WorldWideScience

Sample records for cell-mediated immunity

  1. Cell mediated immunity to fungi: a reassessment.

    Science.gov (United States)

    Romani, Luigina

    2008-09-01

    Protective immunity against fungal pathogens is achieved by the integration of two distinct arms of the immune system, the innate and adaptive responses. Innate and adaptive immune responses are intimately linked and controlled by sets of molecules and receptors that act to generate the most effective form of immunity for protection against fungal pathogens. The decision of how to respond will still be primarily determined by interactions between pathogens and cells of the innate immune system, but the actions of T cells will feed back into this dynamic equilibrium to regulate the balance between tolerogenic and inflammatory responses. In the last two decades, the immunopathogenesis of fungal infections and fungal diseases was explained primarily in terms of Th1/Th2 balance. Although Th1 responses driven by the IL-12/IFN-gamma axis are central to protection against fungi, other cytokines and T cell-dependent pathways have come of age. The newly described Th17 developmental pathway may play an inflammatory role previously attributed to uncontrolled Th1 responses and serves to accommodate the seemingly paradoxical association of chronic inflammatory responses with fungal persistence in the face of an ongoing inflammation. Regulatory T cells in their capacity to inhibit aspects of innate and adaptive antifungal immunity have become an integral component of immune resistance to fungi, and provide the host with immune defense mechanisms adequate for protection, without necessarily eliminating fungal pathogens which would impair immune memory--or causing an unacceptable level of tissue damage. The enzyme indoleamine 2,3-dioxygenase and tryptophan metabolites contribute to immune homeostasis by inducing Tregs and taming overzealous or heightened inflammatory responses.

  2. The role of cell-mediated immunity in typhoid.

    Science.gov (United States)

    Mabel, T J; Paniker, C K

    1979-06-01

    The cell-mediated immunity in typhoid was assessed by the leukocyte migration inhibition test and delayed hypersensitivity skin test in 60 clinical typhoid patients. The property of leukocyte migration inhibition appeared first and was positive in 28 of 60 (46.7%) patients on admission and 45 of 60 (75%) at the time of discharge. This difference was definitely more in blood culture positive patients. The delayed hypersensitivity appeared later and was positive in 18 of 60 (30%) on admission and 31 of 60 (51.7%) at the time of discharge. Patients with positive cellular-immune response against typhoid antigen did not develop relapse. On the whole cell-mediated immunity seems to play an important role in typoid. The control groups--the medical and surgical patients, doctors, clinical students and preclinical students--showed positive cellular immune response of 43.3 81.3, 40.7 and 25% respectively. The significance of these results is discussed.

  3. 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...

  4. Cell mediated immune response in human antirabies revaccination

    Directory of Open Access Journals (Sweden)

    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.

  5. 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.

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

    Science.gov (United States)

    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

  7. 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...

  8. Analysis of cell-mediated immune responses in support of dengue vaccine development efforts.

    Science.gov (United States)

    Rothman, Alan L; Currier, Jeffrey R; Friberg, Heather L; Mathew, Anuja

    2015-12-10

    Dengue vaccine development has made significant strides, but a better understanding of how vaccine-induced immune responses correlate with vaccine efficacy can greatly accelerate development, testing, and deployment as well as ameliorate potential risks and safety concerns. Advances in basic immunology knowledge and techniques have already improved our understanding of cell-mediated immunity of natural dengue virus infection and vaccination. We conclude that the evidence base is adequate to argue for inclusion of assessments of cell-mediated immunity as part of clinical trials of dengue vaccines, although further research to identify useful correlates of protective immunity is needed.

  9. CELL-MEDIATED IMMUNE RESPONSES IN THE SEA-STAR ASTERIAS RUBENS (ECHINODERM

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    Michel Leclerc

    2012-01-01

    Full Text Available Cell-mediated immune responses occur in sea star system. In Asterias rubens it is said that B sea star lymphocytes and T sea star lymphocytes exist in the axial organ which can be considered as an ancestral lymphoid organ. In the same manner the origin of lymphocytes can be found in Invertebrates such as Echinodermal.

  10. 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...

