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Sample records for cell-mediated immune responses

  1. Cell mediated immune response in human antirabies revaccination

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    Débora Regina Veiga

    1987-04-01

    Full Text Available The occurrence of secondary cell mediated immune response (CMI in human antirabies immunization was studied. The Puenzalida & Palácios vaccine was used because it is routinely used in Brazil. CMI was evaluated by lymphoblastic transformation indices obtained in whole blood culture in the presence of rabies and control (nervous tissue antigens. Eleven volunteers submitted to revaccination constituted the group under study, while three other volunteers submitted primo vaccination were utilized as control group. A clear secondary CMI to rabies antigen was detected in all the revaccinated volunteers who showed earlier and more intense response than the control group. Response to the control antigen, however, present in all the components of the first group was not detectable in two out of the three primovaccinated and very low in the third one.

  2. Essential oil of clove (Eugenia caryophyllata) augments the humoral immune response but decreases cell mediated immunity.

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    Halder, Sumita; Mehta, Ashish K; Mediratta, Pramod K; Sharma, Krishna K

    2011-08-01

    The present study was undertaken to explore the effect of the essential oil isolated from the buds of Eugenia caryophyllata on some immunological parameters. Humoral immunity was assessed by measuring the hemagglutination titre to sheep red blood cells and delayed type hypersensitivity was assessed by measuring foot pad thickness. Clove oil administration produced a significant increase in the primary as well as secondary humoral immune response. In addition, it also produced a significant decrease in foot pad thickness compared with the control group. Thus, these results suggest that clove oil can modulate the immune response by augmenting humoral immunity and decreasing cell mediated immunity. PMID:21796701

  3. Assessing humoral and cell-mediated immune response in Hawaiian green turtles, Chelonia mydas

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    Work, T.M.; Balazs, G.H.; Rameyer, R.A.; Chang, S.P.; Berestecky, J.

    2000-01-01

    Seven immature green turtles, Chelonia mydas, captured from Kaneohe Bay on the island of Oahu were used to evaluate methods for assessing their immune response. Two turtles each were immunized intramuscularly with egg white lysozyme (EWL) in Freunda??s complete adjuvant, Gerbu, or ISA-70; a seventh turtle was immunized with saline only and served as a control. Humoral immune response was measured with an indirect enzyme linked immunosorbent assay (ELISA). Cell-mediated immune response was measured using in vitro cell proliferation assays (CPA) using whole blood or peripheral blood mononuclear cells (PBM) cultured with concanavalin A (ConA), phytohaemagglutinin (PHA), or soluble egg EWL antigen. All turtles, except for one immunized with Gerbu and the control, produced a detectable humoral immune response by 6 weeks which persisted for at least 14 weeks after a single immunization. All turtles produced an anamnestic humoral immune response after secondary immunization. Antigen specific cell-mediated immune response in PBM was seen in all turtles either after primary or secondary immunization, but it was not as consistent as humoral immune response; antigen specific cell-mediated immune response in whole blood was rarely seen. Mononuclear cells had significantly higher stimulation indices than whole blood regardless of adjuvant, however, results with whole blood had lower variability. Both Gerbu and ISA-70 appeared to potentiate the cell-mediated immune response when PBM or whole blood were cultured with PHA. This is the first time cell proliferation assays have been compared between whole blood and PBM for reptiles. This is also the first demonstration of antigen specific cell-mediated response in reptiles. Cell proliferation assays allowed us to evaluate the cell-mediated immune response of green turtles. However, CPA may be less reliable than ELISA for detecting antigen specific immune response. Either of the three adjuvants appears suitable to safely elicit a

  4. CALORIE RESTRICTION ENHANCES T CELL MEDIATED IMMUNE RESPONSE IN OVERWEIGHT MEN AND WOMEN

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    It is well known that dietary energy restriction prolongs lifespan and enhances immune responsiveness in a wide range of laboratory animals. However, information on the applicability of these results to humans is limited. In this study we examined the effects of calorie restriction on T cell mediate...

  5. Inhibition of cell mediated immune responses by copper, ceruloplasmin and oral contraceptives

    International Nuclear Information System (INIS)

    We have shown that free copper inhibited lymphocyte transformation in the whole blood lymphocyte cultures. Ceruloplasmin also inhibited lymphocyte transformation in the above tests as well as another test involving purified protein derivative from Mycobacterium tuberculosis. Women on oral contraceptives have elevated serum copper and ceruloplasmin levels, as do cancer patients. We hypothesize that women on oral contraceptives may have decreased cell mediated immune responses and may thus be at higher risk for cancer induction

  6. Curculigoside augments cell-mediated immune responses in metastatic tumor-bearing animals.

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    Murali, Vishnu Priya; Kuttan, Girija

    2016-08-01

    A positive modulation of immune system is necessary for preparing the body to fight against malignant tumor cells. In the present study, the stimulatory effect of Curculigoside on cell-mediated immune response against the metastasis of B16F10 melanoma cells was analyzed in C57BL/6 mice. Curculigoside is a phenolic glucoside present in the plant Curculigo orchioides Gaertn. (Family - Amaryllidaceae). Administration of Curculigoside enhanced the natural killer (NK) cell activity, antibody-dependent cell-mediated cytotoxicity and complement-mediated cytotoxicity in metastatic tumor-bearing animals, when compared to the untreated control animals. The compound was also found to be effective in reducing the levels of proinflammatory cytokines such as TNF-α, IL-1β, IL-6 and GM-CSF during metastasis. Besides these, levels of TH1 cytokines, such as IL-2 and IFN-γ, were significantly enhanced (p immune responses by Curculigoside against B16F10-induced metastatic tumor progression in experimental animals. PMID:27228189

  7. Female Iberian wall lizards prefer male scents that signal a better cell-mediated immune response.

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    López, Pilar; Martín, José

    2005-12-22

    In spite of the importance of chemoreception in sexual selection of lizards, only a few studies have examined the composition of chemical signals, and it is unknown whether and how chemicals provide honest information. Chemical signals might be honest if there were a trade-off between sexual advertisement and the immune system. Here, we show that proportions of cholesta-5,7-dien-3-ol in femoral secretions of male Iberian wall lizards (Podarcis hispanica) were related to their T-cell-mediated immune response. Thus, only males with a good immune system may allocate higher amounts of this chemical to signalling. Furthermore, females selected scents of males with higher proportions of cholesta-5,7-dien-3-ol and lower proportions of cholesterol. Thus, females might base their mate choice on the males' quality as indicated by the composition of their chemical signals. PMID:17148218

  8. Cell-mediated and humoral immune responses in pigs following primary and challenge-exposure to Lawsonia intracellularis

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    Hvass, Henriette Cordes; Riber, Ulla; Jensen, Tim Kåre; Jungersen, Gregers

    2012-01-01

    To investigate immune responses upon re-infection with Lawsonia intracellularis, local and peripheral humoral and cell-mediated immune responses to primary and challenge inoculations were studied in 22 pigs. Pigs were orally inoculated with virulent L. intracellularis at the age of 5-6 weeks...... not boosted by the re-inoculation, since identical intestinal IgA responses developed in response to the inoculation in both the susceptible CC pigs and the protected RE pigs. A memory recall cell-mediated immune response developed in RE pigs which was significantly stronger compared to the primary......-mediated immune responses are likely mediators of protective immunity against L. intracellularis, with CD8+ effector cells and CD4+CD8+ double positive memory T cells as main contributors to the antigen-specific IFN-γ production....

  9. Cell mediated immune response of the Mediterranean sea urchin Paracentrotus lividus after PAMPs stimulation.

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    Romero, A; Novoa, B; Figueras, A

    2016-09-01

    The Mediterranean sea urchin (Paracentrotus lividus) is of great ecological and economic importance for the European aquaculture. Yet, most of the studies regarding echinoderm's immunological defense mechanisms reported so far have used the sea urchin Strongylocentrotus purpuratus as a model, and information on the immunological defense mechanisms of Paracentrotus lividus and other sea urchins, is scarce. To remedy this gap in information, in this study, flow cytometry was used to evaluate several cellular immune mechanisms, such as phagocytosis, cell cooperation, and ROS production in P. lividus coelomocytes after PAMP stimulation. Two cell populations were described. Of the two, the amoeboid-phagocytes were responsible for the phagocytosis and ROS production. Cooperation between amoeboid-phagocytes and non-adherent cells resulted in an increased phagocytic response. Stimulation with several PAMPs modified the phagocytic activity and the production of ROS. The premise that the coelomocytes were activated by the bacterial components was confirmed by the expression levels of two cell mediated immune genes: LPS-Induced TNF-alpha Factor (LITAF) and macrophage migration inhibitory factor (MIF). These results have helped us understand the cellular immune mechanisms in P. lividus and their modulation after PAMP stimulation. PMID:27113124

  10. Stimulatory effect of Eucalyptus essential oil on innate cell-mediated immune response

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    Rasi Guido

    2008-04-01

    Full Text Available Abstract Background Besides few data concerning the antiseptic properties against a range of microbial agents and the anti-inflammatory potential both in vitro and in vivo, little is known about the influence of Eucalyptus oil (EO extract on the monocytic/macrophagic system, one of the primary cellular effectors of the immune response against pathogen attacks. The activities of this natural extract have mainly been recognized through clinical experience, but there have been relatively little scientific studies on its biological actions. Here we investigated whether EO extract is able to affect the phagocytic ability of human monocyte derived macrophages (MDMs in vitro and of rat peripheral blood monocytes/granulocytes in vivo in absence or in presence of immuno-suppression induced by the chemotherapeutic agent 5-fluorouracil (5-FU. Methods Morphological activation of human MDMs was analysed by scanning electron microscopy. Phagocytic activity was tested: i in vitro in EO treated and untreated MDMs, by confocal microscopy after fluorescent beads administration; ii in vivo in monocytes/granulocytes from peripheral blood of immuno-competent or 5-FU immuno-suppressed rats, after EO oral administration, by flow cytometry using fluorescein-labelled E. coli. Cytokine release by MDMs was determined using the BD Cytometric Bead Array human Th1/Th2 cytokine kit. Results EO is able to induce activation of MDMs, dramatically stimulating their phagocytic response. EO-stimulated internalization is coupled to low release of pro-inflammatory cytokines and requires integrity of the microtubule network, suggesting that EO may act by means of complement receptor-mediated phagocytosis. Implementation of innate cell-mediated immune response was also observed in vivo after EO administration, mainly involving the peripheral blood monocytes/granulocytes. The 5-FU/EO combined treatment inhibited the 5-FU induced myelotoxicity and raised the phagocytic activity of the

  11. Cell-mediated immune responses differentiate infections with Brucella suis from Yersinia enterocolitica serotype O : 9 in pigs

    DEFF Research Database (Denmark)

    Riber, Ulla; Jungersen, Gregers

    2007-01-01

    serological Brucellosis reactions. While 36 of the 39 FPSR pigs were also FPSR in a second test, none of the pigs were test positive in whole blood IFN-gamma assay or Brucellergene OCB skin test. In conclusion, use of IFN-gamma assay and skin test as measurements of cell-mediated immune responses to non...

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

    DEFF Research Database (Denmark)

    Rasmussen, Josephine Skovgaard; Riber, Ulla; Lauritsen, Klara Tølbøll; Jakobsen, Jeanne Toft; Ahmad, Sardar; Jungersen, Gregers

    be due to increased systemic infection in the placebo group. Cell-mediated immune response was further characterised by four colour flow cytometry analysis of peripheral blood mononuclear cells (PBMCs) before Mhs challenge (day -1) and at days 6 and 9 after challenge. IFN-γ producing cells were found......-cell memory had occurred....

  13. Cell-mediated immune response of synovial fluid lymphocytes to ureaplasma antigen in Reiter's syndrome

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    Pavlica Ljiljana

    2003-01-01

    Full Text Available INTRODUCTION Reiter's syndrome (RS is an seronegative arthritis that occurs after urogenital or enteric infection which in addition with occular and/or mucocutaneous manifestations presents complete form of disease. According to previous understanding arthritis in the RS is the reactive one, which means that it is impossible to isolate its causative agent. However, there are the more and more authors suggesting that arthritis in the urogenital form of disease is caused by the infective agent in the affected joint. This suggestion is based on numerous studies on the presence of Chlmaydia trachomatis and Ureaplasma urealyticum in the inflamed joint by using new diagnostic methods in molecular biology published in the recent literature [1-3]. Besides, numerous studies of the humoral and cell-mediated immune response to "triggering" bacteria in the affected joint have supported previous suggestions [4-7]. Aim of the study was to determine whether synovial fluid T-cells specifically recognize the "triggering" bacteria presumably responsible for the Reiter's syndrome. METHOD The 3H-thymidine uptake procedure for measuring lymphocyte responses was applied to lymphocytes derived concurrently from synovial fluid (SF and from peripheral blood (PB [8]. Ureaplasma antigen and mitogen PHA stimulated lymphocytes in 24 RS patients (24 PB samples, 9 SF samples and the results were compared with those found in 10 patients with rheumatoid arthritis (RA (10 PB samples, 5 SF samples. Preparation of ureaplasma antigen. Ureaplasma was cultured on cell-free liquid medium [9]. Sample of 8 ml was heat-inactivated for 15 minutes at 601C and permanently stirred with magnetic mixer. The sample was centrifuged at 2000 x g for 40 minutes and than deposits carefully carried to other sterile glass tubes (Corex and recentrifuged at 9000 x g for 30 minutes. The deposit was washed 3 times in sterile 0.9% NaCl, and final sediment was resuspended in 1.2 ml sterile 0.9% Na

  14. Effect of Biophytum sensitivum on cell-mediated immune response in mice.

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    Guruvayoorappan, C; Kuttan, G

    2007-01-01

    Effect of Biophytum sensitivum on cell-mediated immune response was studied in normal as well as Ehrlich ascites tumor bearing BALB/c mice. Administration of Biophytum sensitivum significantly enhanced the proliferation of splenocytes, thymocytes and bone marrow cells by stimulating the mitogenic potential of various mitogens such as Lipopolysaccharide (LPS), Concanavalin A (Con A), Phytohaemagglutinin (PHA) and Poke Weed Mitogen (PWM). Natural killer (NK) cell activity was enhanced significantly by Biophytum sensitivum in both the normal (43.6% cell lysis on day 5) and the tumor bearing group (48.2% cell lysis on day 5), and it was found to be earlier than tumor bearing control animals (maximum of 13.4% cell lysis on day 9). Antibody dependent cellular cytotoxicity (ADCC) was also enhanced significantly in both Biophytum treated normal (35% cell lysis on day 7) as well as tumor bearing animals (40.2% cell lysis on day 7) compared to untreated control tumor bearing animals (maximum of 12.3% cell lysis on day 11). An early antibody dependent complement mediated cytotoxicity (ACC) was also observed in the Biophytum treated normal (22.6% cell lysis, on day 15) and tumor bearing animals (26.4% cell lysis, on day 15). Results of our present study suggest the immunomodulatory property of Biophytum sensitivum. PMID:18075848

  15. Assessment of humoral and cell-mediated immune response to measles–mumps–rubella vaccine viruses among patients with asthma

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    Yoo, Kwang Ha; Agarwal, Kanishtha; Butterfield, Michael; Jacobson, Robert M.; Poland, Gregory A.; Juhn, Young J.

    2010-01-01

    Little is known about the influence of asthma status on humoral and cell-mediated immune responses to measles–mumps–rubella (MMR) vaccine viruses. We compared the virus-specific IgG levels and lymphoproliferative response of peripheral blood mononuclear cells to MMR vaccine viruses between asthmatic and nonasthmatic patients. The study subjects included 342 healthy children aged 12–18 years who had received two doses of the MMR vaccine. We ascertained asthma status by applying predetermined c...

  16. Regulation of NKT cell-mediated immune responses to tumours and liver inflammation by mitochondrial PGAM5-Drp1 signalling

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    Kang, Young Jun; Bang, Bo-Ram; Han, Kyung Ho; Hong, Lixin; Shim, Eun-Jin; Ma, Jianhui; Lerner, Richard A.; Otsuka, Motoyuki

    2015-01-01

    The receptor-interacting protein kinase 3 (RIPK3) plays crucial roles in programmed necrosis and innate inflammatory responses. However, a little is known about the involvement of RIPK3 in NKT cell-mediated immune responses. Here, we demonstrate that RIPK3 plays an essential role in NKT cell function via activation of the mitochondrial phosphatase phosphoglycerate mutase 5 (PGAM5). RIPK3-mediated activation of PGAM5 promotes the expression of cytokines by facilitating nuclear translocation of...

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

    DEFF Research Database (Denmark)

    Utke, Katrin; Kock, Holger; Schuetze, Heike; Bergmann, Sven M.; Lorenzen, Niels; Einer-Jensen, Katja; Köllner, Bernd; Dalmo, Roy A.; Vesely, Tomas; Ototake, Mitsuru; Fischer, Uwe

    2008-01-01

    To identify viral proteins that induce cell-mediated cytotoxicity (CMC) against viral hemorrhagic septicemia virus (VHSV)-infected cells, rainbow trout were immunized with DNA vectors encoding the glycoprotein G or the nucleocapsid protein N of VHSV. The G protein was a more potent trigger of...

  18. Cell-mediated immune deficiency in Hodgkin's disease.

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    Kumar, R K; Penny, R

    1982-10-01

    Disturbances of the immune system frequently accompany the development of lymphomas in man. In the early stages of non-Hodgkin's lymphomas, abnormalities of immunological function are usually minimal, but impairment of both antibody- and cell-mediated immunity is often noted in advanced disease. In contrast, while antibody-mediated immune responses in patients with Hodgkin's disease usually remain intact until late in the course of the illness, cell-mediated immune dysfunction is an early and consistent feature. Here Rakesh Kumar and Ronald Penny discuss the abnormalities of cell-mediated immunity in Hodgkin's disease. PMID:25290229

  19. Empirical evidence of cold stress induced cell mediated and humoral immune response in common myna ( Sturnus tristis)

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    Sandhu, Mansur A.; Zaib, Anila; Anjum, Muhammad S.; Qayyum, Mazhar

    2015-11-01

    Common myna ( Sturnus tristis) is a bird indigenous to the Indian subcontinent that has invaded many parts of the world. At the onset of our investigation, we hypothesized that the immunological profile of myna makes it resistant to harsh/new environmental conditions. In order to test this hypothesis, a number of 40 mynas were caught and divided into two groups, i.e., 7 and 25 °C for 14 days. To determine the effect of cold stress, cell mediated and humoral immune responses were assessed. The macrophage engulfment percentage was significantly ( P immunization by SRBC. To the best of our knowledge, these findings have never been reported in the progression of this bird's invasion in frosty areas of the world. The results revealed a strengthened humoral immune response of myna and made this bird suitable for invasion in the areas of harsh conditions.

  20. Effect of rosemary (Rosmarinus officinalis) extract on weight, hematology and cell-mediated immune response of newborn goat kids

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    Borhan Shokrollahi; Fardin Amini; Shahin Fakour; Mohammad Amiri Andi

    2015-01-01

    This study aimed at evaluating the effects of different levels of rosemary (Rosmarinus officinalis) extract on growth rate, hematology and cell-mediated immune response in Markhoz newborn goat kids. Twenty four goat kids (aged 7 +/- 3 days) were randomly allotted to four groups with six replicates. The groups included: control, T1, T2 and T3 groups which received supplemented-milk with 0, 100, 200 and 400mg aqueous rosemary extract per kg of live body weight per day for 42 days. Body weights ...

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    The objective of this study was to use flow cytometry to assess chicken T cell-mediated immune responses. In this study two inbred genetic chicken lines (L130 and L133) were subjected to two times vaccination against Newcastle disease (ND) and a subsequent challenge by ND virus (NDV) infection....... Furthermore, peripheral lymphocytes from L133 exhibited a significantly higher expression of CD44 and CD45 throughout the experiment. Interestingly, also vaccine-induced differences were observed in L133 as immune chickens had a significantly higher CD45 expression on their lymphocytes than the naïve controls....... Immune chickens from both lines had a significantly higher frequency of circulating γδ T cells than the naïve controls both after vaccination and challenge. Finally, the proliferative capacity of peripheral CD4+ and CD8+ cells specific for NDV was addressed 3 weeks after vaccination and 1 week after...

  2. Potential for Cell-Mediated Immune Responses in Mouse Models of Pelizaeus-Merzbacher Disease

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    Southwood, Cherie M.; Bozena Fykkolodziej; Fabien Dachet; Alexander Gow

    2013-01-01

    Although activation of the innate and adaptive arms of the immune system are undoubtedly involved in the pathophysiology of neurodegenerative diseases, it is unclear whether immune system activation is a primary or secondary event. Increasingly, published studies link primary metabolic stress to secondary inflammatory responses inside and outside of the nervous system. In this study, we show that the metabolic stress pathway known as the unfolded protein response (UPR) leads to secondary acti...

  3. Humanized Mouse Models to Study Cell-Mediated Immune Responses to Liver-Stage Malaria Vaccines.

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    Good, Michael F; Hawkes, Michael T; Yanow, Stephanie K

    2015-11-01

    Malaria vaccine development is hampered by the lack of small animal models that recapitulate human immune responses to Plasmodium falciparum. We review the burgeoning literature on humanized mice for P. falciparum infection, including challenges in engraftment of human immune cells, hepatocytes, and erythrocytes. Recent advances in immune-compromised mouse models and stem cell technology have already enabled proof of concept that the entire parasite life cycle can be sustained in a murine model and that adaptive human immune responses to several parasite stages can be measured. Nonetheless, optimization is needed to achieve a reproducible and relevant murine model for malaria vaccine development. This review is focused on the complexities of T cell development in a mouse humanized with both a lymphoid system and hepatocytes. An understanding of this will facilitate the use of humanized mice in the development of liver-stage vaccines. PMID:26458783

  4. Caloric Restriction reduces inflammation and improves T cell-mediated immune response in obese mice but concomitant consumption of curcumin/piperine adds no further benefit

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    Obesity is associated with low-grade inflammation and impaired immune response. Caloric restriction (CR) has been shown to inhibit inflammatory response and enhance cell-mediated immune function. Curcumin, the bioactive phenolic component of turmeric spice, is proposed to have anti-obesity and anti-...

  5. The role of regulatory T cells in the control of B cell mediated immune responses

    OpenAIRE

    Wollenberg, Ivonne

    2011-01-01

    Tese de doutoramento, Ciências Biomédicas (Imunologia), Universidade de Lisboa, Faculdade de Medicina, 2011 This thesis reports research on the regulation of immune responses leading to a humoral immune reaction. This type of immune phenomena is based on B-T cell interactions. The first part of the thesis is devoted to study the effect of OX40-ligand blockade in preventing allergic airways disease in mice. Allergic airways disease is a Th2-dependent pathology associated with production of ...

  6. IL-10 polymorphism and cell-mediated immune response to Chlamydia trachomatis

    DEFF Research Database (Denmark)

    Öhman, H.; Tiitinen, A; Halttunen, M.; Birkelund, Svend; Christiansen, Gunna; Koskela, P.; Lehtinen, M.; Paavonen, J.; Surcel, H.-M.

    2006-01-01

    Chlamydia trachomatis infection induces an inflammatory response that is crucial in resolving acute infection but may also play a key role in the pathogenesis of C trachomatis associated infertility. The immune response is linked to cytokine secretion pattern which is influenced by the host genet...

  7. Potential for Cell-Mediated Immune Responses in Mouse Models of Pelizaeus-Merzbacher Disease

    Directory of Open Access Journals (Sweden)

    Cherie M. Southwood

    2013-09-01

    Full Text Available Although activation of the innate and adaptive arms of the immune system are undoubtedly involved in the pathophysiology of neurodegenerative diseases, it is unclear whether immune system activation is a primary or secondary event. Increasingly, published studies link primary metabolic stress to secondary inflammatory responses inside and outside of the nervous system. In this study, we show that the metabolic stress pathway known as the unfolded protein response (UPR leads to secondary activation of the immune system. First, we observe innate immune system activation in autopsy specimens from Pelizaeus-Merzbacher disease (PMD patients and mouse models stemming from PLP1 gene mutations. Second, missense mutations in mildly- and severely-affected Plp1-mutant mice exhibit immune-associated expression profiles with greater disease severity causing an increasingly proinflammatory environment. Third, and unexpectedly, we find little evidence for dysregulated expression of major antioxidant pathways, suggesting that the unfolded protein and oxidative stress responses are separable. Together, these data show that UPR activation can precede innate and/or adaptive immune system activation and that neuroinflammation can be titrated by metabolic stress in oligodendrocytes. Whether or not such activation leads to autoimmune disease in humans is unclear, but the case report of steroid-mitigated symptoms in a PMD patient initially diagnosed with multiple sclerosis lends support.

  8. T cell mediated immune responses in patients with tuberculous lymphadenitis from Butajira, southern Ethiopia.

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    Habte, Abebe; Geletu, Mulu; Olobo, Joseph Okao; Kidane, Dawit; Negesse, Yohannes; Yassin, Mohammed Ahmed; Kifle, Bereda; Abate, Getahun; Harboe, Morten; Aseff, Abraham

    2004-04-01

    The control of tuberculosis (TB) requires improved vaccines in addition to chemotherapy. It is essential to understand the immune response in tuberculosis to successfully evaluate potential vaccines. Current investigations have focused on immune responses in pulmonary forms. We studied the T-cell response of peripheral blood mononuclear cells (PBMC) from HIV-infected (n=8) and non-infected patients (n=19) with lymph node tuberculosis to PPD and short-term culture filtrates (ST-CF) of M. tuberculosis. PBMC from HIV-negative TB lymphadenitis patients proliferated in response to both antigens (p<0.001) and produced variably higher levels of IFN-gamma compared to healthy controls (p=0.02) (n=19) from the same area. Such responses were suppressed in HIV co-infected subjects. The results indicate that circulating PBMC in the apparently localized form of tuberculous lymphadenitis react to mycobacterial antigens in a similar pattern as those of patients with pulmonary disease. PMID:16895017

  9. Effect of rosemary (Rosmarinus officinalis extract on weight, hematology and cell-mediated immune response of newborn goat kids

    Directory of Open Access Journals (Sweden)

    Borhan Shokrollahi

    2015-06-01

    Full Text Available This study aimed at evaluating the effects of different levels of rosemary (Rosmarinus officinalis extract on growth rate, hematology and cell-mediated immune response in Markhoz newborn goat kids. Twenty four goat kids (aged 7±3 days were randomly allotted to four groups with six replicates. The groups included: control, T1, T2 and T3 groups which received supplemented-milk with 0, 100, 200 and 400mg aqueous rosemary extract per kg of live body weight per day for 42 days. Body weights of kids were measured weekly until the end of the experiment. On day 42, 10 ml blood samples were collected from each kid through the jugular vein. Cell-mediated immune response was assessed through the double skin thickness after intradermal injection of phyto-hematoglutinin (PHA at day 21 and 42. No significant differences were seen in initial body weight, average daily gain (ADG and total gain. However, significant differences in globulin (P<0.05, and white blood cells (WBC (P<0.001 were observed. There were no significant differences in haemoglobin (Hb, packed cell volume (PCV, red blood cells (RBC, lymphocytes and neutrophils between the treatments. Skin thickness in response to intra dermal injection of PHA significantly increased in the treated groups as compared to the control group at day 42 (P<0.01 with the T3 group showing the highest response to PHA injection. In conclusion, the results indicated that aqueous rosemary extract supplemented-milk had a positive effect on immunity and skin thickness of newborn goat kids.

  10. Plasmodium berghei: immunosuppression of the cell-mediated immune response induced by nonviable antigenic preparations

    International Nuclear Information System (INIS)

    In this work, plasmodial antigens were examined for their ability to suppress the cellular immune response during lethal Plasmodium berghei infection. Splenic enlargement and the number and function of white spleen cells were assessed after injection of normal mice with irradiated parasitized erythrocytes (IPE) or with parasitized erythrocytes (PE) membranes. Both IPE and PE membranes caused splenomegaly and an increase in the number of splenic white cells with concurrent alteration of the relative proportions of T cells and macrophages. The percentage of T lymphocytes was fractionally diminished, but there was a marked increase in Lyt 2.2 positive (suppressor and cytotoxic) T subsets and in the number of splenic macrophage precursors. The pathological enlargement of the spleen was induced by various plasma membrane-derived antigens containing both proteins and carbohydrates. Splenocytes of mice injected with liposomes containing deoxycholate-treated PE or PE fractions showed both diminished interleukin 2 production and a decreased response to mitogen. It appears that some of the changes in the cellular immune response during P. berghei infection are a consequence of the massive provision of a wide spectrum of antigens, capable of suppressing the immune response. Thus, it may be appropriate to evaluate the possible negative effect of parasite epitopes that are candidates for vaccine

  11. Plasmodium berghei: immunosuppression of the cell-mediated immune response induced by nonviable antigenic preparations

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    Gross, A.; Frankenburg, S.

    1989-01-01

    In this work, plasmodial antigens were examined for their ability to suppress the cellular immune response during lethal Plasmodium berghei infection. Splenic enlargement and the number and function of white spleen cells were assessed after injection of normal mice with irradiated parasitized erythrocytes (IPE) or with parasitized erythrocytes (PE) membranes. Both IPE and PE membranes caused splenomegaly and an increase in the number of splenic white cells with concurrent alteration of the relative proportions of T cells and macrophages. The percentage of T lymphocytes was fractionally diminished, but there was a marked increase in Lyt 2.2 positive (suppressor and cytotoxic) T subsets and in the number of splenic macrophage precursors. The pathological enlargement of the spleen was induced by various plasma membrane-derived antigens containing both proteins and carbohydrates. Splenocytes of mice injected with liposomes containing deoxycholate-treated PE or PE fractions showed both diminished interleukin 2 production and a decreased response to mitogen. It appears that some of the changes in the cellular immune response during P. berghei infection are a consequence of the massive provision of a wide spectrum of antigens, capable of suppressing the immune response. Thus, it may be appropriate to evaluate the possible negative effect of parasite epitopes that are candidates for vaccine.

  12. Humoral and cell mediated immune responses to a pertussis containing vaccine in pregnant and nonpregnant women.

    Science.gov (United States)

    Huygen, Kris; Caboré, Raïssa Nadège; Maertens, Kirsten; Van Damme, Pierre; Leuridan, Elke

    2015-08-01

    Vaccination of pregnant women is recommended for some infectious diseases in order to protect both women and offspring through high titres of maternal IgG antibodies. Less is known on the triggering of cellular immune responses by vaccines administered during pregnancy. In an ongoing study on maternal pertussis vaccination (2012-2014) 18 pregnant women were vaccinated with a tetanus-diphtheria-acellular pertussis (Tdap) containing vaccine (Boostrix®) during the third pregnancy trimester. Sixteen age-matched nonpregnant women received the same vaccine in the same time period. A blood sample was taken at the moment of, but before vaccination and one month and one year after vaccination. Anti-Pertussis Toxin (PT), filamentous hemagglutinin (FHA), pertactin (Prn), tetanus toxin (TT) and diphtheria toxin (DT) antibodies were measured by ELISA. Cellular immune responses were analyzed using a diluted whole blood assay, measuring proliferation, and cytokine release in response to vaccine antigens PT, FHA, TT, and to pokeweed mitogen (PWM) as polyclonal stimulus. Antibody levels to all five vaccine components increased significantly and to the same extent after vaccination in pregnant and nonpregnant women. One year after vaccination, antibody titres had decreased particularly to PT, but they were still significantly higher to all antigens than before vaccination. In contrast, proliferative and IFN-γ responses were increased to TT, PT, and FHA in nonpregnant women one month after vaccination, whereas in pregnant women only TT specific T cell responses were increased and to a lesser extent than in the control group. One year after vaccination, cellular responses equaled the baseline levels detected prior to vaccination in both groups. In conclusion, a Tdap vaccination can increase vaccine specific IgG antibodies to the same extent in pregnant and in nonpregnant women, whereas the stimulation of vaccine specific Th1 type cellular immune responses with this acellular vaccine

  13. CD4+ T cells mediate mucosal and systemic immune responses to experimental hookworm infection

    OpenAIRE

    DONDJI, B.; Sun, T.; BUNGIRO, R. D.; VERMEIRE, J. J.; HARRISON, L. M.; BIFULCO, C.; Cappello, M

    2010-01-01

    Hookworm infection is associated with anaemia and malnutrition in many resource-limited countries. Ancylostoma hookworms have previously been shown to modulate host cellular immune responses through multiple mechanisms, including reduced mitogen-mediated lymphocyte proliferation, impaired antigen presentation/processing, and relative reductions in CD4+ T cells in the spleen and mesenteric lymph nodes. Syrian hamsters were depleted of CD4+ for up to 9 days following intraperitoneal injection (...

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

  15. Empirical evidence of cold stress induced cell mediated and humoral immune response in common myna ( Sturnus tristis)

    Science.gov (United States)

    Sandhu, Mansur A.; Zaib, Anila; Anjum, Muhammad S.; Qayyum, Mazhar

    2015-11-01

    Common myna ( Sturnus tristis) is a bird indigenous to the Indian subcontinent that has invaded many parts of the world. At the onset of our investigation, we hypothesized that the immunological profile of myna makes it resistant to harsh/new environmental conditions. In order to test this hypothesis, a number of 40 mynas were caught and divided into two groups, i.e., 7 and 25 °C for 14 days. To determine the effect of cold stress, cell mediated and humoral immune responses were assessed. The macrophage engulfment percentage was significantly ( P blood cells (SRBC). Macrophage engulfment/cell and nitric oxide production behaved in a similar manner. However, splenic cells plaque formation, heterophil to lymphocyte (H/L) ratio, and serum IgM or IgG production remained non-significant. There was a significant increase of IgG antibody production after a second immunization by SRBC. To the best of our knowledge, these findings have never been reported in the progression of this bird's invasion in frosty areas of the world. The results revealed a strengthened humoral immune response of myna and made this bird suitable for invasion in the areas of harsh conditions.

  16. LACK OF IMMUNODEPRESSION IN THE ANTIGEN SPECIFIC CELL MEDIATED IMMUNE RESPONSE AFTER CHALLENGE WITH VIRULENT OR VERY VIRULENT MAREK'S DISEASE VIRUS STRAINS

    Science.gov (United States)

    Infection with Marek's disease is known to produce a generalized "immunodepression" to the cell-mediated immune response as measured by reduced mitogen stimulation. We used the major histocompatibility complex restricted (MHC) cytotoxic T lymphocyte (CTL) response to the avian leukosis virus (ALV) ...

  17. Cell-mediated immune responses to a cloned Plasmodium falciparum antigen

    Energy Technology Data Exchange (ETDEWEB)

    Rollwagen, F.M.; Pacheco, N.D.; Wistar, R. Jr.

    1986-03-05

    A peptide fragment of the Plasmodium falciparum (P.f.) circumsporozoite protein (CSP) containing 32 repeats of the immunodominant tetrapeptide ASN-ALA-ASN-PRO (R32tet32) is currently being evaluated as a vaccine in man. This R32tet32 peptide, prepared by recombinant DNA technology from a cloned P.f. gene fragment, has been examined for its ability to stimulate T-cell proliferation in experimental animals. Groups of mice were injected with either R32tet32 emulsified in Freund's complete adjuvant (CFA), or live, or frozen-thawed P.f. sporozoites. Lymphocytes from such mice were cocultured with varying doses of R32tet32 or irrelevant antigen. Proliferation was assessed by /sup 3/H-thymidine uptake; serum antibody was analyzed by ELISA. A proliferative response was found in mice immunized with R32tet32+CFA as early as day 7 post-injection, and was persistent through at least day 23. No proliferation in response to R32tet32 was observed in lymphocytes taken from mice injected with live or frozen-thawed sporozoites. All three immunogens induced both IgM and IgG antibody to R32tet32. They conclude that exposure to live or frozen-thawed P.f. sporozoites alone is sufficient to generate T-cell helper activity for subsequent antibody production, but that antigen+CFA was necessary to generate significant T-cell proliferative activity.

  18. Cell-mediated immune responses to a cloned Plasmodium falciparum antigen

    International Nuclear Information System (INIS)

    A peptide fragment of the Plasmodium falciparum (P.f.) circumsporozoite protein (CSP) containing 32 repeats of the immunodominant tetrapeptide ASN-ALA-ASN-PRO (R32tet32) is currently being evaluated as a vaccine in man. This R32tet32 peptide, prepared by recombinant DNA technology from a cloned P.f. gene fragment, has been examined for its ability to stimulate T-cell proliferation in experimental animals. Groups of mice were injected with either R32tet32 emulsified in Freund's complete adjuvant (CFA), or live, or frozen-thawed P.f. sporozoites. Lymphocytes from such mice were cocultured with varying doses of R32tet32 or irrelevant antigen. Proliferation was assessed by 3H-thymidine uptake; serum antibody was analyzed by ELISA. A proliferative response was found in mice immunized with R32tet32+CFA as early as day 7 post-injection, and was persistent through at least day 23. No proliferation in response to R32tet32 was observed in lymphocytes taken from mice injected with live or frozen-thawed sporozoites. All three immunogens induced both IgM and IgG antibody to R32tet32. They conclude that exposure to live or frozen-thawed P.f. sporozoites alone is sufficient to generate T-cell helper activity for subsequent antibody production, but that antigen+CFA was necessary to generate significant T-cell proliferative activity

  19. Dendritic cell based immunotherapy using tumor stem cells mediates potent antitumor immune responses.

    Science.gov (United States)

    Dashti, Amir; Ebrahimi, Marzieh; Hadjati, Jamshid; Memarnejadian, Arash; Moazzeni, Seyed Mohammad

    2016-04-28

    Cancer stem cells (CSCs) are demonstrated to be usually less sensitive to conventional methods of cancer therapies, resulting in tumor relapse. It is well-known that an ideal treatment would be able to selectively target and kill CSCs, so as to avoid the tumor reversion. The aim of our present study was to evaluate the effectiveness of a dendritic cell (DC) based vaccine against CSCs in a mouse model of malignant melanoma. C57BL/6 mouse bone marrow derived DCs pulsed with a murine melanoma cell line (B16F10) or CSC lysates were used as a vaccine. Immunization of mice with CSC lysate-pulsed DCs was able to induce a significant prophylactic effect by a higher increase in lifespan and obvious depression of tumor growth in tumor bearing mice. The mice vaccinated with DCs loaded with CSC-lysate were revealed to produce specific cytotoxic responses to CSCs. The proliferation assay and cytokine (IFN-γ and IL-4) secretion of mice vaccinated with CSC lysate-pulsed DCs also showed more favorable results, when compared to those receiving B16F10 lysate-pulsed DCs. These findings suggest a potential strategy to improve the efficacy of DC-based immunotherapy of cancers. PMID:26803056

  20. Defective cell mediated immunity in sarcoidosis: effect of interleukin-2.

    OpenAIRE

    Lyons, D J; Gao, L.; Mitchell, E B; Mitchell, D. N.

    1988-01-01

    Interleukin-2 has been reported to enhance the immune response in diseases characterised by defective cell mediated immunity. The effect of exogenous recombinant interleukin-2 was studied on the proliferative and cytotoxic responses of peripheral blood mononuclear cells from 39 patients with sarcoidosis and 14 healthy control subjects. The proliferative response to purified protein derivative was smaller in patients than in control subjects (p less than 0.001) whereas the response to 80 U int...

  1. The effect of arginine dietary supplementation in broiler breeder hens on offspring humoral and cell-mediated immune responses

    Directory of Open Access Journals (Sweden)

    AE Murakami

    2014-06-01

    Full Text Available The influence of supplementing the diet of broiler breeder hens with arginine (Arg on their offspring's humoral and cell-mediated immune response was evaluated in two experiments. In experiments I and II, breeder hens were fed diets containing graded levels of Arg (0.943, 1.093, 1.243, 1.393 and 1.543% digestible Arg. In experiment I, the offspring was randomly grouped according to the treatment received by the breeder hens, with five levels of Arg in the maternal diet and six replicates, giving a total 30 experimental units. In experiment II, the offspring were grouped in accordance with the treatment received by the breeder hens; however, Arg was added to the starter diet (1.300, 1.450, 1.600, 1.750 and 1.900% digestible Arg and also the growing diet (1.150, 1.300, 1.450, 1.600 and 1.750% digestible Arg. Supplementation of the broiler breeder hen diet did not influence (p > 0.05 the development of the lymphoid organs (cloacal bursa, thymus and spleen of the offspring, whether their diet were supplemented or not. Nevertheless, greater weight and dimensions cloacal bursa were found in the supplemented offspring in comparison with the nonsupplemented offspring. Macrophage phagocytic activity was found to be unaffected (p > 0.05, independently of the Arg supplementation. The offspring fed with supplemented diets showed a linear reduction in the antibody titer against Newcastle Disease (p 0.05 by the breeder hen diet. This study concluded that supplementing the breeder hen diet with arginine is insufficient to improve the humoral and cellular immune response, requiring supplementation of the offspring diet.

  2. Humoral and Cell-Mediated Immune Responses to Alternate Booster Schedules of Anthrax Vaccine Adsorbed in Humans.

    Science.gov (United States)

    Quinn, Conrad P; Sabourin, Carol L; Schiffer, Jarad M; Niemuth, Nancy A; Semenova, Vera A; Li, Han; Rudge, Thomas L; Brys, April M; Mittler, Robert S; Ibegbu, Chris C; Wrammert, Jens; Ahmed, Rafi; Parker, Scott D; Babcock, Janiine; Keitel, Wendy; Poland, Gregory A; Keyserling, Harry L; El Sahly, Hana; Jacobson, Robert M; Marano, Nina; Plikaytis, Brian D; Wright, Jennifer G

    2016-04-01

    Protective antigen (PA)-specific antibody and cell-mediated immune (CMI) responses to annual and alternate booster schedules of anthrax vaccine adsorbed (AVA; BioThrax) were characterized in humans over 43 months. Study participants received 1 of 6 vaccination schedules: a 3-dose intramuscular (IM) priming series (0, 1, and 6 months) with a single booster at 42 months (4-IM); 3-dose IM priming with boosters at 18 and 42 months (5-IM); 3-dose IM priming with boosters at 12, 18, 30, and 42 months (7-IM); the 1970 licensed priming series of 6 doses (0, 0.5, 1, 6, 12, and 18 months) and two annual boosters (30 and 42 months) administered either subcutaneously (SQ) (8-SQ) or IM (8-IM); or saline placebo control at all eight time points. Antibody response profiles included serum anti-PA IgG levels, subclass distributions, avidity, and lethal toxin neutralization activity (TNA). CMI profiles included frequencies of gamma interferon (IFN-γ)- and interleukin 4 (IL-4)-secreting cells and memory B cells (MBCs), lymphocyte stimulation indices (SI), and induction of IFN-γ, IL-2, IL-4, IL-6, IL-1β, and tumor necrosis factor alpha (TNF-α) mRNA. All active schedules elicited high-avidity PA-specific IgG, TNA, MBCs, and T cell responses with a mixed Th1-Th2 profile and Th2 dominance. Anti-PA IgG and TNA were highly correlated (e.g., month 7,r(2)= 0.86,Pvaccination. CMI responses to the 3-dose IM priming remained elevated up to 43 months. (This study has been registered at ClinicalTrials.gov under registration no. NCT00119067.). PMID:26865594

  3. Cell-mediated immunity to Toxoplasma gondii develops primarily by local Th-1 host immune responses in the absence of parasite replication1

    Science.gov (United States)

    Gigley, Jason P.; Fox, Barbara A.; Bzik, David J.

    2008-01-01

    A single inoculation of mice with the live attenuated Toxoplasma gondii uracil auxotroph strain cps1-1 induces long-lasting immunity against lethal challenge with hyper-virulent strain RH. The mechanism for this robust immunity in the absence of parasite replication has not been addressed. The mechanism of long-lasting immunity, the importance of route of immunization, cellular recruitment to the site of infection, and local and systemic inflammation were evaluated. Our results show that infection with cps1-1 elicits long-lasting CD8+ T cell mediated immunity. We show that immunization with cps1-1 infected DCs elicits long-lasting immunity. Intraperitoneal infection with cps1-1 induced a rapid influx of GR1+ neutrophils and 2 stages of GR1+ CD68+ inflammatory monocyte infiltration into the site of inoculation. CD19+ B cells and CD3+ T cells steadily increase for 8 days after infection. CD8+ T cells were rapidly recruited to the site of infection and increased faster than CD4+ T cells. Surprisingly, cps1-1 infection induced high systemic levels of bioactive IL-12p70 and very low level and transient systemic Ifn-γ. Furthermore, we show significant levels of these inflammatory cytokines were locally produced at the site of cps1-1 inoculation. These findings offer new insight into immunological mechanisms and local host responses to a non-replicating Type I parasite infection associated with development of long-lasting immunity to Toxoplasma gondii. PMID:19124750

  4. Cell-mediated immunity to Toxoplasma gondii develops primarily by local Th1 host immune responses in the absence of parasite replication.

    Science.gov (United States)

    Gigley, Jason P; Fox, Barbara A; Bzik, David J

    2009-01-15

    A single inoculation of mice with the live, attenuated Toxoplasma gondii uracil auxotroph strain cps1-1 induces long-lasting immunity against lethal challenge with hypervirulent strain RH. The mechanism for this robust immunity in the absence of parasite replication has not been addressed. The mechanism of long-lasting immunity, the importance of route of immunization, cellular recruitment to the site of infection, and local and systemic inflammation were evaluated. Our results show that infection with cps1-1 elicits long-lasting CD8+ T cell- mediated immunity. We show that immunization with cps1-1-infected dendritic cells elicits long-lasting immunity. Intraperitoneal infection with cps1-1 induced a rapid influx of GR1+ neutrophils and two stages of GR1+CD68+ inflammatory monocyte infiltration into the site of inoculation. CD19+ B cells and CD3+ T cells steadily increase for 8 days after infection. CD8+ T cells were rapidly recruited to the site of infection and increased faster than CD4+ T cells. Surprisingly, cps1-1 infection induced high systemic levels of bioactive IL-12p70 and a very low level and transient systemic IFN-gamma. Furthermore, we show significant levels of these inflammatory cytokines were locally produced at the site of cps1-1 inoculation. These findings offer new insight into immunological mechanisms and local host responses to a non-replicating type I parasite infection associated with development of long-lasting immunity to Toxoplasma gondii. PMID:19124750

  5. In vitro assessment of the cell-mediated immune response to herpes simplex virus in man

    International Nuclear Information System (INIS)

    These studies demonstrated that human peripheral blood mononuclear cells (PBMC) from individuals sensitized to herpes simplex virus type 1 (HSV-1) were capable of producing interleukin 2 (IL 2) following in vitro stimulation with HSV antigen. IL 2 activity was detected by the direct addition of the murine IL 2-dependent cell line, CTLL-20, to γ-irradiated cultures of HSV-1 antigen-stimulated PBMC. It was found that PBMC from sensitized individuals produced IL 2 in a dose-dependent manner after in vitro stimulation with HSV antigen. Furthermore, IL 2 production in response to viral antigen correlated with viral antigen-induced proliferation of PBMC. It was also shown that contact with HSV-1 antigen induced the expression of IL 2 receptors on a small percentage of human PBMC. While this suggested that IL 2 receptor expression was associated with viral antigen-induced proliferation responses, the level of induced IL 2 receptor expression remained close to the lower limit of detectability for cytofluorographic analysis. Experiments to elucidate the role of the macrophage (MO) in the response to viral antigen revealed that HSV antigen-induced IL 2 production by sensitized T lymphocytes was dependent on the presence of an accessory MO. To investigate the signals provided to T lymphocytes by accessory cells, MOs were pulsed with HSV antigen and treated with paraformaldehyde. This allowed HSV antigen display, but prevented monokine (IL 1) secretion. The treated MOs could no longer induce sensitized lymphocytes to produce IL 2

  6. T-Cell Mediated Immune Responses Induced in ret Transgenic Mouse Model of Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Dirk Schadendorf

    2012-04-01

    Full Text Available Poor response of human malignant melanoma to currently available treatments requires a development of innovative therapeutic strategies. Their evaluation should be based on animal models that resemble human melanoma with respect to genetics, histopathology and clinical features. Here we used a transgenic mouse model of spontaneous skin melanoma, in which the ret transgene is expressed in melanocytes under the control of metallothionein-I promoter. After a short latency, around 25% mice develop macroscopic skin melanoma metastasizing to lymph nodes, bone marrow, lungs and brain, whereas other transgenic mice showed only metastatic lesions without visible skin tumors. We found that tumor lesions expressed melanoma associated antigens (MAA tyrosinase, tyrosinase related protein (TRP-1, TRP-2 and gp100, which could be applied as targets for the immunotherapy. Upon peptide vaccination, ret transgenic mice without macroscopic melanomas were able to generate T cell responses not only against a strong model antigen ovalbumin but also against typical MAA TRP-2. Although mice bearing macroscopic primary tumors could also display an antigen-specific T cell reactivity, it was significantly down-regulated as compared to tumor-free transgenic mice or non-transgenic littermates. We suggest that ret transgenic mice could be used as a pre-clinical model for the evaluation of novel strategies of melanoma immunotherapy.

  7. T-Cell Mediated Immune Responses Induced in ret Transgenic Mouse Model of Malignant Melanoma

    International Nuclear Information System (INIS)

    Poor response of human malignant melanoma to currently available treatments requires a development of innovative therapeutic strategies. Their evaluation should be based on animal models that resemble human melanoma with respect to genetics, histopathology and clinical features. Here we used a transgenic mouse model of spontaneous skin melanoma, in which the ret transgene is expressed in melanocytes under the control of metallothionein-I promoter. After a short latency, around 25% mice develop macroscopic skin melanoma metastasizing to lymph nodes, bone marrow, lungs and brain, whereas other transgenic mice showed only metastatic lesions without visible skin tumors. We found that tumor lesions expressed melanoma associated antigens (MAA) tyrosinase, tyrosinase related protein (TRP)-1, TRP-2 and gp100, which could be applied as targets for the immunotherapy. Upon peptide vaccination, ret transgenic mice without macroscopic melanomas were able to generate T cell responses not only against a strong model antigen ovalbumin but also against typical MAA TRP-2. Although mice bearing macroscopic primary tumors could also display an antigen-specific T cell reactivity, it was significantly down-regulated as compared to tumor-free transgenic mice or non-transgenic littermates. We suggest that ret transgenic mice could be used as a pre-clinical model for the evaluation of novel strategies of melanoma immunotherapy

  8. T-Cell Mediated Immune Responses Induced in ret Transgenic Mouse Model of Malignant Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Abschuetz, Oliver [Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim , Heidelberg 69120 (Germany); Osen, Wolfram [Division of Translational Immunology, German Cancer Center, Heidelberg 69120 (Germany); Frank, Kathrin [Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim , Heidelberg 69120 (Germany); Kato, Masashi [Unit of Environmental Health Sciences, Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Aichi 487-8501 (Japan); Schadendorf, Dirk [Department of Dermatology, University Hospital Essen, Essen 45122 (Germany); Umansky, Viktor, E-mail: v.umansky@dkfz.de [Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim , Heidelberg 69120 (Germany)

    2012-04-26

    Poor response of human malignant melanoma to currently available treatments requires a development of innovative therapeutic strategies. Their evaluation should be based on animal models that resemble human melanoma with respect to genetics, histopathology and clinical features. Here we used a transgenic mouse model of spontaneous skin melanoma, in which the ret transgene is expressed in melanocytes under the control of metallothionein-I promoter. After a short latency, around 25% mice develop macroscopic skin melanoma metastasizing to lymph nodes, bone marrow, lungs and brain, whereas other transgenic mice showed only metastatic lesions without visible skin tumors. We found that tumor lesions expressed melanoma associated antigens (MAA) tyrosinase, tyrosinase related protein (TRP)-1, TRP-2 and gp100, which could be applied as targets for the immunotherapy. Upon peptide vaccination, ret transgenic mice without macroscopic melanomas were able to generate T cell responses not only against a strong model antigen ovalbumin but also against typical MAA TRP-2. Although mice bearing macroscopic primary tumors could also display an antigen-specific T cell reactivity, it was significantly down-regulated as compared to tumor-free transgenic mice or non-transgenic littermates. We suggest that ret transgenic mice could be used as a pre-clinical model for the evaluation of novel strategies of melanoma immunotherapy.

  9. Ubiquitin Conjugation of Hepatitis B Virus Core Antigen DNA Vaccine Leads to Enhanced Cell-Mediated Immune Response in BALB/c Mice

    OpenAIRE

    Chen, Jian-Hua; Yu, Yong-Sheng; Liu, Hong-Hong; Chen, Xiao-Hua; Xi, Min; ZANG, GUO-QING; Tang, Zheng-Hao

    2011-01-01

    Background Nearly 350 million persons worldwide are chronically infected with hepatitis B virus (HBV). Ubiquitin (Ub) is a highly conserved small regulatory protein, ubiquitous in eukaryotes, that usually serves as a signal for the target protein that is recognised and degraded in proteasomes . The Ub-mediated processing of antigens is rapid and efficient and stimulates cell-mediated immune responses. Accordingly, Ub-mediated processing of antigens has been widely used in chronic-infection an...

  10. Effect of space flight on cell-mediated immunity

    Science.gov (United States)

    Mandel, A. D.; Balish, E.

    1977-01-01

    The cell-mediated immune response to Listeria monocytogenes was studied in rats subjected to 20 days of flight aboard the Soviet biosatellite Kosmos 7820. Groups of rats were immunized with 1,000,000 formalin-killed Listeria suspended in Freunds Complete Adjuvant, 5 days prior to flight. Immunized rats subjected to the same environmental factors as the flight rats, except flight itself, and immunized and nonimmunized rats held in a normal animal colony served as controls. Following recovery, lymphocyte cultures were harvested from spleens of all rats, cultured in vitro in the presence of L. monocytogenes antigens, Phytohemagglutinin, Conconavlin A, or purified protein derivative (PPD), and measured for their uptake of H-3-thymidine. Although individual rats varied considerably, all flight and immunized control rats gave a blastogenic response to the Listeria antigens and PPD. With several mitogens, the lymphocytes of flight rats showed a significantly increased blastogenic response over the controls. The results of this study do not support a hypothesis of a detrimental effect of space flight on cell-mediated immunity. The data suggest a possible suppressive effect of stress and gravity on an in vitro correlate of cell-mediated immunity.

  11. A suicidal DNA vaccine expressing the fusion protein of peste des petits ruminants virus induces both humoral and cell-mediated immune responses in mice.

    Science.gov (United States)

    Wang, Yong; Yue, Xiaolin; Jin, Hongyan; Liu, Guangqing; Pan, Ling; Wang, Guijun; Guo, Hao; Li, Gang; Li, Yongdong

    2015-12-01

    Peste des petits ruminants (PPR), a highly contagious disease induced by PPR virus (PPRV), affects sheep and goats. PPRV fusion (F) protein is important for the induction of immune responses against PPRV. We constructed a Semliki Forest virus (SFV) replicon-vectored DNA vaccine ("suicidal DNA vaccine") and evaluated its immunogenicity in BALB/c mice. The F gene of PPRV was cloned and inserted into the SFV replicon-based vector pSCA1. The antigenicity of the resultant plasmid pSCA1/F was identified by indirect immunofluorescence and western blotting. BALB/c mice were then intramuscularly injected with pSCA1/F three times at 14-d intervals. Specific antibodies and virus-neutralizing antibodies against PPRV were quantified by indirect ELISA and microneutralization tests, respectively. Cell-mediated immune responses were examined by cytokine and lymphocyte proliferation assays. The pSCA1/F expressed F protein in vitro and induced specific and neutralizing antibody production, and lymphocyte proliferation in mice. Mice vaccinated with pSCA1/F had increased IL-2 and IL-10 levels after 24-h post first immunization. IFN-γ and TNF-α levels increased from that time point and gradually decreased thereafter. Thus, the Semliki Forest virus replicon-vectored DNA vaccine expressing the F protein of PPRV induced both humoral and cell-mediated immune responses in mice. This could be considered as a novel strategy for vaccine development against PPR. PMID:26343487

  12. Establishment of Stable, Cell-Mediated Immunity that Makes "Susceptible" Mice Resistant to Leishmania major

    Science.gov (United States)

    Bretscher, Peter A.; Wei, Guojian; Menon, Juthika N.; Bielefeldt-Ohmann, Helle

    1992-07-01

    Cell-mediated, but not antibody-mediated, immune responses protect humans against certain pathogens that produce chronic diseases such as leishmaniasis. Effective vaccination against such pathogens must therefore produce an immunological "imprint" so that stable, cell-mediated immunity is induced in all individuals after natural infection. BALB/c mice "innately susceptible" to Leishmania major produce antibodies after substantial infection. In the present study, "susceptible" mice injected with a small number of parasites mounted a cell-mediated response and acquired resistance to a larger, normally pathogenic, challenge. This vaccination strategy may be applicable in diseases in which protection is dependent on cell-mediated immunity.

  13. Co-incubation with IL-18 potentiates antigen-specific IFN-γ response in a whole-blood stimulation assay for measurement of cell-mediated immune responses in pigs experimentally infected with Lawsonia intracellularis

    DEFF Research Database (Denmark)

    Riber, Ulla; Boesen, Henriette Toft; Jakobsen, Jeanne Toft; Nguyen, Lien Thi Minh; Jungersen, Gregers

    The whole-blood interferon-gamma (IFN-γ) assay is a quantitative in-vitro assay for a direct read out of Ag-specific cell-mediated immune (CMI) responses to infectious diseases. The IFN-γ assay is robust in severe intracellular infections like Brucella or mycobacteria, but more difficult to evalu...

  14. Changes in cell-mediated immunity in patients undergoing radiotherapy

    International Nuclear Information System (INIS)

    The cell-mediated immune status of 147 patients who received radiotherapy was evaluated using in vitro tests (PHA, E-rosette, and spontaneous blastogenesis) both before and 6 weeks after the end of radiation. All patients have verified malignancies, involving the bronchus in 29 cases, breast in 28, female genital system in 26, head and neck in 20 and bladder in 15. Patients suffering from bronchogenic carcinomas or malignancies of the head and neck showed a relative high degree of immune suppression. Our findings indicate a trend towards some improvement in PHA reactivity, as well as in the percentage of E-rosette-forming cells after treatment, which is more noticeable in patients with pelvic or breast tumors. A relationship seems to exist between the tumor load and the immune status, which reverts to a normal pattern when the former is extinguished. Moreover, patients with poor clinical response display a profoundly depressed level of immune status without any improvement after treatment

  15. Stimulatory effect of Eucalyptus essential oil on innate cell-mediated immune response

    OpenAIRE

    Rasi Guido; Federici Memmo; Mercuri Luana; Zonfrillo Manuela; Andreola Federica; Vallebona Paola; Serafino Annalucia; Garaci Enrico; Pierimarchi Pasquale

    2008-01-01

    Abstract Background Besides few data concerning the antiseptic properties against a range of microbial agents and the anti-inflammatory potential both in vitro and in vivo, little is known about the influence of Eucalyptus oil (EO) extract on the monocytic/macrophagic system, one of the primary cellular effectors of the immune response against pathogen attacks. The activities of this natural extract have mainly been recognized through clinical experience, but there have been relatively little...

  16. Childhood adversity and cell-mediated immunity in young adulthood: Does type and timing matter?

    OpenAIRE

    Slopen, Natalie; McLaughlin, Katie A.; Erin C Dunn; Koenen, Karestan C.

    2012-01-01

    Childhood adversity can have powerful effects on health over the life course. Persistent changes in cell-mediated immune function may be one pathway linking adverse childhood experiences with later disease risk. However, limited research has examined childhood adversity in relation to cell-mediated immune function, and in particular, immune response to latent viruses in adulthood. The present study investigated the association of two types of childhood adversity, socioeconomic disadvantage du...

  17. Subnormal expression of cell-mediated and humoral immune responses in progeny disposed toward a high incidence of tumors after in utero exposure to benzo[a]pyrene

    International Nuclear Information System (INIS)

    Pregnant mice were exposed to 150 μg benzol[a]pyrene (BaP) per gram of body weight during fetogenesis (d 11-17 of gestation) and the progeny were assayed for humoral and cell mediated immune responses at different time intervals after birth. Immature offspring (1-4 wk) were severely suppressed in their ability to produce antibody (plaque-) forming cells (PFC) against sheep red blood cells (SRBC) and in the ability of their lymphocytes to undergo a mixed lymphocyte response (MLR). Lymphocytes from these progeny showed a moderate to weak capacity to inhabit production of colony-forming units (CFU) in host spleens following transfer with semiallogeneic bone marrow (BM) cells into lethally x-irradiated recipients syngeneic to the BM (in vivo graft-versus-host response, GVHR). A severe and sustained suppression in the MLR and the PFC response occurred from the fifth month up to 18 mo. The in vivo GVHR, also subnormal later in life, was not as severely suppressed as the other two parameters. Tumor incidence in the BP-exposed progeny was 8- to 10-fold higher than in those encountering corn oil alone from 18 to 24 mo of age. These data show that in utero exposure to the chemical carcinogen BaP alters development of components needed for establishing competent hemoral and cell-mediated functions of the immune apparatus and leads to severe and sustained postnatal suppression of the defense mechanism. The immunodeficiency exhibited, particularly in the T-cell compartment (MLR, GVHR), before and during the increase in tumor frequency, may provide a favorable environment for the growth of nascent neoplasms induced by BaP. 30 references, 4 figures, 2 tables

  18. In vitro cell-mediated immunity assay using 125I-iododeoxyuridine

    International Nuclear Information System (INIS)

    We investigated an in vitro cell-mediated immunity assay using incorporation of 125I-iododeoxyuridine as an indicator of lymphocyte responsiveness to mitogen stimulation. The system permits the use of whole-blood cultures in rats and dogs

  19. HPV-E7 Delivered by Engineered Exosomes Elicits a Protective CD8+ T Cell-Mediated Immune Response

    Directory of Open Access Journals (Sweden)

    Paola Di Bonito

    2015-03-01

    Full Text Available We developed an innovative strategy to induce a cytotoxic T cell (CTL immune response against protein antigens of choice. It relies on the production of exosomes, i.e., nanovesicles spontaneously released by all cell types. We engineered the upload of huge amounts of protein antigens upon fusion with an anchoring protein (i.e., HIV-1 Nefmut, which is an inactive protein incorporating in exosomes at high levels also when fused with foreign proteins. We compared the immunogenicity of engineered exosomes uploading human papillomavirus (HPV-E7 with that of lentiviral virus-like particles (VLPs incorporating equivalent amounts of the same antigen. These exosomes, whose limiting membrane was decorated with VSV-G, i.e., an envelope protein inducing pH-dependent endosomal fusion, proved to be as immunogenic as the cognate VLPs. It is noteworthy that the immunogenicity of the engineered exosomes remained unaltered in the absence of VSV-G. Most important, we provide evidence that the inoculation in mouse of exosomes uploading HPV-E7 induces production of anti-HPV E7 CTLs, blocks the growth of syngeneic tumor cells inoculated after immunization, and controls the development of tumor cells inoculated before the exosome challenge. These results represent the proof-of-concept about both feasibility and efficacy of the Nefmut-based exosome platform for the induction of CD8+ T cell immunity.

  20. Stress effect on humoral and cell mediated immune response: Indispensable part of corticosterone and cytokine in neutrophil function

    Directory of Open Access Journals (Sweden)

    Sakthivel Srinivasan

    2016-01-01

    Conclusion: This result further concludes that prior immunization of SRBC in animal’s act as a vaccination, which helps to prevent noise stress induced impairment in immune system. Orally administered I. tinctoria prevented noise altered immune system. These results also concluded that I. tinctoria supplementation could act as an immunomodulators and suggesting its therapeutic efficacy as an antistressor.

  1. Role of macrophage inflammatory protein-1alpha in T-cell-mediated immunity to viral infection

    DEFF Research Database (Denmark)

    Madsen, Andreas N; Nansen, Anneline; Christensen, Jan P; Thomsen, Allan R

    2003-01-01

    The immune response to lymphocytic choriomeningitis virus in mice lacking macrophage inflammatory protein-1alpha (MIP-1alpha) was evaluated. Generation of virus-specific effector T cells is unimpaired in MIP-1alpha-deficient mice. Furthermore, MIP-1alpha is not required for T-cell-mediated virus...... control or virus-induced T-cell-dependent inflammation. Thus, MIP-1alpha is not mandatory for T-cell-mediated antiviral immunity....

  2. Nano-curcumin inhibits proliferation of esophageal adenocarcinoma cells and enhances the T cell mediated immune response

    Directory of Open Access Journals (Sweden)

    FrancescaMilano

    2013-05-01

    Full Text Available In Western countries the incidence of the esophageal adenocarcinoma (EAC has risen at a more rapid rate than that of any other malignancy. Despite intensive therapies this cancer is associated with extreme high morbidity and mortality. For this reason, novel effective therapeutic strategies are urgently required. Dendritic Cell (DC-based immunotherapy is a promising novel treatment strategy, which combined with other anti-cancer strategies has been proven to be beneficial for cancer patients. Curcumin (diferuloylmethane, is a natural polyphenol that is known for its anti-cancer effects however, in it’s free form, curcumin has poor bioavailability. The aim of this study was to investigate whether using a highly absorptive form of curcumin, dispersed with colloidal nano-particles, named Theracurmin would be more effective against EAC cells and to analyze if this new compound affects DC-induced T cell response. As a result, we show efficient uptake of nano-curcumin by the EAC cell lines, OE33 and OE19. Moreover, nano-curcumin significantly decreased the proliferation of the EAC cells, while did not affect the normal esophageal cell line HET-1A. We also found that nano-curcumin significanly upregulated the expression of the co-stimulatory molecule CD86 in DCs and significantly decreased the secretion of pro-inflammatory cytokines from in-vitro activated T cells. When we combined T cells with nano-curcumin treatment in OE19 and OE33, we found that the basic levels of T cell induced cytotoxicity of 6.4% and 4.1%, increased to 15% and 13%, respectively. In conclusion, we found that nano-curcumin is effective against EAC, sensitizes EAC cells to T cell induced cytotoxicity and decreases the pro-inflammatory signals from T cells. Combining DC immunotherapy with nano-curcumin is potentially a promising approach for future treatment of EAC.

  3. Cell-mediated immunity to Toxoplasma gondii develops primarily by local Th-1 host immune responses in the absence of parasite replication1

    OpenAIRE

    Gigley, Jason P.; Fox, Barbara A.; Bzik, David J.

    2009-01-01

    A single inoculation of mice with the live attenuated Toxoplasma gondii uracil auxotroph strain cps1-1 induces long-lasting immunity against lethal challenge with hyper-virulent strain RH. The mechanism for this robust immunity in the absence of parasite replication has not been addressed. The mechanism of long-lasting immunity, the importance of route of immunization, cellular recruitment to the site of infection, and local and systemic inflammation were evaluated. Our results show that infe...

  4. Levamisole Enhances Cell-Mediated Immune Responses and Reduces Shedding of H9N2 Avian Influenza Virus in Japanese Quails (Coturnix coturnix japonica

    Directory of Open Access Journals (Sweden)

    Tahoora Shomali

    2012-01-01

    Full Text Available Problem statement: Regarding the role of Japanese quails (Coturnix coturnix japonica in reassortment and spreading of avian influenza (AI viruses and inadequate protection of vaccination in this species, the present study aimed to evaluate the effect of levamisole as an immunomodulatory agent on cell-mediated immunity (CMI, antibody responses and shedding of H9N2 AI virus in experimentally infected quails. Approach: On day 20 of age, 100 quails randomly allocated into 4 equal groups. Birds in groups 2, 3 and 4 were inoculated with virus where group 1 kept as control. Groups 3 and 4 orally received 15 mg kg-1 levamisole for three consecutive days just before virus inoculation which was repeated 10 days post inoculation (PI only in group 4. Antibody titers and CMI of all birds were assayed by HI and delayed type hypersensitivity (DTH test respectively and virus detection in fecal and tracheal samples performed by RT-PCR method. Data analyzed by one-way ANOVA and Tukey’s test. Results: Levamisole in both regimens had no appreciable effect on antibody titers (p>0.05 while repeated regimen resulted in higher CMI response than group 2 at 48 and 72 h post DTH test (p = 0.011 and p = 0.031 respectively. Total fecal samples positive for virus from birds in group 3 and 4 were 34.4 and 40% lower than group 2 respectively. For trachea, the positive samples were 33.3% (group 3 and 46.7% (group 4 lower than group 2. Moreover; fecal and tracheal samples from levamisole treated birds (especially from group 4 became void of virus earlier than group 2. Conclusion/Recommendations: Levamisole administration in a repeated regimen enhances CMI response against H9N2 AI virus and reduces virus shedding in quails. This may pave the road for further investigations on potential positive effects of this agent on prevention and management of H9N2 AI infections in quail industry.

  5. In vitro assays for cell-mediated immunity in dogs with radiation-induced osteosarcoma

    International Nuclear Information System (INIS)

    The Radiobiology Laboratory experimental study on 226Ra toxicity provides a model for the study of immune response in high-risk dogs and dogs with radiation-induced osteosarcoma. Studies were undertaken to measure both general immune response and specific immune response of dogs following amputation of the tumor-bearing limb using autochthonous cultured tumors. The cell-mediated immune competence (CMI) of dogs as measured by degree of stimulation of purified lymphocytes with phytohemagglutinin (PHA) has been determined in five available amputated dogs. The stimulation index was computed as the net ratio of 3H-thymidine incorporation in stimulated vs unstimulated cells

  6. Immunocyto-adherence test for the detection of cell mediated immune response in lambs vaccinated with irradiated amphistome metacercariae (Cercariae indicae XXVI)

    International Nuclear Information System (INIS)

    Adherence of lymphocytes and peritoneal macrophages on amphistome metacercariae (Cercaries indicae XXVI) and Paramphistomum epiclitum adult flukes was observed with cells obtained from lambs immunized with either normal or irradiated amphistome metacercariae (Cercariae indicae XXVI). The cell adherence reaction around metacercariae and adult flukes was comparatively more pronounced with cells obtained from lambs immunized with 2.5 or 3 krad irradiated metacercariae in comparison to cells obtained from lambs immunized with normal of 2 krad irradiated metacercariae. Possibly better CMI response was involved in the operation of immunity against the amphistome in the former two groups of lambs. (author)

  7. Gender-specific effects of genetic variants within Th1 and Th17 cell-mediated immune response genes on the risk of developing rheumatoid arthritis.

