironment (TME), prompting variations in host immune response to tumor growth, and dissemination based on tissue type. In order to understand if such variations existed among other immune cells, and if such alteration occurs in response to tumor growth at the primary site or due to bone dissemination, we characterized immune cells, examining localized growth and in the tibia. In addition, immune cells from the spleen were examined from animals of both tumor locations by flow cytometry. The study demonstrates that location of tumor, and not simply the tumor itself, has a definitive role in regulating immune effectors. Among all immune cells characterized, macrophages were decreased and myeloid dendritic cell were increased in both tumor locations. This difference was more evident in subcutaneous tumors. Additionally, spleens from mice with subcutaneous tumors contained greater increases in both macrophages and myeloid dendritic cells than in mice with bone tumors. Furthermore, in subcutaneous tumors there was an increase in CD4 + and CD8 + T-cell numbers, which was also observed in their spleens. These data indicate that alterations in tumor-reactive immune cells are more pronounced at the primary site, and exert a similar change at the major secondary lymphoid organ than in the bone TME. These findings could provide translational insight into designing therapeutic strategies that account for location of metastatic foci.

  5. The immune gene repertoire of an important viral reservoir, the Australian black flying fox

    Directory of Open Access Journals (Sweden)

    Papenfuss Anthony T

    2012-06-01

    Full Text Available Abstract Background Bats are the natural reservoir host for a range of emerging and re-emerging viruses, including SARS-like coronaviruses, Ebola viruses, henipaviruses and Rabies viruses. However, the mechanisms responsible for the control of viral replication in bats are not understood and there is little information available on any aspect of antiviral immunity in bats. Massively parallel sequencing of the bat transcriptome provides the opportunity for rapid gene discovery. Although the genomes of one megabat and one microbat have now been sequenced to low coverage, no transcriptomic datasets have been reported from any bat species. In this study, we describe the immune transcriptome of the Australian flying fox, Pteropus alecto, providing an important resource for identification of genes involved in a range of activities including antiviral immunity. Results Towards understanding the adaptations that have allowed bats to coexist with viruses, we have de novo assembled transcriptome sequence from immune tissues and stimulated cells from P. alecto. We identified about 18,600 genes involved in a broad range of activities with the most highly expressed genes involved in cell growth and maintenance, enzyme activity, cellular components and metabolism and energy pathways. 3.5% of the bat transcribed genes corresponded to immune genes and a total of about 500 immune genes were identified, providing an overview of both innate and adaptive immunity. A small proportion of transcripts found no match with annotated sequences in any of the public databases and may represent bat-specific transcripts. Conclusions This study represents the first reported bat transcriptome dataset and provides a survey of expressed bat genes that complement existing bat genomic data. In addition, these data provide insight into genes relevant to the antiviral responses of bats, and form a basis for examining the roles of these molecules in immune response to viral infection.

  6. Insight in psychosis : Metacognitive processes and treatment

    NARCIS (Netherlands)

    de Vos, Annerieke

    2016-01-01

    Insight is impaired in 50- 80% of the patients with schizophrenia. Annerieke de Vos working at GGZ Drenthe and the University Medical Hospital Groningen, aimed to elucidate which processes underlie impaired insight and tried to improve insight in patients by targeting these processes. On September

  7. Quantifying the Qualitative: Measuring the Insight Experience

    Science.gov (United States)

    Jarman, Matthew S.

    2014-01-01

    No scales currently exist that measure variability in the insight experience. Two scales were created to measure two factors hypothesized to be key drivers of the insight experience: insight radicality (i.e., perceived deviation between previous and new problem representations) and restructuring experience (i.e., the subjective experience of the…

  8. CRISPR-Cas adaptation: insights into the mechanism of action.

    Science.gov (United States)

    Amitai, Gil; Sorek, Rotem

    2016-02-01

    Since the first demonstration that CRISPR-Cas systems provide bacteria and archaea with adaptive immunity against phages and plasmids, numerous studies have yielded key insights into the molecular mechanisms governing how these systems attack and degrade foreign DNA. However, the molecular mechanisms underlying the adaptation stage, in which new immunological memory is formed, have until recently represented a major unresolved question. In this Progress article, we discuss recent discoveries that have shown both how foreign DNA is identified by the CRISPR-Cas adaptation machinery and the molecular basis for its integration into the chromosome to form an immunological memory. Furthermore, we describe the roles of each of the specific CRISPR-Cas components that are involved in memory formation, and consider current models for their evolutionary origin.

  9. Microbial genome-enabled insights into plant-microorganism interactions.

    Science.gov (United States)

    Guttman, David S; McHardy, Alice C; Schulze-Lefert, Paul

    2014-12-01

    Advances in genome-based studies on plant-associated microorganisms have transformed our understanding of many plant pathogens and are beginning to greatly widen our knowledge of plant interactions with mutualistic and commensal microorganisms. Pathogenomics has revealed how pathogenic microorganisms adapt to particular hosts, subvert innate immune responses and change host range, as well as how new pathogen species emerge. Similarly, culture-independent community profiling methods, coupled with metagenomic and metatranscriptomic studies, have provided the first insights into the emerging field of research on plant-associated microbial communities. Together, these approaches have the potential to bridge the gap between plant microbial ecology and plant pathology, which have traditionally been two distinct research fields.

  10. Delbruck Prize Award: Insights into HIV Dynamics and Cure

    Science.gov (United States)

    Perelson, Alan S.

    A large effort is being made to find a means to cure HIV infection. I will present a dynamical model of a phenomenon called post-treatment control (PTC) or functional cure of HIV-infection in which some patients treated with suppressive antiviral therapy have been taken off of therapy and then spontaneously control HIV infection. The model relies on an immune response and bistability to explain PTC. I will then generalize the model to explicitly include immunotherapy with monoclonal antibodies approved for use in cancer to show that one can induce PTC with a limited number of antibody infusions and compare model predictions with experiments in SIV infected macaques given immunotherapy. Lastly, I will argue that quantitative insights derived from models of HIV infection have and will continue to play an important role in medicine.

  11. Breast Cancer Vaccines: New Insights

    Directory of Open Access Journals (Sweden)

    Rosaria Benedetti

    2017-10-01

    Full Text Available Breast cancer (BC is a persistent global challenge for its high frequency in women (although it seldom occurs in men, due to the large diffusion of risk factors and gene mutations, and for its peculiar biology and microenvironment. To date, BC can benefit from different therapeutic strategies involving surgery, ablation, chemotherapy, radiotherapy, and more specific approaches such as hormone therapy and the administration of various substances impairing cancer growth, aggressivity, and recurrence with different modalities. Despite these relatively wide chances, also used in combinatory protocols, relevant mortality and relapse rates, often associated with resistant phenotypes, stress the need for a personalized-medicine based on prompting the patient’s immune system (IS against cancer cells. BC immunogenicity was latterly proven, so the whole immunotherapy field for BC is still at a very early stage. This immunotherapeutic approach exploits both the high specificity of adaptive immune response and the immunological memory. This review is focused on some of the majorly relevant BC vaccines available (NeuVax, AVX901, and INO-1400, providing a description of the more promising clinical trials. The efficacy of cancer vaccines highly depends on the patient’s IS, and a wide optimization is needed in terms of targets’ selection, drug design and combinations, dose finding, protocol structuring, and patients’ recruitment; moreover, new standards are being discussed for the outcome evaluation. However, early-phases excellent results suggest that the manipulation of the IS via specific vaccines is a highly attractive approach for BC.

  12. Immune defense and host life history.

    Science.gov (United States)

    Zuk, Marlene; Stoehr, Andrew M

    2002-10-01

    Recent interest has focused on immune response in an evolutionary context, with particular attention to disease resistance as a life-history trait, subject to trade-offs against other traits such as reproductive effort. Immune defense has several characteristics that complicate this approach, however; for example, because of the risk of autoimmunity, optimal immune defense is not necessarily maximum immune defense. Two important types of cost associated with immunity in the context of life history are resource costs, those related to the allocation of essential but limited resources, such as energy or nutrients, and option costs, those paid not in the currency of resources but in functional or structural components of the organism. Resource and option costs are likely to apply to different aspects of resistance. Recent investigations into possible trade-offs between reproductive effort, particularly sexual displays, and immunity have suggested interesting functional links between the two. Although all organisms balance the costs of immune defense against the requirements of reproduction, this balance works out differently for males than it does for females, creating sex differences in immune response that in turn are related to ecological factors such as the mating system. We conclude that immune response is indeed costly and that future work would do well to include invertebrates, which have sometimes been neglected in studies of the ecology of immune defense.

  13. Local and systemic tumor immune dynamics

    Science.gov (United States)

    Enderling, Heiko

    Tumor-associated antigens, stress proteins, and danger-associated molecular patterns are endogenous immune adjuvants that can both initiate and continually stimulate an immune response against a tumor. In retaliation, tumors can hijack intrinsic immune regulatory programs that are intended to prevent autoimmune disease, thereby facilitating continued growth despite the activated antitumor immune response. In metastatic disease, this ongoing tumor-immune battle occurs at each site. Adding an additional layer of complexity, T cells activated at one tumor site can cycle through the blood circulation system and extravasate in a different anatomic location to surveil a distant metastasis. We propose a mathematical modeling framework that incorporates the trafficking of activated T cells between metastatic sites. We extend an ordinary differential equation model of tumor-immune system interactions to multiple metastatic sites. Immune cells are activated in response to tumor burden and tumor cell death, and are recruited from tumor sites elsewhere in the body. A model of T cell trafficking throughout the circulatory system can inform the tumor-immune interaction model about the systemic distribution and arrival of T cells at specific tumor sites. Model simulations suggest that metastases not only contribute to immune surveillance, but also that this contribution varies between metastatic sites. Such information may ultimately help harness the synergy of focal therapy with the immune system to control metastatic disease.