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

    DEFF Research Database (Denmark)

    Öhman, H.; Tiitinen, A; Halttunen, M.;

    2006-01-01

    background. To study a relationship between interleukin-10 (IL-10) promoter -1082 polymorphism and cell-mediated immune response during C trachomatis infection in vitro, lymphocyte proliferation and cytokine (IL-10, IFN-gamma, TNF-alpha, IL-2, IL-4 and IL-5) secretion were analysed in subjects with different...

  12. 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;

    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...

  13. 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. ...

  14. 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.)

  15. Prospects for a nonliving vaccine against Schistosomiasis based on cell-mediated immune resistance mechanisms

    Directory of Open Access Journals (Sweden)

    Stephanie L. James

    1987-01-01

    Full Text Available We have designed a vaccine model based on induction of cell-mediated immunity and shown that it protects mice against Schistosoma mansoni infection. Mice are immunized by intradermal injection with schistosome antigens plus BCG. Resistance is dependent on the route of antigen presentation and the adjuvant chosen. The pattern of resistance correlates with sensitization of T lymphocytes for production of gamma interferon, a macrophage activating lymphokine that stimulates the cellular effector mechanism of protection. Purified schistosome paramyosin, a muscle cell component present in soluble parasite antigenic preparations, is immunogenic for T lymphocytes and induces resistance when given intradermally with BCG. It is likely that this protein, and possibly other soluble molecules that are released by the parasites of a challenge infection, induce a cellular inflammatory response resulting in larval trapping and/or killing by activated macrophages. These results verify the feasibility of a vaccine against schistosomiasis based on induction of cell-mediated immune resistance mechanisms.

  16. 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

    is still a problem worldwide. The broad host range of CDV creates a constant viral reservoir among wildlife animals. Our results demonstrated early humoral and cell-mediated immune responses (IFN-gamma) in DNA vaccinated mink compared to mock-vaccinated mink after challenge with a Danish wild-type CDV...

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

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    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.

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    Jeffrey Schlom

    2012-12-01

    Full Text Available 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.

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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

  5. 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

  6. Antigenic role of stress-induced catalase of Salmonella typhimurium in cell-mediated immunity.

    OpenAIRE

    Kagaya, K; Miyakawa, Y; Watanabe, K.; Fukazawa, Y.

    1992-01-01

    The ability of the H2O2-induced catalase of Salmonella typhimurium to induce cell-mediated immunity against S. typhimurium infection in mice was examined. When exponentially growing cells of S. typhimurium were treated with 20 microM H2O2, the cells resisted killing by 1 mM H2O2 and showed the induction of a new species of catalase in addition to the constitutively produced one. Two molecules of catalases in S. typhimurium were isolated from mutant strains: H2O2-induced catalase (catalase II,...

  7. 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

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

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    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.

  9. Neo-lymphoid aggregates in the adult liver can initiate potent cell-mediated immunity.

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    Melanie Greter

    2009-05-01

    Full Text Available Subcutaneous immunization delivers antigen (Ag to local Ag-presenting cells that subsequently migrate into draining lymph nodes (LNs. There, they initiate the activation and expansion of lymphocytes specific for their cognate Ag. In mammals, the structural environment of secondary lymphoid tissues (SLTs is considered essential for the initiation of adaptive immunity. Nevertheless, cold-blooded vertebrates can initiate potent systemic immune responses even though they lack conventional SLTs. The emergence of lymph nodes provided mammals with drastically improved affinity maturation of B cells. Here, we combine the use of different strains of alymphoplastic mice and T cell migration mutants with an experimental paradigm in which the site of Ag delivery is distant from the site of priming and inflammation. We demonstrate that in mammals, SLTs serve primarily B cell priming and affinity maturation, whereas the induction of T cell-driven immune responses can occur outside of SLTs. We found that mice lacking conventional SLTs generate productive systemic CD4- as well as CD8-mediated responses, even under conditions in which draining LNs are considered compulsory for the initiation of adaptive immunity. We describe an alternative pathway for the induction of cell-mediated immunity (CMI, in which Ag-presenting cells sample Ag and migrate into the liver where they induce neo-lymphoid aggregates. These structures are insufficient to support antibody affinity maturation and class switching, but provide a novel surrogate environment for the initiation of CMI.