    Directory of Open Access Journals (Sweden)

    Rafael Cáliz

    Full Text Available The present study was conducted to explore whether single nucleotide polymorphisms (SNPs in Th1 and Th17 cell-mediated immune response genes differentially influence the risk of rheumatoid arthritis (RA in women and men. In phase one, 27 functional/tagging polymorphisms in C-type lectins and MCP-1/CCR2 axis were genotyped in 458 RA patients and 512 controls. Carriers of Dectin-2 rs4264222T allele had an increased risk of RA (OR = 1.47, 95%CI 1.10-1.96 whereas patients harboring the DC-SIGN rs4804803G, MCP-1 rs1024611G, MCP-1 rs13900T and MCP-1 rs4586C alleles had a decreased risk of developing the disease (OR = 0.66, 95%CI 0.49-0.88; OR = 0.66, 95%CI 0.50-0.89; OR = 0.73, 95%CI 0.55-0.97 and OR = 0.68, 95%CI 0.51-0.91. Interestingly, significant gender-specific differences were observed for Dectin-2 rs4264222 and Dectin-2 rs7134303: women carrying the Dectin-2 rs4264222T and Dectin-2 rs7134303G alleles had an increased risk of RA (OR = 1.93, 95%CI 1.34-2.79 and OR = 1.90, 95%CI 1.29-2.80. Also five other SNPs showed significant associations only with one gender: women carrying the MCP-1 rs1024611G, MCP-1 rs13900T and MCP-1 rs4586C alleles had a decreased risk of RA (OR = 0.61, 95%CI 0.43-0.87; OR = 0.67, 95%CI 0.47-0.95 and OR = 0.60, 95%CI 0.42-0.86. In men, carriers of the DC-SIGN rs2287886A allele had an increased risk of RA (OR = 1.70, 95%CI 1.03-2.78, whereas carriers of the DC-SIGN rs4804803G had a decreased risk of developing the disease (OR = 0.53, 95%CI 0.32-0.89. In phase 2, we genotyped these SNPs in 754 RA patients and 519 controls, leading to consistent gender-specific associations for Dectin-2 rs4264222, MCP-1 rs1024611, MCP-1 rs13900 and DC-SIGN rs4804803 polymorphisms in the pooled sample (OR = 1.38, 95%CI 1.08-1.77; OR = 0.74, 95%CI 0.58-0.94; OR = 0.76, 95%CI 0.59-0.97 and OR = 0.56, 95%CI 0.34-0.93. SNP-SNP interaction analysis of significant SNPs also showed a

  8. IL-33-Responsive Lineage−CD25+CD44hi Lymphoid Cells Mediate Innate Type-2 Immunity and Allergic Inflammation in the Lungs1

    OpenAIRE

    Bartemes, Kathleen R.; Iijima, Koji; Kobayashi, Takao; Gail M Kephart; McKenzie, Andrew N; Kita, Hirohito

    2011-01-01

    Innate immunity provides the first line of response to invading pathogens and a variety of environmental insults. Recent studies identified novel subsets of innate lymphoid cells that are capable of mediating immune responses in mucosal organs. Here we describe a subset of lymphoid cells that is involved in innate type-2 immunity in the lungs. Airway exposure of naïve BALB/c or C57BL mice to IL-33 results in a rapid (< 12 h) production of IL-5 and IL-13 and marked airway eosinophilia independ...

  9. VARICELLA ZOSTER VIRUS-ITS PATHOGENESIS, LATENCY & CELL-MEDIATED IMMUNITY

    Directory of Open Access Journals (Sweden)

    Anis Ahmed

    2013-07-01

    Full Text Available Varicella zoster virus causes primary infection as chickenpox, at which time latencyis established in the neurons of the dorsal root ganglia or ganglia of the cranial nerves.Reactivation produces herpes zoster infection (HZI, commonly called shingles. Anunderstanding of the mechanisms of latency is crucial in developing effective therapies forVZV infections of the nervous system. This article describes the pathogenesis of VZVwhich includes immune response to the virus, immune evasion by the virus, mechanism ofits latency and cell-mediated immunity.

  10. T cell mediated cerebral hemorrhages and microhemorrhages during passive Aβ immunization in APPPS1 transgenic mice

    Directory of Open Access Journals (Sweden)

    de Calignon Alix

    2011-03-01

    Full Text Available Abstract Background Immunization against amyloid-β (Aβ, the peptide that accumulates in the form of senile plaques and in the cerebrovasculature in Alzheimer's disease (AD, causes a dramatic immune response that prevents plaque formation and clears accumulated Aβ in transgenic mice. In a clinical trial of Aβ immunization, some patients developed meningoencephalitis and hemorrhages. Neuropathological investigations of patients who died after the trial showed clearance of amyloid pathology, but also a powerful immune response involving activated T cells probably underlying the negative effects of the immunization. Results To define the impact of T cells on this inflammatory response we used passive immunization and adoptive transfer to separate the effect of IgG and T cell mediated effects on microhemorrhage in APPPS1 transgenic mice. Neither anti Aβ IgG nor adoptively transferred T cells, alone, led to increased cerebrovascular damage. However, the combination of adoptively transferred T cells and passive immunization led to massive cerebrovascular bleeding that ranged from multiple microhemorrhages in the parenchyma to large hematomas. Conclusions Our results indicate that vaccination can lead to Aβ and T cell induced cerebral micro-hemorrhages and acute hematomas, which are greatly exacerbated by T cell mediated activity.

  11. Immunotherapy: Shifting the Balance of Cell-Mediated Immunity and Suppression in Human Prostate Cancer

    International Nuclear Information System (INIS)

    Active immunotherapy is dependent on the ability of the immune system to recognize and respond to tumors. Despite overwhelming evidence to support a cell-mediated immune response to prostate cancer, it is insufficient to eradicate the disease. This is likely due to a high level of suppression at the tumor site from a variety of sources, including immunosuppressive cells. Immune cells entering the tumor microenvironment may be inhibited directly by the tumor, stromal cells or other immune cells that have been induced to adopt a suppressive phenotype. The resurgence of interest in immunotherapy following the approval of sipuleucel-T and ipilimumab by the Food and Drug Administration has brought about new strategies for overcoming tumor-mediated suppression and bolstering anti-tumor responses. Improved understanding of the immune response to prostate cancer can lead to new combination therapies, such as the use of vaccine with small molecule and checkpoint inhibitors or other immunotherapies

  12. Immunotherapy: Shifting the Balance of Cell-Mediated Immunity and Suppression in Human Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Tucker, Jo A.; Jochems, Caroline [Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Gulley, James L. [Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Schlom, Jeffrey, E-mail: js141c@nih.gov; Tsang, Kwong Y. [Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

    2012-12-11

    Active immunotherapy is dependent on the ability of the immune system to recognize and respond to tumors. Despite overwhelming evidence to support a cell-mediated immune response to prostate cancer, it is insufficient to eradicate the disease. This is likely due to a high level of suppression at the tumor site from a variety of sources, including immunosuppressive cells. Immune cells entering the tumor microenvironment may be inhibited directly by the tumor, stromal cells or other immune cells that have been induced to adopt a suppressive phenotype. The resurgence of interest in immunotherapy following the approval of sipuleucel-T and ipilimumab by the Food and Drug Administration has brought about new strategies for overcoming tumor-mediated suppression and bolstering anti-tumor responses. Improved understanding of the immune response to prostate cancer can lead to new combination therapies, such as the use of vaccine with small molecule and checkpoint inhibitors or other immunotherapies.

  13. Local cell-mediated immune reactions in cancer patients

    International Nuclear Information System (INIS)

    The analysis of 178 cases of stage I-II breast cancer showed morphological features of local cell-mediated immune reactions to be of limited prognostic value. A comparative evaluation of some characteristics of cell surface receptors, such as ability to spontaneous rosette formation with sheep erythrocytes and sensitivty to theophylline, was carried out in lymphocyte samples obtained from tumor tissue and peripheral blood of 76 cancer patients subjected to preoperative radiotherapy. The said parameters were studied in breast cancer patients of rosette-forming cell reaction to theophylline were identified, the incidence of some of them being determined by the presence or absence of regional metastases. The level and functional activity of surface receptors of tumor mononuclear cells proved to influence prognosis

  14. Enhanced early innate and T cell-mediated responses in subjects immunized with Anthrax Vaccine Adsorbed Plus CPG 7909 (AV7909).

    Science.gov (United States)

    Minang, Jacob T; Inglefield, Jon R; Harris, Andrea M; Lathey, Janet L; Alleva, David G; Sweeney, Diane L; Hopkins, Robert J; Lacy, Michael J; Bernton, Edward W

    2014-11-28

    NuThrax™ (Anthrax Vaccine Adsorbed with CPG 7909 Adjuvant) (AV7909) is in development. Samples obtained in a phase Ib clinical trial were tested to confirm biomarkers of innate immunity and evaluate effects of CPG 7909 (PF-03512676) on adaptive immunity. Subjects received two intramuscular doses of commercial BioThrax(®) (Anthrax Vaccine Adsorbed, AVA), or two intramuscular doses of one of four formulations of AV7909. IP-10, IL-6, and C-reactive protein (CRP) levels were elevated 24-48 h after administration of AV7909 formulations, returning to baseline by Day 7. AVA (no CPG 7909) resulted in elevated IL-6 and CRP, but not IP-10. Another marker of CpG, transiently decreased absolute lymphocyte counts (ALCs), correlated with transiently increased IP-10. Cellular recall responses to anthrax protective antigen (PA) or PA peptides were assessed by IFN-γ ELISpot assay performed on cryopreserved PBMCs obtained from subjects prior to immunization and 7 days following the second immunization (study day 21). One-half of subjects that received AV7909 with low-dose (0.25mg/dose) CPG 7909 possessed positive Day 21 T cell responses to PA. In contrast, positive T cell responses occurred at an 11% average rate (1/9) for AVA-treated subjects. Differences in cellular responses due to dose level of CPG 7909 were not associated with differences in humoral anti-PA IgG responses, which were elevated for recipients of AV7909 compared to recipients of AVA. Serum markers at 24 or 48 h (i.e. % ALC decrease, or increase in IL-6, IP-10, or CRP) correlated with the humoral (antibody) responses 1 month later, but did not correlate with cellular ELISpot responses. In summary, biomarkers of early responses to CPG 7909 were confirmed, and adding a CpG adjuvant to a vaccine administered twice resulted in increased T cell effects relative to vaccine alone. Changes in early biomarkers correlated with subsequent adaptive humoral immunity but not cellular immunity. PMID:24530403

  15. Impact of oral meloxicam and long-distance transport on cell-mediated and humoral immune responses in feedlot steers receiving modified live BVDV booster vaccination on arrival.

    Science.gov (United States)

    Van Engen, N K; Platt, R; Roth, J A; Stock, M L; Engelken, T; Vann, R C; Wulf, L W; Busby, W D; Wang, C; Kalkwarf, E M; Coetzee, J F

    2016-07-01

    The objective of this study was to investigate the impact of oral meloxicam (MEL) and long-distance transportation on cell-mediated immunity (CMI) in preconditioned steers receiving a booster vaccination on arrival. We hypothesized that steers treated with MEL at 1mg/kg body weight, 6h before night-time transport, would be less immunocompromised on arrival (day 0) and after 7days, and that CMI following vaccination with a modified live bovine viral diarrhea virus (BVDV) recall antigen would be increased. Brahman crossbreed steers, 13-17 months of age (n=87), were randomly assigned to one of four treatment groups: MEL, transported (MTR) (n=22), MEL, non-transported (MNT) (n=22), lactose placebo, transported (CTR) (n=21), and lactose placebo, non-transported (CNT) (n=22). MTR and CTR steers were transported for approximately 16h non-stop on a truck from Mississippi to Iowa (approximately 1300km), whereas steers in the MNT and CNT groups remained in Mississippi as non-transported controls. Body weight was measured and jugular blood was collected at -1, 0, and 7days from all steers at the same time, regardless of location. Multi-parameter flow cytometry (MP-FCM) was used to identify T-cell subsets and detect the expression of three activation markers (CD25 [interleukin (IL)-2 receptor], intracellular interferon-gamma [IFNγ], and IL-4) after in vitro stimulation with BVDV recall antigen. Plasma cortisol concentration was measured on day -1, 0, and 7 as a marker of transport-associated stress. Serum antibody titer to BVDV was assessed on day -1 and day 7 post-booster vaccination. Whole-blood samples were analyzed using MP-FCM on days 0 and 7. Results were log transformed and analyzed using repeated measures of analysis of variance. Compared with non-transported controls, transport led to an increase in BVDV-induced expression of CD25, IFNγ, and IL-4 in CD4(+), CD8(+), and γδ(+) T-cell subsets (P0.10). A treatment*transport interaction was noted for the increase in IL

  16. Cell-Mediated Immunity in Elite Controllers Naturally Controlling HIV Viral Load.

    Science.gov (United States)

    Genovese, Luca; Nebuloni, Manuela; Alfano, Massimo

    2013-01-01

    The natural course of human immunodeficiency virus (HIV) infection is characterized by high viral load, depletion of immune cells, and immunodeficiency, ultimately leading to acquired immunodeficiency syndrome phase and the occurrence of opportunistic infections and diseases. Since the discovery of HIV in the early 1980s a naturally selected population of infected individuals has been emerged in the last years, characterized by being infected for many years, with viremia constantly below detectable level and poor depletion of immune cells. These individuals are classified as "elite controllers (EC) or suppressors" and do not develop disease in the absence of anti-retroviral therapy. Unveiling host factors and immune responses responsible for the elite status will likely provide clues for the design of therapeutic vaccines and functional cures. Scope of this review was to examine and discuss differences of the cell-mediated immune responses between HIV+ individuals with disease progression and EC. PMID:23577012

  17. Cell-mediated Immunity in Elite Controllers Naturally Controlling HIV Viral Load

    Directory of Open Access Journals (Sweden)

    Luca eGenovese

    2013-04-01

    Full Text Available The natural course of HIV infection is characterized by high viral load, depletion of immune cells and immunodeficiency, ultimately leading to acquired immunodeficiency syndrome (AIDS phase and the occurrence of opportunistic infections and diseases.Since the discovery of HIV in the early 80’s a naturally selected population of infected individuals has been emerged in the last years, characterized by being infected for many years, with viremia constantly below detectable level and poor depletion of immune cells. These individuals are classified as elite controllers or suppressors and do not develop disease in the absence of anti-retroviral therapy.Unveiling host factors and immune responses responsible for the elite status will likely provide clues for the design of therapeutic vaccines and functional cures. Scope of this review was to examine and discuss differences of the cell-mediated immune responses between HIV+ individuals with disease progression and elite controllers.

  18. Cell-mediated immune responses to Plasmodium falciparum purified soluble antigens in sickle-cell trait subjects

    DEFF Research Database (Denmark)

    Bayoumi, R A; Abu-Zeid, Y A; Abdulhadi, N H;

    1990-01-01

    To determine the possible differences in the immune response to Plasmodium falciparum between sickle-cell trait (Hb AS) and normal haemoglobin (Hb AA) individuals, we examined 35 Hb AS and 24 Hb AA subjects matched for age and microenvironment. Their age was 2-55 years and all lived in a malaria...... individuals (P less than 0.025). Responses of BMNCs to PPD and PHA were also higher among Hb AS individuals and correlated positively with responses to SPAg. These findings support the hypotheses that the sickle-cell trait protects individuals from P. falciparum infections, at least in part, by modulating the...... endemic area 300 km south of Khartoum. Antibodies to ring-infected erythrocyte surface antigen (Pf155/RESA) and to circumsporozoite (CS) protein (anti-NANP40) indicated equal exposure to falciparum malaria. Peripheral blood mononuclear cells (BMNCs) from 20/35 (57%) Hb AS subjects compared with 10/24 (42...

  19. Novel engineered HIV-1 East African Clade-A gp160 plasmid construct induces strong humoral and cell-mediated immune responses in vivo

    International Nuclear Information System (INIS)

    HIV-1 sequences are highly diverse due to the inaccuracy of the viral reverse transcriptase. This diversity has been studied and used to categorize HIV isolates into subtypes or clades, which are geographically distinct. To develop effective vaccines against HIV-1, immunogens representing different subtypes may be important for induction of cross-protective immunity, but little data exist describing and comparing the immunogenicity induced by different subtype-based vaccines. This issue is further complicated by poor expression of HIV structural antigens due to rev dependence. One costly approach is to codon optimize each subtype construct to be examined. Interestingly, cis-acting transcriptional elements (CTE) can also by pass rev restriction by a rev independent export pathway. We reasoned that rev+CTE constructs might have advantages for such expression studies. A subtype A envelope sequence from a viral isolate from east Africa was cloned into a eukaryotic expression vector under the control of the CMV-IE promoter. The utility of inclusion of the Mason-Pfizer monkey virus (MPV)-CTE with/without rev for driving envelope expression and immunogenicity was examined. Expression of envelope (gp120) was confirmed by immunoblot analysis and by pseudotype virus infectivity assays. The presence of rev and the CTE together increased envelope expression and viral infection. Furthermore the CTE+rev construct was significantly more immunogenic then CTE alone vector. Isotype analysis and cytokine profiles showed strong Th1 response in plasmid-immunized mice, which also demonstrated the superior nature of the rev+CTE construct. These responses were of similar or greater magnitude to a codon-optimized construct. The resulting cellular immune responses were highly cross-reactive with a HIV-1 envelope subtype B antigen. This study suggests a simple strategy for improving the expression and immunogenicity of HIV subtype-specific envelope antigens as plasmid or vector

  20. The T-cell-mediated immune response and return rate of fledgling American kestrels are positively correlated with parental clutch size.

    OpenAIRE

    Tella, J L; Bortolotti, G. R.; Dawson, R.D.; Forero, M.G.

    2000-01-01

    Life-history theory predicts that parents face a trade-off between the number and viability of the progeny they produce. We found evidence for an apparent trade-off in a free-living population of American kestrels (Falco sparverius), as larger clutches produced more but lighter fledglings. However, while the body mass of fledglings has traditionally been used as a measure of survival prospect, offspring immunocompetence should also play an important role. We thus measured the T-cell-mediated ...

  1. Role of very late antigen-1 in T-cell-mediated immunity to systemic viral infection

    DEFF Research Database (Denmark)

    Ørding Kauffmann, Susanne; Thomsen, Allan Randrup; Christensen, Jan Pravsgaard

    2006-01-01

    The T-cell response to lymphocytic choriomeningitis virus was studied in mice lacking very late antigen-1 (VLA-1). The generation of virus-specific effector T cells was unimpaired in VLA-1(-/-) mice. In the memory phase, VLA-1 deficiency did not influence the number of memory CD8(+) T cells or th...... current findings indicate that the expression of VLA-1 is not pivotal for T-cell-mediated antiviral immunity to a systemic infection....... their distribution between lymphoid and nonlymphoid organs. Regarding a functional role of VLA-1, we found that intracerebral infection of both VLA-1(-/-) and wild-type (wt) mice resulted in lethal T-cell-mediated meningitis, and quantitative and qualitative analyses of the cellular exudate did not...

  2. Natural killer cell mediated cytotoxic responses in the Tasmanian devil.

    Science.gov (United States)

    Brown, Gabriella K; Kreiss, Alexandre; Lyons, A Bruce; Woods, Gregory M

    2011-01-01

    The Tasmanian devil (Sarcophilus harrisii), the world's largest marsupial carnivore, is under threat of extinction following the emergence of an infectious cancer. Devil facial tumour disease (DFTD) is spread between Tasmanian devils during biting. The disease is consistently fatal and devils succumb without developing a protective immune response. The aim of this study was to determine if Tasmanian devils were capable of forming cytotoxic antitumour responses and develop antibodies against DFTD cells and foreign tumour cells. The two Tasmanian devils immunised with irradiated DFTD cells did not form cytotoxic or humoral responses against DFTD cells, even after multiple immunisations. However, following immunisation with xenogenic K562 cells, devils did produce cytotoxic responses and antibodies against this foreign tumour cell line. The cytotoxicity appeared to occur through the activity of natural killer (NK) cells in an antibody dependent manner. Classical NK cell responses, such as innate killing of DFTD and foreign cancer cells, were not observed. Cells with an NK-like phenotype comprised approximately 4 percent of peripheral blood mononuclear cells. The results of this study suggest that Tasmanian devils have NK cells with functional cytotoxic pathways. Although devil NK cells do not directly recognise DFTD cancer cells, the development of antibody dependent cell-mediated cytotoxicity presents a potential pathway to induce cytotoxic responses against the disease. These findings have positive implications for future DFTD vaccine research. PMID:21957452

  3. Biomarkers of CD4+ CTL cell Mediated Immunity to Tuberculosis

    Science.gov (United States)

    The immune responses mediated by interactions between T-lymphocyte subsets and mycobacteria-infected macrophages are critical for control of tuberculosis. In these studies, the bovine model was used to characterize the cytolytic and mycobactericidal CD4+ T cell response induced by BCG vaccination. ...

  4. Effect of vitamin E levels on the cell-mediated immunity of broilers vaccinated against coccidiosis

    Directory of Open Access Journals (Sweden)

    ICM da Silva

    2011-03-01

    Full Text Available Studies on the relationships between animal nutrition and immunity have sought reliable methodologies to measure responses. Cell-mediated immune response is similarly studied in humans. The cutaneous basophil hypersensitivity test (CBH is one of the methods to measure that response and consists in the infiltration of inflammatory cells, particularly of lymphocytes and basophils, as result of the application of substances capable of inducing cell proliferation in determined sites, such as wings, wattle, and interdigital space in birds. CBH is considered a simple and fast method and can be applied in birds of different ages. In immunocompetence studies with poultry, phytohemagglutinin-P (PHA-P is a commonly used substance, despite the variability of the response related to the method of application (intradermal injection and the antigens used. In the present experiment, PHA-P was used to observe the cell-mediated immune response of 216 chicks fed three dietary levels of vitamin E from 1 to 36 days of age. All birds were immunologically challenged by vaccination against coccidiosis at three days of age and against Newcastle Disease (NCD at 14 and 30 days of age. At 36 days of age, birds were submitted to the CBH test according to the methodology of Corrier & DeLoach (1990. Birds fed 65mg/kg of vitamin E presented lasting cell reaction (p<0.08, which indicates that this vitamin E level improved cell immune response of birds due to its antioxidant and immunomodulating properties. The use of this vitamin E level can be considered by nutritionists under practical conditions, aiming to improve broiler immunity.

  5. Safety, humoral and cell mediated immune responses to two formulations of an inactivated, split-virion influenza A/H5N1 vaccine in children.

    Directory of Open Access Journals (Sweden)

    Tawee Chotpitayasunondh

    Full Text Available BACKGROUND: Highly pathogenic influenza A/H5N1 has caused outbreaks in wild birds and poultry in Asia, Africa and Europe. It has also infected people, especially children, causing severe illness and death. Although the virus shows limited ability to transmit between humans, A/H5N1 represents a potential source of the next influenza pandemic. This study assesses the safety and immunogenicity of aluminium hydroxide adjuvanted (Al and non adjuvanted influenza A/Vietnam/1194/2004 NIBRG-14 (H5N1 vaccine in children. METHODS AND FINDINGS: In a Phase II, open, randomised, multicentre trial 180 children aged 6 months to 17 years received two injections, 21 days apart, of vaccine containing either: 30 microg haemagglutinin (HA with adjuvant (30 microg+Al or 7.5 microg HA without adjuvant. An additional 60 children aged 6-35 months received two "half dose" injections (ie 15 microg+Al or 3.8 microg. Safety was followed for 21 days after vaccination. Antibody responses were assessed 21 days after each injection and cellular immune responses were explored. Vaccination appeared well tolerated in all age groups. The 30 microg+Al formulation was more immunogenic than 7.5 microg in all age groups: in these two groups 79% and 46% had haemagglutinination inhibition antibody titres > or =32 (1/dil. Among 6-35 month-olds, the full doses were more immunogenic than their half dose equivalents. Vaccination induced a predominantly Th2 response against H5 HA. CONCLUSIONS: This influenza A(H5N1 vaccine was well tolerated and immunogenic in children and infants, with Al adjuvant providing a clear immunogenic advantage. These results demonstrate that an H5N1 Al-adjuvanted vaccine, previously shown to be immunogenic and safe in adults, can also be used in children, the group most at risk for pandemic influenza.

  6. Modulations in cell-mediated immunity of Mytilus edulis following the 'Sea Empress' oil spill

    International Nuclear Information System (INIS)

    The 'Sea Empress' oil tanker grounded outside Milford Haven (Wales, UK) in February 1996, spilling ∼ 70,000 tonnes of crude oil and contaminating over 100 km of coastline, causing mass mortalities and strandings of at least 11 mollusc species. Intensive field monitoring commenced after the spill, examining immunity and hydrocarbon levels in the mussel, Mytilus edulis (Mollusca: Bivalvia), a commercially-harvested species which can accumulate contaminants. Comparisons of mussels from oiled and reference sites revealed significant modulations in cell-mediated immunity. Elevations in blood cell (haemocyte) numbers and decreases in superoxide generation and phagocytosis were identified in contaminated animals. The immune response of contaminated mussels gradually improved and generally showed no significant differences compared with clean mussels after 11 weeks. By then, total hydrocarbon content in contaminated mussels had declined by 70-90%, while polycyclic aromatic hydrocarbon content had decreased by over 90%. (author)

  7. Explanatory style and cell-mediated immunity in elderly men and women.

    Science.gov (United States)

    Kamen-Siegel, L; Rodin, J; Seligman, M E; Dwyer, J

    1991-01-01

    Correlated pessimistic explanatory style--the belief that negative events are caused by internal, stable, and global factors--with lowered immunocompetence in a sample of 26 older adults. Two measures of cell-mediated immunity--T-helper cell/T-suppressor cell ratio and T-lymphocyte response to mitogen challenge--were lower in individuals with a pessimistic style, controlling for the influence of current health, depression, medication, recent weight change, sleep, and alcohol use. A relative increase in the percentage of T-suppressor cells seemed to underlie this immunosuppression. Although the mechanism by which explanatory style might influence immune function remains unknown, we speculate that a pessimistic style might be an important psychological risk factor--at least among older people--in the early course of certain immune-mediated diseases. PMID:1915208

  8. The Effects of Reduced Gluten Barley Diet on Humoral and Cell-Mediated Systemic Immune Responses of Gluten-Sensitive Rhesus Macaques

    Directory of Open Access Journals (Sweden)

    Karol Sestak

    2015-03-01

    Full Text Available Celiac disease (CD affects approximately 1% of the general population while an estimated additional 6% suffers from a recently characterized, rapidly emerging, similar disease, referred to as non-celiac gluten sensitivity (NCGS. The only effective treatment of CD and NCGS requires removal of gluten sources from the diet. Since required adherence to a gluten-free diet (GFD is difficult to accomplish, efforts to develop alternative treatments have been intensifying in recent years. In this study, the non-human primate model of CD/NCGS, e.g., gluten-sensitive rhesus macaque, was utilized with the objective to evaluate the treatment potential of reduced gluten cereals using a reduced gluten (RG; 1% of normal gluten barley mutant as a model. Conventional and RG barleys were used for the formulation of experimental chows and fed to gluten-sensitive (GS and control macaques to determine if RG barley causes a remission of dietary gluten-induced clinical and immune responses in GS macaques. The impacts of the RG barley diet were compared with the impacts of the conventional barley-containing chow and the GFD. Although remission of the anti-gliadin antibody (AGA serum responses and an improvement of clinical diarrhea were noted after switching the conventional to the RG barley diet, production of inflammatory cytokines, e.g., interferon-gamma (IFN-γ, tumor necrosis factor (TNF and interleukin-8 (IL-8 by peripheral CD4+ T helper lymphocytes, persisted during the RG chow treatment and were partially abolished only upon re-administration of the GFD. It was concluded that the RG barley diet might be used for the partial improvement of gluten-induced disease but its therapeutic value still requires upgrading—by co-administration of additional treatments.

  9. The 3 major types of innate and adaptive cell-mediated effector immunity.

    Science.gov (United States)

    Annunziato, Francesco; Romagnani, Chiara; Romagnani, Sergio

    2015-03-01

    The immune system has tailored its effector functions to optimally respond to distinct species of microbes. Based on emerging knowledge on the different effector T-cell and innate lymphoid cell (ILC) lineages, it is clear that the innate and adaptive immune systems converge into 3 major kinds of cell-mediated effector immunity, which we propose to categorize as type 1, type 2, and type 3. Type 1 immunity consists of T-bet(+) IFN-γ-producing group 1 ILCs (ILC1 and natural killer cells), CD8(+) cytotoxic T cells (TC1), and CD4(+) TH1 cells, which protect against intracellular microbes through activation of mononuclear phagocytes. Type 2 immunity consists of GATA-3(+) ILC2s, TC2 cells, and TH2 cells producing IL-4, IL-5, and IL-13, which induce mast cell, basophil, and eosinophil activation, as well as IgE antibody production, thus protecting against helminthes and venoms. Type 3 immunity is mediated by retinoic acid-related orphan receptor γt(+) ILC3s, TC17 cells, and TH17 cells producing IL-17, IL-22, or both, which activate mononuclear phagocytes but also recruit neutrophils and induce epithelial antimicrobial responses, thus protecting against extracellular bacteria and fungi. On the other hand, type 1 and 3 immunity mediate autoimmune diseases, whereas type 2 responses can cause allergic diseases. PMID:25528359

  10. Heme oxygenase-1 exerts a protective role in ovalbumin-induced neutrophilic airway inflammation by inhibiting Th17 cell-mediated immune response.

    Science.gov (United States)

    Zhang, Yanjie; Zhang, Liya; Wu, Jinhong; Di, Caixia; Xia, Zhenwei

    2013-11-29

    Allergic asthma is conventionally considered as a Th2 immune response characterized by eosinophilic inflammation. Recent investigations revealed that Th17 cells play an important role in the pathogenesis of non-eosinophilic asthma (NEA), resulting in steroid-resistant neutrophilic airway inflammation. Heme oxygenase-1 (HO-1) has anti-inflammation, anti-oxidation, and anti-apoptosis functions. However, its role in NEA is still unclear. Here, we explore the role of HO-1 in a mouse model of NEA. HO-1 inducer hemin or HO-1 inhibitor tin protoporphyrin IX was injected intraperitoneally into ovalbumin-challenged DO11.10 mice. Small interfering RNA (siRNA) was delivered into mice to knock down HO-1 expression. The results show that induction of HO-1 by hemin attenuated airway inflammation and decreased neutrophil infiltration in bronchial alveolar lavage fluid and was accompanied by a lower proportion of Th17 cells in mediastinal lymph nodes and spleen. More importantly, induction of HO-1 down-regulated Th17-related transcription factor retinoic acid-related orphan receptor γt (RORγt) expression and decreased IL-17A levels, all of which correlated with a decrease in phosphorylated STAT3 (p-STAT3) level and inhibition of Th17 cell differentiation. Consistently, the above events could be reversed by tin protoporphyrin IX. Also, HO-1 siRNA transfection abolished the effect of hemin induced HO-1 in vivo. Meanwhile, the hemin treatment promoted the level of Foxp3 expression and enhanced the proportion of regulatory T cells (Tregs). Collectively, our findings indicate that HO-1 exhibits anti-inflammatory activity in the mouse model of NEA via inhibition of the p-STAT3-RORγt pathway, regulating kinetics of RORγt and Foxp3 expression, thus providing a possible novel therapeutic target in asthmatic patients. PMID:24097973

  11. Epistasis between MicroRNAs 155 and 146a during T Cell-Mediated Antitumor Immunity

    Directory of Open Access Journals (Sweden)

    Thomas B. Huffaker

    2012-12-01

    Full Text Available An increased understanding of antitumor immunity is necessary for improving cell-based immunotherapies against human cancers. Here, we investigated the roles of two immune system-expressed microRNAs (miRNAs, miR-155 and miR-146a, in the regulation of antitumor immune responses. Our results indicate that miR-155 promotes and miR-146a inhibits interferon γ (IFNγ responses by T cells and reduces solid tumor growth in vivo. Using a double-knockout (DKO mouse strain deficient in both miR-155 and miR-146a, we have also identified an epistatic relationship between these two miRNAs. DKO mice had defective T cell responses and tumor growth phenotypes similar to miR-155−/− mice. Further analysis of the T cell compartment revealed that miR-155 modulates IFNγ expression through a mechanism involving repression of Ship1. Our work reveals critical roles for miRNAs in the reciprocal regulation of CD4+ and CD8+ T cell-mediated antitumor immunity and demonstrates the dominant nature of miR-155 during its promotion of immune responses.

  12. Enhanced Early Innate and T Cell-mediated Responses in Subjects Immunized with Anthrax Vaccine Adsorbed Plus CPG 7909 (AV7909)

    OpenAIRE

    Minang, Jacob T.; Inglefield, Jon R.; Harris, Andrea M.; Lathey, Janet L.; Alleva, David G.; Sweeney, Diane L.; Hopkins, Robert J; Lacy, Michael J.; Bernton, Edward W.

    2014-01-01

    NuThrax™ (Anthrax Vaccine Adsorbed with CPG 7909 Adjuvant) (AV7909) is in development. Samples obtained in a Phase Ib clinical trial were tested to confirm biomarkers of innate immunity and evaluate effects of CPG 7909 (PF-03512676) on adaptive immunity. Subjects received two intramuscular doses of commercial BioThrax® (Anthrax Vaccine Adsorbed, AVA), or two intramuscular doses of one of four formulations of AV7909. IP-10, IL-6, and C-reactive protein (CRP) levels were elevated 24 to 48 hours...

  13. Cell-mediated immunity elicited by the blood stage malaria vaccine apical membrane antigen 1 in Malian adults: Results of a Phase I randomized trial

    OpenAIRE

    Lyke, Kirsten E; Daou, Modibo; DIARRA, ISSA; Kone, Abdoulaye; Kouriba, Bourema; Thera, Mohamadou A.; Dutta, Sheetij; Lanar, David E.; Heppner, D Gray; Doumbo, Ogobara K.; Plowe, Christopher V.; Sztein, Marcelo B.

    2009-01-01

    The development of a safe and effective malaria vaccine is impeded by the complexity of the Plasmodium life cycle. A vaccine that elicits both cell-mediated and humoral immune responses might be needed for protection against this multistage parasitic infection. Apical membrane antigen 1 (AMA-1) plays a key role in erythrocytic invasion but is also expressed in sporozoites and in late stage liver schizonts, where it may provide a target of protective cell-mediated immunity (CMI). A Phase 1 tri...

  14. Suppression of cell-mediated immunity to challenge with P 815 mastocytoma in concanavalin A-treated mice.

    Science.gov (United States)

    Ekstedt, R D; Merdian, D J

    1983-01-01

    C57Bl/6 (B6) mice allogeneic to the P 815 mastocytoma tumor cell line when treated with concanavalin A prior to and at frequent intervals following challenge intraperitoneally with 10(7) tumor cells showed a significant suppression of their cell-mediated immune response at 9-10 days when compared with untreated animals. Suppression of the immune response of mice syngeneic (DBA/2) or hybrid (BDF1) to the tumor was also evidenced by increased mortality rates in concanavalin A-treated animals. The suppression of cell-mediated cytotoxicity observed in B6 mice treated with concanavalin A could be reversed by pretreatment with 20 mg silica injected intraperitoneally 7 days prior to challenge. These results suggest that macrophages play a significant role in the concanavalin A-induced immune suppression observed in this in vivo tumor-host system. PMID:6297806

  15. Recombinant human interleukin-2 reverses in vitro-deficient cell-mediated immune responses to tuberculin purified protein derivative by lymphocytes of tuberculous patients.

    OpenAIRE

    Shiratsuchi, H; Okuda, Y.; Tsuyuguchi, I

    1987-01-01

    In vitro lymphocyte proliferative response to purified protein derivative of tuberculin (PPD) was investigated in patients with tuberculosis. Peripheral blood lymphocytes (PBL) from patients with advanced, refractory tuberculosis showed a significantly depressed response compared with the response of PBL from patients with newly diagnosed tuberculosis (P less than 0.01). A further characterization of this low responsiveness to PPD revealed that PBL from these advanced tuberculous patients fai...

  16. Effects of chronic whole-body gamma irradiation on cell mediated immunity

    International Nuclear Information System (INIS)

    The whole blood lymphocyte stimulation test has been used to estimate the effects of chronic, whole-body, gamma irradiation in the dog. At lower dose levels, 0.07 and 0.33 R/day to cumulative dose of about 50 and 250 R, there was no change in cell mediated immunity. Dogs at high dose levels were affected. Dogs which succumbed to aplastic anemia at high doses had reduced immunological responses. Dogs which survived these high doses showed a temporary depression. When aplastic anemia was initially noted, there was a differential response to PHA and Con-A stimulation. The response to the former mitogen was profoundly reduced, but Con-A stimulated cells were unaffected, indicative of the development of radioresistant cell lines. As the dogs progressed toward aplastic anemia, all T lympocytes were negatively affected

  17. T-cell-mediated drug hypersensitivity: immune mechanisms and their clinical relevance.

    Science.gov (United States)

    Yun, James; Cai, Fenfen; Lee, Frederick J; Pichler, Werner J

    2016-04-01

    T-cell-mediated drug hypersensitivity represents a significant proportion of immune mediated drug hypersensitivity reactions. In the recent years, there has been an increase in understanding the immune mechanisms behind T-cell-mediated drug hypersensitivity. According to hapten mechanism, drug specific T-cell response is stimulated by drug-protein conjugate presented on major histocompatibility complex (MHC) as it is presented as a new antigenic determinant. On the other hand, p-i concept suggests that a drug can stimulate T cells via noncovalent direct interaction with T-cell receptor and/or peptide-MHC. The drug binding site is quite variable and this leads to several different mechanisms within p-i concept. Altered peptide repertoire can be regarded as an 'atypical' subset of p-i concept since the mode of the drug binding and the binding site are essentially identical to p-i concept. However, the intracellular binding of abacavir to HLA-B(*)57:01 additionally results in alteration in peptide repertoire. Furthermore the T-cell response to altered peptide repertoire model is only shown for abacavir and HLA-B(*)57:01 and therefore it may not be generalised to other drug hypersensitivity. Danger hypothesis has been postulated to play an important role in drug hypersensitivity by providing signal 2 but its experimental data is lacking at this point in time. Furthermore, the recently described allo-immune response suggests that danger signal may be unnecessary. Finally, in view of these new understanding, the classification and the definition of type B adverse drug reaction should be revised. PMID:27141480

  18. Induction of humoral and cell-mediated immune responses by hepatitis B virus epitope displayed on the virus-like particles of prawn nodavirus.

    Science.gov (United States)

    Yong, Chean Yeah; Yeap, Swee Keong; Goh, Zee Hong; Ho, Kok Lian; Omar, Abdul Rahman; Tan, Wen Siang

    2015-02-01

    Hepatitis B virus (HBV) is a deadly pathogen that has killed countless people worldwide. Saccharomyces cerevisiae-derived HBV vaccines based upon hepatitis B surface antigen (HBsAg) is highly effective. However, the emergence of vaccine escape mutants due to mutations on the HBsAg and polymerase genes has produced a continuous need for the development of new HBV vaccines. In this study, the "a" determinant within HBsAg was displayed on the recombinant capsid protein of Macrobrachium rosenbergii nodavirus (MrNV), which can be purified easily in a single step through immobilized metal affinity chromatography (IMAC). The purified protein self-assembled into virus-like particles (VLPs) when observed under a transmission electron microscope (TEM). Immunization of BALB/c mice with this chimeric protein induced specific antibodies against the "a" determinant. In addition, it induced significantly more natural killer and cytotoxic T cells, as well as an increase in interferon gamma (IFN-γ) secretion, which are vital for virus clearance. Collectively, these findings demonstrated that the MrNV capsid protein is a potential carrier for the HBV "a" determinant, which can be further extended to display other foreign epitopes. This paper is the first to report the application of MrNV VLPs as a novel platform to display foreign epitopes. PMID:25416760

  19. Vaccination of pigs with attenuated Lawsonia intracellularis induced acute phase protein responses and primed cell-mediated immunity without reduction in bacterial shedding after challenge

    DEFF Research Database (Denmark)

    Riber, Ulla; Heegaard, Peter M. H.; Hvass, Henriette Cordes; Ståhl, Marie; Jensen, Tim Kåre; Jungersen, Gregers

    2015-01-01

    same extent as non-vaccinated pigs after challenge,however less L. intracellularis in ileum and lymph nodes was seen post mortem. In the RE group, challengedid not lead to L. intracellularis shedding and no challenge bacteria were found post mortem. In both VACand RE the acute phase haptoglobin...... response was diminished and L. intracellularis specific IgG responseswere delayed and reduced compared to non-vaccinated pigs. On the other hand L. intracellularis specificIFN- responses tended to develop faster in the VAC group compared to controls.Conclusion: Although vaccinated and non-vaccinated pigs...

  20. Induction of cell-mediated immunity to Mycobacterium leprae in mice

    Energy Technology Data Exchange (ETDEWEB)

    Patel, P.J.; Lefford, M.J.

    1978-01-01

    The immune response of mice to armadillo-derived, irradiation-killed Mycobacterium leprae (I-ML) was investigated. Following injection of 100 microgram of I-ML into the left hind footpads of mice, a state of cell-mediated immunity (CMI) was engendered to antigens of M. leprae. The evidence for CMI was as follows: (1) development of delayed-type hypersensitivity to both human tuberculin purified protein derivative and soluble M. leprae antigens; (2) T-lymphocyte-dependent macrophage activation at the inoculation site; (3) specific systemaic resistance to the cross-reactive species M. tuberculosis; and (4) immunopotentiation of the delayed-type hypersensitivity response to an unrelated antigen. The CMI induced by I-ML in aqueous suspension was greater than that obtained with the same antigen in water-in-oil emulsion, even though the latter generated a more severe reaction at the site of immunization. I-ML also induced a stronger CMI response than the corresponding dose of heat-killed BCG.

  1. A longitudinal study of cell-mediated immunity in pigs infected with porcine parvovirus

    DEFF Research Database (Denmark)

    Ladekjaer-Mikkelsen, A.S.; Nielsen, Jens

    2002-01-01

    Porcine parvovirus (PPV) is an ubiquitous pathogen causing reproductive failure in swine. Protection against reproductive failure caused by acute PPV infection has commonly been related to the presence of specific antibodies in the dam. However, the role of cell-mediated immunity during chronic PPV...... infection remains to be elucidated, and may be relevant to the pathogenesis of novel diseases such as postweaning multisystemic wasting syndrome (PMWS), which may be triggered by coinfection with PPV and porcine circovirus type 2 (PCV2). To investigate whether pigs infected with PPV generate a cell...... isolated, and virus-specific lymphoproliferative responses and the cytolytic activities of cytotoxic T-lymphocytes (CTL) and natural killer (NK) cells were examined. Cytolytic assays were performed by the chromium release method, using as targets a syngeneic porcine kidney cell line established for the...

  2. Hypothalamus-Pituitary-Adrenal cell-mediated immunity regulation in the Immune Restoration Inflammatory Syndrome.

    Science.gov (United States)

    Khakshooy, Allen; Chiappelli, Francesco

    2016-01-01

    Over one third of the patients sero-positive for the human immunodeficiency virus (HIV) with signs of the acquired immune deficiency syndrome (AIDS), and under treatment with anti-retroviral therapy (ART), develop the immune reconstitution inflammatory syndrome (IRIS). It is not clear what variables are that determine whether a patient with HIV/AIDS will develop ART-related IRIS, but the best evidence base thus far indicates that HIV/AIDS patients with low CD4 cell count, and HIV/AIDS patients whose CD4 count recovery shows a sharp slope, suggesting a particularly fast "immune reconstitution", are at greater risk of developing IRIS. Here, we propose the hypothesis that one important variable that can contribute to low CD4 cell count number and function in ART-treated HIV/AIDS patients is altered hypothalamic-pituitary-adrenal (HPA) cell-mediated immune (CMI) regulation. We discuss HPA-CMI deregulation in IRIS as the new frontier in comparative effectiveness research (CRE) for obtaining and utilizing the best evidence base for treatment of patients with HIV/AIDS in specific clinical settings. We propose that our hypothesis about altered HPA-CMI may extend to the pathologies observed in related viral infection, including Zika. PMID:27212842

  3. Vaccine-induced T cell-mediated immunity plays a critical role in early protection against pseudorabies virus (suid herpes virus type 1) infection in pigs

    NARCIS (Netherlands)

    Rooij, van E.M.A.; Bruin, de M.G.M.; Visser-Hendriksen, de Y.E.; Middel, W.G.; Boersma, W.J.A.; Bianchi, A.T.J.

    2004-01-01

    The aim of our study was to evaluate the relative importance of antibody and T cell-mediated immunity in protection against pseudorabies virus (suid herpes virus type 1) infection in pigs. We induced different levels of immune responses by using: (1) a modified live vaccine; (2) the same modified li

  4. Induction of cell-mediated immunity during early stages of infection with intracellular protozoa

    Directory of Open Access Journals (Sweden)

    Gazzinelli R.T.

    1998-01-01

    Full Text Available Toxoplasma gondii and Trypanosoma cruzi are intracellular parasites which, as part of their life cycle, induce a potent cell-mediated immunity (CMI maintained by Th1 lymphocytes and IFN-g. In both cases, induction of a strong CMI is thought to protect the host against rapid parasite multiplication and consequent pathology and lethality during the acute phase of infection. However, the parasitic infection is not eliminated by the immune system and the vertebrate host serves as a parasite reservoir. In contrast, Leishmania sp, which is a slow growing parasite, appears to evade induction of CMI during early stages of infection as a strategy for surviving in a hostile environment (i.e., inside the macrophages which are their obligatory niche in the vertebrate host. Recent reports show that the initiation of IL-12 synthesis by macrophages during these parasitic infections is a key event in regulating CMI and disease outcome. The studies reviewed here indicate that activation/inhibition of distinct signaling pathways and certain macrophage functions by intracellular protozoa are important events in inducing/modulating the immune response of their vertebrate hosts, allowing parasite and host survival and therefore maintaining parasite life cycles.

  5. Contribution of T cell-mediated immunity to the resistance to staphlococcal infection

    International Nuclear Information System (INIS)

    Abscess formation in nude mice after subcutaneous inoculation of Staphylococcus aureus (S. aureus) was more extensive and prolonged as compared with that in phenotypically normal littermates. Abscess formation in nude mice was augmented markedly by whole-body irradiation. Not only T cell-mediated immunity but also radiosensitive, nonimmune phagocytosis appear to contribute to the resistance against staphylococcal infection

  6. A longitudinal study of cell-mediated immunity in pigs infected with porcine parvovirus

    DEFF Research Database (Denmark)

    Ladekjaer-Mikkelsen, A.S.; Nielsen, Jens

    2002-01-01

    Porcine parvovirus (PPV) is an ubiquitous pathogen causing reproductive failure in swine. Protection against reproductive failure caused by acute PPV infection has commonly been related to the presence of specific antibodies in the dam. However, the role of cell-mediated immunity during chronic PPV...

  7. Effect of iron deficiency anemia and its treatment on cell mediated immunity

    OpenAIRE

    Attia, Mohamed Attia; Salwa A. Essa; Nosair, Nahla A; Amin, Ahmed M; El-Agamy, Osama A.

    2009-01-01

    Iron deficiency anemia (IDA) is one of the most prevalent micronutrient deficiencies particularly in the developing countries. While there is evidence of an altered immune profile in iron deficiency, the exact immunoregulatory role of iron is not known. Knowledge particularly in children, who are vulnerable to iron deficiency and infection, is lacking. We aimed to study the effects of IDA and its treatment with oral iron supplementation on cell-mediated immunity. The levels of T-lymphocytes, ...

  8. Cell-mediated immunity in patients with carcinoma under immunotheraphy

    International Nuclear Information System (INIS)

    'In vivo' and 'in vitro' cellular immunity is evaluated in 32 patients with carcinoma under immunotheraphy with subcutaneous or endovenous glucan, transfer factor and levamisole. The immunotheraphy is done relatively by intradermal tests with common antigens, by sensitization with dinitrochlorinebenzene and lymphocytes culture from whole blood. The levels of blood serum of human T lymphotocyte soluble receptor for sheep erythrocytes are detected. (M.A.C.)

  9. Effects of injectable trace minerals on humoral and cell-mediated immune responses to Bovine viral diarrhea virus, Bovine herpes virus 1 and Bovine respiratory syncytial virus following administration of a modified-live virus vaccine in dairy calves.

    Science.gov (United States)

    Palomares, R A; Hurley, D J; Bittar, J H J; Saliki, J T; Woolums, A R; Moliere, F; Havenga, L J; Norton, N A; Clifton, S J; Sigmund, A B; Barber, C E; Berger, M L; Clark, M J; Fratto, M A

    2016-10-01

    Our objective was to evaluate the effect of an injectable trace mineral (ITM) supplement containing zinc, manganese, selenium, and copper on the humoral and cell mediated immune (CMI) responses to vaccine antigens in dairy calves receiving a modified-live viral (MLV) vaccine containing BVDV, BHV1, PI3V and BRSV. A total of 30 dairy calves (3.5 months of age) were administered a priming dose of the MLV vaccine containing BHV1, BVDV1 & 2, BRSV, PI3V, and an attenuated-live Mannheimia-Pasteurella bacterin subcutaneously (SQ). Calves were randomly assigned to 1 of 2 groups: (1) administration of ITM SQ (ITM, n=15) or (2) injection of sterile saline SQ (Control; n=15). Three weeks later, calves received a booster of the same vaccine combination SQ, and a second administration of ITM, or sterile saline, according to the treatment group. Blood samples were collected on days 0, 7, 14, 21, 28, 42, 56, and 90 post-vaccination for determination of antibody titer, viral recall antigen-induced IFN-γ production, and viral antigen-induced proliferation by peripheral blood mononuclear cells (PBMC). Administration of ITM concurrently with MLV vaccination resulted in higher antibody titers to BVDV1 on day 28 after priming vaccination compared to the control group (P=0.03). Calves treated with ITM showed an earlier enhancement in PBMC proliferation to BVDV1 following vaccination compared to the control group. Proliferation of PBMC after BVDV stimulation tended to be higher on day 14 after priming vaccination in calves treated with ITM than in the control group (P=0.08). Calves that received ITM showed higher PBMC proliferation to BRSV stimulation on day 7 after priming vaccination compared to the control group (P=0.01). Moreover, calves in the ITM group also had an enhanced production IFN-γ by PBMC after stimulation with BRSV on day 21 after priming vaccination compared to day 0 (P<0.01). In conclusion, administration of ITM concurrently with MLV vaccination in dairy calves

  10. Self-adjuvanting influenza candidate vaccine presenting epitopes for cell-mediated immunity on a proteinaceous multivalent nanoplatform.

    Science.gov (United States)

    Szurgot, Inga; Szolajska, Ewa; Laurin, David; Lambrecht, Benedicte; Chaperot, Laurence; Schoehn, Guy; Chroboczek, Jadwiga

    2013-09-13

    We exploit the features of a virus-like particle, adenoviral dodecahedron (Ad Dd), for engineering a multivalent vaccination platform carrying influenza epitopes for cell-mediated immunity. The delivery platform, Ad Dd, is a proteinaceous, polyvalent, and biodegradable nanoparticle endowed with remarkable endocytosis activity that can be engineered to carry 60 copies of a peptide. Influenza M1 is the most abundant influenza internal protein with the conserved primary structure. Two different M1 immunodominant epitopes were separately inserted in Dd external positions without destroying the particles' dodecahedric structure. Both kinds of DdFluM1 obtained through expression in baculovirus system were properly presented by human dendritic cells triggering efficient activation of antigen-specific T cells responses. Importantly, the candidate vaccine was able to induce cellular immunity in vivo in chickens. These results warrant further investigation of Dd as a platform for candidate vaccine, able to stimulate cellular immune responses. PMID:23880363

  11. Evaluation of innate, humoral and cell-mediated immunity in mice following in vivo implantation of electrospun polycaprolactone

    International Nuclear Information System (INIS)

    Electrospun polycaprolactone (EPCL) is currently being investigated for use in tissue engineering applications such as vascular grafts. However, the effects of electrospun polymers on systemic immune responses following in vivo exposure have not previously been examined. The work presented evaluates whether EPCL in either a microfibrous or nanofibrous form affects innate, humoral and/or cell-mediated immunity using a standard immunotoxicological testing battery. Holistic in vivo endpoints examined include the antibody-forming cell assay (AFC or plaque assay) and the delayed-type hypersensitivity response to Candida albicans. In addition, natural killer cell cytotoxic activity was assessed using an ex vivo assay and splenic cell population phenotypes were analyzed by flow cytometry for material exposure-related changes. Results indicated that 28 day subcutaneous implantation of EPCL, either in microfibrous or nanofibrous form, did not affect the systemic functions of the immune system in 12–16 week old female B6C3F1 mice. (paper)

  12. Activation of cell-mediated immunity by Morinda citrifolia fruit extract and its constituents.

    Science.gov (United States)

    Murata, Kazuya; Abe, Yumi; Futamura-Masudaa, Megumi; Uwaya, Akemi; Isami, Fumiyuki; Matsuda, Hideaki

    2014-04-01

    Morinda citrifolia, commonly known as noni, is a traditional natural medicine in French Polynesia and Hawaii. Functional foods derived from M. citrifolia fruit have been marketed to help prevent diseases and promote good health. The objective of this study was to assess the effects of M. citrifolia fruit on cell-mediated immunity. In the picryl chloride-induced contact dermatitis test, M. citrifolia fruit extract (Noni-ext) inhibited the suppression of cell-mediated immunity by immunosuppressive substances isolated from freeze-dried ascites of Ehrlich carcinoma-bearing mice (EC-sup). In addition, Noni-ext inhibited reduction of IL-2 production in EC-sup-treated mice and activated natural killer cells in normal mice. These results suggest that Noni-ext has multiple effects on the recovery of cell-mediated immunity. Furthermore, we investigated the active principles of Noni-ext and identified an iridoid glycoside, deacetylasperulosidic acid. Oral administration of deacetylasperulosidic acid inhibited the reduction of ear swelling, and also cancelled the suppression of IL-2 production along with the activation of natural killer cells in the same manner as that of Noni-ext. PMID:24868850

  13. Characteristics of Cell-mediated, Anti-listerial Immunity Induced by A Naturally Avirulent Listeria monocytogenes Serotype 4a Strain HCC23

    Science.gov (United States)

    The characteristics of cell-mediated, anti-listerial immune response initiated by an avirulent Listeria monocytogenes serotype 4a strain HCC23 was assessed. Similar to virulent strain EGD, avirulent strain HCC23 grew readily within macrophage-like J774 cells, but nonhemolytic strain ATCC 15313 did n...

  14. Effect of Zinc on Humoral and Cell-Mediated Immunity of Broilers Vaccinated Against Coccidiosis

    Directory of Open Access Journals (Sweden)

    Milad Moazeni

    2013-09-01

    Full Text Available Background: The aim of the present study was the comparison of humoral and cell-mediated immunity in ‎broilers fed with different levels of zinc during a coccidiosis challenge.‎Methods: One hundred and forty-‎four one-day-old broiler chicks were used with three ‎dietary zinc ‎(40, 120 and 200 mg/kg. At 14 d of age, all birds were inoculated orally with 5×103 sporulated oocysts of E. Tenella. ‎At ‎2, 22, 32, 42 ‎days of age, the blood serums were tested for ‎antibody titer against‎ Newcas­tle disease vaccine, using ‎the standard HI test. On day 42 the sum of nitrite ‎and nitrate based on the reduction of nitrate ‎to nitrite by cadmium ‎and white blood cell count (WBC using a hemocytometer were measured.Results: At 42 d, levels of ‎120 and 200 mg significantly (P< 0.05 increased the antibody titer in compare with the control. The peak response of CBH was observed at the level of 200 mg Zn/kg diet. Also both level of 120 and 200 mg Zn/kg diet increased WBC count and sum of nitrite and nitrate‎ in serum compared with the control.Conclusion: The levels of 120 and 200 mg Zn/kg diet could be considered as a non-pharmacologic booster of immunity in broilers chicks infected with E. Tenella.

  15. Cell-mediated response at the muscle phase of Trichinella pseudospiralis and Trichinella spiralis infections.

    Science.gov (United States)

    Lee, K M; Ko, R C

    2006-06-01

    The cell-mediated response in BALB/c mice infected either by Trichinella pseudospiralis or Trichinella spiralis was compared at days 30-50 post-infection (muscle phase). The former species is non-encapsulated, whereas the latter is encapsulated in host muscles. The pattern of response against the two species was similar. Both species elicited T(H)0 or T(H)1/T(H)2 response, with the last one being dominant. Productions of interferon gamma (IFN-gamma), interleukin (IL)-4 and IL-5 were observed after antigenic restimulation of splenocytes from infected mice. No significant difference was observed between the levels of response to concanavalin A (Con-A) by the splenocytes from both infected and non-infected animals. There was a significant increase in serum IgG(1) and IgG(2a). Flow cytometric analysis revealed a marked proliferative response of splenocytes from infected mice to worm antigens, dominated by B (CD19) lymphoblasts. Only a few helper (CD4+) and cytotoxic (CD8+) T lymphoblasts were present. This was confirmed by an up-regulation of CD69, with a dominant expression on B lymphoblasts. In conclusion, the minimal or lack of intense cellular response against T. pseudospiralis in muscles is likely not due to depression of cell-mediated immunity. PMID:16489472

  16. Impact of iron deficiency anemia on cell-mediated and humoral immunity in children: A case control study

    OpenAIRE

    Das, Indranil; SAHA, Kaushik; Mukhopadhyay, Debanjan; Roy, Shreosee; Raychaudhuri, Gargi; Chatterjee, Mitali; Mitra, Pradip Kumar

    2014-01-01

    Objective: The precise role of iron in immune regulation especially in children vulnerable to iron deficiency is not fully known. Hence, this study was conducted to evaluate the effects of iron deficiency anemia (IDA) and its treatment with oral iron supplementation on cell-mediated immunity (CMI) and humoral immunity (HMI) in children. Materials and Methods: A total of 40 children (

  17. Immune responses to infectious laryngotracheitis virus.

    Science.gov (United States)

    Coppo, Mauricio J C; Hartley, Carol A; Devlin, Joanne M

    2013-11-01

    Infectious laryngotracheitis (ILT) is an upper respiratory tract disease in chickens caused by infectious laryngotracheitis virus (ILTV), an alphaherpesvirus. Despite the extensive use of attenuated, and more recently recombinant, vaccines for the control of this disease, ILT continues to affect the intensive poultry industries worldwide. Innate and cell-mediated, rather than humoral immune responses, have been identified as responsible for protection against disease. This review examines the current understandings in innate and adaptive immune responses towards ILTV, as well as the role of ILTV glycoprotein G in modulating the host immune response towards infection. Protective immunity induced by ILT vaccines is also examined. The increasing availability of tools and reagents for the characterisation of avian innate and cell-mediated immune responses are expected to further our understanding of immunity against ILTV and drive the development of new generation vaccines towards enhanced control of this disease. PMID:23567343

  18. Natural Killer Cell Mediated Cytotoxic Responses in the Tasmanian Devil

    OpenAIRE

    Brown, Gabriella K.; Kreiss, Alexandre; Lyons, A. Bruce; Woods, Gregory M.

    2011-01-01

    The Tasmanian devil (Sarcophilus harrisii), the world's largest marsupial carnivore, is under threat of extinction following the emergence of an infectious cancer. Devil facial tumour disease (DFTD) is spread between Tasmanian devils during biting. The disease is consistently fatal and devils succumb without developing a protective immune response. The aim of this study was to determine if Tasmanian devils were capable of forming cytotoxic antitumour responses and develop antibodies against D...

  19. Cordyceps militaris Enhances Cell-Mediated Immunity in Healthy Korean Men.

    Science.gov (United States)

    Kang, Ho Joon; Baik, Hyun Wook; Kim, Sang Jung; Lee, Seong Gyu; Ahn, Hong Yup; Park, Ju Sang; Park, Sang Jong; Jang, Eun Jeong; Park, Sang Woon; Choi, Jin Young; Sung, Ji Hee; Lee, Seung Min

    2015-10-01

    Cordyceps militaris is a mushroom traditionally used for diverse pharmaceutical purposes in East Asia, including China, and has been found to be effective for enhancing immunity through various types of animal testing. The aim of this study is to determine the efficacy of C. militaris for enhancing cell-mediated immunity and its safety in healthy male adults. Healthy male adults were divided into the experimental group (n = 39), given 1.5 g/day of ethanol treated C. militaris in capsules, and the control group (n = 40), given the same number of identical placebo capsules filled with microcrystalline cellulose and lactose for 4 weeks from February 13 to March 14, 2012; the natural killer (NK) cell activity, lymphocyte proliferation index (PI), and T-helper cell 1 (Th1) cytokine cluster (interferon [IFN]-γ, interleukin [IL]-12, IL-2, and tumor necrosis factor [TNF]-α) were measured, along with stability test, at weeks 0, 2, and 4. The C. militaris group showed a statistically significant greater increase in NK200 (P = .0010), lymphocyte PI (P ≤ .0001), IL-2 (P = .0096), and IFN-γ (P = .0126), compared with the basal level, than the placebo group. There was no statistically significant adverse reaction. C. militaris enhanced the NK cell activity and lymphocyte proliferation and partially increased Th1 cytokine secretion. Therefore, C. militaris is safe and effective for enhancing cell-mediated immunity of healthy male adults. PMID:26284906

  20. Pulmonary delivery of an inulin-stabilized influenza subunit vaccine prepared by spray-freeze drying induces systemic, mucosal humoral as well as cell-mediated immune responses in BALB/c mice

    NARCIS (Netherlands)

    Amorij, J-P.; Saluja, V.; Petersen, A.H.; Hinrichs, W.L.J.; Huckriede, A.; Frijlink, H.W.

    2007-01-01

    In this study pulmonary vaccination with a new influenza subunit vaccine powder was evaluated. Vaccine powder was produced by spray-freeze drying (SFD) using the oligosaccharide inulin as stabilizer. Immune responses after pulmonary vaccination of BALB/c mice with vaccine powder were determined and

  1. The measurement of cell mediated immunity by radioimmunoassay in desensitizing treatment with acupoints for allergic asthma

    International Nuclear Information System (INIS)

    Three mitogens consisted of PHA, PWM, LPS were used to activate lymphocytes. Lymphocyte transformation with radioisotope incorporation of 3H-TdR was done in 20 patients with allergic asthma and 14 healthy persons as control groups. Cell mediated immune in these cases of desensitizing treatment with acupoints were studied. The experiments showed that the incorporation rates of 3H-TdR, acupoints were studied. The experiments showed that the incorporation rates of 3H-TdR, activated by PHA, PWM, LPS, of the allergic asthma patients were P>0.05, P3H-TdR in lymphocytes after desensitizing treatment with acupoints compared with that before the treatment tended to be normal. Lymphocyte transformation difference of 3H-TdR incorporation rates between this group and A or B control groups was significant (P<0.01). This study provides scientific clinical experimental evidences for researching cell mediated immune in attack and curative effects of allergic asthma

  2. Potentiation of T cell-mediated immunity by low dose radiation

    International Nuclear Information System (INIS)

    Full text: Low dose radiation is reported to have beneficial effect on organisms in some cases, though high dose radiation is harmful. Attenuation of diabetes, auto-immune diseases and cancer is the example of this beneficial effect of radiation, i.e. radiation hormesis. Because the disorder of accommodation in immune system is involved in such diseases, immunological network is assumed to be one of the targets for radiation hormesis. In this study, we utilized mice immunized with allogeneic tumor cells to evaluate the hormetic effect of continuous irradiation with low dose rate gamma-ray on the host immune system. C57BL/6 mice (H-2b) were exposed to gamma-ray in an irradiation room bearing 50,000 Ci 60Co at 97 μGy/h, the dose rate where no significant effect on life span is detected by continuous whole body irradiation. Ninety-eight hour after the initiation of the irradiation, they were intraperitoneally immunized with an allogeneic mastocytoma, P815 (H-2b), and further irradiated for 335 h. We found that antigen-specific killer T cell activity was significantly enhanced by the irradiation. Ability of spleen cells to produce T cell lymphokines such as IL-2, IL-4 and IL-10 was also significantly elevated. Antigen-specific IgG1 titer in serum which is highly dependent on T cells, increased, while IgM titer was not marginally affected. In addition, T cell population in spleen was increased and B cell population decreased in naive mice irradiated with the same schedule, while natural killer activity decreased. These results suggest that the continuous whole body exposure to low dose rate gamma-ray potentiates T cell mediated immunity and shifts the immunological balance from humoral immunity to cellular immunity. Modulation of such immunological balance might be involved in the beneficial effect of low dose rate radiation

  3. THE STATE OF CELL MEDIATED IMMUNITY AMONG HEPATITIS B SURFACE ,ANTGENI CARRIERS IN IRAN,

    Directory of Open Access Journals (Sweden)

    A. MASSOUD

    1987-06-01

    Full Text Available Cell-mediated immune (CMI s t a t us and sub- popul at i ons o f pe r ipheral b l ood lymphocytes were investigated in one hundre d volunt a ry blood donors who were car r ier s of Ag • HE S A signi f i c ant decr e ase of t otal T-cells observed in HB Ag carri e rs as compared t o normal controls. The percenS t age o f active T-cells a nd B-lymphocytes did not d i f f e r signi f icant ly between the t wo groups ."nAddi t ion of aut ologous serum from HE Ag c a r r iers t o s t heir l ymphocyt e s reduced the numbe r of detectabl e cells in HE Ag carriers . This reduction coul d be due to the s presence of a r osette i nhi bitory f actor in their serum. Our studies demonstrated a failur e o f CMI among HB Ags car r i ers detected by the l e ukocyte migr ation i nhibition (LMI test. This failure cannot be attributed to the presence of HE Ag-AB complexes in their serum. It is s possible that specific failure of CMI allows the hepatitis B virus to remain harmless in carriers a Hepatitis B surface-antigen (HE Ag; Hepatitis Bs coreantigen (HE Ag and Hepatitis Be-antigen (HE Ag, c e have been established as indicating ineffectivity in viral hepatitis B ({I, 6 , 20, 28."nA number of infected individuals also developed clini cal evidence of disease and HE Ag may s the serum of some subjects for a long rema•ln present I•n time (18. It has been suggested that to a defect in CMI, the persistence of HB Ag s whether liver disease is is related present or not, and impairment of the lymphocyte response to phytohaemagglutinin (PHA in this group is presented in evide•"nnee (8, •9 , 13, 24, 25 .In contrast, other workers report a normal respons e t o PHA in healthy carriers of HE Ag and s they concludE that the defective T-cell response is relat ed to the live!' disease rather than the immune system (31. Dudley et al (8 have suggested that liver damage occurring after hepatitis B infection, may be an effect of thymus-dependent lymphocytes (12."n

  4. Effect of Astragalus Polysaccharide on the Cell-mediated Immunity of Traumatic Stress Mice

    Institute of Scientific and Technical Information of China (English)

    曾广仙; 熊金蓉; 刘俊英; 廖奕华; 代丽红; 李杏娟; 沈关心

    2004-01-01

    To investigate the changes of immune functions and the effects of Astragaius polysaccharide (ASP) on the cell-mediated immunity of the traumatic stress model of mouse by amputation, 50 mice were randomly divided into 5 groups for study, in which the group A and B served as the normal control (by injecton of 0.5 ml of saline intra-peritoneally daily), and as the stress control (by intra-peritoneal injecton of 0.5 ml of normal saline into mice after amputation) respectively, to the group C, D and E of mice, 1000 mg/kg (high dose), 300 mg/kg (median dose) and 250 mg/kg (low dose). The CD4+ and CD8+ T cells as well as the expression of the c-fos protein were determined by immunohistochemical techniques, and the expressions of NF-κB mRNA and IL-10 mRNA were assayed by hybridization in situ. The experimental results showed that in comparison with the normal control group of mice (group A), the expression levels of NF-κB mRNA, IL-10 mRNA and the c-fos protein in the tissues of thymus and spleen in the stress controls were significantly elevated and the CD4+ T cells and CD4/CD8 ratio were decreased. However, in comparison with the stress control of mice (group B), the expressions of NF-κB mRNA and IL-10 mRNA were inhibited by ASP, and the CD4+ T cells and CD4/CD8 ratio were increased in groups C, D and E, but the level of c-fos protein was decreased. There was no significant difference in these parameters among group C, D and E. It is con-cluded that the functions of cell-mediated immunity of mice were disturbed under the stress condition of the traumatic injuries after amputation. And the immune functions can be effectively restored by the use of Astraga/us polysaccharide.

  5. CD4 T cells mediate both positive and negative regulation of the immune response to HIV infection: complex role of T follicular helper cells and Regulatory T cells in pathogenesis

    Directory of Open Access Journals (Sweden)

    Chansavath ePhetsouphanh

    2015-01-01

    Full Text Available HIV-1 infection results in chronic activation of cells in lymphoid tissue, including T cells, B cells and myeloid lineage cells. The resulting characteristic hyperplasia is an amalgam of proliferating host immune cells in the adaptive response, increased concentrations of innate response mediators due to viral and bacterial products, and homeostatic responses to inflammation. While it is generally thought that CD4 T cells are greatly depleted, in fact, two types of CD4 T cells appear to be increased, namely regulatory T cells (Tregs and T follicular helper cells (Tfh. These cells have opposing roles, but may both be important in the pathogenic process. Whether Tregs are failing in their role to limit lymphocyte activation is unclear, but there is no doubt now that Tfh are associated with B cell hyperplasia and increased germinal centre activity. Antiretroviral therapy (ART may reduce the lymphocyte activation, but not completely, and therefore there is a need for interventions that selectively enhance normal CD4 function without exacerbating Tfh, B cell or Treg dysfunction.

  6. TRESK channel as a potential target to treat T-cell mediated immune dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Han, Jaehee [Medical Research Center for Neural Dysfunction, Department of Physiology, Institute of Health Sciences, Gyeongsang National University, School of Medicine, Jinju 660-751 (Korea, Republic of); Kang, Dawon, E-mail: dawon@gnu.ac.kr [Medical Research Center for Neural Dysfunction, Department of Physiology, Institute of Health Sciences, Gyeongsang National University, School of Medicine, Jinju 660-751 (Korea, Republic of)

    2009-12-25

    In this review, we propose that TRESK background K{sup +} channel could serve as a potential therapeutic target for T-cell mediated immune dysfunction. TRESK has many immune function-related properties. TRESK is abundantly expressed in the thymus, the spleen, and human leukemic T-lymphocytes. TRESK is highly activated by Ca{sup 2+}, calcineurin, acetylcholine, and histamine which induce hypertrophy, whereas TRESK is inhibited by immunosuppressants, such as cyclosporin A and FK506. Cyclosporine A and FK506 target the binding site of nuclear factor of activated T-cells (NFAT) to inhibit calcineurin. Interestingly, TRESK possesses an NFAT-like docking site that is present at its intracellular loop. Calcineurin has been found to interact with TRESK via specific NFAT-like docking site. When the T-cell is activated, calcineurin can bind to the NFAT-docking site of TRESK. The activation of both TRESK and NFAT via Ca{sup 2+}-calcineurin-NFAT/TRESK pathway could modulate the transcription of new genes in addition to regulating several aspects of T-cell function.

  7. TRESK channel as a potential target to treat T-cell mediated immune dysfunction

    International Nuclear Information System (INIS)

    In this review, we propose that TRESK background K+ channel could serve as a potential therapeutic target for T-cell mediated immune dysfunction. TRESK has many immune function-related properties. TRESK is abundantly expressed in the thymus, the spleen, and human leukemic T-lymphocytes. TRESK is highly activated by Ca2+, calcineurin, acetylcholine, and histamine which induce hypertrophy, whereas TRESK is inhibited by immunosuppressants, such as cyclosporin A and FK506. Cyclosporine A and FK506 target the binding site of nuclear factor of activated T-cells (NFAT) to inhibit calcineurin. Interestingly, TRESK possesses an NFAT-like docking site that is present at its intracellular loop. Calcineurin has been found to interact with TRESK via specific NFAT-like docking site. When the T-cell is activated, calcineurin can bind to the NFAT-docking site of TRESK. The activation of both TRESK and NFAT via Ca2+-calcineurin-NFAT/TRESK pathway could modulate the transcription of new genes in addition to regulating several aspects of T-cell function.

  8. Hypothalamus-Pituitary-Adrenal cell-mediated immunity regulation in the Immune Restoration Inflammatory Syndrome

    OpenAIRE

    Khakshooy, Allen; Chiappelli, Francesco

    2016-01-01

    Over one third of the patients sero-positive for the human immunodeficiency virus (HIV) with signs of the acquired immune deficiency syndrome (AIDS), and under treatment with anti-retroviral therapy (ART), develop the immune reconstitution inflammatory syndrome (IRIS). It is not clear what variables are that determine whether a patient with HIV/AIDS will develop ART-related IRIS, but the best evidence base thus far indicates that HIV/AIDS patients with low CD4 cell count, and HIV/AIDS patient...

  9. Identification of GLA/SE as an effective adjuvant for the induction of robust humoral and cell-mediated immune responses to EBV-gp350 in mice and rabbits.