  14. NEUROTRANSMITTERS AND IMMUNITY: 1. DOPAMINE

    Directory of Open Access Journals (Sweden)

    Lucian Hritcu

    2007-08-01

    Full Text Available Dopamine is one of the principal neurotransmitters in the central nervous system (CNC, and its neuronal pathways are involved in several key functions such as behavior (Hefco et al., 2003a,b, control of movement, endocrine regulation, immune response (Fiserova et al., 2002; Levite et al., 2001, Hritcu et al., 2006a,b,c, and cardiovascular function. Dopamine has at least five G-protein, coupled receptor subtypes, D1-D5, each arising from a different gene (Sibley et al., 1993. Traditionally, these receptors have been classified into D1-like (the D1 and D5 and D2-like (D2, D3 and D4 receptors subtypes, primarily according to their ability to stimulate or inhibit adenylate cyclase, respectively, and to their pharmacological characteristics (Seeman et al., 1993. Receptors for dopamine (particularly of D2 subclass are the primary therapeutic target in a number of neuropathological disorders including schizophrenia, Parkinson’s disease and Huntington’s chorea (Seeman et al., 1987. Neither dopamine by itself, nor dopaminergic agonists by themselves, has been shown to activate T cell function. Nevertheless, lymphocytes are most probably exposed to dopamine since the primary and secondary lymphoid organs of various mammals are markedly innervated, and contain nerve fibers which stain for tyrosine hydroxylase (Weihe et al., 1991, the enzyme responsible for dopamine synthesis. Moreover, cathecolamines and their metabolites are present in single lymphocytes and in extracts of T and B cell clones, and pharmacological inhibition of tyrosine hydroxylase reduces catecholamine levels, suggesting catecholamine synthesis by lymphocytes (Bergquist et al., 1994. The existence of putative dopamine receptors of D2, D3, D4 and D5 subtypes on immune cells has been proposed of several authors, primarily on the basis of dopaminergic ligand binding assays and specific mRNA expression as monitored by reverse transcription-PCR. Several experiments evoked the idea of a

  15. Investing in Immunity: Prepandemic Immunization to Combat Future Influenza Pandemics.

    Science.gov (United States)

    Goodman, Jesse L

    2016-02-15

    We are unlikely, with current technologies, to have sufficient pandemic influenza vaccine ready in time to impact the first wave of the next pandemic. Emerging data show that prior immunization with an immunologically distinct hemagglutinin of the same subtype offers the potential to "prime" recipients for rapid protection with a booster dose, years later, of a vaccine then manufactured to match the pandemic strain. This article proposes making prepandemic priming vaccine(s) available for voluntary use, particularly to those at high risk of early occupational exposure, such as first responders and healthcare workers, and to others maintaining critical infrastructure. In addition to providing faster protection and potentially reducing social disruption, being able, early in a pandemic, to immunize those who had received prepandemic vaccine with one dose of the pandemic vaccine, rather than the 2 doses typically required, would reduce the total doses of pandemic vaccine then needed, extending vaccine supplies. Published by Oxford University Press for the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  16. Vitamin C and Immune Function

    Directory of Open Access Journals (Sweden)

    Anitra C. Carr

    2017-11-01

    Full Text Available Vitamin C is an essential micronutrient for humans, with pleiotropic functions related to its ability to donate electrons. It is a potent antioxidant and a cofactor for a family of biosynthetic and gene regulatory enzymes. Vitamin C contributes to immune defense by supporting various cellular functions of both the innate and adaptive immune system. Vitamin C supports epithelial barrier function against pathogens and promotes the oxidant scavenging activity of the skin, thereby potentially protecting against environmental oxidative stress. Vitamin C accumulates in phagocytic cells, such as neutrophils, and can enhance chemotaxis, phagocytosis, generation of reactive oxygen species, and ultimately microbial killing. It is also needed for apoptosis and clearance of the spent neutrophils from sites of infection by macrophages, thereby decreasing necrosis/NETosis and potential tissue damage. The role of vitamin C in lymphocytes is less clear, but it has been shown to enhance differentiation and proliferation of B- and T-cells, likely due to its gene regulating effects. Vitamin C deficiency results in impaired immunity and higher susceptibility to infections. In turn, infections significantly impact on vitamin C levels due to enhanced inflammation and metabolic requirements. Furthermore, supplementation with vitamin C appears to be able to both prevent and treat respiratory and systemic infections. Prophylactic prevention of infection requires dietary vitamin C intakes that provide at least adequate, if not saturating plasma levels (i.e., 100–200 mg/day, which optimize cell and tissue levels. In contrast, treatment of established infections requires significantly higher (gram doses of the vitamin to compensate for the increased inflammatory response and metabolic demand.

  17. Adaptive immunity in autoimmune hepatitis.

    Science.gov (United States)

    Longhi, Maria Serena; Ma, Yun; Mieli-Vergani, Giorgina; Vergani, Diego

    2010-01-01

    The histological lesion of interface hepatitis, with its dense portal cell infiltrate consisting of lymphocytes, monocytes/macrophages and plasma cells, was the first to suggest an autoaggressive cellular immune attack in the pathogenesis of autoimmune hepatitis (AIH). Immunohistochemical studies, focused on the phenotype of inflammatory cells infiltrating the liver parenchyma, have shown a predominance of alphabeta-T cells. Amongst these cells, the majority have been CD4 helper/inducers, while a sizeable minority have consisted of CD8 cytotoxic/suppressors. Lymphocytes on non-T cell lineage included natural killer cells, monocytes/macrophages and B lymphocytes. For autoimmunity to arise, the self-antigenic peptide, embraced by an human leukocyte antigen (HLA) class II molecule, must be presented to an uncommitted T helper (T(H)0) lymphocyte by professional antigen-presenting cells. Once activated and according to the presence in the milieu of interleukin 12 (IL-12) or IL-4, T(H)0 lymphocytes can differentiate into T(H)1 cells, which are pivotal to macrophage activation; enhance HLA class I expression, rendering liver cells vulnerable to CD8 T-cell attack; and induce HLA class II expression on hepatocytes; or they can differentiate into T(H)2 cells, which produce IL-4, IL-10 and IL-13, cytokines favouring autoantibody production by B lymphocytes. Autoantigen recognition is tightly controlled by regulatory mechanisms, such as those exerted by CD4+CD25(high) regulatory T cells. Numerical and functional regulatory T cell impairment characterises AIH and permits the perpetuation of effector immune responses with ensuing persistent liver destruction. Advances in the study of autoreactive T cells stem mostly from AIH type 2, where the main autoantigen, cytochrome P450IID6 (CYP2D6), is known to enable characterisation of antigen-specific immune responses. Copyright 2010 S. Karger AG, Basel.

  18. Stressor Controllability and Immune Function

    Science.gov (United States)

    1986-10-17

    susceptibility to infectious disease . In E. Kurstak, P. V. Morozov, & Z. P. Lipowski (Eds.), Viruses , immunity, and mental health. Plenum Press, in press. w...following inmunization . a. ELISA Procedure. We-Tsof a flat bottomed microtiter plate (NUNC, certified Immunopla.e I) were coated with KLH (0.2 mi/well, 0.5 mg...because the, rats were being infected with viruses and other agents tnat could alter proliferation. We thus began to purchase pathogen-free animals and

  19. The Immune System: Basis of so much Health and Disease: 3. Adaptive Immunity.

    Science.gov (United States)

    Scully, Crispian; Georgakopoulou, Eleni A; Hassona, Yazan

    2017-04-01

    The immune system is the body’s primary defence mechanism against infections, and disturbances in the system can cause disease if the system fails in defence functions (in immunocompromised people), or if the activity is detrimental to the host (as in auto-immune and auto-inflammatory states). A healthy immune system is also essential to normal health of dental and oral tissues. This series presents the basics for the understanding of the immune system; this article covers adaptive immunity. Clinical relevance: Dental clinicians need a basic understanding of the immune system as it underlies health and disease.

  20. Modulation of T-Cell Activation in an Experimental Model of Mammary Carcinoma.

    Science.gov (United States)

    1998-07-01

    K. R., A. D. Kirk, G. Pecher, F. W.W., and 0. J. Finn. 1997. A survivor of breast cancer with immunity to MUC-1 mucin, and lactational mastitis ...experiments, mice were injected with in DMEM:F12 (Biowhittaker) supplemented with 2% bovine anti-CD4 (GK 1.5,400 pg), anti-CD8 (2.43,600 pg), a combination

  1. Implications of immune dysfunction on endometriosis associated infertility.

    Science.gov (United States)

    Miller, Jessica E; Ahn, Soo Hyun; Monsanto, Stephany P; Khalaj, Kasra; Koti, Madhuri; Tayade, Chandrakant

    2017-01-24

    Endometriosis is a complex, inflammatory disease that affects 6-10% of reproductive-aged women. Almost half of the women with endometriosis experience infertility. Despite the excessive prevalence, the pathogenesis of endometriosis and its associated infertility is unknown and a cure is not available. While many theories have been suggested to link endometriosis and infertility, a consensus among investigators has not emerged. In this extensive review of the literature as well as research from our laboratory, we provide potential insights into the role of immune dysfunction in endometriosis associated infertility. We discuss the implication of the peritoneal inflammatory microenvironment on various factors that contribute to infertility such as hormonal imbalance, oxidative stress and how these could further lead to poor oocyte, sperm and embryo quality, impaired receptivity of the endometrium and implantation failure.