  10. 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

  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

    infections. In addition, a field evaluation of the diagnostic use of cell-mediated immune responses by IFN-gamma assay and skin test to resolve serological suspicions of Brucella was conducted in an YeO:9 infected pig herd. Following a screening of 200 pigs 39 pigs were identified with false positive...... of antibody responses it was hypothesized that cell-mediated immune responses to non-LPS antigens of the two bacteria can be used to separate immune responses to these two biologically very different infections. Following subclinical experimental infections with Brucella suis biovar 2, high interferon...... with YeO:9 were all negative, except for solitary false positives in 3.7% of the samples from both the experimentally YeO:9 infected pigs and control pigs. Skin tests using the same commercial Brucella antigen confirmed the ability of cell-mediated immune responses to differentiate between the two...

  12. The impact of long-term haemofiltration (continuous veno-venous haemofiltration) on cell-mediated immunity during endotoxaemia

    DEFF Research Database (Denmark)

    Toft, P; Nilsen, B U; Bollen, P;

    2007-01-01

    BACKGROUND: Increased survival with high-volume continuous veno-venous haemofiltration (CVVH) has been demonstrated in critically ill patients. This may be the result of intensified blood purification or an effect on the immune system. We hypothesized that CVVH modifies the cell-mediated immunity...

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  19. 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.

  20. 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

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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

  3. Melatonin treatment prevents modulation of cell-mediated immune response induced by propoxur in rats.

    Science.gov (United States)

    Suke, Sanvidhan G; Pathak, Rahul; Ahmed, Rafat S; Tripathi, A K; Banerjee, B D

    2008-08-01

    The effect of melatonin, a major secretory product of the pineal gland, in attenuation of propoxur (2-isopropoxy phenyl N-methyl carbamate)-induced modulation of cell-mediated immune (CMI) response was studied in rats. Male Wistar albino rats were exposed to propoxur (a widely used pesticide) orally (10 mg/kg) and/or melatonin (10 mg/kg) orally for 4 weeks. CMI was measured by delayed-type hypersensitivity (DTH), leucocyte and macrophage migration inhibition (LMI and MMI) responses and estimation of cytokines TNF-alpha and IFN-gamma levels. Rats exposed to propoxur for 4 weeks showed significant decrease in DTH, LMI and MMI responses. Propoxur also suppressed TNF-alpha and IFN-gamma production significantly. Administration of melatonin alone caused a significant increase in DTH response. Although there were no changes in the LMI and MMI response, the cytokine levels were significantly increased, as compared to control. Co-administration of melatonin along with propoxur significantly nullified the effect of the pesticide on the CMI response, except DTH and reversed levels of cytokines to near control/normal values. Thus, melatonin treatment considerably attenuated immunomodulation caused by sub-chronic treatment of propoxur in experimental animals.

  4. 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.

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

    OpenAIRE

    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...

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

    OpenAIRE

    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...

  7. 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

  8. 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

    or 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 reveal any...

  9. 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...

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

    OpenAIRE

    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 ...

  11. 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;

    Early stage Mycobacterium avium subsp. paratuberculosis (MAP) infection of cattle can be detected by measuring specific cell mediated immune responses, using the interferon gamma (IFN-γ) test. Available IFN-γ tests are using purified protein derivatives of MAP (PPDj) which are crude products...... on the 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...

  12. 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

    Paratuberculosis is a chronic infection of the intestine of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). Early stage MAP infection can be detected by measuring specific cell mediated immune responses, using the whole blood interferon-γ (IFN-γ) assay. Available IFN-γ assays...... 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...

  13. 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

  14. 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

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

    Science.gov (United States)

    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-...

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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 ...

  1. 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.

  2. 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.

  3. 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

    by either SPag or PPD in the presence of immune serum. Studies on subpopulations of PBMC indicated that the inhibitory cells resided among the adherent cell fraction. Furthermore we tested PBMC for cytotoxic activity against P. falciparum-infected autologous or heterologous erythrocytes. Experiments were...... done both in the absence and the presence of immune serum. Neither fresh PBMC nor PBMC activated by SPag or PPD for 7 days prior to assay were cytotoxic, indicating that cytotoxic T cells, natural killer (NK) cells, and K cells did not possess cytotoxic activity directed against parasitized...

  4. 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...