    Science.gov (United States)

    Heeke, Darren S; Lin, Rui; Rao, Eileen; Woo, Jennifer C; McCarthy, Michael P; Marshall, Jason D

    2016-05-17

    Childhood infection with Epstein-Barr virus (EBV) is often asymptomatic and may result in mild flu-like symptoms, but exposure during adolescence and young adulthood can lead to acute infectious mononucleosis (AIM) with a pathology characterized by swollen lymph nodes, sore throat, and severe fatigue lasting weeks or months. A vaccine targeting the envelope glycoprotein gp350 adjuvanted with aluminum hydroxide complexed with the TLR4 agonist monophosphoryl lipid A (MPLA) achieved a 78% reduction in AIM incidence in a small phase II trial of college-age individuals, but development of this vaccine was halted by the manufacturer. Here, we report the evaluation in mice and rabbits of an EBV-gp350 vaccine combined with an adjuvant composed of the synthetic TLR4 agonist glucopyranosyl lipid A (GLA) integrated into stable emulsion (SE). In mice, GLA/SE-adjuvanted gp350 generated high IgG titers (both IgG1 and IgG2a/c subtypes), elevated EBV-neutralizing antibody titers, and robust poly-functional anti-gp350 CD4(+) T cell responses. In addition, GLA/SE routinely demonstrated superior performance over aluminum hydroxide in all immunological readouts, including induction of durable neutralizing antibody titers out to at least 1 year post-vaccination. Both components of the GLA/SE adjuvant were found to be required to get optimal responses in both arms of the immune response: specifically, SE for neutralizing antibodies and GLA for induction of T cell responses. Furthermore, this vaccine also elicited high neutralizing antibody titers in a second species, rabbit. These promising results suggest that clinical development of a vaccine comprised of EBV-gp350 plus GLA/SE has the potential to prevent AIM in post-adolescents. PMID:27085175

  10. Trypanosoma cruzi adjuvants potentiate T cell-mediated immunity induced by a NY-ESO-1 based antitumor vaccine.

    Directory of Open Access Journals (Sweden)

    Caroline Junqueira

    Full Text Available Immunological adjuvants that induce T cell-mediate immunity (TCMI with the least side effects are needed for the development of human vaccines. Glycoinositolphospholipids (GIPL and CpGs oligodeoxynucleotides (CpG ODNs derived from the protozoa parasite Trypanosoma cruzi induce potent pro-inflammatory reaction through activation of Toll-Like Receptor (TLR4 and TLR9, respectively. Here, using mouse models, we tested the T. cruzi derived TLR agonists as immunological adjuvants in an antitumor vaccine. For comparison, we used well-established TLR agonists, such as the bacterial derived monophosphoryl lipid A (MPL, lipopeptide (Pam3Cys, and CpG ODN. All tested TLR agonists were comparable to induce antibody responses, whereas significant differences were noticed in their ability to elicit CD4(+ T and CD8(+ T cell responses. In particular, both GIPLs (GTH, and GY and CpG ODNs (B344, B297 and B128 derived from T. cruzi elicited interferon-gamma (IFN-γ production by CD4(+ T cells. On the other hand, the parasite derived CpG ODNs, but not GIPLs, elicited a potent IFN-γ response by CD8(+ T lymphocytes. The side effects were also evaluated by local pain (hypernociception. The intensity of hypernociception induced by vaccination was alleviated by administration of an analgesic drug without affecting protective immunity. Finally, the level of protective immunity against the NY-ESO-1 expressing melanoma was associated with the magnitude of both CD4(+ T and CD8(+ T cell responses elicited by a specific immunological adjuvant.

  11. Bacterial kidney disease as a model for studies of cell mediated immunity in rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Jansson, Eva; Hongslo, Thorbjörn; Johannisson, Anders; Pilström, Lars; Timmusk, Sirje; Norrgren, Leif

    2003-04-01

    A cell mediated immune (CMI) response was measured in vitro to heat-killed and to paraformaldehyde fixed Renibacterium salmoninarum (Rs) in rainbow trout (Oncorhynchus mykiss) experimentally challenged with live Rs. The mitogenic response to the T lymphocyte mitogen Concanavalin A (Con A) was reduced during samplings 4 to 6 weeks after immersion, but no effect of the response to the B lymphocyte mitogen lipopolysaccharide (LPS) was detected. The subpopulation of lymphocytes, detected by the monoclonal antibody 1C2, was decreased from the 4th week to the 5th week of infection, and remained at the decreased level up to 10 weeks post immersion. The proportion of Immunoglobulin (Ig) bearing lymphocytes was not affected during the Rs infection period. The humoral antibody level to heat-stable Rs-antigens was increased up to 10 weeks after immersion but after 27 weeks was reduced to a level similar to that of the non-challenged fish. An anamnestic response was demonstrated in challenged fish, as intraperitoneal injection of heat-treated Rs bacteria into Rs challenged fish elicited a stronger humoral antibody response compared with injection into non-challenged fish. PMID:12657537

  12. Direct and Indirect Role of Toll-Like Receptors in T Cell Mediated Immunity

    Institute of Scientific and Technical Information of China (English)

    DamoXu; HaiyingLiu; MousaKomai-Koma

    2004-01-01

    Toll-like receptors (TLR) are pathogen-associated molecular patterns (PAMPs) recognition receptors that play an important role in protective immunity against infection and inflammation. They act as central integrators of a wide variety of signals, responding to diverse agonists of microbial products. Stimulation of Toll-like receptors by microbial products leads to signaling pathways that activate not only innate, but also adaptive immunity by APC dependent or independent mechanisms. Recent evidence revealed that TLR signals played a determining role in the skewing of naive T cells towards either Thl or Th2 responses. Activation of Toll-like receptors also directly or indirectly influences regulatory T cell functions. Therefore, TLRs are required in both immune activation and immune regulation. Study of TLRs has significantly enhanced our understanding of innate and adaptive immune responses and provides novel therapeutic approaches against infectious and inflammatory diseases. Cellular & Molecular Immunology.

  13. Direct and Indirect Role of Toll-Like Receptors in T Cell Mediated Immunity

    Institute of Scientific and Technical Information of China (English)

    Damo Xu; Haiying Liu; Mousa Komai-Koma

    2004-01-01

    Toll-like receptors (TLR) are pathogen-associated molecular patterns (PAMPs) recognition receptors that play an important role in protective immunity against infection and inflammation. They act as central integrators of a wide variety of signals, responding to diverse agonists of microbial products. Stimulation of Toll-like receptors by microbial products leads to signaling pathways that activate not only innate, but also adaptive immunity by APC dependent or independent mechanisms. Recent evidence revealed that TLR signals played a determining role in the skewing of na(i)ve T cells towards either Th1 or Th2 responses. Activation of Toll-like receptors also directly or indirectly influences regulatory T cell functions. Therefore, TLRs are required in both immune activation and immune regulation. Study of TLRs has significantly enhanced our understanding of innate and adaptive immune responses and provides novel therapeutic approaches against infectious and inflammatory diseases.

  14. Influence of Ganoderma lucidum (Curt.: Fr.) P. Karst. on T-cell-mediated immunity in normal and immunosuppressed mice line CBA/Ca.

    Science.gov (United States)

    Nizhenkovska, Iryna V; Pidchenko, Vitalii T; Bychkova, Nina G; Bisko, Nina A; Rodnichenko, Angela Y; Kozyko, Natalya O

    2015-09-01

    The article presents the results of the investigation of the effect of biomass powder of the fungus Ganoderma lucidum on T-cell-mediated immunity in normal and immunosuppressed mice CBA/Ca. Delayed-type hypersensitivity assay was used. Experimental immunodeficiency was established with intraperitoneal injection of the immunosuppressant cyclophosphamide at a single dose of 150 mg/kg on the first day of the experiment. Results of the study show that the administration of biomass powder of Ganoderma lucidum in a dose of 0.5 mg/kg orally for 10 days increases the delayed-type hypersensitivity response in normal mice CBA/Ca. Administration of 0.5 mg/kg of biomass powder of the fungus Ganoderma lucidum for 10 days blocked the development of the T-cell-mediated immunosuppression, induced by administration of cyclophosphamide and restored the delayed-type hypersensitivity response in immunosuppressed mice. Key words: fungus Ganoderma lucidum cyclophosphamide immunodeficiency T-cell-mediated immunity delayed-type hypersensitivity. PMID:26459128

  15. Effect of early vitamin A supplementation on cell-mediated immunity in infants younger than 6 mo.

    Science.gov (United States)

    Rahman, M M; Mahalanabis, D; Alvarez, J O; Wahed, M A; Islam, M A; Habte, D

    1997-01-01

    One hundred twenty infants were randomly assigned to receive either 15 mg vitamin A or placebo with each of three DPT/OPV (diphtheria, pertussis, tetanus/oral polio vaccine) immunizations at monthly intervals. Sixty-two received vitamin A and 58 received placebo. One month after the third supplementation dose, the response to the delayed cutaneous hypersensitivity test [multitest cell-mediated immunity (CMI) skin evaluation] for tetanus, diphtheria, and tuberculin (purified protein derivative, PPD) was the same in the vitamin A and placebo infants. The number of anergic infants was 17 (27%) and 19 (33%) in the vitamin A and placebo groups, respectively. The number of positive tests among well-nourished infants was significantly higher than that in malnourished infants irrespective of supplementation (P 0.7 mumol/L) after supplementation, the vitamin A-supplemented infants had a significantly higher proportion of positive CMI tests than the placebo infants (chi-square test: 8.99, P = 0.008). Among the infants with low serum retinol concentrations ( 0.7 mumol/L) at the time of the CMI test. CMI was consistently better in well-nourished infants irrespective of supplementation. PMID:8988926

  16. Coupling of HIV-1 Antigen to the Selective Autophagy Receptor SQSTM1/p62 Promotes T-Cell-Mediated Immunity

    Science.gov (United States)

    Andersen, Aram Nikolai; Landsverk, Ole Jørgen; Simonsen, Anne; Bogen, Bjarne; Corthay, Alexandre; Øynebråten, Inger

    2016-01-01

    Vaccines aiming to promote T-cell-mediated immune responses have so far showed limited efficacy, and there is a need for novel strategies. Studies indicate that autophagy plays an inherent role in antigen processing and presentation for CD4+ and CD8+ T cells. Here, we report a novel vaccine strategy based on fusion of antigen to the selective autophagy receptor sequestosome 1 (SQSTM1)/p62. We hypothesized that redirection of vaccine antigen from proteasomal degradation into the autophagy pathway would increase the generation of antigen-specific T cells. A hybrid vaccine construct was designed in which the antigen is fused to the C-terminus of p62, a signaling hub, and a receptor that naturally delivers ubiquitinated cargo for autophagic degradation. Fusion of the human immunodeficiency virus-1 antigen Gagp24 to p62 resulted in efficient antigen delivery into the autophagy pathway. Intradermal immunization of mice revealed that, in comparison to Gagp24 delivered alone, fusion to p62 enhanced the number of Gagp24-specific interferon-γ-producing T cells, including CD8+ T cells. The strategy may also have the potential to modulate the antigenic peptide repertoire. Because p62 and autophagy are highly conserved between species, we anticipate this strategy to be a candidate for the development of T-cell-based vaccines in humans.

  17. Global dynamics of cell mediated immunity in viral infection models with distributed delays

    CERN Document Server

    Nakata, Yukihiko

    2010-01-01

    In this paper, we investigate global dynamics for a system of delay differential equations which describes a virus-immune interaction in \\textit{vivo}. The model has two distributed time delays describing time needed for infection of cell and virus replication. Our model admits three possible equilibria, an uninfected equilibrium and infected equilibrium with or without immune response depending on the basic reproduction number for viral infection $R_{0}$ and for CTL response $R_{1}$ such that $R_{1}1$. The immune activation has a positive role in the reduction of the infection cells and the increasing of the uninfected cells if $R_{1}>1$.

  18. Inducible nitric-oxide synthase plays a minimal role in lymphocytic choriomeningitis virus-induced, T cell-mediated protective immunity and immunopathology

    DEFF Research Database (Denmark)

    Bartholdy, C; Nansen, A; Christensen, Jeanette Erbo; Marker, O; Thomsen, Allan Randrup

    . This might suggest a role of NO in regulating vascular reactivity in the context of T cell-mediated inflammation. In conclusion, these findings indicate a minimal role for iNOS/NO in the host response to LCMV. Except for a reduced local oedema in the knockout mice, iNOS/NO seems to be redundant in......By using mice with a targetted disruption in the gene encoding inducible nitric-oxide synthase (iNOS), we have studied the role of nitric oxide (NO) in lymphocytic choriomeningitis virus (LCMV)-induced, T cell-mediated protective immunity and immunopathology. The afferent phase of the T cell...... the up-regulation of proinflammatory cytokine/chemokine genes significantly, nor did it influence the development of fatal meningitis. However, a reduced virus-specific delayed-type hypersensitivity reaction was observed in iNOS-deficient mice compared with both IFN-gamma-deficient and wild-type mice...

  19. Alterations of cell-mediated immune response in children with febrile seizures Alterações da resposta imune celular em crianças portadoras de convulsão febril

    Directory of Open Access Journals (Sweden)

    Terezinha C.B. Montelli

    1997-06-01

    Full Text Available The aim of the present investigation was to study the distribution of T-cell subsets in peripheral blood defined by monoclonal antibodies and by the lymphocyte proliferative response to phytohemagglutinin (PH A in 30 children with febrile seizures and in 14 age-matched control subjects. Frequent respiratory, urinary and dermatologic infections were observed in 22 patients. The immunologic parameters showed that 64% of the patients presented an increased number of CD8+ cells and a low helper/suppressor ratio was observed in 60% of the patients. In addition, the proliferative response of lymphocytes to PHA was impaired in the patients. It was observed the presence of inhibitory activity on lymphocyte function in the plasma of 33% of children with febrile seizures. These results suggest that patients with febrile seizures have an impairment of cellular immunity that may be connected with this epileptic syndrome and explain the infections observed.O objetivo da presente investigação foi estudar a distribuição das subpopulações de células T por meio de anticorpos monoclonais e a resposta proliferativa de linfócitos em resposta a fito-hemaglutinina (PHA em 30 crianças portadoras de convulsão febril e em 14 crianças saudáveis de mesma faixa etária dos pacientes. Infecções respiratórias, urinárias e dermatológicas frequentes foram observadas em 22 pacientes. Os parâmetros imunológicos demonstraram que 64% dos pacientes apresentaram valores elevados de células CD8+. Diminuição da relação de células CD4/CD8 foi observada em 60% dos pacientes. Além disso, a resposta proliferativa de linfócitos frente a PHA apresentou-se deprimida nos pacientes. Foi observada a presença de atividade inibidora da função de linfócitos no plasma de 33% das crianças com convulsão febril. Esses resultados sugerem que pacientes com convulsão febril apresentam depressão da resposta imune celular que poderia implicar em associação patog

  20. Montanide™ ISA 71 VG adjuvant enhances antibody and cell-mediated immune responses to profilin subunit antigen vaccination and promotes protection against Eimeria acervulina and Eimeria tenella. Experimental Parasitology

    Science.gov (United States)

    The present study was conducted to investigate the immunoenhancing effects of MontanideTM ISA 71 VG adjuvant on profilin subunit antigen vaccination. Broiler chickens were immunized subcutaneously with a purified Eimeria acervulina recombinant profilin protein, either alone or mixed with ISA 71 VG, ...

  1. A novel liposome adjuvant DPC mediates Mycobacterium tuberculosis subunit vaccine well to induce cell-mediated immunity and high protective efficacy in mice.

    Science.gov (United States)

    Liu, Xun; Da, Zejiao; Wang, Yue; Niu, Hongxia; Li, Ruiying; Yu, Hongjuan; He, Shanshan; Guo, Ming; Wang, Yong; Luo, Yanping; Ma, Xingming; Zhu, Bingdong

    2016-03-01

    Tuberculosis (TB) is a serious disease around the world, and protein based subunit vaccine is supposed to be a kind of promising novel vaccine against it. However, there is no effective adjuvant available in clinic to activate cell-mediated immune responses which is required for TB subunit vaccine. Therefore, it is imperative to develop new adjuvant. Here we reported an adjuvant composed of dimethyl dioctadecylammonium (DDA), Poly I:C and cholesterol (DPC for short). DDA can form a kind of cationic liposome with the ability to deliver and present antigen and can induce Th1 type cell-mediated immune response. Poly I:C, a ligand of TLR3 receptor, could attenuate the pathologic reaction induced by following Mycobacterium tuberculosis challenge. Cholesterol, which could enhance rigidity of lipid bilayer, is added to DDA and Poly I:C to improve the stability of the adjuvant. The particle size and Zeta-potential of DPC were analyzed in vitro. Furthermore, DPC was mixed with a TB fusion protein ESAT6-Ag85B-MPT64(190-198)-Mtb8.4-Rv2626c (LT70) to construct a subunit vaccine. The subunit vaccine-induced immune responses and protective efficacy against M. tuberculosis H37Rv infection in C57BL/6 mice were investigated. The results showed that the DPC adjuvant with particle size of 400nm and zeta potential of 40mV was in good stability. LT70 in the adjuvant of DPC generated strong antigen-specific humoral and cell-mediated immunity, and induced long-term higher protective efficacy against M. tuberculosis infection (5.41±0.38log10CFU) than traditional vaccine Bacillus Calmette-Guerin (BCG) (6.01±0.33log10CFU) and PBS control (6.53±0.26log10CFU) at 30 weeks post-vaccination. In conclusion, DPC would be a promising vaccine adjuvant with the ability to stimulate Th1 type cell-mediated immunity, and could be used in TB subunit vaccine. PMID:26845736

  2. Protective immune responses in lawsonia intracellularis infections

    DEFF Research Database (Denmark)

    Cordes, Henriette; Riber, Ulla; Boutrup, Torsten; Jensen, Tim Kåre; Nguyen, Lien Thi Minh; Jungersen, Gregers

    increase in acute phase response after challenge with a pathogenic isolate. Here we show results from measurements of serology as well as cell-mediated immune responses from this experiment. We found that Lawsonia-specific IgA peaked in serum around day 17-24 after a primary infection in experimentally...... exhibited a high, but short-lasting peak after re-infection. Specific IFN responses were also measured using a whole blood IFN-γ assay. These were very high in challenge infected and re-infected animals as compared to controls. These specific immune responses may contribute to the explanation of mechanisms...

  3. Effect of renal and non-renal ischemia/reperfusion on cell-mediated immunity in organs and plasma

    DEFF Research Database (Denmark)

    Brøchner, Anne Craveiro; Dagnæs-Hansen, Frederik; Toft, Palle

    2010-01-01

    mortality rate still remains above 50%. The causes of death are primarily extra-renal and include infection, shock, septicemia, and respiratory failure. We wanted to evaluate the cell-mediated inflammatory response of renal ischemia-reperfusion (I/R) and non-renal I/R, in blood and in distant organs. In our...

  4. Lack of immune deficiency in sarcoidosis: compartmentalisation of the immune response.

    OpenAIRE

    Hudspith, B N; Flint, K C; Geraint-James, D; Brostoff, J; Johnson, N. M.

    1987-01-01

    The original findings of peripheral anergy in sarcoidosis led to the conclusion that sarcoidosis was a disease associated with immune deficiency, but patients with sarcoidosis do not appear to suffer from repeated infections suggestive of immune suppression. With the technique of bronchoalveolar lavage it is now possible to examine the local immune response within the lung, the most commonly affected organ in sarcoidosis. In this study three different indices of cell mediated immunity (lympho...

  5. Astragaloside IV promotes haematopoiesis and enhances cytokines release by mesenchymal stromal cells mediated immune regulation

    OpenAIRE

    Deng, Ruixia; 邓瑞霞

    2012-01-01

    Although tremendous efforts have been made to search for other novel growth factors in promoting marrow recovery after irradiation or chemotherapy, there have not been any efficient and safe agents discovered so far. Danggui Buxue Tang (當歸補血湯) as a traditional Chinese herbal decoction, is commonly used for replenishing blood loss in menstruating women, or enhancing erythropoiesis and immune responses in various settings. Our previous study confirmed that Danggui Buxue Tang promotes haematopoi...

  6. Activated T cells sustain myeloid-derived suppressor cell-mediated immune suppression

    Science.gov (United States)

    Damuzzo, Vera; Francescato, Samuela; Pozzuoli, Assunta; Berizzi, Antonio; Mocellin, Simone; Rossi, Carlo Riccardo; Bronte, Vincenzo; Mandruzzato, Susanna

    2016-01-01

    The expansion of myeloid derived suppressor cells (MDSCs), a suppressive population able to hamper the immune response against cancer, correlates with tumor progression and overall survival in several cancer types. We have previously shown that MDSCs can be induced in vitro from precursors present in the bone marrow and observed that these cells are able to actively proliferate in the presence of activated T cells, whose activation level is critical to drive the suppressive activity of MDSCs. Here we investigated at molecular level the mechanisms involved in the interplay between MDSCs and activated T cells. We found that activated T cells secrete IL-10 following interaction with MDSCs which, in turn, activates STAT3 phosphorylation on MDSCs then leading to B7-H1 expression. We also demonstrated that B7-H1+ MDSCs are responsible for immune suppression through a mechanism involving ARG-1 and IDO expression. Finally, we show that the expression of ligands B7-H1 and MHC class II both on in vitro-induced MDSCs and on MDSCs in the tumor microenvironment of cancer patients is paralleled by an increased expression of their respective receptors PD-1 and LAG-3 on T cells, two inhibitory molecules associated with T cell dysfunction. These findings highlight key molecules and interactions responsible for the extensive cross-talk between MDSCs and activated T cells that are at the basis of immune suppression. PMID:26700461

  7. Ascaridia galli infection influences the development of both humoral and cell-mediated immunity after Newcastle Disease vaccination in chickens.

    Science.gov (United States)

    Pleidrup, Janne; Dalgaard, Tina S; Norup, Liselotte R; Permin, Anders; Schou, Torben W; Skovgaard, Kerstin; Vadekær, Dorte F; Jungersen, Gregers; Sørensen, Poul; Juul-Madsen, Helle R

    2014-01-01

    Potent vaccine efficiency is crucial for disease control in both human and livestock vaccination programmes. Free range chickens and chickens with access to outdoor areas have a high risk of infection with parasites including Ascaridia galli, a gastrointestinal nematode with a potential influence on the immunological response to vaccination against other infectious diseases. The purpose of this study was to investigate whether A. galli infection influences vaccine-induced immunity to Newcastle Disease (ND) in chickens from an MHC-characterized inbred line. Chickens were experimentally infected with A. galli at 4 weeks of age or left as non-parasitized controls. At 10 and 13 weeks of age half of the chickens were ND-vaccinated and at 16 weeks of age, all chickens were challenged with a lentogenic strain of Newcastle disease virus (NDV). A. galli infection influenced both humoral and cell-mediated immune responses after ND vaccination. Thus, significantly lower NDV serum titres were found in the A. galli-infected group as compared to the non-parasitized group early after vaccination. In addition, the A. galli-infected chickens showed significantly lower frequencies of NDV-specific T cells in peripheral blood three weeks after the first ND vaccination as compared to non-parasitized chickens. Finally, A. galli significantly increased local mRNA expression of IL-4 and IL-13 and significantly decreased TGF-ß4 expression in the jejunum two weeks after infection with A. galli. At the time of vaccination (six and nine weeks after A. galli infection) the local expression in the jejunum of both IFN-? and IL-10 was significantly decreased in A. galli-infected chickens. Upon challenge with the NDV LaSota strain, viral genomes persisted in the oral cavity for a slightly longer period of time in A. galli-infected vaccinees as compared to non-parasitized vaccinees. However, more work is needed in order to determine if vaccine-induced protective immunity is impaired in A. galli

  8. Cyclophosphamide chemotherapy sensitizes tumor cells to TRAIL-dependent CD8 T cell-mediated immune attack resulting in suppression of tumor growth.

    Directory of Open Access Journals (Sweden)

    Robbert G van der Most

    Full Text Available BACKGROUND: Anti-cancer chemotherapy can be simultaneously lymphodepleting and immunostimulatory. Pre-clinical models clearly demonstrate that chemotherapy can synergize with immunotherapy, raising the question how the immune system can be mobilized to generate anti-tumor immune responses in the context of chemotherapy. METHODS AND FINDINGS: We used a mouse model of malignant mesothelioma, AB1-HA, to investigate T cell-dependent tumor resolution after chemotherapy. Established AB1-HA tumors were cured by a single dose of cyclophosphamide in a CD8 T cell- and NK cell-dependent manner. This treatment was associated with an IFN-alpha/beta response and a profound negative impact on the anti-tumor and total CD8 T cell responses. Despite this negative effect, CD8 T cells were essential for curative responses. The important effector molecules used by the anti-tumor immune response included IFN-gamma and TRAIL. The importance of TRAIL was supported by experiments in nude mice where the lack of functional T cells could be compensated by agonistic anti-TRAIL-receptor (DR5 antibodies. CONCLUSION: The data support a model in which chemotherapy sensitizes tumor cells for T cell-, and possibly NK cell-, mediated apoptosis. A key role of tumor cell sensitization to immune attack is supported by the role of TRAIL in tumor resolution and explains the paradox of successful CD8 T cell-dependent anti-tumor responses in the absence of CD8 T cell expansion.

  9. The short effect of pelvic radiotherapy of gynecological cancers on humoral and cell mediated immunity

    International Nuclear Information System (INIS)

    An analysis of short effect of pelvic irradiation on cellular and humoral immunity was made in 24 patients treated by irradiation alone or a combination of surgery and irradiation for uterine carcinoma, at 2, 6, 12 months after loco-regional therapy. Twelve months later there is a decrease of T lymphocytes (P = 0.01), whereas the B lymphocytes count is normal; the percentage of T and B lymphocytes remains stable, but the lymphocyte response to PHA after 3 days is reduced (p = 0.03). A significant decrease of immunoglobulins G, A and M is observed

  10. Effects of depression on parameters of cell-mediated immunity in patients with digestive tract cancers

    Institute of Scientific and Technical Information of China (English)

    Ke-Jun Nan; Yong-Chang Wei; Fu-Ling Zhou; Chun-Li Li; Chen-Guang Sui; Ling-Yun Hui; Cheng-Ge Gao

    2004-01-01

    AIM: To evaluate the effects of depression on parameters of cell-mediated immunity in patients with cancers of the digestive tract.METHODS: One hundred and eight adult patients of both sexes with cancers of the digestive tract admitted between March 2001 and February 2002 in the Department of Medical Oncology, First Affiliated Hospital of Xi'an Jiaotong University were randomly enrolled in the study. The Zung self-rating depression scale (SDS), Zung self-rating anxiety scale(SAS), numeric rating scale (NRS) and social support rating scale (SSRS) were employed to evaluate the degree of depression and their contributing factors. In terms of their SDS index scores, the patients were categorized into depression group (SDS≥50) and non-depression group(SDS<50). Immunological parameters such as T-lymphocyte subsets and natural killer (NK) cell activities in peripheral blood were determined and compared between the two groups of patients.RESULTS: The SDS index was from 33.8 to 66.2 in the 108 cases, 50% of these patients had a SDS index more than 50. Similarly, the SAS index of all the patients ranged from 35.0 to 62.0 and 46.3% of the cases had a SAS index above 50. Cubic curve estimation showed that the depression was positively correlated with anxiety and negatively with social support. Furthermore, the depression correlated with the tumor type, which manifested in a descending order as stomach, gallbladder, pancreas, intestine, esophagus,duodenum and rectum, according to their correlativity. Step-wise regression analysis suggested that hyposexuality,dispidtment, agitation, palpitation, low CD56 and anxiety were the significant factors contributing to depression. More severe anxiety (49.7±7.5 vs 45.3±6.9, P<0.05), pain (6.5±2.8 vs4.6±3.2, P<0.05), poor social support (6.8±2.0 vs 7.6±2.1,P<0.05), as well as decline of lymphocyte count (0.33±0.09vs0.39±0.87, P<0.05) and CD56 (0.26±0.11 vs0.29±0.11,P<0.05) were noted in the depression group compared

  11. Serotype-Specific Cell-Mediated Immunity Associated With Clearance of Homotypic Group B Streptococcus Rectovaginal Colonization in Pregnant Women.

    Science.gov (United States)

    Kwatra, Gaurav; Adrian, Peter V; Shiri, Tinevimbo; Izu, Alane; Cutland, Clare L; Buchmann, Eckhart J; Madhi, Shabir A

    2016-06-15

    We investigated the association between group B Streptococcus (GBS) serotype-specific capsular polysaccharide cellular immunity, measured with enzyme-linked immunospot (ELISPOT) interferon γ release assay at 20 weeks gestation in pregnant women, and its effect on rectovaginal serotype-specific GBS colonization up to 37 weeks gestation. Among women colonized by serotype III at enrollment, interferon γ ELISPOT positivity was more common in those in whom colonization was cleared (44.4%) than in those in whom colonization persisted (7.4%; P = .008), with a similar trend observed for serotype Ia. Presence of serotype-specific capsular polysaccharide cell-mediated immunity contributes to the clearance of GBS rectovaginal colonization. PMID:27029777

  12. Iron oxide nanoparticles suppressed T helper 1 cell-mediated immunity in a murine model of delayed-type hypersensitivity

    Directory of Open Access Journals (Sweden)

    Shen CC

    2012-06-01

    Full Text Available Chien-Chang Shen,1,* Hong-Jen Liang,2,* Chia-Chi Wang,3 Mei-Hsiu Liao,4 Tong-Rong Jan11Department and Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei, 2Innovation and Incubation Center, Yuanpei University, Hsinchu, 3School of Pharmacy, Kaohsiung Medical University, Kaohsiung, 4Division of Isotope Application, Institute of Energy Research, Taoyuan, Taiwan*These authors contributed equally to this workBackground: It was recently reported that iron oxide nanoparticles attenuated antigen-specific humoral responses and T cell cytokine expression in ovalbumin-sensitized mice. It is presently unclear whether iron oxide nanoparticles influence T helper 1 cell-mediated immunity. The present study aimed to investigate the effect of iron oxide nanoparticles on delayed-type hypersensitivity (DTH, whose pathophysiology requires the participation of T helper 1 cells and macrophages.Methods: DTH was elicited by a subcutaneous challenge with ovalbumin to the footpads of mice sensitized with ovalbumin. Iron oxide nanoparticles (0.2–10 mg iron/kg were administered intravenously 1 hour prior to ovalbumin sensitization. Local inflammatory responses were examined by footpad swelling and histological analysis. The expression of cytokines by splenocytes was measured by enzyme-linked immunosorbent assay.Results: Administration of iron oxide nanoparticles, in a dose-dependent fashion, significantly attenuated inflammatory reactions associated with DTH, including the footpad swelling, the infiltration of T cells and macrophages, and the expression of interferon-γ, interleukin-6, and tumor necrosis factor-α in the inflammatory site. Iron oxide nanoparticles also demonstrated a suppressive effect on ovalbumin-stimulated production of interferon-γ by splenocytes and the phagocytic activity of splenic CD11b+ cells.Conclusion: These results demonstrated that a single dose of iron oxide nanoparticles attenuated

  13. Combined local and systemic immunization is essential for durable T-cell mediated heterosubtypic immunity against influenza A virus.

    Science.gov (United States)

    Uddback, Ida E M; Pedersen, Line M I; Pedersen, Sara R; Steffensen, Maria A; Holst, Peter J; Thomsen, Allan R; Christensen, Jan P

    2016-01-01

    The threat from unpredictable influenza virus pandemics necessitates the development of a new type of influenza vaccine. Since the internal proteins are highly conserved, induction of T cells targeting these antigens may provide the solution. Indeed, adenoviral (Ad) vectors expressing flu nucleoprotein have previously been found to induce short-term protection in mice. In this study we confirm that systemic (subcutaneous (s.c.) immunization rapidly induced heterosubtypic protection predominantly mediated by CD8 T cells, but within three months clinical protection completely disappeared. Local (intranasal (i.n.)) immunization elicited delayed, but more lasting protection despite relatively inefficient immunization. However, by far, the most robust protection was induced by simultaneous, combined (i.n. + s.c.) vaccination, and, notably, in this case clinical protection lasted at least 8 months without showing any evidence of fading. Interestingly, the superior ability of the latter group to resist reinfection correlated with a higher number of antigen-specific CD8 T cells in the spleen. Thus, detailed analysis of the underlying CD8 T cell responses highlights the importance of T cells already positioned in the lungs prior to challenge, but at the same time underscores an important back-up role for circulating antigen-specific cells with the capacity to expand and infiltrate the infected lungs. PMID:26831578

  14. Immunotoxicity of aflatoxin B1: Impairment of the cell-mediated response to vaccine antigen and modulation of cytokine expression

    International Nuclear Information System (INIS)

    Aflatoxin B1 (AFB1), a mycotoxin produced by Aspergillus flavus or A. parasiticus, is a frequent contaminant of food and feed. This toxin is hepatotoxic and immunotoxic. The present study analyzed in pigs the influence of AFB1 on humoral and cellular responses, and investigated whether the immunomodulation observed is produced through interference with cytokine expression. For 28 days, pigs were fed a control diet or a diet contaminated with 385, 867 or 1807 μg pure AFB1/kg feed. At days 4 and 15, pigs were vaccinated with ovalbumin. AFB1 exposure, confirmed by an observed dose-response in blood aflatoxin-albumin adduct, had no major effect on humoral immunity as measured by plasma concentrations of total IgA, IgG and IgM and of anti-ovalbumin IgG. Toxin exposure did not impair the mitogenic response of lymphocytes but delayed and decreased their specific proliferation in response to the vaccine antigen, suggesting impaired lymphocyte activation in pigs exposed to AFB1. The expression level of pro-inflammatory (TNF-α, IL-1β, IL-6, IFN-γ) and regulatory (IL-10) cytokines was assessed by real-time PCR in spleen. A significant up-regulation of all 5 cytokines was observed in spleen from pigs exposed to the highest dose of AFB1. In pigs exposed to the medium dose, IL-6 expression was increased and a trend towards increased IFN-γ and IL-10 was observed. In addition we demonstrate that IL-6 impaired in vitro the antigenic- but not the mitogenic-induced proliferation of lymphocytes from control pigs vaccinated with ovalbumin. These results indicate that AFB1 dietary exposure decreases cell-mediated immunity while inducing an inflammatory response. These impairments in the immune response could participate in failure of vaccination protocols and increased susceptibility to infections described in pigs exposed to AFB1

  15. Sequential immune responses: The weapons of immunity

    OpenAIRE

    Mills, Charles; Ley, Klaus; Buchmann, Kurt; Canton, Jonathan

    2015-01-01

    Sequential immune responses (SIR) is a new model that describes what ‘immunity’ means in higher animals. Existing models, such as self/nonself discrimination or danger, focus on how immune responses are initiated. However, initiation is not protection. SIR describes the actual immune responses that provide protection. SIR resulted from a comprehensive analysis of the evolution of immune systems that revealed that several very different types of host innate responses occur (and at different te...

  16. Cell-mediated immunity in operable bronchial carcinoma: the effect of injecting irradiated autologous tumour cells and BCG

    International Nuclear Information System (INIS)

    In 52 patients undergoing tests of cell-mediated immunity before surgical resection of bronchial carcinoma a positive tuberculin test result was found in 71% compared with 68% of age - and sex-matched controls. Sensitization to DNCB occurred in 52% of 37 patients but in 78% controls. There was depression of lymphocyte transformation by PPD in 19 patients compared with controls (p=0.001), but there was no difference in lymphocyte transformation by PHA pr pokeweed mitogen between 34 patients and controls. In a pilot study patients were randomly allocated to autograft (eight) or non-autograft (seven) groups. The autograft group were given an intradermal injection of a suspension of irradiated autologous tumour-cells mixed with intradermal BCG on the day of operation. Tests of cell-mediated immunity were repeated two weeks after operation. Five patients in each group received a course of radiotherapy to the mediastinum three weeks after operation. There was a rise in a cutaneous tuberculin reactivity (p=0.08) and total leucocyte count (p=0.09) in the autograft group postoperatively with a fall in total lymphocyte and T lymphocyte counts in the non-autograft group (p<0.05). These differences, however, were not followed by any difference in the frequency of tumour recurrence or the survival rate two years after operation. The results show that the immunological surveillance mechanism is impaired even in patients with early bronchial carcinoma and that it is possible to overcome postoperative immunological depression with specific immunotherapy combined with BCG. This treatment did not produce any clinical advantage in this small number of patients and the skin lesions caused the patients considerable discomfort. (author)

  17. Adaptive immune responses of legumin nanoparticles.

    Science.gov (United States)

    Mirshahi, T; Irache, J M; Nicolas, C; Mirshahi, M; Faure, J P; Gueguen, J; Hecquet, C; Orecchioni, A M

    2002-12-01

    Legumin is one of the main storage proteins in the pea seeds (Pisum sativum L.) and the molecules of this protein have the capacity of binding together to form nanoparticles after aggregation and chemical cross-linkage with glutaraldehyde. The aim of this work was to study the adaptive immune response of legumin nanoparticles in rats. Following intradermal immunisation with the native protein legumin and legumin nanoparticles of about 250 nm, the humoral and cell-mediated immune responses were analysed in rats. The humoral responses against legumin and legumin nanoparticles were examined by western blot and ELISA analysis. Both techniques clearly showed that sera from rats immunised with legumin strongly expressed antibodies against this protein. On the contrary, serum samples from rats inoculated with legumin nanoparticles did not contain detectable amounts of antibodies. These results may be explained by a reduction on the antigenic epitopes of the protein induced by the glutaraldehyde used during the cross-linking step. Concerning the cell-mediated response, neither legumin nor legumin nanoparticles stimulated an immunogenic response. This absence of response of spleen lymphocytes for legumin and legumin nanoparticles may be explained by a cytostatic effect of legumin which was corroborated by the evaluation of the middle phase of cell apoptose. In fact, both legumin and legumin nanoparticles are potent inductors of a cytostatic phenomenon and showed a significant increase of the chromatin condensation (p < 0.05) as compared with control. PMID:12683667

  18. SEX DIFFERENCES AND ESTROGEN MODULATION OF THE CELLULAR IMMUNE RESPONSE AFTER INJURY

    OpenAIRE

    Bird, Melanie D.; Karavitis, John; Kovacs, Elizabeth J

    2008-01-01

    Cell-mediated immunity is extremely important for resolution of infection and for proper healing from injury. However, the cellular immune response is dysregulated following injuries such as burn and hemorrhage. Sex hormones are known to regulate immunity, and a well-documented dichotomy exists in the immune response to injury between the sexes. This disparity is caused by differences in immune cell activation, infiltration, and cytokine production during and after injury. Estrogen and testos...

  19. Vitamin E, immune response, and disease resistance.

    Science.gov (United States)

    Tengerdy, R P

    1989-01-01

    Vitamin E as a dietary supplement or as part of an adjuvant vaccine formulation increases humoral and cell-mediated immunity and disease resistance in laboratory animals, farm animals, and humans. Adjuvant administration has far greater effect than dietary supplementation. Vitamin E as an antioxidant protects the cells of the immune response from peroxidative damage; possibly through a modulation of lipoxygenation of arachidonic acid, vitamin E alters cell membrane functions and cell-cell interactions. The most pronounced effect of vitamin E is on immune phagocytosis. Dietary supplementation is beneficial to animals, especially under stress, in decreasing susceptibility to infections. Vitamin E adjuvant vaccines have provided greater immunoprotection against enterotoxemia and epididymitis in sheep than conventional vaccines. PMID:2698109

  20. Late effects of selected immunosuppressants on immunocompetence, disease incidence, and mean life-span. II. Cell-mediated immune activity. [Mice, X radiation

    Energy Technology Data Exchange (ETDEWEB)

    Peterson, W.J.; Perkins, E.H.; Goodman, S.A.; Hori, Y.; Halsall, M.K.; Makinodan, T.

    1975-01-01

    The late effects of various immunosuppressive insults on cell-mediated immunity in mice were studied in an attempt to assess the role of immune surveillance in the aging process. Results were obtained using susceptibility to allogeneic tumor cell challenge, graft-versus-host reaction (GVHR), blastogenic response to PHA, a thymus derived T cell-specific plant mitogen, and cytolytic activity against allogeneic tumor cells as measures of immunologic activity. In vivo studies late in life show that resistance to allogeneic tumor cells is significantly decreased in thymectomized mice, whereas those treated with cortisone, cyclophosphamide and sublethal x-ray remain unchanged. Spleen cells from only the thymectomized and the sublethally irradiated mice show reduced activity in the GVHR. No difference is seen in the activity of bone marrow cells. Results consistent with these findings were obtained in in vitro studies. Thus spleen cells from thymectomized or sublethally irradiated mice show decreased activity in response to PHA, whereas no change is seen in spleen cells from other treated groups. Hence, surgical and physical insults are more likely to induce long-lasting immunosuppression in those immunocompetent tissues whose activity normally diminishes with advancing age. Furthermore, the degree of immunosuppression seen in this study is not of the order of magnitude that one could reasonably predict a significant decrease in mean life-span.

  1. Cell-Mediated Immunity in Elite Controllers Naturally Controlling HIV Viral Load

    OpenAIRE

    Genovese, Luca; Nebuloni, Manuela; Alfano, Massimo

    2013-01-01

    The natural course of human immunodeficiency virus (HIV) infection is characterized by high viral load, depletion of immune cells, and immunodeficiency, ultimately leading to acquired immunodeficiency syndrome phase and the occurrence of opportunistic infections and diseases. Since the discovery of HIV in the early 1980s a naturally selected population of infected individuals has been emerged in the last years, characterized by being infected for many years, with viremia constantly below dete...

  2. Role of the immune cells, mediators and cytokines in pathogenesis of asthma: a review article

    Directory of Open Access Journals (Sweden)

    Sedigheh Bahrami Mahne

    2014-08-01

    Full Text Available Asthma is a chronic inflammatory disorder of the airways, associated with airway re-modeling and hyperresponsiveness. It is expressed that asthma influences about 300 million people around the world, which is estimated to increase to about 400 million by 2025. The prevalence rate is 15 to 20 percent in children and 5 to 10 percent in adults, while its trend is still increasing. Inflammation plays an important role in the patho-physiology of asthma, which involves an interaction of different types of the immune cells and mediators. It leads to a number of pathophysiology changes, including bron-chial inflammation, airway obstruction, and clinical episodes such as cough, wheeze and shortness of breath. Asthma is now greatly being introduced as a heterogeneous disorder and it is pointed out to the role of T cells, including Th1, Th2, Th17, and regu-latory T cells. Other immune cells, especially neutrophils, macrophages and dendritic cells, as well structural cells such as epithelial and airway smooth muscle cells also pro-duce disease-associated cytokines in asthma. Increased levels of these immune cells and cytokines have been recognized in clinical samples and mouse models of asthma. Different cytokines, including pro-inflammatory cytokines (such as TNFα, IL-1, and IL-6, T helper 2 cytokines (such as IL-4, IL-5, IL-9, IL-13, and growth factors (such as GM-CSF, PDGF play a role in the pathogenesis of asthma. Indeed chemokines (such as MPC-1, RANTES , MIP-1 and the chemokine receptors (such as CCR3, CCR4, CCL11, CCL24, and CCL26 play an important role in the recruitment of circu-lating inflammatory cells into the airways in asthmatic patients and also is related with increased T helper 2 cytokines after inhaled allergens. Among new approaches, treat-ment of asthma with anti-cytokine drugs such as antibodies blocking IL-4, IL-5, IL-9 could reduce recruitment inflammatory cells into the airways and remodeling. The final perspective of asthma

  3. Studies of Immune Responses in Candida vaginitis.

    Science.gov (United States)

    De Bernardis, Flavia; Arancia, Silvia; Sandini, Silvia; Graziani, Sofia; Norelli, Sandro

    2015-01-01

    The widespread occurrence of vaginal candidiasis and the development of resistance against anti-fungal agents has stimulated interest in understanding the pathogenesis of this disease. The aim of our work was to characterize, in an animal model of vaginal candidiasis, the mechanisms that play a role in the induction of mucosal immunity against C. albicans and the interaction between innate and adaptive immunity. Our studies evidenced the elicitation of cell-mediated immunity (CMIs) and antibody (Abs)-mediated immunity with a Th1 protective immunity. An immune response of this magnitude in the vagina was very encouraging to identify the proper targets for new strategies for vaccination or immunotherapy of vaginal candidiasis. Overall, our data provide clear evidence that it is possible to prevent C. albicans vaginal infection by active intravaginal immunization with aspartyl proteinase expressed as recombinant protein. This opens the way to a modality for anti-Candida protection at the mucosa. The recombinant protein Sap2 was assembled with virosomes, and a vaccine PEVION7 (PEV7) was obtained. The results have given evidence that the vaccine, constituted of virosomes and Secretory aspartyl proteinase 2 (Sap2) (PEV7), has an encouraging therapeutic potential for the treatment of recurrent vulvovaginal candidiasis. PMID:26473934

  4. Studies of Immune Responses in Candida vaginitis

    Directory of Open Access Journals (Sweden)

    Flavia De Bernardis

    2015-10-01

    Full Text Available The widespread occurrence of vaginal candidiasis and the development of resistance against anti-fungal agents has stimulated interest in understanding the pathogenesis of this disease. The aim of our work was to characterize, in an animal model of vaginal candidiasis, the mechanisms that play a role in the induction of mucosal immunity against C. albicans and the interaction between innate and adaptive immunity. Our studies evidenced the elicitation of cell-mediated immunity (CMIs and antibody (Abs-mediated immunity with a Th1 protective immunity. An immune response of this magnitude in the vagina was very encouraging to identify the proper targets for new strategies for vaccination or immunotherapy of vaginal candidiasis. Overall, our data provide clear evidence that it is possible to prevent C. albicans vaginal infection by active intravaginal immunization with aspartyl proteinase expressed as recombinant protein. This opens the way to a modality for anti-Candida protection at the mucosa. The recombinant protein Sap2 was assembled with virosomes, and a vaccine PEVION7 (PEV7 was obtained. The results have given evidence that the vaccine, constituted of virosomes and Secretory aspartyl proteinase 2 (Sap2 (PEV7, has an encouraging therapeutic potential for the treatment of recurrent vulvovaginal candidiasis.

  5. Studies of Immune Responses in Candida vaginitis

    Science.gov (United States)

    De Bernardis, Flavia; Arancia, Silvia; Sandini, Silvia; Graziani, Sofia; Norelli, Sandro

    2015-01-01

    The widespread occurrence of vaginal candidiasis and the development of resistance against anti-fungal agents has stimulated interest in understanding the pathogenesis of this disease. The aim of our work was to characterize, in an animal model of vaginal candidiasis, the mechanisms that play a role in the induction of mucosal immunity against C. albicans and the interaction between innate and adaptive immunity. Our studies evidenced the elicitation of cell-mediated immunity (CMIs) and antibody (Abs)-mediated immunity with a Th1 protective immunity. An immune response of this magnitude in the vagina was very encouraging to identify the proper targets for new strategies for vaccination or immunotherapy of vaginal candidiasis. Overall, our data provide clear evidence that it is possible to prevent C. albicans vaginal infection by active intravaginal immunization with aspartyl proteinase expressed as recombinant protein. This opens the way to a modality for anti-Candida protection at the mucosa. The recombinant protein Sap2 was assembled with virosomes, and a vaccine PEVION7 (PEV7) was obtained. The results have given evidence that the vaccine, constituted of virosomes and Secretory aspartyl proteinase 2 (Sap2) (PEV7), has an encouraging therapeutic potential for the treatment of recurrent vulvovaginal candidiasis. PMID:26473934

  6. Review: Adjuvant effects of saponins on animal immune responses

    Institute of Scientific and Technical Information of China (English)

    RAJPUT Zahid Iqbal; HU Song-hua; XIAO Chen-wen; ARIJO Abdullah G.

    2007-01-01

    Vaccines require optimal adjuvants including immunopotentiator and delivery systems to offer long term protection from infectious diseases in animals and man. Initially it was believed that adjuvants are responsible for promoting strong and sustainable antibody responses. Now it has been shown that adjuvants influence the isotype and avidity of antibody and also affect the properties of cell-mediated immunity. Mostly oil emulsions, lipopolysaccharides, polymers, saponins, liposomes, cytokines,ISCOMs (immunostimulating complexes), Freund's complete adjuvant, Freund's incomplete adjuvant, alums, bacterial toxins etc.,are common adjuvants under investigation. Saponin based adjuvants have the ability to stimulate the cell mediated immune system as well as to enhance antibody production and have the advantage that only a low dose is needed for adjuvant activity. In the present study the importance of adjuvants, their role and the effect of saponin in immune system is reviewed.

  7. Tc17 cells mediate vaccine immunity against lethal fungal pneumonia in immune deficient hosts lacking CD4+ T cells.

    Directory of Open Access Journals (Sweden)

    Som Gowda Nanjappa

    Full Text Available Vaccines may help reduce the growing incidence of fungal infections in immune-suppressed patients. We have found that, even in the absence of CD4(+ T-cell help, vaccine-induced CD8(+ T cells persist and confer resistance against Blastomyces dermatitidis and Histoplasma capsulatum. Type 1 cytokines contribute to that resistance, but they also are dispensable. Although the role of T helper 17 cells in immunity to fungi is debated, IL-17 producing CD8(+ T cells (Tc17 cells have not been investigated. Here, we show that Tc17 cells are indispensable in antifungal vaccine immunity in hosts lacking CD4(+ T cells. Tc17 cells are induced upon vaccination, recruited to the lung on pulmonary infection, and act non-redundantly in mediating protection in a manner that requires neutrophils. Tc17 cells did not influence type I immunity, nor did the lack of IL-12 signaling augment Tc17 cells, indicating a distinct lineage and function. IL-6 was required for Tc17 differentiation and immunity, but IL-1R1 and Dectin-1 signaling was unexpectedly dispensable. Tc17 cells expressed surface CXCR3 and CCR6, but only the latter was essential in recruitment to the lung. Although IL-17 producing T cells are believed to be short-lived, effector Tc17 cells expressed low levels of KLRG1 and high levels of the transcription factor TCF-1, predicting their long-term survival and stem-cell like behavior. Our work has implications for designing vaccines against fungal infections in immune suppressed patients.

  8. Tc17 Cells Mediate Vaccine Immunity against Lethal Fungal Pneumonia in Immune Deficient Hosts Lacking CD4+ T Cells

    OpenAIRE

    Som Gowda Nanjappa; Erika Heninger; Marcel Wüthrich; David Joseph Gasper; Bruce S Klein

    2012-01-01

    Vaccines may help reduce the growing incidence of fungal infections in immune-suppressed patients. We have found that, even in the absence of CD4(+) T-cell help, vaccine-induced CD8(+) T cells persist and confer resistance against Blastomyces dermatitidis and Histoplasma capsulatum. Type 1 cytokines contribute to that resistance, but they also are dispensable. Although the role of T helper 17 cells in immunity to fungi is debated, IL-17 producing CD8(+) T cells (Tc17 cells) have not been inve...

  9. Effects of alcohol consumption on the allergen-specific immune response in mice

    DEFF Research Database (Denmark)

    Linneberg, Allan; Roursgaard, Martin; Hersoug, Lars-Georg;

    2008-01-01

    There is evidence that chronic alcohol consumption impairs the T-helper 1 (Th1) lymphocyte-regulated cell-mediated immune response possibly favoring a Th2 deviation of the immune response. Moreover, a few epidemiological studies have linked alcohol consumption to allergen-specific IgE sensitization....

  10. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis

    DEFF Research Database (Denmark)

    Sawcer, Stephen; Hellenthal, Garrett; Pirinen, Matti;

    2011-01-01

    genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the...... 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the...

  11. Nizatidine, a small molecular compound, enhances killed H5N1 vaccine cell-mediated responses and protects mice from lethal viral challenge.

    Science.gov (United States)

    Wang, Shuang; Wu, Bing; Xue, Jia; Wang, Ming; Chen, Ruiai; Wang, Bin

    2014-01-01

    Nizatidine (NIZ), closely related to Cimetidine, is a histamine H2 receptor inverse agonist used primarily as an anti-acid drug. Recent studies showed that this class of compounds may also modulate immune responses. To evaluate adjuvant effects of NIZ on vaccine immune modulation, we formulated NIZ with a H5N1 killed viral antigen and tested in vitro and in vivo. NIZ activated DC maturation and stimulated Th1 and Th2 immune responses to H5N1 vaccine. As a result, it enhanced both antibody and T cell-mediated immune responses. We also observed that a single immunization into C57BL/6 mice blocked IL-10 upregulation and potentiated Th1/Th2 dual polarization. Importantly, the inoculation of H5N1 vaccine with NIZ significantly improved protection of animals from death after challenge and reduced virus loads in the lung tissues. Considering its water-soluble nature, compared with Cimetidine, Nizatidine may be a better choice to use as a vaccine adjuvant. PMID:24253609

  12. Hemagglutinin-based polyanhydride nanovaccines against H5N1 influenza elicit protective virus neutralizing titers and cell-mediated immunity

    Directory of Open Access Journals (Sweden)

    Ross KA

    2014-12-01

    Full Text Available Kathleen A Ross,1 Hyelee Loyd,2 Wuwei Wu,2 Lucas Huntimer,3 Shaheen Ahmed,4 Anthony Sambol,5 Scott Broderick,6 Zachary Flickinger,2 Krishna Rajan,6 Tatiana Bronich,4 Surya Mallapragada,1 Michael J Wannemuehler,3 Susan Carpenter,2 Balaji Narasimhan1 1Chemical and Biological Engineering, Iowa State University, Ames, IA, USA; 2Animal Science, Iowa State University, Ames, IA, USA; 3Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, IA, USA; 4Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA; 5Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA; 6Materials Science and Engineering, Iowa State University, Ames, IA, USA Abstract: H5N1 avian influenza is a significant global concern with the potential to become the next pandemic threat. Recombinant subunit vaccines are an attractive alternative for pandemic vaccines compared to traditional vaccine technologies. In particular, polyanhydride nanoparticles encapsulating subunit proteins have been shown to enhance humoral and cell-mediated immunity and provide protection upon lethal challenge. In this work, a recombinant H5 hemagglutinin trimer (H53 was produced and encapsulated into polyanhydride nanoparticles. The studies performed indicated that the recombinant H53 antigen was a robust immunogen. Immunizing mice with H53 encapsulated into polyanhydride nanoparticles induced high neutralizing antibody titers and enhanced CD4+ T cell recall responses in mice. Finally, the H53-based polyanhydride nanovaccine induced protective immunity against a low-pathogenic H5N1 viral challenge. Informatics analyses indicated that mice receiving the nanovaccine formulations and subsequently challenged with virus were similar to naïve mice that were not challenged. The current studies provide a basis to further exploit the advantages of polyanhydride nanovaccines in pandemic scenarios. Keywords: polymer, nanoparticle, vaccine, subunit

  13. Effect of daily iron supplementation on iron status, cell-mediated immunity, and incidence of infections in 6-36 month old Togolese children

    OpenAIRE

    Berger, Jacques; Dyck, Jean-Luc; Galan, P; Aplogan, A; Schneider, Dominique; Traissac, Pierre; Hercberg, S.

    2000-01-01

    Objective : to assess the impact of a daily oral iron supplementation on hematological status, cell-mediated immunity and susceptibility to infections in children living in an environment where iron deficiency, malaria and other infections are frequent. Design : randomized, double-blind iron supplementation including a placebo group. Setting : a village in Togo, West Africa. Subjects : of the 229 6-36-month-old children of both sexes recruited, 197 with hemoglobin concentration of greater tha...

  14. The Impact of Ultraviolet Radiation on Immune Responses (invited paper)

    International Nuclear Information System (INIS)

    In addition to its genotoxic and mutagenic effects, UV has the capacity to suppress immune responses. The mechanism involved is complex, beginning with chromophores located in the skin which absorb UV, this leading in turn to changes in the production of a range of immune mediators locally and systemically which then induce phenotypic and functional alterations in antigen presentation. The cascade ends with the promotion of a subset of T-cells downregulating cell-mediated immunity. The possible consequences of this immunomodulation for the control of tumours and infectious diseases require careful evaluation from laboratory and human studies. (author)

  15. Effect of blueberries on the immune response of obese mice induced by high fat diet

    Science.gov (United States)

    Both high fat diet and obesity have been linked to impaired cell-mediated immune response. Blueberry, rich in antioxidant phytochemicals, has been shown to impact biologic functions in several tissues. However, no information is available on immune cells. We investigated whether blueberry consumptio...

  16. Cell-mediated immunity and lymphocyte populations in experimental Argentine hemorrhagic fever (Junín Virus).

    OpenAIRE

    Carballal, G; Oubiña, J. R.; Rondinone, S N; Elsner, B; Frigerio, M J

    1981-01-01

    Guinea pigs infected with the XJ prototype strain of Junín virus reproduce the main features of Argentine hemorrhagic fever, showing hemorrhages, leukothrombocytopenia, and focal lymphoid tissue necrosis. Viral lymphotropism is shown by the presence of viral antigens, severe cytopathic effect, and high virus titers in lymphoid organs. A pronounced depression of humoral immune response to sheep erythrocytes as well as to the virus is described. This study was carried out to determine whether c...

  17. The Role of Antibody Isotypes Against Fasciola Gigantica In Immune Response With An Emphasis On Antibody Dependent Cell Mediated Cytoxicity%抗巨片形吸虫同型抗体在动物巨片形吸虫感染所致的抗体依赖性细胞介导的细胞毒反应( ADCC )免疫应答作用的研究

    Institute of Scientific and Technical Information of China (English)

    陈思礼; 陈强; 周雨丝; 李玲; 陈思义; 吴风娇; 陈思祗; 丁书茂; SPITHILL Terry

    2003-01-01

    The study was carried out in two breeds of sheep, Indonesia Thin Tail (ITT) and Merino, both infected with F. gigantica. Kinetic analysis of Fasciola gigantica specific antibody responses revealed that resistant ITT do not produce a parasite specific IgG2 response; whereas susceptible Merino sheep produce a high parasite specific IgG2 response. The IgG2 produced in Merino sheep might act as a blocking antibody for antibody dependant cell mediated cytotoxicity by macrophages. Whereas, ITT appeared to down regulate IgG2 response, which might enable these sheep to possess an enhanced capacity of killing F. gigantica. The purified IgG1 and IgG2 were used in in vitro killing assays. IgG1 promotes the highest amount of killing compared to immune sera and IgG2 using purified Merino sera antibodies for in vitro killing assays. F. gigantica cultured in increasing amount of IgG1 had a trend of increasing the death rate. Parasites cultured in 10 ug/ml of IgG1 showed the highest amount of death. F. gigantica cultured in eosinophils with immune ITT sera (Day35) was 55% death after 24 hours. It should be that using purified eosinophils with immune ITT serum resulted in a strong trend of killing occurring in those wells which contained a combination of immune sera complement, IL-5 and eosinophils.%以印尼短尾羊(ITT)和美利奴细毛羊( Merino )两种品系的绵羊为实验动物,研究动物感染巨片形吸虫后所产生的抗体依赖性细胞介导的细胞毒反应的免疫应答.结果显示:对巨片形吸虫感染具有抗性的印尼短尾羊不产生特异性的IgG2, 而易感品系的美利奴细毛羊感染巨片形吸虫后体内产生高滴度特异性IgG2抗体.特异性IgG2抗体在免疫应答中起着封闭抗体的作用,抑制巨噬细胞抗体依赖性细胞介导的细胞毒反应.由于印尼短尾羊不产生特异性IgG2抗体,对巨噬细胞抗体依赖性细胞介导的细胞毒反应不产生抑制作用,因此印尼短尾羊对巨片形吸

  18. A preliminary study to evaluate the immune responses induced by immunization of dogs with inactivated Ehrlichia canis organisms

    Directory of Open Access Journals (Sweden)

    Sunita Mahan

    2005-09-01

    Full Text Available Ehrlichia canis is an intracellular pathogen that causes canine monocytic ehrlichiosis. Although the role of antibody responses cannot be discounted, control of this intracellular pathogen is expected to be by cell mediated immune responses. The immune responses in dogs immunized with inactivated E. canis organisms in combination with Quil A were evaluated. Immunization provoked strong humoral and cellular immune responses, which were demonstrable by Western blotting and lymphocyte proliferation assays. By Western blotting antibodies to several immunodominant E. canis proteins were detected in serum from immunized dogs and antibody titres increased after each immunization. The complement of immunogenic proteins recognized by the antisera were similar to those recognized in serum from infected dogs. Upon challenge with live E. canis, rapid anamnestic humoral responses were detected in the serum of immunized dogs and primary antibody responses were detected in the serum from control dogs. Following immunization, a lymphocyte proliferative response (cellular immunity was detected in peripheral blood mononuclear cells (PBMNs of immunized dogs upon stimulation with E. canis antigens. These responses were absent from non-immunized control dogs until after infection with live E. canis, when antigen specific-lymphocyte proliferation responses were also detected in the PBMNs of the control dogs. It can be thus concluded that immunization against canine monocytic ehrlichiosis may be feasible. However, the immunization regimen needs to be optimized and a detailed investigation needs to be done to determine if this regimen can prevent development of acute and chronic disease.

  19. Alarmin IL-33 elicits potent TB-specific cell-mediated responses.

    Science.gov (United States)

    Villarreal, Daniel O; Siefert, Rebekah J; Weiner, David B

    2015-01-01

    Tuberculosis (TB) still remains a major public health issue despite the current available vaccine for TB, Bacille Calmette Guerin (BCG). An effective vaccine against TB remains a top priority in the fight against this pandemic bacterial infection. Adequate protection against TB is associated with the development of TH1-type and CD8(+) T cell responses. One alarmin cytokine, interleukin 33 (IL-33), has now been implicated in the development of both CD4(+) TH1 and CD8(+) T cell immunity. In this study, we determined whether the administration of IL-33 as an adjuvant, encoded in a DNA plasmid, could enhance the immunogenicity of a TB DNA vaccine. We report that the co-immunization of IL-33 with a DNA vaccine expressing the Mycobacterium Tuberculosis (Mtb) antigen 85B (Ag85B) induced robust Ag85B-specific IFNγ responses by ELISpot compared to Ag85B alone. Furthermore, these enhanced responses were characterized by higher frequencies of Ag85B-specific, multifunctional CD4(+) and CD8(+) T cells. Vaccination with IL-33 also increased the ability of the Ag85B-specific CD8(+) T cells to undergo degranulation and to secrete IFNγ and TNFα cytokines. These finding highlights IL-33 as a promising adjuvant to significantly improve the immunogenicity of TB DNA vaccines and support further study of this effective vaccine strategy against TB. PMID:26091147

  20. Effect of doxycycline on immune response in mice.

    OpenAIRE

    Bellahsene, A; Forsgren, A

    1985-01-01

    The effect of doxycycline on immune response has been studied in mice, cell-mediated immunity being evaluated with the split heart allograft technique. Survival duration of heart transplants in animals treated with 2.5 mg of doxycycline per kg per day from the day of transplantation until rejection was slightly but significantly longer than in untreated animals, 18.8 days (P less than 0.05) as compared with 14.5 days. In doxycycline-treated animals, both agglutinating and hemolytic antibody r...

  1. Dendritic cell mediated delivery of plasmid DNA encoding LAMP/HIV-1 Gag fusion immunogen enhances T cell epitope responses in HLA DR4 transgenic mice.

    Directory of Open Access Journals (Sweden)

    Gregory G Simon

    Full Text Available This report describes the identification and bioinformatics analysis of HLA-DR4-restricted HIV-1 Gag epitope peptides, and the application of dendritic cell mediated immunization of DNA plasmid constructs. BALB/c (H-2d and HLA-DR4 (DRA1*0101, DRB1*0401 transgenic mice were immunized with immature dendritic cells transfected by a recombinant DNA plasmid encoding the lysosome-associated membrane protein-1/HIV-1 Gag (pLAMP/gag chimera antigen. Three immunization protocols were compared: 1 primary subcutaneous immunization with 1x10(5 immature dendritic cells transfected by electroporation with the pLAMP/gag DNA plasmid, and a second subcutaneous immunization with the naked pLAMP/gag DNA plasmid; 2 primary immunization as above, and a second subcutaneous immunization with a pool of overlapping peptides spanning the HIV-1 Gag sequence; and 3 immunization twice by subcutaneous injection of the pLAMP/gag DNA plasmid. Primary immunization with pLAMP/gag-transfected dendritic cells elicited the greatest number of peptide specific T-cell responses, as measured by ex vivo IFN-gamma ELISpot assay, both in BALB/c and HLA-DR4 transgenic mice. The pLAMP/gag-transfected dendritic cells prime and naked DNA boost immunization protocol also resulted in an increased apparent avidity of peptide in the ELISpot assay. Strikingly, 20 of 25 peptide-specific T-cell responses in the HLA-DR4 transgenic mice contained sequences that corresponded, entirely or partially to 18 of the 19 human HLA-DR4 epitopes listed in the HIV molecular immunology database. Selection of the most conserved epitope peptides as vaccine targets was facilitated by analysis of their representation and variability in all reported sequences. These data provide a model system that demonstrates a the superiority of immunization with dendritic cells transfected with LAMP/gag plasmid DNA, as compared to naked DNA, b the value of HLA transgenic mice as a model system for the identification and evaluation

  2. Cross-reactivity of cell-mediated immunity between interstitial (type I) and basement membrane (type IV) collagens

    OpenAIRE

    1982-01-01

    In the present study, we demonstrate delayed-type hypersensitivity (DTH) to homologous type I collagen that cross-reacts with type IV collagen. Mice immunized with native or denatured type I collagens and challenged with these same antigens or native type IV collagen develop a peak DTH response on day 7. Challenge with denatured type IV collagen or collagenase-treated type IV collagen failed to elicit DTH in type I collagen-sensitized mice. Type I collagen-sensitized spleen cells adoptively t...

  3. Active Immunization with Extracellular Vesicles Derived from Staphylococcus aureus Effectively Protects against Staphylococcal Lung Infections, Mainly via Th1 Cell-Mediated Immunity.

    Directory of Open Access Journals (Sweden)

    Seng Jin Choi

    Full Text Available Staphylococcus aureus is an important pathogenic bacterium that causes various infectious diseases. Extracellular vesicles (EVs released from S. aureus contain bacterial proteins, nucleic acids, and lipids. These EVs can induce immune responses leading to similar symptoms as during staphylococcal infection condition and have the potential as vaccination agent. Here, we show that active immunization (vaccination with S. aureus-derived EVs induce adaptive immunity of antibody and T cell responses. In addition, these EVs have the vaccine adjuvant ability to induce protective immunity such as the up-regulation of co-stimulatory molecules and the expression of T cell polarizing cytokines in antigen-presenting cells. Moreover, vaccination with S. aureus EVs conferred protection against lethality induced by airway challenge with lethal dose of S. aureus and also pneumonia induced by the administration of sub-lethal dose of S. aureus. These protective effects were also found in mice that were adoptively transferred with splenic T cells isolated from S. aureus EV-immunized mice, but not in serum transferred mice. Furthermore, this protective effect of S. aureus EVs was significantly reduced by the absence of interferon-gamma, but not by the absence of interleukin-17. Together, the study herein suggests that S. aureus EVs are a novel vaccine candidate against S. aureus infections, mainly via Th1 cellular response.

  4. Induction of protective CD4+ T cell-mediated immunity by a Leishmania peptide delivered in recombinant influenza viruses.

    Directory of Open Access Journals (Sweden)

    Katherine Kedzierska

    Full Text Available The available evidence suggests that protective immunity to Leishmania is achieved by priming the CD4(+ Th1 response. Therefore, we utilised a reverse genetics strategy to generate influenza A viruses to deliver an immunogenic Leishmania peptide. The single, immunodominant Leishmania-specific LACK(158-173 CD4(+ peptide was engineered into the neuraminidase stalk of H1N1 and H3N2 influenza A viruses. These recombinant viruses were used to vaccinate susceptible BALB/c mice to determine whether the resultant LACK(158-173-specific CD4(+ T cell responses protected against live L. major infection. We show that vaccination with influenza-LACK(158-173 triggers LACK(158-173-specific Th1-biased CD4(+ T cell responses within an appropriate cytokine milieu (IFN-γ, IL-12, essential for the magnitude and quality of the Th1 response. A single intraperitoneal exposure (non-replicative route of immunisation to recombinant influenza delivers immunogenic peptides, leading to a marked reduction (2-4 log in parasite burden, albeit without reduction in lesion size. This correlated with increased numbers of IFN-γ-producing CD4(+ T cells in vaccinated mice compared to controls. Importantly, the subsequent prime-boost approach with a serologically distinct strain of influenza (H1N1->H3N2 expressing LACK(158-173 led to a marked reduction in both lesion size and parasite burdens in vaccination trials. This protection correlated with high levels of IFN-γ producing cells in the spleen, which were maintained for 6 weeks post-challenge indicating the longevity of this protective effector response. Thus, these experiments show that Leishmania-derived peptides delivered in the context of recombinant influenza viruses are immunogenic in vivo, and warrant investigation of similar vaccine strategies to generate parasite-specific immunity.

  5. Effects of in ovo exposure to PCBs (coplanar congener, kanechlor mixture, hydroxylated metabolite) on the developing cell-mediated immunity in chickens

    Energy Technology Data Exchange (ETDEWEB)

    Hasegawa, J.; Matsuda, M.; Kawano, M.; Wakimoto, T. [Faculty of Agriculture, Ehime Univ., Matsuyama, Ehime (Japan); Kashima, Y. [Dept. of Hygiene, Yokohama City Univ. School of Medicine, Yokohama (Japan)

    2004-09-15

    Polychlorinated biphenyls (PCBs) are wide spread environmental contaminants and known to cause various adverse effects on health of human and wildlife. Immune system is one of the several targets for toxic effects of PCBs and its normal balance is often disrupted by the exposure of the compounds. For example, PCBs may induce immune suppression and result in increased susceptibility to bacterial and viral infections, or conversely, excessive immune enhancement may cause adverse outcomes including as autoimmune disease and anergy. Therefore immune function is regarded as one of an important endpoint in toxicological risk assessment. There are a number of studies shown that neonatal organisms perinatally exposed to polyhalogenated aromatic hydrocarbons (PHAHs) such as PCBs have severer effects on their immune system than adult. Dioxins and coplanar PCB congeners, structurally planar PHAHs are known to have high affinity for aryl hydrocarbon receptor (AhR). 2,3,7,8-tetrachlorinated dibenzo-p-dioxin (TCDD) have the strongest affinity among such compounds and these are considered to act on immune system through AhR. On the other hand, such as non-planar PCB congeners with low affinity for AhR, which are abundantly contained in commercial PCB preparations have non-additive (antagonistic) effects on immune function. Prenatal exposure of TCDD to rodent induced abnormal lymphoid development in the thymus and thymus-dependent immune functions were remarkably disturbed. Although several experimental studies in mammals have been carried out on the developmental immunotoxicity of PCBs, there are still limited information available on avian species. Thus in this study, prenatal exposure to low level of PCBs and the effects on the developing immune system were investigated with chicken as a model animal of avian species, especially it is focused on the cell-mediated immune function.