  2. Zinc and immunity: An essential interrelation.

    Science.gov (United States)

    Maares, Maria; Haase, Hajo

    2016-12-01

    The significance of the essential trace element zinc for immune function has been known for several decades. Zinc deficiency affects immune cells, resulting in altered host defense, increased risk of inflammation, and even death. The micronutrient zinc is important for maintenance and development of immune cells of both the innate and adaptive immune system. A disrupted zinc homeostasis affects these cells, leading to impaired formation, activation, and maturation of lymphocytes, disturbed intercellular communication via cytokines, and weakened innate host defense via phagocytosis and oxidative burst. This review outlines the connection between zinc and immunity by giving a survey on the major roles of zinc in immune cell function, and their potential consequences in vivo. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Mucosal immunity to pathogenic intestinal bacteria.

    Science.gov (United States)

    Perez-Lopez, Araceli; Behnsen, Judith; Nuccio, Sean-Paul; Raffatellu, Manuela

    2016-03-01

    The intestinal mucosa is a particularly dynamic environment in which the host constantly interacts with trillions of commensal microorganisms, known as the microbiota, and periodically interacts with pathogens of diverse nature. In this Review, we discuss how mucosal immunity is controlled in response to enteric bacterial pathogens, with a focus on the species that cause morbidity and mortality in humans. We explain how the microbiota can shape the immune response to pathogenic bacteria, and we detail innate and adaptive immune mechanisms that drive protective immunity against these pathogens. The vast diversity of the microbiota, pathogens and immune responses encountered in the intestines precludes discussion of all of the relevant players in this Review. Instead, we aim to provide a representative overview of how the intestinal immune system responds to pathogenic bacteria.

  4. Neuromuscular complications of immune checkpoint inhibitor therapy.

    Science.gov (United States)

    Kolb, Noah A; Trevino, Christopher R; Waheed, Waqar; Sobhani, Fatemeh; Landry, Kara K; Thomas, Alissa A; Hehir, Mike

    2018-01-17

    Immune checkpoint inhibitor (ICPI) therapy unleashes the body's natural immune system to fight cancer. ICPIs improve overall cancer survival, however, the unbridling of the immune system may induce a variety of immune-related adverse events. Neuromuscular immune complications are rare but they can be severe. Myasthenia gravis and inflammatory neuropathy are the most common neuromuscular adverse events but a variety of others including inflammatory myopathy are reported. The pathophysiologic mechanism of these autoimmune disorders may differ from that of non-ICPI-related immune diseases. Accordingly, while the optimal treatment for ICPI-related neuromuscular disorders generally follows a traditional paradigm, there are important novel considerations in selecting appropriate immunosuppressive therapy. This review presents 2 new cases, a summary of neuromuscular ICPI complications, and an approach to the diagnosis and treatment of these disorders. Muscle Nerve, 2018. © 2018 Wiley Periodicals, Inc.

  5. Immunity to Trichinella spiralis in irradiated mice

    International Nuclear Information System (INIS)

    Wakelin, D.; Wilson, M.M.

    1980-01-01

    Irradiation prevented the accelerated expulsion of Trichinella spiralis from mice immunized by transfer of immune mesenteric lymph node cells (IMLNC) or by prior infection. Nevertheless, worms in irradiated immune mice were smaller and less fecund than those in controls. In adoptively immunized and irradiated mice expulsion could not be achieved by increasing the numbers of IMLNC transferred, although the effect upon worm length was more severe. Thus IMLNC express a direct, anti-worm immunity which is independent of their role in worm expulsion. IMLNC cause expulsion in irradiated mice only when adequate levels of bone marrow-derived cells are available. The results are discussed in terms of a possible antibody-mediated basis for direct anti-worm immunity. (author)

  6. Incomplete immune recovery in HIV infection

    DEFF Research Database (Denmark)

    Gaardbo, Julie C; Hartling, Hans J; Gerstoft, Jan

    2012-01-01

    -infected patients do not achieve optimal immune reconstitution despite suppression of viral replication. These patients are referred to as immunological nonresponders (INRs). INRs present with severely altered immunological functions, including malfunction and diminished production of cells within lymphopoetic...... tissue, perturbed frequencies of immune regulators such as regulatory T cells and Th17 cells, and increased immune activation, immunosenescence, and apoptosis. Importantly, INRs have an increased risk of morbidity and mortality compared to HIV-infected patients with an optimal immune reconstitution....... Additional treatment to HAART that may improve immune reconstitution has been investigated, but results thus far have proved disappointing. The reason for immunological nonresponse is incompletely understood. This paper summarizes the known and unknown factors regarding the incomplete immune reconstitution...

  7. The immune system vs. Pseudomonas aeruginosa biofilms

    DEFF Research Database (Denmark)

    Jensen, Peter Østrup; Givskov, Michael; Bjarnsholt, Thomas

    2010-01-01

    Ilya Metchnikoff and Paul Ehrlich were awarded the Nobel price in 1908. Since then, numerous studies have unraveled a multitude of mechanistically different immune responses to intruding microorganisms. However, in the vast majority of these studies, the underlying infectious agents have appeared...... in the planktonic state. Accordingly, much less is known about the immune responses to the presence of biofilm-based infections (which is probably also due to the relatively short period of time in which the immune response to biofilms has been studied). Nevertheless, more recent in vivo and in vitro studies have...... revealed both innate as well as adaptive immune responses to biofilms. On the other hand, measures launched by biofilm bacteria to achieve protection against the various immune responses have also been demonstrated. Whether particular immune responses to biofilm infections exist remains to be firmly...

  8. Cardiac allograft immune activation: current perspectives

    Directory of Open Access Journals (Sweden)

    Chang D

    2014-12-01

    Full Text Available David Chang, Jon Kobashigawa Cedars-Sinai Heart Institute, Los Angeles, CA, USA Abstract: Heart transplant remains the most durable option for end-stage heart disease. Cardiac allograft immune activation and heart transplant rejection remain among the main complications limiting graft and recipient survival. Mediators of the immune system can cause different forms of rejection post-heart transplant. Types of heart transplant rejection include hyperacute rejection, cellular rejection, antibody-mediated rejection, and chronic rejection. In this review, we will summarize the innate and adaptive immune responses which influence the post-heart transplant recipient. Different forms of rejection and their clinical presentation, detection, and immune monitoring will be discussed. Treatment of heart transplant rejection will be examined. We will discuss potential treatment strategies for preventing rejection post-transplant in immunologically high-risk patients with antibody sensitization. Keywords: heart transplant, innate immunity, adaptive immunity, rejection, immunosuppression

  9. 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.

  10. Immunization of networks with community structure

    International Nuclear Information System (INIS)

    Masuda, Naoki

    2009-01-01

    In this study, an efficient method to immunize modular networks (i.e. networks with community structure) is proposed. The immunization of networks aims at fragmenting networks into small parts with a small number of removed nodes. Its applications include prevention of epidemic spreading, protection against intentional attacks on networks, and conservation of ecosystems. Although preferential immunization of hubs is efficient, good immunization strategies for modular networks have not been established. On the basis of an immunization strategy based on eigenvector centrality, we develop an analytical framework for immunizing modular networks. To this end, we quantify the contribution of each node to the connectivity in a coarse-grained network among modules. We verify the effectiveness of the proposed method by applying it to model and real networks with modular structure.

  11. Honeybee immunity and colony losses

    Directory of Open Access Journals (Sweden)

    F. Nazzi

    2014-10-01

    Full Text Available The decline of honeybee colonies and their eventual collapse is a widespread phenomenon in the Northern hemisphere of the globe, which severely limits the beekeeping industry. This dramatic event is associated with an enhanced impact of parasites and pathogens on honeybees, which is indicative of reduced immunocompetence. The parasitic mite Varroa destructor and the vectored viral pathogens appear to play a key-role in the induction of this complex syndrome. In particular, the Deformed Wing Virus (DWV is widespread and is now considered, along with Varroa, one of the major causes of bee colony losses. Several lines of evidence indicate that this mite/DWV association severely affects the immune system of honeybees and makes them more sensitive to the action of other stress factors. The molecular mechanisms underpinning these complex interactions are currently being investigated and the emerging information has allowed the development of a new functional model, describing how different stress factors may synergistically concur in the induction of bee immune alteration and health decline. This provides a new logical framework in which to interpret the proposed multifactorial origin of bee colony losses and sets the stage for a more comprehensive and integrated analysis of the effect that multiple stress agents may have on honeybees.

  12. Rab GTPases in Immunity and Inflammation

    Directory of Open Access Journals (Sweden)

    Akriti Prashar

    2017-09-01

    Full Text Available Strict spatiotemporal control of trafficking events between organelles is critical for maintaining homeostasis and directing cellular responses. This regulation is particularly important in immune cells for mounting specialized immune defenses. By controlling the formation, transport and fusion of intracellular organelles, Rab GTPases serve as master regulators of membrane trafficking. In this review, we discuss the cellular and molecular mechanisms by which Rab GTPases regulate immunity and inflammation.