  5. Isolation of Mallory bodies and an attempt to demonstrate cell mediated immunity to Mallory body isolate in patients with alcoholic liver disease

    DEFF Research Database (Denmark)

    Gluud, C; Hardt, F; Aldershvile, J;

    1981-01-01

    in haematoxylin-eosin stained smears. Electron microscopy confirmed the presence of Mallory bodies in the isolates. The Mallory body isolate was used as antigen in the agarose leucocyte migration inhibition test in order to test the cell-mediated immunity. No significant difference in leucocyte migration...

  6. Clinical study of non-specific cell mediated immunity in the patients with esophageal cancer. Influence of preoperative irradiation and surgical intervention

    Energy Technology Data Exchange (ETDEWEB)

    Nakata, Yoshitaka

    1987-06-01

    Few data are available to elucidate the influence of combined preoperative irradiation and surgery on the non-specific cell mediated immunity of patients with esophageal cancer. In vitro and in vivo examinations of the non-specific cell mediated immunity were made before and after irradiation and surgery in 108 patients with esophageal cancer. Decreased immune competence was noticeable one month after surgery in the irradiated group, as compared with the non-irradiated group. Simultaneously, the ratio of concanavalin A to phytohemagglutinin was significantly higher in the irradiated group than the non-irradiated group (p < 0.01). Two months later, both findings in the two groups were similar. There was no consistent tendency toward altered immune competence between the group with curative surgery and the group with non-curative surgery. (Namekawa, K.).

  7. Antibody- and cell-mediated immune responses of Actinobacillus pleuropneumoniae-infected and bacterin-vaccinated pigs.

    Science.gov (United States)

    Furesz, S E; Mallard, B A; Bossé, J T; Rosendal, S; Wilkie, B N; MacInnes, J I

    1997-01-01

    Current porcine pleuropneumonia bacterins afford only partial protection by decreasing mortality but not morbidity. In order to better understand the type(s) of immune response associated with protection, antibody- and cell-mediated immune responses (CMIR) were compared for piglets before and after administration of a commercial bacterin, which confers partial protection, or a low-dose (10(5) CFU/ml) aerosol challenge with Actinobacillus pleuropneumoniae CM5 (LD), which induces complete protection. Control groups received phosphate-buffered saline or adjuvant. Serum antibody response, antibody avidity, delayed-type hypersensitivity (DTH), and lymphocyte blastogenic responses were measured and compared among treatment groups to the lipopolysaccharide (LPS), capsular polysaccharide (CPS), hemolysin (HLY), and outer membrane proteins (OMP) of A. pleuropneumoniae. Peripheral blood lymphocytes and sera were collected prior to and following primary and secondary immunization-infection and high-dose A. pleuropneumoniae CM5 (10(7) CFU/ml) aerosol challenge. Serum antibody and DTH, particularly that to HLY, differed significantly between treatment groups, and increases were associated with protection. LD-infected piglets had higher antibody responses (P < or = 0.01) and antibody avidity (P < or = 0.10) than bacterin-vaccinated and control groups. Anti-HLY antibodies were consistently associated with protection, whereas anti-LPS and anti-CPS antibodies were not. LD-infected animals had higher DTH responses, particularly to HLY, than bacterin-vaccinated pigs (P < or = 0.03). The LD-infected group maintained consistent blastogenic responses to HLY, LPS, CPS, and OMP over the course of infection, unlike the bacterin-vaccinated and control animals. These data suggest that the immune responses induced by a commercial bacterin are very different from those induced by LD aerosol infection and that current bacterins may be modified, for instance, by addition of HLY, so as to

  8. 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

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

    Science.gov (United States)

    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

  10. 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...

  11. 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 (...

  12. 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

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

    Science.gov (United States)

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

    2016-01-12

    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.

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

    Science.gov (United States)

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

    2011-01-01

    SUMMARY 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 (200 μg) of a murine anti-mouse CD4 monoclonal IgG (clone GK1·5). CD4+ T-cell-depleted hamsters infected with the hookworm Ancylostoma ceylanicum exhibited a threefold higher mean intestinal worm burden and more severe anaemia than animals that received isotype control IgG. In addition, depletion of CD4+ T cells was associated with impaired cellular and humoral (serum and mucosal) immune responses to hookworm antigens. These data demonstrate an effector role for CD4+ T cells in hookworm immunity and disease pathogenesis. Ultimately, these studies may yield important insights into the relationship between intestinal nematode infections and diseases that are associated with CD4+ T-cell depletion, including HIV. PMID:20500671

  15. 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

  16. 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

  17. 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.