  6. Immune responses in cattle vaccinated with gamma-irradiated Anaplasma marginale

    International Nuclear Information System (INIS)

    The infectivity and immunogenecity of gamma-irradiated Anaplasma marginale organisms were studied in bovine calves. The severity of Anaplasma infection based on per cent infected red blood cells, haematological values and mortality was more in animals immunized with blood exposed to 60 kR in comparison to those inoculated with blood irradiated at 70, 80 and 90 kR. The immunizing controls demonstrated a significantly high parasitaemia, marked anaemia and more deaths. Marked and prolonged cell-mediated and humoral immune responses detectable in the first 3 weeks of post-immunization may be responsible for conferring of protective immunity. (author)

  7. Isotope-based immunological techniques. Their use in assessment of immune competence and the study of immune responses to pathogens

    International Nuclear Information System (INIS)

    The influence of isotope-based techniques on both assessment of immune competence and immune response to pathogens is discussed. Immunodeficiencies acquired as a result of factors like malnutrition and concomitant disease can severely affect not only attempts to intensify and improve production but also successful immune response against important vaccines such as rinderpest and foot-and-mouth disease. Isotope-based techniques, with their accuracy, speed and small sample volume, are ideally suited for assessing immunocompetence. One of the main drawbacks remains antigen purity, an area where research should now be concentrated. Lymphocyte transformation is widely used to assess cell-mediated immuno-competence but techniques to assess biological functions such as phagocytosis and cell-mediated cytotoxicity could more usefully reflect immune status. These latter techniques utilize isotopes such as 3H, 14C, 32P and 125I. Investigation of specific cell-mediated immune response often requires a labelled target. Suitable isotopes such as 51Cr, 99Tcsup(m), 75Se and 3H are compared for their capacity to label both mammalian and parasite targets. Suggestions are made on a number of areas of research that might usefully be encouraged and supported in order to improve applied veterinary immunology in tropical countries. (author)

  8. Proteasome function shapes innate and adaptive immune responses.

    Science.gov (United States)

    Kammerl, Ilona E; Meiners, Silke

    2016-08-01

    The proteasome system degrades more than 80% of intracellular proteins into small peptides. Accordingly, the proteasome is involved in many essential cellular functions, such as protein quality control, transcription, immune responses, cell signaling, and apoptosis. Moreover, degradation products are loaded onto major histocompatibility class I molecules to communicate the intracellular protein composition to the immune system. The standard 20S proteasome core complex contains three distinct catalytic active sites that are exchanged upon stimulation with inflammatory cytokines to form the so-called immunoproteasome. Immunoproteasomes are constitutively expressed in immune cells and have different proteolytic activities compared with standard proteasomes. They are rapidly induced in parenchymal cells upon intracellular pathogen infection and are crucial for priming effective CD8(+) T-cell-mediated immune responses against infected cells. Beyond shaping these adaptive immune reactions, immunoproteasomes also regulate the function of immune cells by degradation of inflammatory and immune mediators. Accordingly, they emerge as novel regulators of innate immune responses. The recently unraveled impairment of immunoproteasome function by environmental challenges and by genetic variations of immunoproteasome genes might represent a currently underestimated risk factor for the development and progression of lung diseases. In particular, immunoproteasome dysfunction will dampen resolution of infections, thereby promoting exacerbations, may foster autoimmunity in chronic lung diseases, and possibly contributes to immune evasion of tumor cells. Novel pharmacological tools, such as site-specific inhibitors of the immunoproteasome, as well as activity-based probes, however, hold promises as innovative therapeutic drugs for respiratory diseases and biomarker profiling, respectively. PMID:27343191

  9. Remune. Immune Response.

    Science.gov (United States)

    Lai, Derhsing; Jones, Taff

    2002-03-01

    The Immune Response Corp (IRC) is developing Remune, a potential HIV therapeutic vaccine. Remune is based on the Salk Immunogen, which is derived from an HIV isolate which has been inactivated by chemical depletion of glycoprotein 120 (gp120). Preliminary data suggested that Remune, in combination with antiviral drug therapy, results in undetectable levels of HIV. Phase III trials commenced in May 1997 and it was initially expected that registration filings would be made in 1999. However, following interim analysis of the 2500-patient, multicenter, double-blind, pivotal phase III study (study 806) in May 1999, an independent panel recommended concluding the clinical endpoint trial and IRC and licensee, Agouron, decided to pursue alternative regulatory strategies, including initiating two additional phase III surrogate marker trials. Despite this, Agouron gave IRC notice of termination of its continued development in July 2001. In August 2001, IRC informed Agouron that, due to the total number of endpoints to date falling short of that previously assumed by Agouron, it did not intend to continue Agouron's Study 202 of Remune. In July 2001, licensee Trinity Medical Group filed an NDA with the governing health authorities in Thailand for Remune. The Thai FDA certified Immune Response's Remune manufacturing facility as being in compliance with GMP standards, following an on site inspection by Thai officials in November 2001 that was performed as a requirement of Trinity's Thai NDA. As a result of this certification, Trinity expected that a "timely determination" could be made by the Thai FDA. Rhĵne-Poulenc Rorer discontinued its part in the development of Remune, with all manufacturing, marketing and distribution rights reverting to IRC. After Agouron returned rights to Remune in July 2001, IRC heldfull rights in the US, Europe and Japan, while collaborating with its partners Trinity Medical Group and Roemmers Laboratory in the Southeast Asian and Latin American

  10. MHC class II-associated invariant chain linkage of antigen dramatically improves cell-mediated immunity induced by adenovirus vaccines

    DEFF Research Database (Denmark)

    Holst, Peter Johannes; Mandrup Jensen, Camilla Maria; Orskov, Cathrine; Thomsen, Allan Randrup; Christensen, Jan Pravsgaard; Sørensen, Maria Rathmann

    2008-01-01

    potent and versatile Ag delivery vehicles available. However, the impact of chronic infections like HIV and hepatitis C virus underscore the need for further improvements. In this study, we show that the protective immune response to an adenovirus-encoded vaccine Ag can be accelerated, enhanced......, broadened, and prolonged by tethering of the rAg to the MHC class II-associated invariant chain (Ii). Thus, adenovirus-vectored vaccines expressing lymphocytic choriomeningitis virus (LCMV)-derived glycoprotein linked to Ii increased the CD4+ and CD8+ T cell stimulatory capacity in vitro and in vivo....... Furthermore, mice vaccinated with a single dose of adenovirus-expressing LCMV-derived glycoprotein linked to Ii were protected against lethal virus-induced choriomeningitis, lethal challenge with strains mutated in immunodominant T cell epitopes, and systemic infection with a highly invasive strain. In...

  11. NK Cell-Mediated Regulation of Protective Memory Responses against Intracellular Ehrlichial Pathogens.

    Directory of Open Access Journals (Sweden)

    Samar Habib

    Full Text Available Ehrlichiae are gram-negative obligate intracellular bacteria that cause potentially fatal human monocytic ehrlichiosis. We previously showed that natural killer (NK cells play a critical role in host defense against Ehrlichia during primary infection. However, the contribution of NK cells to the memory response against Ehrlichia remains elusive. Primary infection of C57BL/6 mice with Ehrlichia muris provides long-term protection against a second challenge with the highly virulent Ixodes ovatus Ehrlichia (IOE, which ordinarily causes fatal disease in naïve mice. Here, we show that the depletion of NK cells in E. muris-primed mice abrogates the protective memory response against IOE. Approximately, 80% of NK cell-depleted E. muris-primed mice succumbed to lethal IOE infection on days 8-10 after IOE infection, similar to naïve mice infected with the same dose of IOE. The lack of a recall response in NK cell-depleted mice correlated with an increased bacterial burden, extensive liver injury, decreased frequency of Ehrlichia-specific IFN-γ-producing memory CD4+ and CD8+ T-cells, and a low titer of Ehrlichia-specific antibodies. Intraperitoneal infection of mice with E. muris resulted in the production of IL-15, IL-12, and IFN-γ as well as an expansion of activated NKG2D+ NK cells. The adoptive transfer of purified E. muris-primed hepatic and splenic NK cells into Rag2-/-Il2rg-/- recipient mice provided protective immunity against challenge with E. muris. Together, these data suggest that E. muris-induced memory-like NK cells, which contribute to the protective, recall response against Ehrlichia.

  12. Gender-Specific Effects on Immune Response and Cardiac Function after Trauma Hemorrhage and Sepsis

    OpenAIRE

    Albertsmeier, Markus; Pratschke, Sebastian; Chaudry, Irshad; Angele, Martin K

    2014-01-01

    Summary Background Studies in human as well as animal models indicate a gender-specific responsiveness of the immune and organ systems with regard to shock, trauma, and sepsis. Methods A literature review was performed. Results Cell-mediated immune responses and cardiovascular functions are suppressed in males following trauma hemorrhage, whereas they are maintained or even enhanced in females in the proestrus state of the estrus cycle. Experimental studies have demonstrated that divergent im...

  13. Pulmonary immune response of dogs after exposure to 239PuO2

    International Nuclear Information System (INIS)

    This study evaluated the cell-mediated (CMI) and humoral immune responses in four Beagle dogs five to six years after single inhalation exposures to different monodisperse 239PuO2 aerosols (0.72-1.4μm activity median aerodynamic diameter). These exposures resulted in initial lung burdens ranging from 19 to 35kBq. The immune responses induced by lung immunization of dogs that had inhaled 239PuO2 were not suppressed by large doses of chronic alpha irradiation of the lungs and tracheobronchial lymph nodes, indicating that local pulmonary immune responses are preserved despite severe radiation-induced alteration of these tissues. (author)

  14. COMPARATIVE IMMUNE RESPONSE OF BROILER CHICKS TO NEWCASTLE

    Directory of Open Access Journals (Sweden)

    M. Shuaib, M. Ashfaque, Sajjad-ur-Rahman, M.K. Mansoor and I. Yousaf1

    2003-04-01

    Full Text Available An experimental study was designed to asses the humoral and cell mediated immune response in the broiler chicks double vaccinated against Newcastle disease (ND using Lasota strain of ND virus vaccine. Double vaccination 7 days following Ist vaccination gave haemagglutination inhibition (HI titers ranging from 1:16 to 1:128, that was significantly higher than the HI antibody titer recorded after single vaccination. Similarly, macrophage migration inhibition (MMI activity ranged from 28.57 to 40.86%, with mean activity of 36.07%. No correlation was found between HI titer and MMI test.

  15. Chlamydia trachomatis and chlamydial heat shock protein 60-specific antibody and cell-mediated responses predict tubal factor infertility

    DEFF Research Database (Denmark)

    Tiitinen, A.; Surcel, H.-M.; Halttunen, M.;

    2006-01-01

    BACKGROUND: To evaluate the role of Chlamydia trachomatis-induced humoral and cell-mediated immune (CMI) responses in predicting tubal factor infertility (TFI). METHODS: Blood samples were taken from 88 women with TFI and 163 control women. C. trachomatis and chlamydial heat shock protein 60 (CHSP......-specific IgG antibodies were found more frequently (43.2 versus 13.5%), and the antibody levels were higher in the TFI cases than in the controls (P < 0.001). C. trachomatis EB-induced lymphocyte responses were positive in 81.8% of the TFI cases and 58.9% of the controls (P < 0.001). Similarly, CHSP60-induced...... lymphocyte responses were found in 45.5% of the TFI cases and 30.7% of the controls (P < 0.001). CHSP60 antibody test was the best single test predicting TFI. Compared to cases with all four markers negative, the estimated risk for TFI was 4.1 (95% CI 1.4-11.9) among those with one positive marker and 19...

  16. Towards Developing a Malaria Vaccine Based on CD4 T Cell Mediated Immunity in Blood Stage of Malaria Infection

    Institute of Scientific and Technical Information of China (English)

    徐沪济

    2004-01-01

    Twenty-one years after malaria antigens were first cloned a vaccine still appears to be a long way off. There have been periods of great excitement and in model systems subunit vaccine homologues can induce robust protection. However, significant challenges exist concerning antigenic variation and polymorphism, immunological non-respons-iveness to individual vaccine antigens, parasite-induced apoptosis of immune effector and memory cells and immune deviation as a result of maternal immtmity and alterations of dendritic cell function.

  17. Immune responses and protection in bovine anaplasmosis and babesiosis

    International Nuclear Information System (INIS)

    For many decades there was a consensus of opinion that an induction of effective protective immunity against bovine anaplasmosis and babesiosis requires prior exposure of the host to live, preferably replicating, causative agents of these diseases. A procedure for inducing protective immunity by infection and treatment, known as premunization, is the oldest one. Since then, safer immunization procedures have been developed by altering the virulence of the immunizing organism by fast serial passages in splenectomized calves (B. bovis), exposure of the infective blood to irradiation (B. bigemina), and selection of a mutant (A. marginale) by adapting the organism to growth in an atypical host (sheep). The immune response to live immunogens includes both humoral and cell-mediated components (CMI). Some antibodies appear to be protective; however, the exact mechanism of humoral protection and that of parasite killing by the CMI system are not known. Use of live immunogens under field conditions (whole blood) has met with serious obstacles. Apart from difficulties of maintenance and field dispensation of blood-derived vaccines, there were reports of reversion to virulence of the immunizing agent, and actual broadening of the source of infectious agent for the disease vector. In addition, immunization by infection frequently sets forth a series of host-parasite interacting processes that exert an excessive demand on the host's immune system, leading to immunosuppression and interference with selective anti-parasitic action. (author)

  18. Relationships between T-cell.mediated immnune response and Pb, Zn. Cu, Cd, and as concetration in blood of nestling white storks (Ciconia ciconia) and black kites (Milvus migrans) from Doñana (southwestern Spain) after the Aznalcollar toxic spill

    OpenAIRE

    Baos, Raquel; Jovani, Roger; Forero, Manuela G.; Tella, José Luis; Gómez, Gemma; Jiménez, Begoña; María J. Gónzalez; Hiraldo, F.

    2006-01-01

    In the Aznalco´ llar mining accident (April 1998), nearly six million cubic meters of toxic wastes were spilled in the surroundings of the Don˜ ana National Park (southwestern Spain). The present study focused on the likely effects of metal pollution on the immune system of nestling white storks (Ciconia ciconia) and black kites (Milvus migrans) sampled in the nearby area. Using the phytohaemagglutinin skin test, we examined cell-mediated immune response (CMI) in r...

  19. Iron, folacin, vitamin B12 and zinc status and immune response in the elderly

    International Nuclear Information System (INIS)

    The relationships of iron, folacin, vitamin B12 and zinc status to cell-mediated immune response were investigated among 125 healthy, elderly persons (60-87 years of age). Plasma ferritin, plasma and red cell folate, and plasma vitamin B12 levels were assayed immuno-radiometrically. Plasma and hair zinc levels were determined by atomic absorption spectroscopy. Immune response was determined by transformation of peripheral blood lymphocytes after stimulation with phytohemagglutinin (PHA) and concanavalin A (con A), and in mixed lymphocyte reaction. Deficiencies of iron, folacin vitamin B12 and zinc were each associated (independently) with significantly lower lymphocyte responses to PHA and con A, and mixed lymphocyte reaction (P 12 or zinc. Further, they suggest that deficiencies of these nutrients may play a role in the depression of cell-mediated immunity with age, which in turn may lead to increased susceptibility to infectious diseases and cancer in the elderly

  20. Distinct gut-derived lactic acid bacteria elicit divergent dendritic cell-mediated NK cell responses

    DEFF Research Database (Denmark)

    Fink, Lisbeth Nielsen; Zeuthen, Louise Hjerrild; Christensen, Hanne;

    2007-01-01

    Lactic acid bacteria (LAB) are abundant in the gastrointestinal tract where they continuously regulate the immune system. NK cells are potently activated by dendritic cells (DCs) matured by inflammatory stimuli, and NK cells are present in the gut epithelium and in mesenteric lymph nodes, but it is...

  1. Immune markers and correlates of protection for vaccine induced immune responses

    DEFF Research Database (Denmark)

    Thakur, Aneesh; Pedersen, Lasse Eggers; Jungersen, Gregers

    2012-01-01

    Vaccines have been a major innovation in the history of mankind and still have the potential to address the challenges posed by chronic intracellular infections including tuberculosis, HIV and malaria which are leading causes of high morbidity and mortality across the world. Markers of an...... appropriate humoral response currently remain the best validated correlates of protective immunity after vaccination. Despite advancements in the field of immunology over the past few decades currently there are, however, no sufficiently validated immune correlates of vaccine induced protection against...... chronic infections in neither human nor veterinary medicine. Technological and conceptual advancements within cell-mediated immunology have led to a number of new immunological read-outs with the potential to emerge as correlates of vaccine induced protection. For TH1 type responses, antigen...

  2. Immune responses to improving welfare.

    Science.gov (United States)

    Berghman, L R

    2016-09-01

    The relationship between animal welfare and the immune status of an animal has a complex nature. Indeed, the intuitive notion that "increased vigilance of the immune system is by definition better" because it is expected to better keep the animal healthy, does not hold up under scrutiny. This is mostly due to the fact that the immune system consists of 2 distinct branches, the innate and the adaptive immune system. While they are intimately intertwined and synergistic in the living organism, they are profoundly different in their costs, both in terms of performance and wellbeing. In contrast to the adaptive immune system, the action of the innate immune system has a high metabolic cost as well as undesirable behavioral consequences. When a pathogen breaches the first line of defense (often a mucosal barrier), that organism's molecular signature is recognized by resident macrophages. The macrophages respond by releasing a cocktail of pro-inflammatory cytokines (including interleukin-1 and -6) that signal the brain via multiple pathways (humoral as well as neural) of the ongoing peripheral innate immune response. The behavioral response to the release of proinflammatory cytokines, known as "sickness behavior," includes nearly all the behavioral aspects that are symptomatic for clinical depression in humans. Hence, undesired innate immune activity, such as chronic inflammation, needs to be avoided by the industry. From an immunological standpoint, one of the most pressing poultry industry needs is the refinement of our current veterinary vaccine arsenal. The response to a vaccine, especially to a live attenuated vaccine, is often a combination of innate and adaptive immune activities, and the desired immunogenicity comes at the price of high reactogenicity. The morbidity, albeit limited and transient, caused by live vaccines against respiratory diseases and coccidiosis are good examples. Thankfully, the advent of various post-genomics technologies, such as DNA

  3. Influence of Flavonoid of Astragalus Membranaceus's Stem and Leaf on the Function of Cell Mediated Immunity in Mice

    Institute of Scientific and Technical Information of China (English)

    焦艳; 闻杰; 于晓红; 张德山

    2001-01-01

    Objective: To investigate the immune regulation of flavonoid of Astragalus membranaceus's stem and leaf(FAM-sl). Methods: Changes of total T cell count and subsets in mice were determined by monoclonal antibody assay before and after treatment with FAM-sl, and the lymphokine activated killer cell (LAK) activity was tested simultaneously by isotope label method.Results: FAM-sl could promote the proliferation of lymphocytes induced by ConA, raise the total T cell count and regulate the T cell subsets disturbance, and elevate the LAK activity induced by recombinant interleukin-2 (rIL-2).Conclusion: FAM-sl possesses effects of immune stimulation and immune regulation in treating immunosuppressive mice. This study provides experimental evidence for clinical application of FAM-sl.

  4. [Immune response in experimental animals immunized with Burkholderia pseudomallei surface antigens].

    Science.gov (United States)

    Avrorova, I V; Piven', N N; Zhukova, S I; Viktorov, D V; Khrapova, N P; Popov, S F

    2004-01-01

    The influence of the chromatographic fractions of B. pseudomallei surface antigenic complex (C, C1, D, H) on immune response in white rats and white mice was under study. These antigenic complexes were noted to produce perceptible stimulating effect on the immune system of white rats, in contrast to that of white mice. The immunization of the mice the above-mentioned fractions suppressed the phagocytic activity of peritoneal macrophages (PM) and slightly enhanced cell-mediated immunity. In experiments on white rats, fraction C induced the growth of specific antibody titers and stimulated the phagocytic activity of PM, as well as the indices of delayed hypersensitivity (DH). Fraction D showed a lower level of the induction of the phagocytic activity of PM and was inactive in the manifestation of cell-mediated immunity, but induced a high level of humoral immunity. Antigenic complexes C1 and H increased the phagocytic activity of PM and DH characteristics with a low level of antibody production. The studied fractions of the causative agent of melioidosis decreased the content of bactericidal cationic proteins (BCP) in rat blood neutrophils, and in mice a decreased content of BCP in phagocytes was registered. The fractions increased the activity of myeloperoxidase in blood neutrophils in mice and rats. As revealed with the use of immunoelectrophoresis, SDS PAAG electrophoresis and immunoblotting, the surface antigenic complex contained proteins of 18, 22, 39 kD and glycoproteins 42, 55, 90 kD. The latter glycoprotein was found in all the fractions under study, having protective properties. PMID:15554321

  5. Immune response to H pylori

    Institute of Scientific and Technical Information of China (English)

    Giovanni Suarez; Victor E Reyes; Ellen J Beswick

    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.

  6. MAP Kinases in Immune Responses

    Institute of Scientific and Technical Information of China (English)

    Yongliang Zhang; Chen Dong

    2005-01-01

    MAP kinases are evolutionarily conserved signaling regulators from budding yeast to mammals and play essential roles in both innate and adaptive immune responses. There are three main families of MAPKs in mammals. Each of them has its own activators, inactivators, substrates and scaffolds, which altogether form a fine signaling network in response to different extracellular or intracellular stimulation. In this review, we summarize recent advances in understanding of the regulation of MAP kinases and the roles of MAP kinases in innate and adaptive immune responses.

  7. Immune Response After Measles Vaccination

    Directory of Open Access Journals (Sweden)

    Bhardwaj A.K

    1991-01-01

    Full Text Available Measles immunization of 192 under 5 years of age children was undertaken and the overall seroconversion was 76.0%. Seroconversion rate in the age group of 9-12 months was 70.9% and it was 100% after one year. Immune response in malnourished children was more as compared to normal children. There were negligible side reactions after measles vaccination, and this vaccine passed normal potency tests under field conditions.

  8. Cell-mediated immunity to Plasmodium falciparum infection: evidence against the involvement of cytotoxic lymphocytes

    DEFF Research Database (Denmark)

    Theander, T G; Andersen, B J; Pedersen, B K;

    1988-01-01

    Blood mononuclear cells (PBMC) recognizing soluble malaria antigens (SPag) are present in the peripheral blood of individuals clinically immune to malaria, and they proliferate after exposure to such antigens. To test whether these cells have effector activity against Plasmodium falciparum, we...

  9. Immune responses in space flight

    Science.gov (United States)

    Sonnenfeld, G.

    1998-01-01

    Space flight has been shown to have profound effects on immunological parameters of humans, monkeys and rodents. These studies have been carried out by a number of different laboratories. Among the parameters affected are leukocyte blastogenesis, natural killer cell activity, leukocyte subset distribution, cytokine production - including interferons and interleukins, and macrophage maturation and activity. These changes start to occur only after a few days space flight, and some changes continue throughout long-term space flight. Antibody responses have received only very limited study, and total antibody levels have been shown to be increased after long-term space flight. Several factors could be involved in inducing these changes. These factors could include microgravity, lack of load-bearing, stress, acceleration forces, and radiation. The mechanism(s) for space flight-induced changes in immune responses remain(s) to be established. Certainly, there can be direct effects of microgravity, or other factors, on cells that play a fundamental role in immune responses. However, it is now clear that there are interactions between the immune system and other physiological systems that could play a major role. For example, changes occurring in calcium use in the musculoskeletal system induced by microgravity or lack of use could have great impact on the immune system. Most of the changes in immune responses have been observed using samples taken immediately after return from space flight. However, there have been two recent studies that have used in-flight testing. Delayed-type hypersensitivity responses to common recall antigens of astronauts and cosmonauts have been shown to be decreased when tested during space flights. Additionally, natural killer cell and blastogenic activities are inhibited in samples taken from rats during space flight. Therefore, it is now clear that events occurring during space flight itself can affect immune responses. The biological

  10. Toll-like receptor activation enhances cell-mediated immunity induced by an antibody vaccine targeting human dendritic cells

    Directory of Open Access Journals (Sweden)

    Berger Marc A

    2007-01-01

    Full Text Available Abstract Previously, we have successfully targeted the mannose receptor (MR expressed on monocyte-derived dendritic cells (DCs using a fully human MR-specific antibody, B11, as a vehicle to deliver whole protein tumor antigens such as the human chorionic gonadotropin hormone (hCGβ. Since MRs play a role in bridging innate immunity with adaptive immunity we have explored several toll-like receptor (TLR-specific ligands that may synergize with MR targeting and be applicable as adjuvants in the clinic. We demonstrate that antigen-specific helper and cytolytic T cells from both healthy donors and cancer patients were effectively primed with B11-hCGβ-treated autologous DCs when a combination of one or several TLR ligands is used. Specifically, concomitant signaling of DCs via TLR3 with dsRNA (poly I:C and DC TLR 7/8 with Resiquimod (R-848, respectively, elicited efficient antigen presentation-mediated by MR-targeting. We demonstrate that MR and TLRs contribute towards maturation and activation of DCs by a mechanism that may be driven by a combination of adjuvant and antibody vaccines that specifically deliver antigenic targets to DCs.

  11. Bovine anaplasmosis with emphasis on immune responses and protection

    International Nuclear Information System (INIS)

    Anaplasmosis is an infectious and transmissible disease manifested by progressive anaemia and the appearance of other characteristic disease symptoms. It is a world-wide tick-borne disease of cattle and some wild ruminants caused by the rickettsia Anaplasma marginale. By drawing on information obtained from studies of plasmodial cell cultures, a method has recently been developed for short-term in vitro cultivation of A. marginale. An attenuated Anaplasma organism capable of growth in both ovine and bovine erythrocytes was used to demonstrate that the in vitro system provided the necessary requirements for active transfer of the organism from cell to cell. Organismal antigens are found in the erythrocytes of infected animals, whereas soluble antigens are derived from their erythrocytes and serum. Serums from convalescing animals interact with these antigens in agglutination, complement fixation, fluorescent antibody and precipitation tests. Passive transfer of sera from immune to susceptible cattle, however, does not seem to confer protection against the infection and development of the disease. Studies that employed various tests for measuring cell-mediated immune (CMI) responses (leukocyte migration inhibition, blast transformation and cytotoxicity), in association with information collected simultaneously on antibody activity, have shown that both humoral and cellular immune responses are needed for the development of protective immunity in anaplasmosis. It was further shown that an active replication of Anaplasma is essential for induction of these two types of immune responses. Consequently, live virulent and attenuated immunogens fulfil requirements for induction of protective immunity. With the virulent agent, however, development of protective immunity is preceded by induction of auto-immune responses apparently associated with pathogenesis of anaemia in anaplasmosis. Inactivated immunogens derived from blood of infected cattle and used in combination with

  12. Apolipophorins and insects immune response

    Directory of Open Access Journals (Sweden)

    A Zdybicka-Barabas

    2013-08-01

    Full Text Available Insect lipoproteins, called lipophorins, are non-covalent assemblies of lipids and proteins serving as lipid transport vehicles. The protein moiety of lipophorin comprises two glycosylated apolipoproteins, apolipophorin I (apoLp-I and apolipophorin II (apoLp-II, constantly present in a lipophorin particle, and an exchangeable protein, apolipophorin III (apoLp-III. ApoLp-III is an abundant protein occurring in hemolymph in lipid-free and lipid-bound state and playing an important role in lipid transport and insect innate immunity. In immune response apoLp-III serves as a pattern recognition molecule. It binds and detoxifies microbial cell wall components, i.e., lipopolysaccharide, lipoteichoic acid, and β-1,3-glucan. ApoLp-III activates expression of antimicrobial peptides and proteins, stimulates their antimicrobial activity, participates in regulation of the phenoloxidase system and in hemolymph clotting. In addition, the protein is involved in cellular immune response, influencing hemocyte adhesion, phagocytosis and nodule formation, and in gut immunity. Although apoLp-III is the best studied apolipophorin in insect immunity so far, a literature review suggests that all the three apolipoproteins, apoLp-I, apoLp-II and apoLp-III, function together in a coordinated defense against pathogens

  13. Cytotoxic T-Cell-Mediated Response against Yersinia pseudotuberculosis in HLA-B27 Transgenic Rat

    OpenAIRE

    Falgarone, Géraldine; Blanchard, Hervé S.; Riot, Bertrand; Simonet, Michel; Breban, Maxime

    1999-01-01

    Yersinia-induced reactive arthritis is highly associated with HLA-B27, the role of which in defense against the triggering bacteria remains unclear. The aim of this study was to examine the capacity of rats transgenic for HLA-B27 to mount a cytotoxic T-lymphocyte (CTL) response against Y. pseudotuberculosis and to determine the influence of the HLA-B27 transgene on this response. Rats transgenic for HLA-B*2705 and human β2-microglobulin of the 21-4L line, which do not spontaneously develop di...

  14. Mast Cell-Mediated Mechanisms of Nociception

    Science.gov (United States)

    Aich, Anupam; Afrin, Lawrence B.; Gupta, Kalpna

    2015-01-01

    Mast cells are tissue-resident immune cells that release immuno-modulators, chemo-attractants, vasoactive compounds, neuropeptides and growth factors in response to allergens and pathogens constituting a first line of host defense. The neuroimmune interface of immune cells modulating synaptic responses has been of increasing interest, and mast cells have been proposed as key players in orchestrating inflammation-associated pain pathobiology due to their proximity to both vasculature and nerve fibers. Molecular underpinnings of mast cell-mediated pain can be disease-specific. Understanding such mechanisms is critical for developing disease-specific targeted therapeutics to improve analgesic outcomes. We review molecular mechanisms that may contribute to nociception in a disease-specific manner. PMID:26690128

  15. Mast Cell-Mediated Mechanisms of Nociception

    Directory of Open Access Journals (Sweden)

    Anupam Aich

    2015-12-01

    Full Text Available Mast cells are tissue-resident immune cells that release immuno-modulators, chemo-attractants, vasoactive compounds, neuropeptides and growth factors in response to allergens and pathogens constituting a first line of host defense. The neuroimmune interface of immune cells modulating synaptic responses has been of increasing interest, and mast cells have been proposed as key players in orchestrating inflammation-associated pain pathobiology due to their proximity to both vasculature and nerve fibers. Molecular underpinnings of mast cell-mediated pain can be disease-specific. Understanding such mechanisms is critical for developing disease-specific targeted therapeutics to improve analgesic outcomes. We review molecular mechanisms that may contribute to nociception in a disease-specific manner.

  16. The Potential of Intralesional Rose Bengal to Stimulate T-Cell Mediated Anti-Tumor Responses

    OpenAIRE

    Maker, Ajay V; Prabhakar, Bellur; Pardiwala, Krunal

    2015-01-01

    Rose Bengal (RB) is a red synthetic dye that was initially used in the garment industry and has been used safely for decades as a corneal stain by ophthalmologists. Antineoplastic properties of RB have also been observed, though the mechanism of action remained to be elucidated. Recently, interest in RB as a therapeutic cancer treatment has increased due to significant anti-tumor responses with direct tumor injection in human clinical trials for metastatic melanoma. In these patients, there h...

  17. PD-L1 Expression on Retrovirus-Infected Cells Mediates Immune Escape from CD8+ T Cell Killing.

    Directory of Open Access Journals (Sweden)

    Ilseyar Akhmetzyanova

    2015-10-01

    Full Text Available Cytotoxic CD8+ T Lymphocytes (CTL efficiently control acute virus infections but can become exhausted when a chronic infection develops. Signaling of the inhibitory receptor PD-1 is an important mechanism for the development of virus-specific CD8+ T cell dysfunction. However, it has recently been shown that during the initial phase of infection virus-specific CD8+ T cells express high levels of PD-1, but are fully competent in producing cytokines and killing virus-infected target cells. To better understand the role of the PD-1 signaling pathway in CD8+ T cell cytotoxicity during acute viral infections we analyzed the expression of the ligand on retrovirus-infected cells targeted by CTLs. We observed increased levels of PD-L1 expression after infection of cells with the murine Friend retrovirus (FV or with HIV. In FV infected mice, virus-specific CTLs efficiently eliminated infected target cells that expressed low levels of PD-L1 or that were deficient for PD-L1 but the population of PD-L1high cells escaped elimination and formed a reservoir for chronic FV replication. Infected cells with high PD-L1 expression mediated a negative feedback on CD8+ T cells and inhibited their expansion and cytotoxic functions. These findings provide evidence for a novel immune escape mechanism during acute retroviral infection based on PD-L1 expression levels on virus infected target cells.

  18. Immune Privilege as an Intrinsic CNS Property: Astrocytes Protect the CNS against T-Cell-Mediated Neuroinflammation

    Directory of Open Access Journals (Sweden)

    Ulrike Gimsa

    2013-01-01

    Full Text Available Astrocytes have many functions in the central nervous system (CNS. They support differentiation and homeostasis of neurons and influence synaptic activity. They are responsible for formation of the blood-brain barrier (BBB and make up the glia limitans. Here, we review their contribution to neuroimmune interactions and in particular to those induced by the invasion of activated T cells. We discuss the mechanisms by which astrocytes regulate pro- and anti-inflammatory aspects of T-cell responses within the CNS. Depending on the microenvironment, they may become potent antigen-presenting cells for T cells and they may contribute to inflammatory processes. They are also able to abrogate or reprogram T-cell responses by inducing apoptosis or secreting inhibitory mediators. We consider apparently contradictory functions of astrocytes in health and disease, particularly in their interaction with lymphocytes, which may either aggravate or suppress neuroinflammation.

  19. "Immuknow" to measurement of cell-mediated immunity in renal transplant recipients undergoing short-term evaluation.

    Science.gov (United States)

    De Paolis, P; Favarò, A; Piola, A; Martini, F; Cristiana, G; Agrati, C; Iappelli, M; Di Giulio, S

    2011-05-01

    The aim of this preliminary, observational study was to evaluate the value of ImmuKnow (IK), a new tool to measure the net state of immunefunction among renal transplant recipients, in correlation with clinical and laboratory data among unselected renal transplant recipients. Forty-nine recipients of mean age of 51 years were enrolled and followed for 1 year after transplantation. All subjects received the same immunosuppressive strategy with basiliximab induction and tacrolimus, mycophenolate mofetil and steroid maintenance therapy. Samples for IK were collected before transplantation as well as at 7, 14, 21 and 42 days and after 3, 6, and 12 months. There were 54 samples with IK 525 ng/mL. We divided recipients into 3 groups with respect to their basal IK values: Group 1 (Gr1; IK 525 ng/mL). At 1 year, we observed a significant difference among IK values at the start and the end of the study: Gr1 vs Gr2, P<.0001; Gr2 vs Gr3, P<.06 and Gr 1 vs Gr 3, P<.01). We observed reduced IK values to predict an increased risk of infection, particularly with cytomegalovirus (CMV) replication while higher IK value did not correlate with an increased risk of acute rejection episodes. Reduction of serum creatine levels occurred within 1 year in all groups (P<.005), but there was a significant difference between Gr 2 versus Grs 1 and 3 (P<.0001 and P<.0005, respectively). There findings suggested that more stable IK values were associated with clinical quiescence and laboratory stability. In conclusion, our preliminary analysis showed a beneficial capacity of this assay to represent the global depression of the immune system. We noted that reduced IK values, as a sign of excessive immunosuppressive therapy, were associated with an increased risk of infection. We did not confirm the predictive value of higher IK values for an increased risk of an acute rejection episode. PMID:21620039

  20. Synthetic B- and T-cell epitope peptides of porcine reproductive and respiratory syndrome virus with Gp96 as adjuvant induced humoral and cell-mediated immunity.

    Science.gov (United States)

    Chen, Caiwei; Li, Jing; Bi, Yuhai; Yang, Limin; Meng, Shanshan; Zhou, Yuancheng; Jia, Xiaojuan; Meng, Songdong; Sun, Lei; Liu, Wenjun

    2013-04-01

    Highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) has recently caused huge economic losses in the pig industry worldwide. Commercial vaccines, including inactivated vaccines and attenuated live vaccines, are available but fail to provide sustainable protection, especially against genetically heterologous strains. Thus several approaches have been used to develop more effective PRRSV vaccines and/or immune modulators to accelerate and magnify immune responses to PRRSV vaccines. Heat shock protein Gp96 is one such modulator that enhances both the innate and adaptive immune responses. In the present study, two B-cell epitopes and seven T-cell epitopes from PRRSV and a Pan DR T-helper cell epitope were synthesized and mixed with the N-terminal 22-355 aa of Gp96 (Gp96N) as an adjuvant, and immune responses were evaluated. Our results show that Gp96N activated PRRSV-specific humoral immune responses elicited by BCE-peptides and promoted the PRRSV-specific cellular immunity induced by TCE-peptides. Moreover, higher levels of IL-12 and TNF-α and lower levels of IL-4 and IL-10 were observed in the serum of Gp96N-vaccinated piglets compared to piglets immunized with no Gp96N, displaying a predominant Th1 type of immune response induced by Gp96N. Following challenge with the virulent HP-PRRSV isolate JXwn06, piglets vaccinated with the mixture of peptides and Gp96N presented with milder clinical symptoms, lower viremia, and less pathological lesions in their lungs, however, this vaccine could not provide lasting and effective protection against HP-PRRSV infection. These data provide important bases for the development of PRRSV epitope-based synthetic peptide vaccines combined with Gp96N as attractive immunomodulators in swine. PMID:23395588

  1. Cell signalling in the immune response of mussel hemocytes

    Directory of Open Access Journals (Sweden)

    L Canesi

    2006-05-01

    Full Text Available In this work data on immune cell signallling in the circulating hemocytes of the edible bivalve, themussel Mytilus spp, are summarized. Studies with different bacterial species and strains, heterologouscytokines and natural hormones, as well as with organic environmental chemicals, led to theidentification of the role of conserved components of kinase-mediated transduction pathways,including cytosolic kinases (such as MAPKs and PKC and kinase-activated transcription factors (suchas STATs, CREB, NF-kB, in the immune response. From these data a general scenario emergedindicating that close similarities exist in the signalling pathways involved in cell mediated immunity inbivalve and mammalian immunocytes. In particular, the results indicate that both the extent andduration of activation of components of kinase-mediated cascades are crucial in determining thehemocyte response to extracellular stimuli. The identification of the basic mechanisms of immunityand its modulation in mussels can give important information for the possible utilization of thesespecies as an invertebrate model for studies on innate immunity. Moreover, the application of thisknowledge to the understanding of the actual adaptive responses of bivalves when exposed to microorganismsin their natural environment can represent significant ecological, economical and publichealth-related interest.

  2. [Two recombinant adenovirus vaccine candidates containing neuraminidase Gene of H5N1 influenza virus (A/Anhui/1/2005) elicited effective cell-mediated immunity in mice].

    Science.gov (United States)

    Ma, Jing; Zhang, Xiao-Guang; Chen, Hong; Li, Kui-Biao; Zhang, Xiao-Mei; Zhang, Ke; Yang, Liang; Xu, Hong; Shu, Yue-Long; Tan, Wen-Jie; Zeng, Yi

    2009-09-01

    The aim of this study is to develop the recombinant adenovirus vaccine (rAdV) candidates containing neuraminidase (NA) gene of H5N1 influenza virus and test in BALB/c mice the effect of cell-mediated immunity. In this study, two kind of NA gene (WtNA gene, the wild type; Mod. NA gene, the codon-modified type) derived from H5N1 influenza virus (A/Anhui/1/2005) were cloned and inserted respectively into plasmid of adenovirus vector, then the rAdV vaccines candidates (rAdV-WtNA and rAdV-Mod. NA) were developed and purified, followed by immunization intramuscularly (10(9) TCID50 per dose, double injection at 0 and 4th week) in BALB/c mice, the effect of cell-mediated immunity were analysed at 5th week. Results indicated that: (i) NA protein expression was detected in two rAdV vaccines candidates by Western blotting; (ii) the rAdV-Mod. NA vaccine could elicit more robust NA specific cell-mediated immunity in mice than that of rAdV-WtNA vaccine (P = 0. 016) by IFN-gamma ELIspot assay. These findings suggested rAdV-Mod. NA vaccine was a potential vaccine candidate against H5N1 influenza and worthy of further investigation. PMID:19954107

  3. Th17 Responses in Chronic Allergic Airway Inflammation Abrogate Regulatory T cell-mediated Tolerance and Contribute to Airway Remodeling

    OpenAIRE

    Zhao, Jingyue; Lloyd, Clare M.; Noble, Alistair

    2012-01-01

    The role of Th17 responses in airway remodeling in asthma is currently unknown. We demonstrate that both parenteral and mucosal allergen sensitization followed by allergen inhalation leads to Th17-biased lung immune responses. Unlike Th17 cells generated in vitro, lung Th17 cells did not produce TNF-α or IL-22. Eosinophilia predominated in acute inflammation while neutrophilia and IL-17 increased in chronic disease. Allergen-induced tolerance involved Foxp3, Helios and GARP expressing regulat...

  4. T-helper cell-mediated proliferation and cytokine responses against recombinant Merkel cell polyomavirus-like particles.

    Science.gov (United States)

    Kumar, Arun; Chen, Tingting; Pakkanen, Sari; Kantele, Anu; Söderlund-Venermo, Maria; Hedman, Klaus; Franssila, Rauli

    2011-01-01

    The newly discovered Merkel Cell Polyomavirus (MCPyV) resides in approximately 80% of Merkel cell carcinomas (MCC). Causal role of MCPyV for this rare and aggressive skin cancer is suggested by monoclonal integration and truncation of large T (LT) viral antigen in MCC cells. The mutated MCPyV has recently been found in highly purified leukemic cells from patients with chronic lymphocytic leukemia (CLL), suggesting a pathogenic role also in CLL. About 50-80% of adults display MCPyV-specific antibodies. The humoral immunity does not protect against the development of MCC, as neutralizing MCPyV antibodies occur in higher levels among MCC patients than healthy controls. Impaired T-cell immunity has been linked with aggressive MCC behavior. Therefore, cellular immunity appears to be important in MCPyV infection surveillance. In order to elucidate the role of MCPyV-specific Th-cell immunity, peripheral blood mononuclear cells (PBMC) of healthy adults were stimulated with MCPyV VP1 virus-like particles (VLPs), using human bocavirus (HBoV) VLPs and Candida albicans antigen as positive controls. Proliferation, IFN-γ, IL-13 and IL-10 responses were examined in 15 MCPyV-seropositive and 15 seronegative volunteers. With the MCPyV antigen, significantly stronger Th-cell responses were found in MCPyV-seropositive than MCPyV-seronegative subjects, whereas with the control antigens, the responses were statistically similar. The most readily detectable cytokine was IFN-γ. The MCPyV antigen tended to induce stronger IFN-γ responses than HBoV VLP antigen. Taken together, MCPyV-specific Th-cells elicit vigorous IFN-γ responses. IFN-γ being a cytokine with major antiviral and tumor suppressing functions, Th-cells are suggested to be important mediators of MCPyV-specific immune surveillance. PMID:21991346

  5. T-helper cell-mediated proliferation and cytokine responses against recombinant Merkel cell polyomavirus-like particles.

    Directory of Open Access Journals (Sweden)

    Arun Kumar

    Full Text Available The newly discovered Merkel Cell Polyomavirus (MCPyV resides in approximately 80% of Merkel cell carcinomas (MCC. Causal role of MCPyV for this rare and aggressive skin cancer is suggested by monoclonal integration and truncation of large T (LT viral antigen in MCC cells. The mutated MCPyV has recently been found in highly purified leukemic cells from patients with chronic lymphocytic leukemia (CLL, suggesting a pathogenic role also in CLL. About 50-80% of adults display MCPyV-specific antibodies. The humoral immunity does not protect against the development of MCC, as neutralizing MCPyV antibodies occur in higher levels among MCC patients than healthy controls. Impaired T-cell immunity has been linked with aggressive MCC behavior. Therefore, cellular immunity appears to be important in MCPyV infection surveillance. In order to elucidate the role of MCPyV-specific Th-cell immunity, peripheral blood mononuclear cells (PBMC of healthy adults were stimulated with MCPyV VP1 virus-like particles (VLPs, using human bocavirus (HBoV VLPs and Candida albicans antigen as positive controls. Proliferation, IFN-γ, IL-13 and IL-10 responses were examined in 15 MCPyV-seropositive and 15 seronegative volunteers. With the MCPyV antigen, significantly stronger Th-cell responses were found in MCPyV-seropositive than MCPyV-seronegative subjects, whereas with the control antigens, the responses were statistically similar. The most readily detectable cytokine was IFN-γ. The MCPyV antigen tended to induce stronger IFN-γ responses than HBoV VLP antigen. Taken together, MCPyV-specific Th-cells elicit vigorous IFN-γ responses. IFN-γ being a cytokine with major antiviral and tumor suppressing functions, Th-cells are suggested to be important mediators of MCPyV-specific immune surveillance.

  6. Anticoagulation inhibits tumor cell-mediated release of platelet angiogenic proteins and diminishes platelet angiogenic response.

    Science.gov (United States)

    Battinelli, Elisabeth M; Markens, Beth A; Kulenthirarajan, Rajesh A; Machlus, Kellie R; Flaumenhaft, Robert; Italiano, Joseph E

    2014-01-01

    Platelets are a reservoir for angiogenic proteins that are secreted in a differentially regulated process. Because of the propensity for clotting, patients with malignancy are often anticoagulated with heparin products, which paradoxically offer a survival benefit by an unknown mechanism. We hypothesized that antithrombotic agents alter the release of angiogenesis regulatory proteins from platelets. Our data revealed that platelets exposed to heparins released significantly decreased vascular endothelial growth factor (VEGF) in response to adenosine 5'-diphosphate or tumor cells (MCF-7 cells) and exhibited a decreased angiogenic potential. The releasate from these platelets contained decreased proangiogenic proteins. The novel anticoagulant fondaparinux (Xa inhibitor) demonstrated a similar impact on the platelet angiogenic potential. Because these anticoagulants decrease thrombin generation, we hypothesized that they disrupt signaling through the platelet protease-activated receptor 1 (PAR1) receptor. Addition of PAR1 antagonists to platelets decreased VEGF release and angiogenic potential. Exposure to a PAR1 agonist in the presence of anticoagulants rescued the angiogenic potential. In vivo studies demonstrated that platelets from anticoagulated patients had decreased VEGF release and angiogenic potential. Our data suggest that the mechanism by which antithrombotic agents increase survival and decrease metastasis in cancer patients is through attenuation of platelet angiogenic potential. PMID:24065244

  7. HIV-1 DNA vaccine with adjuvant cytokines induces specific immune responses against HIV-1 infection in mice

    Institute of Scientific and Technical Information of China (English)

    WANG Fu-xiang; SUN Yong-tao; WANG Lin-xu; LIU Juan

    2006-01-01

    @@ There is mounting evidence that the induction of strong mucosal and cell-mediated immune responses is key element to consider in constructing efficacious HIV-1 vaccine. Therapeutic vaccines that induce high levels of CTL specific to HIV are currently being developed worldwide.

  8. Immune responses to Mycoplasma bovis proteins formulated with different adjuvants.

    Science.gov (United States)

    Prysliak, Tracy; Perez-Casal, Jose

    2016-06-01

    Most vaccines for protection against Mycoplasma bovis disease are made of bacterins, and they offer varying degrees of protection. Our focus is on the development of a subunit-based protective vaccine, and to that end, we have identified 10 novel vaccine candidates. After formulation of these candidates with TriAdj, an experimental tri-component novel vaccine adjuvant developed at VIDO-InterVac, we measured humoral and cell-mediated immune responses in vaccinated animals. In addition, we compared the immune responses after formulation with TriAdj with the responses measured in animals vaccinated with a mix of a commercial adjuvant (Emulsigen™) and 2 of the components of the TriAdj, namely polyinosinic:polycytidylic acid (poly I:C) and the cationic innate defense regulator (IDR) peptide 1002 (VQRWLIVWRIRK). In this latter trial, we detected significant IgG1 humoral immune responses to 8 out of 10 M. bovis proteins, and IgG2 responses to 7 out of 10 proteins. Thus, we concluded that the commercial adjuvant formulated with poly I:C and the IDR peptide 1002 is the best formulation for the experimental vaccine. PMID:27105454

  9. Quantitative PCR evaluation of cellular immune responses in Kenyan children vaccinated with a candidate malaria vaccine.

    Directory of Open Access Journals (Sweden)

    Jedidah Mwacharo

    Full Text Available BACKGROUND: The T-cell mediated immune response plays a central role in the control of malaria after natural infection or vaccination. There is increasing evidence that T-cell responses are heterogeneous and that both the quality of the immune response and the balance between pro-inflammatory and regulatory T-cells determines the outcome of an infection. As Malaria parasites have been shown to induce immunosuppressive responses to the parasite and non-related antigens this study examined T-cell mediated pro-inflammatory and regulatory immune responses induced by malaria vaccination in children in an endemic area to determine if these responses were associated with vaccine immunogenicity. METHODS: Using real-time RT- PCR we profiled the expression of a panel of key markers of immunogenecity at different time points after vaccination with two viral vector vaccines expressing the malaria TRAP antigen (FP9-TRAP and MVA-TRAP or following rabies vaccination as a control. PRINCIPAL FINDINGS: The vaccine induced modest levels of IFN-gamma mRNA one week after vaccination. There was also an increase in FoxP3 mRNA expression in both TRAP stimulated and media stimulated cells in the FFM ME-TRAP vaccine group; however, this may have been driven by natural exposure to parasite rather than by vaccination. CONCLUSION: Quantitative PCR is a useful method for evaluating vaccine induced cell mediated immune responses in frozen PBMC from children in a malaria endemic country. Future studies should seek to use vaccine vectors that increase the magnitude and quality of the IFN-gamma immune response in naturally exposed populations and should monitor the induction of a regulatory T cell response.

  10. Surgical Stress Abrogates Pre-Existing Protective T Cell Mediated Anti-Tumor Immunity Leading to Postoperative Cancer Recurrence.

    Science.gov (United States)

    Ananth, Abhirami A; Tai, Lee-Hwa; Lansdell, Casey; Alkayyal, Almohanad A; Baxter, Katherine E; Angka, Leonard; Zhang, Jiqing; Tanese de Souza, Christiano; Stephenson, Kyle B; Parato, Kelley; Bramson, Jonathan L; Bell, John C; Lichty, Brian D; Auer, Rebecca C

    2016-01-01

    Anti-tumor CD8+ T cells are a key determinant for overall survival in patients following surgical resection for solid malignancies. Using a mouse model of cancer vaccination (adenovirus expressing melanoma tumor-associated antigen (TAA)-dopachrome tautomerase (AdDCT) and resection resulting in major surgical stress (abdominal nephrectomy), we demonstrate that surgical stress results in a reduction in the number of CD8+ T cell that produce cytokines (IFNγ, TNFα, Granzyme B) in response to TAA. This effect is secondary to both reduced proliferation and impaired T cell function following antigen binding. In a prophylactic model, surgical stress completely abrogates tumor protection conferred by vaccination in the immediate postoperative period. In a clinically relevant surgical resection model, vaccinated mice undergoing a positive margin resection with surgical stress had decreased survival compared to mice with positive margin resection alone. Preoperative immunotherapy with IFNα significantly extends survival in surgically stressed mice. Importantly, myeloid derived suppressor cell (MDSC) population numbers and functional impairment of TAA-specific CD8+ T cell were altered in surgically stressed mice. Our observations suggest that cancer progression may result from surgery-induced suppression of tumor-specific CD8+ T cells. Preoperative immunotherapies aimed at targeting the prometastatic effects of cancer surgery will reduce recurrence and improve survival in cancer surgery patients. PMID:27196057

  11. Myeloid IKKβ promotes antitumor immunity by modulating CCL11 and the innate immune response.

    Science.gov (United States)

    Yang, Jinming; Hawkins, Oriana E; Barham, Whitney; Gilchuk, Pavlo; Boothby, Mark; Ayers, Gregory D; Joyce, Sebastian; Karin, Michael; Yull, Fiona E; Richmond, Ann

    2014-12-15

    Myeloid cells are capable of promoting or eradicating tumor cells and the nodal functions that contribute to their different roles are still obscure. Here, we show that mice with myeloid-specific genetic loss of the NF-κB pathway regulatory kinase IKKβ exhibit more rapid growth of cutaneous and lung melanoma tumors. In a BRAF(V600E/PTEN(-/-)) allograft model, IKKβ loss in macrophages reduced recruitment of myeloid cells into the tumor, lowered expression of MHC class II molecules, and enhanced production of the chemokine CCL11, thereby negatively regulating dendritic-cell maturation. Elevated serum and tissue levels of CCL11 mediated suppression of dendritic-cell differentiation/maturation within the tumor microenvironment, skewing it toward a Th2 immune response and impairing CD8(+) T cell-mediated tumor cell lysis. Depleting macrophages or CD8(+) T cells in mice with wild-type IKKβ myeloid cells enhanced tumor growth, where the myeloid cell response was used to mediate antitumor immunity against melanoma tumors (with less dependency on a CD8(+) T-cell response). In contrast, myeloid cells deficient in IKKβ were compromised in tumor cell lysis, based on their reduced ability to phagocytize and digest tumor cells. Thus, mice with continuous IKKβ signaling in myeloid-lineage cells (IKKβ(CA)) exhibited enhanced antitumor immunity and reduced melanoma outgrowth. Collectively, our results illuminate new mechanisms through which NF-κB signaling in myeloid cells promotes innate tumor surveillance. PMID:25336190

  12. Delivery of antigenic candidates by a DNA/MVA heterologous approach elicits effector CD8+T cell mediated immunity against Trypanosoma cruzi

    OpenAIRE

    Gupta, Shivali; Garg, Nisha Jain

    2012-01-01

    In this study, we have characterized the immune mechanisms elicited by antigenic candidates, TcG2 and TcG4, delivered by a DNA-prime/MVA-boost approach, and evaluated the host responses to T. cruzi infection in C57BL/6 mice. Immunization of mice with antigenic candidates elicited antigen-specific, high-avidity, trypanolytic antibody response (IgG2b>IgG1) and CD8+T cells that exhibited type-1 cytolytic effector (CD8+CD107a+IFN-γ+Perforin+) phenotype. The extent of TcG2-dependent type 1 B and T...

  13. An Oral Salmonella-Based Vaccine Inhibits Liver Metastases by Promoting Tumor-Specific T-Cell-Mediated Immunity in Celiac and Portal Lymph Nodes: A Preclinical Study

    Science.gov (United States)

    Vendrell, Alejandrina; Mongini, Claudia; Gravisaco, María José; Canellada, Andrea; Tesone, Agustina Inés; Goin, Juan Carlos; Waldner, Claudia Inés

    2016-01-01

    Primary tumor excision is one of the most widely used therapies of cancer. However, the risk of metastases development still exists following tumor resection. The liver is a common site of metastatic disease for numerous cancers. Breast cancer is one of the most frequent sources of metastases to the liver. The aim of this work was to evaluate the efficacy of the orally administered Salmonella Typhi vaccine strain CVD 915 on the development of liver metastases in a mouse model of breast cancer. To this end, one group of BALB/c mice was orogastrically immunized with CVD 915, while another received PBS as a control. After 24 h, mice were injected with LM3 mammary adenocarcinoma cells into the spleen and subjected to splenectomy. This oral Salmonella-based vaccine produced an antitumor effect, leading to a decrease in the number and volume of liver metastases. Immunization with Salmonella induced an early cellular immune response in mice. This innate stimulation rendered a large production of IFN-γ by intrahepatic immune cells (IHIC) detected within 24 h. An antitumor adaptive immunity was found in the liver and celiac and portal lymph nodes (LDLN) 21 days after oral bacterial inoculation. The antitumor immune response inside the liver was associated with increased CD4+ and dendritic cell populations as well as with an inflammatory infiltrate located around liver metastatic nodules. Enlarged levels of inflammatory cytokines (IFN-γ and TNF) were also detected in IHIC. Furthermore, a tumor-specific production of IFN-γ and TNF as well as tumor-specific IFN-γ-producing CD8 T cells (CD8+IFN-γ+) were found in the celiac and portal lymph nodes of Salmonella-treated mice. This study provides first evidence for the involvement of LDLN in the development of an efficient cellular immune response against hepatic tumors, which resulted in the elimination of liver metastases after oral Salmonella-based vaccination. PMID:26973649

  14. Cellular Immune Responses in HIV-Negative Immunodeficiency with Anti-Interferon-γ Antibodies and Opportunistic Intracellular Microorganisms

    OpenAIRE

    Wipasa, Jiraprapa; Wongkulab, Panuwat; Chawansuntati, Kriangkrai; Chaiwarit, Romanee; Supparatpinyo, Khuanchai

    2014-01-01

    Background Cell-mediated immunity plays a crucial role in resistance to intracellular infection. We previously reported antibodies against interferon-gamma (IFN-γ) in HIV− negative (HIV−) patients with acquired immunodeficiency presenting with repeated episodes of disseminated infection caused by uncommon opportunistic intracellular fungal, bacterial, and viral pathogens. This follow-up study aimed to investigate cellular immune responses in these unusual patients. Methods Twenty HIV− patient...

  15. Cell-mediated immune response to Leishmania chagasi experimental infection of BALB/c immunosuppressed mice

    Directory of Open Access Journals (Sweden)

    JG Machado

    2010-01-01

    Full Text Available Leishmaniasis, a zoonosis of worldwide distribution, presents a significant impact on immunosupressed patients. This study aimed to evaluate Leishmania chagasi infection in BALB/c mice immunosuppressed with dexamethasone. Spleen cells stimulated or not with L. chagasi were cultured for cytokine quantification (IFN-γ, IL-2, IL-4 and IL-10 by sandwich ELISA. Parasite loads in the spleen and liver were determined by means of culture microtitration. Immunosuppressed groups showed statistically lower spleen weight and CD4-cell percentage in blood on the day of infection and produced Th1 and Th2 cytokines on other days of the study. The other infected groups, weather immunosupressed or not, also produced Th1 and Th2 cytokines. Parasite loads in the spleen and liver were not statistically different among the groups. It was concluded that L. chagasi infection was not affected by dexamethasone-induced immunosuppression, probably due the reversible effect of the treatment.

  16. A genetic inference on cancer immune responsiveness

    OpenAIRE

    Wang, Ena; Uccellini, Lorenzo; Marincola, Francesco M.

    2012-01-01

    A cancer immune signature implicating good prognosis and responsiveness to immunotherapy was described that is observed also in other aspects of immune-mediated, tissue-specific destruction (TSD). Its determinism remains, however, elusive. Based on limited but unique clinical observations, we propose a multifactorial genetic model of human cancer immune responsiveness.

  17. Tilapia show immunization response against Ich

    Science.gov (United States)

    This study compares the immune response of Nile tilapia and red tilapia against parasite Ichthyophthirius multifiliis (Ich) using a cohabitation challenge model. Both Nile and red tilapia showed strong immune response post immunization with live Ich theronts by IP injection or immersion. Blood serum...

  18. T Cell-Mediated Modulation of Mast Cell Function: Heterotypic Adhesion-Induced Stimulatory or Inhibitory Effects

    OpenAIRE

    Mekori, Yoseph A.; Hershko, Alon Y.

    2012-01-01

    Close physical proximity between mast cells and T cells has been demonstrated in several T cell mediated inflammatory processes such as rheumatoid arthritis and sarcoidosis. However, the way by which mast cells are activated in these T cell-mediated immune responses has not been fully elucidated. We have identified and characterized a novel mast cell activation pathway initiated by physical contact with activated T cells, and showed that this pathway is associated with degranulation and cytok...

  19. Murine immune responses to oral BCG immunization in the presence or absence of prior BCG sensitization.

    Science.gov (United States)

    Cross, Martin L; Lambeth, Matthew R; Aldwell, Frank E

    2010-02-01

    Oral delivery of live Mycobacterium bovis BCG in a lipid matrix invokes cell-mediated immune (CMI) responses in mice and consequent protection against pulmonary challenge with virulent mycobacteria. To investigate the influence of prior BCG sensitization on oral vaccine efficacy, we assessed CMI responses and BCG colonization of the alimentary tract lymphatics 5 months after oral vaccination, in both previously naive mice and in mice that had been sensitized to BCG by injection 6 months previously. CMI responses did not differ significantly between mice that received subcutaneous BCG followed by oral BCG and those that received either injected or oral BCG alone. In vivo BCG colonization was predominant in the mesenteric lymph nodes after oral vaccination; this colonizing ability was not influenced by prior BCG sensitization. From this murine model study, we conclude that although prior parenteral-route BCG sensitization does not detrimentally affect BCG colonization after oral vaccination, there is no significant immune-boosting effect of the oral vaccine either. PMID:19918257

  20. Mathematical Modelling of Immune Response in Tissues

    OpenAIRE

    Su, B; Zhou, W; K. S. Dorman; Jones, D. E.

    2009-01-01

    We have developed a spatial–temporal mathematical model (PDE) to capture fundamental aspects of the immune response to antigen. We have considered terms that broadly describe intercellular communication, cell movement, and effector function (activation or inhibition). The PDE model is robust to variation in antigen load and it can account for (1) antigen recognition, (2) an innate immune response, (3) an adaptive immune response, (4) the elimination of antigen and subsequent resolution of the...

  1. Mosquito immune responses to arbovirus infections

    OpenAIRE

    Carol D. Blair; Olson, Ken E

    2014-01-01

    The principal mosquito innate immune response to virus infections, RNA interference (RNAi), differs substantially from the immune response to bacterial and fungal infections. The exo-siRNA pathway constitutes the major anti-arboviral RNAi response and its essential genetic components have been identified. Recent research has also implicated the Piwi-interacting RNA pathway in mosquito anti-arboviral immunity, but Piwi gene-family components involved are not well-defined. Arboviruses must evad...

  2. Immune cellular response to HPV: current concepts

    Directory of Open Access Journals (Sweden)

    Maria Alice Guimarães Gonçalves

    2004-02-01

    Full Text Available Although cellular immunity is essential for the elimination of human papillomavirus (HPV, the mechanisms involved are still poorly understood. We summarize the main mechanisms involved in cellular immune response to infections caused by HPV. Immunotherapies for HPV-related cancers require the disruption of T-cell response control mechanisms, associated with the stimulation of the Th1 cytokine response.

  3. Repeatedly administered antidepressant drugs modulate humoral and cellular immune response in mice through action on macrophages.

    Science.gov (United States)

    Nazimek, Katarzyna; Kozlowski, Michael; Bryniarski, Pawel; Strobel, Spencer; Bryk, Agata; Myszka, Michal; Tyszka, Anna; Kuszmiersz, Piotr; Nowakowski, Jaroslaw; Filipczak-Bryniarska, Iwona

    2016-08-01

    Depression is associated with an altered immune response, which could be normalized by antidepressant drugs. However, little is known about the influence of antidepressants on the peripheral immune response and function of macrophages in individuals not suffering from depression. Our studies were aimed at determining the influence of antidepressant drugs on the humoral and cellular immune response in mice. Mice were treated intraperitoneally with imipramine, fluoxetine, venlafaxine, or moclobemide and contact immunized with trinitrophenyl hapten followed by elicitation and measurement of contact sensitivity by ear swelling response. Peritoneal macrophages from drug-treated mice were either pulsed with sheep erythrocytes or conjugated with trinitrophenyl and transferred into naive recipients to induce humoral or contact sensitivity response, respectively. Secretion of reactive oxygen intermediates, nitric oxide, and cytokines by macrophages from drug-treated mice was assessed, respectively, in chemiluminometry, Griess-based colorimetry and enzyme-linked immunosorbent assay, and the expression of macrophage surface markers was analyzed cytometrically. Treatment of mice with fluoxetine, venlafaxine, and moclobemide results in suppression of humoral and cell-mediated immunity with a reduction of the release of macrophage proinflammatory mediators and the expression of antigen-presentation markers. In contrast, treatment with imipramine enhanced the humoral immune response and macrophage secretory activity but slightly suppressed active contact sensitivity. Our studies demonstrated that systemically delivered antidepressant drugs modulate the peripheral humoral and cell-mediated immune responses, mostly through their action on macrophages. Imipramine was rather proinflammatory, whereas other tested drugs expressed immunosuppressive potential. Current observations may be applied to new therapeutic strategies dedicated to various disorders associated with excessive

  4. Host Immune Response to Histophilus somni.

    Science.gov (United States)

    Corbeil, Lynette B

    2016-01-01

    Histophilus somni is known to cause several overlapping syndromes or to be found in genital or upper respiratory carrier states in ruminants. Vaccines have been used for decades, yet efficacy is controversial and mechanisms of protective immunity are not well understood. Since H. somni survives phagocytosis, it has sometimes been considered to be a facultative intercellular parasite, implying that cell-mediated immunity would be critical in protection. However, H. somni not only inhibits phagocyte function, but also is cytotoxic for macrophages. Therefore, it does not live for long periods in healthy phagocytes. Protection of calves against H. somni pneumonia by passive immunization is also evidence that H. somni is more like an extracellular pathogen than an intracellular pathogen. Several studies showed that bovine IgG2 antibodies are more protective than IgG1 antibodies. Even the IgG2 allotypes tend to vary in protection. Of course, antigenic specificity also determines protection. So far, there is most evidence for protection by a 40 K outer membrane protein and by Immunoglobulin binding protein A fibrils. Serology and immunohistochemistry have both been used for immunodiagnosis. Many evasive mechanisms by H. somni have been defined, including decreased phagocyte function, antibodies bound by shed antigens, decreased immune stimulation, and antigenic variation. Interaction of H. somni with other bovine respiratory disease organisms is another layer of pathogenesis. Studies of bovine respiratory syncytial virus (BRSV) and H. somni in calfhood pneumonia revealed an increase in IgE antibodies to H. somni, which were associated with more severe disease of longer duration than with either agent alone. Innate immune mechanisms at the epithelial cell level are also affected by dual infection by BRSV and H. somni as compared to either pathogen alone. Although much more work needs to be done, the complex mechanisms of H. somni immunity are becoming clearer. PMID

  5. Effect of cell mediated immunity regulation of duck enhanced by duck IFN-α eukaryon expression plasmid and inoculated with DPV attenuated vaccine by gene-gun

    Institute of Scientific and Technical Information of China (English)

    Zhiping CHENG; Anchun CHENG; Mingshu WANG; Bin CHEN; Chuang LIU; Kun DUAN; Xue ZHOU; Xiaoyue CHEN

    2008-01-01

    In order to study the effect of cell mediated immunity regulation of duck IFN-α eukaryon expression plasmid (pcDNA-SDIFN-α) on duck plague virus (DPV)attenuated vaccine in ducks,pcDNA-SDIFN-α was administered to 28-day-old ducks at doses of 1,3 and 6 μg per duck,respectively,by gene-gun.PBS and empty vector pcDNA were used as control.Fifteen days later,all ducks were injected with DPV attenuated vaccine and blood samples were collected at 3,7,14,21,28,35,49,63 and 84 days after injection.T-lymphocyte proliferation tests (MTT) were used to detect the T-lymphocyte proliferation in the peripheral blood (PBL) of ducks.Blood samples collected at 7,14,21,28,35 and 49 days after injection were detected by fluorescence-activated cell sorter (FACS) for recording the number of CD3+ T-lymphocytes of ducks.Results were as follows:(1) Reaction of T-lymphocytes in PBL to ConA (OD value) of ducks treated with pcDNA-SDIFN-α was higher than that of PBS and pcDNA control groups in 3-84 days.There were highly significant differences between the 1 μg per duck group and the two control groups in 3-84 days (P ≤ 0.01),between the 3 μg per duck group and the two control groups in 3-84 days (P ≤ 0.01,P ≤ 0.05),and between the 6 μg per duck group and the two control groups in 7-49 days (P ≤ 0.01,P ≤ 0.05).The significant difference was also present between the groups of 1,3 and 6 μg per duck in 3-35 days (P ≤ 0.05).However,there was no significant difference between the 3 and 6 μg per duck groups (P ≥ 0.05).The pcDNA control group was higher than PBS control group,but no difference was detected (P ≥ 0.05).(2) Change of the number of CD3+ T-lymphocytes in ducks administered with different doses of pcDNA-SDIFN-α was higher than that of PBS and pcDNA control groups in 7-49 days.The change in the 1 μg per duck group was significantly higher than that in PBS and pcDNA control groups in 14-49 days (P ≤ 0.01).There were significant differences between the 3 μg per

  6. Gestational zinc deficiency impairs humoral and cellular immune responses to hepatitis B vaccination in offspring mice.

    Directory of Open Access Journals (Sweden)

    Ning Zhao

    Full Text Available BACKGROUND: Gestational zinc deficiency has been confirmed to impair the infant immune function. However, knowledge about effects of maternal mild zinc deficiency during pregnancy on hepatitis B vaccine responsiveness in offspring is limited. In this report, we aimed to examine how maternal zinc deficiency during pregnancy influences humoral and cellular immune responses to hepatitis B vaccination in offspring of BALB/c mice. METHODOLOGY/PRINCIPAL FINDINGS: From day 1 of pregnancy upon delivery, maternal mice were given a standard diet (30 mg/kg/day zinc, zinc deficient diet (8 mg/kg/day zinc, or combination of zinc deficient diet (8 mg/kg/day zinc in the first 2 weeks of gestation and zinc supplement diet (150 mg/kg/day zinc for the last week of pregnancy, respectively. Newborn pups of these maternal mice were immunized with hepatitis B vaccine at postnatal weeks 0, 2 and 4. Then, splenocytes and blood samples from the offspring mice were harvested for detection of serum zinc concentrations, humoral and cell-mediated immune responses, expression of cytokines using ELISA, CCK-8 and flow cytometric analysis. Results from the present study demonstrated that gestational zinc deficiency inhibited antibody responses, and decreased the proliferative capacity of T cells in offsprings immunized with hepatitis B vaccine. Additionally, HBsAg-specific cytokines analysis revealed that gestational zinc deficiency could inhibit secretion of IFN-γ from splenocytes, and decrease IFN-γ expression of CD4(+ and CD8(+ T cells. CONCLUSIONS/SIGNIFICANCE: Gestational zinc deficiency can weaken the humoral and cell-mediated immune responses to hepatitis B vaccine via decreasing B cell counts and hepatitis B virus-specific immunoglobulin G production, as well as reducing T cell proliferation, CD4(+/CD8(+ T cell ratio, and Th1-type immune responses.

  7. Differences in immune responses against Leishmania induced by infection and by immunization with killed parasite antigen: implications for vaccine discovery.

    Science.gov (United States)

    Mendonça, Sergio C F

    2016-01-01

    The leishmaniases are a group of diseases caused by different species of the protozoan genus Leishmania and transmitted by sand fly vectors. They are a major public health problem in almost all continents. There is no effective control of leishmaniasis and its geographical distribution is expanding in many countries. Great effort has been made by many scientists to develop a vaccine against leishmaniasis, but, so far, there is still no effective vaccine against the disease. The only way to generate protective immunity against leishmaniasis in humans is leishmanization, consisting of the inoculation of live virulent Leishmania as a means to acquire long-lasting immunity against subsequent infections. At present, all that we know about human immune responses to Leishmania induced by immunization with killed parasite antigens came from studies with first generation candidate vaccines (killed promastigote extracts). In the few occasions that the T cell-mediated immune responses to Leishmania induced by infection and immunization with killed parasite antigens were compared, important differences were found both in humans and in animals. This review discusses these differences and their relevance to the development of a vaccine against leishmaniasis, the major problems involved in this task, the recent prospects for the selection of candidate antigens and the use of attenuated Leishmania as live vaccines. PMID:27600664

  8. A palindromic CpG-containing phosphodiester oligodeoxynucleotide as a mucosal adjuvant stimulates plasmacytoid dendritic cell-mediated T(H1 immunity.

    Directory of Open Access Journals (Sweden)

    Jun-ichi Maeyama

    Full Text Available BACKGROUND: CpG oligodeoxynucleotides (ODNs, resembling bacterial DNA, are currently tested in clinical trials as vaccine adjuvants. They have the nuclease-resistant phosphorothioate bond; the immune responses elicited differ according to the CpG ODN sequence and vaccination method. To develop a CpG ODN that can induce plasmacytoid dendritic cell (pDC-mediated T(H1 immunity through the mucosa, we constructed phosphodiester G9.1 comprising one palindromic CpG motif with unique polyguanosine-runs that allows degradation similar to naturally occurring bacterial DNA. METHODS: T(H1 and T(H2 immunity activation was evaluated by cytokine production pattern and T-bet/GATA-3 ratio in human peripheral blood mononuclear cells and mouse bone marrow cells. Adjuvanticity was evaluated in mice administered G9.1 with diphtheria toxoid (DT through nasal vaccination. RESULTS: G9.1 exhibited stronger IFN-α-inducing activity than A-class CpG ODN2216 and increased T-bet/GATA-3 ratio by enhancing T-bet expression. Nasally administered G9.1 plus DT induced DT-specific mucosal IgA and serum IgG, but not IgE, responses with antitoxin activity in C57BL/6 and BALB/c mice, possibly due to IFN/BAFF production. Induction of T(H1, but not T(H2-type Abs depended completely on pDCs, the first in vivo demonstration by CpG ODNs. CONCLUSIONS: G9.1 is a promising mucosal adjuvant for induction of pDC-mediated T(H1 immunity.