  13. Rab GTPases in Immunity and Inflammation.

    Science.gov (United States)

    Prashar, Akriti; Schnettger, Laura; Bernard, Elliott M; Gutierrez, Maximiliano G

    2017-01-01

    Strict spatiotemporal control of trafficking events between organelles is critical for maintaining homeostasis and directing cellular responses. This regulation is particularly important in immune cells for mounting specialized immune defenses. By controlling the formation, transport and fusion of intracellular organelles, Rab GTPases serve as master regulators of membrane trafficking. In this review, we discuss the cellular and molecular mechanisms by which Rab GTPases regulate immunity and inflammation.

  14. Noise immunity of optimal tracking demodulators

    Science.gov (United States)

    Uriadnikov, Iu. F.; Vasilev, N. A.

    1982-05-01

    The noise immunity of optimal discrete tracking demodulators, used in space communication systems, is analyzed in the case of an arbitrary relationship between the signal pulse repetition period and the interval of message correlation. Expressions are obtained which are then used to compare the noise immunities of discrete and continuous tracking demodulators, used for the transmission of messages with spectra approximated by Butterworth polynomials. It is shown that the noise immunity of the discrete demodulator significantly deteriorates

  15. Reversibility of alcohol-induced immune depression

    DEFF Research Database (Denmark)

    Tønnesen, H; Kaiser, A H; Nielsen, B B

    1992-01-01

    Alcohol abusers have suppressed cellular immune function. The aim of the study was to investigate the time of sobriety required to normalize immune function. Delayed hypersensitivity was investigated during disulfiram controlled abstinence in ten heavy alcoholics and in seven moderate drinkers...... months of abstinence. The results suggest that while 2 weeks of abstinence from alcohol will improve the depressed cellular immunity, 2 months of sobriety is necessary to normalize it....

  16. Poppers: more evidence of suppressed immunity.

    Science.gov (United States)

    James, J S

    1999-08-20

    Evidence from studies in mice shows that exposure to isobutyl nitrite suppresses the immune system. This immune suppression allows for bacterial growth in the lungs and livers of infected mice and can inhibit the ability of mediastinal lymph nodes to respond to antigen-specific stimulation. The mechanism for immune suppression may be a reduction in CD4+ and CD8+ T cell populations in the mediastinal lymph nodes following pulmonary infection with Listeria monocytogenes.

  17. Insect Immunity: The Post-Genomic Era

    OpenAIRE

    Bangham, Jenny; Jiggins, Frank; Lemaitre, Bruno

    2006-01-01

    Insects have a complex and effective immune system, many components of which are conserved in mammals. But only in the last decade have the molecular mechanisms that regulate the insect immune response--and their relevance to general biology and human immunology--become fully appreciated. A meeting supported by the Centre National de la Récherche Scientifique (France) was held to bring together the whole spectrum of researchers working on insect immunity. The meeting addressed diverse aspects...

  18. Evolution of transgenerational immunity in invertebrates

    OpenAIRE

    Pigeault, R.; Garnier, R.; Rivero, A.; Gandon, S.

    2016-01-01

    Over a decade ago, the discovery of transgenerational immunity in invertebrates shifted existing paradigms on the lack of sophistication of their immune system. Nonetheless, the prevalence of this trait and the ecological factors driving its evolution in invertebrates remain poorly understood. Here, we develop a theoretical host–parasite model and predict that long lifespan and low dispersal should promote the evolution of transgenerational immunity. We also predict that in species that produ...

  19. GOES-R: Satellite Insight

    Science.gov (United States)

    Fitzpatrick, Austin J.; Leon, Nancy J.; Novati, Alexander; Lincoln, Laura K.; Fisher, Diane K.

    2012-01-01

    GOES-R: Satellite Insight seeks to bring awareness of the GOES-R (Geostationary Operational Environmental Satellite -- R Series) satellite currently in development to an audience of all ages on the emerging medium of mobile games. The iPhone app (Satellite Insight) was created for the GOES-R Program. The app describes in simple terms the types of data products that can be produced from GOES-R measurements. The game is easy to learn, yet challenging for all audiences. It includes educational content and a path to further information about GOESR, its technology, and the benefits of the data it collects. The game features action-puzzle game play in which the player must prevent an overflow of data by matching falling blocks that represent different types of GOES-R data. The game adds more different types of data blocks over time, as long as the player can prevent a data overflow condition. Points are awarded for matches, and players can compete with themselves to beat their highest score.

  20. Feeding Our Immune System: Impact on Metabolism

    Directory of Open Access Journals (Sweden)

    Isabelle Wolowczuk

    2008-01-01

    Full Text Available Endogenous intestinal microflora and environmental factors, such as diet, play a central role in immune homeostasis and reactivity. In addition, microflora and diet both influence body weight and insulin-resistance, notably through an action on adipose cells. Moreover, it is known since a long time that any disturbance in metabolism, like obesity, is associated with immune alteration, for example, inflammation. The purpose of this review is to provide an update on how nutrients-derived factors (mostly focusing on fatty acids and glucose impact the innate and acquired immune systems, including the gut immune system and its associated bacterial flora. We will try to show the reader how the highly energy-demanding immune cells use glucose as a main source of fuel in a way similar to that of insulin-responsive adipose tissue and how Toll-like receptors (TLRs of the innate immune system, which are found on immune cells, intestinal cells, and adipocytes, are presently viewed as essential actors in the complex balance ensuring bodily immune and metabolic health. Understanding more about these links will surely help to study and understand in a more fundamental way the common observation that eating healthy will keep you and your immune system healthy.

  1. An Immunization Strategy Based on Propagation Mechanism

    Directory of Open Access Journals (Sweden)

    Yixin Zhu

    2014-01-01

    Full Text Available With the ubiquity of smart phones, wearable equipment, and wireless sensors, the topologies of networks composed by them change along with time. The immunization strategies in which network immune nodes are chosen by analyzing the static aggregation network topologies have been challenged. The studies about interaction propagations between two pathogens show that the interaction can change propagation threshold and the final epidemic size of each other, which provides a new thinking of immunization method. The eradication or inhibition of the virus can be achieved through the spread of its opposite party. Here, we put forward an immunization strategy whose implementation does not depend on the analysis of network topology. The immunization agents are randomly placed on a few of individuals of network and spread out from these individuals on network in a propagation method. The immunization agents prevent virus infecting their habitat nodes with certain immune success rate. The analysis and simulation of evolution equation of the model show that immune propagation has a significant impact on the spread threshold and steady-state density of virus on a finite size of BA networks. Simulations on some real-world networks also suggest that the immunization strategy is feasible and effective.

  2. Training pharmacy technicians to administer immunizations.

    Science.gov (United States)

    McKeirnan, Kimberly C; Frazier, Kyle R; Nguyen, Maryann; MacLean, Linda Garrelts

    To evaluate the effectiveness of an immunization training program for pharmacy technicians on technicians' self-reported confidence, knowledge, and number of vaccines administered. A one-group pre- and posttest study was conducted with certified pharmacy technicians from Albertsons and Safeway community pharmacies in Idaho. Thirty pharmacy technicians were recruited to participate in an immunization administration training program comprising a 2-hour home study and a 2-hour live training. Pharmacy technician scores on a 10-question knowledge assessment, responses on a pre- and posttraining survey, and number of immunizations administered in the 6-month period following the training were collected. Twenty-five pharmacy technicians completed the home study and live portions of the immunization training program. All 29 pharmacy technicians who took the home study assessment passed with greater than 70% competency on the first attempt. Technicians self-reported increased confidence with immunization skills between the pretraining survey and the posttraining survey. From December 2016 to May 2017, the technicians administered 953 immunizations with 0 adverse events reported. For the first time, pharmacy technicians have legally administered immunizations in the United States. Trained pharmacy technicians demonstrated knowledge of vaccination procedures and self-reported improved confidence in immunization skills and administered immunizations after participating in a 4-hour training program. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  3. Overcoming Challenges to Childhood Immunizations Status.

    Science.gov (United States)

    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.

  4. Frank A. Beach award: programming of neuroendocrine function by early-life experience: a critical role for the immune system.

    Science.gov (United States)

    Bilbo, Staci D

    2013-05-01

    Many neuropsychiatric disorders are associated with a strong dysregulation of the immune system, and several have a striking etiology in development as well. Our recent evidence using a rodent model of neonatal Escherichia coli infection has revealed novel insight into the mechanisms underlying cognitive deficits in adulthood, and suggests that the early-life immune history of an individual may be critical to understanding the relative risk of developing later-life mental health disorders in humans. A single neonatal infection programs the function of immune cells within the brain, called microglia, for the life of the rodent such that an adult immune challenge results in exaggerated cytokine production within the brain and associated cognitive deficits. I describe the important role of the immune system, notably microglia, during brain development, and discuss some of the many ways in which immune activation during early brain development can affect the later-life outcomes of neural function, immune function, and cognition. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Biomaterials innovation for next generation ex vivo immune tissue engineering.