  18. Multivalent TB vaccines targeting the esx gene family generate potent and broad cell-mediated immune responses superior to BCG.

    Science.gov (United States)

    Villarreal, Daniel O; Walters, Jewell; Laddy, Dominick J; Yan, Jian; Weiner, David B

    2014-01-01

    Development of a broad-spectrum synthetic vaccine against TB would represent an important advance to the limited vaccine armamentarium against TB. It is believed that the esx family of TB antigens may represent important vaccine candidates. However, only 4 esx antigens have been studied as potential vaccine antigens. The challenge remains to develop a vaccine that simultaneously targets all 23 members of the esx family to induce enhanced broad-spectrum cell-mediated immunity. We sought to investigate if broader cellular immune responses could be induced using a multivalent DNA vaccine representing the esx family protein members delivered via electroporation. In this study, 15 designed esx antigens were created to cross target all members of the esx family. They were distributed into groups of 3 self-processing antigens each, resulting in 5 trivalent highly optimized DNA plasmids. Vaccination with all 5 constructs elicited robust antigen-specific IFN-γ responses to all encoded esx antigens and induced multifunctional CD4 Th1 and CD8 T cell responses. Importantly, we show that when all constructs are combined into a cocktail, the RSQ-15 vaccine, elicited substantial broad Ag-specific T cell responses to all esx antigens as compared with vaccination with BCG. Moreover, these vaccine-induced responses were highly cross-reactive with BCG encoded esx family members and were highly immune effective in a BCG DNA prime-boost format. Furthermore, we demonstrate the vaccine potential and immunopotent profile of several novel esx antigens never previously studied. These data highlight the likely importance of these novel immunogens for study as preventative or therapeutic synthetic TB vaccines in combination or as stand alone antigens.

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

    Science.gov (United States)

    Junqueira, Caroline; Guerrero, Ana Tereza; Galvão-Filho, Bruno; Andrade, Warrison A; Salgado, Ana Paula C; Cunha, Thiago M; Ropert, Catherine; Campos, Marco Antônio; Penido, Marcus L O; Mendonça-Previato, Lúcia; Previato, José Oswaldo; Ritter, Gerd; Cunha, Fernando Q; Gazzinelli, Ricardo T

    2012-01-01

    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 (TLR)4 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.

  20. Host genetic background influences the response to the opportunistic Pseudomonas aeruginosa infection altering cell-mediated immunity and bacterial replication.

    Directory of Open Access Journals (Sweden)

    Maura De Simone

    Full Text Available Pseudomonas aeruginosa is a common cause of healthcare-associated infections including pneumonia, bloodstream, urinary tract, and surgical site infections. The clinical outcome of P. aeruginosa infections may be extremely variable among individuals at risk and patients affected by cystic fibrosis. However, risk factors for P. aeruginosa infection remain largely unknown. To identify and track the host factors influencing P. aeruginosa lung infections, inbred immunocompetent mouse strains were screened in a pneumonia model system. A/J, BALB/cJ, BALB/cAnNCrl, BALB/cByJ, C3H/HeOuJ, C57BL/6J, C57BL/6NCrl, DBA/2J, and 129S2/SvPasCRL mice were infected with P. aeruginosa clinical strain and monitored for body weight and mortality up to seven days. The most deviant survival phenotypes were observed for A/J, 129S2/SvPasCRL and DBA/2J showing high susceptibility while BALB/cAnNCrl and C3H/HeOuJ showing more resistance to P. aeruginosa infection. Next, one of the most susceptible and resistant mouse strains were characterized for their deviant clinical and immunological phenotype by scoring bacterial count, cell-mediated immunity, cytokines and chemokines profile and lung pathology in an early time course. Susceptible A/J mice showed significantly higher bacterial burden, higher cytokines and chemokines levels but lower leukocyte recruitment, particularly neutrophils, when compared to C3H/HeOuJ resistant mice. Pathologic scores showed lower inflammatory severity, reduced intraluminal and interstitial inflammation extent, bronchial and parenchymal involvement and diminished alveolar damage in the lungs of A/J when compared to C3H/HeOuJ. Our findings indicate that during an early phase of infection a prompt inflammatory response in the airways set the conditions for a non-permissive environment to P. aeruginosa replication and lock the spread to other organs. Host gene(s may have a role in the reduction of cell-mediated immunity playing a critical role in

  1. Host genetic background influences the response to the opportunistic Pseudomonas aeruginosa infection altering cell-mediated immunity and bacterial replication.