  9. Priming B cell-mediated anti-HIV envelope responses by vaccination allows for the long-term control of infection in macaques exposed to a R5-tropic SHIV

    International Nuclear Information System (INIS)

    The potential of vaccine-elicited anti-HIV envelope antibodies to control HIV-infection was evaluated by immunizing macaques with the HIV envelope protein and transiently depleting them of their CD8+ cells before intravenous challenge with the pathogenic CCR5-tropic SIV/HIV chimeric virus, SHIVSF162P4. Although sterilizing immunity was not achieved, all vaccinated animals effectively controlled infection and remained free of disease for the duration of observation (over 3 years). In contrast, during the same period, the control animals progressed to disease. Both the vaccinees and the controls developed robust cell-mediated antiviral and neutralizing antibody responses following infection. A comparative analysis of these responses suggests that the more effective long-term control of infection by the vaccinated animals is due to the more rapid development of anti-HIV envelope antibodies. These studies suggest that priming by vaccination of B cell anti-HIV envelope responses maybe crucial for the long-term control of HIV infection

  10. Hypothalamic neurohormones and immune responses

    Science.gov (United States)

    Quintanar, J. Luis; Guzmán-Soto, Irene

    2013-01-01

    The aim of this review is to provide a comprehensive examination of the current literature describing the neural-immune interactions, with emphasis on the most recent findings of the effects of neurohormones on immune system. Particularly, the role of hypothalamic hormones such as Thyrotropin-releasing hormone (TRH), Corticotropin-releasing hormone (CRH) and Gonadotropin-releasing hormone (GnRH). In the past few years, interest has been raised in extrapituitary actions of these neurohormones due to their receptors have been found in many non-pituitary tissues. Also, the receptors are present in immune cells, suggesting an autocrine or paracrine role within the immune system. In general, these neurohormones have been reported to exert immunomodulatory effects on cell proliferation, immune mediators release and cell function. The implications of these findings in understanding the network of hypothalamic neuropeptides and immune system are discussed. PMID:23964208

  11. Immune response to Encephalitozoon cuniculi infection

    OpenAIRE

    Khan, Imtiaz A.; Moretto, Magali; Weiss, Louis M.

    2001-01-01

    Microsporidia are obligate intracellular parasites, which can cause complications in immunocompromised individuals. Very little is known about the host immune response generated against these infectious agents. Encephalitozoon cuniculi is the best studied microsporidian and the protective immune response against this parasite is mediated by cytotoxic CD8+ T cells.

  12. Differential effects of NOX4 and NOX1 on immune cell-mediated inflammation in the aortic sinus of diabetic ApoE-/- mice.

    Science.gov (United States)

    Di Marco, Elyse; Gray, Stephen P; Chew, Phyllis; Kennedy, Kit; Cooper, Mark E; Schmidt, Harald H H W; Jandeleit-Dahm, Karin A M

    2016-08-01

    Oxidative stress and inflammation are central mediators of atherosclerosis particularly in the context of diabetes. The potential interactions between the major producers of vascular reactive oxygen species (ROS), NADPH oxidase (NOX) enzymes and immune-inflammatory processes remain to be fully elucidated. In the present study we investigated the roles of the NADPH oxidase subunit isoforms, NOX4 and NOX1, in immune cell activation and recruitment to the aortic sinus atherosclerotic plaque in diabetic ApoE(-/-) mice. Plaque area analysis showed that NOX4- and NOX1-derived ROS contribute to atherosclerosis in the aortic sinus following 10 weeks of diabetes. Immunohistochemical staining of the plaques revealed that NOX4-derived ROS regulate T-cell recruitment. In addition, NOX4-deficient mice showed a reduction in activated CD4(+) T-cells in the draining lymph nodes of the aortic sinus coupled with reduced pro-inflammatory gene expression in the aortic sinus. Conversely, NOX1-derived ROS appeared to play a more important role in macrophage accumulation. These findings demonstrate distinct roles for NOX4 and NOX1 in immune-inflammatory responses that drive atherosclerosis in the aortic sinus of diabetic mice. PMID:27190136

  13. Micronutrients influencing the immune response in leprosy

    Directory of Open Access Journals (Sweden)

    Cecília Maria Passos Vázquez

    2014-01-01

    Full Text Available Leprosy is a chronic infectious disease caused by Mycobacterium leprae, an intracellular bacillus of airborne transmission. The disease affects the skin and peripheral nerves and can cause neurological sequelae. The bacillus multiplies slowly in the host and the disease probably occurs due to malfunctioning in host immune response. This review addresses the role of some specific micronutrients in the immune response, such as Vitamins A, D, E, C, Zinc and Selenium, detailing their mechanisms of actions in infectious diseases, and in leprosy. The immune response to pathogens releases harmful substances, which lead to tissue damage. This review discusses how a decreased level of antioxidants may contribute to an increased oxidative stress and complications of infectious diseases and leprosy. As the nutrients have a regulatory effect in the innate and adaptative immune responses, a perfect balance in their concentrations is important to improve the immune response against the pathogens.

  14. Cutaneous sensitivity induced by immunization with irradiated Schistosoma mansoni cercariae. I. Induction, elicitation, and adoptive transfer analysis of cell-mediated cutaneous sensitivity

    International Nuclear Information System (INIS)

    Exposure of C57BL/6 mice to highly irradiated (50 kR) cercariae of Schistosoma mansoni leads to the development of partial resistance against subsequent challenge with unattenuated cercariae. We have analyzed the cellular immune responses that occur during the afferent and efferent phases of this protective sensitization. Mice were immunized by exposure to irradiated S. mansoni cercariae. After challenge with irradiated cercariae, delayed-type (18-72 hr) cutaneous sensitivity reaction sites were rich in mononuclear cells and eosinophils. This reactivity was established by 4 days after sensitization, reached its maximum between 7 and 14 days after sensitization, and was maintained for over 20 weeks. These challenge reactions could be abrogated by treatment with either 200 mg/kg cyclophosphamide or 5 mg of hydrocortisone. Syngeneic adoptive transfer of cutaneous sensitivity was accomplished with lymphoid cells from the draining lymph nodes or spleens of mice sensitized 7-14 days previously. Negative selection studies of nylon-wool non-adherent cells from sensitized donors demonstrated that the cells responsible for transferring this eosinophil-rich, delayed-type cutaneous sensitivity to S. mansoni irradiated cercariae were Thy-1+, Lyt1+, Lyt2-, surface Ig- lymphocytes

  15. Cutaneous sensitivity induced by immunization with irradiated Schistosoma mansoni cercariae. I. Induction, elicitation, and adoptive transfer analysis of cell-mediated cutaneous sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Ch' ang, L.Y.; Colley, D.G.

    1986-06-01

    Exposure of C57BL/6 mice to highly irradiated (50 kR) cercariae of Schistosoma mansoni leads to the development of partial resistance against subsequent challenge with unattenuated cercariae. We have analyzed the cellular immune responses that occur during the afferent and efferent phases of this protective sensitization. Mice were immunized by exposure to irradiated S. mansoni cercariae. After challenge with irradiated cercariae, delayed-type (18-72 hr) cutaneous sensitivity reaction sites were rich in mononuclear cells and eosinophils. This reactivity was established by 4 days after sensitization, reached its maximum between 7 and 14 days after sensitization, and was maintained for over 20 weeks. These challenge reactions could be abrogated by treatment with either 200 mg/kg cyclophosphamide or 5 mg of hydrocortisone. Syngeneic adoptive transfer of cutaneous sensitivity was accomplished with lymphoid cells from the draining lymph nodes or spleens of mice sensitized 7-14 days previously. Negative selection studies of nylon-wool non-adherent cells from sensitized donors demonstrated that the cells responsible for transferring this eosinophil-rich, delayed-type cutaneous sensitivity to S. mansoni irradiated cercariae were Thy/sup -1 +/, Lyt/sup 1 +/, Lyt/sup 2 -/, surface Ig/sup -/ lymphocytes.

  16. Epigenetics and the Adaptive Immune Response

    OpenAIRE

    Kondilis-Mangum, Hrisavgi D.; Wade, Paul A.

    2012-01-01

    Cells of the adaptive immune response undergo dynamic epigenetic changes as they develop and respond to immune challenge. Plasticity is a necessary prerequisite for the chromosomal dynamics of lineage specification, development, and the immune effector function of the mature cell types. The alterations in DNA methylation and histone modification that characterize activation may be integral to the generation of immunologic memory, thereby providing an advantage on secondary exposure to pathoge...

  17. The immune response to surgery and infection

    OpenAIRE

    Dąbrowska, Aleksandra M.; Słotwiński, Robert

    2014-01-01

    Surgical trauma affects both the innate and acquired immunity. The severity of immune disorders is proportional to the extent of surgical trauma and depends on a number of factors, including primarily the basic disease requiring surgical treatment (e.g. cancer), often coexisting infections and impaired nutritional status. Disorder of the immune response following surgical trauma may predispose to septic complications burdened with the highest mortality rate. Extensive surgery in cancer patien...

  18. Immune responses of pigs immunized with a recombinant porcine reproductive and respiratory syndrome virus expressing porcine GM-CSF.

    Science.gov (United States)

    Li, Zhijun; Wang, Gang; Wang, Yan; Zhang, Chong; Huang, Baicheng; Li, Qiongyi; Li, Liangliang; Xue, Biyun; Ding, Peiyang; Cai, Xuehui; Wang, Chengbao; Zhou, En-Min

    2015-11-15

    Porcine reproductive and respiratory syndrome virus (PRRSV) has spread worldwide, causing huge economic losses to the swine industry. The current PRRSV vaccines have failed to provide broad protection against various strains. Granulocyte macrophage colony-stimulating factor (GM-CSF), an efficacious adjuvant, has been shown to enhance the immunogenicity of various vaccines. The purpose of this study was to construct a recombinant live attenuated PRRSV that expresses porcine GM-CSF (pGM-CSF) and evaluate the immune responses of pigs immunized with the recombinant virus. The results showed that the recombinant PRRSV was successfully rescued and had similar growth properties to parental virus grown in Marc-145 cells. The recombinant virus was stable for 10 passages in cell culture. Pigs intramuscularly immunized with the recombinant virus produced a similar humoral response to that elicited using parental virus. With regard to cell-mediated immunity assessed in peripheral blood, the recombinant virus induced higher proportion of CD4(+)CD8(+) double-positive T cells (DPT), higher IFN-γ level at 0 and 7 days post-challenge (DPC), and lower viremia at 21 DPC than pigs immunized with parental virus. These results indicate that recombinant PRRSV expressing pGM-CSF can induce a significant higher cellular immune response and reduce the persistent infection compared pigs vaccinated with the parental virus. This is first report of evaluation of immune response in pigs elicited by a recombinant live attenuated PRRSV expressing porcine GM-CSF. It may represent a novel strategy for future development of genetic engineered vaccines against PRRSV infection. PMID:26300317

  19. Innate immune responses to Pseudomonas aeruginosa infection

    OpenAIRE

    Lavoie, Elise G.; Wangdi, Tamding; Kazmierczak, Barbara I.

    2011-01-01

    Innate immune responses play a critical role in controlling acute infections due to Pseudomonas aeruginosa in both mice and in humans. In this review we focus on innate immune recognition and clearance mechanisms that are important for controlling P. aeruginosa in the mammalian lung, with particular attention to those that influence the outcome of in vivo infection in murine models.

  20. Soluble β-glucan from Grifola frondosa induces tumor regression in synergy with TLR9 agonist via dendritic cell-mediated immunity.

    Science.gov (United States)

    Masuda, Yuki; Nawa, Daiki; Nakayama, Yoshiaki; Konishi, Morichika; Nanba, Hiroaki

    2015-12-01

    The maturation of dendritic cells into more-immunostimulatory dendritic cells by stimulation with different combinations of immunologic agents is expected to provide efficient, adoptive immunotherapy against cancer. Soluble β-glucan maitake D-fraction, extracted from the maitake mushroom Grifola frondosa, acts as a potent immunotherapeutic agent, eliciting innate and adoptive immune responses, thereby contributing to its antitumor activity. Here, we evaluated the efficacy of maitake D-fraction, in combination with a Toll-like receptor agonist, to treat tumors in a murine model. Our results showed that maitake D-fraction, in combination with the Toll-like receptor 9 agonist, cytosine-phosphate-guanine oligodeoxynucleotide, synergistically increased the expression of dendritic cell maturation markers and interleukin-12 production in dendritic cells, but it did not increase interleukin-10 production, generating strong effector dendritic cells with an augmented capacity for efficiently priming an antigen-specific, T helper 1-type T cell response. Maitake D-fraction enhances cytosine-phosphate-guanine oligodeoxynucleotide-induced dendritic cell maturation and cytokine responses in a dectin-1-dependent pathway. We further showed that a combination therapy using cytosine-phosphate-guanine oligodeoxynucleotide and maitake D-fraction was highly effective, either as adjuvants for dendritic cell vaccination or by direct administration against murine tumor. Therapeutic responses to direct administration were associated with increased CD11c(+) dendritic cells in the tumor site and the induction of interferon-γ-producing CD4(+) and CD8(+) T cells. Our results indicate that maitake D-fraction and cytosine-phosphate-guanine oligodeoxynucleotide synergistically activated dendritic cells, resulting in tumor regression via an antitumor T helper cell 1-type response. Our findings provide the basis for a potent antitumor therapy using a novel combination of immunologic agents for

  1. Innate immune cell response upon Candida albicans infection.

    Science.gov (United States)

    Qin, Yulin; Zhang, Lulu; Xu, Zheng; Zhang, Jinyu; Jiang, Yuan-Ying; Cao, Yongbing; Yan, Tianhua

    2016-07-01

    Candida albicans is a polymorphic fungus which is the predominant cause of superficial and deep tissue fungal infections. This microorganism has developed efficient strategies to invade the host and evade host defense systems. However, the host immune system will be prepared for defense against the microbe by recognition of receptors, activation of signal transduction pathways and cooperation of immune cells. As a consequence, C. albicans could either be eliminated by immune cells rapidly or disseminate hematogenously, leading to life-threatening systemic infections. The interplay between Candida albicans and the host is complex, requiring recognition of the invaded pathogens, activation of intricate pathways and collaboration of various immune cells. In this review, we will focus on the effects of innate immunity that emphasize the first line protection of host defense against invaded C. albicans including the basis of receptor-mediated recognition and the mechanisms of cell-mediated immunity. PMID:27078171

  2. Exosomes in the Immune Response and Tolerance

    Institute of Scientific and Technical Information of China (English)

    修方明; 曹雪涛

    2004-01-01

    Exosomes, secreted by many live cells, are small non-cell vesicles with nanoparticle-grade size. In addition to the original function of discarding the uselessful membrane molecules, exosomes are involved in a range of immunoregulatory functions. Dendritic cell-derived exosomes and tumor-derived exosomes are the best characterized vesicles with potent antitumor effect by efficienfly inducing immune response. Down-regtdation of immune response or induction of immune tolerance is another interesting function of exosomes, Further functional studies of the exosomes will shed light on the application of exosomes。

  3. Dietary supplementation of mannan-oligosaccharide enhances neonatal immune responses in chickens during natural exposure to Eimeria spp

    Directory of Open Access Journals (Sweden)

    Nava Gerardo M

    2009-03-01

    Full Text Available Abstract Background Control and eradication of intestinal infections caused by protozoa are important biomedical challenges worldwide. Prophylactic control of coccidiosis has been achieved with the use of anticoccidial drugs; however, the increase in anticoccidial resistance has raised concerns about the need for new alternatives for the control of coccidial infections. In fact, new strategies are needed to induce potent protective immune responses in neonatal individuals. Methods The effects of a dietary supplementation of mannan-oligosaccharide (yeast cell wall; YCW on the local, humoral and cell-mediated immune responses, and intestinal replication of coccidia were evaluated in a neonatal animal model during natural exposure to Eimeria spp. A total of 840 one-day-old chicks were distributed among four dietary regimens: A Control diet (no YCW plus anticoccidial vaccine; B Control diet plus coccidiostat; C YCW diet plus anticoccidial vaccination; and D YCW diet plus coccidiostat. Weight gain, feed consumption and immunological parameters were examined within the first seven weeks of life. Results Dietary supplementation of 0.05% of YCW increased local mucosal IgA secretions, humoral and cell-mediated immune responses, and reduced parasite excretion in feces. Conclusion Dietary supplementation of yeast cell wall in neonatal animals can enhance the immune response against coccidial infections. The present study reveals the potential of YCW as adjuvant for modulating mucosal immune responses.

  4. Immune Response to Giardia duodenalis

    OpenAIRE

    Faubert, Gaétan

    2000-01-01

    The intestinal protozoan Giardia duodenalis is a widespread opportunistic parasite of humans and animals. This parasite inhabits the upper part of the small intestine and has a direct life cycle. After ingestion of cysts, which are the infective stage, the trophozoites emerge from the cysts in the duodenum and attach to the small intestinal mucosa of the host. Since the migration of trophozoites from the lumen of the intestine into surrounding tissues is an unusual occurrence, the immune resp...

  5. Differential immune responses to albumin adducts of reactive intermediates of trichloroethene in MRL+/+ mice

    International Nuclear Information System (INIS)

    Trichloroethene (TCE) is an industrial degreasing solvent and widespread environmental contaminant. Exposure to TCE is associated with autoimmunity. The mode of action of TCE is via its oxidative metabolism, and most likely, immunotoxicity is mediated via haptenization of macromolecules and subsequent induction of immune responses. To better understand the role of protein haptenization through TCE metabolism, we immunized MRL+/+ mice with albumin adducts of various TCE reactive intermediates. Serum immunoglobulins and cytokine levels were measured to determine immune responses against haptenized albumin. We found antigen-specific IgG responses of the IgG subtypes IgG1, IgG2a, and IgG2b, with IgG1 predominating. Serum levels of G-CSF were increased in immunized mice, suggesting macrophage activation. Liver histology revealed lymphocyte infiltration in the lobules and the portal area following immunization with formyl-albumin. Our findings suggest that proteins haptenized by metabolites of TCE may act as neo-antigens that can induce humoral immune responses and T cell-mediated hepatitis

  6. A cascade reaction network mimicking the basic functional steps of adaptive immune response

    Science.gov (United States)

    Han, Da; Wu, Cuichen; You, Mingxu; Zhang, Tao; Wan, Shuo; Chen, Tao; Qiu, Liping; Zheng, Zheng; Liang, Hao; Tan, Weihong

    2015-10-01

    Biological systems use complex ‘information-processing cores’ composed of molecular networks to coordinate their external environment and internal states. An example of this is the acquired, or adaptive, immune system (AIS), which is composed of both humoral and cell-mediated components. Here we report the step-by-step construction of a prototype mimic of the AIS that we call an adaptive immune response simulator (AIRS). DNA and enzymes are used as simple artificial analogues of the components of the AIS to create a system that responds to specific molecular stimuli in vitro. We show that this network of reactions can function in a manner that is superficially similar to the most basic responses of the vertebrate AIS, including reaction sequences that mimic both humoral and cellular responses. As such, AIRS provides guidelines for the design and engineering of artificial reaction networks and molecular devices.

  7. Modulating immune responses with probiotic bacteria.

    Science.gov (United States)

    Matsuzaki, T; Chin, J

    2000-02-01

    For many years, probiotic bacteria have been known to confer health benefits to the consumer. One possible mechanism for this may be the ability of probiotic bacteria to modulate immune responses. Oral administration of Lactobacillus casei strain Shirota (LcS) has been found to enhance innate immunity by stimulating the activity of splenic NK cells. Oral feeding with killed LcS was able to stimulate the production of Th1 cytokines, resulting in repressed production of IgE antibodies against Ovalbumin in experimental mice. The ability to switch mucosal immune responses towards Th1 with probiotic bacteria provides a strategy for treatment of allergic disorders. Growth of Meth A tumour cells in the lungs was also inhibited by intrapleural injection of LcS. Oral administration of other probiotic bacteria, such as Streptococcus thermophilus (St), Lactobacillus fermentum (Lf) and yeast (Y), elicited different immune responses. Mice that were prefed yeast or Lf followed by feeding with ovalbumin (OVA) responded better to vaccination with OVA than mice not given either probiotic or OVA or mice that had been prefed only OVA. However, antibody responses were significantly suppressed in response to vaccination with OVA in mice that had been prefed yeast followed by yeast and OVA as well as mice prefed Lf followed by Lf and OVA. Prefeeding St followed by OVA feeding enhanced cellular immune responses against ovalbumin. In contrast, mice prefed St followed by St + OVA were hyporesponsive against OVA. While antigen feeding alone appears to prime for an immune response, cofeeding antigen with probiotic bacteria can suppress both antibody and cellular immune responses and may provide an efficacious protocol to attenuate autoimmune diseases, such as experimental allergic encephalomyelitis, by jointly dosing with myelin basic protein and probiotic bacteria. PMID:10651931

  8. Plasticity of immunity in response to eating.

    Science.gov (United States)

    Luoma, Rachel L; Butler, Michael W; Stahlschmidt, Zachary R

    2016-07-01

    Following a meal, an animal can exhibit dramatic shifts in physiology and morphology, as well as a substantial increase in metabolic rate associated with the energetic costs of processing a meal (i.e. specific dynamic action, SDA). However, little is known about the effects of digestion on another important physiological and energetically costly trait: immune function. Thus, we tested two competing hypotheses. (1) Digesting animals up-regulate their immune systems (putatively in response to the increased microbial exposure associated with ingested food). (2) Digesting animals down-regulate their immune systems (presumably to allocate energy to the breakdown of food). We assayed innate immunity (lytic capacity and agglutination) in cornsnakes (Pantherophis guttatus) during and after meal digestion. Lytic capacity was higher in females, and (in support of our first hypothesis) agglutination was higher during absorption. Given its potential energetic cost, immune up-regulation may contribute to SDA. PMID:27099367

  9. Nizatidine, a small molecular compound, enhances killed H5N1 vaccine cell-mediated responses and protects mice from lethal viral challenge

    OpenAIRE

    Wang, Shuang; Wu, Bing; Xue, Jia; Wang, Ming; Chen, Ruiai; Wang, Bin

    2013-01-01

    Nizatidine (NIZ), closely related to Cimetidine, is a histamine H2 receptor inverse agonist used primarily as an anti-acid drug. Recent studies showed that this class of compounds may also modulate immune responses. To evaluate adjuvant effects of NIZ on vaccine immune modulation, we formulated NIZ with a H5N1 killed viral antigen and tested in vitro and in vivo. NIZ activated DC maturation and stimulated Th1 and Th2 immune responses to H5N1 vaccine. As a result, it enhanced both antibody and...

  10. Biochemical and Functional Insights into the Integrated Regulation of Innate Immune Cell Responses by Teleost Leukocyte Immune-Type Receptors

    Directory of Open Access Journals (Sweden)

    Chenjie Fei

    2016-03-01

    Full Text Available Across vertebrates, innate immunity consists of a complex assortment of highly specialized cells capable of unleashing potent effector responses designed to destroy or mitigate foreign pathogens. The execution of various innate cellular behaviors such as phagocytosis, degranulation, or cell-mediated cytotoxicity are functionally indistinguishable when being performed by immune cells isolated from humans or teleost fishes; vertebrates that diverged from one another more than 450 million years ago. This suggests that vital components of the vertebrate innate defense machinery are conserved and investigating such processes in a range of model systems provides an important opportunity to identify fundamental features of vertebrate immunity. One characteristic that is highly conserved across vertebrate systems is that cellular immune responses are dependent on specialized immunoregulatory receptors that sense environmental stimuli and initiate intracellular cascades that can elicit appropriate effector responses. A wide variety of immunoregulatory receptor families have been extensively studied in mammals, and many have been identified as cell- and function-specific regulators of a range of innate responses. Although much less is known in fish, the growing database of genomic information has recently allowed for the identification of several immunoregulatory receptor gene families in teleosts. Many of these putative immunoregulatory receptors have yet to be assigned any specific role(s, and much of what is known has been based solely on structural and/or phylogenetic relationships with mammalian receptor families. As an attempt to address some of these shortcomings, this review will focus on our growing understanding of the functional roles played by specific members of the channel catfish (Ictalurus punctatus leukocyte immune-type receptors (IpLITRs, which appear to be important regulators of several innate cellular responses via classical as well

  11. Long-term moderate calorie restriction inhibits inflammation without impairing cell-mediated immunity: a randomized controlled trial in non obese humans

    Science.gov (United States)

    Calorie restriction (CR) inhibits inflammation and slows aging in many animal species, but in rodents housed in pathogen-free facilities, CR impairs immunity against certain pathogens. However, little is known about the effects of long-term moderate CR on immune function in humans. In this multi-cen...

  12. Effect of cellular mobility on immune response

    Science.gov (United States)

    Pandey, R. B.; Mannion, R.; Ruskin, H. J.

    2000-08-01

    Mobility of cell types in our HIV immune response model is subject to an intrinsic mobility and an explicit directed mobility, which is governed by Pmob. We investigate how restricting the explicit mobility, while maintaining the innate mobility of a viral-infected cell, affects the model's results. We find that increasing the explicit mobility of the immune system cells leads to viral dominance for certain levels of viral mutation. We conclude that increasing immune system cellular mobility indirectly increases the virus’ inherent mobility.

  13. The immune responses of the coral

    OpenAIRE

    C Toledo-Hernández; CP Ruiz-Diaz

    2014-01-01

    Corals are among the most ancient extant animals on earth. Currently, coral viability is threatened, due in part to the increased number of diseases affecting them in recent decades. Understanding how the innate immune systems of corals function is important if we want to predict the fate of corals and their response to the environmental and biological changes they face. In this review we discuss the latest findings regarding the innate immune systems of corals. The review is organized follow...

  14. Role of levamisole immunotherapy as an adjuvant to radiotherapy in oral cancer - Immune responses

    International Nuclear Information System (INIS)

    Investigations were carried out to assess the effect of levamisole immunotherapy as an adjuvant to radiotherapy, on the immune response of patients with squamous cell carcinoma of the oral cavity. Parameters assessed were leukocyte migration inhibition, response to PPD and oral cancer extract (OCA), lymphocyte transformation to PHA, circulating antibodies to OCA and circulating immune complexes (CIC). Comparisons were made between groups receiving levamisole, those receiving placebo and normal controls. The results of a thirty-month follow-up are presented. Radiotherapy resulted in a depression of cell-mediated functions, reduction in antibody titre also showed a gradual increase with time of follow-up. Levamisole, however, appeared to reduce the levels of CIC. (author). 2 figs., 1 tab., 38 refs

  15. Immune response of mice and sheep to bluetongue virus inactivated by gamma irradiation

    International Nuclear Information System (INIS)

    Gamma irradiation is being tested as a means of inactivating bluetongue virus (BTV) for use in vaccines. Exposure of BTV 17 to various levels of irradiation revealed that a dose of approximately 0.6 megarad was required to reduce the virus titer by one log10, or 90%. To test the immunogenicity of irradiated BTV, mouse brain passaged virus and concentrated cell culture passaged virus were inactivated by 6 megarads of gamma irradiation, and vaccines were prepared by emulsifying the virus preparations in equal volumes of a modified incomplete Freund's adjuvant. These vaccines stimulated the production of neutralizing antibodies in mice and sheep, a cell mediated immune response in mice, and a protective immune response in sheep. The results suggest that gamma irradiation would be an effective means of inactivating BTV for the preparation of vaccines

  16. Lentiviral vector encoding ubiquitinated hepatitis B core antigen induces potent cellular immune responses and therapeutic immunity in HBV transgenic mice.

    Science.gov (United States)

    Dai, Shenglan; Zhuo, Meng; Song, Linlin; Chen, Xiaohua; Yu, Yongsheng; Zang, Guoqing; Tang, Zhenghao

    2016-07-01

    Predominant T helper cell type 1 (Th1) immune responses accompanied by boosted HBV-specific cytotoxic T lymphocyte (CTL) activity are essential for the clearance of hepatitis B virus (HBV) in chronic hepatitis B (CHB) patients. Ubiquitin (Ub) serves as a signal for the target protein to be recognized and degraded through the ubiquitin-proteasome system (UPS). Ubiquitinated hepatitis B core antigen (Ub-HBcAg) has been proved to be efficiently degraded into the peptides, which can be presented by major histocompatibility complex (MHC) class I resulting in stimulating cell-mediated responses. In the present study, lentiviral vectors encoding Ub-HBcAg (LV-Ub-HBcAg) were designed and constructed as a therapeutic vaccine for immunotherapy. HBcAg-specific cellular immune responses and anti-viral effects induced by LV-Ub-HBcAg were evaluated in HBV transgenic mice. We demonstrated that immunization with LV-Ub-HBcAg promoted the secretion of cytokines interleukin-2 (IL-2), interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α), generated remarkably high percentages of IFN-γ-secreting CD8(+) T cells and CD4(+) T cells, and enhanced HBcAg-specific CTL activity in HBV transgenic mice. More importantly, vaccination with LV-Ub-HBcAg could efficiently decreased the levels of serum hepatitis B surface antigen (HBsAg), HBV DNA and the expression of HBsAg and HBcAg in liver tissues of HBV transgenic mice. In addition, LV-Ub-HBcAg could upregulate the expression of T cell-specific T-box transcription factor (T-bet) and downregulate the expression of GATA-binding protein 3 (GATA-3) in spleen T lymphocytes. The therapeutic vaccine LV-Ub-HBcAg could break immune tolerance, and induce potent HBcAg specific cellular immune responses and therapeutic effects in HBV transgenic mice. PMID:26874581

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

    Directory of Open Access Journals (Sweden)

    Selvakumar Subbian

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

  18. Successful Therapy of Murine Visceral Leishmaniasis with Astrakurkurone, a Triterpene Isolated from the Mushroom Astraeus hygrometricus, Involves the Induction of Protective Cell-Mediated Immunity and TLR9.

    Science.gov (United States)

    Mallick, Suvadip; Dutta, Aritri; Chaudhuri, Ankur; Mukherjee, Debasri; Dey, Somaditya; Halder, Subhadra; Ghosh, Joydip; Mukherjee, Debarati; Sultana, Sirin Salma; Biswas, Gunjan; Lai, Tapan Kumar; Patra, Pradyumna; Sarkar, Indranil; Chakraborty, Sibani; Saha, Bhaskar; Acharya, Krishnendu; Pal, Chiranjib

    2016-05-01

    In our previous report, we showed that astrakurkurone, a triterpene isolated from the Indian mushroom Astraeus hygrometricus (Pers.) Morgan, induced reactive oxygen species, leading to apoptosis in Leishmania donovani promastigotes, and also was effective in inhibiting intracellular amastigotes at the 50% inhibitory concentration of 2.5 μg/ml. The aim of the present study is to characterize the associated immunomodulatory potentials and cellular activation provided by astrakurkurone, leading to effective antileishmanial activity in vitro and in vivo Astrakurkurone-mediated antileishmanial activity was evaluated by real-time PCR and flow cytometry. The involvement of Toll-like receptor 9 (TLR9) was studied by in vitro assay in the presence of a TLR9 agonist and antagonist and by in silico modeling of a three-dimensional structure of the ectodomain of TLR9 and its interaction with astrakurkurone. Astrakurkurone caused a significant increase in TLR9 expression of L. donovani-infected macrophages along with the activation of proinflammatory responses. The involvement of TLR9 in astrakurkurone-mediated amastigote killing has been evidenced from the fact that a TLR9 agonist (CpG, ODN 1826) in combination with astrakurkurone enhanced the amastigote killing, while a TLR9 antagonist (bafilomycin A1) alone or in combination with astrakurkurone curbed the amastigote killing, which could be further justified by in silico evidence of docking between mouse TLR9 and astrakurkurone. Astrakurkurone was found to reduce the parasite burden in vivo by inducing protective cytokines, gamma interferon and interleukin 17. Moreover, astrakurkurone was nontoxic toward peripheral blood mononuclear cells of immunocompromised patients with visceral leishmaniasis. Astrakurkurone, a nontoxic antileishmanial, enhances the immune efficiency of host cells, leading to parasite clearance in vitro and in vivo. PMID:26883702

  19. One dose of a porcine circovirus 2 subunit vaccine induces humoral and cell-mediated immunity and protects against porcine circovirus-associated disease under field conditions.

    Science.gov (United States)

    Martelli, Paolo; Ferrari, Luca; Morganti, Marina; De Angelis, Elena; Bonilauri, Paolo; Guazzetti, Stefano; Caleffi, Antonio; Borghetti, Paolo

    2011-05-01

    This study investigated the efficacy of a one-dose porcine circovirus 2 (PCV2) subunit vaccine based on the PCV2 Cap protein expressed in a baculovirus system on two different farms at which a history of porcine circovirus-associated disease (PCVD) was present. Morbidity, mortality, average daily weight gain, carcass weight, PCV2 load in serum and vaccine immunogenicity were assessed. Serology to porcine reproductive and respiratory syndrome virus (PRRSV) and Mycoplasma hyopneumoniae was performed. A double-blind, randomised, and controlled field trial was performed distributing 818 piglets between two treatment groups. At inclusion (weaning at 21 ± 3 days of age), 408 animals (group B) received a 2-mL intramuscular dose of Porcilis PCV(®) (vaccinated group). Controls (group A, 410 pigs) received 2 mL of the adjuvant Diluvac Forte(®) intramuscularly. Weights were recorded at inclusion and at 12 and 26 weeks of age, and the average daily weight gain (ADWG) was calculated. The carcass weights of the pigs from farm 2 were recorded at slaughter (274 days old). All dead animals (died or culled) underwent autopsy to classify them as PMWS-affected or not. At each farm, blood samples were taken from 22 pigs/group for serologic studies. A beneficial effect was found after vaccination with a single dose of a PCV2 Cap vaccine against PCVD. The vaccination reduced the mortality rate and morbidity, reduced PCV2 viremia and viral load, improved productive performances (e.g. ADWG: +70 g/day between 12 and 26 weeks of age when viremia and the specific disease occurred) as well as carcass weight at slaughter age (+4.5 kg). These effects were associated with virologic and clinical protection from the immunogenicity of the vaccine measured as activation of both a humoral and a cellular immune response. PMID:21216540

  20. The immune responses of the coral

    Directory of Open Access Journals (Sweden)

    C Toledo-Hernández

    2014-11-01

    Full Text Available Corals are among the most ancient extant animals on earth. Currently, coral viability is threatened, due in part to the increased number of diseases affecting them in recent decades. Understanding how the innate immune systems of corals function is important if we want to predict the fate of corals and their response to the environmental and biological changes they face. In this review we discuss the latest findings regarding the innate immune systems of corals. The review is organized following the chronology of steps taken by corals from the initial encounter with a potential pathogen and recognition of threats to the orchestration of a response. We begin with the literature describing the repertory of immune-related receptors involved in the recognition of threats and the subsequent pathways leading to an immune response. We then review the effector responses that eliminate the threats described for corals. Finally, we acknowledge the literature of coral microbiology to access the potential role of microbes as an essential constituent of the coral immune system.

  1. Immune Response to Ebola Virus Infection

    Directory of Open Access Journals (Sweden)

    Alain Alonso Remedios

    2016-06-01

    Full Text Available Ebola virus belongs to the family Filoviridae and causes a highly lethal hemorrhagic fever. Affected patients show an impaired immune response as a result of the evasion mechanisms employed by the virus. Cathepsin is an enzyme present in the granules of phagocytes which cleaves viral surface glycoproteins, allowing virus entry into the host cell. In addition, this virus is resistant to the antiviral effects of type I interferon, promotes the synthesis of proinflammatory cytokines and induces apoptosis of monocytes and lymphocytes. It also induces an incomplete activation of dendritic cells, thus avoiding the presentation of viral antigens. Although specific antibodies are produced after the first week, their neutralizing capacity is doubtful. The virus evades the immune response and replicates uncontrollably in the host. This paper aims to summarize the main characteristics of the immune response to Ebola virus infection.

  2. Antimicrobial peptides in innate immune responses

    DEFF Research Database (Denmark)

    Sorensen, O.E.; Borregaard, N.; Cole, A.M.

    2008-01-01

    novo synthesis or by proteolytic cleavage from antimicrobially inactive proproteins. Studies of human diseases and animal studies have given important clues to the in vivo role of AMPs. It is now evident that dysregulation of the generation of AMPs in innate immune responses plays a role in certain......Antimicrobial peptides (AMPs) are ancient effector molecules in the innate immune response of eukaryotes. These peptides are important for the antimicrobial efficacy of phagocytes and for the innate immune response mounted by epithelia of humans and other mammals. AMPs are generated either by de...... diseases like Crohn's disease and atopic dermatitis. AMPs are attractive candidates for development of novel antibiotics due to their in vivo activity profile and some peptides may serve as templates for further drug development Udgivelsesdato: 2008...

  3. Injury-induced immune responses in Hydra.

    Science.gov (United States)

    Wenger, Yvan; Buzgariu, Wanda; Reiter, Silke; Galliot, Brigitte

    2014-08-01

    The impact of injury-induced immune responses on animal regenerative processes is highly variable, positive or negative depending on the context. This likely reflects the complexity of the innate immune system that behaves as a sentinel in the transition from injury to regeneration. Early-branching invertebrates with high regenerative potential as Hydra provide a unique framework to dissect how injury-induced immune responses impact regeneration. A series of early cellular events likely require an efficient immune response after amputation, as antimicrobial defence, epithelial cell stretching for wound closure, migration of interstitial progenitors toward the wound, cell death, phagocytosis of cell debris, or reconstruction of the extracellular matrix. The analysis of the injury-induced transcriptomic modulations of 2636 genes annotated as immune genes in Hydra identified 43 genes showing an immediate/early pulse regulation in all regenerative contexts examined. These regulations point to an enhanced cytoprotection via ROS signaling (Nrf, C/EBP, p62/SQSMT1-l2), TNFR and TLR signaling (TNFR16-like, TRAF2l, TRAF5l, jun, fos-related, SIK2, ATF1/CREB, LRRC28, LRRC40, LRRK2), proteasomal activity (p62/SQSMT1-l1, Ced6/Gulf, NEDD8-conjugating enzyme Ubc12), stress proteins (CRYAB1, CRYAB2, HSP16.2, DnaJB9, HSP90a1), all potentially regulating NF-κB activity. Other genes encoding immune-annotated proteins such as NPYR4, GTPases, Swap70, the antiproliferative BTG1, enzymes involved in lipid metabolism (5-lipoxygenase, ACSF4), secreted clotting factors, secreted peptidases are also pulse regulated upon bisection. By contrast, metalloproteinases and antimicrobial peptide genes largely follow a context-dependent regulation, whereas the protease inhibitor α2macroglobulin gene exhibits a sustained up-regulation. Hence a complex immune response to injury is linked to wound healing and regeneration in Hydra. PMID:25086685

  4. Optically Triggered Immune Response through Photocaged Oligonucleotides

    Science.gov (United States)

    Govan, Jeane M.; Young, Douglas D.; Lively, Mark O.

    2015-01-01

    Bacterial and viral CpG oligonculeotides are unmethylated cytosine-phosphate-guanosine dinucleotide sequences and trigger an innate immune response through activation of the toll-like receptor 9 (TLR9). We have developed synthetic photocaged CpGs via site-specific incorporation of nitropiperonyloxymethyl (NPOM)-caged thymidine residues. These oligonucleotides enable the optical control of TLR9 function and thereby provide light-activation of an immune response. We provide a proof-of-concept model by applying a reporter assay in live cells and by quantification of endogenous production of interleukin 6. PMID:26034339

  5. Immune response from a resource allocation perspective

    Directory of Open Access Journals (Sweden)

    Wendy Mercedes Rauw

    2012-12-01

    Full Text Available The immune system is a life history trait that can be expected to trade off against other life history traits. Whether or not a trait is considered to be a life history trait has consequences for the expectation on how it responds to natural selection and evolution; in addition, it may have consequences for the outcome of artificial selection when included in the breeding objective. The immune system involved in pathogen resistance comprises multiple mechanisms that define a host’s defensive capacity. Immune resistance involves employing mechanisms that either prevent pathogens from invading or eliminate the pathogens when they do invade. On the other hand, tolerance involves limiting the damage that is caused by the infection. Both tolerance and resistance traits require (reallocation of resources and carry physiological costs. Examples of trade-offs between immune function and growth, reproduction and stress response are provided in this review, in addition to consequences of selection for increased production on immune function and vice versa. Reaction norms are used to deal with questions of immune resistance versus tolerance to pathogens that relate host health to infection intensity. In essence, selection for immune tolerance in livestock is a particular case of selection for animal robustness. Since breeding goals that include robustness traits are required in the implementation of more sustainable agricultural production systems, it is of interest to investigate whether immune tolerance is a robustness trait that is positively correlated with overall animal robustness. Considerably more research is needed to estimate the shapes of the cost functions of different immune strategies, and investigate trade-offs and cross-over benefits of selection for disease resistance and/or disease tolerance in livestock production.

  6. MicroRNA-155 drives TH17 immune response and tissue injury in experimental crescentic GN.

    Science.gov (United States)

    Krebs, Christian F; Kapffer, Sonja; Paust, Hans-Joachim; Schmidt, Tilman; Bennstein, Sabrina B; Peters, Anett; Stege, Gesa; Brix, Silke R; Meyer-Schwesinger, Catherine; Müller, Roman-Ulrich; Turner, Jan-Eric; Steinmetz, Oliver M; Wolf, Gunter; Stahl, Rolf A K; Panzer, Ulf

    2013-12-01

    CD4(+) T cells play a pivotal role in the pathogenesis of autoimmune disease, including human and experimental crescentic GN. Micro-RNAs (miRs) have emerged as important regulators of immune cell development, but the impact of miRs on the regulation of the CD4(+) T cell immune response remains to be fully clarified. Here, we report that miR-155 expression is upregulated in the kidneys of patients with ANCA-associated crescentic GN and a murine model of crescentic GN (nephrotoxic nephritis). To elucidate the potential role of miR-155 in T cell-mediated inflammation, nephritis was induced in miR-155(-/-) and wild-type mice. The systemic and renal nephritogenic TH17 immune response decreased markedly in nephritic miR-155(-/-) mice. Consistent with this finding, miR-155-deficient mice developed less severe nephritis, with reduced histologic and functional injury. Adoptive transfer of miR-155(-/-) and wild-type CD4(+) T cells into nephritic recombination activating gene 1-deficient (Rag-1(-/-)) mice showed the T cell-intrinsic importance of miR-155 for the stability of pathogenic TH17 immunity. These findings indicate that miR-155 drives the TH17 immune response and tissue injury in experimental crescentic GN and show that miR-155 is a potential therapeutic target in TH17-mediated diseases. PMID:23949802

  7. MicroRNA-155 Drives TH17 Immune Response and Tissue Injury in Experimental Crescentic GN

    Science.gov (United States)

    Krebs, Christian F.; Kapffer, Sonja; Paust, Hans-Joachim; Schmidt, Tilman; Bennstein, Sabrina B.; Peters, Anett; Stege, Gesa; Brix, Silke R.; Meyer-Schwesinger, Catherine; Müller, Roman-Ulrich; Turner, Jan-Eric; Steinmetz, Oliver M.; Wolf, Gunter; Stahl, Rolf A. K.

    2013-01-01

    CD4+ T cells play a pivotal role in the pathogenesis of autoimmune disease, including human and experimental crescentic GN. Micro-RNAs (miRs) have emerged as important regulators of immune cell development, but the impact of miRs on the regulation of the CD4+ T cell immune response remains to be fully clarified. Here, we report that miR-155 expression is upregulated in the kidneys of patients with ANCA-associated crescentic GN and a murine model of crescentic GN (nephrotoxic nephritis). To elucidate the potential role of miR-155 in T cell-mediated inflammation, nephritis was induced in miR-155−/− and wild-type mice. The systemic and renal nephritogenic TH17 immune response decreased markedly in nephritic miR-155−/− mice. Consistent with this finding, miR-155–deficient mice developed less severe nephritis, with reduced histologic and functional injury. Adoptive transfer of miR-155−/− and wild-type CD4+ T cells into nephritic recombination activating gene 1-deficient (Rag-1−/−) mice showed the T cell-intrinsic importance of miR-155 for the stability of pathogenic TH17 immunity. These findings indicate that miR-155 drives the TH17 immune response and tissue injury in experimental crescentic GN and show that miR-155 is a potential therapeutic target in TH17-mediated diseases. PMID:23949802

  8. Enhancing Immune Responses for Cancer Therapy

    Institute of Scientific and Technical Information of China (English)

    Shao-An Xue; Hans J Stauss

    2007-01-01

    Although the immune system possesses the means to respond to cancer, it often fails to control the spread of malignancy. Nonetheless, equipping endogenous immunity to release a strong antitumor response has significant advantages over conventional therapies. This review explores some of the options available to accomplish this,focusing first on vaccinations with tumor antigens to stimulate the immune system and empower stronger antitumor responses. We then compare and contrast the so-far limited clinical success of vaccination with the well-documented curative potential of adoptive therapy using T lymphocytes transfer. Finally, we highlight novel approaches using T cell receptor (TCR) gene transfer strategy to exploit allogeneic T cell repertoires in conjunction with receptors selected in vitro for defined MHC/peptide combinations, as a basis for antigen-specific gene therapy of cancers.

  9. A nonhuman primate scrub typhus model: protective immune responses induced by pKarp47 DNA vaccination in cynomolgus macaques.

    Science.gov (United States)

    Paris, Daniel H; Chattopadhyay, Suchismita; Jiang, Ju; Nawtaisong, Pruksa; Lee, John S; Tan, Esterlina; Dela Cruz, Eduardo; Burgos, Jasmin; Abalos, Rodolfo; Blacksell, Stuart D; Lombardini, Eric; Turner, Gareth D; Day, Nicholas P J; Richards, Allen L

    2015-02-15

    We developed an intradermal (ID) challenge cynomolgus macaque (Macaca fascicularis) model of scrub typhus, the leading cause of treatable undifferentiated febrile illness in tropical Asia, caused by the obligate intracellular bacterium, Orientia tsutsugamushi. A well-characterized animal model is required for the development of clinically relevant diagnostic assays and evaluation of therapeutic agents and candidate vaccines. We investigated scrub typhus disease pathophysiology and evaluated two O. tsutsugamushi 47-kDa, Ag-based candidate vaccines, a DNA plasmid vaccine (pKarp47), and a virus-vectored vaccine (Kp47/47-Venezuelan equine encephalitis virus replicon particle) for safety, immunogenicity, and efficacy against homologous ID challenge with O. tsutsugamushi Karp. Control cynomolgus macaques developed fever, classic eschars, lymphadenopathy, bacteremia, altered liver function, increased WBC counts, pathogen-specific Ab (IgM and IgG), and cell-mediated immune responses. Vaccinated macaques receiving the DNA plasmid pKarp47 vaccine had significantly increased O. tsutsugamushi-specific, IFN-γ-producing PBMCs (p = 0.04), reduced eschar frequency and bacteremia duration (p ≤ 0.01), delayed bacteremia onset (p < 0.05), reduced circulating bacterial biomass (p = 0.01), and greater reduction of liver transaminase levels (p < 0.03) than controls. This study demonstrates a vaccine-induced immune response capable of conferring sterile immunity against high-dose homologous ID challenge of O. tsutsugamushi in a nonhuman primate model, and it provides insight into cell-mediated immune control of O. tsutsugamushi and dissemination dynamics, highlights the importance of bacteremia indices for evaluation of both natural and vaccine-induced immune responses, and importantly, to our knowledge, has determined the first phenotypic correlates of immune protection in scrub typhus. We conclude that this model is suitable for detailed investigations into vaccine-induced immune

  10. Immune Response in Mussels To Environmental Pollution.

    Science.gov (United States)

    Pryor, Stephen C.; Facher, Evan

    1997-01-01

    Describes the use of mussels in measuring the extent of chemical contamination and its variation in different coastal regions. Presents an experiment to introduce students to immune response and the effects of environmental pollution on marine organisms. Contains 14 references. (JRH)

  11. Anti-CD40 antibody and toll-like receptor 3 ligand restore dendritic cell-mediated anti-tumor immunity suppressed by morphine

    Science.gov (United States)

    Chang, Ming-Cheng; Chen, Yu-Li; Chiang, Ying-Cheng; Cheng, Ya-Jung; Jen, Yu-Wei; Chen, Chi-An; Cheng, Wen-Fang; Sun, Wei-Zen

    2016-01-01

    The influence of morphine on host immunity and the underlying mechanism are still unclear. In the current study, we investigated the influence of morphine on dendritic cells (DCs), its possible mechanism of action, and the molecules that could reverse these effects. Morphine suppressed DC maturation, antigen presenting abilities, and the ability to activate antigen-specific CD8+ T cells. Morphine-treated DCs also secreted higher concentrations of IL-10, but lower IL-6 and TNF-α. Morphine-treated DCs showed decreased ERK1/2 phosphorylation and reduced p38 dephosphorylation. The in vivo administration of immuno-modulators, anti-CD40 Ab and TLR3 ligand-poly(I:C), enhanced antigen-specific immunity, promoted the anti-tumor effects, and prolonged the survival of morphine-treated, tumor-bearing mice by promoting the maturation and function of BMM-derived DCs by enhancing ERK1/2 phosphorylation and p38 dephosphorylation. We concluded that morphine can inhibit DC-mediated anti-tumor immunity by suppressing DC maturation and function. Immuno-modulators, such as anti-CD40 Abs and TLR agonists, can restore the DC-mediated anti-tumor immunity. Use of immuno-modulators could serve as a useful approach to overcome the immunocompromised state generated by morphine. PMID:27186393

  12. Immunomodulatory effects and adaptive immune response to daratumumab in multiple myeloma

    DEFF Research Database (Denmark)

    Krejcik, Jakub; Casneuf, T.; Nijhof, I.;

    2015-01-01

    assays. T-cell subpopulation counts were modelled over time with linear mixed modelling. Two group comparisons were performed using non-parametric Wilcoxon rank sum tests. Results: Data from 148 patients receiving 16 mg/kg DARA in GEN501 (n = 42) and Sirius (n = 106) were analyzed for changes in immune......Introduction: Daratumumab (DARA) is a novel human monoclonal antibody that targets CD38, a protein that is highly expressed on multiple myeloma (MM) cells. DARA acts through multiple immune effector-mediated mechanisms, including complement-dependent cytotoxicity, antibody-dependent cell......-mediated cytotoxicity, and antibody-dependent cellular phagocytosis. In two clinical studies (NCT00574288 [GEN501] and NCT01985126 [Sirius]) of DARA monotherapy in patients with relapsed and refractory MM, overall response rates were 36% and 29%, respectively. CD38 is highly expressed in myeloma cells but also...

  13. Possible Implication of Local Immune Response in Darier's Disease: An Immunohistochemical Characterization of Lesional Inflammatory Infiltrate

    Directory of Open Access Journals (Sweden)

    Clelia Miracco

    2010-01-01

    Full Text Available Cell-mediated immunity is considered to be normal in Darier's Disease (DD, an inherited skin disorder complicated by skin infections. To date, there are no investigations on the local inflammatory infiltrate in DD skin lesions. In this immunohistochemical study we characterized and quantified it, making comparisons with two other inflammatory skin disorders, that is, pemphigus vulgaris (PV and lichen ruber planus (LRP, and with the normal skin (NSk. We found a significant (<.05 decrease of CD1a+ Langerhans cells (LCs in DD, compared to PV, LRP, and NSk, and of CD123+ plasmacytoid dendritic cells (pDCs, compared to PV and LRP. We hypothesize that the genetic damage of keratinocytes might result in a loss of some subsets of dendritic cells and, consequently, in an impaired local immune response, which might worsen the infections that inevitably occur in this disease.

  14. Phagocytosis, a cellular immune response in insects

    Directory of Open Access Journals (Sweden)

    C Rosales

    2011-06-01

    Full Text Available Insects like many other organisms are exposed to a wide range of infectious agents. Defense against these agents is provided by innate immune systems, which include physical barriers, humoral responses, and cellular responses. The humoral responses are characterized by the production of antimicrobial peptides, while the cellular defense responses include nodulation, encapsulation, melanization and phagocytosis. The phagocytic process, whereby cells ingest large particles, is of fundamental importance for insects’ development and survival. Phagocytic cells recognize foreign particles through a series of receptors on their cell membrane for pathogen-associated molecules. These receptors in turn initiate a series of signaling pathways that instruct the cell to ingest and eventually destroy the foreign particle. This review describes insect innate humoral and cellular immune functions with emphasis on phagocytosis. Recent advances in our understanding of the phagocytic cell types in various insect species; the receptors involved and the signaling pathways activated during phagocytosis are discussed.

  15. MDV-1 VP22 conjugated VP2 enhancing immune response against infectious bursal disease virus by DNA vaccination in mice

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    VP22 of Marek’s disease virus serotype 1 (MDV-1) could function in protein transduction. In this study, an infectious bursal disease virus VP2 gene was fused to the carboxyl termini of VP22. It showed that the fusion protein did not spread into the bystander cells from the cells transfected with pVP22-VP2, as the VP22 alone could. The VP22 proteins were found to be translocated into all the nuclei in the neighboring COS-1 cells, as analyzed by a fluorescence assay. Although mice were immunized with the recombinant DNAs mixed with polyethylenimine (PEI) at a dose of 1:2, it failed to enhance the antibody response against IBDV VP2, as measured by the indirect ELISA assay, yet the cell mediated immune response was significantly increased. The ratio of CD8+/CD4+ T cells was significantly increased in the immunized group with the fusion genes, compared with the group immunized with VP2 (P<0.05). Our results demonstrated that VP22 indeed enhances the cell-mediated response in the fused VP2 in a mice model system, possibly due to the fact that the IBDV VP2 could be carried into the surrounding cells at a limited level under pressure from MDV VP22.

  16. Ovine model for studying pulmonary immune responses

    Energy Technology Data Exchange (ETDEWEB)

    Joel, D.D.; Chanana, A.D.

    1984-11-25

    Anatomical features of the sheep lung make it an excellent model for studying pulmonary immunity. Four specific lung segments were identified which drain exclusively to three separate lymph nodes. One of these segments, the dorsal basal segment of the right lung, is drained by the caudal mediastinal lymph node (CMLN). Cannulation of the efferent lymph duct of the CMLN along with highly localized intrabronchial instillation of antigen provides a functional unit with which to study factors involved in development of pulmonary immune responses. Following intrabronchial immunization there was an increased output of lymphoblasts and specific antibody-forming cells in efferent CMLN lymph. Continuous divergence of efferent lymph eliminated the serum antibody response but did not totally eliminate the appearance of specific antibody in fluid obtained by bronchoalveolar lavage. In these studies localized immunization of the right cranial lobe served as a control. Efferent lymphoblasts produced in response to intrabronchial antigen were labeled with /sup 125/I-iododeoxyuridine and their migrational patterns and tissue distribution compared to lymphoblasts obtained from the thoracic duct. The results indicated that pulmonary immunoblasts tend to relocate in lung tissue and reappear with a higher specific activity in pulmonary lymph than in thoracic duct lymph. The reverse was observed with labeled intestinal lymphoblasts. 35 references, 2 figures, 3 tables.

  17. Ovine model for studying pulmonary immune responses

    International Nuclear Information System (INIS)

    Anatomical features of the sheep lung make it an excellent model for studying pulmonary immunity. Four specific lung segments were identified which drain exclusively to three separate lymph nodes. One of these segments, the dorsal basal segment of the right lung, is drained by the caudal mediastinal lymph node (CMLN). Cannulation of the efferent lymph duct of the CMLN along with highly localized intrabronchial instillation of antigen provides a functional unit with which to study factors involved in development of pulmonary immune responses. Following intrabronchial immunization there was an increased output of lymphoblasts and specific antibody-forming cells in efferent CMLN lymph. Continuous divergence of efferent lymph eliminated the serum antibody response but did not totally eliminate the appearance of specific antibody in fluid obtained by bronchoalveolar lavage. In these studies localized immunization of the right cranial lobe served as a control. Efferent lymphoblasts produced in response to intrabronchial antigen were labeled with 125I-iododeoxyuridine and their migrational patterns and tissue distribution compared to lymphoblasts obtained from the thoracic duct. The results indicated that pulmonary immunoblasts tend to relocate in lung tissue and reappear with a higher specific activity in pulmonary lymph than in thoracic duct lymph. The reverse was observed with labeled intestinal lymphoblasts. 35 references, 2 figures, 3 tables

  18. Whole blood assay to access T cell-immune responses to Mycobacterium tuberculosis antigens in healthy Brazilian individuals

    Directory of Open Access Journals (Sweden)

    Paulo RZ Antas

    2004-02-01

    Full Text Available The production of interferon gamma (IFNgamma guarantees effective T cell-mediated immunity against Mycobacterium tuberculosis infection. In the present study, we simply compare the in vitro immune responses to Mycobacterium antigens in terms of IFNg production in a total of 10 healthy Brazilian volunteers. Whole blood and mononuclear cells were cultivated in parallel with PPD, Ag85B, and M. bovis hsp65, and five-days supernatants were harvested for cytokine detection by ELISA. The inter-assay result was that the overall profile of agreement in response to antigens was highly correlated (r² = 0.9266; p = 0.0102. Potential analysis is in current progress to dictate the usefulness of this method to access the immune responses also in tuberculosis patients and its contacts.

  19. The effect of doxycycline treatment on the postvaccinal immune response in pigs

    International Nuclear Information System (INIS)

    The effect of a seven-day antibiotic therapy with doxycycline was investigated on the postvaccinal humoral and cellular immune response in pigs. The selected parameters of non-specific immunity were also studied. Fifty pigs were used (control not vaccinated (C, n = 10), control vaccinated (CV, n = 20), and experimental — received doxycycline (DOXY, n = 20)). For vaccination live-attenuated vaccine against pseudorabies (PR) was used. From day − 1 to day 5 pigs from DOXY group received doxycycline orally with drinking water, at the recommended dose. Pigs from DOXY and CV groups were vaccinated at 8 and 10 weeks of age. The results of the present study showed that cell-mediated postvaccinal immune response can be modulated by oral treatment with doxycycline. Significantly lower values of stimulation index were observed after PRV restimulation in doxycycline-treated pigs. Moreover, in the DOXY group a significant decrease in IFN-γ production after PRV restimulation was noted. The significantly lower number of CD4+CD8 + cells was also observed in doxy-treated, vaccinated pigs, 2 weeks after final vaccination. Simultaneously, specific humoral response was not disturbed. This study demonstrated the importance of defining the immune modulatory activity of doxycycline because it may alter the immune responses to vaccines. The exact mechanism of T-cell response suppression by doxycycline remains to be elucidated, however the influence of doxycycline on the secretion of various cytokines, including IFN-γ, may be considered as a possible cause. The present observations should prompt further studies on the practical significance of such phenomena in terms of clinical implications. - Highlights: • We examine the postvaccinal immune response in pigs treated with doxycycline. • Doxycycline negatively influenced the specific proliferation after recall stimulation. • Doxycycline negatively influenced secretion of IFN-γ after recall stimulation. • The lower number of

  20. The effect of doxycycline treatment on the postvaccinal immune response in pigs

    Energy Technology Data Exchange (ETDEWEB)

    Pomorska-Mól, Małgorzata, E-mail: mpomorska@piwet.pulawy.pl; Kwit, Krzysztof; Markowska-Daniel, Iwona; Pejsak, Zygmunt

    2014-07-01

    The effect of a seven-day antibiotic therapy with doxycycline was investigated on the postvaccinal humoral and cellular immune response in pigs. The selected parameters of non-specific immunity were also studied. Fifty pigs were used (control not vaccinated (C, n = 10), control vaccinated (CV, n = 20), and experimental — received doxycycline (DOXY, n = 20)). For vaccination live-attenuated vaccine against pseudorabies (PR) was used. From day − 1 to day 5 pigs from DOXY group received doxycycline orally with drinking water, at the recommended dose. Pigs from DOXY and CV groups were vaccinated at 8 and 10 weeks of age. The results of the present study showed that cell-mediated postvaccinal immune response can be modulated by oral treatment with doxycycline. Significantly lower values of stimulation index were observed after PRV restimulation in doxycycline-treated pigs. Moreover, in the DOXY group a significant decrease in IFN-γ production after PRV restimulation was noted. The significantly lower number of CD4+CD8 + cells was also observed in doxy-treated, vaccinated pigs, 2 weeks after final vaccination. Simultaneously, specific humoral response was not disturbed. This study demonstrated the importance of defining the immune modulatory activity of doxycycline because it may alter the immune responses to vaccines. The exact mechanism of T-cell response suppression by doxycycline remains to be elucidated, however the influence of doxycycline on the secretion of various cytokines, including IFN-γ, may be considered as a possible cause. The present observations should prompt further studies on the practical significance of such phenomena in terms of clinical implications. - Highlights: • We examine the postvaccinal immune response in pigs treated with doxycycline. • Doxycycline negatively influenced the specific proliferation after recall stimulation. • Doxycycline negatively influenced secretion of IFN-γ after recall stimulation. • The lower number of

  1. The aging of the immune system

    OpenAIRE

    Grubeck-Loebenstein, B.; Weinberger, B.; Weiskopf, D.

    2009-01-01

    An age-related decline in immune functions, referred to as immunosenescence, is partially responsible for the increased prevalence and severity of infectious diseases, and the low efficacy of vaccination in elderly persons. Immunosenescence is characterized by a decrease in cell-mediated immune function as well as by reduced humoral immune responses. Age-dependent defects in T- and B-cell function coexist with age-related changes within the innate immune system. In this review, we discuss the...

  2. Antibody Titer Threshold Predicts Anti-Candidal Vaccine Efficacy Even though the Mechanism of Protection Is Induction of Cell-Mediated Immunity

    OpenAIRE

    Spellberg, Brad; Ibrahim, Ashraf S.; Lin, Lin; Avanesian, Valentina; Fu, Yue; Lipke, Peter; Otoo, Henry; Ho, Tiffany; Edwards, John E.

    2008-01-01

    We previously reported that vaccination with Freund’s adjuvant plus the recombinant N-terminus of the candidal adhesin, Als3p (rAls3p-N), protects mice from disseminated candidiasis. Here we report that the rAls3p-N vaccine is effective when combined with aluminum hydroxide adjuvant. Antibody titers of ≥1:6400 accurately predicted protection from infection. Nevertheless, neither B lymphocytes nor serum from immunized animals transferred protection to vaccine-naive animals. In contrast, CD3+, ...

  3. Regulatory T cells in cutaneous immune responses.

    OpenAIRE

    Honda, Tetsuya; MIYACHI, YOSHIKI; Kabashima, Kenji

    2011-01-01

    Regulatory T cells (Treg) are a subset of T cells with strong immunosuppressive activity. In the skin, it has recently been revealed that Treg play important roles not only in the maintenance of skin homeostasis but also in the regulation of the immune responses, such as contact hypersensitivity and atopic dermatitis. Furthermore, the skin plays important roles in the induction of Treg in the periphery. In this review, we will provide an overview of the mechanism of Treg-mediated immunosuppre...

  4. Humoral and Cell-Mediated Immunity to Pandemic H1N1 Influenza in a Canadian Cohort One Year Post-Pandemic: Implications for Vaccination

    OpenAIRE

    Wagar, Lisa E.; Rosella, Laura; Crowcroft, Natasha; Lowcock, Beth; Drohomyrecky, Paulina C.; Foisy, Julie; Gubbay, Jonathan; Rebbapragada, Anu; Winter, Anne-Luise; Achonu, Camille; Brian J Ward; Watts, Tania H

    2011-01-01

    We evaluated a cohort of Canadian donors for T cell and antibody responses against influenza A/California/7/2009 (pH1N1) at 8-10 months after the 2nd pandemic wave by flow cytometry and microneutralization assays. Memory CD8 T cell responses to pH1N1 were detectable in 58% (61/105) of donors. These responses were largely due to cross-reactive CD8 T cell epitopes as, for those donors tested, similar recall responses were obtained to A/California 2009 and A/PR8 1934 H1N1 Hviruses. Longitudinal ...

  5. Chimeric flagellin expressed by Salmonella typhimurium induces an ESAT-6-specific Th 1-type immune response and CTL effects following intranasal immunization

    Institute of Scientific and Technical Information of China (English)

    Hui Zhang; Liu Liu; Ke Wen; Jinlin Huang; Shizhong Geng; Junsong Shen; Zhiming Pan; Xinan Jiao

    2011-01-01

    The flagellin component FliC of Salmonella typhimurium is capable of activating the innate immune system via specific interactions with TLR5 and can also act as a carrier of foreign antigen to elicit antigen-specific immune responses.Thus,we constructed an attenuated Salmonella strain SL5928(fliC/esat) expressing chimeric flagellin that contained the ESAT-6 antigen coding sequence of Mycobacterium tuberculosis inserted into the highly variable region of the Salmonella flagellin coding gene fliCi.The chimeric flagellin functioned normally,as demonstrated using a flagella swarming assay and electron microscopy.To analyze the effects of chimeric flagellin,the cell-mediated immune response and cytotoxic T lymphocyte (CTL) effects specific for ESAT-6antigen were tested after intranasal immunization of mice with flagellated Salmonella SL5928(fliC/esat).The results showed that SL5928(fliC/esat) intranasal immunization can strongly elicit an ESAT-6-specific T helper (Th) 1-type immune response in mucosal lymphoid tissues,such as nasopharynx-associated lymph nodes,lung and Peyer's patches,and a Th 1/Th2 response was elicited in spleen and mesenteric lymph nodes.Furthermore,intranasal immunization of SL5928(fliC/esat) produced efficient CTL effects,as demonstrated using a 5-and 6-carboxyfluorescein diacetate succinimidyl ester (CFSE) assay.Thus,our study revealed that Salmonella flagellin acts as a carrier for foreign antigen and triggers strong Th 1 and CTL responses during intranasal immunization.Chimeric flagellin is potentially an effective strategy for the development of novel vaccines against tuberculosis in humans and animals.

  6. Augmented Designs to Assess Immune Response in Vaccine Trials

    OpenAIRE

    Follmann, Dean

    2006-01-01

    This article introduces methods for use in vaccine clinical trials to help determine whether the immune response to a vaccine is actually causing a reduction in the infection rate. This is not easy because immune response to the (say HIV) vaccine is only observed in the HIV vaccine arm. If we knew what the HIV-specific immune response in placebo recipients would have been, had they been vaccinated, this immune response could be treated essentially like a baseline covariate and an interaction ...

  7. Protective immune responses in lawsonia intracellularis infections

    DEFF Research Database (Denmark)

    Cordes, Henriette; Riber, Ulla; Boutrup, Torsten;

    primary L. intracellularis experimental infection in pigs protects against re-colonisation (re-infection) with a virulent L. intracellularis isolate. After re-infection the animals had reduced L. intracellularis colonisation of the intestinal mucosa compared to controls, no bacterial shedding and no...... exhibited a high, but short-lasting peak after re-infection. Specific IFN responses were also measured using a whole blood IFN-γ assay. These were very high in challenge infected and re-infected animals as compared to controls. These specific immune responses may contribute to the explanation of mechanisms...... behind the observed protection against re-infection with L. intracellularis....

  8. Regulation of immune cell responses by semaphorins and their receptors

    OpenAIRE

    Takamatsu, Hyota; Okuno, Tatsusada; Kumanogoh, Atsushi

    2010-01-01

    Semaphorins were originally identified as axon guidance factors involved in the development of the neuronal system. However, accumulating evidence indicates that several members of semaphorins, so-called ‘immune semaphorins', are crucially involved in various phases of immune responses. These semaphorins regulate both immune cell interactions and immune cell trafficking during physiological and pathological immune responses. Here, we review the following two functional aspects of semaphorins ...

  9. Relationships between maternal malaria and malarial immune responses in mothers and neonates

    DEFF Research Database (Denmark)

    Rasheed, F N; Bulmer, J N; De Francisco, A;

    1995-01-01

    and schizonts (190L and 190N) were higher in neonates than mothers. There was no clear relationship between maternal malaria and neonatal mean lymphoproliferation to malarial antigens, although fewer neonates responded when mothers were actively infected. Matched maternal and neonatal...... lymphoproliferation responses did not correlate. However, first born neonatal lymphoproliferation to PPD and malarial antigens appeared lower than other neonates, in agreement with lower lymphoproliferation in primigravidae compared with multigravidae. Also in common with mothers, autologous plasma suppressed...... neonatal lymphoproliferation to PPD and malarial antigens, suggesting common immunoregulation. Higher cortisol or other circulating factors in first pregnancies may be implicated. The relevance of cell-mediated malarial immune responses detected at birth remains to be established....

  10. Immune Responses to Trichloroethylene and Skin Gene Expression Profiles in Sprague Dawley Rats

    Institute of Scientific and Technical Information of China (English)

    XIAO-YAN CHEN; ZHI-XIONG ZHUANG; XIAO-HUI WANG; JIN-ZHOU ZHANG

    2006-01-01

    Objective To characterize the immune reaction in SD rats exposed to trichloroethylene (TCE) and to identify the gene expression profiles involved in skin after TCE exposure. Methods Fifteen percent of TCE was injected intradermally into the rat back (100 μL/120 g) at intervals of 7 days. Whole blood was collected 24 h after the fifth or seventh intradermic administration of TCE. The percentages of CD4+ and CD8+ of T lymphocytes were measured by a flow cytometer. The concentrations of IFN-gamma and IL-4 in the serum were semi-quantified by ELISA. Total RNAs of skin samples at 3 h or 24 h after the seventh dose of TCE in SD rats were extracted, and gene expression profiles of these tissues were analyszed by rat toxicology U34 array of Affymetrix. Results Obvious decline of CD4+ in T lymphocytes was observed in theTCE-administer group. No significant concentration differences in IFN-gamma and IL-4 were found between TCE-treated and control rats. Gadd45a and Mel were significantly up regulated in skin tissue 24 h after TCE exposure. The expression regulation of immune response factors was as active as proteins associated with lipid metabolism and synthesis process in these skin samples of SD rats exposed to TCE. Conclusion T-helper type 1 cells mediate immune response can not be elicited in TCE-treated SD rats, but certain immune disorder can be induced.

  11. Immune Responses to ESAT-6 and CFP-10 by FASCIA and Multiplex Technology for Diagnosis of M. tuberculosis Infection; IP-10 Is a Promising Marker

    OpenAIRE

    Emilie Borgström; Peter Andersen; Fredrik Atterfelt; Inger Julander; Gunilla Källenius; Markus Maeurer; Ida Rosenkrands; Maria Widfeldt; Judith Bruchfeld; Hans Gaines

    2012-01-01

    BACKGROUND: There is a need for reliable markers to diagnose active and latent tuberculosis (TB). The interferon gamma release assays (IGRAs) are compared to the tuberculin skin test (TST) more specific, but cannot discriminate between recent or remote TB infection. Here the Flow-cytometric Assay for Specific Cell-mediated Immune-response in Activated whole blood (FASCIA), which quantifies expanded T-lymphoblasts by flow-cytometric analysis after long-term antigen stimulation of whole blood, ...