    Science.gov (United States)

    Singh, Ankur

    2017-06-01

    Primary and secondary lymphoid organs are tissues that facilitate differentiation of B and T cells, leading to the induction of adaptive immune responses. These organs are present in the body from birth and are also recognized as locations where self-reactive B and T cells can be eliminated during the natural selection process. Many insights into the mechanisms that control the process of immune cell development and maturation in response to infection come from the analysis of various gene-deficient mice that lack some or all hallmark features of lymphoid tissues. The complexity of such animal models limits our ability to modulate the parameters that control the process of immune cell development, differentiation, and immunomodulation. Engineering functional, living immune tissues using biomaterials can grant researchers the ability to reproduce immunological events with tunable parameters for more rapid development of immunotherapeutics, cell-based therapy, and enhancing our understanding of fundamental biology as well as improving efforts in regenerative medicine. Here the author provides his review and perspective on the bioengineering of primary and secondary lymphoid tissues, and biomaterials innovation needed for the construction of these immune organs in tissue culture plates and on-chip. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Constant illumination reduces circulating melatonin and impairs immune function in the cricket Teleogryllus commodus

    Directory of Open Access Journals (Sweden)

    Joanna Durrant

    2015-07-01

    Full Text Available Exposure to constant light has a range of negative effects on behaviour and physiology, including reduced immune function in both vertebrates and invertebrates. It is proposed that the associated suppression of melatonin (a ubiquitous hormone and powerful antioxidant in response to the presence of light at night could be an underlying mechanistic link driving the changes to immune function. Here, we investigated the relationship between constant illumination, melatonin and immune function, using a model invertebrate species, the Australian black field cricket, Teleogryllus commodus. Crickets were reared under either a 12 h light: 12 h dark regimen or a constant 24 h light regimen. Circulating melatonin concentration and immune function (haemocyte concentration, lytic activity and phenoloxidase (PO activity were assessed in individual adult crickets through the analysis of haemolymph. Constant illumination reduced melatonin and had a negative impact on haemocyte concentrations and lytic activity, but its effect on PO activity was less apparent. Our data provide the first evidence, to our knowledge, of a link between exposure to constant illumination and variation in haemocyte concentration in an invertebrate model, while also highlighting the potential complexity of the immune response following exposure to constant illumination. This study provides insight into the possible negative effect of artificial night-time lighting on the physiology of invertebrates, but whether lower and potentially more ecologically relevant levels of light at night produce comparable results, as has been reported in several vertebrate taxa, remains to be tested.

  7. PCSK9 at the crossroad of cholesterol metabolism and immune function during infections.

    Science.gov (United States)

    Paciullo, Francesco; Fallarino, Francesca; Bianconi, Vanessa; Mannarino, Massimo R; Sahebkar, Amirhossein; Pirro, Matteo

    2017-09-01

    Sepsis, a complex and dynamic syndrome resulting from microbial invasion and immune system dysregulation, is associated with an increased mortality, reaching up to 35% worldwide. Cholesterol metabolism is often disturbed during sepsis, with low plasma cholesterol levels being associated with poor prognosis. Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes degradation of the low-density lipoprotein receptor (LDLR), thus regulating intracellular and plasma cholesterol levels. PCSK9 is often upregulated during sepsis and might have a detrimental effect on immune host response and survival. Accordingly, PCSK9 reduces lipopolysaccharide uptake and clearance by human hepatocytes. Moreover, PCSK9 upregulation exacerbates organ dysfunction and tissue inflammation during sepsis, whereas a protective effect of PCSK9 deficiency has been documented in septic patients. Although a possible detrimental impact of PCSK9 on survival has been described, some beneficial effects of PCSK9 on immune response may be hypothesized. First, PCSK9 is associated with increased plasma cholesterol levels, which might be protective during sepsis. Second, PCSK9, by stimulating LDLR degradation and inhibiting reverse cholesterol transport (RCT), might promote preferential cholesterol accumulation in macrophages and other immune cells; these events might improve lipid raft composition and augment toll-like receptor function thus supporting inflammatory response. Hence, a more clear definition of the role of PCSK9 in septic states might provide additional insight in the understanding of the sepsis-associated immune dysregulation and enhance therapeutic outcomes. © 2017 Wiley Periodicals, Inc.

  8. Efficacy of multiple anticancer therapies may depend on host immune response

    Directory of Open Access Journals (Sweden)

    Kritika Karri

    2017-06-01

    Full Text Available The host immune system is a key player in anticancer therapy response and resistance. Although the impact of host immune response in the ‘war against cancer’ has been studied and it has been the basis for immunotherapy, understanding of its role in attenuating the action of conventional anticancer therapies is an area that has not been fully explored. In spite of advances in systemic therapy, the 5-year survival rate for adenocarcinoma is still a mere 13% and the primary reason for treatment failure is believed to be due to acquired resistance to therapy. Hence, there is a need for identifying reliable biomarkers for guided treatment of lung and colon adenocarcinoma and to better predict the outcomes of specific anticancer therapies. In this work, gene expression data were analyzed using public resources and this study shows how host immune competence underscores the efficacy of various anticancer therapies. Additionally, the result provides insight on the regulation of certain biochemical pathways relating to the immune system, and suggests that smart chemotherapeutic intervention strategies could be based on a patient’s immune profile.

  9. Construction of an integrated gene regulatory network link to stress-related immune system in cattle.

    Science.gov (United States)

    Behdani, Elham; Bakhtiarizadeh, Mohammad Reza

    2017-10-01

    The immune system is an important biological system that is negatively impacted by stress. This study constructed an integrated regulatory network to enhance our understanding of the regulatory gene network used in the stress-related immune system. Module inference was used to construct modules of co-expressed genes with bovine leukocyte RNA-Seq data. Transcription factors (TFs) were then assigned to these modules using Lemon-Tree algorithms. In addition, the TFs assigned to each module were confirmed using the promoter analysis and protein-protein interactions data. Therefore, our integrated method identified three TFs which include one TF that is previously known to be involved in immune response (MYBL2) and two TFs (E2F8 and FOXS1) that had not been recognized previously and were identified for the first time in this study as novel regulatory candidates in immune response. This study provides valuable insights on the regulatory programs of genes involved in the stress-related immune system.

  10. Evolution of JAK-STAT pathway components: mechanisms and role in immune system development.

    Directory of Open Access Journals (Sweden)

    Clifford Liongue

    Full Text Available BACKGROUND: Lying downstream of a myriad of cytokine receptors, the Janus kinase (JAK-Signal transducer and activator of transcription (STAT pathway is pivotal for the development and function of the immune system, with additional important roles in other biological systems. To gain further insight into immune system evolution, we have performed a comprehensive bioinformatic analysis of the JAK-STAT pathway components, including the key negative regulators of this pathway, the SH2-domain containing tyrosine phosphatase (SHP, Protein inhibitors against Stats (PIAS, and Suppressor of cytokine signaling (SOCS proteins across a diverse range of organisms. RESULTS: Our analysis has demonstrated significant expansion of JAK-STAT pathway components co-incident with the emergence of adaptive immunity, with whole genome duplication being the principal mechanism for generating this additional diversity. In contrast, expansion of upstream cytokine receptors appears to be a pivotal driver for the differential diversification of specific pathway components. CONCLUSION: Diversification of JAK-STAT pathway components during early vertebrate development occurred concurrently with a major expansion of upstream cytokine receptors and two rounds of whole genome duplications. This produced an intricate cell-cell communication system that has made a significant contribution to the evolution of the immune system, particularly the emergence of adaptive immunity.

  11. A Mathematical Model of Skeletal Muscle Disease and Immune Response in the mdx Mouse

    Directory of Open Access Journals (Sweden)

    Abdul Salam Jarrah

    2014-01-01

    Full Text Available Duchenne muscular dystrophy (DMD is a genetic disease that results in the death of affected boys by early adulthood. The genetic defect responsible for DMD has been known for over 25 years, yet at present there is neither cure nor effective treatment for DMD. During early disease onset, the mdx mouse has been validated as an animal model for DMD and use of this model has led to valuable but incomplete insights into the disease process. For example, immune cells are thought to be responsible for a significant portion of muscle cell death in the mdx mouse; however, the role and time course of the immune response in the dystrophic process have not been well described. In this paper we constructed a simple mathematical model to investigate the role of the immune response in muscle degeneration and subsequent regeneration in the mdx mouse model of Duchenne muscular dystrophy. Our model suggests that the immune response contributes substantially to the muscle degeneration and regeneration processes. Furthermore, the analysis of the model predicts that the immune system response oscillates throughout the life of the mice, and the damaged fibers are never completely cleared.

  12. Theory of mind correlates with clinical insight but not cognitive insight in patients with schizophrenia.

    Science.gov (United States)

    Zhang, Qi; Li, Xu; Parker, Giverny J; Hong, Xiao-Hong; Wang, Yi; Lui, Simon S Y; Neumann, David L; Cheung, Eric F C; Shum, David H K; Chan, Raymond C K

    2016-03-30

    Research on the relationship between insight and social cognition, in particular Theory of Mind (ToM), in schizophrenia has yielded mixed findings to date. Very few studies, however, have assessed both clinical insight and cognitive insight when examining their relationships with ToM in schizophrenia. The current study thus investigated the relationship between clinical insight, cognitive insight, and ToM in a sample of 56 patients with schizophrenia and 30 healthy controls. Twenty-seven patients were classified as low in clinical insight according to their scores on the 'insight' item (G12) of the Positive and Negative Syndrome Scale (PANSS). Moreover, cognitive insight and ToM were assessed with the Beck Cognitive Insight Scale (BCIS) and the Yoni task, respectively. The results indicated that patients with poor clinical insight performed worse on tasks of second-order cognitive and affective ToM, while the ToM performance of patients with high clinical insight was equivalent to that of healthy controls. Furthermore, while clinical insight was correlated with ToM and clinical symptoms, cognitive insight did not correlate with clinical insight, ToM, or clinical symptoms. Clinical insight thus appears to be an important factor related to ToM in schizophrenia. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Development of immune organs and functioning in humans and test animals: Implications for immune intervention studies.