    Science.gov (United States)

    De Simone, Maura; Spagnuolo, Lorenza; Lorè, Nicola Ivan; Rossi, Giacomo; Cigana, Cristina; De Fino, Ida; Iraqi, Fuad A; Bragonzi, Alessandra

    2014-01-01

    Pseudomonas aeruginosa is a common cause of healthcare-associated infections including pneumonia, bloodstream, urinary tract, and surgical site infections. The clinical outcome of P. aeruginosa infections may be extremely variable among individuals at risk and patients affected by cystic fibrosis. However, risk factors for P. aeruginosa infection remain largely unknown. To identify and track the host factors influencing P. aeruginosa lung infections, inbred immunocompetent mouse strains were screened in a pneumonia model system. A/J, BALB/cJ, BALB/cAnNCrl, BALB/cByJ, C3H/HeOuJ, C57BL/6J, C57BL/6NCrl, DBA/2J, and 129S2/SvPasCRL mice were infected with P. aeruginosa clinical strain and monitored for body weight and mortality up to seven days. The most deviant survival phenotypes were observed for A/J, 129S2/SvPasCRL and DBA/2J showing high susceptibility while BALB/cAnNCrl and C3H/HeOuJ showing more resistance to P. aeruginosa infection. Next, one of the most susceptible and resistant mouse strains were characterized for their deviant clinical and immunological phenotype by scoring bacterial count, cell-mediated immunity, cytokines and chemokines profile and lung pathology in an early time course. Susceptible A/J mice showed significantly higher bacterial burden, higher cytokines and chemokines levels but lower leukocyte recruitment, particularly neutrophils, when compared to C3H/HeOuJ resistant mice. Pathologic scores showed lower inflammatory severity, reduced intraluminal and interstitial inflammation extent, bronchial and parenchymal involvement and diminished alveolar damage in the lungs of A/J when compared to C3H/HeOuJ. Our findings indicate that during an early phase of infection a prompt inflammatory response in the airways set the conditions for a non-permissive environment to P. aeruginosa replication and lock the spread to other organs. Host gene(s) may have a role in the reduction of cell-mediated immunity playing a critical role in the control of P

  2. Cyclic AMP represents a crucial component of Treg cell-mediated immune regulation

    Directory of Open Access Journals (Sweden)

    Tobias Bopp

    2016-08-01

    Full Text Available T regulatory (Treg cells are one of the key players in the immune tolerance network (ITN and a plethora of manuscripts has described their development and function in the course of the last two decades. Nevertheless, it is still a matter of debate which mechanisms and agents are employed by Treg cells, providing the basis of their suppressive potency. One of the important candidates is cyclic AMP (cAMP which is long known as a potent suppressor at least of T cell activation and function. While this suppressive function by itself is widely accepted the source and the mechanism of action of cAMP are less clear and a multitude of seemingly contradictory data allow for in principle two different scenarios of cAMP-mediated suppression. In one scenario Treg cells contain high amounts of cAMP and convey this small molecule via gap junction intercellular communication (GJIC directly to the effector T cells (Teff leading to their suppression. Alternatively, it was shown that Treg cells represent the origin of considerable amounts of adenosine which trigger the adenylate cyclases (AC in Teff via A2A and A2B receptors thus strongly increasing intracellular cAMP. This review will present and discuss initial findings and recent developments concerning the function of cAMP for Treg cells and its impact on immune regulation.

  3. 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

  4. 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.

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

    Science.gov (United States)

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

    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 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.

  6. 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...