  12. Standardized extract of Tinospora crispa stimulates innate and adaptive immune responses in Balb/c mice.

    Science.gov (United States)

    Ahmad, Waqas; Jantan, Ibrahim; Kumolosasi, Endang; Bukhari, Syed Nasir Abbas

    2016-03-01

    Standardized extract of Tinospora crispa has been shown to exhibit immunostimulatory effects on innate immune responses in Wistar-Kyoto rats by enhancing neutrophil and T cell-mediated immunity. In this study the immunostimulatory effects of T. crispa were further investigated on the cellular immune response by determining its effect on nitric oxide (NO) production ability, peritoneal macrophage phagocytosis and delayed type hypersensitivity (DTH), whereas the humoral immune response was evaluated through the measurement of serum immunoglobulins (IgG and IgM) and serum lysozyme levels. Male Balb/c mice were immunized with 200 μL of 5 × 10(9) sheep red blood cells (sRBCs) per mL on day 0 and orally administered with 50, 100 and 200 mg per kg of ethanol extract of T. crispa for 14 days. Syringin and magnoflorine were qualitatively and quantitatively analyzed in the extract as chemical markers by using a validated reversed-phase high performance liquid chromatography method. T. crispa extract (TCE) considerably improved the peritoneal macrophages' ability to engulf FITC-labeled E. coli in a dose-dependent manner. TCE also dose-dependently promoted NO production in peritoneal macrophages activated by a lipopolysaccharide (LPS) and markedly potentiated the sRBS-induced swelling rate of the mice paw in DTH. The extract significantly enhanced the level of serum immunoglobulins, showing maximum activity at 100 mg kg(-1). Compared to the control groups, the serum lysozyme level and myeloperoxidase (MPO) activity were significantly higher in extract-treated groups. These findings suggest that T. crispa possesses strong immunostimulatory activities and might act as a natural immunomodulator as well as a potential nutraceutical for the modulation of the immune response. PMID:26839149

  13. Selective induction of cell-mediated immunity and protection of rhesus macaques from chronic SHIVKU2 infection by prophylactic vaccination with a conserved HIV-1 envelope peptide-cocktail

    International Nuclear Information System (INIS)

    Infection of Indian-origin rhesus macaques by the simian human immunodeficiency virus (SHIV) is considered to be a suitable preclinical model for directly testing efficacy of vaccine candidates based on the HIV-1 envelope. We used this model for prophylactic vaccination with a peptide-cocktail comprised of highly conserved HIV-1 envelope sequences immunogenic/antigenic in macaques and humans. Separate groups of macaques were immunized with the peptide-cocktail by intravenous and subcutaneous routes using autologous dendritic cells (DC) and Freund's adjuvant, respectively. The vaccine elicited antigen specific IFN-γ-producing cells and T-cell proliferation, but not HIV-neutralizing antibodies. The vaccinated animals also exhibited efficient cross-clade cytolytic activity against target cells expressing envelope proteins corresponding to HIV-1 strains representative of multiple clades that increased after intravenous challenge with pathogenic SHIVKU2. Virus-neutralizing antibodies were either undetectable or present only transiently at low levels in the control as well as vaccinated monkeys after infection. Significant control of plasma viremia leading to undetectable levels was achieved in majority of vaccinated monkeys compared to mock-vaccinated controls. Monkeys vaccinated with the peptide-cocktail using autologous DC, compared to Freund's adjuvant, and the mock-vaccinated animals, showed significantly higher IFN-γ production, higher levels of vaccine-specific IFN-γ producing CD4+ cells and significant control of plasma viremia. These results support DC-based vaccine delivery and the utility of the conserved HIV-1 envelope peptide-cocktail, capable of priming strong cell-mediated immunity, for potential inclusion in HIV vaccination strategies

  14. Flavobacterium psychrophilum - Experimental challenge and immune response

    DEFF Research Database (Denmark)

    Henriksen, Maya Maria Mihályi

    the immune system of the fry is not fully developed. Theoretically, the infection pressure could be subdued by vaccinating larger fish, but no commercial vaccine is yet available. Diagnostic methods are well described and the disease is treated with antibiotics. To prevent disease outbreaks and...... periods without disease. The main purpose and focus of the present thesis was to increase knowledge of the immune response following infection with F. psychrophilum, which may contribute to the future development of vaccines and other preventive measures. The project consisted of three main tasks: 1......The disease rainbow trout fry syndrome (RTFS) is caused by the bacterial fish pathogen Flavobacterium psychrophilum. It has been the cause of great losses of rainbow trout in aquacultures both in Denmark and around the world. It was estimated that RTFS resulted in the death of 88 million fry in...

  15. Detailing profiles of Lawsonia intracellularis specific lymphocytes in the immune response to a challenge inoculation after oral vaccination or primary inoculation with virulent bacteria

    DEFF Research Database (Denmark)

    Riber, Ulla; Hvass, Henriette Cordes; Heegaard, Peter M. H.; Ståhl, Marie; Jensen, Tim Kåre; Jungersen, Gregers

    2012-01-01

    not induce measurable primary humoral or cell-mediated immune responses, nor was it able to reduce faecal shedding of bacteria from eight vaccinated pigs compared to seven age-matched naïve challenge-control pigs. Vaccinated pigs did, however, respond to vaccination with an acute phase protein...... IFN-γ producing cells in the vaccinated pigs showed profiles primarily of CD8+(CD4neg) and CD4+CD8+ double positive lymphocytes. Similar profiles of IFN-γ producing cells were found in re-inoculated immune pigs, which experienced a boost in CMI responses. Cellular proliferation was identified in...

  16. Radiation-therapeutic properties of living and killed antitularensis vaccine applied after polysaccharide modulation of immune response

    International Nuclear Information System (INIS)

    The popular conception of modern immunology that the most reliable remedy against tularensis infection is the living antitularensis vaccine is considered. Similar conception exists in the radiobiology, where the radioresistance enhancement with different biological response modifiers is mainly due to the stimulation of the cell mediated immune protection. The comparative study is performed of the radiotherapeutic features of living and killed antitularensis vaccines, applied after polysaccharide stimulation. It is established that the best effect has been observed with the killed antitularensis vaccine applied 14 days before gamma irradiation (cobalt-60, 6.8 Gy). (author)

  17. Novel antigens for detection of cell mediated immune responses to Mycobacterium avium subsp. paratuberculosis infection in cattle

    DEFF Research Database (Denmark)

    Mikkelsen, Heidi; Aagaard, Claus; Nielsen, Søren Saxmose;

    2011-01-01

    included blood samples from 26 heifers from a MAP infected herd, collected three times with four to five-week intervals, and blood samples from 60 heifers of a non-infected herd collected once. Heifers of the non-infected herd were used to establish cut-off values for each antigen. The case definition was...

  18. Novel antigens used to detect cell-mediated immune responses over time in Mycobacterium avium subsp. paratuberculosis infected cattle

    DEFF Research Database (Denmark)

    Mikkelsen, Heidi; Aagaard, Claus; Nielsen, Søren Saxmose;

    same 30 heifers from a known MAP infected herd. Determination of cut-off for each antigen was based on samples from a non-infected herd, including 60 heifers. Based on PPDj stimulations, more than 50% of the heifers tested MAP positive at the first two samplings, whereas only 20% tested positive at...

  19. N-Acetyl-D-glucosamine substituted calix [4]arenes as stimulators of NK cell-mediated antitumor immune response

    Czech Academy of Sciences Publication Activity Database

    Křenek, Karel; Kuldová, Markéta; Huliková, Katarína; Stibor, I.; Lhoták, P.; Dudič, M.; Budka, J.; Pelantová, Helena; Bezouška, Karel; Fišerová, Anna; Křen, Vladimír

    2007-01-01

    Roč. 342, - (2007), s. 1781-1792. ISSN 0008-6215 R&D Projects: GA AV ČR IAA400200503; GA AV ČR IAA500200620; GA MŠk(CZ) LC06010 Grant ostatní: MŠk(CZ) COST D34; GA ČR(CZ) GA203/06/1796 Institutional research plan: CEZ:AV0Z50200510 Source of funding: V - iné verejné zdroje ; V - iné verejné zdroje Keywords : natural killer cell receptors * cd69 * calix(4)arene Subject RIV: EE - Microbiology, Virology Impact factor: 1.723, year: 2007

  20. Bacterial DNA activates cell mediated immune response and nitric oxide overproduction in peritoneal macrophages from patients with cirrhosis and ascites

    OpenAIRE

    Francés, R; Muñoz, C.; Zapater, P; Uceda, F; Gascón, I; Pascual, S.; Pérez-Mateo, M; J. Such

    2004-01-01

    Background and aims: Translocation of intestinal bacteria to ascitic fluid is probably the first step in the development of episodes of spontaneous bacterial peritonitis in patients with cirrhosis. We have recently reported the detection of bacterial DNA in blood and ascitic fluid from patients with advanced cirrhosis, what we consider as molecular evidence of bacterial translocation. Several studies have shown the immunogenic role of bacterial DNA in vitro, and we hypothesised that the prese...

  1. CD117+ Dendritic and Mast Cells Are Dependent on RasGRP4 to Function as Accessory Cells for Optimal Natural Killer Cell-Mediated Responses to Lipopolysaccharide.

    Science.gov (United States)

    Zhou, Saijun; Tanaka, Kumiko; O'Keeffe, Meredith; Qi, Miao; El-Assaad, Fatima; Weaver, James C; Chen, Gang; Weatherall, Christopher; Wang, Ying; Giannakopoulos, Bill; Chen, Liming; Yu, DeMint; Hamilton, Matthew J; Wensing, Lislaine A; Stevens, Richard L; Krilis, Steven A

    2016-01-01

    Ras guanine nucleotide-releasing protein-4 (RasGRP4) is an evolutionarily conserved calcium-regulated, guanine nucleotide exchange factor and diacylglycerol/phorbol ester receptor. While an important intracellular signaling protein for CD117+ mast cells (MCs), its roles in other immune cells is less clear. In this study, we identified a subset of in vivo-differentiated splenic CD117+ dendritic cells (DCs) in wild-type (WT) C57BL/6 mice that unexpectedly contained RasGRP4 mRNA and protein. In regard to the biologic significance of these data to innate immunity, LPS-treated splenic CD117+ DCs from WT mice induced natural killer (NK) cells to produce much more interferon-γ (IFN-γ) than comparable DCs from RasGRP4-null mice. The ability of LPS-responsive MCs to cause NK cells to increase their expression of IFN-γ was also dependent on this intracellular signaling protein. The discovery that RasGRP4 is required for CD117+ MCs and DCs to optimally induce acute NK cell-dependent immune responses to LPS helps explain why this signaling protein has been conserved in evolution. PMID:26982501

  2. CD117+ Dendritic and Mast Cells Are Dependent on RasGRP4 to Function as Accessory Cells for Optimal Natural Killer Cell-Mediated Responses to Lipopolysaccharide

    Science.gov (United States)

    Zhou, Saijun; Tanaka, Kumiko; O’Keeffe, Meredith; Qi, Miao; El-Assaad, Fatima; Weaver, James C.; Chen, Gang; Weatherall, Christopher; Wang, Ying; Giannakopoulos, Bill; Chen, Liming; Yu, DeMint; Hamilton, Matthew J.; Wensing, Lislaine A.; Stevens, Richard L.; Krilis, Steven A.

    2016-01-01

    Ras guanine nucleotide-releasing protein-4 (RasGRP4) is an evolutionarily conserved calcium-regulated, guanine nucleotide exchange factor and diacylglycerol/phorbol ester receptor. While an important intracellular signaling protein for CD117+ mast cells (MCs), its roles in other immune cells is less clear. In this study, we identified a subset of in vivo-differentiated splenic CD117+ dendritic cells (DCs) in wild-type (WT) C57BL/6 mice that unexpectedly contained RasGRP4 mRNA and protein. In regard to the biologic significance of these data to innate immunity, LPS-treated splenic CD117+ DCs from WT mice induced natural killer (NK) cells to produce much more interferon-γ (IFN-γ) than comparable DCs from RasGRP4-null mice. The ability of LPS-responsive MCs to cause NK cells to increase their expression of IFN-γ was also dependent on this intracellular signaling protein. The discovery that RasGRP4 is required for CD117+ MCs and DCs to optimally induce acute NK cell-dependent immune responses to LPS helps explain why this signaling protein has been conserved in evolution. PMID:26982501

  3. CD117+ Dendritic and Mast Cells Are Dependent on RasGRP4 to Function as Accessory Cells for Optimal Natural Killer Cell-Mediated Responses to Lipopolysaccharide.

    Directory of Open Access Journals (Sweden)

    Saijun Zhou

    Full Text Available Ras guanine nucleotide-releasing protein-4 (RasGRP4 is an evolutionarily conserved calcium-regulated, guanine nucleotide exchange factor and diacylglycerol/phorbol ester receptor. While an important intracellular signaling protein for CD117+ mast cells (MCs, its roles in other immune cells is less clear. In this study, we identified a subset of in vivo-differentiated splenic CD117+ dendritic cells (DCs in wild-type (WT C57BL/6 mice that unexpectedly contained RasGRP4 mRNA and protein. In regard to the biologic significance of these data to innate immunity, LPS-treated splenic CD117+ DCs from WT mice induced natural killer (NK cells to produce much more interferon-γ (IFN-γ than comparable DCs from RasGRP4-null mice. The ability of LPS-responsive MCs to cause NK cells to increase their expression of IFN-γ was also dependent on this intracellular signaling protein. The discovery that RasGRP4 is required for CD117+ MCs and DCs to optimally induce acute NK cell-dependent immune responses to LPS helps explain why this signaling protein has been conserved in evolution.

  4. Immune Response of Amebiasis and Immune Evasion by Entamoeba histolytica

    Science.gov (United States)

    Nakada-Tsukui, Kumiko; Nozaki, Tomoyoshi

    2016-01-01

    Entamoeba histolytica is a protozoan parasite and the causative agent of amebiasis. It is estimated approximately 1% of humans are infected with E. histolytica, resulting in an estimate of 100,000 deaths annually. Clinical manifestations of amebic infection range widely from asymptomatic to severe symptoms, including dysentery and extra-intestinal abscesses. Like other infectious diseases, it is assumed that only ~20% of infected individuals develop symptoms, and genetic factors of both the parasite and humans as well as the environmental factors, e.g., microbiota, determine outcome of infection. There are multiple essential steps in amebic infection: degradation of and invasion into the mucosal layer, adherence to the intestinal epithelium, invasion into the tissues, and dissemination to other organs. While the mechanisms of invasion and destruction of the host tissues by the amebae during infection have been elucidated at the molecular levels, it remains largely uncharacterized how the parasite survive in the host by evading and attacking host immune system. Recently, the strategies for immune evasion by the parasite have been unraveled, including immunomodulation to suppress IFN-γ production, elimination of immune cells and soluble immune mediators, and metabolic alterations against reactive oxygen and nitrogen species to fend off the attack from immune system. In this review, we summarized the latest knowledge on immune reaction and immune evasion during amebiasis. PMID:27242782

  5. Immune Response of Amebiasis and Immune Evasion by Entamoeba histolytica.

    Science.gov (United States)

    Nakada-Tsukui, Kumiko; Nozaki, Tomoyoshi

    2016-01-01

    Entamoeba histolytica is a protozoan parasite and the causative agent of amebiasis. It is estimated approximately 1% of humans are infected with E. histolytica, resulting in an estimate of 100,000 deaths annually. Clinical manifestations of amebic infection range widely from asymptomatic to severe symptoms, including dysentery and extra-intestinal abscesses. Like other infectious diseases, it is assumed that only ~20% of infected individuals develop symptoms, and genetic factors of both the parasite and humans as well as the environmental factors, e.g., microbiota, determine outcome of infection. There are multiple essential steps in amebic infection: degradation of and invasion into the mucosal layer, adherence to the intestinal epithelium, invasion into the tissues, and dissemination to other organs. While the mechanisms of invasion and destruction of the host tissues by the amebae during infection have been elucidated at the molecular levels, it remains largely uncharacterized how the parasite survive in the host by evading and attacking host immune system. Recently, the strategies for immune evasion by the parasite have been unraveled, including immunomodulation to suppress IFN-γ production, elimination of immune cells and soluble immune mediators, and metabolic alterations against reactive oxygen and nitrogen species to fend off the attack from immune system. In this review, we summarized the latest knowledge on immune reaction and immune evasion during amebiasis. PMID:27242782

  6. The early antitumor immune response is necessary for tumor growth

    OpenAIRE

    Parmiani, Giorgio; Maccalli, Cristina

    2012-01-01

    Early events responsible of tumor growth in patients with a normal immune system are poorly understood. Here, we discuss, in the context of human melanoma, the Prehn hypothesis according to which a weak antitumor immune response may be required for tumor growth before weakly or non-immunogenic tumor cell subpopulations are selected by the immune system.

  7. Nature and specificity of the immune response to collagen in type II collagen-induced arthritis in mice.

    OpenAIRE

    Stuart, J. M.; Townes, A S; Kang, A H

    1982-01-01

    To determine the role of collagen-immunity in the development of collagen-induced arthritis, DBA/1 mice were immunized with type II collagen and observed for the development of polyarthritis. 96% of the mice immunized with native type II collagen developed inflammatory arthritis between 4 and 5 wk after primary immunization. Immunization with denatured type II collagen in exactly the same manner was not effective in inducing arthritis. Cell-mediated immunity in arthritic mice was assessed by ...

  8. Transgenic carrot expressing fusion protein comprising M. tuberculosis antigens induces immune response in mice.

    Science.gov (United States)

    Permyakova, Natalia V; Zagorskaya, Alla A; Belavin, Pavel A; Uvarova, Elena A; Nosareva, Olesya V; Nesterov, Andrey E; Novikovskaya, Anna A; Zav'yalov, Evgeniy L; Moshkin, Mikhail P; Deineko, Elena V

    2015-01-01

    Tuberculosis remains one of the major infectious diseases, which continues to pose a major global health problem. Transgenic plants may serve as bioreactors to produce heterologous proteins including antibodies, antigens, and hormones. In the present study, a genetic construct has been designed that comprises the Mycobacterium tuberculosis genes cfp10, esat6 and dIFN gene, which encode deltaferon, a recombinant analog of the human γ-interferon designed for expression in plant tissues. This construct was transferred to the carrot (Daucus carota L.) genome by Agrobacterium-mediated transformation. This study demonstrates that the fusion protein CFP10-ESAT6-dIFN is synthesized in the transgenic carrot storage roots. The protein is able to induce both humoral and cell-mediated immune responses in laboratory animals (mice) when administered either orally or by injection. It should be emphasized that M. tuberculosis antigens contained in the fusion protein have no cytotoxic effect on peripheral blood mononuclear cells. PMID:25949997

  9. Transgenic Carrot Expressing Fusion Protein Comprising M. tuberculosis Antigens Induces Immune Response in Mice

    Directory of Open Access Journals (Sweden)

    Natalia V. Permyakova

    2015-01-01

    Full Text Available Tuberculosis remains one of the major infectious diseases, which continues to pose a major global health problem. Transgenic plants may serve as bioreactors to produce heterologous proteins including antibodies, antigens, and hormones. In the present study, a genetic construct has been designed that comprises the Mycobacterium tuberculosis genes cfp10, esat6 and dIFN gene, which encode deltaferon, a recombinant analog of the human γ-interferon designed for expression in plant tissues. This construct was transferred to the carrot (Daucus carota L. genome by Agrobacterium-mediated transformation. This study demonstrates that the fusion protein CFP10-ESAT6-dIFN is synthesized in the transgenic carrot storage roots. The protein is able to induce both humoral and cell-mediated immune responses in laboratory animals (mice when administered either orally or by injection. It should be emphasized that M. tuberculosis antigens contained in the fusion protein have no cytotoxic effect on peripheral blood mononuclear cells.

  10. Immune response induced by HPV18 E2 DNA vaccine combined with IL-12

    Institute of Scientific and Technical Information of China (English)

    Yang Fan; SuFang Chen; Zhang Qin; CuiMing Zhu; Chen Jie; YanPing Wan

    2012-01-01

    Objective:To study the effectiveness of human papillomavirus type 18 E2 gene (HPV18-E2) vaccine and interleukin-12(IL-12) on their immune effects. Methods:Thirty-five Balb/c female mice aged 6-8-week-old were randomly divided into five groups (each n =7).The mice were given instramuscular injection of DNA vaccines at 2-week four 4 times(100mg/time).The tails were cut to draw blood at the 0,2,4,6 weeks,and then the mice were executed by eyeball blood letting at 8 weeks.ELISA was used for the quantitative detection of the specific lgG antibody in the srea of Balb/c mice and the cytokine IFN-γ and IL-4 in mice MTT assay.Results: after 8 weeks immunization, antibody IgA in E2 vaccine group andE2 +IL-12 vaccine group was statistically increased as compared with that of control group, and the difference was statistically significant (P<0.01). IFN-γand IL-4 levels of mice spleen lymphocyte culture supernatant inE2 group and E2 + IL-12 were significantly higher than other control groups (P<0.01). the spleen lymphopoiesis activeness of E2 + IL-12 group was significant enhanced as compared with the E2 group, there were statistically significant differences (P<0.01) . Conclusions: E2 DNA vaccine combined with IL-12 immune mice can effectively induce cell-mediated immunity and humoral immune responses, their capabilities of inducing immune response might be more stronger than that of single one.

  11. Neuroendocrine and Immune System Responses with Spaceflights

    Science.gov (United States)

    Tipton, Charles M.; Greenleaf, John E.; Jackson, Catherine G. R.

    1996-01-01

    Despite the fact that the first human was in space during 1961 and individuals have existed in a microgravity environment for more than a year, there are limited spaceflight data available on the responses of the neuroendocrine and immune systems. Because of mutual interactions between these respective integrative systems, it is inappropriate to assume that the responses of one have no impact on functions of the other. Blood and plasma volume consistently decrease with spaceflight; hence, blood endocrine and immune constituents will be modified by both gravitational and measurement influences. The majority of the in-flight data relates to endocrine responses that influence fluids and electrolytes during the first month in space. Adrenocorticotropin (ACTH), aldo-sterone. and anti-diuretic hormone (ADH) appear to be elevated with little change in the atrial natriuretic peptides (ANP). Flight results longer than 60 d show increased ADH variability with elevations in angiotensin and cortisol. Although post-flight results are influenced by reentry and recovery events, ACTH and ADH appear to be consistently elevated with variable results being reported for the other hormones. Limited in-flight data on insulin and growth hormone levels suggest they are not elevated to counteract the loss in muscle mass. Post-flight results from short- and long-term flights indicate that thyroxine and insulin are increased while growth hormone exhibits minimal change. In-flight parathyroid hormone (PTH) levels are variable for several weeks after which they remain elevated. Post-flight PTH was increased on missions that lasted either 7 or 237 d, whereas calcitonin concentrations were increased after 1 wk but decreased after longer flights. Leukocytes are elevated in flights of various durations because of an increase in neutrophils. The majority of post-flight data indicates immunoglobulin concentrations are not significantly changed from pre-flight measurements. However, the numbers of T

  12. Rotavirus Antagonism of the Innate Immune Response

    Directory of Open Access Journals (Sweden)

    Michelle M. Arnold

    2009-11-01

    Full Text Available Rotavirus is a primary cause of severe dehydrating gastroenteritis in infants and young children. The virus is sensitive to the antiviral effects triggered by the interferon (IFN-signaling pathway, an important component of the host cell innate immune response. To counteract these effects, rotavirus encodes a nonstructural protein (NSP1 that induces the degradation of proteins involved in regulating IFN expression, such as members of the IFN regulatory factor (IRF family. In some instances, NSP1 also subverts IFN expression by causing the degradation of a component of the E3 ubiquitin ligase complex responsible for activating NF-κB. By antagonizing multiple components of the IFN-induction pathway, NSP1 aids viral spread and contributes to rotavirus pathogenesis.

  13. Gliadin Peptides as Triggers of the Proliferative and Stress/Innate Immune Response of the Celiac Small Intestinal Mucosa

    Directory of Open Access Journals (Sweden)

    Maria Vittoria Barone

    2014-11-01

    Full Text Available Celiac disease (CD is a frequent inflammatory intestinal disease, with a genetic background, caused by gliadin-containing food. Undigested gliadin peptides induce innate and adaptive T cell-mediated immune responses. The major mediator of the stress and innate immune response to gliadin peptides (i.e., peptide 31–43, P31–43 is the cytokine interleukin-15 (IL-15. The role of epithelial growth factor (EGF as a mediator of enterocyte proliferation and the innate immune response has been described. In this paper, we review the most recent literature on the mechanisms responsible for triggering the up-regulation of these mediators in CD by gliadin peptides. We will discuss the role of P31–43 in enterocyte proliferation, structural changes and the innate immune response in CD mucosa in cooperation with EGF and IL-15, and the mechanism of up-regulation of these mediators related to vesicular trafficking. We will also review the literature that focuses on constitutive alterations of the structure, signalling/proliferation and stress/innate immunity pathways of CD cells. Finally, we will discuss how these pathways can be triggered by gliadin peptide P31–43 in controls, mimicking the celiac cellular phenotype.

  14. Assessment of cellular and mucosal immune responses in chicks to Newcastle disease oral pellet vaccine (D58 strain) using qPCR.

    Science.gov (United States)

    Shilpa, P; Kirubaharan, J John; Chandran, N Daniel Joy; Gnanapriya, N

    2014-12-01

    To assess the cell mediated and mucosal immune responses in chicks to Newcastle disease vaccine, expression levels of certain genes encoding cytokines and chemokines were quantified by q-PCR. The utility of cytokine and chemokine gene expression profile in estimating the cell mediated and humoral immune response has been established. The cell mediated immune response was assessed by quantifying the IFN-γ gene expression in splenocytes and compared with colorimetric blastogenesis assay. The mucosal immune response was assessed by quantifying the expression of IL-8, IL1-β, MIP1-β, K60 and K203 in the intestinal cells and compared with IgA ELISA. On 14th day post vaccination, the expression of IFN-γ was upregulated by 12-folds in the Group I, which have received oral pellet vaccine and fourfolds in the Group II where birds have received live thermostable vaccine as occulonasal instillation. 3 and 7 days after receiving booster, the same cytokine gene was upregulated by 12-folds and 27-folds respectively in the Group III, where birds have received live thermostable ND vaccine as priming vaccine and oral pellet vaccine as booster. On 21st day post vaccination the expression of IL-8 was upregulated by 42.8-folds in Group I and 3.3-folds in the Group II. The expression of IL-1β was upregulated by eightfolds on 3rd day post vaccination and 23-folds on 21st day post vaccination in Group I. The expression of macrophage inflammatory protein-1β (MIP-1β) was upregulated by 16-folds in Group I and 70-folds in Group II on 14th day post vaccination. No significant change in expression of chemokine genes K60 and K203 in vaccinated birds. The results were comparable with the results of conventional tests and proved the utility of qPCR in estimating the cellular and mucosal immune responses. PMID:25674624

  15. Molecular immune response of channel catfish immunized with live theronts of Ichthyophthirius multifiliis.

    Science.gov (United States)

    Xu, De-Hai; Zhang, Qi-Zhong; Shoemaker, Craig A; Zhang, Dunhua; Moreira, Gabriel S A

    2016-07-01

    The parasite Ichthyophthirius multifiliis (Ich) has been reported in various freshwater fishes worldwide and results in severe losses to both food and aquarium fish production. The fish surviving natural infections or immunized with live theronts develop strong specific and non-specific immune responses. Little is known about how these immune genes are induced or how they interact and lead to specific immunity against Ichthyophthirius multifiliis in channel catfish Ictalurus punctatus. This study evaluated the differential expression of immune-related genes, including immunoglobulin, immune cell receptor, cytokine, complement factor and toll-like receptors in head kidney from channel catfish at different time points after immunization with live theronts of I. multifiliis. The immunized fish showed significantly higher anti-Ich antibody expressed as immobilization titer and ELISA titer than those of control fish. The vast majority of immunized fish (95%) survived theront challenge. Expression of IgM and IgD heavy chain genes exhibited a rapid increase from 4 hour (h4) to 2 days (d2) post immunization. Expression of immune cell receptor genes (CD4, CD8-α, MHC I, MHC II β, TcR-α, and TcR-β) showed up-regulation from h4 to d6 post immunization, indicating that different immune cells were actively involved in cellular immune response. Cytokine gene expression (IL-1βa, IL-1βb, IFN-γ and TNF-α) increased rapidly at h4 post immunization and were at an up-regulated level until d2 compared to the bovine serum albumin control. Expression of complement factor and toll-like receptor genes exhibited a rapid increase from h4 to d2 post immunization. Results of this study demonstrated differential expression of genes involved in the specific or non-specific immune response post immunization and that the vaccination against Ich resulted in protection against infection by I. multifiliis. PMID:27044331

  16. Factors affecting immune responsiveness in vitro of germfree allogeneic radiation chimeras. I. Differences between donor and host strains

    International Nuclear Information System (INIS)

    An important aspect of bone marrow transplantation has been focused upon. It has been demonstrated that significant differences between in vitro responses of germfree DBA/2 mice (donor strain) and of C3H/He (recipient strain) exist. The PHA response of spleen cells from germfree C3H/He mice is greater than that of DBA/2 mice. However, the reverse is true in regard to Con A responsiveness. In fact, calculation of a Con A/PHA ratio reveals a striking difference between strains. B cell reactivity as assessed by LPS mitogenic responsiveness is similar in both strains. The cell mediated responsiveness of DBA/2 mice is also diminished as measured by mixed lymphocyte reaction and cell mediated cytotoxicity. An inverse correlation between plaque forming cell (PFC) responses in vitro and the Con A/PHA ratio in DBA/2 mice is suggestive of a predominance of inherent suppressor cell activity in this strain. These characteristics of the DBA/2 immune responsiveness may be a factor in the apparent T cell unresponsiveness seen in DBA/2 leads to C3H/He mouse allogeneic bone marrow chimeras

  17. Divergent immune responses to Mycobacterium avium subsp. paratuberculosis infection correlate with kinome responses at the site of intestinal infection.

    Science.gov (United States)

    Määttänen, Pekka; Trost, Brett; Scruten, Erin; Potter, Andrew; Kusalik, Anthony; Griebel, Philip; Napper, Scott

    2013-08-01

    Mycobacterium avium subsp. paratuberculosis is the causative agent of Johne's disease (JD) in cattle. M. avium subsp. paratuberculosis infects the gastrointestinal tract of calves, localizing and persisting primarily in the distal ileum. A high percentage of cattle exposed to M. avium subsp. paratuberculosis do not develop JD, but the mechanisms by which they resist infection are not understood. Here, we merge an established in vivo bovine intestinal segment model for M. avium subsp. paratuberculosis infection with bovine-specific peptide kinome arrays as a first step to understanding how infection influences host kinomic responses at the site of infection. Application of peptide arrays to in vivo tissue samples represents a critical and ambitious step in using this technology to understand host-pathogen interactions. Kinome analysis was performed on intestinal samples from 4 ileal segments subdivided into 10 separate compartments (6 M. avium subsp. paratuberculosis-infected compartments and 4 intra-animal controls) using bovine-specific peptide arrays. Kinome data sets clustered into two groups, suggesting unique binary responses to M. avium subsp. paratuberculosis. Similarly, two M. avium subsp. paratuberculosis-specific immune responses, characterized by different antibody, T cell proliferation, and gamma interferon (IFN-γ) responses, were also observed. Interestingly, the kinomic groupings segregated with the immune response groupings. Pathway and gene ontology analyses revealed that differences in innate immune and interleukin signaling and particular differences in the Wnt/β-catenin pathway distinguished the kinomic groupings. Collectively, kinome analysis of tissue samples offers insight into the complex cellular responses induced by M. avium subsp. paratuberculosis in the ileum and provides a novel method to understand mechanisms that alter the balance between cell-mediated and antibody responses to M. avium subsp. paratuberculosis infection. PMID

  18. Wolbachia symbiosis and insect immune response

    Institute of Scientific and Technical Information of China (English)

    Stefanos Siozios; Panagiotis Sapountzis; Panagiotis Ioannidis; Kostas Bourtzis

    2008-01-01

    Bacterial intracellular symbiosis is very common in insects, having significant consequences in promoting the evolution of life and biodiversity. The bacterial group that has recently attracted particular attention is Wolbachia pipientis which probably represents the most ubiquitous endosymbiont on the planet. W. pipientis is a Gram-negative obligatory intracellular and maternally transmitted α-proteobacterium, that is able to establish symbiotic associations with arthropods and nematodes. In arthropods, Wolbachia pipientis infections have been described in Arachnida, in Isopoda and mainly in Insecta. They have been reported in almost all major insect orders including Diptera, Coleoptera, Hemiptera,Hymenoptera, Orthoptera and Lepidoptera. To enhance its transmission, W. pipientis can manipulate host reproduction by inducing parthenogenesis, feminization, male killing and cytoplasmic incompatibility. Several polymerase chain reaction surveys have indicated that up to 70% of all insect species may be infected with W. pipientis. How does W. pipientis manage to get established in diverse insect host species? How is this intracellular bacterial symbiont species so successful in escaping the host immune response? The present review presents recent advances and ongoing scientific efforts in the field. The current body of knowledge in the field is summarized, revelations from the available genomic information are presented and as yet unanswered questions are discussed in an attempt to present a comprehensive picture of the unique ability of W. pipientis to establish symbiosis and to manipulate reproduction while evading the host's immune system.

  19. Nanomaterial Induced Immune Responses and Cytotoxicity.

    Science.gov (United States)

    Ali, Ashraf; Suhail, Mohd; Mathew, Shilu; Shah, Muhammad Ali; Harakeh, Steve M; Ahmad, Sultan; Kazmi, Zulqarnain; Alhamdan, Mohammed Abdul Rahman; Chaudhary, Adeel; Damanhouri, Ghazi Abdullah; Qadri, Ishtiaq

    2016-01-01

    Nanomaterials are utilized in a wide array of end user products such as pharmaceuticals, electronics, clothes and cosmetic products. Due to its size (< 100 nm), nanoparticles have the propensity to enter through the airway and skin, making its path perilous with the potential to cause damages of varying severity. Once within the body, these particles have unconstrained access to different tissues and organs including the brain, liver, and kidney. As a result, nanomaterials may cause the perturbation of the immune system eliciting an inflammatory response and cytotoxicity. This potential role is dependent on many factors such as the characteristics of the nanomaterials, presence or absence of diseases, and genetic predisposition. Cobalt and nickel nanoparticles, for example, were shown to have inflammogenic properties, while silver nanoparticles were shown to reduce allergic inflammation. Just as asbestos fibers, carbon nanotubes were shown to cause lungs damage. Some nanomaterials were shown, based on animal studies, to result in cell damage, leading to the formation of pre-cancerous lesions. This review highlights the impact of nanomaterials on immune system and its effect on human health with toxicity consideration. It recommends the development of suitable animal models to study the toxicity and bio-clearance of nanomaterials and propose safety guidelines. PMID:27398432

  20. Malaria vaccines and human immune responses.

    Science.gov (United States)

    Long, Carole A; Zavala, Fidel

    2016-08-01

    Despite reductions in malaria episodes and deaths over the past decade, there is still significant need for more effective tools to combat this serious global disease. The positive results with the Phase III trial of RTS,S directed to the circumsporozoite protein of Plasmodium falciparum have established that a vaccine against malaria can provide partial protection to children in endemic areas, but its limited efficacy and relatively short window of protection mandate that new generations of more efficacious vaccines must be sought. Evidence shows that anti-parasite immune responses can control infection against other stages as well, but translating these experimental findings into vaccines for blood stages has been disappointing and clinical efforts to test a transmission blocking vaccine are just beginning. Difficulties include the biological complexity of the organism with a large array of stage-specific genes many of which in the erythrocytic stages are antigenically diverse. In addition, it appears necessary to elicit high and long-lasting antibody titers, address the redundant pathways of merozoite invasion, and still seek surrogate markers of protective immunity. Most vaccine studies have focused on a single or a few antigens with an apparent functional role, but this is likely to be too restrictive, and broad, multi-antigen, multi-stage vaccines need further investigation. Finally, novel tools and biological insights involving parasite sexual stages and the mosquito vector will provide new avenues for reducing or blocking malaria transmission. PMID:27262417

  1. Local Immune Response in Helicobacter pylori Infection.

    Science.gov (United States)

    Kivrak Salim, Derya; Sahin, Mehmet; Köksoy, Sadi; Adanir, Haydar; Süleymanlar, Inci

    2016-05-01

    There have been few studies concerning the cytokine profiles in gastric mucosa of Helicobacter pylori-infected patients with normal mucosa, chronic gastritis, and gastric carcinoma (GAC).In the present study, we aimed to elucidate the genomic expression levels and immune pathological roles of cytokines-interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-6, IL-10, transforming growth factor (TGF)-β, IL-17A, IL-32-in H pylori-infected patients with normal gastric mucosa (NGM; control), chronic active gastritis (CAG), and GAC. Genomic expression levels of these cytokines were assayed by real-time PCR analysis in gastric biopsy specimens obtained from 93 patients.We found that the genomic expression levels of IFN-γ, TNF-α, IL-6, IL-10, IL-17A mRNA were increased in the CAG group and those of TNF-α, IL-6, IL-10, IL-17A, TGF-β mRNA were increased in the GAC group with reference to H pylori-infected NGM group.This study is on the interest of cytokine profiles in gastric mucosa among individuals with normal, gastritis, or GAC. Our findings suggest that the immune response of gastric mucosa to infection of H pylori differs from patient to patient. For individual therapy, levels of genomic expression of IL-6 or other cytokines may be tracked in patients. PMID:27196487

  2. Local immune response and protection in the guinea pig keratoconjunctivitis model following immunization with Shigella vaccines.

    OpenAIRE

    Hartman, A B; Van De Verg, L L; Collins, H H; Tang, D B; Bendiuk, N O; Taylor, D N; Powell, C J

    1994-01-01

    This study used the guinea pig keratoconjunctivitis model to examine the importance of route of administration (mucosal versus parenteral), frequency and timing of immunization (primary versus boosting immunization), and form of antigen given (live attenuated vaccine strain versus O-antigen-protein conjugate) on the production of protective immunity against Shigella infection. Since local immune response to the lipopolysaccharide (LPS) O-antigen of Shigella spp. is thought to be important for...

  3. Iron, folacin, vitamin B12 and zinc status and immune response in elderly subjects in the Washington D.C. metropolitan area

    International Nuclear Information System (INIS)

    The iron, folacin, vitamin B12, and zinc status of a group of economically and socially disadvantaged elderly persons in the Washington Metropolitan Area was evaluated. Factors related to deficiencies of these nutrients, the relationships between the status of these nutrients and cell-mediated immunity, and the relationships of iron, folacin and vitamin B12 status to hemoglobin levels in the subjects were also examined. It was also determined whether there were any interactions among iron, folacin, vitamin B12 and zinc status in their relationships to cell-mediated immunity. Socio-demographic and nutritional data on the subjects were obtained using a questionnaire. Dietary data were obtained using a dietary record. A fasting blood sample was drawn and the levels of ferritin, folate and vitamin B12, and the erythrocyte levels of folate were determined by radioassay. Plasma and hair zinc levels were determined by atomic absorption spectrophotometry. Cell-mediated immune response was determined by transformation of peripheral blood lymphocytes after stimulation by mitogens, and by allogenic lymphocytes in the mixed lymphocyte reaction

  4. Meeting report VLPNPV: Session 3: Immune responses.

    Science.gov (United States)

    Morrison, Trudy G

    2014-01-01

    Virus-like particles (VLPs) and nano-particles (NP) are increasingly considered for both prophylactic and therapeutic vaccines for a wide variety of human and animal diseases. Indeed, 2 VLPs have already been licensed for use in humans, the human papilloma virus vaccine and the hepatitis B virus vaccine. (1) Reflecting this increased interest, a second international conference with a specific focus on VLPs and NP was held at the Salk Institute for Biological Studies in La Jolla, California, in June 2014. Approximately 100 attendees, hailing from many nations, came from academic institutions, research institutes, and biotech companies. A wide variety of topics were discussed, ranging from development and characterization of specific VLP and NP vaccine candidates to methods of production of these particles. Session three was focused on the general question of immune responses to VLPs. PMID:25529229

  5. Population-expression models of immune response

    International Nuclear Information System (INIS)

    The immune response to a pathogen has two basic features. The first is the expansion of a few pathogen-specific cells to form a population large enough to control the pathogen. The second is the process of differentiation of cells from an initial naive phenotype to an effector phenotype which controls the pathogen, and subsequently to a memory phenotype that is maintained and responsible for long-term protection. The expansion and the differentiation have been considered largely independently. Changes in cell populations are typically described using ecologically based ordinary differential equation models. In contrast, differentiation of single cells is studied within systems biology and is frequently modeled by considering changes in gene and protein expression in individual cells. Recent advances in experimental systems biology make available for the first time data to allow the coupling of population and high dimensional expression data of immune cells during infections. Here we describe and develop population-expression models which integrate these two processes into systems biology on the multicellular level. When translated into mathematical equations, these models result in non-conservative, non-local advection-diffusion equations. We describe situations where the population-expression approach can make correct inference from data while previous modeling approaches based on common simplifying assumptions would fail. We also explore how model reduction techniques can be used to build population-expression models, minimizing the complexity of the model while keeping the essential features of the system. While we consider problems in immunology in this paper, we expect population-expression models to be more broadly applicable. (paper)

  6. Population-expression models of immune response

    Science.gov (United States)

    Stromberg, Sean P.; Antia, Rustom; Nemenman, Ilya

    2013-06-01

    The immune response to a pathogen has two basic features. The first is the expansion of a few pathogen-specific cells to form a population large enough to control the pathogen. The second is the process of differentiation of cells from an initial naive phenotype to an effector phenotype which controls the pathogen, and subsequently to a memory phenotype that is maintained and responsible for long-term protection. The expansion and the differentiation have been considered largely independently. Changes in cell populations are typically described using ecologically based ordinary differential equation models. In contrast, differentiation of single cells is studied within systems biology and is frequently modeled by considering changes in gene and protein expression in individual cells. Recent advances in experimental systems biology make available for the first time data to allow the coupling of population and high dimensional expression data of immune cells during infections. Here we describe and develop population-expression models which integrate these two processes into systems biology on the multicellular level. When translated into mathematical equations, these models result in non-conservative, non-local advection-diffusion equations. We describe situations where the population-expression approach can make correct inference from data while previous modeling approaches based on common simplifying assumptions would fail. We also explore how model reduction techniques can be used to build population-expression models, minimizing the complexity of the model while keeping the essential features of the system. While we consider problems in immunology in this paper, we expect population-expression models to be more broadly applicable.

  7. Immune Response in Thyroid Cancer: Widening the Boundaries

    OpenAIRE

    Laura Sterian Ward

    2014-01-01

    The association between thyroid cancer and thyroid inflammation has been repeatedly reported and highly debated in the literature. In fact, both molecular and epidemiological data suggest that these diseases are closely related and this association reinforces that the immune system is important for thyroid cancer progression. Innate immunity is the first line of defensive response. Unlike innate immune responses, adaptive responses are highly specific to the particular antigen that induced th...

  8. Immune response markers in sentinel nodes may predict melanoma progression

    OpenAIRE

    Rodolfo, Monica; Castelli, Chiara; Rivoltini, Licia

    2014-01-01

    We recently reported that variable expression of immune-response genes distinguishes tumor positive sentinel nodes in melanoma patients with malignant progression from those with non-progressing disease. Our results depict sentinel nodes as sites in which immune functions are associated with metastatic disease and identify CD30 as a host immune-related cancer prognostic marker and potential therapeutic target.

  9. Vaccines against Human Carcinomas: Strategies to Improve Antitumor Immune Responses

    Directory of Open Access Journals (Sweden)

    Claudia Palena

    2010-01-01

    Full Text Available Multiple observations in preclinical and clinical studies support a role for the immune system in controlling tumor growth and progression. Various components of the innate and adaptive immune response are able to mediate tumor cell destruction; however, certain immune cell populations can also induce a protumor environment that favors tumor growth and the development of metastasis. Moreover, tumor cells themselves are equipped with various mechanisms that allow them to evade surveillance by the immune system. The goal of cancer vaccines is to induce a tumor-specific immune response that ultimately will reduce tumor burden by tipping the balance from a protumor to an antitumor immune environment. This review discusses common mechanisms that govern immune cell activation and tumor immune escape, and some of the current strategies employed in the field of cancer vaccines aimed at enhancing activation of tumor-specific T-cells with concurrent reduction of immunosuppression.

  10. Long-term functional duration of immune responses to HCV NS3/4A induced by DNA vaccination.

    Science.gov (United States)

    Ahlén, G; Holmström, F; Gibbs, A; Alheim, M; Frelin, L

    2014-08-01

    We have investigated the ability of hepatitis C virus non-structural (NS) 3/4A-DNA-based vaccines to activate long-term cell-mediated immune responses in mice. Wild-type and synthetic codon optimized (co) NS3/4A DNA vaccines have previously been shown to be immunogenic in mice, rabbits and humans, although we have very poor knowledge about the longevity of the immune responses primed. We therefore analyzed the functionality of primed NS3/4A-specific immune responses in BALB/c (H-2(d)) and/or C57BL/6J (H-2(b)) mice 1, 2, 3, 4, 6, 12 and 16 months after the last immunization. Mice were immunized one, two, three or four times using gene gun delivery to the skin or by intramuscular administration. Immunological responses after immunization were monitored by protection against in vivo challenge of NS3/4A-expressing syngeneic tumor cells. In addition, functionality of the NS3/4A-specific T cells was analyzed by a standard cytotoxicity assay. First, we identified a new unique murine H-2(d)-restricted NS3/4A cytotoxic T lymphocyte (CTL) epitope, which enabled us to study the epitope-specific immune responses. Our results show that the coNS3/4A vaccine was highly immunogenic by determination of interferon-γ/tumor necrosis factor-α production and lytic cytotoxic T cells, which could efficiently inhibit in vivo tumor growth. Importantly, we showed that one to four monthly immunizations protected mice from tumor development when challenged up to 16 months after the last immunization. When determining the functionality of NS3/4A-specific T cells in vitro, we showed detectable lytic activity up to 12 months after the last immunization. Thus, NS3/4A-based DNA vaccines activate potent cellular immune responses that are present and function in both BALB/c and C57BL/6J mice up to 12-16 months after the last immunization. The induction of long-term immunity after NS3/4A DNA immunization has not been shown previously and supports the use of NS3/4A in hepatitis C virus vaccine

  11. The other way around: probiotic Lactobacillus acidophilus NP51 restrict progression of Mycobacterium avium subspecies paratuberculosis (MAP) infection in Balb/c mice via activiation of CD8 alpha+ immune cell-mediated immunity

    Science.gov (United States)

    The objective of this study was to examine the immune-modulating effects of feeding a novel probiotic Lactobacillus acidophilus strain NP51 to specific pathogen-free Balb/c mice challenged with Mycobacterium avium subspecies paratuberculosis (MAP), the causative agent of Johne’s disease (JD) in rumi...

  12. Modulation of immune responses of Rhynchophorus ferrugineus (Insecta: Coleoptera) induced by the entomopathogenic nematode Steinernema carpocapsae (Nematoda: Rhabditida).

    Science.gov (United States)

    Mastore, Maristella; Arizza, Vincenzo; Manachini, Barbara; Brivio, Maurizio F

    2015-12-01

    Aim of this study was to investigate relationships between the red palm weevil (RPW) Rhynchophorus ferrugineus (Olivier) and the entomopathogenic nematode Steinernema carpocapsae (EPN); particularly, the work was focused on the immune response of the insect host in naive larvae and after infection with the EPN. Two main immunological processes have been addressed: the activity and modulation of host prophenoloxidase-phenoloxidase (proPO) system, involved in melanization of not-self and hemocytes recognition processes responsible for not-self encapsulation. Moreover, immune depressive and immune evasive strategies of the parasite have been investigated. Our results suggest that RPW possess an efficient immune system, however in the early phase of infection, S. carpocapsae induces a strong inhibition of the host proPO system. In addition, host cell-mediated mechanisms of encapsulation, are completely avoided by the parasite, the elusive strategies of S. carpocapsae seem to be related to the structure of its body-surface, since induced alterations of the parasite cuticle resulted in the loss of its mimetic properties. S. carpocapsae before the release of its symbiotic bacteria, depress and elude RPW immune defenses, with the aim to arrange a favorable environment for its bacteria responsible of the septicemic death of the insect target. PMID:24846780

  13. Mucosal priming of newborn mice with S. Typhi Ty21a expressing anthrax protective antigen (PA) followed by parenteral PA-boost induces B and T cell-mediated immunity that protects against infection bypassing maternal antibodies.

    Science.gov (United States)

    Ramirez, Karina; Ditamo, Yanina; Galen, James E; Baillie, Les W J; Pasetti, Marcela F

    2010-08-23

    The currently licensed anthrax vaccine has several limitations and its efficacy has been proven only in adults. Effective immunization of newborns and infants requires adequate stimulation of their immune system, which is competent but not fully activated. We explored the use of the licensed live attenuated S. Typhi vaccine strain Ty21a expressing Bacillus anthracis protective antigen [Ty21a(PA)] followed PA-alum as a strategy for immunizing the pediatric population. Newborn mice primed with a single dose of Ty21a(PA) exhibited high frequencies of mucosal IgA-secreting B cells and IFN-gamma-secreting T cells during the neonatal period, none of which was detected in newborns immunized with a single dose of PA-alum. Priming with Ty21a(PA) followed by PA-boost resulted in high levels of PA-specific IgG, toxin neutralizing and opsonophagocytic antibodies and increased frequency of bone marrow IgG plasma cells and memory B cells compared with repeated immunization with PA-alum alone. Robust B and T cell responses developed even in the presence of maternal antibodies. The prime-boost protected against systemic and respiratory infection. Mucosal priming with a safe and effective S. Typhi-based anthrax vaccine followed by PA-boost could serve as a practical and effective prophylactic approach to prevent anthrax early in life. PMID:20619377

  14. Spaceflight and immune responses of rhesus monkeys

    Science.gov (United States)

    Sonnenfeld, Gerald; Morton, Darla S.; Swiggett, Jeanene P.; Hakenewerth, Anne M.; Fowler, Nina A.

    1995-01-01

    The effects of restraint on immunological parameters was determined in an 18 day ARRT (adult rhesus restraint test). The monkeys were restrained for 18 days in the experimental station for the orbiting primate (ESOP), the chair of choice for Space Shuttle experiments. Several immunological parameters were determined using peripheral blood, bone marrow, and lymph node specimens from the monkeys. The parameters included: response of bone marrow cells to GM-CSF (granulocyte-macrophage colony stimulating factor), leukocyte subset distribution, and production of IFN-a (interferon-alpha) and IFN-gamma (interferon-gamma). The only parameter changed after 18 days of restraint was the percentage of CD8+ T cells. No other immunological parameters showed changes due to restraint. Handling and changes in housing prior to the restraint period did apparently result in some restraint-independent immunological changes. Handling must be kept to a minimum and the animals allowed time to recover prior to flight. All experiments must be carefully controlled. Restraint does not appear to be a major issue regarding the effects of space flight on immune responses.

  15. The role of transcription factors of the IRF family, IRF-1 and IRF-8, in the generation of dendritic cells-mediated tumor immunity: novel approaches to cancer therapy

    International Nuclear Information System (INIS)

    The principal aim of the project was to investigate whether the expression in Dendritic Cells of the two Interferon Regulatory Factors, IRF-1 and IRF-8, resulted in superior antigen presentation and/or evocation of a long lasting antitumor T and B cell response. In the last year of the project at the ISS it has been completed the study of the fine regulation of DCs development and maturation in response to the expression of IRF-1 and it has been defined the role of this transcription factor in the stimulation of an active immune response

  16. Seasonal changes in human immune responses to malaria

    DEFF Research Database (Denmark)

    Hviid, L; Theander, T G

    1993-01-01

    Cellular as well as humorol immune responses to malaria antigens fluctuate in time in individuals living in molono-endemic areas, particularly where malaria transmission is seasonal. The most pronounced changes are seen in association with clinical attacks, but osymptomatic infection can also lead...... to apparent immune depression. However, recent data have shown that seasonal variation in cellular immune responses may occur even in the absence of detectable porositaemia. Here, Lars Hviid and Thor G. Theonder review the seasonal variation in human immune responses to malaria, and discuss its...

  17. The unfolded protein response in immunity and inflammation.

    Science.gov (United States)

    Grootjans, Joep; Kaser, Arthur; Kaufman, Randal J; Blumberg, Richard S

    2016-08-01

    The unfolded protein response (UPR) is a highly conserved pathway that allows the cell to manage endoplasmic reticulum (ER) stress that is imposed by the secretory demands associated with environmental forces. In this role, the UPR has increasingly been shown to have crucial functions in immunity and inflammation. In this Review, we discuss the importance of the UPR in the development, differentiation, function and survival of immune cells in meeting the needs of an immune response. In addition, we review current insights into how the UPR is involved in complex chronic inflammatory diseases and, through its role in immune regulation, antitumour responses. PMID:27346803

  18. Endocrine Factors Modulating Immune Responses in Pregnancy

    OpenAIRE

    Schumacher, Anne; Costa, Serban-Dan; Zenclussen, Ana Claudia

    2014-01-01

    How the semi-allogeneic fetus is tolerated by the maternal immune system remains a fascinating phenomenon. Despite extensive research activity in this field, the mechanisms underlying fetal tolerance are still not well understood. However, there are growing evidences that immune–immune interactions as well as immune–endocrine interactions build up a complex network of immune regulation that ensures fetal survival within the maternal uterus. In the present review, we aim to summarize emerging ...

  19. Immune response inhibits associative learning in insects.

    OpenAIRE

    Mallon, Eamonn B.; Brockmann, Axel; Schmid-Hempel, Paul

    2003-01-01

    In vertebrates, it is well established that there are many intricate interactions between the immune system and the nervous system, and vice versa. Regarding insects, until now little has been known about the link between these two systems. Here, we present behavioural evidence indicating a link between the immune system and the nervous system in insects. We show that otherwise non-infected honeybees whose immune systems are challenged by a non-pathogenic immunogenic elicitor lipopolysacchari...

  20. Activation and Regulation of DNA-Driven Immune Responses

    OpenAIRE

    Paludan, Søren R

    2015-01-01

    The innate immune system provides early defense against infections and also plays a key role in monitoring alterations of homeostasis in the body. DNA is highly immunostimulatory, and recent advances in this field have led to the identification of the innate immune sensors responsible for the recognition of DNA as well as the downstream pathways that are activated. Moreover, information on how cells regulate DNA-driven immune responses to avoid excessive inflammation is now emerging. Finally,...

  1. Respons imun humoral pada pulpitis (Humoral immune response on pulpitis)

    OpenAIRE

    Trijoedani Widodo

    2005-01-01

    Pulpitis is an inflammation process on dental pulp tissue, and usually as the continuous of caries. The microorganism in the caries is a potential immunogenic triggering the immune respons, both humoral and celluler immune responses. The aim of this research is to explain the humoral immune response changes in the dental pulp tissues of pulpitis. This research was done on three group samples: Irreversible pulpitis, Reversible pulpitis and sound teeth as the control group. The result showed th...

  2. B7h-expressing dendritic cells and plasma B cells mediate distinct outcomes of ICOS costimulation in T cell-dependent antibody responses

    Directory of Open Access Journals (Sweden)

    Larimore Kevin

    2012-06-01

    Full Text Available Abstract Background The ICOS-B7h costimulatory receptor-ligand pair is required for germinal center formation, the production of isotype-switched antibodies, and antibody affinity maturation in response to T cell-dependent antigens. However, the potentially distinct roles of regulated B7h expression on B cells and dendritic cells in T cell-dependent antibody responses have not been defined. Results We generated transgenic mice with lineage-restricted B7h expression to assess the cell-type specific roles of B7h expression on B cells and dendritic cells in regulating T cell-dependent antibody responses. Our results show that endogenous B7h expression is reduced on B cells after activation in vitro and is also reduced in vivo on antibody-secreting plasma B cells in comparison to both naïve and germinal center B cells from which they are derived. Increasing the level of B7h expression on activated and plasma B cells in B-B7hTg mice led to an increase in the number of antibody-secreting plasma cells generated after immunization and a corresponding increase in the concentration of antigen-specific high affinity serum IgG antibodies of all isotypes, without affecting the number of responding germinal center B cells. In contrast, ICOS costimulation mediated by dendritic cells in DC-B7hTg mice contributed to germinal center formation and selectively increased IgG2a production without affecting the overall magnitude of antibody responses. Conclusions Using transgenic mice with lineage-restricted B7h expression, we have revealed distinct roles of ICOS costimulation mediated by dendritic cells and B cells in the regulation of T cell-dependent antibody responses.

  3. Effects of vitamin nutrition on the immune response of hatchery-reared salmonids. Annual report, 1984

    International Nuclear Information System (INIS)

    Results demonstrate that immunological assays. Lymphocytes from both of the major lymphoid organs (spleen and anterior kidney) produce significant in vitro antibody responses to the antigen, trinitrophenyl-lipopolysaccharide. These cells also demonstrate significant mitogenic stimulation (proliferation) in response to bacterial lipopolysaccharide, phytohemagglutinin, and to a novel mitogen, Vibrio anguillarum extract. As an assessment of cell-mediated immunity, we have found that lymphocytes are capable of responding in a mixed lymphocyte reaction as demonstrated by increased incorporation of tritiated thymidine. Results also indicate that phagocytosis can be quantified by the uptake of radioiodinated Renibacterium salmoninarum and that production of migration inhibition factor (MIF)-like activity can be induced in immunized animals. Polyclonal activation of chinook lymphocytes was elicited by both Vibrio anguillarum extract and E. coli lipopolysaccharide. Groups of spring chinook salmon were fed a formula diet containing five dietary levels of pyridoxine (15, 30, 60, 120, and 1500 mg/kg diet). Data collected on growth and feed efficiency in the first eighteen weeks show no significant difference between these formulations. 46 refs., 20 figs., 7 tabs

  4. Osthole promotes anti-tumor immune responses in tumor-bearing mice with hepatocellular carcinoma.

    Science.gov (United States)

    Zhang, Lurong; Jiang, Guorong; Yao, Fei; Liang, Guoqiang; Wang, Fei; Xu, Heng; Wu, Yan; Yu, Xiao; Liu, Haiyan

    2015-06-01

    Osthole, a natural coumarin derivative, has been shown to have anti-tumor and anti-inflammatory activity. However, the effect of osthole on anti-tumor immune responses in tumor-bearing mice has not yet been reported. In the present study, osthole treatment did not affect the weight and the coefficient of thymus and spleen in tumor-bearing mice with hepatocellular carcinoma (HCC). However, osthole administration significantly elevated the proportion and number of the splenic CD8(+) T cells, the proportion of CD4(+) T and CD8(+) T cells in tumor tissues, and the levels of IL-2 and TNF-α in the serum of HCC tumor-bearing mice. Our results suggested that osthole could promote the activation of the tumor-infiltrating CD4(+) T and CD8(+) T cells, and elevate the proportion of CD4(+) and CD8(+) effector T cells. Osthole treatment also significantly decreased the proportion of CD4(+)CD25(+)Foxp3(+) regulatory T cells in the spleen. Taken together, osthole could enhance the T cell mediated anti-tumor immune responses in the tumor-bearing mice with HCC. PMID:25975579

  5. Secondary specific immune response in vitro to MSV tumor cells.

    Science.gov (United States)

    Senik, A; Hebrero, F P; Levy, J P

    1975-12-15

    The interactions which occur between antigenic tumor cells and normal or immune lymphoid cells in a 3-day in vitro culture, have been studied with a murine sarcoma virus (MSV)-induced tumor. The 3H-thymidine incorporation of lymphoma cells growing in suspension, and the radioactive-chromium release of freshly sampled lymphoma cells regularly added to the culture, have been compared to determine the part played by immune lymphoid cells in cytolysis and cytostasis of the tumor-cell population. The cytolytic activity increases in the culture from day 0 to day 3. It is due, predominantly, to T-cells, and remains specific to antigens shared by MSV tumors and related lymphomas. This activity would be difficult to detect unless freshly sampled ascitic cells were used as targets, since the lymphoma cells spontaneously lose a part of their sensitivity to immune cytolysis during in vitro culture. The method used in the present experiments is a secondary chromium release test (SCRT), which measures the invitro secondary stimulation of cytotoxic T-lymphocytes (CTL) by tumor cells. In the absence of stimulatory cells, the CTL activity would have rapidly fallen in vitro. The cytostatic activity also increases during the 3 days in vitro, in parallel to the cytolytic activity: it is due to non-T-cells and remains mainly non-specific. The significance of these data for the interpretation of invitro demonstrated cell-mediated anti-tumor immune reactions is briefly discussed, as well as their relevance in the in vivo role of immune CTL. PMID:53210

  6. Innate immune response development in nestling tree swallows

    Science.gov (United States)

    Stambaugh, T.; Houdek, B.J.; Lombardo, M.P.; Thorpe, P.A.; Caldwell, Hahn D.

    2011-01-01

    We tracked the development of innate immunity in nestling Tree Swallows (Tachycineta bicolor) and compared it to that of adults using blood drawn from nestlings during days 6, 12, and 18 of the ???20-day nestling period and from adults. Innate immunity was characterized using an in vitro assay of the ability of whole blood to kill Escherichia coli. The ability of whole blood to kill E. coli increased as nestlings matured. Neither this component of innate immunity nor right wing chord length on day18 were as developed as in adults indicating that development of the innate immune system and growth both continued after fledging. Narrow sense heritability analyses suggest that females with strong immune responses produced nestlings with strong immune responses. These data suggest nestling Tree Swallows allocated sufficient energy to support rapid growth to enable fledging by day 18, but that further development of innate immunity occurred post-fledging. ?? 2011 by the Wilson Ornithological Society.

  7. The Mycobacterium bovis BCG prime-Rv0577 DNA boost vaccination induces a durable Th1 immune response in mice.

    Science.gov (United States)

    Gu, Dongqing; Chen, Wei; Mi, Youjun; Gong, Xueli; Luo, Tao; Bao, Lang

    2016-04-01

    Tuberculosis remains a major global health problem and effective vaccines are urgently needed. In this study, we used the combined DNA- and protein-based vaccines of immunodominant antigen Rv0577 to boost BCG and evaluated their immunogenicity in BALB/c mice. Our data suggest that the booster vaccine may substantially enhance the immunogenicity of BCG and strengthen both CD4+ T cell-mediated Th1 and CD8+ T cell-mediated cytolytic responses. Compared with the protein-based vaccine, the DNA-based vaccine can induce more durable Th1 immune response, characterized by high levels of antibody response, proliferation response, percentages of CD4+/CD8+ and cytokine secretion in antigen-stimulated splenocyte cultures. In conclusion, we for the first time, developed a protein- and plasmid DNA-based booster vaccine based on Rv0577. Our findings suggest that antigen Rv0577-based DNA vaccine is immunogenic and can efficiently boost BCG, which could be helpful in the design of an efficient vaccination strategy against TB. PMID:26922320

  8. Epitope DNA vaccines against tuberculosis: spacers and ubiquitin modulates cellular immune responses elicited by epitope DNA vaccine

    Institute of Scientific and Technical Information of China (English)

    Wang QM; Sun SH; Hu ZL; Zhou FJ; Yin M; Xiao CJ; Zhang JC

    2005-01-01

    Cell-mediated immune responses are crucial in the protection against tuberculosis. In this study, we constructed epitope DNA vaccines (p3-M-38) encoding cytotoxic T lymphocyte (CTL) epitopes of MPT64 and 38 kDa proteins of Mycobacterium tuberculosis. In order to observe the influence of spacer sequence (Ala-Ala-Tyr) or ubiquitin (UbGR) on the efficacy of the two CTL epitopes, we also constructed DNA vaccines, p3-M-S(spacer)-38, p3-Ub (UbGR)-M-S-38 and p3-Ub-M-38. The immune responses elicited by the four DNA vaccines were tested in C57BL/6 (H-2b) mice. The cytotoxicity of T cells was detected by LDH-release method and by enzyme-linked immunospot assay for epitope-specific cells secreting interferon-gamma. The results showed that DNA immunization with p3-M-38 vaccine could induce epitope-specific CD8+ CTL response and that the spacer sequence (AAY) only enhanced M epitope presentation. The protein-targeting sequence (UbGR) enhanced the immunogenicity of the two epitopes. The finding that defined spacer sequences at C-terminus and protein-targeting degradation modulated the immune response of epitope string DNA vaccines will be of importance for the further development of multi-epitope DNA vaccines against tuberculosis.

  9. A New Mechanism to Curb Over-reactive Immune Responses

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ The human immune system is a truly amazing constellation of responses to attacks from the outside. It could defend you against millions of bacteria, microbes, viruses, toxins and parasites that would invade your body. However, there are cases where the immune response to innocuous substances is inappropriate and over-reactive, leading to diseases such as allergies and arthritis.

  10. Murine major histocompatibility complex and immune response to Eimeria falciformis.

    OpenAIRE

    Mahrt, J L; Shi, Y F

    1988-01-01

    The genetics of the immune response to Eimeria falciformis were investigated in three inbred and six congenic strains of mice. There were significant differences among strains in oocyst production and age-related mortality from parasitic infection. Genes within the H-2 complex and also non-H-2 genes share in the immune response to eimerian infection.

  11. Reduced Epithelial Na+/H+ Exchange Drives Gut Microbial Dysbiosis and Promotes Inflammatory Response in T Cell-Mediated Murine Colitis.

    Directory of Open Access Journals (Sweden)

    Daniel Laubitz

    Full Text Available Inflammatory bowel diseases (IBD are associated with functional inhibition of epithelial Na+/H+ exchange. In mice, a selective disruption of NHE3 (Slc9a3, a major apical Na+/H+ exchanger, also promotes IBD-like symptoms and gut microbial dysbiosis. We hypothesized that disruption of Na+/H+ exchange is necessary for the development of dysbiosis, which promotes an exacerbated mucosal inflammatory response. Therefore, we performed a temporal analysis of gut microbiota composition, and mucosal immune response to adoptive T cell transfer was evaluated in Rag2-/- and NHE3-/-/Rag2-/- (DKO mice with and without broad-spectrum antibiotics. Microbiome (16S profiling, colonic histology, T cell and neutrophil infiltration, mucosal inflammatory tone, and epithelial permeability were analyzed. In adoptive T cell transfer colitis model, Slc9a3 status was the most significant determinant of gut microbial community. In DKO mice, NHE3-deficiency and dysbiosis were associated with dramatically accelerated and exacerbated disease, with rapid body weight loss, increased mucosal T cell and neutrophil influx, increased mucosal cytokine expression, increased permeability, and expansion of CD25-FoxP3+ Tregs; this enhanced susceptibility was alleviated by oral broad-spectrum antibiotics. Based on these results and our previous work, we postulate that epithelial electrolyte homeostasis is an important modulator in the progression of colitis, acting through remodeling of the gut microbial community.

  12. Short communication: Cytokine profiles from blood mononuclear cells of dairy cows classified with divergent immune response phenotypes.

    Science.gov (United States)

    Martin, C E; Paibomesai, M A; Emam, S M; Gallienne, J; Hine, B C; Thompson-Crispi, K A; Mallard, B A

    2016-03-01

    Genetic selection for enhanced immune response has been shown to decrease disease occurrence in dairy cattle. Cows can be classified as high (H), average, or low responders based on antibody-mediated immune response (AMIR), predominated by type-2 cytokine production, and cell-mediated immune response (CMIR) through estimated breeding values for these traits. The purpose of this study was to identify in vitro tests that correlate with in vivo immune response phenotyping in dairy cattle. Blood mononuclear cells (BMC) isolated from cows classified as H-AMIR and H-CMIR through estimated breeding values for immune response traits were stimulated with concanavalin A (ConA; Sigma Aldrich, St. Louis, MO) and gene expression, cytokine production, and cell proliferation was determined at multiple time points. A repeated measures model, which included the effects of immune response group, parity, and stage of lactation, was used to compare differences between immune response phenotype groups. The H-AMIR cows produced more IL-4 protein than H-CMIR cows at 48h; however, no difference in gene expression of type-2 transcription factor GATA3 or IL4 was noted. The BMC from H-CMIR cows had increased production of IFN-γ protein at 48, 72, and 96h compared with H-AMIR animals. Further, H-CMIR cows had increased expression of the IFNG gene at 16, 24, and 48h post-treatment with ConA, although expression of the type-1 transcription factor gene TBX21 did not differ between immune response groups. Although proliferation of BMC increased from 24 to 72h after ConA stimulation, no differences were found between the immune response groups. Overall, stimulation of H-AMIR and H-CMIR bovine BMC with ConA resulted in distinct cytokine production profiles according to genetically defined groups. These distinct cytokine profiles could be used to define disease resistance phenotypes in dairy cows according to stimulation in vitro; however, other immune response phenotypes should be assessed. PMID

  13. Immunization with Immune Complexes Modulates the Fine Specificity of Antibody Responses to a Flavivirus Antigen

    OpenAIRE

    Tsouchnikas, Georgios; Zlatkovic, Juergen; Jarmer, Johanna; Strauß, Judith; Vratskikh, Oksana; Kundi, Michael; Stiasny, Karin; Heinz, Franz X.

    2015-01-01

    The antibody response to proteins may be modulated by the presence of preexisting antigen-specific antibodies and the formation of immune complexes (ICs). Effects such as a general increase or decrease of the response as well as epitope-specific phenomena have been described. In this study, we investigated influences of IC immunization on the fine specificity of antibody responses in a structurally well-defined system, using the envelope (E) protein of tick-borne encephalitis (TBE) virus as a...

  14. Characteristics of immune response to protozoan infections

    OpenAIRE

    Arsić-Arsenijević Valentina S.; Džamić Aleksandar M.; Mitrović Sanja M.; Radonjić Ivana V.; Kranjčić-Zec Ivana F.

    2003-01-01

    Introduction When protozoa enter the blood stream or tissues they can often survive and replicate because they adapt to the resisting natural host defenses. The interaction of immune system with infectious organisms is a dynamic interplay of host mechanisms aimed at eliminating infections and microbial strategies designed to permit survival in the face of powerful effectors mechanisms. Protozoa cause chronic and persistent infections, because natural immunity against them is weak and because ...

  15. Endocrine factors modulating immune responses in pregnancy.

    Science.gov (United States)

    Schumacher, Anne; Costa, Serban-Dan; Zenclussen, Ana Claudia

    2014-01-01

    How the semi-allogeneic fetus is tolerated by the maternal immune system remains a fascinating phenomenon. Despite extensive research activity in this field, the mechanisms underlying fetal tolerance are still not well understood. However, there are growing evidences that immune-immune interactions as well as immune-endocrine interactions build up a complex network of immune regulation that ensures fetal survival within the maternal uterus. In the present review, we aim to summarize emerging research data from our and other laboratories on immune modulating properties of pregnancy hormones with a special focus on progesterone, estradiol, and human chorionic gonadotropin. These pregnancy hormones are critically involved in the successful establishment, maintenance, and termination of pregnancy. They suppress detrimental maternal alloresponses while promoting tolerance pathways. This includes the reduction of the antigen-presenting capacity of dendritic cells (DCs), monocytes, and macrophages as well as the blockage of natural killer cells, T and B cells. Pregnancy hormones also support the proliferation of pregnancy supporting uterine killer cells, retain tolerogenic DCs, and efficiently induce regulatory T (Treg) cells. Furthermore, they are involved in the recruitment of mast cells and Treg cells into the fetal-maternal interface contributing to a local accumulation of pregnancy-protective cells. These findings highlight the importance of endocrine factors for the tolerance induction during pregnancy and encourage further research in the field. PMID:24847324

  16. Endocrine factors modulating immune responses in pregnancy

    Directory of Open Access Journals (Sweden)

    Anne eSchumacher

    2014-05-01

    Full Text Available How the semi-allogeneic fetus is tolerated by the maternal immune system remains a fascinating phenomenon. Despite extensive research activity in this field the mechanisms underlying fetal tolerance are still not well understood. However, there are growing evidences that immune-immune interactions as well as immune-endocrine interactions build up a complex network of immune regulation that ensures fetal survival within the maternal uterus. In the present review, we aim to summarize emerging research data from our and other laboratories on immune modulating properties of pregnancy hormones with a special focus on progesterone, estradiol and human Chorionic Gonadotropin. These pregnancy hormones are critically involved in the successful establishment, maintenance and termination of pregnancy. They suppress detrimental maternal alloresponses while promoting tolerance pathways. This includes the reduction of the antigen-presenting capacity of dendritic cells, monocytes and macrophages as well as the blockage of natural killer cells, T and B cells. Pregnancy hormones also support the proliferation of pregnancy supporting uterine killer cells, retain tolerogenic dendritic cells and efficiently induce regulatory T cells. Furthermore, they are involved in the recruitment of mast cells and regulatory T cells into the fetal-maternal interface contributing to a local accumulation of pregnancy-protective cells. These findings highlight the importance of endocrine factors for the tolerance induction during pregnancy and encourage further research in the field.