    Science.gov (United States)

    Kuper, C Frieke; van Bilsen, Jolanda; Cnossen, Hilde; Houben, Geert; Garthoff, Jossie; Wolterbeek, Andre

    2016-09-01

    A healthy immune status is mostly determined during early life stages and many immune-related diseases may find their origin in utero and the first years of life. Therefore, immune health optimization may be most effective during early life. This review is an inventory of immune organ maturation events in relation to developmental timeframes in minipig, rat, mouse and human. It is concluded that time windows of immune organ development in rodents can be translated to human, but minipig reflects the human timeframes better; however the lack of prenatal maternal-fetal immune interaction in minipig may cause less responsiveness to prenatal intervention. It is too early to conclude which immune parameters are most appropriate, because there are not enough comparative immune parameters. Filling these gaps will increase the predictability of results observed in experimental animals, and guide future intervention studies by assessing relevant parameters in the right corresponding developmental time frames. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. The twilight of immunity: emerging concepts in aging of the immune system.

    Science.gov (United States)

    Nikolich-Žugich, Janko

    2018-01-01

    Immunosenescence is a series of age-related changes that affect the immune system and, with time, lead to increased vulnerability to infectious diseases. This Review addresses recent developments in the understanding of age-related changes that affect key components of immunity, including the effect of aging on cells of the (mostly adaptive) immune system, on soluble molecules that guide the maintenance and function of the immune system and on lymphoid organs that coordinate both the maintenance of lymphocytes and the initiation of immune responses. I further address the effect of the metagenome and exposome as key modifiers of immune-system aging and discuss a conceptual framework in which age-related changes in immunity might also affect the basic rules by which the immune system operates.

  15. 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

  16. Immune response in pemphigus and beyond: progresses and emerging concepts.

    Science.gov (United States)

    Di Zenzo, Giovanni; Amber, Kyle T; Sayar, Beyza S; Müller, Eliane J; Borradori, Luca

    2016-01-01

    Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are two severe autoimmune bullous diseases of the mucosae and/or skin associated with autoantibodies directed against desmoglein (Dsg) 3 and/or Dsg1. These two desmosomal cadherins, typifying stratified epithelia, are components of cell adhesion complexes called desmosomes and represent extra-desmosomal adhesion receptors. We herein review the advances in our understanding of the immune response underlying pemphigus, including human leucocyte antigen (HLA) class II-associated genetic susceptibility, characteristics of pathogenic anti-Dsg antibodies, antigenic mapping studies as well as findings about Dsg-specific B and T cells. The pathogenicity of anti-Dsg autoantibodies has been convincingly demonstrated. Disease activity and clinical phenotype correlate with anti-Dsg antibody titers and profile while passive transfer of anti-Dsg IgG from pemphigus patients' results in pemphigus-like lesions in neonatal and adult mice. Finally, adoptive transfer of splenocytes from Dsg3-knockout mice immunized with murine Dsg3 into immunodeficient mice phenotypically recapitulates PV. Although the exact pathogenic mechanisms leading to blister formation have not been fully elucidated, intracellular signaling following antibody binding has been found to be necessary for inducing cell-cell dissociation, at least for PV. These new insights not only highlight the key role of Dsgs in maintenance of tissue homeostasis but are expected to progressively change pemphigus management, paving the way for novel targeted immunologic and pharmacologic therapies.

  17. Yersinia type III effectors perturb host innate immune responses

    Science.gov (United States)

    Pha, Khavong; Navarro, Lorena

    2016-01-01

    The innate immune system is the first line of defense against invading pathogens. Innate immune cells recognize molecular patterns from the pathogen and mount a response to resolve the infection. The production of proinflammatory cytokines and reactive oxygen species, phagocytosis, and induced programmed cell death are processes initiated by innate immune cells in order to combat invading pathogens. However, pathogens have evolved various virulence mechanisms to subvert these responses. One strategy utilized by Gram-negative bacterial pathogens is the deployment of a complex machine termed the type III secretion system (T3SS). The T3SS is composed of a syringe-like needle structure and the effector proteins that are injected directly into a target host cell to disrupt a cellular response. The three human pathogenic Yersinia spp. (Y. pestis, Y. enterocolitica, and Y. pseudotuberculosis) are Gram-negative bacteria that share in common a 70 kb virulence plasmid which encodes the T3SS. Translocation of the Yersinia effector proteins (YopE, YopH, YopT, YopM, YpkA/YopO, and YopP/J) into the target host cell results in disruption of the actin cytoskeleton to inhibit phagocytosis, downregulation of proinflammatory cytokine/chemokine production, and induction of cellular apoptosis of the target cell. Over the past 25 years, studies on the Yersinia effector proteins have unveiled tremendous knowledge of how the effectors enhance Yersinia virulence. Recently, the long awaited crystal structure of YpkA has been solved providing further insights into the activation of the YpkA kinase domain. Multisite autophosphorylation by YpkA to activate its kinase domain was also shown and postulated to serve as a mechanism to bypass regulation by host phosphatases. In addition, novel Yersinia effector protein targets, such as caspase-1, and signaling pathways including activation of the inflammasome were identified. In this review, we summarize the recent discoveries made on Yersinia

  18. Barriers to Immunizations and Strategies to Enhance Immunization Rates in Adults with Autoimmune Inflammatory Diseases.

    Science.gov (United States)

    Kirchner, Elizabeth; Ruffing, Victoria

    2017-02-01

    For as long as there have been immunizations, there have been barriers to them. Immunization rates in the United States are below target. Rheumatologists and rheumatology practitioners need to understand the issues of immunizations in patients with autoimmune inflammatory disease to identify and overcome barriers to immunization. Several strategies for overcoming these barriers are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. The genomic features of parasitism, Polyembryony and immune evasion in the endoparasitic wasp Macrocentrus cingulum.

    Science.gov (United States)

    Yin, Chuanlin; Li, Meizhen; Hu, Jian; Lang, Kun; Chen, Qiming; Liu, Jinding; Guo, Dianhao; He, Kang; Dong, Yipei; Luo, Jiapeng; Song, Zhenkun; Walters, James R; Zhang, Wenqing; Li, Fei; Chen, Xuexin

    2018-05-30

    new insights into the polyembryony and immune evasion.

  20. A clinically parameterized mathematical model of Shigella immunity to inform vaccine design.

    Directory of Open Access Journals (Sweden)

    Courtney L Davis

    Full Text Available We refine and clinically parameterize a mathematical model of the humoral immune response against Shigella, a diarrheal bacteria that infects 80-165 million people and kills an estimated 600,000 people worldwide each year. Using Latin hypercube sampling and Monte Carlo simulations for parameter estimation, we fit our model to human immune data from two Shigella EcSf2a-2 vaccine trials and a rechallenge study in which antibody and B-cell responses against Shigella's lipopolysaccharide (LPS and O-membrane proteins (OMP were recorded. The clinically grounded model is used to mathematically investigate which key immune mechanisms and bacterial targets confer immunity against Shigella and to predict which humoral immune components should be elicited to create a protective vaccine against Shigella. The model offers insight into why the EcSf2a-2 vaccine had low efficacy and demonstrates that at a group level a humoral immune response induced by EcSf2a-2 vaccine or wild-type challenge against Shigella's LPS or OMP does not appear sufficient for protection. That is, the model predicts an uncontrolled infection of gut epithelial cells that is present across all best-fit model parameterizations when fit to EcSf2a-2 vaccine or wild-type challenge data. Using sensitivity analysis, we explore which model parameter values must be altered to prevent the destructive epithelial invasion by Shigella bacteria and identify four key parameter groups as potential vaccine targets or immune correlates: 1 the rate that Shigella migrates into the lamina propria or epithelium, 2 the rate that memory B cells (BM differentiate into antibody-secreting cells (ASC, 3 the rate at which antibodies are produced by activated ASC, and 4 the Shigella-specific BM carrying capacity. This paper underscores the need for a multifaceted approach in ongoing efforts to design an effective Shigella vaccine.

  1. Tweaking Innate Immunity: The Promise of Innate Immunologicals as Anti-Infectives

    Directory of Open Access Journals (Sweden)

    Kenneth L Rosenthal

    2006-01-01

    Full Text Available New and exciting insights into the importance of the innate immune system are revolutionizing our understanding of immune defense against infections, pathogenesis, and the treatment and prevention of infectious diseases. The innate immune system uses multiple families of germline-encoded pattern recognition receptors (PRRs to detect infection and trigger a variety of antimicrobial defense mechanisms. PRRs are evolutionarily highly conserved and serve to detect infection by recognizing pathogen-associated molecular patterns that are unique to microorganisms and essential for their survival. Toll-like receptors (TLRs are transmembrane signalling receptors that activate gene expression programs that result in the production of proinflammatory cytokines and chemokines, type I interferons and antimicrobial factors. Furthermore, TLR activation facilitates and guides activation of adaptive immune responses through the activation of dendritic cells. TLRs are localized on the cell surface and in endosomal/lysosomal compartments, where they detect bacterial and viral infections. In contrast, nucleotide-binding oligomerization domain proteins and RNA helicases are located in the cell cytoplasm, where they serve as intracellular PRRs to detect cytoplasmic infections, particularly viruses. Due to their ability to enhance innate immune responses, novel strategies to use ligands, synthetic agonists or antagonists of PRRs (also known as 'innate immunologicals' can be used as stand-alone agents to provide immediate protection or treatment against bacterial, viral or parasitic infections. Furthermore, the newly appreciated importance of innate immunity in initiating and shaping adaptive immune responses is contributing to our understanding of vaccine adjuvants and promises to lead to improved next-generation vaccines.

  2. A clinically parameterized mathematical model of Shigella immunity to inform vaccine design.

    Science.gov (United States)

    Davis, Courtney L; Wahid, Rezwanul; Toapanta, Franklin R; Simon, Jakub K; Sztein, Marcelo B

    2018-01-01

    We refine and clinically parameterize a mathematical model of the humoral immune response against Shigella, a diarrheal bacteria that infects 80-165 million people and kills an estimated 600,000 people worldwide each year. Using Latin hypercube sampling and Monte Carlo simulations for parameter estimation, we fit our model to human immune data from two Shigella EcSf2a-2 vaccine trials and a rechallenge study in which antibody and B-cell responses against Shigella's lipopolysaccharide (LPS) and O-membrane proteins (OMP) were recorded. The clinically grounded model is used to mathematically investigate which key immune mechanisms and bacterial targets confer immunity against Shigella and to predict which humoral immune components should be elicited to create a protective vaccine against Shigella. The model offers insight into why the EcSf2a-2 vaccine had low efficacy and demonstrates that at a group level a humoral immune response induced by EcSf2a-2 vaccine or wild-type challenge against Shigella's LPS or OMP does not appear sufficient for protection. That is, the model predicts an uncontrolled infection of gut epithelial cells that is present across all best-fit model parameterizations when fit to EcSf2a-2 vaccine or wild-type challenge data. Using sensitivity analysis, we explore which model parameter values must be altered to prevent the destructive epithelial invasion by Shigella bacteria and identify four key parameter groups as potential vaccine targets or immune correlates: 1) the rate that Shigella migrates into the lamina propria or epithelium, 2) the rate that memory B cells (BM) differentiate into antibody-secreting cells (ASC), 3) the rate at which antibodies are produced by activated ASC, and 4) the Shigella-specific BM carrying capacity. This paper underscores the need for a multifaceted approach in ongoing efforts to design an effective Shigella vaccine.

  3. Acquired and innate immunity to polyaromatic hydrocarbons

    International Nuclear Information System (INIS)

    Yusuf, Nabiha; Timares, Laura; Seibert, Megan D.; Xu Hui; Elmets, Craig A.

    2007-01-01

    Polyaromatic hydrocarbons are ubiquitous environmental pollutants that are potent mutagens and carcinogens. Researchers have taken advantage of these properties to investigate the mechanisms by which chemicals cause cancer of the skin and other organs. When applied to the skin of mice, several carcinogenic polyaromatic hydrocarbons have also been shown to interact with the immune system, stimulating immune responses and resulting in the development of antigen-specific T-cell-mediated immunity. Development of cell-mediated immunity is strain-specific and is governed by Ah receptor genes and by genes located within the major histocompatibility complex. CD8 + T cells are effector cells in the response, whereas CD4 + T cells down-regulate immunity. Development of an immune response appears to have a protective effect since strains of mice that develop a cell-mediated immune response to carcinogenic polyaromatic hydrocarbons are less likely to develop tumors when subjected to a polyaromatic hydrocarbon skin carcinogenesis protocol than mice that fail to develop an immune response. With respect to innate immunity, TLR4-deficient C3H/HeJ mice are more susceptible to polyaromatic hydrogen skin tumorigenesis than C3H/HeN mice in which TLR4 is normal. These findings support the hypothesis that immune responses, through their interactions with chemical carcinogens, play an active role in the prevention of chemical skin carcinogenesis during the earliest stages. Efforts to augment immune responses to the chemicals that cause tumors may be a productive approach to the prevention of tumors caused by these agents

  4. Managing complexity insights, concepts, applications

    CERN Document Server

    Helbing, Dirk

    2007-01-01

    Each chapter in Managing Complexity focuses on analyzing real-world complex systems and transferring knowledge from the complex-systems sciences to applications in business, industry and society. The interdisciplinary contributions range from markets and production through logistics, traffic control, and critical infrastructures, up to network design, information systems, social conflicts and building consensus. They serve to raise readers' awareness concerning the often counter-intuitive behavior of complex systems and to help them integrate insights gained in complexity research into everyday planning, decision making, strategic optimization, and policy. Intended for a broad readership, the contributions have been kept largely non-technical and address a general, scientifically literate audience involved in corporate, academic, and public institutions.

  5. Immune-directed therapy for type 1 diabetes at the clinical level: the Immune Tolerance Network (ITN) experience.

    Science.gov (United States)

    Ehlers, Mario R; Nepom, Gerald T

    2012-01-01

    Reestablishing immune tolerance in type 1 diabetes (T1D), a chronic autoimmune disease, is a major goal. The Immune Tolerance Network (ITN) has initiated eight clinical trials of immunomodulatory therapies in recent-onset T1D over the past decade. Results have been mixed in terms of clinical efficacy, but the studies have provided valuable mechanistic insight that are enhancing our understanding of the disease and guiding the design of future trials. Trials of non-Fc-binding anti-CD3 mAbs have revealed that modulation of this target leads to partial responses, and ITN's AbATE trial led to identification of a robust responder group that could be distinguished from non-responders by baseline metabolic and immunologic features. A pilot study of the combination of IL-2 and rapamycin gave the first demonstration that frequency and function of regulatory T cells (Tregs) can be enhanced in T1D subjects, although the therapy triggered the activation of effectors with transient β-cell dysfunction. Similarly, therapy with anti-thymocyte globulin led to substantial lymphocyte depletion, but also to the activation of the acute-phase response with no clinical benefit during preliminary analyses. These and other results provide mechanistic tools that can be used as biomarkers for safety and efficacy in future trials. Furthermore, our results, together with those of other organizations, notably TrialNet, delineate the roles of the major components of the immune response in T1D. This information is setting the stage for future combination therapy trials. The development of disease-relevant biomarkers will also enable the implementation of innovative trial designs, notably adaptive trials, which will increase efficiencies in terms of study duration and sample size, and which will expedite the conduct of trials in which there are uncertainties about dose response and effect size.

  6. Integrated Circuit Electromagnetic Immunity Handbook

    Science.gov (United States)

    Sketoe, J. G.

    2000-08-01

    This handbook presents the results of the Boeing Company effort for NASA under contract NAS8-98217. Immunity level data for certain integrated circuit parts are discussed herein, along with analytical techniques for applying the data to electronics systems. This handbook is built heavily on the one produced in the seventies by McDonnell Douglas Astronautics Company (MDAC, MDC Report E1929 of 1 August 1978, entitled Integrated Circuit Electromagnetic Susceptibility Handbook, known commonly as the ICES Handbook, which has served countless systems designers for over 20 years). Sections 2 and 3 supplement the device susceptibility data presented in section 4 by presenting information on related material required to use the IC susceptibility information. Section 2 concerns itself with electromagnetic susceptibility analysis and serves as a guide in using the information contained in the rest of the handbook. A suggested system hardening requirements is presented in this chapter. Section 3 briefly discusses coupling and shielding considerations. For conservatism and simplicity, a worst case approach is advocated to determine the maximum amount of RF power picked up from a given field. This handbook expands the scope of the immunity data in this Handbook is to of 10 MHz to 10 GHz. However, the analytical techniques provided are applicable to much higher frequencies as well. It is expected however, that the upper frequency limit of concern is near 10 GHz. This is due to two factors; the pickup of microwave energy on system cables and wiring falls off as the square of the wavelength, and component response falls off at a rapid rate due to the effects of parasitic shunt paths for the RF energy. It should be noted also that the pickup on wires and cables does not approach infinity as the frequency decreases (as would be expected by extrapolating the square law dependence of the high frequency roll-off to lower frequencies) but levels off due to mismatch effects.

  7. Inside the mucosal immune system.

    Directory of Open Access Journals (Sweden)

    Jerry R McGhee

    Full Text Available An intricate network of innate and immune cells and their derived mediators function in unison to protect us from toxic elements and infectious microbial diseases that are encountered in our environment. This vast network operates efficiently by use of a single cell epithelium in, for example, the gastrointestinal (GI and upper respiratory (UR tracts, fortified by adjoining cells and lymphoid tissues that protect its integrity. Perturbations certainly occur, sometimes resulting in inflammatory diseases or infections that can be debilitating and life threatening. For example, allergies in the eyes, skin, nose, and the UR or digestive tracts are common. Likewise, genetic background and environmental microbial encounters can lead to inflammatory bowel diseases (IBDs. This mucosal immune system (MIS in both health and disease is currently under intense investigation worldwide by scientists with diverse expertise and interests. Despite this activity, there are numerous questions remaining that will require detailed answers in order to use the MIS to our advantage. In this issue of PLOS Biology, a research article describes a multi-scale in vivo systems approach to determine precisely how the gut epithelium responds to an inflammatory cytokine, tumor necrosis factor-alpha (TNF-α, given by the intravenous route. This article reveals a previously unknown pathway in which several cell types and their secreted mediators work in unison to prevent epithelial cell death in the mouse small intestine. The results of this interesting study illustrate how in vivo systems biology approaches can be used to unravel the complex mechanisms used to protect the host from its environment.