  17. Strain variations in the murine cellular immune response to the phenolic glycolipid I antigen of Mycobacterium leprae.

    Science.gov (United States)

    Koster, F T; Teuscher, C; Matzner, P; Umland, E; Yanagihara, D; Brennan, P J; Tung, K S

    1986-01-01

    The cellular immune response to the Mycobacterium leprae-specific phenolic glycolipid I was examined in inbred mice immunized with M. leprae by in vivo delayed cutaneous hypersensitivity and in vitro lymphocyte proliferation. Whereas all mouse strains responded to M.leprae-induced delayed-type hypersensitivity and lymphocyte proliferation, only BALB.K was responsive in both assays to the glycolipid. Responsiveness was determined in part by non-H-2 genes, while the influence of H-2 genes was not apparent. Among congenic BALB/c mice differing only at Igh-C allotype loci, variations in responsiveness were found in both delayed-type hypersensitivity and lymphocytes proliferation assays, indicating a possible role for Igh-C loci-linked genes. Unresponsiveness in the lymphocyte proliferation assay to the glycolipid was inherited as a dominant trait in one set of responder X nonresponder F1 progeny. We conclude that after immunization with M. leprae organisms, the cell-mediated responses to the glycolipid, endowed with a single carbohydrate epitope, are under polygenic control, predominantly non-H-2-linked genes. PMID:3510979

  18. Enhancing antibody: a novel component of the immune response.

    OpenAIRE

    Nemazee, D A; Sato, V L

    1982-01-01

    Current descriptions of the immune response identify two classes of antigenic stimuli that result in the production of specific antibody: (i) exogenous antigens and (ii) endogenous variable-region determinants of the immune system. We expand this scheme to include a third class of antigenic stimulus--new determinants created by the binding of antibody to antigen. This paper describes a set of monoclonal antibodies which arose after repeated immunization with antigen alone but which bound anti...

  19. The innate immune response during urinary tract infection and pyelonephritis

    OpenAIRE

    Spencer, John David; Schwaderer, Andrew L.; Becknell, Brian; Watson, Joshua; Hains, David S.

    2013-01-01

    Despite its proximity to the fecal flora, the urinary tract is considered sterile. The precise mechanisms by which the urinary tract maintains sterility are not well understood. Host immune responses are critically important in the antimicrobial defense of the urinary tract. During recent years, considerable advances have been made in our understanding of the mechanisms underlying immune homeostasis of the kidney and urinary tract. Dysfunctions in these immune mechanisms may result in acute d...

  20. Innate immune responses of Drosophila melanogaster are altered by spaceflight.

    Directory of Open Access Journals (Sweden)

    Oana Marcu

    Full Text Available Alterations and impairment of immune responses in humans present a health risk for space exploration missions. The molecular mechanisms underpinning innate immune defense can be confounded by the complexity of the acquired immune system of humans. Drosophila (fruit fly innate immunity is simpler, and shares many similarities with human innate immunity at the level of molecular and genetic pathways. The goals of this study were to elucidate fundamental immune processes in Drosophila affected by spaceflight and to measure host-pathogen responses post-flight. Five containers, each containing ten female and five male fruit flies, were housed and bred on the space shuttle (average orbit altitude of 330.35 km for 12 days and 18.5 hours. A new generation of flies was reared in microgravity. In larvae, the immune system was examined by analyzing plasmatocyte number and activity in culture. In adults, the induced immune responses were analyzed by bacterial clearance and quantitative real-time polymerase chain reaction (qPCR of selected genes following infection with E. coli. The RNA levels of relevant immune pathway genes were determined in both larvae and adults by microarray analysis. The ability of larval plasmatocytes to phagocytose E. coli in culture was attenuated following spaceflight, and in parallel, the expression of genes involved in cell maturation was downregulated. In addition, the level of constitutive expression of pattern recognition receptors and opsonins that specifically recognize bacteria, and of lysozymes, antimicrobial peptide (AMP pathway and immune stress genes, hallmarks of humoral immunity, were also reduced in larvae. In adults, the efficiency of bacterial clearance measured in vivo following a systemic infection with E. coli post-flight, remained robust. We show that spaceflight altered both cellular and humoral immune responses in Drosophila and that the disruption occurs at multiple interacting pathways.

  1. The Effect of Maternal Helminth Infection on Maternal and Neonatal Immune Function and Immunity to Tuberculosis

    OpenAIRE

    Gebreegziabiher, Dawit; Desta, Kassu; Desalegn, Girmay; Howe, Rawleigh; Abebe, Markos

    2014-01-01

    Background M. tuberculosis and helminth infection each affects one third of the world population. Helminth infections down regulate cell mediated immune responses and this may contribute to lower efficacy of BCG vaccination and higher prevalence of tuberculosis. Objective To determine the effect of maternal helminth infection on maternal and neonatal immune function and immunity to TB. Methods In this cross sectional study, eighty five pregnant women were screened for parasitic and latent TB ...

  2. Immune responses to cancer: are they potential biomarkers of prognosis?

    Directory of Open Access Journals (Sweden)

    Theresa L Whiteside

    2013-05-01

    Full Text Available Recent technical improvements in evaluations of immune cells in situ and immune monitoring of patients with cancer have provided a wealth of new data confirming that immune cells play a key role in human cancer progression. This, in turn, has revived the expectation that immune endpoints might serve as reliable biomarkers of outcome or response to therapy in cancer. The recent successes in linking the T-cell signature in human colorectal carcinoma (CRC with prognosis have provided a strong motive for searching for additional immune biomarkers that could serve as intermediate endpoints of response to therapy and outcome in human cancers. A number of potentially promising immune biomarkers have emerged, but most remain to be validated. Among them, the B-cell signature, as exemplified by expression of the immunoglobulin G kappa chain (IGKC in tumor-infiltrating lymphocytes (TIL, has been validated as a biomarker of response to adjuvant therapy and better survival in patients with breast carcinoma and several other types of human solid tumors. Additional immune endpoints are being currently tested as potentially promising biomarkers in cancer. In view of currently growing use of immune cancer therapies, the search for immune biomarkers of prognosis are critically important for identifying patients who would benefit the most from adjuvant immunotherapy.

  3. Chemical Tools To Monitor and Manipulate Adaptive Immune Responses.

    Science.gov (United States)

    Doran, Todd M; Sarkar, Mohosin; Kodadek, Thomas

    2016-05-18

    Methods to monitor and manipulate the immune system are of enormous clinical interest. For example, the development of vaccines represents one of the earliest and greatest accomplishments of the biomedical research enterprise. More recently, drugs capable of "reawakening" the immune system to cancer have generated enormous excitement. But, much remains to be done. All drugs available today that manipulate the immune system cannot distinguish between "good" and "bad" immune responses and thus drive general and systemic immune suppression or activation. Indeed, with the notable exception of vaccines, our ability to monitor and manipulate antigen-specific immune responses is in its infancy. Achieving this finer level of control would be highly desirable. For example, it might allow the pharmacological editing of pathogenic immune responses without restricting the ability of the immune system to defend against infection. On the diagnostic side, a method to comprehensively monitor the circulating, antigen-specific antibody population could provide a treasure trove of clinically useful biomarkers, since many diseases expose the immune system to characteristic molecules that are deemed foreign and elicit the production of antibodies against them. This Perspective will discuss the state-of-the-art of this area with a focus on what we consider seminal opportunities for the chemistry community to contribute to this important field. PMID:27115249

  4. The Role of the Immune Response in Merkel Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Triozzi, Pierre L., E-mail: triozzp@ccf.org [Taussig Cancer Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195 (United States); Fernandez, Anthony P. [Departments of Dermatology and Anatomic Pathology, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195 (United States)

    2013-02-28

    Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer. The Merkel cell polyomavirus (MCPyV) is implicated in its pathogenesis. Immune mechanisms are also implicated. Patients who are immunosuppressed have an increased risk. There is evidence that high intratumoral T-cell counts and immune transcripts are associated with favorable survival. Spontaneous regressions implicate immune effector mechanisms. Immunogenicity is also supported by observation of autoimmune paraneoplastic syndromes. Case reports suggest that immune modulation, including reduction of immune suppression, can result in tumor regression. The relationships between MCPyV infection, the immune response, and clinical outcome, however, remain poorly understood. Circulating antibodies against MCPyV antigens are present in most individuals. MCPyV-reactive T cells have been detected in both MCC patients and control subjects. High intratumoral T-cell counts are also associated with favorable survival in MCPyV-negative MCC. That the immune system plays a central role in preventing and controlling MCC is supported by several observations. MCCs often develop, however, despite the presence of humoral and cellular immune responses. A better understanding on how MCPyV and MCC evade the immune response will be necessary to develop effective immunotherapies.

  5. The Role of the Immune Response in Merkel Cell Carcinoma

    International Nuclear Information System (INIS)

    Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer. The Merkel cell polyomavirus (MCPyV) is implicated in its pathogenesis. Immune mechanisms are also implicated. Patients who are immunosuppressed have an increased risk. There is evidence that high intratumoral T-cell counts and immune transcripts are associated with favorable survival. Spontaneous regressions implicate immune effector mechanisms. Immunogenicity is also supported by observation of autoimmune paraneoplastic syndromes. Case reports suggest that immune modulation, including reduction of immune suppression, can result in tumor regression. The relationships between MCPyV infection, the immune response, and clinical outcome, however, remain poorly understood. Circulating antibodies against MCPyV antigens are present in most individuals. MCPyV-reactive T cells have been detected in both MCC patients and control subjects. High intratumoral T-cell counts are also associated with favorable survival in MCPyV-negative MCC. That the immune system plays a central role in preventing and controlling MCC is supported by several observations. MCCs often develop, however, despite the presence of humoral and cellular immune responses. A better understanding on how MCPyV and MCC evade the immune response will be necessary to develop effective immunotherapies

  6. Heavy metal pollution disturbs immune response in wild ant populations

    Energy Technology Data Exchange (ETDEWEB)

    Sorvari, Jouni [Section of Ecology, Department of Biology, University of Turku, FIN-20014 Turku (Finland)]. E-mail: jouni.sorvari@utu.fi; Rantala, Liisa M. [Department of Biological and Environmental Science, University of Jyvaeskylae, P.O. Box 35, FIN-40351 Jyvaeskylae (Finland); Rantala, Markus J. [Section of Ecology, Department of Biology, University of Turku, FIN-20014 Turku (Finland); Department of Biology, University of California, Riverside, CA 92521 USA (United States); Hakkarainen, Harri [Section of Ecology, Department of Biology, University of Turku, FIN-20014 Turku (Finland); Eeva, Tapio [Section of Ecology, Department of Biology, University of Turku, FIN-20014 Turku (Finland)

    2007-01-15

    Concern about the effects of environmental contaminants on immune function in both humans and wildlife is growing and practically nothing is known about this impact on terrestrial invertebrates, even though they are known to easily accumulate pollutants. We studied the effect of industrial heavy metal contamination on immune defense of a free-living wood ant (Formica aquilonia). To find out whether ants show an adapted immune function in a polluted environment, we compared encapsulation responses between local and translocated colonies. Local colonies showed higher heavy metal levels than the translocated ones but the encapsulation response was similar between the two groups, indicating that the immune system of local ants has not adapted to high contamination level. The encapsulation response was elevated in moderate whereas suppressed in high heavy metal levels suggesting higher risk for infections in heavily polluted areas. - Heavy metal pollution affects immune function in ants.

  7. Immune response induction in the central nervous system

    DEFF Research Database (Denmark)

    Owens, Trevor; Babcock, Alicia

    2002-01-01

    The primary function of the immune response is protection of the host against infection with pathogens, including viruses. Since viruses can infect any tissue of the body, including the central nervous system (CNS), it is logical that cells of the immune system should equally have access to all...... tissues. Nevertheless, the brain and spinal cord are noted for their lack of immune presence. Relative to other organ systems, the CNS appears immunologically privileged. Furthermore, when immune responses do occur in the CNS, they are frequently associated with deleterious effects such as inflammatory...... and/or demyelinating pathology. This article will review the molecular and cellular dynamics of immune responses in the CNS, with particular emphasis on autoimmune inflammation, as has been studied in the authors' laboratory....

  8. Heavy metal pollution disturbs immune response in wild ant populations

    International Nuclear Information System (INIS)

    Concern about the effects of environmental contaminants on immune function in both humans and wildlife is growing and practically nothing is known about this impact on terrestrial invertebrates, even though they are known to easily accumulate pollutants. We studied the effect of industrial heavy metal contamination on immune defense of a free-living wood ant (Formica aquilonia). To find out whether ants show an adapted immune function in a polluted environment, we compared encapsulation responses between local and translocated colonies. Local colonies showed higher heavy metal levels than the translocated ones but the encapsulation response was similar between the two groups, indicating that the immune system of local ants has not adapted to high contamination level. The encapsulation response was elevated in moderate whereas suppressed in high heavy metal levels suggesting higher risk for infections in heavily polluted areas. - Heavy metal pollution affects immune function in ants

  9. Paradoxical acclimation responses in the thermal performance of insect immunity.

    Science.gov (United States)

    Ferguson, Laura V; Heinrichs, David E; Sinclair, Brent J

    2016-05-01

    Winter is accompanied by multiple stressors, and the interactions between cold and pathogen stress potentially determine the overwintering success of insects. Thus, it is necessary to explore the thermal performance of the insect immune system. We cold-acclimated spring field crickets, Gryllus veletis, to 6 °C for 7 days and measured the thermal performance of potential (lysozyme and phenoloxidase activity) and realised (bacterial clearance and melanisation) immune responses. Cold acclimation decreased the critical thermal minimum from -0.5 ± 0.25 to -2.1 ± 0.18 °C, and chill coma recovery time after 72 h at -2 °C from 16.8 ± 4.9 to 5.2 ± 2.0 min. Measures of both potential and realised immunity followed a typical thermal performance curve, decreasing with decreasing temperature. However, cold acclimation further decreased realised immunity at low, but not high, temperatures; effectively, immune activity became paradoxically specialised to higher temperatures. Thus, cold acclimation induced mismatched thermal responses between locomotor and immune systems, as well as within the immune system itself. We conclude that cold acclimation in insects appears to preferentially improve cold tolerance over whole-animal immune performance at low temperatures, and that the differential thermal performance of physiological responses to multiple pressures must be considered when predicting ectotherms' response to climate change. PMID:26846428

  10. Altered Allogeneic Immune Responses in Middle-Aged Mice

    Institute of Scientific and Technical Information of China (English)

    YiminSun; HanhanLi; AlanN.Langnas

    2004-01-01

    It is well known that leukocyte composition, T cell phenotypes and immune function change in aged mice and humans. However, limited and conflicting results on the age-related immune changes in middle-aged mice were reported. Identification of the characteristics of allogeneic immune responses in aging mice may offer important information for transplantation immunology. The major age-related changes in the immune cell phenotypes and function of 12 months old mice include: 1) the significantly decreased CD4+ cell population in the peripheral blood, the major peripheral CD4+ cells is CD45RBlowCD62Llow memory phenotype; 2) the in vitro responses to alloantigens and Con A of splenocytes markedly reduced; 3) the in vivo secondary humoral immune responses to alloantigens significantly declined; 4) the age-related alteration in the thymus mainly occurred in CD4/CD8 double positive (DP) stage; and 5) increased CD80+ and MHC class II+ cell population in spleens. Thus, the major age-related immune changes in 12 months old mice occurred in CD4+ T cells in the periphery and DP stage in the thymus, which may subsequently lead to the decreased allogeneic immune responses and the different sensitivity to immunosuppressive drugs and treatments. Further studies on the characteristics of allogeneic immunity in aging individuals may help to determine the appropriated treatment for transplant aging individuals. Cellular & Molecular Immunology. 2004;1(6):440-446.

  11. Altered Allogeneic Immune Responses in Middle-Aged Mice

    Institute of Scientific and Technical Information of China (English)

    Yimin Sun; Hanhan Li; Alan N. Langnas; Yong Zhao

    2004-01-01

    It is well known that leukocyte composition, T cell phenotypes and immune function change in aged mice and humans. However, limited and conflicting results on the age-related immune changes in middle-aged mice were reported. Identification of the characteristics of allogeneic immune responses in aging mice may offer important information for transplantation immunology. The major age-related changes in the immune cell phenotypes and function of 12 months old mice include: 1) the significantly decreased CD4+ cell population in the peripheral blood, the major peripheral CD4+ cells is CD45RBlowCD62Llow memory phenotype; 2) the in vitro responses to alloantigens and Con A of splenocytes markedly reduced; 3) the in vivo secondary humoral immune responses to alloantigens significantly declined; 4) the age-related alteration in the thymus mainly occurred in CD4/CD8 double positive (DP) stage; and 5) increased CD80+ and MHC class Ⅱ+ cell population in spleens. Thus, the major age-related immune changes in 12 months old mice occurred in CD4+ T cells in the periphery and DP stage in the thymus, which may subsequently lead to the decreased allogeneic immune responses and the different sensitivity to immunosuppressive drugs and treatments. Further studies on the characteristics of allogeneic immunity in aging individuals may help to determine the appropriated treatment for transplant aging individuals. Cellular & Molecular Immunology. 2004; 1(6) :440-446.

  12. Measuring antigen-specific immune responses: 2008 Update

    NARCIS (Netherlands)

    J.W. Gratama (Jan-Willem); F. Kern (Florian); F. Manca (Fabrizio); M. Roederer (Mario)

    2008-01-01

    textabstractOverall, the last 10 years have seen an explosion in the field of antigen-specific immune response monitoring. As summarized in this issue of Cytometry and at the MASIR conferences, these technologies have provided new insights into the basic biology of the immune system and are beginnin

  13. Sublingual nucleotides and immune response to exercise

    Directory of Open Access Journals (Sweden)

    Ostojic Sergej M

    2012-07-01

    Full Text Available Abstract Evidence exists regarding the potential role of exogenous nucleotides as regulators of the immune function in physically active humans, yet the potential use of nucleotides has been hindered by their low bioavailability after oral administration. We conducted a double-blind, placebo-controlled, randomized trial to assess the effect of sublingual nucleotides (50 mg/day on salivary and serum immunity indicators as compared to placebo, both administered to healthy males aged 20 to 25 years for 14 days. Sublingual administration of nucleotides for 14 days increased serum immunoglobulin A, natural killer cells count and cytotoxic activity, and offset the post-exercise drop of salivary immunoglobulins and lactoferrin (P  0.05. It seems that sublingual administration of nucleotides for two weeks considerably affected immune function in healthy males.

  14. Carbohydrate Mimetic Peptides Augment Carbohydrate-Reactive Immune Responses in the Absence of Immune Pathology

    Energy Technology Data Exchange (ETDEWEB)

    Hennings, Leah; Artaud, Cecile; Jousheghany, Fariba; Monzavi-Karbassi, Behjatolah; Pashov, Anastas; Kieber-Emmons, Thomas, E-mail: tke@uams.edu [Winthrop P. Rockefeller Cancer Institute and Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States)

    2011-11-11

    Among the most challenging of clinical targets for cancer immunotherapy are Tumor Associated Carbohydrate Antigens (TACAs). To augment immune responses to TACA we are developing carbohydrate mimetic peptides (CMPs) that are sufficiently potent to activate broad-spectrum anti-tumor reactivity. However, the activation of immune responses against terminal mono- and disaccharide constituents of TACA raises concerns regarding the balance between “tumor destruction” and “tissue damage”, as mono- and disaccharides are also expressed on normal tissue. To support the development of CMPs for clinical trial testing, we demonstrate in preclinical safety assessment studies in mice that vaccination with CMPs can enhance responses to TACAs without mediating tissue damage to normal cells expressing TACA. BALB/c mice were immunized with CMPs that mimic TACAs reactive with Griffonia simplicifolia lectin 1 (GS-I), and tissue reactivity of serum antibodies were compared with the tissue staining profile of GS-I. Tissues from CMP immunized mice were analyzed using hematoxylin and eosin stain, and Luxol-fast blue staining for myelination. Western blots of membranes from murine mammary 4T1 cells, syngeneic with BALB/c mice, were also compared using GS-I, immunized serum antibodies, and naive serum antibodies. CMP immunization enhanced glycan reactivities with no evidence of pathological autoimmunity in any immunized mice demonstrating that tissue damage is not an inevitable consequence of TACA reactive responses.

  15. Carbohydrate Mimetic Peptides Augment Carbohydrate-Reactive Immune Responses in the Absence of Immune Pathology

    International Nuclear Information System (INIS)

    Among the most challenging of clinical targets for cancer immunotherapy are Tumor Associated Carbohydrate Antigens (TACAs). To augment immune responses to TACA we are developing carbohydrate mimetic peptides (CMPs) that are sufficiently potent to activate broad-spectrum anti-tumor reactivity. However, the activation of immune responses against terminal mono- and disaccharide constituents of TACA raises concerns regarding the balance between “tumor destruction” and “tissue damage”, as mono- and disaccharides are also expressed on normal tissue. To support the development of CMPs for clinical trial testing, we demonstrate in preclinical safety assessment studies in mice that vaccination with CMPs can enhance responses to TACAs without mediating tissue damage to normal cells expressing TACA. BALB/c mice were immunized with CMPs that mimic TACAs reactive with Griffonia simplicifolia lectin 1 (GS-I), and tissue reactivity of serum antibodies were compared with the tissue staining profile of GS-I. Tissues from CMP immunized mice were analyzed using hematoxylin and eosin stain, and Luxol-fast blue staining for myelination. Western blots of membranes from murine mammary 4T1 cells, syngeneic with BALB/c mice, were also compared using GS-I, immunized serum antibodies, and naive serum antibodies. CMP immunization enhanced glycan reactivities with no evidence of pathological autoimmunity in any immunized mice demonstrating that tissue damage is not an inevitable consequence of TACA reactive responses

  16. Virus-like nanostructures for tuning immune response

    Science.gov (United States)

    Mammadov, Rashad; Cinar, Goksu; Gunduz, Nuray; Goktas, Melis; Kayhan, Handan; Tohumeken, Sehmus; Topal, Ahmet E.; Orujalipoor, Ilghar; Delibasi, Tuncay; Dana, Aykutlu; Ide, Semra; Tekinay, Ayse B.; Guler, Mustafa O.

    2015-11-01

    Synthetic vaccines utilize viral signatures to trigger immune responses. Although the immune responses raised against the biochemical signatures of viruses are well characterized, the mechanism of how they affect immune response in the context of physical signatures is not well studied. In this work, we investigated the ability of zero- and one-dimensional self-assembled peptide nanostructures carrying unmethylated CpG motifs (signature of viral DNA) for tuning immune response. These nanostructures represent the two most common viral shapes, spheres and rods. The nanofibrous structures were found to direct immune response towards Th1 phenotype, which is responsible for acting against intracellular pathogens such as viruses, to a greater extent than nanospheres and CpG ODN alone. In addition, nanofibers exhibited enhanced uptake into dendritic cells compared to nanospheres or the ODN itself. The chemical stability of the ODN against nuclease-mediated degradation was also observed to be enhanced when complexed with the peptide nanostructures. In vivo studies showed that nanofibers promoted antigen-specific IgG production over 10-fold better than CpG ODN alone. To the best of our knowledge, this is the first report showing the modulation of the nature of an immune response through the shape of the carrier system.

  17. Evaluation of immune response elicited by inulin as an adjuvant with filarial antigens in mice model.

    Science.gov (United States)

    Mahalakshmi, N; Aparnaa, R; Kaliraj, P

    2014-10-01

    Filariasis caused by infectious parasitic nematodes has been identified as the second leading source of permanent and long-term disability in Sub-Saharan Africa, Asia and Latin America. Several vaccine candidates were identified from infective third-stage larvae (L3) which involves in the critical transition from arthropod to human. Hitherto studies of these antigens in combination with alum adjuvant have shown to elicit its characteristic Th2 responses. Inulin is a safe, non-toxic adjuvant that principally stimulates the innate immune response through the alternative complement pathway. In the present study, the immune response elicited by inulin and alum as adjuvants were compared with filarial antigens from different aetiological agents: secreted larval acidic protein 1 (SLAP1) from Onchocerca volvulus and venom allergen homologue (VAH) from Brugia malayi as single or as cocktail vaccines in mice model. The study revealed that inulin can induce better humoral response against these antigens than alum adjuvant. Antibody isotyping disclosed inulin's ability to elevate the levels of IgG2a and IgG3 antibodies which mediates in complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity (ADCC), respectively, in mice. Splenocyte analysis showed that T cells prestimulated with inulin have higher stimulation index (P < 0.05) than alum except for BmVAH antigen. In vitro ADCC assay showed that inulin formulation had induced higher cytotoxicity with filarial antigens (as single P < 0.01 and as cocktail P < 0.05, respectively) than alum. The results had confirmed the capability of inulin to deplete the levels of Treg and brought a balance in Th1/Th2 arms against filarial antigens in mice. PMID:25041426

  18. 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. PMID:21395512

  19. Nanoparticles for nasal delivery of vaccines : monitoring adaptive immune responses

    NARCIS (Netherlands)

    Keijzer, C.

    2013-01-01

    The continuous emergence of new pathogens and growing drug resistance of microorganisms asks for innovative vaccination strategies. An alternative to conventional multiple injection vaccines is the nasal route of vaccine delivery. The immune response induced following nasal antigen delivery depends

  20. Role of T-cell-mediated inflammation in psoriasis: pathogenesis and targeted therapy

    Directory of Open Access Journals (Sweden)

    Flatz L

    2013-02-01

    Full Text Available Lukas Flatz, Curdin ConradDepartment of Dermatology, University Hospital of Lausanne (CHUV, Lausanne, SwitzerlandAbstract: Psoriasis is one of the most common chronic, inflammatory, T-cell-mediated autoimmune diseases. Over the past decade, increased knowledge of disease pathogenesis has fundamentally changed psoriasis treatment, with the introduction of biologics, and this has led to a multitude of improved selective targets providing potential therapeutic options. Indeed, numerous pathogenesis-based treatments are currently in development, as psoriasis has also become increasingly relevant for proof-of-concept studies. The purpose of this review was to summarize current knowledge of psoriasis immunopathogenesis, focusing on the T-cell-mediated immune response and its initiation. The authors describe recent advances in psoriasis treatment and discuss pathogenesis-based therapies that are currently in development or which could be envisioned for the future. Although current biologics are well tolerated, several issues such as long-term efficacy, long-term safety, and high costs keep driving the search for new and better therapies. With further advances in understanding disease pathogenesis, more genomic data from psoriasis patients becoming available, and potentially the identification of autoantigens in psoriasis, current research should lead to the development of a growing arsenal of improved targeted treatments and to further breakthrough immunotherapies.Keywords: autoimmunity, autoimmune disease, immune response, immunopathogenesis

  1. Tasquinimod modulates tumor-infiltrating myeloid cells and improves the antitumor immune response to PD-L1 blockade in bladder cancer

    Science.gov (United States)

    Nakhlé, Jessica; Pierron, Valérie; Bauchet, Anne-Laure; Plas, Pascale; Thiongane, Amath; Meyer-Losic, Florence; Schmidlin, Fabien

    2016-01-01

    ABSTRACT The infiltration of myeloid cells helps tumors to overcome immune surveillance and imparts resistance to cancer immunotherapy. Thus, strategies to modulate the effects of these immune cells may offer a potential therapeutic benefit. We report here that tasquinimod, a novel immunotherapy which targets S100A9 signaling, reduces the immunosuppressive properties of myeloid cells in preclinical models of bladder cancer (BCa). As single anticancer agent, tasquinimod treatment was effective in preventing early stage tumor growth, but did not achieve a clear antitumor effect in advanced tumors. Investigations of this response revealed that tasquinimod induces an increase in the expression of a negative regulator of T cell activation, Programmed-death-ligand 1 (PD-L1). This markedly weakens its antitumor immunity, yet provokes an “inflamed” milieu rendering tumors more prone to T cell-mediated immune attack by PD-L1 blockade. Interestingly, the combination of tasquinimod with an Anti-PD-L1 antibody enhanced the antitumor immune response in bladder tumors. This combination synergistically modulated tumor-infiltrating myeloid cells, thereby strongly affecting proliferation and activation of effector T cells. Together, our data provide insight into the rational combination of therapies that activate both innate and adaptive immune system, such as the association of S100A9-targeting agents with immune checkpoints inhibitors, to improve the response to cancer immunotherapeutic agents in BCa.

  2. Immunization with Surface Antigen Vaccine Alone and after Treatment with 1-(2-Fluoro-5-Methyl-β-l-Arabinofuranosyl)-Uracil (l-FMAU) Breaks Humoral and Cell-Mediated Immune Tolerance in Chronic Woodchuck Hepatitis Virus Infection

    OpenAIRE

    Menne, Stephan; Roneker, Carol A.; Korba, Brent E.; Gerin, John L.; Tennant, Bud C.; Cote, Paul J

    2002-01-01

    Woodchucks chronically infected with the woodchuck hepatitis virus (WHV) were treated with the antiviral drug 1-(2-fluoro-5-methyl-β-l-arabinofuranosyl)-uracil (l-FMAU) or placebo for 32 weeks. Half the woodchucks in each group then received four injections of surface antigen vaccine during the next 16 weeks. Vaccination alone elicited a low-level antibody response to surface antigen in most carriers but did not affect serum WHV DNA and surface antigen. Carriers treated first with l-FMAU to r...

  3. Role of nutrients in the development of neonatal immune response.

    Science.gov (United States)

    Cunningham-Rundles, Susanna; Lin, Hong; Ho-Lin, Deborah; Dnistrian, Ann; Cassileth, Barrie R; Perlman, Jeffrey M

    2009-11-01

    Nutrients exert unique regulatory effects in the perinatal period that mold the developing immune system. The interactions of micronutrients and microbial and environmental antigens condition the post-birth maturation of the immune system, influencing reactions to allergens, fostering tolerance towards the emerging gastrointestinal flora and ingested antigens, and defining patterns of host defense against potential pathogens. The shared molecular structures that are present on microbes or certain plants, but not expressed by human cells, are recognized by neonatal innate immune receptors. Exposure to these activators in the environment through dietary intake in early life can modify the immune response to allergens and prime the adaptive immune response towards pathogens that express the corresponding molecular structures. PMID:19906219

  4. Effect of mycotoxins on swine in immune responses

    OpenAIRE

    Fornalés Pallàs, Clara

    2014-01-01

    Póster Mycotoxins are secondary metabolites of fungi, hazardous to human and animal health. Their effect has been mostly studied in medium or half doses. It has been stated that, at lower, subclinical doses, mycotoxins may alter immune response, thus predisposing the appearance of diseases. Swine are a good model for studying the effect of mycotoxins to extrapolate to humans. This review is focused on the effect of most common mycotoxins on Swine immune response.

  5. Immune response to measles vaccine in Peruvian children.

    OpenAIRE

    Bautista-López Norma L.; Vaisberg Abraham; Kanashiro Rosa; Hernández Herminio; Ward Brian J.

    2001-01-01

    OBJECTIVE: To evaluate the immune response in Peruvian children following measles vaccination. METHODS: Fifty-five Peruvian children received Schwarz measles vaccine (about 10(3) plaque forming units) at about 9 months of age. Blood samples were taken before vaccination, then twice after vaccination: one sample at between 1 and 4 weeks after vaccination and the final sample 3 months post vaccination for evaluation of immune cell phenotype and lymphoproliferative responses to measles and non-m...

  6. Respons imun humoral pada pulpitis (Humoral immune response on pulpitis

    Directory of Open Access Journals (Sweden)

    Trijoedani Widodo

    2005-06-01

    Full Text Available Pulpitis is an inflammation process on dental pulp tissue, and usually as the continuous of caries. The microorganism in the caries is a potential immunogenic triggering the immune respons, both humoral and celluler immune responses. The aim of this research is to explain the humoral immune response changes in the dental pulp tissues of pulpitis. This research was done on three group samples: Irreversible pulpitis, Reversible pulpitis and sound teeth as the control group. The result showed that there were three pulpitis immunopathologic patterns: the sound teeth immunopathologic pattern showing a low humoral immune response, in a low level of IgG, IgA and IgM, the reversible pulpitis pattern showing that in a higher humoral immune response, IgG and IgA decreased but IgM increased, the irreversible pulpitis pattern showing that IgG and IgM increased, but it couldn't be repaired although it has highly immunity, and it showed an unusually low level of IgA. This low level of IgA meant that irreversible pulpitis had a low mucosal immunity.

  7. Modeling the interactions between pathogenic bacteria, bacteriophage and immune response

    Science.gov (United States)

    Leung, Chung Yin (Joey); Weitz, Joshua S.

    The prevalence of antibiotic-resistant strains of pathogenic bacteria has led to renewed interest in the use of bacteriophage (phage), or virus that infects bacteria, as a therapeutic agent against bacterial infections. However, little is known about the theoretical mechanism by which phage therapy may work. In particular, interactions between the bacteria, the phage and the host immune response crucially influences the outcome of the therapy. Few models of phage therapy have incorporated all these three components, and existing models suffer from unrealistic assumptions such as unbounded growth of the immune response. We propose a model of phage therapy with an emphasis on nonlinear feedback arising from interactions with bacteria and the immune response. Our model shows a synergistic effect between the phage and the immune response which underlies a possible mechanism for phage to catalyze the elimination of bacteria even when neither the immune response nor phage could do so alone. We study the significance of this effect for different parameters of infection and immune response, and discuss its implications for phage therapy.

  8. A novel vaccine p846 encoding Rv3615c, Mtb10.4, and Rv2660c elicits robust immune response and alleviates lung injury induced by Mycobacterium infection.

    Science.gov (United States)

    Kong, Hongmei; Dong, Chunsheng; Xiong, Sidong

    2014-01-01

    Development of effective anti-tuberculosis (TB) vaccines is one of the important steps to improve control of TB. Cell-mediated immune response significantly affects the control of M. tuberculosis infection. Thus, vaccines able to elicit strong cellular immune response hold special advantages against TB. In this study, three well-defined mycobacterial antigens (Rv3615c, Mtb10.4 [Rv0228], and Rv2660c) were engineered as a novel triple-antigen fusion DNA vaccine p846. The p846 vaccine consists of a high density of CD4(+) and CD8(+) T-cell epitopes. Intramuscular immunization of p846 induced robust T cells mediated immune response comparable to that of bacillus Calmette-Guérin (BCG) vaccination but more effective than that of individual antigen vaccination. After mycobacterial challenge, p846 immunization decreased bacterial burden at least 15-fold compared with individual antigen-based vaccination. Notably, the lungs of mice immunized with p846 exhibited fewer inflammatory cell infiltrates and less damage than those of control group mice. Our data demonstrate that the potential of p846 vaccine to protect against TB and the feasibility of this design strategy for further TB vaccine development. PMID:24280763

  9. Risk of Crew Adverse Health Event Due to Altered Immune Response

    Science.gov (United States)

    Crucian, Brian; Kunz, Hawley; Sams, Clarence F.

    2015-01-01

    Determining the effect of space travel on the human immune system has proven to be extremely challenging. Limited opportunities for in-flight studies, varying mission durations, technical and logistical obstacles, small subject numbers, and a broad range of potential assays have contributed to this problem. Additionally, the inherent complexity of the immune system, with its vast array of cell populations, sub-populations, diverse regulatory molecules, and broad interactions with other physiological systems, makes determining precise variables to measure very difficult. There is also the challenge of determining the clinical significance of any observed immune alterations. Will such a change lead to disease, or is it a transient subclinical observation related to short-term stress? The effect of this problem may be observed by scanning publications associated with immunity and spaceflight, which began to appear during the 1970s. Although individually they are each valid studies, the comprehensive literature to date suffers from widely varying sampling methods and assay techniques, low subject counts, and sometimes a disparate focus on narrow aspects of immunity. The most clinically relevant data are derived from in-flight human studies, which have demonstrated altered cell-mediated immunity and reactivation of latent herpes viruses. Much more data are available from post-flight testing of humans, with clear evidence of altered cytokine production patterns, altered leukocyte distribution, continued latent viral reactivation, and evidence of dramatically altered virus-specific immunity. It is unknown if post-flight assessments relate to the in-flight condition or are a response to landing stress and readaptation. In-flight culture of cells has clearly demonstrated that immune cells are gravity-sensitive and display altered functional characteristics. It is unknown if these data are related to in vivo immune cell function or are an artifact of microgravity culture

  10. Supplementation with Natural Forms of Vitamin E Augments Antigen-Specific TH1-Type Immune Response to Tetanus Toxoid

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    Ammu Kutty Radhakrishnan

    2013-01-01

    Full Text Available This study compared the ability of three forms of vitamin E [tocotrienol-rich fraction (TRF, alpha-tocopherol (α-T, and delta-tocotrienol (δ-T3] to enhance immune response to tetanus toxoid (TT immunisation in a mouse model. Twenty BALB/c mice were divided into four groups of five mice each. The mice were fed with the different forms of vitamin E (1 mg or vehicle daily for two weeks before they were given the TT vaccine [4 Lf] intramuscularly (i.m.. Booster vaccinations were given on days 28 and 42. Serum was collected (days 0, 28, and 56 to quantify anti-TT levels. At autopsy, splenocytes harvested were cultured with TT or mitogens. The production of anti-TT antibodies was augmented (P<0.05 in mice that were fed with δ-T3 or TRF compared to controls. The production of IFN-γ and IL-4 by splenocytes from the vitamin E treated mice was significantly (P<0.05 higher than that from controls. The IFN-γ production was the highest in animals supplemented with δ-T3 followed by TRF and finally α-T. Production of TNF-α was suppressed in the vitamin E treated group compared to vehicle-supplemented controls. Supplementation with δ-T3 or TRF can enhance immune response to TT immunisation and production of cytokines that promote cell-mediated (TH1 immune response.

  11. Evaluation of mucosal and systemic immune responses elicited by GPI-0100- adjuvanted influenza vaccine delivered by different immunization strategies.

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    Heng Liu

    Full Text Available 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 often results in poor systemic immunity. In order to find an immunization strategy which satisfies the need for induction of both mucosal and systemic immunity, we compared local and systemic immune responses elicited by two mucosal immunizations, given either by the intranasal (IN or the intrapulmonary (IPL route, with responses elicited by a mucosal prime followed by a systemic boost immunization. The study was conducted in BALB/c mice and the vaccine formulation was an influenza subunit vaccine supplemented with GPI-0100, a saponin-derived adjuvant. While optimal mucosal antibody titers were obtained after two intrapulmonary vaccinations, optimal systemic antibody responses were achieved by intranasal prime followed by intramuscular boost. The latter strategy also resulted in the best T cell response, yet, it was ineffective in inducing nose or lung IgA. Successful induction of secretory IgA, IgG and T cell responses was only achieved with prime-boost strategies involving intrapulmonary immunization and was optimal when both immunizations were given via the intrapulmonary route. Our results underline that immunization via the lungs is particularly effective for priming as well as boosting of local and systemic immune responses.

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

    Science.gov (United States)

    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 often results in poor systemic immunity. In order to find an immunization strategy which satisfies the need for induction of both mucosal and systemic immunity, we compared local and systemic immune responses elicited by two mucosal immunizations, given either by the intranasal (IN) or the intrapulmonary (IPL) route, with responses elicited by a mucosal prime followed by a systemic boost immunization. The study was conducted in BALB/c mice and the vaccine formulation was an influenza subunit vaccine supplemented with GPI-0100, a saponin-derived adjuvant. While optimal mucosal antibody titers were obtained after two intrapulmonary vaccinations, optimal systemic antibody responses were achieved by intranasal prime followed by intramuscular boost. The latter strategy also resulted in the best T cell response, yet, it was ineffective in inducing nose or lung IgA. Successful induction of secretory IgA, IgG and T cell responses was only achieved with prime-boost strategies involving intrapulmonary immunization and was optimal when both immunizations were given via the intrapulmonary route. Our results underline that immunization via the lungs is particularly effective for priming as well as boosting of local and systemic immune responses. PMID:23936066

  13. Chemical agents and the immune response.

    OpenAIRE

    Luster, M I; Rosenthal, G J

    1993-01-01

    Our desire to understand the potential adverse human health effects of environmental chemical exposure has coincided with an increased understanding of the immune system and an appreciation of its complex regulatory network. This has spawned a broad interest in the area of immunotoxicology within the scientific community as well as certain concerns in the public sector regarding chemical-induced hypersensitivity and immunosuppression. The incidence of alleged human sensitization to chemicals ...

  14. Legionella secreted effectors and innate immune responses

    OpenAIRE

    Luo, Zhao-Qing

    2011-01-01

    Legionella pneumophila is a facultative intracellular pathogen capable of replicating in a wide spectrum of cells. Successful infection by Legionella requires the Dot/Icm type IV secretion system, which translocates a large number of effector proteins into infected cells. By co-opting numerous host cellular processes, these proteins function to establish a specialized organelle that allows bacterial survival and proliferation. Even within the vacuole, L. pneumophila triggers robust immune res...

  15. The role of lysosomal cysteine proteases in crustacean immune response

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    FL Garcia-Carreño

    2014-04-01

    Full Text Available Over the long course of evolution and under the selective pressure exerted by pathogens and parasites, animals have selectively fixed a number of defense mechanisms against the constant attack of intruders. The immune response represents a key component to optimize the biological fitness of individuals. Two decades ago, prevention and control of diseases in crustacean aquaculture systems were considered priorities in most shrimp-producing countries, but knowledge was scarce and various pathogens have severely affected aquaculture development around the world. Scientific contributions have improved our understanding of the crustacean immune response. Several studies confirm the central role played by proteases in the immune response of animals, and the cooperative interaction of these enzymes in a wide variety of organisms is well known. This review summarizes the current information regarding the role of cysteine proteases in the immune system of Crustacea and points to aspects that are needed to provide a better integration of our knowledge.

  16. Modulation of systemic immune responses through commensal gastrointestinal microbiota.

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    Kyle M Schachtschneider

    Full Text Available Colonization of the gastrointestinal (GI tract is initiated during birth and continually seeded from the individual's environment. Gastrointestinal microorganisms play a central role in developing and modulating host immune responses and have been the subject of investigation over the last decades. Animal studies have demonstrated the impact of GI tract microbiota on local gastrointestinal immune responses; however, the full spectrum of action of early gastrointestinal tract stimulation and subsequent modulation of systemic immune responses is poorly understood. This study explored the utility of an oral microbial inoculum as a therapeutic tool to affect porcine systemic immune responses. For this study a litter of 12 pigs was split into two groups. One group of pigs was inoculated with a non-pathogenic oral inoculum (modulated, while another group (control was not. DNA extracted from nasal swabs and fecal samples collected throughout the study was sequenced to determine the effects of the oral inoculation on GI and respiratory microbial communities. The effects of GI microbial modulation on systemic immune responses were evaluated by experimentally infecting with the pathogen Mycoplasma hyopneumoniae. Coughing levels, pathology, toll-like receptors 2 and 6, and cytokine production were measured throughout the study. Sequencing results show a successful modulation of the GI and respiratory microbiomes through oral inoculation. Delayed type hypersensitivity responses were stronger (p = 0.07, and the average coughing levels and respiratory TNF-α variance were significantly lower in the modulated group (p<0.0001 and p = 0.0153, respectively. The M. hyopneumoniae infection study showed beneficial effects of the oral inoculum on systemic immune responses including antibody production, severity of infection and cytokine levels. These results suggest that an oral microbial inoculation can be used to modulate microbial communities, as well as

  17. Acquired and innate immunity to polyaromatic hydrocarbons

    International Nuclear Information System (INIS)

    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

  18. [Effect of anabolic steroid on immune response].

    Science.gov (United States)

    Yamagishi, H; Kobayashi, M; Konosu, H; Kurioka, H; Naito, K; Sonoyama, T; Nishimoto, T; Hashimoto, I

    1984-03-01

    Using lymphocyte, monocyte and eosinophil counts of the peripheral blood, PHA-blastoid transformation, immunoglobulin and beta 2-microglobulin, the influence of anabolic steroid on the immune reactivity of the host was dissected by administration of Deca-Durabolin ( nandrolone decanoate) to both tumor-bearing host and tumor-free host after operation for alimentary tract. The number of peripheral lymphocytes and monocytes, the PHA-blastoid transformation of peripheral lymphocytes and the IgG level were increased, and the beta 2-microglobulin level showed the tendency of decrease after the administration of Deca-Durabolin. PMID:6367663

  19. Genetic immunization in the lung induces potent local and systemic immune responses.

    Science.gov (United States)

    Song, Kaimei; Bolton, Diane L; Wei, Chih-Jen; Wilson, Robert L; Camp, Jeremy V; Bao, Saran; Mattapallil, Joseph J; Herzenberg, Leonore A; Herzenberg, Leonard A; Andrews, Charla A; Sadoff, Jerald C; Goudsmit, Jaap; Pau, Maria Grazia; Seder, Robert A; Kozlowski, Pamela A; Nabel, Gary J; Roederer, Mario; Rao, Srinivas S

    2010-12-21

    Successful vaccination against respiratory infections requires elicitation of high levels of potent and durable humoral and cellular responses in the lower airways. To accomplish this goal, we used a fine aerosol that targets the entire lung surface through normal respiration to deliver replication-incompetent recombinant adenoviral vectors expressing gene products from several infectious pathogens. We show that this regimen induced remarkably high and stable lung T-cell responses in nonhuman primates and that it also generated systemic and respiratory tract humoral responses of both IgA and IgG isotypes. Moreover, strong immunogenicity was achieved even in animals with preexisting antiadenoviral immunity, overcoming a critical hurdle to the use of these vectors in humans, who commonly are immune to adenoviruses. The immunogenicity profile elicited with this regimen, which is distinct from either intramuscular or intranasal delivery, has highly desirable properties for protection against respiratory pathogens. We show that it can be used repeatedly to generate mucosal humoral, CD4, and CD8 T-cell responses and as such may be applicable to other mucosally transmitted pathogens such as HIV. Indeed, in a lethal challenge model, we show that aerosolized recombinant adenoviral immunization completely protects ferrets against H5N1 highly pathogenic avian influenza virus. Thus, genetic immunization in the lung offers a powerful platform approach to generating protective immune responses against respiratory pathogens. PMID:21135247

  20. Immunomodulator-based enhancement of anti smallpox immune responses.

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    Osmarie Martínez

    Full Text Available The current live vaccinia virus vaccine used in the prevention of smallpox is contraindicated for millions of immune-compromised individuals. Although vaccination with the current smallpox vaccine produces protective immunity, it might result in mild to serious health complications for some vaccinees. Thus, there is a critical need for the production of a safe virus-free vaccine against smallpox that is available to everyone. For that reason, we investigated the impact of imiquimod and resiquimod (Toll-like receptors agonists, and the codon-usage optimization of the vaccinia virus A27L gene in the enhancement of the immune response, with intent of producing a safe, virus-free DNA vaccine coding for the A27 vaccinia virus protein.We analyzed the cellular-immune response by measuring the IFN-γ production of splenocytes by ELISPOT, the humoral-immune responses measuring total IgG and IgG2a/IgG1 ratios by ELISA, and the TH1 and TH2 cytokine profiles by ELISA, in mice immunized with our vaccine formulation.The proposed vaccine formulation enhanced the A27L vaccine-mediated production of IFN-γ on mouse spleens, and increased the humoral immunity with a TH1-biased response. Also, our vaccine induced a TH1 cytokine milieu, which is important against viral infections.These results support the efforts to find a new mechanism to enhance an immune response against smallpox, through the implementation of a safe, virus-free DNA vaccination platform.

  1. Signaling molecules involved in immune responses in mussels

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    S Koutsogiannaki

    2010-01-01

    Full Text Available Immune system of molluscs is constituted by hemocytes and humoral factors that cooperate for the protection of the organism, triggering a wide range of immune responses. In molluscs, immune responses include phagocytosis, encapsulation, respiratory burst leading to reactive oxygen species (ROS production and nitric oxide (NO synthesis, release of antimicrobial molecules and the activation of phenoloxidase system. These responses are mediated firstly by a variety of hemocyte receptors binding to ligands that results to a cascade of signaling events. The processes of hemocytes adhesion to and migration through extracellular matrix (ECM proteins play a crucial role in cell immunity. Results suggest that cadmium and oxidants induce adhesion to and migration through ECM proteins in Mytilus gallorovincialis hemocytes with the involvement of Na+/H+ exchanger (NHE, phosphatidylinositol-3 kinase (PI-3K, protein kinase C (PKC, NADPH oxidase, ROS and NO as well as with α2 integrin subunit. Furthermore, the data so far suggests the involvement of additional signaling molecules such as mitogen-activated protein kinases (MAPKs, signal transducers and activators of transcription (STATs, c-Jun N-terminal kinase (JNK, extracellular signal-regulated kinase (ERK, cyclic adenosine monophosphate (cAMP, responsive element binding protein (CREB and nuclear factor kappa B (NF-kB in molluscs immunity. Further research in mollusc immune system may lead to a more sufficient protection and to a better control of these economically important organisms.

  2. Recombinant HPV16 E7 assembled into particles induces an immune response and specific tumour protection administered without adjuvant in an animal model

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    Giorgi Colomba

    2011-05-01

    Full Text Available Abstract Background The HPV16 E7 protein is both a tumour-specific and a tumour-rejection antigen, the ideal target for developing therapeutic vaccines for the treatment of HPV16-associated cancer and its precursor lesions. E7, which plays a key role in virus-associated carcinogenesis, contains 98 amino acids and has two finger-type structures which bind a Zn++ ion. The ability of an Escherichia coli-produced E7-preparation, assembled into particles, to induce protective immunity against a HPV16-related tumour in the TC-1-C57BL/6 mouse tumour model, was evaluated. Methods E7 was expressed in E. coli, purified via a one-step denaturing protocol and prepared as a soluble suspension state after dialysis in native buffer. The presence in the E7 preparation of particulate forms was analysed by non-reducing SDS-PAGE and negative staining electron microscopy (EM. The Zn++ ion content was analysed by mass-spectrometry. Ten μg of protein per mouse was administered to groups of animals, once, twice or three times without adjuvant. The E7-specific humoral response was monitored in mice sera using an E7-based ELISA while the cell-mediated immune response was analysed in mice splenocytes with lymphoproliferation and IFN-γ ELISPOT assays. The E7 immunized mice were challenged with TC-1 tumour cells and the tumour growth monitored for two months. Results In western blot analysis E7 appears in multimers and high molecular mass oligomers. The EM micrographs show the protein dispersed as aggregates of different shape and size. The protein appears clustered in micro-, nano-aggregates, and structured particles. Mice immunised with this protein preparation show a significant E7-specific humoral and cell-mediated immune response of mixed Th1/Th2 type. The mice are fully protected from the tumour growth after vaccination with three E7-doses of 10 μg without any added adjuvant. Conclusions This report shows that a particulate form of HPV16 E7 is able to induce

  3. Balancing immune protection and immune pathology by CD8+ T cell responses to influenza infection

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    Susu eDuan

    2016-02-01

    Full Text Available Influenza A virus (IAV is a significant human pathogen causing annual epidemics and periodic pandemics. CD8+ cytotoxic T lymphocyte (CTL-mediated immunity contributes to clearance of virus-infected cells; CTL immunity targeting the conserved internal proteins of IAVs is a key protection mechanism when neutralizing antibodies are absent during heterosubtypic IAV infection. However, CTL infiltration into the airways, their cytotoxicity, and the effects of produced pro-inflammatory cytokines can cause severe lung tissue injury, thereby contributing to immunopathology. Studies have discovered complicated and exquisite stimulatory and inhibitory mechanisms that regulate CTL magnitude and effector activities during IAV infection. Here, we review the state of knowledge on the roles of IAV-specific CTLs in immune protection and immunopathology during IAV infection in animal models, highlighting the key findings of various requirements and constraints regulating the balance of immune protection and pathology involved in CTL immunity. We also discuss the evidence of cross-reactive CTL immunity as a positive correlate of cross-subtype protection during secondary IAV infection in both animal and human studies. We argue that the effects of CTL immunity on protection and immunopathology depend on multiple layers of host and viral factors, including complex host mechanisms to regulate CTL magnitude and effector activity, the pathogenic nature of the IAV, the innate response milieu, and the host historical immune context of influenza infection. Future efforts are needed to further understand these key host and viral factors, especially to differentiate those that constrain optimally effective CTL anti-viral immunity from those necessary to restrain CTL-mediated nonspecific immunopathology in the various contexts of IAV infection, in order to develop better vaccination and therapeutic strategies for modifying protective CTL immunity.

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

    Science.gov (United States)

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

    1994-01-01

    The aim of this work was to estimate influence of activated immune response on hematopoiesis in vitro, using the experimental model of BCG immunized BALB/c mice and in patients with chronic immunoactivation: long-lasting infections, autoimmunity or malignancy. We correlated changes in long term bone marrow cultures (Dexter) and NBT reduction with appearance of anemia in patients and experimental model of immunization by BCG. Increased spontaneous NBT reduction pointed out role of macrophage activation in bone marrow stroma damage. Long-term bone marrow cultures showed reduced number of hematopoietic cells, with predomination of fibroblasts and loss of fat cells. This results correlated with anemia and leucocytosis with stimulated myelopoiesis in peripheral blood. Activation of immune response, or acting of any agent that directly changes extracellular matrix and cellularity of bone marrow, may result in microenviroment bone marrow damage that modify hematopoiesis. PMID:18173180

  5. Modulation of Immune Response Using Engineered Nanoparticle Surfaces.

    Science.gov (United States)

    Moyano, Daniel F; Liu, Yuanchang; Peer, Dan; Rotello, Vincent M

    2016-01-01

    Nanoparticles (NPs) coated with a monolayer of ligands can be recognized by different components of the immune system, opening new doors for the modulation of immunological responses. By the use of different physical or chemical properties at the NP surface (such as charge, functional groups, and ligand density), NPs can be designed to have distinct cellular uptake, cytokine secretion, and immunogenicity, factors that influence the distribution and clearance of these particles. Understanding these immunological responses is critical for the development of new NP-based carriers for the delivery of therapeutic molecules, and as such several studies have been performed to understand the relationships between immune responses and NP surface functionality. In this review, we will discuss recent reports of these structure-activity relationships, and explore how these motifs can be controlled to elicit therapeutically useful immune responses. PMID:26618755

  6. The Immune Response and Its Therapeutic Modulation in Bronchiectasis

    OpenAIRE

    Massoud Daheshia; Prahl, James D.; Carmichael, Jacob J.; Parrish, John S.; Gilbert Seda

    2012-01-01

    Bronchiectasis (BC) is a chronic pulmonary disease with tremendous morbidity and significant mortality. As pathogen infection has been advocated as a triggering insult in the development of BC, a central role for the immune response in this process seems obvious. Inflammatory cells are present in both the airways as well as the lung parenchyma, and multiple mediators of immune cells including proteases and cytokines or their humoral products are increased locally or in the periphery. Interest...

  7. Interactions between dietary chicory, gut microbiota and immune responses

    OpenAIRE

    Liu, Haoyu

    2013-01-01

    This thesis provides a better understanding of interactions between diet, gut microbiota, and immune responses to a specific dietary fiber source, chicory (Cichorium intybus L). This was achieved by examining the impact of chicory fiber on animal performance, digestibility, gut development, commensal bacteria community structure in small and large intestine, and follow-up reactions with specific immune components, cytoprotective heat shock protein (HSP) 27 and 72, in vivo and in vitro. T...

  8. Extracellular Adenosine Mediates a Systemic Metabolic Switch during Immune Response

    OpenAIRE

    Lazzaro, Brian P.

    2015-01-01

    Life history theory predicts that trait evolution should be constrained by competing physiological demands on an organism. Immune defense provides a classic example in which immune responses are presumed to be costly and therefore come at the expense of other traits related to fitness. One strategy for mitigating the costs of expensive traits is to render them inducible, such that the cost is paid only when the trait is utilized. In the current issue of PLOS Biology, Bajgar and colleagues ele...

  9. A Humoral Immune Response Confers Protection against Haemophilus ducreyi Infection

    OpenAIRE

    Cole, Leah E.; Toffer, Kristen L.; Fulcher, Robert A.; San Mateo, Lani R; Orndorff, Paul E.; Kawula, Thomas H.

    2003-01-01

    Haemophilus ducreyi is the etiologic agent of the sexually transmitted genital ulcer disease chancroid. Neither naturally occurring chancroid nor experimental infection with H. ducreyi results in protective immunity. Likewise, a single inoculation of H. ducreyi does not protect pigs against subsequent infection. Accordingly, we used the swine model of chancroid infection to examine the impact of multiple inoculations on a host's immune response. After three successive inoculations with H. duc...

  10. Scaling of immune responses against intracellular bacterial infection

    OpenAIRE

    Abdullah, Zeinab; Knolle, Percy A.

    2014-01-01

    Macrophages detect bacterial infection through pattern recognition receptors (PRRs) localized at the cell surface, in intracellular vesicles or in the cytosol. Discrimination of viable and virulent bacteria from non-virulent bacteria (dead or viable) is necessary to appropriately scale the anti-bacterial immune response. Such scaling of anti-bacterial immunity is necessary to control the infection, but also to avoid immunopathology or bacterial persistence. PRR-mediated detection of bacterial...

  11. ENDOCANNABINOIDS AND EICOSAMOIDS: BIOSYNTHESIS AND INTERACTIONS WITH IMMUNE RESPONSE

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    Yu. K. Karaman

    2014-07-01

    Full Text Available The review is dedicated to modern concepts of arachidonic acid metabolites, i.e., endocannabinoids and eicosanoids, their biosynthetic pathways, cross-talk mechanisms and participation in immune response. New information from literature and own results include data concerning overlapping enzymatic pathways controlling biosynthesis of endocannabinoids and eicosanoids. Impact of synthetic cannabinoid receptor ligands upon production rates of proinflammatory cytokines and eicosanoids is discussed, as like as relationships among immune system reactivity and expression levels of cannabinoid receptors.

  12. Ageing and the humoral immune response in mice

    International Nuclear Information System (INIS)

    The study presented in this thesis is concerned with changes in the humoral immune system as a function of age in different inbred mouse strains. Their capacity to develop humoral immune responses to experimentally given thymus-dependent and thymus-independent antigens under various conditions is compared. Furthermore, experiments employing thymus transplantation and thymic humoral factors which are directed at the restoration of the diminished T cell functions in old age are reported. (Auth.)

  13. Myeloid-derived suppressor cells: more mechanisms for inhibiting antitumor immunity

    OpenAIRE

    Ostrand-Rosenberg, Suzanne

    2010-01-01

    Myeloid-derived suppressor cells (MDSC) accumulate in most cancer patients and experimental animals with cancer. They accumulate in response to pro-inflammatory mediators and they use a variety of mechanisms to block both innate and adaptive antitumor immunity. Because of their critical role in obstructing immune responses, MDSC are a strategic obstacle to immunotherapies that require activation of the host’s cell-mediated and innate immune responses. Following a brief description of the fact...

  14. Dengue encephalitis-associated immunopathology in the mouse model: Implications for vaccine developers and antigens inducer of cellular immune response.

    Science.gov (United States)

    Marcos, Ernesto; Lazo, Laura; Gil, Lázaro; Izquierdo, Alienys; Suzarte, Edith; Valdés, Iris; Blanco, Aracelys; Ancizar, Julio; Alba, José Suárez; Pérez, Yusleydis de la C; Cobas, Karen; Romero, Yaremis; Guillén, Gerardo; Guzmán, María G; Hermida, Lisset

    2016-08-01

    Despite the many efforts made by the scientific community in the development of vaccine candidates against dengue virus (DENV), no vaccine has been licensed up to date. Although the immunopathogenesis associated to the disease is a key factor to take into account by vaccine developers, the lack of animal models that reproduce the clinical signs of the disease has hampered the vaccine progress. Non-human primates support viral replication, but they are very expensive and do not show signs of disease. Immunocompromised mice develop viremia and some signs of the disease; however, they are not valuable for vaccine testing. Nowadays, immunocompetent mice are the most used model to evaluate the immunogenicity of vaccine candidates. These animals are resistant to DENV infection; therefore, the intracranial inoculation with neuroadapted virus, which provokes viral encephalitis, represents an alternative to evaluate the protective capacity of vaccine candidates. Previous results have demonstrated the crucial role of cellular immune response in the protection induced by the virus and vaccine candidates in this mouse encephalitis model. However, in the present work we are proposing that the magnitude of the cell-mediated immunity and the inflammatory response generated by the vaccine can modulate the survival rate after viral challenge. We observed that the intracranial challenge of naïve mice with DENV-2 induces the recruitment of immune cells that contribute to the reduction of viral load, but does not increase the survival rate. On the contrary, animals treated with cyclophosphamide, an immunosuppressive drug that affects proliferating lymphocytes, had a higher viral load but a better survival rate than untreated animals. These results suggest that the immune system is playing an immunopathogenic role in this model and the survival rate may not be a suitable endpoint in the evaluation of vaccine candidates based on antigens that induce a strong cellular immune response

  15. Differential and site specific impact of B cells in the protective immune response to Mycobacterium tuberculosis in the mouse.

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    Egídio Torrado

    Full Text Available Cell-mediated immune responses are known to be critical for control of mycobacterial infections whereas the role of B cells and humoral immunity is unclear. B cells can modulate immune responses by secretion of immunoglobulin, production of cytokines and antigen-presentation. To define the impact of B cells in the absence of secreted immunoglobulin, we analyzed the progression of Mycobacterium tuberculosis (Mtb infection in mice that have B cells but which lack secretory immunoglobulin (AID(-/-µS(-/-mice. AID(-/-µS(-/- mice accumulated a population of activated B cells in the lungs when infected and were more susceptible to aerosol Mtb when compared to wild type (C57BL/6 mice or indeed mice that totally lack B cells. The enhanced susceptibility of AID(-/-µS(-/- mice was not associated with defective T cell activation or expression of a type 1 immune response. While delivery of normal serum to AID(-/-µS(-/- mice did not reverse susceptibility, susceptibility in the spleen was dependent upon the presence of B cells and susceptibility in the lungs of AID(-/-µS(-/-mice was associated with elevated expression of the cytokines IL-6, GM-CSF, IL-10 and molecules made by alternatively activated macrophages. Blocking of IL-10 signaling resulted in reversal of susceptibility in the spleens and lungs of AID(-/-µS(-/- mice. These data support the hypothesis that B cells can modulate immunity to Mtb in an organ specific manner via the modulation of cytokine production and macrophage activation.

  16. Differential and site specific impact of B cells in the protective immune response to Mycobacterium tuberculosis in the mouse.

    Science.gov (United States)

    Torrado, Egídio; Fountain, Jeffrey J; Robinson, Richard T; Martino, Cynthia A; Pearl, John E; Rangel-Moreno, Javier; Tighe, Michael; Dunn, Robert; Cooper, Andrea M

    2013-01-01

    Cell-mediated immune responses are known to be critical for control of mycobacterial infections whereas the role of B cells and humoral immunity is unclear. B cells can modulate immune responses by secretion of immunoglobulin, production of cytokines and antigen-presentation. To define the impact of B cells in the absence of secreted immunoglobulin, we analyzed the progression of Mycobacterium tuberculosis (Mtb) infection in mice that have B cells but which lack secretory immunoglobulin (AID(-/-)µS(-/-)mice). AID(-/-)µS(-/-) mice accumulated a population of activated B cells in the lungs when infected and were more susceptible to aerosol Mtb when compared to wild type (C57BL/6) mice or indeed mice that totally lack B cells. The enhanced susceptibility of AID(-/-)µS(-/-) mice was not associated with defective T cell activation or expression of a type 1 immune response. While delivery of normal serum to AID(-/-)µS(-/-) mice did not reverse susceptibility, susceptibility in the spleen was dependent upon the presence of B cells and susceptibility in the lungs of AID(-/-)µS(-/-)mice was associated with elevated expression of the cytokines IL-6, GM-CSF, IL-10 and molecules made by alternatively activated macrophages. Blocking of IL-10 signaling resulted in reversal of susceptibility in the spleens and lungs of AID(-/-)µS(-/-) mice. These data support the hypothesis that B cells can modulate immunity to Mtb in an organ specific manner via the modulation of cytokine production and macrophage activation. PMID:23613902

  17. The immune response to sand fly salivary proteins and its influence on Leishmania immunity

    Directory of Open Access Journals (Sweden)

    Regis eGomes

    2012-05-01

    Full Text Available Leishmaniasis is a vector-borne disease transmitted by bites of phlebotomine sand flies. During Leishmania transmission, sand fly saliva is co-inoculated with parasites into the skin of the mammalian host. Sand fly saliva consists of roughly thirty different salivary proteins, many with known roles linked to blood feeding facilitation. Apart from the anti-hemostatic capacity of saliva, several sand fly salivary proteins have been shown to be immunogenic upon multiple contacts with a mammalian host. Immunization with single immunogenic salivary proteins or exposure to uninfected bites can produce protective immune responses against leishmaniasis. These sand fly salivary proteins induce cellular immune responses and/or antibodies. Antibodies to saliva are not required for protection in a mouse model against leishmaniasis. A strong body of evidence points to the role for saliva-specific T cells producing IFN-γ in the form of a delayed-type hypersensitivity reaction at the bite site as the main protective response. Herein, we review immunity to sand fly salivary proteins in the context of its vector-parasite-host combinations and vaccine potential, as well as some recent advances to shed light on the mechanism of how an immune response to sand fly saliva protects against leishmaniasis.

  18. Innate Immune Response to Intramammary Mycoplasma bovis Infection

    Science.gov (United States)

    Mastitis caused by Mycoplasma bovis is a growing concern for the dairy industry. M. bovis intramammary infection commonly results in an untreatable case of chronic mastitis. The innate immune system is responsible for initial recognition of, and immediate host responses to, infectious pathogens. ...

  19. Flavobacterium psychrophilum, prevention and immune response

    DEFF Research Database (Denmark)

    Henriksen, Maya Maria Mihályi; Dalsgaard, Inger

    The fish pathogen Flavobacterium psychrophilum is one of the main causes of mortality in farmed rainbow trout and other salmonid fish. The disease following infection is often called bacterial coldwater disease (BCWD) in USA or rainbow trout fry syndrome (RTFS) in Europe. An infected farm can...... expect mortality rates around 50-60% in fry and 2-10% in juvenile fish within few weeks, which causes significant economical losses worldwide. Presently no commercial vaccine exists, and fish farmers control the disease with antibiotics. The project is currently in its preliminary phase but the overall...... goal is to examine gene expression and location of transcription products in rainbow trout fry, in order to optimize vaccination or immune-stimulation. The presentation will focus on the future plans for the project, since no data have yet been obtained....

  20. Opposing effects of CXCR3 and CCR5 deficiency on CD8+ T cell-mediated inflammation in the central nervous system of virus-infected mice

    DEFF Research Database (Denmark)

    de Lemos, Carina; Christensen, Jeanette Erbo; Nansen, Anneline;

    2005-01-01

    T cells play a key role in the control of viral infection in the CNS but may also contribute to immune-mediated cell damage. To study the redundancy of the chemokine receptors CXCR3 and CCR5 in regulating virus-induced CD8+ T cell-mediated inflammation in the brain, CXCR3/CCR5 double-deficient mice...... and therefore protect mice against the otherwise fatal CD8+ T cell-mediated immune attack. Contrary to expectations, the accumulation of mononuclear cells in cerebrospinal fluid was only slightly delayed compared with mice with normal expression of both receptors. Even more surprising, CXCR3/CCR5...... plays an important role in controlling CNS inflammation, other receptors but not CCR5 also contribute significantly. Additionally, our results suggest that CCR5 primarily functions as a negative regulator of the antiviral CD8+ T cell response....

  1. Modulation of immune responses in stress by Yoga

    Directory of Open Access Journals (Sweden)

    Arora Sarika

    2008-01-01

    Full Text Available Stress is a constant factor in today′s fastpaced life that can jeopardize our health if left unchecked. It is only in the last half century that the role of stress in every ailment from the common cold to AIDS has been emphasized, and the mechanisms involved in this process have been studied. Stress influences the immune response presumably through the activation of the hypothalamic-pituitary adrenal axis, hypothalamic pituitary-gonadal axis, and the sympathetic-adrenal-medullary system. Various neurotransmitters, neuropeptides, hormones, and cytokines mediate these complex bidirectional interactions between the central nervous system (CNS and the immune system. The effects of stress on the immune responses result in alterations in the number of immune cells and cytokine dysregulation. Various stress management strategies such as meditation, yoga, hypnosis, and muscle relaxation have been shown to reduce the psychological and physiological effects of stress in cancers and HIV infection. This review aims to discuss the effect of stress on the immune system and examine how relaxation techniques such as Yoga and meditation could regulate the cytokine levels and hence, the immune responses during stress.

  2. Characterization of the immune response of domestic fowl following immunization with proteins extracted from Dermanyssus gallinae.

    Science.gov (United States)

    Harrington, David; Din, Hatem Mohi El; Guy, Jonathan; Robinson, Karen; Sparagano, Olivier

    2009-03-23

    Dermanyssus gallinae is the most significant ectoparasite of European poultry egg laying production systems due to high costs of control and associated production losses as well as adverse effects on bird welfare. In this study, soluble proteins were extracted from unfed D. gallinae (DGE) using a urea-based detergent and ultra-filtration, passed through a 0.22 microm filter and blended aseptically with adjuvant. One group of laying hens was immunized with DGE and adjuvant (Montanide ISA 50 V) whilst another group (Control) received physiological saline and adjuvant. All birds were immunized on two occasions, 21 days apart. Antibody response to immunization was determined by ELISA and western blotting using immunoglobulins (Igs) extracted from egg yolk. DGE immunization of hens resulted in a significant (P<0.05) IgY response compared to controls, although there was no significant difference in IgM response between treatments. A number of proteins were identified by western blotting using IgY antibodies from DGE immunized birds, most prominently at 40 and 230kDa. Analysis of proteins from approximately corresponding bands on SDS-PAGE confirmed the identity of tropomyosin, whilst other proteins showed high sequence homology with myosin and actin from other arachnid and insect species. Immunization of hens with DGE resulted in a 50.6% increase in mite mortality (P<0.001) 17h after feeding when tested by an in vitro mite feeding model. Data in this study demonstrate that somatic antigens from D. gallinae can be used to stimulate a protective immune response in laying hens. Further work is needed to identify other proteins of interest that could confer higher protection against D. gallinae, as well as optimization of the vaccination and in vitro testing protocol. PMID:19091480

  3. Immune responses in multiple myeloma: role of the natural immune surveillance and potential of immunotherapies.

    Science.gov (United States)

    Guillerey, Camille; Nakamura, Kyohei; Vuckovic, Slavica; Hill, Geoffrey R; Smyth, Mark J

    2016-04-01

    Multiple myeloma (MM) is a tumor of terminally differentiated B cells that arises in the bone marrow. Immune interactions appear as key determinants of MM progression. While myeloid cells foster myeloma-promoting inflammation, Natural Killer cells and T lymphocytes mediate protective anti-myeloma responses. The profound immune deregulation occurring in MM patients may be involved in the transition from a premalignant to a malignant stage of the disease. In the last decades, the advent of stem cell transplantation and new therapeutic agents including proteasome inhibitors and immunoregulatory drugs has dramatically improved patient outcomes, suggesting potentially key roles for innate and adaptive immunity in disease control. Nevertheless, MM remains largely incurable for the vast majority of patients. A better understanding of the complex interplay between myeloma cells and their immune environment should pave the way for designing better immunotherapies with the potential of very long term disease control. Here, we review the immunological microenvironment in myeloma. We discuss the role of naturally arising anti-myeloma immune responses and their potential corruption in MM patients. Finally, we detail the numerous promising immune-targeting strategies approved or in clinical trials for the treatment of MM. PMID:26801219

  4. LIGHT May Improve Immune Checkpoint Blockade Response.

    Science.gov (United States)

    2016-06-01

    A new study suggests that insufficient T-cell infiltration may explain why a majority of patients do not respond to immunotherapy. Combining PD-L1 inhibitors with antibody-guided LIGHT, a protein that recruits tumor-infiltrating lymphocytes, increased antitumor response in mice, and may have the potential to improve patient response rates to immunotherapy. PMID:27080334

  5. Effects of inhalation of 239PuO2 on immune responses following lung immunization

    International Nuclear Information System (INIS)

    Results of this study indicated that the number of antibody-forming cells in lung-associated lymph nodes after intratracheal immunization was significantly lower in animals exposed to 239PuO2. Only a few antibody-forming cells were found in spleen and cervical lymph nodes. Thus, 239PuO2 exposure suppressed immune responses in lung-associated lymph nodes, although their filtering capacity was unaffected and antigen did not translocate to the spleen. Changes in immunologic responses were observed as the animals aged and the number of antibody-forming cells gradually decreased in the lung-associated lymph nodes and increased in the spleen

  6. The genetic regulation of infant immune responses to vaccination

    Directory of Open Access Journals (Sweden)

    Melanie eNewport

    2015-02-01

    Full Text Available A number of factors are recognised to influence immune responses to vaccinations including age, gender, the dose and quality of the antigen used, the number of doses given, the route of administration and the nutritional status of the recipient. Additionally, several immunogenetic studies have identified associations between polymorphisms in genes encoding immune response proteins, both innate and adaptive, and variation in responses to vaccines. Variants in the genes encoding Toll-like receptors, HLA molecules, cytokines, cytokine receptors have associated with heterogeneity of responses to a wide range of vaccines including measles, hepatitis B, influenza A, BCG, Haemophilus influenzae type b and certain Neisseria meningitidis serotypes, amongst others. However, the vast majority of these studies have been conducted in older children and adults and there are very few data available from studies conducted in infants. This paper reviews the evidence to date that host genes influencing vaccines responses in these older population and identifies a large gap in our understanding of the genetic regulation of responses in early life. . Given the high mortality from infection in early life and the challenges of developing vaccines that generate effective immune responses in the context of the developing immune system further research on infant populations is required.

  7. Bacterial Outer Membrane Vesicles Induce Plant Immune Responses.

    Science.gov (United States)

    Bahar, Ofir; Mordukhovich, Gideon; Luu, Dee Dee; Schwessinger, Benjamin; Daudi, Arsalan; Jehle, Anna Kristina; Felix, Georg; Ronald, Pamela C

    2016-05-01

    Gram-negative bacteria continuously pinch off portions of their outer membrane, releasing membrane vesicles. These outer membrane vesicles (OMVs) are involved in multiple processes including cell-to-cell communication, biofilm formation, stress tolerance, horizontal gene transfer, and virulence. OMVs are also known modulators of the mammalian immune response. Despite the well-documented role of OMVs in mammalian-bacterial communication, their interaction with plants is not well studied. To examine whether OMVs of plant pathogens modulate the plant immune response, we purified OMVs from four different plant pathogens and used them to treat Arabidopsis thaliana. OMVs rapidly induced a reactive oxygen species burst, medium alkalinization, and defense gene expression in A. thaliana leaf discs, cell cultures, and seedlings, respectively. Western blot analysis revealed that EF-Tu is present in OMVs and that it serves as an elicitor of the plant immune response in this form. Our results further show that the immune coreceptors BAK1 and SOBIR1 mediate OMV perception and response. Taken together, our results demonstrate that plants can detect and respond to OMV-associated molecules by activation of their immune system, revealing a new facet of plant-bacterial interactions. PMID:26926999

  8. Acute psychological stress induces short-term variable immune response.

    Science.gov (United States)

    Breen, Michael S; Beliakova-Bethell, Nadejda; Mujica-Parodi, Lilianne R; Carlson, Joshua M; Ensign, Wayne Y; Woelk, Christopher H; Rana, Brinda K

    2016-03-01

    In spite of advances in understanding the cross-talk between the peripheral immune system and the brain, the molecular mechanisms underlying the rapid adaptation of the immune system to an acute psychological stressor remain largely unknown. Conventional approaches to classify molecular factors mediating these responses have targeted relatively few biological measurements or explored cross-sectional study designs, and therefore have restricted characterization of stress-immune interactions. This exploratory study analyzed transcriptional profiles and flow cytometric data of peripheral blood leukocytes with physiological (endocrine, autonomic) measurements collected throughout the sequence of events leading up to, during, and after short-term exposure to physical danger in humans. Immediate immunomodulation to acute psychological stress was defined as a short-term selective up-regulation of natural killer (NK) cell-associated cytotoxic and IL-12 mediated signaling genes that correlated with increased cortisol, catecholamines and NK cells into the periphery. In parallel, we observed down-regulation of innate immune toll-like receptor genes and genes of the MyD88-dependent signaling pathway. Correcting gene expression for an influx of NK cells revealed a molecular signature specific to the adrenal cortex. Subsequently, focusing analyses on discrete groups of coordinately expressed genes (modules) throughout the time-series revealed immune stress responses in modules associated to immune/defense response, response to wounding, cytokine production, TCR signaling and NK cell cytotoxicity which differed between males and females. These results offer a spring-board for future research towards improved treatment of stress-related disease including the impact of stress on cardiovascular and autoimmune disorders, and identifies an immune mechanism by which vulnerabilities to these diseases may be gender-specific. PMID:26476140

  9. Escaping Deleterious Immune Response in Their Hosts: Lessons from Trypanosomatids

    Science.gov (United States)

    Geiger, Anne; Bossard, Géraldine; Sereno, Denis; Pissarra, Joana; Lemesre, Jean-Loup; Vincendeau, Philippe; Holzmuller, Philippe

    2016-01-01

    The Trypanosomatidae family includes the genera Trypanosoma and Leishmania, protozoan parasites displaying complex digenetic life cycles requiring a vertebrate host and an insect vector. Trypanosoma brucei gambiense, Trypanosoma cruzi, and Leishmania spp. are important human pathogens causing human African trypanosomiasis (HAT or sleeping sickness), Chagas’ disease, and various clinical forms of Leishmaniasis, respectively. They are transmitted to humans by tsetse flies, triatomine bugs, or sandflies, and affect millions of people worldwide. In humans, extracellular African trypanosomes (T. brucei) evade the hosts’ immune defenses, allowing their transmission to the next host, via the tsetse vector. By contrast, T. cruzi and Leishmania sp. have developed a complex intracellular lifestyle, also preventing several mechanisms to circumvent the host’s immune response. This review seeks to set out the immune evasion strategies developed by the different trypanosomatids resulting from parasite–host interactions and will focus on: clinical and epidemiological importance of diseases; life cycles: parasites–hosts–vectors; innate immunity: key steps for trypanosomatids in invading hosts; deregulation of antigen-presenting cells; disruption of efficient specific immunity; and the immune responses used for parasite proliferation. PMID:27303406

  10. Role of DNA repair in host immune response and inflammation.

    Science.gov (United States)

    Fontes, Fabrícia Lima; Pinheiro, Daniele Maria Lopes; Oliveira, Ana Helena Sales de; Oliveira, Rayssa Karla de Medeiros; Lajus, Tirzah Braz Petta; Agnez-Lima, Lucymara Fassarella

    2015-01-01

    In recent years, the understanding of how DNA repair contributes to the development of innate and acquired immunity has emerged. The DNA damage incurred during the inflammatory response triggers the activation of DNA repair pathways, which are required for host-cell survival. Here, we reviewed current understanding of the mechanism by which DNA repair contributes to protection against the oxidized DNA damage generated during infectious and inflammatory diseases and its involvement in innate and adaptive immunity. We discussed the functional role of DNA repair enzymes in the immune activation and the relevance of these processes to: transcriptional regulation of cytokines and other genes involved in the inflammatory response; V(D)J recombination; class-switch recombination (CSR); and somatic hypermutation (SHM). These three last processes of DNA damage repair are required for effective humoral adaptive immunity, creating genetic diversity in developing T and B cells. Furthermore, viral replication is also dependent on host DNA repair mechanisms. Therefore, the elucidation of the pathways of DNA damage and its repair that activate innate and adaptive immunity will be important for a better understanding of the immune and inflammatory disorders and developing new therapeutic interventions for treatment of these diseases and for improving their outcome. PMID:25795123

  11. Mitochondrial DNA in the regulation of innate immune responses.

    Science.gov (United States)

    Fang, Chunju; Wei, Xiawei; Wei, Yuquan

    2016-01-01

    Mitochondrion is known as the energy factory of the cell, which is also a unique mammalian organelle and considered to be evolved from aerobic prokaryotes more than a billion years ago. Mitochondrial DNA, similar to that of its bacterial ancestor’s, consists of a circular loop and contains significant number of unmethylated DNA as CpG islands. The innate immune system plays an important role in the mammalian immune response. Recent research has demonstrated that mitochondrial DNA (mtDNA) activates several innate immune pathways involving TLR9, NLRP3 and STING signaling, which contributes to the signaling platforms and results in effector responses. In addition to facilitating antibacterial immunity and regulating antiviral signaling, mounting evidence suggests that mtDNA contributes to inflammatory diseases following cellular damage and stress. Therefore, in addition to its well-appreciated roles in cellular metabolism and energy production,mtDNA appears to function as a key member in the innate immune system. Here, we highlight the emerging roles of mtDNA in innate immunity. PMID:26498951

  12. Control of the adaptive immune response by tumor vasculature

    Directory of Open Access Journals (Sweden)

    Laetitia eMauge

    2014-03-01

    Full Text Available The endothelium is nowadays described as an entire organ that regulates various processes: vascular tone, coagulation, inflammation, and immune cell trafficking, depending on the vascular site and its specific microenvironment as well as on endothelial cell-intrinsic mechanisms like epigenetic changes. In this review, we will focus on the control of the adaptive immune response by the tumor vasculature. In physiological conditions, the endothelium acts as a barrier regulating cell trafficking by specific expression of adhesion molecules enabling adhesion of immune cells on the vessel, and subsequent extravasation. This process is also dependent on chemokine and integrin expression, and on the type of junctions defining the permeability of the endothelium. Endothelial cells can also regulate immune cell activation. In fact, the endothelial layer can constitute immunological synapses due to its close interactions with immune cells, and the delivery of co-stimulatory or co-inhibitory signals. In tumor conditions, the vasculature is characterized by abnormal vessel structure and permeability, and by specific phenotype of endothelial cells. All these abnormalities lead to a modulation of intratumoral immune responses and contribute to the development of intratumoral immunosuppression, which is a major mechanism for promoting the development, progression and treatment resistance of tumors. The in-depth analysis of these various abnormalities will help defining novel targets for the development of antitumoral treatments. Furthermore, eventual changes of the endothelial cell phenotype identified by plasma biomarkers could secondarily be selected to monitor treatment efficacy.

  13. Danger signals activating the immune response after trauma

    OpenAIRE

    Stefanie Hirsiger; Hans-Peter Simmen; Werner, Clément M. L.; Wanner, Guido A; Daniel Rittirsch

    2012-01-01

    Sterile injury can cause a systemic inflammatory response syndrome (SIRS) that resembles the host response during sepsis. The inflammatory response following trauma comprises various systems of the human body which are cross-linked with each other within a highly complex network of inflammation. Endogenous danger signals (danger-associated molecular patterns; DAMPs; alarmins) as well as exogenous pathogen-associated molecular patterns (PAMPs) play a crucial role in the initiation of the immun...

  14. Nanotechnology, neuromodulation & the immune response: discourse, materiality & ethics.

    Science.gov (United States)

    Fins, Joseph J

    2015-04-01

    Drawing upon the American Pragmatic tradition in philosophy and the more recent work of philosopher Karen Barad, this paper examines how scientific problems are both obscured, and resolved by our use of language describing the natural world. Using the example of the immune response engendered by neural implants inserted in the brain, the author explains how this discourse has been altered by the advent of nanotechnology methods and devices which offer putative remedies that might temper the immune response in the central nervous system. This emergent nanotechnology has altered this problem space and catalyzed one scientific community to acknowledge a material reality that was always present, if not fully acknowledged. PMID:25681046

  15. The immune system in space and microgravity

    Science.gov (United States)

    Sonnenfeld, Gerald

    2002-01-01

    Space flight and models that created conditions similar to those that occur during space flight have been shown to affect a variety of immunological responses. These have primarily been cell-mediated immune responses including leukocyte proliferation, cytokine production, and leukocyte subset distribution. The mechanisms and biomedical consequences of these changes remain to be established. Among the possible causes of space flight-induced alterations in immune responses are exposure to microgravity, exposure to stress, exposure to radiation, and many more as yet undetermined causes. This review chronicles the known effects of space flight on the immune system and explores the possible role of stress in contributing to these changes.

  16. Bifidobacterium longum CECT 7347 modulates immune responses in a gliadin-induced enteropathy animal model.

    Directory of Open Access Journals (Sweden)

    José Moisés Laparra

    Full Text Available Coeliac disease (CD is an autoimmune disorder triggered by gluten proteins (gliadin that involves innate and adaptive immunity. In this study, we hypothesise that the administration of Bifidobacterium longum CECT 7347, previously selected for reducing gliadin immunotoxic effects in vitro, could exert protective effects in an animal model of gliadin-induced enteropathy. The effects of this bacterium were evaluated in newborn rats fed gliadin alone or sensitised with interferon (IFN-γ and fed gliadin. Jejunal tissue sections were collected for histological, NFκB mRNA expression and cytokine production analyses. Leukocyte populations and T-cell subsets were analysed in peripheral blood samples. The possible translocation of the bacterium to different organs was determined by plate counting and the composition of the colonic microbiota was quantified by real-time PCR. Feeding gliadin alone reduced enterocyte height and peripheral CD4+ cells, but increased CD4+/Foxp3+ T and CD8+ cells, while the simultaneous administration of B. longum CECT 7347 exerted opposite effects. Animals sensitised with IFN-γ and fed gliadin showed high cellular infiltration, reduced villi width and enterocyte height. Sensitised animals also exhibited increased NFκB mRNA expression and TNF-α production in tissue sections. B. longum CECT 7347 administration increased NFκB expression and IL-10, but reduced TNF-α, production in the enteropathy model. In sensitised gliadin-fed animals, CD4+, CD4+/Foxp3+ and CD8+ T cells increased, whereas the administration of B. longum CECT 7347 reduced CD4+ and CD4+/Foxp3+ cell populations and increased CD8+ T cell populations. The bifidobacterial strain administered represented between 75-95% of the total bifidobacteria isolated from all treated groups, and translocation to organs was not detected. These findings indicate that B. longum attenuates the production of inflammatory cytokines and the CD4+ T-cell mediated immune response in

  17. Complement Activation Pathways: A Bridge between Innate and Adaptive Immune Responses in Asthma

    OpenAIRE

    Wills-Karp, Marsha

    2007-01-01

    Although it is widely accepted that allergic asthma is driven by T helper type 2 (Th2)-polarized immune responses to innocuous environmental allergens, the mechanisms driving these aberrant immune responses remain elusive. Recent recognition of the importance of innate immune pathways in regulating adaptive immune responses have fueled investigation into the role of innate immune pathways in the pathogenesis of asthma. The phylogenetically ancient innate immune system, the complement system, ...

  18. Photodynamic therapy for cancer and activation of immune response

    Science.gov (United States)

    Mroz, Pawel; Huang, Ying-Ying; Hamblin, Michael R.

    2010-02-01

    Anti-tumor immunity is stimulated after PDT for cancer due to the acute inflammatory response, exposure and presentation of tumor-specific antigens, and induction of heat-shock proteins and other danger signals. Nevertheless effective, powerful tumor-specific immune response in both animal models and also in patients treated with PDT for cancer, is the exception rather than the rule. Research in our laboratory and also in others is geared towards identifying reasons for this sub-optimal immune response and discovering ways of maximizing it. Reasons why the immune response after PDT is less than optimal include the fact that tumor-antigens are considered to be self-like and poorly immunogenic, the tumor-mediated induction of CD4+CD25+foxP3+ regulatory T-cells (T-regs), that are able to inhibit both the priming and the effector phases of the cytotoxic CD8 T-cell anti-tumor response and the defects in dendritic cell maturation, activation and antigen-presentation that may also occur. Alternatively-activated macrophages (M2) have also been implicated. Strategies to overcome these immune escape mechanisms employed by different tumors include combination regimens using PDT and immunostimulating treatments such as products obtained from pathogenic microorganisms against which mammals have evolved recognition systems such as PAMPs and toll-like receptors (TLR). This paper will cover the use of CpG oligonucleotides (a TLR9 agonist found in bacterial DNA) to reverse dendritic cell dysfunction and methods to remove the immune suppressor effects of T-regs that are under active study.

  19. Immune responses in DNA vaccine formulated with PMMA following immunization and after challenge with Leishmania major.

    Science.gov (United States)

    Zarrati, Somayeh; Mahdavi, Mehdi; Tabatabaie, Fatemeh

    2016-06-01

    Leishmaniasis is a major infectious disease caused by protozoan parasites of the genus Leishmania. Despite of many efforts toward vaccine against Leishmania no effective vaccine has been approved yet. DNA vaccines can generate more powerful and broad immune responses than conventional vaccines. In order to increase immunity, the DNA vaccine has been supplemented with adjuvant. In this study a new nano-vaccine containing TSA recombinant plasmid and poly(methylmethacrylate) nanoparticles (act as adjuvant) was designed and its immunogenicity tested on BALB/c mouse. After three intramuscular injection of nano-vaccine (100 μg), the recombinant TSA protein (20 μg) was injected subcutaneously. Finally as a challenge animals were infected by Leishmania major. After the last injection of nano-vaccine, after protein booster injection, and also after challenge, cellular immune and antibody responses were evaluated by ELISA method. The findings of this study showed the new nano-vaccine was capable of induction both cytokines secretion and specific antibody responses, but predominant Th1 immune response characterized by IFN-γ production compared to control groups. Moreover, results revealed that nano-vaccine was effective in reducing parasite burden in the spleen of Leishmania major-infected BALB/c mice. Base on results, current candidate vaccine has potency for further studies. PMID:27413316

  20. The host immune response to gastrointestinal nematode infection in sheep.

    Science.gov (United States)

    McRae, K M; Stear, M J; Good, B; Keane, O M

    2015-12-01

    Gastrointestinal nematode infection represents a major threat to the health, welfare and productivity of sheep populations worldwide. Infected lambs have a reduced ability to absorb nutrients from the gastrointestinal tract, resulting in morbidity and occasional mortality. The current chemo-dominant approach to nematode control is considered unsustainable due to the increasing incidence of anthelmintic resistance. In addition, there is growing consumer demand for food products from animals not subjected to chemical treatment. Future mechanisms of nematode control must rely on alternative, sustainable strategies such as vaccination or selective breeding of resistant animals. Such strategies take advantage of the host's natural immune response to nematodes. The ability to resist gastrointestinal nematode infection is considered to be dependent on the development of a protective acquired immune response, although the precise immune mechanisms involved in initiating this process remain to be fully elucidated. In this study, current knowledge on the innate and acquired host immune response to gastrointestinal nematode infection in sheep and the development of immunity is reviewed. PMID:26480845

  1. Effect of produced water on cod (Gadus morhua) immune responses

    Energy Technology Data Exchange (ETDEWEB)

    Hamoutene, D.; Mabrouk, G.; Samuelson, S.; Mansour, A.; Lee, K. [Fisheries and Oceans Canada, Dartmouth, NS (Canada). Maritimes Region, Ocean Sciences Division; Volkoff, H.; Parrish, C. [Memorial Univ. of Newfoundland, St. John' s, NL (Canada); Mathieu, A. [Oceans Ltd., St. John' s, NL (Canada)

    2007-07-01

    Studies have shown that produced water (PW) discharged from North Sea offshore platforms affects the biota at greater distances from operational platforms than originally presumed. According to PW dispersion simulations, dilution by at least 240 times occurs within 50-100 m, and up to 9000 times by 20 km from the discharge. In this study, the effect of PW on cod immunity was investigated by exposing fish to 0, 100 ppm (x 10,000 dilution) or 200 ppm (x 500) of PW for 76 days. Immune responses were evaluated at the end of the exposure. Fish from the 3 groups were injected with Aeromonas salmonicida lipopolysaccharides (LPS). Blood cell observation and flow cytometry were used to investigate the serum cortisol levels and gill histology along with ratios and respiratory burst (RB) responses of both circulating and head-kidney white blood cells (WBCs). The study revealed that baseline immunity and stress response were not affected by PW, other than an irritant-induced change in gill cells found in treated cod. In all groups, LPS injection resulted in a pronounced decrease in RB of head-kidney cells and an increase in serum cortisol and protein levels. However, the group exposed to 200 ppm of PW exhibited the most significant changes. LPS injection was also shown to influence WBC ratios, but further studies are needed to determine if this impact is stronger in fish exposed to PW. This study suggested an effect of PW on cod immunity after immune challenge with LPS.

  2. Effect of produced water on cod (Gadus morhua) immune responses

    International Nuclear Information System (INIS)

    Studies have shown that produced water (PW) discharged from North Sea offshore platforms affects the biota at greater distances from operational platforms than originally presumed. According to PW dispersion simulations, dilution by at least 240 times occurs within 50-100 m, and up to 9000 times by 20 km from the discharge. In this study, the effect of PW on cod immunity was investigated by exposing fish to 0, 100 ppm (x 10,000 dilution) or 200 ppm (x 500) of PW for 76 days. Immune responses were evaluated at the end of the exposure. Fish from the 3 groups were injected with Aeromonas salmonicida lipopolysaccharides (LPS). Blood cell observation and flow cytometry were used to investigate the serum cortisol levels and gill histology along with ratios and respiratory burst (RB) responses of both circulating and head-kidney white blood cells (WBCs). The study revealed that baseline immunity and stress response were not affected by PW, other than an irritant-induced change in gill cells found in treated cod. In all groups, LPS injection resulted in a pronounced decrease in RB of head-kidney cells and an increase in serum cortisol and protein levels. However, the group exposed to 200 ppm of PW exhibited the most significant changes. LPS injection was also shown to influence WBC ratios, but further studies are needed to determine if this impact is stronger in fish exposed to PW. This study suggested an effect of PW on cod immunity after immune challenge with LPS

  3. Verification of immune response optimality through cybernetic modeling.

    Science.gov (United States)

    Batt, B C; Kompala, D S

    1990-02-01

    An immune response cascade that is T cell independent begins with the stimulation of virgin lymphocytes by antigen to differentiate into large lymphocytes. These immune cells can either replicate themselves or differentiate into plasma cells or memory cells. Plasma cells produce antibody at a specific rate up to two orders of magnitude greater than large lymphocytes. However, plasma cells have short life-spans and cannot replicate. Memory cells produce only surface antibody, but in the event of a subsequent infection by the same antigen, memory cells revert rapidly to large lymphocytes. Immunologic memory is maintained throughout the organism's lifetime. Many immunologists believe that the optimal response strategy calls for large lymphocytes to replicate first, then differentiate into plasma cells and when the antigen has been nearly eliminated, they form memory cells. A mathematical model incorporating the concept of cybernetics has been developed to study the optimality of the immune response. Derived from the matching law of microeconomics, cybernetic variables control the allocation of large lymphocytes to maximize the instantaneous antibody production rate at any time during the response in order to most efficiently inactivate the antigen. A mouse is selected as the model organism and bacteria as the replicating antigen. In addition to verifying the optimal switching strategy, results showing how the immune response is affected by antigen growth rate, initial antigen concentration, and the number of antibodies required to eliminate an antigen are included. PMID:2338827

  4. Elevated EBNA1 Immune Responses Predict Conversion to Multiple Sclerosis

    Science.gov (United States)

    Lünemann, Jan D.; Tintoré, Mar; Messmer, Brady; Strowig, Till; Rovira, Álex; Perkal, Héctor; Caballero, Estrella; Münz, Christian; Montalban, Xavier; Comabella, Manuel

    2009-01-01

    Objective The aims of the study were to determine the immune responses to candidate viral triggers of multiple sclerosis (MS) in patients with clinically isolated syndromes (CIS), and to evaluate their potential value in predicting conversion to MS. Methods Immune responses to Epstein-Barr virus (EBV), human herpesvirus 6, cytomegalovirus (HCMV), and measles were determined in a cohort of 147 CIS patients with a mean follow-up of 7 years and compared with 50 demographically matched controls. Results Compared to controls, CIS patients showed increased humoral (p<0.0001) and cellular (p=0.007) immune responses to the EBV-encoded nuclear antigen-1 (EBNA1), but not to other EBV-derived proteins. IgG responses to other virus antigens and frequencies of T cells specific for HCMV and influenza virus gene products were unchanged in CIS patients. EBNA1 was the only viral antigen towards which immune responses correlated with number of T2 lesions (p=0.006) and number of Barkhof criteria (p=0.001) at baseline, and with number of T2 lesions (p=0.012 both at 1 and 5 years), presence of new T2 lesions (p=0.003 and p=0.028 at 1 and 5 years), and EDSS (p=0.015 and p=0.010 at 1 and 5 years) during follow-up. In a univariate Cox regression model, increased EBNA1-specific IgG responses predicted conversion to MS based on McDonald criteria [hazard ratio (95% confidence interval), 2.2 (1.2–4.3); p=0.003]. Interpretation Our results indicate that elevated immune responses towards EBNA1 are selectively increased in CIS patients and suggest that EBNA1-specific IgG titers could be used as a prognostic marker for disease conversion and disability progression. PMID:20225269

  5. The role of complement in the acquired immune response

    DEFF Research Database (Denmark)

    Nielsen, C H; Fischer, E M; Leslie, R G

    2000-01-01

    specific T cells; the activation of a CD21/CD19 complex-mediated signalling pathway in B cells, which provides a stimulus synergistic to that induced by antigen interaction with the B-cell receptor (BCR); and promotion of the interaction between B cells and FDC, where C3d-bearing immune complexes......Studies over the past three decades have clearly established a central role for complement in the promotion of a humoral immune response. The primary function of complement, in this regard, is to opsonize antigen or immune complexes for uptake by complement receptor type 2 (CR2, CD21) expressed on...... B cells, follicular dendritic cells (FDC) and some T cells. A variety of mechanisms appear to be involved in complement-mediated promotion of the humoral response. These include: enhancement of antigen (Ag) uptake and processing by both Ag-specific and non-specific B cells for presentation to...

  6. Durable and sustained immune tolerance to ERT in Pompe disease with entrenched immune responses

    Science.gov (United States)

    Kazi, Zoheb B.; Prater, Sean N.; Kobori, Joyce A.; Viskochil, David; Bailey, Carrie; Gera, Renuka; Stockton, David W.; McIntosh, Paul; Rosenberg, Amy S.; Kishnani, Priya S.

    2016-01-01

    BACKGROUND Enzyme replacement therapy (ERT) has prolonged survival and improved clinical outcomes in patients with infantile Pompe disease (IPD), a rapidly progressive neuromuscular disorder. Yet marked interindividual variability in response to ERT, primarily attributable to the development of antibodies to ERT, remains an ongoing challenge. Immune tolerance to ongoing ERT has yet to be described in the setting of an entrenched immune response. METHODS Three infantile Pompe patients who developed high and sustained rhGAA IgG antibody titers (HSAT) and received a bortezomib-based immune tolerance induction (ITI) regimen were included in the study and were followed longitudinally to monitor the long-term safety and efficacy. A trial to taper the ITI protocol was attempted to monitor if true immune tolerance was achieved. RESULTS Bortezomib-based ITI protocol was safely tolerated and led to a significant decline in rhGAA antibody titers with concomitant sustained clinical improvement. Two of the 3 IPD patients were successfully weaned off all ITI protocol medications and continue to maintain low/no antibody titers. ITI protocol was significantly tapered in the third IPD patient. B cell recovery was observed in all 3 IPD patients. CONCLUSION This is the first report to our knowledge on successful induction of long-term immune tolerance in patients with IPD and HSAT refractory to agents such as cyclophosphamide, rituximab, and methotrexate, based on an approach using the proteasome inhibitor bortezomib. As immune responses limit the efficacy and cost-effectiveness of therapy for many conditions, proteasome inhibitors may have new therapeutic applications. FUNDING This research was supported by a grant from the Genzyme Corporation, a Sanofi Company (Cambridge, Massachusetts, USA), and in part by the Lysosomal Disease Network, a part of NIH Rare Diseases Clinical Research Network (RDCRN).

  7. Kupffer cell-mediated exacerbation of methimazole-induced acute liver injury in rats.

    Science.gov (United States)

    Akai, Sho; Uematsu, Yasuaki; Tsuneyama, Koichi; Oda, Shingo; Yokoi, Tsuyoshi

    2016-05-01

    Methimazole (MTZ), an anti-thyroid drug, is known to cause liver injury in humans. It has been demonstrated that MTZ-induced liver injury in Balb/c mice is accompanied by T helper (Th) 2 cytokine-mediated immune responses; however, there is little evidence for immune responses associated with MTZ-induced liver injury in rats. To investigate species differences in MTZ-induced liver injury, we administered MTZ with a glutathione biosynthesis inhibitor, L-buthionine-S,R-sulfoximine (BSO), to F344 rats and subsequently observed an increase in plasma alanine aminotransferase (ALT) and high-mobility group box 1 (HMGB1), which are associated with hepatic lesions. The hepatic mRNA expression of innate immune-related genes significantly increased in BSO- and MTZ-treated rats, but the change in Th2-related genes was not much greater than the change observed in the previous mouse study. Moreover, an increase in Kupffer cells and an induction of the phosphorylation of extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK) proteins were accompanied by an increase in Toll-like receptor 4 (TLR4) expression, indicating that Kupffer cell activation occurs through HMGB1-TLR4 signaling. To elucidate the mechanism of liver injury in rats, gadolinium chloride, which inactivates the function of Kupffer cells, was administered before BSO and MTZ administration. The gadolinium chloride treatment significantly suppressed the increased ALT, which was accompanied by decreased hepatic mRNA expression related to innate immune responses and ERK/JNK phosphorylation. In conclusion, Kupffer cell-mediated immune responses are crucial factors for the exacerbation of MTZ-induced liver injury in rats, indicating apparent species differences in the immune-mediated exacerbation of liver injury between mice and rats. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26177832

  8. Immune Responses in Pigs Induced by Recombinant DNA Vaccine Co-Expressing Swine IL-18 and Membrane Protein of Porcine Reproductive and Respiratory Syndrome Virus

    Directory of Open Access Journals (Sweden)

    Zhuang Ding

    2012-05-01

    Full Text Available In this study, two DNA vaccines, which express the membrane (M protein of porcine respiratory and reproductive syndrome virus (PRRSV (pEGFP-M and co-express both M and swine IL-18 (pEGFP-IL18-M, were constructed and their abilities to induce humoral and cellular responses in piglets were comparatively evaluated. Experimental results showed that both recombinant DNA vaccines could not elicit neutralizing antibodies in the immunized piglets. However, both DNA vaccines elicited Th1-biased cellular immune responses. Notably, pigs immunized with the plasmid pEGFP-IL18-M developed significantly higher levels of IFN-γ and IL-2 production response and stronger specific T-lymphocyte proliferation response than the pigs inoculated with the plasmids pEGFP-M and pEGFP-IL18 (P < 0.05. These results illustrated that co-expression of M and IL-18 proteins could significantly improve the potency of DNA vaccination on the activation of vaccine-induced virus-specific cell-mediated immune responses in pigs, which may be used as a strategy to develop a new generation of vaccines against highly pathogenic PRRSV.

  9. A Drosophila immune response against Ras-induced overgrowth

    Directory of Open Access Journals (Sweden)

    Thomas Hauling

    2014-03-01

    Full Text Available Our goal is to characterize the innate immune response against the early stage of tumor development. For this, animal models where genetic changes in specific cells and tissues can be performed in a controlled way have become increasingly important, including the fruitfly Drosophila melanogaster. Many tumor mutants in Drosophila affect the germline and, as a consequence, also the immune system itself, making it difficult to ascribe their phenotype to a specific tissue. Only during the past decade, mutations have been induced systematically in somatic cells to study the control of tumorous growth by neighboring cells and by immune cells. Here we show that upon ectopic expression of a dominant-active form of the Ras oncogene (RasV12, both imaginal discs and salivary glands are affected. Particularly, the glands increase in size, express metalloproteinases and display apoptotic markers. This leads to a strong cellular response, which has many hallmarks of the granuloma-like encapsulation reaction, usually mounted by the insect against larger foreign objects. RNA sequencing of the fat body reveals a characteristic humoral immune response. In addition we also identify genes that are specifically induced upon expression of RasV12. As a proof-of-principle, we show that one of the induced genes (santa-maria, which encodes a scavenger receptor, modulates damage to the salivary glands. The list of genes we have identified provides a rich source for further functional characterization. Our hope is that this will lead to a better understanding of the earliest stage of innate immune responses against tumors with implications for mammalian immunity.

  10. Immune modulation following immunization with polyvalent vaccines in dogs.

    Science.gov (United States)

    Strasser, Alois; May, Bettina; Teltscher, Andrea; Wistrela, Eva; Niedermüller, Hans

    2003-08-15

    A decline in T-cell-mediated immunity and transient state of immunosuppression after immunization has been reported in dogs. Nevertheless, dogs are still routinely vaccinated with polyvalent live vaccines and severe disease does not generally occur. In order to investigate these effects on the canine immune system and to elucidate possible mechanisms we determined the following immune parameters in the blood of 33 clinically sound German shepherd dogs before and after standard vaccination with a polyvalent vaccine against distemper, parvovirus, viral hepatitis, leptospirosis, kennel cough and rabies: white and differential blood cell count, the serum concentrations and/or activities of IL-1, IL-2, IFN-gamma, TNF-alpha, neopterin and IgG, natural killer (NK) cell activity, bactericidal activity and complement hemolytic activity, lymphocyte proliferation test (LPT) and nitroblue tetrazolium test (NBT). Our major findings were that significant postvaccinal decreases in T-cell mitogenic response to PHA and in neutrophil function and neopterin serum concentration were accompanied by simultaneous increase in plasma IgG and hemolytic complement activity. This suggests a transient shift in the balance between cell-mediated and humoral (T(H)1/T(H)2) immunity rather than immunosuppression. These results do not imply that dogs should not receive live vaccines, as the response to vaccines just seems to create a state of altered homeostasis when immunization elicits protection by humoral and cell-mediated immunity. However, these recognized compromises of immune function should be considered and vaccines still be applied only in healthy animals and strictly according to the rules and regulations given by the manufacturer. PMID:12909408

  11. Platelets in Pulmonary Immune Responses and Inflammatory Lung Diseases.

    Science.gov (United States)

    Middleton, Elizabeth A; Weyrich, Andrew S; Zimmerman, Guy A

    2016-10-01

    Platelets are essential for physiological hemostasis and are central in pathological thrombosis. These are their traditional and best known activities in health and disease. In addition, however, platelets have specializations that broaden their functional repertoire considerably. These functional capabilities, some of which are recently discovered, include the ability to sense and respond to infectious and immune signals and to act as inflammatory effector cells. Human platelets and platelets from mice and other experimental animals can link the innate and adaptive limbs of the immune system and act across the immune continuum, often also linking immune and hemostatic functions. Traditional and newly recognized facets of the biology of platelets are relevant to defensive, physiological immune responses of the lungs and to inflammatory lung diseases. The emerging view of platelets as blood cells that are much more diverse and versatile than previously thought further predicts that additional features of the biology of platelets and of megakaryocytes, the precursors of platelets, will be discovered and that some of these will also influence pulmonary immune defenses and inflammatory injury. PMID:27489307

  12. Mechanism of protection from graft-vs-host disease in murine mixed allogeneic chimeras. I. Development of a null cell population suppressive of cell-mediated lympholysis responses and derived from the syngeneic bone marrow component

    International Nuclear Information System (INIS)

    Splenocyte populations from whole body-irradiated recipients of mixed T cell-depleted (TCD) syngeneic and allogeneic (complete H-2 disparity) bone marrow, or of TCD syngeneic marrow alone, contain cells with the ability to suppress the generation of cell-mediated lympholysis responses in vitro. This activity, which is present by 8 days after bone marrow transplantation and persists for several weeks, has been analyzed for possible veto-like or other specificity. Although reproducible patterns of suppression were observed, depending both on host strain and on the genetic combination of the response examined, the overall suppression in vitro most closely resembles that which has been ascribed to natural suppressor cells in other systems. The suppression appears to be mediated by a non-T cell, non-B cell, nonadherent, asialo GM1-negative population. Cold target inhibition and CTL activity of chimeric cells have been ruled out as factors contributing to the observed suppression. Significantly, in mixed chimeras, suppression was found to be mediated exclusively by cells which were syngeneic to the recipient in both recipient strains tested. The rapid development of this suppressive activity may explain the resistance to graft-vs-host disease conferred on whole body-irradiated mice by the addition of TCD syngeneic marrow to an allogeneic graft-vs-host disease-producing inoculum

  13. Systems biology of neutrophil differentiation and immune response

    DEFF Research Database (Denmark)

    Theilgaard-Mönch, Kim; Porse, Bo T; Borregaard, Niels

    2005-01-01

    Systems biology has emerged as a new scientific field, which aims at investigating biological processes at the genomic and proteomic levels. Recent studies have unravelled aspects of neutrophil differentiation and immune responses at the systems level using high-throughput technologies. These...

  14. Polysaccharides isolated from Acai fruit induce innate immune responses.

    Directory of Open Access Journals (Sweden)

    Jeff Holderness

    Full Text Available The Açaí (Acai fruit is a popular nutritional supplement that purportedly enhances immune system function. These anecdotal claims are supported by limited studies describing immune responses to the Acai polyphenol fraction. Previously, we characterized γδ T cell responses to both polyphenol and polysaccharide fractions from several plant-derived nutritional supplements. Similar polyphenol and polysaccharide fractions are found in Acai fruit. Thus, we hypothesized that one or both of these fractions could activate γδ T cells. Contrary to previous reports, we did not identify agonist activity in the polyphenol fraction; however, the Acai polysaccharide fraction induced robust γδ T cell stimulatory activity in human, mouse, and bovine PBMC cultures. To characterize the immune response to Acai polysaccharides, we fractionated the crude polysaccharide preparation and tested these fractions for activity in human PBMC cultures. The largest Acai polysaccharides were the most active in vitro as indicated by activation of myeloid and γδ T cells. When delivered in vivo, Acai polysaccharide induced myeloid cell recruitment and IL-12 production. These results define innate immune responses induced by the polysaccharide component of Acai and have implications for the treatment of asthma and infectious disease.

  15. Primary immune response to blood group antigens in burned children.

    Science.gov (United States)

    Bacon, N; Patten, E; Vincent, J

    1991-01-01

    Delayed hemolytic transfusion reactions (DHTRs) are generally attributed to an anamnestic immune response. Case reports of DHTRs due to a primary immune response are rare. Transfusion reactions occurring in patients on the pediatric burn unit from 1981 to September 1988 were reviewed, and additional information was obtained for patients for whom a DHTR was documented. Of 62 transfusion reactions, 11 were classified as a primary immune response (DHTR), with either a positive antibody screen, a positive direct antiglobulin test (DAT), or both. None of the 11 patients included in the study had been previously tranfused or pregnant. The average number of units transfused prior to antibody identification was 19. The average time elapsed between the first transfusion and antibody identification was 3.6 weeks. Anti-K and anti-E were the most frequently identified. Three patients had a decrease in hemoglobin (average 1.5 g/dL) and hematocrit at the time that a positive DAT was detected. Such changes could not be demonstrated for the remaining eight patients. The conclusion was that a DHTR may he caused by a primary immune response in burned children more often than expected, but DHTR signs and symptoms are often not apparent due to the complications of burn trauma. PMID:15946011

  16. HTLV-1, Immune Response and Autoimmunity.

    Science.gov (United States)

    Quaresma, Juarez A S; Yoshikawa, Gilberto T; Koyama, Roberta V L; Dias, George A S; Fujihara, Satomi; Fuzii, Hellen T

    2016-01-01

    Human T-lymphotropic virus type-1 (HTLV-1) infection is associated with adult T-cell leukemia/lymphoma (ATL). Tropical spastic paraparesis/HTLV-1-associated myelopathy (PET/HAM) is involved in the development of autoimmune diseases including Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE), and Sjögren's Syndrome (SS). The development of HTLV-1-driven autoimmunity is hypothesized to rely on molecular mimicry, because virus-like particles can trigger an inflammatory response. However, HTLV-1 modifies the behavior of CD4⁺ T cells on infection and alters their cytokine production. A previous study showed that in patients infected with HTLV-1, the activity of regulatory CD4⁺ T cells and their consequent expression of inflammatory and anti-inflammatory cytokines are altered. In this review, we discuss the mechanisms underlying changes in cytokine release leading to the loss of tolerance and development of autoimmunity. PMID:26712781

  17. Glassy Dynamics in the Adaptive Immune Response Prevents Autoimmune Disease

    Science.gov (United States)

    Sun, Jun; Deem, Michael

    2006-03-01

    The immune system normally protects the human host against death by infection. However, when an immune response is mistakenly directed at self antigens, autoimmune disease can occur. We describe a model of protein evolution to simulate the dynamics of the adaptive immune response to antigens. Computer simulations of the dynamics of antibody evolution show that different evolutionary mechanisms, namely gene segment swapping and point mutation, lead to different evolved antibody binding affinities. Although a combination of gene segment swapping and point mutation can yield a greater affinity to a specific antigen than point mutation alone, the antibodies so evolved are highly cross-reactive and would cause autoimmune disease, and this is not the chosen dynamics of the immune system. We suggest that in the immune system a balance has evolved between binding affinity and specificity in the mechanism for searching the amino acid sequence space of antibodies. Our model predicts that chronic infection may lead to autoimmune disease as well due to cross-reactivity and suggests a broad distribution for the time of onset of autoimmune disease due to chronic exposure. The slow search of antibody sequence space by point mutation leads to the broad of distribution times.

  18. Synergistic innate and adaptive immune response to combination immunotherapy with anti-tumor antigen antibodies and extended serum half-life IL-2.

    Science.gov (United States)

    Zhu, Eric F; Gai, Shuning A; Opel, Cary F; Kwan, Byron H; Surana, Rishi; Mihm, Martin C; Kauke, Monique J; Moynihan, Kelly D; Angelini, Alessandro; Williams, Robert T; Stephan, Matthias T; Kim, Jacob S; Yaffe, Michael B; Irvine, Darrell J; Weiner, Louis M; Dranoff, Glenn; Wittrup, K Dane

    2015-04-13

    Cancer immunotherapies under development have generally focused on either stimulating T cell immunity or driving antibody-directed effector functions of the innate immune system such as antibody-dependent cell-mediated cytotoxicity (ADCC). We find that a combination of an anti-tumor antigen antibody and an untargeted IL-2 fusion protein with delayed systemic clearance induces significant tumor control in aggressive isogenic tumor models via a concerted innate and adaptive response involving neutrophils, NK cells, macrophages, and CD8(+) T cells. This combination therapy induces an intratumoral "cytokine storm" and extensive lymphocyte infiltration. Adoptive transfer of anti-tumor T cells together with this combination therapy leads to robust cures of established tumors and development of immunological memory. PMID:25873172

  19. The influence of quartz and surfactant on immune responses

    OpenAIRE

    Zetterberg, Göran

    1998-01-01

    Pulmonary surfactant is a mixture of lipids and proteins that embeds the alveolar cells, has surface tension reducing properties but also influences the immune response. To further investigate this, quartz was used to initiate an inflammatory response in two different models. Firstly, in vitro exposures of resting and activated human leukocytes to combinations of quartz and surfactant were done, and secondly in vivo exposures of rats to instilled quartz were performed. W...

  20. Immune Response to Electromagnetic Fields through Cybernetic Modeling

    Science.gov (United States)

    Godina-Nava, J. J.; Segura, M. A. Rodríguez; Cadena, S. Reyes; Sierra, L. C. Gaitán

    2008-08-01

    We study the optimality of the humoral immune response through a mathematical model, which involves the effect of electromagnetic fields over the large lymphocytes proliferation. Are used the so called cybernetic variables in the context of the matching law of microeconomics or mathematical psychology, to measure the large lymphocytes population and to maximize the instantaneous antibody production rate in time during the immunologic response in order to most efficiently inactivate the antigen.

  1. Immune Response to Electromagnetic Fields through Cybernetic Modeling

    International Nuclear Information System (INIS)

    We study the optimality of the humoral immune response through a mathematical model, which involves the effect of electromagnetic fields over the large lymphocytes proliferation. Are used the so called cybernetic variables in the context of the matching law of microeconomics or mathematical psychology, to measure the large lymphocytes population and to maximize the instantaneous antibody production rate in time during the immunologic response in order to most efficiently inactivate the antigen

  2. Reprogramming immune responses via microRNA modulation

    Science.gov (United States)

    Cubillos-Ruiz, Juan R.; Rutkowski, Melanie R; Tchou, Julia; Conejo-Garcia, Jose R.

    2013-01-01

    It is becoming increasingly clear that there are unique sets of miRNAs that have distinct governing roles in several aspects of both innate and adaptive immune responses. In addition, new tools allow selective modulation of the expression of individual miRNAs, both in vitro and in vivo. Here, we summarize recent advances in our understanding of how miRNAs drive the activity of immune cells, and how their modulation in vivo opens new avenues for diagnostic and therapeutic interventions in multiple diseases, from immunodeficiency to cancer. PMID:25285232

  3. Mechanisms of immune response regulation in lung cancer

    OpenAIRE

    Domagala-Kulawik, Joanna; Osinska, Iwona; Hoser, Grazyna

    2014-01-01

    Lung cancer is a leading cause of cancer deaths. As a solid tumor with low antigenicity and heterogenic phenotype lung cancer evades host immune defense. The cytotoxic anticancer effect is suppressed by a complex mechanism in tumor microenvironment. The population of regulatory T cells (Tregs) plays a crucial role in this inhibition of immune response. Tregs are defined by presence of forkhead box P3 (Foxp3) molecule. The high expression of Foxp3 was found in lung cancer cells and in tumor in...

  4. Oropharyngeal Candidiasis in HIV Infection: Analysis of Impaired Mucosal Immune Response to Candida albicans in Mice Expressing the HIV-1 Transgene

    Directory of Open Access Journals (Sweden)

    Louis de Repentigny

    2015-06-01

    Full Text Available IL-17-producing Th17 cells are of critical importance in host defense against oropharyngeal candidiasis (OPC. Speculation about defective Th17 responses to oral C. albicans infection in the context of HIV infection prompted an investigation of innate and adaptive immune responses to Candida albicans in transgenic mice expressing the genome of HIV-1 in immune cells and displaying an AIDS-like disease. Defective IL-17 and IL-22-dependent mucosal responses to C. albicans were found to determine susceptibility to OPC in these transgenic mice. Innate phagocytes were quantitatively and functionally intact, and individually dispensable for control of OPC and to prevent systemic dissemination of Candida to deep organs. CD8+ T-cells recruited to the oral mucosa of the transgenic mice limited the proliferation of C. albicans in these conditions of CD4+ T-cell deficiency. Therefore, the immunopathogenesis of OPC in the context of HIV infection involves defective T-cell-mediated immunity, failure of crosstalk with innate mucosal immune effector mechanisms, and compensatory cell responses, which limit Candida infection to the oral mucosa and prevent systemic dissemination.

  5. Oropharyngeal Candidiasis in HIV Infection: Analysis of Impaired Mucosal Immune Response to Candida albicans in Mice Expressing the HIV-1 Transgene.

    Science.gov (United States)

    de Repentigny, Louis; Goupil, Mathieu; Jolicoeur, Paul

    2015-01-01

    IL-17-producing Th17 cells are of critical importance in host defense against oropharyngeal candidiasis (OPC). Speculation about defective Th17 responses to oral C. albicans infection in the context of HIV infection prompted an investigation of innate and adaptive immune responses to Candida albicans in transgenic mice expressing the genome of HIV-1 in immune cells and displaying an AIDS-like disease. Defective IL-17 and IL-22-dependent mucosal responses to C. albicans were found to determine susceptibility to OPC in these transgenic mice. Innate phagocytes were quantitatively and functionally intact, and individually dispensable for control of OPC and to prevent systemic dissemination of Candida to deep organs. CD8+ T-cells recruited to the oral mucosa of the transgenic mice limited the proliferation of C. albicans in these conditions of CD4+ T-cell deficiency. Therefore, the immunopathogenesis of OPC in the context of HIV infection involves defective T-cell-mediated immunity, failure of crosstalk with innate mucosal immune effector mechanisms, and compensatory cell responses, which limit Candida infection to the oral mucosa and prevent systemic dissemination. PMID:26110288

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

    Science.gov (United States)

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

    2015-03-01

    VirB proteins from Brucella spp. constitute the type IV secretion system, a key virulence factor mediating the intracellular survival of these bacteria. Here, we assessed whether a Th1-type immune response against VirB proteins may protect mice from Brucella infection and whether this response can be induced in the dog, a natural host for Brucella. Splenocytes from mice immunized with VirB7 or VirB9 responded to their respective antigens with significant and specific production of gamma interferon (IFN-γ), whereas interleukin-4 (IL-4) was not detected. Thirty days after an intraperitoneal challenge with live Brucella abortus, the spleen load of bacteria was almost 1 log lower in mice immunized with VirB proteins than in unvaccinated animals. As colonization reduction seemed to correlate with a Th1-type immune response against VirB proteins, we decided to assess whether such a response could be elicited in the dog. Peripheral blood mononuclear cells (PBMCs) from dogs immunized with VirB proteins (three subcutaneous doses in QuilA adjuvant) produced significantly higher levels of IFN-γ than cells from control animals upon in vitro stimulation with VirB proteins. A skin test to assess specific delayed-type hypersensitivity was positive in 4 out of 5 dogs immunized with either VirB7 or VirB9. As both proteins are predicted to locate in the outer membrane of Brucella organisms, the ability of anti-VirB antibodies to mediate complement-dependent bacteriolysis of B. canis was assessed in vitro. Sera from dogs immunized with either VirB7 or VirB9, but not from those receiving phosphate-buffered saline (PBS), produced significant bacteriolysis. These results suggest that VirB-specific responses that reduce organ colonization by Brucella in mice can be also elicited in dogs. PMID:25540276

  7. Inflammation and Immune Response in COPD: Where Do We Stand?

    Directory of Open Access Journals (Sweden)

    Nikoletta Rovina

    2013-01-01

    Full Text Available Increasing evidence indicates that chronic inflammatory and immune responses play key roles in the development and progression of COPD. Recent data provide evidence for a role in the NLRP3 inflammasome in the airway inflammation observed in COPD. Cigarette smoke activates innate immune cells by triggering pattern recognition receptors (PRRs to release “danger signal”. These signals act as ligands to Toll-like receptors (TLRs, triggering the production of cytokines and inducing innate inflammation. In smokers who develop COPD there appears to be a specific pattern of inflammation in the airways and parenchyma as a result of both innate and adaptive immune responses, with the predominance of CD8+ and CD4+ cells, and in the more severe disease, with the presence of lymphoid follicles containing B lymphocytes and T cells. Furthermore, viral and bacterial infections interfere with the chronic inflammation seen in stable COPD and exacerbations via pathogen-associated molecular patterns (PAMPs. Finally, autoimmunity is another novel aspect that may play a critical role in the pathogenesis of COPD. This review is un update of the currently discussed roles of inflammatory and immune responses in the pathogenesis of COPD.

  8. The Effect of Radiation on the Immune Response to Cancers

    Directory of Open Access Journals (Sweden)

    Bonggoo Park

    2014-01-01

    Full Text Available In cancer patients undergoing radiation therapy, the beneficial effects of radiation can extend beyond direct cytotoxicity to tumor cells. Delivery of localized radiation to tumors often leads to systemic responses at distant sites, a phenomenon known as the abscopal effect which has been attributed to the induction and enhancement of the endogenous anti-tumor innate and adaptive immune response. The mechanisms surrounding the abscopal effect are diverse and include trafficking of lymphocytes into the tumor microenvironment, enhanced tumor recognition and killing via up-regulation of tumor antigens and antigen presenting machinery and, induction of positive immunomodulatory pathways. Here, we discuss potential mechanisms of radiation-induced enhancement of the anti-tumor response through its effect on the host immune system and explore potential combinational immune-based strategies such as adoptive cellular therapy using ex vivo expanded NK and T cells as a means of delivering a potent effector population in the context of radiation-enhanced anti-tumor immune environment.

  9. Immunization with avian metapneumovirus harboring chicken Fc induces higher immune responses.

    Science.gov (United States)

    Paudel, Sarita; Easwaran, Maheswaran; Jang, Hyun; Jung, Ho-Kyoung; Kim, Joo-Hun; Shin, Hyun-Jin

    2016-07-15

    In this study, we evaluated the immune responses of avian metapneumovirus harboring chicken Fc molecule. Stable Vero cells expressing chicken Fc chimera on its surface (Vero-cFc) were established, and we confirmed that aMPV grown in Vero-cFc incorporated host derived chimera Fc into the aMPV virions. Immunization of chicken with aMPV-cFc induced higher level of antibodies and inflammatory cytokines; (Interferon (IFN)-γ and Interleukin (IL)-1β) compared to those of aMPV. The increased levels of antibodies and inflammatory cytokines in chicken immunized with aMPV-cFc were statistically significantly (p<0.05) to that of aMPV and control. The aMPV-cFc group also generated the highest neutralizing antibody response. After challenges, chickens immunized with aMPV-cFc showed much less pathological signs in nasal turbinates and trachea so that we could confirm aMPV-cFc induced higher protection than that of aMPV. The greater ability of aMPV harboring chicken Fc to that of aMPV presented it as a possible vaccine candidate. PMID:27130629

  10. Functional characterization of Foxp3-specific spontaneous immune responses

    DEFF Research Database (Denmark)

    Larsen, Susanne Købke; Munir, S; Andersen, Anders Woetmann;

    2013-01-01

    Tumor-infiltrating CD4+CD25+ regulatory T cells (Tregs) are associated with an impaired prognosis in several cancers. The transcription factor forkhead box P3 (Foxp3) is generally expressed in Tregs. Here, we identify and characterize spontaneous cytotoxic immune responses to Foxp3-expressing cells...... Foxp3 protein indicating that this protein was indeed internalized, processed and cross-presented in the context of HLA-A2. More importantly, however, Foxp3-specific T cells were able to specifically recognize Tregs. Similarly, Foxp3+ malignant T cells established from a Cutaneous T-cell lymphomas...... (CTCL) patient were readily killed by the Foxp3-specific cytotoxic T lymphocytes. The spontaneous presence of Foxp3-specific cytotoxic T-cell responses suggest a general role of such T cells in the complex network of immune regulation as such responses may eliminate Tregs, that is, suppression of the...

  11. Immune dysfunction following infection with chicken anemia agent and infectious bursal disease virus. II. Alterations of in vitro lymphoproliferation and in vivo immune responses.

    Science.gov (United States)

    Cloud, S S; Rosenberger, J K; Lillehoj, H S

    1992-11-01

    To determine the functional impact of alterations in lymphocyte concentrations and ratios following infection with chicken anemia agent (CAA) alone or in combination with infectious bursal disease virus (IBDV) on the immune system of young chickens, in vitro lymphoproliferation assays and in vivo responses to vaccination with several common viral agents were assessed at various time intervals post-inoculation (PI). Concanavalin A (Con A), phytohemagglutinin (PHA) and pokeweed mitogen (PWM) stimulation of splenic lymphocytes (SPL) collected from control birds could not be detected until 10-14 days PI. Infection with CAA was characterized by significantly higher PWM stimulation of SPL at 17 days PI and significantly lower PWM stimulation of peripheral blood lymphocytes (PBL) at 14 days PI, compared with uninfected controls. Concanavalin A and PWM stimulation of SPL was significantly increased in birds inoculated with IBDV alone. Lymphocytes harvested from birds inoculated simultaneously with CAA and IBDV had significantly lower responses. Effects on humoral and cell-mediated immunity following CAA and/or IBDV were determined by evaluating vaccination responses to Newcastle disease virus (NDV), fowl pox virus (FPV) and infectious laryngotracheitis virus (ILTV) during the acute phase of CAA infection (2 weeks PI). Vaccination of birds 2 weeks following CAA infection at 1 day of age resulted in decreased protection against NDV (85.7%) and ILTV (7.1%) challenge compared with protection rates in control birds (100% and 53.3% respectively). Infectious bursal disease virus infection was associated with decreased protection against NDV (60%) only. Concomitant infection at 1 day of age resulted in a greater reduction in NDV challenge protection (33.3%), slightly decreased FPV protection (87.5%), increased numbers of persistent FPV vaccination lesions and increased protection against ILTV challenge (71.4%). Vaccination of birds 2 weeks following CAA infection at 2 weeks of age

  12. No apparent cost of evolved immune response in Drosophila melanogaster.

    Science.gov (United States)

    Gupta, Vanika; Venkatesan, Saudamini; Chatterjee, Martik; Syed, Zeeshan A; Nivsarkar, Vaishnavi; Prasad, Nagaraj G

    2016-04-01

    Maintenance and deployment of the immune system are costly and are hence predicted to trade-off with other resource-demanding traits, such as reproduction. We subjected this longstanding idea to test using laboratory experimental evolution approach. In the present study, replicate populations of Drosophila melanogaster were subjected to three selection regimes-I (Infection with Pseudomonas entomophila), S (Sham-infection with MgSO4 ), and U (Unhandled Control). After 30 generations of selection flies from the I regime had evolved better survivorship upon infection with P. entomophila compared to flies from U and S regimes. However, contrary to expectations and previous reports, we did not find any evidence of trade-offs between immunity and other life history related traits, such as longevity, fecundity, egg hatchability, or development time. After 45 generations of selection, the selection was relaxed for a set of populations. Even after 15 generations, the postinfection survivorship of populations under relaxed selection regime did not decline. We speculate that either there is a negligible cost to the evolved immune response or that trade-offs occur on traits such as reproductive behavior or other immune mechanisms that we have not investigated in this study. Our research suggests that at least under certain conditions, life-history trade-offs might play little role in maintaining variation in immunity. PMID:26932243

  13. Persistence of the immune response induced by BCG vaccination

    Directory of Open Access Journals (Sweden)

    Blitz Rose

    2008-01-01

    Full Text Available Abstract Background Although BCG vaccination is recommended in most countries of the world, little is known of the persistence of BCG-induced immune responses. As novel TB vaccines may be given to boost the immunity induced by neonatal BCG vaccination, evidence concerning the persistence of the BCG vaccine-induced response would help inform decisions about when such boosting would be most effective. Methods A randomised control study of UK adolescents was carried out to investigate persistence of BCG immune responses. Adolescents were tested for interferon-gamma (IFN-γ response to Mycobacterium tuberculosis purified protein derivative (M.tb PPD in a whole blood assay before, 3 months, 12 months (n = 148 and 3 years (n = 19 after receiving teenage BCG vaccination or 14 years after receiving infant BCG vaccination (n = 16. Results A gradual reduction in magnitude of response was evident from 3 months to 1 year and from 1 year to 3 years following teenage vaccination, but responses 3 years after vaccination were still on average 6 times higher than before vaccination among vaccinees. Some individuals (11/86; 13% failed to make a detectable antigen-specific response three months after vaccination, or lost the response after 1 (11/86; 13% or 3 (3/19; 16% years. IFN-γ response to Ag85 was measured in a subgroup of adolescents and appeared to be better maintained with no decline from 3 to 12 months. A smaller group of adolescents were tested 14 years after receiving infant BCG vaccination and 13/16 (81% made a detectable IFN-γ response to M.tb PPD 14 years after infant vaccination as compared to 6/16 (38% matched unvaccinated controls (p = 0.012; teenagers vaccinated in infancy were 19 times more likely to make an IFN-γ response of > 500 pg/ml than unvaccinated teenagers. Conclusion BCG vaccination in infancy and adolescence induces immunological memory to mycobacterial antigens that is still present and measurable for at least 14 years in the

  14. DMPD: Innate immune responses during infection. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15576198 Innate immune responses during infection. Ulevitch RJ, Mathison JC, da Sil...va Correia J. Vaccine. 2004 Dec 6;22 Suppl 1:S25-30. (.png) (.svg) (.html) (.csml) Show Innate immune response...s during infection. PubmedID 15576198 Title Innate immune responses during infection. Authors Ulevitch RJ,

  15. Inhibition of the immune response to experimental fresh osteoarticular allografts

    International Nuclear Information System (INIS)

    The immune response to osteoarticular allografts is capable of destroying the cartilage--a tissue that has antigens on its cells identical to those on the bone and marrow cells. Osteoarticular allografts of the distal femur were performed in rats using various methods to attempt to temporarily inhibit the antibody response. The temporary systemic immunosuppressant regimens investigated were cyclophosphamide, azathioprine and prednisolone, cyclosporine A, and total lymphoid irradiation. The most successful appeared to be cyclosporine A, but significant side effects were observed. To specifically inhibit the immune response in the allograft antigens without systemically inhibiting the entire immune system, passive enhancement and preadministration of donor blood were tried. Neither was as effective as coating the donor bone with biodegradable cements, a method previously found to be successful. Cyclosporine A was investigated in dogs in a preliminary study of medial compartmental knee allografts and was found to be successful in inhibiting the antibody response and in producing a more successful graft; however, some significant side effects were similarly observed

  16. Inhibition of the immune response to experimental fresh osteoarticular allografts

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigo, J.J.; Schnaser, A.M.; Reynolds, H.M. Jr.; Biggart, J.M. 3d.; Leathers, M.W.; Chism, S.E.; Thorson, E.; Grotz, T.; Yang, Q.M. (Univ. of California, Davis, Sacramento (USA))

    1989-06-01

    The immune response to osteoarticular allografts is capable of destroying the cartilage--a tissue that has antigens on its cells identical to those on the bone and marrow cells. Osteoarticular allografts of the distal femur were performed in rats using various methods to attempt to temporarily inhibit the antibody response. The temporary systemic immunosuppressant regimens investigated were cyclophosphamide, azathioprine and prednisolone, cyclosporine A, and total lymphoid irradiation. The most successful appeared to be cyclosporine A, but significant side effects were observed. To specifically inhibit the immune response in the allograft antigens without systemically inhibiting the entire immune system, passive enhancement and preadministration of donor blood were tried. Neither was as effective as coating the donor bone with biodegradable cements, a method previously found to be successful. Cyclosporine A was investigated in dogs in a preliminary study of medial compartmental knee allografts and was found to be successful in inhibiting the antibody response and in producing a more successful graft; however, some significant side effects were similarly observed.

  17. Immune responses of Helicoverpa armigera to different kinds of pathogens

    Directory of Open Access Journals (Sweden)

    Zhao Xiao-Fan

    2010-03-01

    Full Text Available Abstract Background Insects react against pathogens through innate immunity. The cotton bollworm Helicoverpa armigera (H. armigera is an important defoliator and an extremely destructive pest insect of many crops. The elucidation of the mechanism of the immune response of H. armigera to various pathogens can provide a theoretical basis for new approaches to biologically control this pest. Results Four kinds of pathogens Bacillus thuringiensis, Klebsiella pneumoniae, Candida albicans, and Autographa californica multiple nucleocapsid nucleopolyhedrovirus harbored green fluorescence protein and polyhedron (AcMNPV-GFP were used to challenge the insect. The cellular and humoral immune responses to the pathogens were analyzed in the challenged H. armigera. The results show that in the five kinds of haemocytes, only granulocytes phagocytized the Gram-negative and Gram-positive bacteria and fungi. All haemocytes can be infected by AcMNPV. Fourteen immune-related genes including pattern recognition receptors (PRRs such as peptidoglycan recognition proteins (HaPGRP and HaPGRP C and Gram-Negative Bacteria-Binding Protein (HaGNBP, and antimicrobial peptides (AMPs such as cecropin-1, 2 and 3 (HaCec-1, 2 and 3, lysozyme (HaLys, attacin (HaAtt, gallerimycin-like (HaGall, gloverin-like (HaGlo, moricin-like (HaMor, cobatoxin-like (HaCob, galiomicin-like (HaGali, and immune inducible protein (HaIip appeared in different expression profiles to different pathogen infections. The transcripts of 13 immune related genes (except HaPGRPC are obviously up-regulated by Gram-positive bacteria. HaCec-1 and 3, HaMor, HaAtt, HaLys, HaIip, HaPGRP and HaGNBP are greatly up-regulated after fungal infection. HaGNBP, HaCec-2, HaGall, HaGlo, HaMor, HaCob, HaGali obviously increased in Gram-negative bacterial infection. Only five genes, HaGNBP, HaCec-1, HaGali, HaGlo, and HaLys, are weakly up-regulated after viral infection. The AMP transcripts had higher expression levels than the

  18. FEATURES OF THE IMMUNE RESPONSE DURING VIRAL INFECTION

    Directory of Open Access Journals (Sweden)

    G. A. Borisov

    2015-06-01

    Full Text Available The aim of the investigation was to select using cluster analysis and comparatively characterize immune disorders types in acute and chronic viral infections. Patients with acute and chronic viral infections (n = 896 were examined: 77 patients with acute viral hepatitis B, 94 — chronic viral hepatitis B, 119 — chronic hepatitis C, 531 — recurrent herpes, 75 — human papillomavirus infection. Healthy persons (n = 466 were examined as control. The research of blood lymphocyte phenotype was performed by flow cytometry. Four-color immunophenotyping were used in the following panels: Т-lymphocytes (CD3+CD19–CD16/56–CD45+, Т-helpers (CD3+CD4+CD45+, cytotoxic Т-cells (CD3+CD8+CD45+, NKcells (CD3–CD16/56+CD45+, B-lymphocytes (CD3–CD19+CD16/56+CD45+. Absolute values were obtained on a dualplatform technology using the results of haematological analysis. The immunoglobulin concentrations were determined by ELISA. The clustering was performed by a single linkage method. The number of clusters was determined on the basis of calculating the values of the Euclidean distance between the mean group values. It was found that the parameters, characterizing the functional state of the various parts of the immune system in acute and chronic viral infections, considerable diversity values. Custer analysis allows to allocate 6 immunotypes defined different states of innate and adaptive immunity: characterized by activation of the innate (increasing the number of neutrophils and NK-cells and adaptive immunity humoral response (increasing the concentration of IgG, characterized by hyperreaction of adaptive immunity (a significant increase in the concentration of IgG, discoordinated (multidirectional changes in the values of immunological parameters, immunodeficiency and unresponsiveness (did not differ from the control parameters immunotypes. It is proved that in patients with viral infections most often determined by the

  19. Durable pharmacological responses from the peptide ShK-186, a specific Kv1.3 channel inhibitor that suppresses T cell mediators of autoimmune disease.

    Science.gov (United States)

    Tarcha, Eric J; Chi, Victor; Muñoz-Elías, Ernesto J; Bailey, David; Londono, Luz M; Upadhyay, Sanjeev K; Norton, Kayla; Banks, Amy; Tjong, Indra; Nguyen, Hai; Hu, Xueyou; Ruppert, Greg W; Boley, Scott E; Slauter, Richard; Sams, James; Knapp, Brian; Kentala, Dustin; Hansen, Zachary; Pennington, Michael W; Beeton, Christine; Chandy, K George; Iadonato, Shawn P

    2012-09-01

    The Kv1.3 channel is a recognized target for pharmaceutical development to treat autoimmune diseases and organ rejection. ShK-186, a specific peptide inhibitor of Kv1.3, has shown promise in animal models of multiple sclerosis and rheumatoid arthritis. Here, we describe the pharmacokinetic-pharmacodynamic relationship for ShK-186 in rats and monkeys. The pharmacokinetic profile of ShK-186 was evaluated with a validated high-performance liquid chromatography-tandem mass spectrometry method to measure the peptide's concentration in plasma. These results were compared with single-photon emission computed tomography/computed tomography data collected with an ¹¹¹In-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-conjugate of ShK-186 to assess whole-blood pharmacokinetic parameters as well as the peptide's absorption, distribution, and excretion. Analysis of these data support a model wherein ShK-186 is absorbed slowly from the injection site, resulting in blood concentrations above the Kv1.3 channel-blocking IC₅₀ value for up to 7 days in monkeys. Pharmacodynamic studies on human peripheral blood mononuclear cells showed that brief exposure to ShK-186 resulted in sustained suppression of cytokine responses and may contribute to prolonged drug effects. In delayed-type hypersensitivity, chronic relapsing-remitting experimental autoimmune encephalomyelitis, and pristane-induced arthritis rat models, a single dose of ShK-186 every 2 to 5 days was as effective as daily administration. ShK-186's slow distribution from the injection site and its long residence time on the Kv1.3 channel contribute to the prolonged therapeutic effect of ShK-186 in animal models of autoimmune disease. PMID:22637724

  20. Anti-tumor immune response after photodynamic therapy

    Science.gov (United States)

    Mroz, Pawel; Castano, Ana P.; Wu, Mei X.; Kung, Andrew L.; Hamblin, Michael R.

    2009-06-01

    Anti-tumor immunity is stimulated after PDT due a number of factors including: the acute inflammatory response caused by PDT, release of antigens from PDT-damaged tumor cells, priming of the adaptive immune system to recognize tumor-associated antigens (TAA), and induction of heat-shock proteins. The induction of specific CD8+ T-lymphocyte cells that recognize major histocompatibility complex class I (MHC-I) restricted epitopes of TAAs is a highly desirable goal in cancer therapy as it would allow the treatment of tumors that may have already metastasized. The PDT killed tumor cells may be phagocytosed by dendritic cells (DC) that then migrate to draining lymph nodes and prime naÃve T-cells that recognize TAA epitopes. We have carried out in vivo PDT with a BPD-mediated vascular regimen using a pair of BALB/c mouse colon carcinomas: CT26 wild type expressing the naturally occurring retroviral antigen gp70 and CT26.CL25 additionally expressing beta-galactosidase (b-gal) as a model tumor rejection antigen. PDT of CT26.CL25 cured 100% of tumors but none of the CT26WT tumors (all recurred). Cured CT26.CL25 mice were resistant to rechallenge. Moreover mice with two bilateral CT26.CL25 tumors that had only one treated with PDT demonstrated spontaneous regression of 70% of untreated contralateral tumors. T-lymphocytes were isolated from lymph nodes of PDT cured mice that recognized a particular peptide specific to b-gal antigen. T-lymphocytes from LN were able to kill CT26.CL25 target cells in vitro but not CT26WT cells as shown by a chromium release assay. CT26.CL25 tumors treated with PDT and removed five days later had higher levels of Th1 cytokines than CT26 WT tumors showing a higher level of immune response. When mice bearing CT26WT tumors were treated with a regimen of low dose cyclophosphamide (CY) 2 days before, PDT led to 100% of cures (versus 0% without CY) and resistance to rechallenge. Low dose CY is thought to deplete regulatory T-cells (Treg, CD4+CD25+foxp