  8. [Immunization against varicella and zoster].

    Science.gov (United States)

    Floret, Daniel

    2007-06-01

    Two vaccines against varicella-zoster virus are available in France. These live attenuated vaccines are derived from the Oka strain used in Japan since 1974. They are indicated for healthy subjects from 12 months of age, at a dose of one injection until 12 years of age, and two injections 4-8 weeks apart for older children and adults. Seroconversion occurs in 95% of cases and the antibodies persist beyond 5 years. Clinical efficacy is about 85% against all forms of varicella and nearly 100% against severe forms. Post-exposure vaccination within 3 days may also prevent the disease. A universal immunization program against varicella was implemented in the USA in 1995. Now, with vaccine coverage at about 80%, the incidence of the disease has been reduced by 85%, with the largest decrease in 1- to 4-year-olds. Tolerability is generally good, with only mild reactions at the injection site and moderate fever The length of protection is not yet known. A two-dose schedule seems advisable to avoid breakthrough varicella, which occurs in 4% of vaccinees each year. Insufficient coverage is expected to lead to later disease onset, with more severe cases in adolescents and adults. Universal immunization could also increase the incidence of zoster. These problems indeed seem to be emerging in the United States. France has adopted restrictive guidelines on VZV vaccination, but they are expected to be revised when the combined MMR-V vaccine becomes available. Zoster vaccine, prepared with the same strain but at a higher concentration, has moderate efficacy on zoster and on post-zoster neuralgia in patients over 70. This vaccine is not yet recommended in France, because the length of protection is not known and there is a potential risk of delaying the occurrence of zoster and, thus, of increasing the risk of post zoster neuralgia.

  9. Self-consuming innate immunity in Arabidopsis

    DEFF Research Database (Denmark)

    Hofius, Daniel; Mundy, John; Petersen, Morten

    2009-01-01

    Programmed cell death (PCD) associated with the pathogen-induced hypersensitive response (HR) is a hallmark of plant innate immunity. HR PCD is triggered upon recognition of pathogen effector molecules by host immune receptors either directly or indirectly via effector modulation of host targets...

  10. Immunization registries in the EMR Era

    Science.gov (United States)

    Stevens, Lindsay A.; Palma, Jonathan P.; Pandher, Kiran K.; Longhurst, Christopher A.

    2013-01-01

    Background: The CDC established a national objective to create population-based tracking of immunizations through regional and statewide registries nearly 2 decades ago, and these registries have increased coverage rates and reduced duplicate immunizations. With increased adoption of commercial electronic medical records (EMR), some institutions have used unidirectional links to send immunization data to designated registries. However, access to these registries within a vendor EMR has not been previously reported. Purpose: To develop a visually integrated interface between an EMR and a statewide immunization registry at a previously non-reporting hospital, and to assess subsequent changes in provider use and satisfaction. Methods: A group of healthcare providers were surveyed before and after implementation of the new interface. The surveys addressed access of the California Immunization Registry (CAIR), and satisfaction with the availability of immunization information. Information Technology (IT) teams developed a “smart-link” within the electronic patient chart that provides a single-click interface for visual integration of data within the CAIR database. Results: Use of the tool has increased in the months since its initiation, and over 20,000 new immunizations have been exported successfully to CAIR since the hospital began sharing data with the registry. Survey data suggest that providers find this tool improves workflow and overall satisfaction with availability of immunization data. (p=0.009). Conclusions: Visual integration of external registries into a vendor EMR system is feasible and improves provider satisfaction and registry reporting. PMID:23923096

  11. Modulation of host immunity by tick saliva

    Czech Academy of Sciences Publication Activity Database

    Kotál, Jan; Langhansová, H.; Lieskovská, J.; Andersen, J. F.; Francischetti, I.M.B.; Chavakis, T.; Kopecký, J.; Pedra, J. H. F.; Kotsyfakis, Michalis; Chmelař, J.

    2015-01-01

    Roč. 128, OCT 14 2015 (2015), s. 58-68 ISSN 1874-3919 R&D Projects: GA ČR GAP502/12/2409 Institutional support: RVO:60077344 Keywords : Adaptive immunity * Innate immunity * Saliva * Salivary glands * Tick Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.867, year: 2015

  12. 45 CFR 61.16 - Immunity.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Immunity. 61.16 Section 61.16 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION HEALTHCARE INTEGRITY AND PROTECTION DATA BANK... Information by the Healthcare Integrity and Protection Data Bank § 61.16 Immunity. Individuals, entities or...

  13. Complement anaphylatoxins as immune regulators in cancer.

    Science.gov (United States)

    Sayegh, Eli T; Bloch, Orin; Parsa, Andrew T

    2014-08-01

    The role of the complement system in innate immunity is well characterized. However, a recent body of research implicates the complement anaphylatoxins C3a and C5a as insidious propagators of tumor growth and progression. It is now recognized that certain tumors elaborate C3a and C5a and that complement, as a mediator of chronic inflammation and regulator of immune function, may in fact foster rather than defend against tumor growth. A putative mechanism for this function is complement-mediated suppression of immune effector cells responsible for immunosurveillance within the tumor microenvironment. This paradigm accords with models of immune dysregulation, such as autoimmunity and infectious disease, which have defined a pathophysiological role for abnormal complement signaling. Several types of immune cells express the cognate receptors for the complement anaphylatoxins, C3aR and C5aR, and demonstrate functional modulation in response to complement stimulation. In turn, impairment of antitumor immunity has been intimately tied to tumor progression in animal models of cancer. In this article, the literature was systematically reviewed to identify studies that have characterized the effects of the complement anaphylatoxins on the composition and function of immune cells within the tumor microenvironment. The search identified six studies based upon models of lymphoma and ovarian, cervical, lung, breast, and mammary cancer, which collectively support the paradigm of complement as an immune regulator in the tumor microenvironment. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  14. Immunity to Babesia in mice I. Adoptive transfer of immunity to Babesia rodhaini with immune spleen cells and the effect of irradiation on the protection of immune mice

    NARCIS (Netherlands)

    Kuil, H.; Zivkovic, D.; Seinen, W.; Albers-van Bemmel, C.M.G.; Speksnijder, J.E.

    1984-01-01

    Immunisation of Balb/c mice against Babesia rodhaini by an amicarbalide- controlled infection resulted in a solid immunity which lasted for 216 days. With spleen cells of immune mice protection could be transferred both to naive mice pretreated with cyclophosphamide. Treatment of naive mice with

  15. Necroptotic signaling in adaptive and innate immunity.

    Science.gov (United States)

    Lu, Jennifer V; Chen, Helen C; Walsh, Craig M

    2014-11-01

    The vertebrate immune system is highly dependent on cell death for efficient responsiveness to microbial pathogens and oncogenically transformed cells. Cell death pathways are vital to the function of many immune cell types during innate, humoral and cellular immune responses. In addition, cell death regulation is imperative for proper adaptive immune self-tolerance and homeostasis. While apoptosis has been found to be involved in several of these roles in immunity, recent data demonstrate that alternative cell death pathways are required. Here, we describe the involvement of a programmed form of cellular necrosis called "necroptosis" in immunity. We consider the signaling pathways that promote necroptosis downstream of death receptors, type I transmembrane proteins of the tumor necrosis factor (TNF) receptor family. The involvement of necroptotic signaling through a "RIPoptosome" assembled in response to innate immune stimuli or genotoxic stress is described. We also characterize the induction of necroptosis following antigenic stimulation in T cells lacking caspase-8 or FADD function. While necroptotic signaling remains poorly understood, it is clear that this pathway is an essential component to effective vertebrate immunity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. 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,

  17. how to evade the immune system?

    Indian Academy of Sciences (India)

    HCV usually induces robust immune responses, but it frequently escapes the immune defense to establish persistent infection. The fact that HCV exists as an evolving quasispecies plays an important role in the selection of escape mutants. Furthermore, several viral proteins interfere with cellular functions, in particular, ...

  18. Pathogen Pressure Puts Immune Defense into Perspective

    NARCIS (Netherlands)

    Horrocks, Nicholas P. C.; Matson, Kevin D.; Tieleman, B. Irene

    2011-01-01

    The extent to which organisms can protect themselves from disease depends on both the immune defenses they maintain and the pathogens they face. At the same time, immune systems are shaped by the antigens they encounter, both over ecological and evolutionary time. Ecological immunologists often

  19. Performance, immunity, serum biochemical and hematological ...

    African Journals Online (AJOL)

    ... results suggest that supplementing broilers' diet with 5 g/kg thyme can indicate favorable influences of antibiotic growth promoter on performance without any detrimental impacts on immune responses and blood parameters. Key words: Broiler, thyme, growth performance, immunity, serum biochemistry, hematology.

  20. Determinants Of Missed Opportunities For Immunization Among ...

    African Journals Online (AJOL)

    Factors responsible for the missed opportunities included the attitude of the health worker, prolonged time of waiting to receive vaccine, immunization clashing with other schedules and transportation problem. Respondents' level ofknowledge on immunization and educational background were significantly associated with ...