  7. Cell-Mediated Immunity Imbalance in Patients with Intrahepatic Cholestasis of Pregnancy

    Institute of Scientific and Technical Information of China (English)

    Bin Ling; Fengqiu Yao; Ying Zhou; Zhengzheng Chen; Guodong Shen; Yuanyuan Zhu

    2007-01-01

    Decidual lymphocytes may mediate fetal trophoblast recognition and regulate maternal immune reaction and play an essential role in the maintenance of normal pregnancy. The aim of this study was to compare the percentage of T cells, natural killer (NK) cells and natural killer T (NKT) cells within decidual parietalis of normal pregnant controls (NP) and patients with intraheptic cholestasis of pregnancy (ICP), and to investigate the production of interleukin-4 (IL-4), interferon-γ (IFN-γ) in the culture supernatant of decidual parietalis mononuclear cells (DPMCs). Compared with controls, the decidua parietalis from ICP were characterized with significant increased percentages of CD3-CD56+ cells, CD3+CD56+ cells, CD56+CD16+ cells, CD56+CD16- cells, CD56+NKG2D+ cells, and the significant decreased percentages of CD3+ cells, CD3+CD4+ cells. There were no differences found for the percentage of CD3+CD8+ cells, CD56+NKG2A+ cells between control and study group. In addition, the enhanced concentration of IFN-γ was presented in culture supernatant of DPMCs from ICP. It was suggested that the increased NK cells, NKT cells and the decreased T cells in the decidual parietalis and over-secretion of IFN-γ could be correlated with the pathophysiology of ICP patients.

  8. 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

  9. 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

  10. Better Understanding of the Immunosuppressive Link between the Lymphocytic Immune Cells and the Decreased Cell Mediated Immunity in Head and Neck Cancer Patients

    Directory of Open Access Journals (Sweden)

    A. S. Abdulamir

    2008-01-01

    Full Text Available The purpose of this study was to determine the phenotyping of Peripheral Blood Lymphocytes (PBL in Head and Neck Cancers (HNCA patients and to relate this with the level of Cell-Mediated Immunity (CMI measured by in vitro lymphoproliferative assay, in order to evaluate immune suppression in HNCA patients and its possible mechanisms. Accordingly, one hundred twenty two HNCA patients and 100 control subjects were enrolled in this study. HNCA patients were classified into 42 nasopharyngeal carcinoma, 66 carcinoma of larynx and 14 Hypo Pharyngeal Carcinoma (HPC. For measuring CMI, Microculture Tetrazolium assay (MTT was applied on the freshly isolated lymphocytes of HNCA patients and control group. Immunophenotyping of PBL was carried out for monitoring the blood level of CD3+, CD4+, CD8+, CD21+ cells in HNCA patients in comparison with controls. The results of both assays have been integrated, revealed the presence of remarked immune suppression in HNCA patients in comparison with the controls, especially for NasoPharyngeal Carcinoma (NPC patients who were immunosuppressed more than other studied HNCA types. Surprisingly, NPC group showed the lowest CMI level along with the highest level of PBL subsets, particularly NPC patients expressed the highest level of CD8+ cells among HNCA. It was inferred that CD8+ cells were more likely immune suppressor rather than cytotoxic cells and this is the principal factor for inducing sustained immunosuppression in HNCA and in NPC in particular. Furthermore CD4/CD8 ratio proved to be a reliable index for assessing the immunological status of HNCA patients and more dependable index than other immunity-evaluating factors.

  11. Alterations of Cell-Mediated Immunity in Patients with Type 2 Diabetes Mellitus%2型糖尿病细胞免疫功能的变化

    Institute of Scientific and Technical Information of China (English)

    姚远; 郑佳; 杨敏

    2002-01-01

    Objective To investigate the alterations of cell- mediated immunity in patients with type 2 diabetes mellitus. Methods The level of CD3 CD4 CD8 in 30 normal subjects (NC group) and47 type 2 diabetes mellitus was measured by flow cytometry. Result Type - 2 diabetics had lower levels of CD4 and higher levels of CD8 than the non - diabetic control,especially during the 5 ~ 15 years of diabetes courses. The ratios of CD4 to CD8 was decreased. The correlation analysis showed that the level of CD3 CD4 CD8 and CD4/CD8 was not positively correlated with c - peptide. Conclusion Type - 2 diabeties have alterations of cell- mediated immunity.

  12. 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...

  13. 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

  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.

  15. 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

  16. 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

  17. 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

  18. INCREASED URINARY NEOPTERIN: CREATININE RATIO AS A MARKER OF ACTIVATION OF CELL-MEDIATED IMMUNITY AND OXIDATIVE STRESS IN THE IRANIAN PATIENTS WITH MULTIPLE SCLEROSIS

    Directory of Open Access Journals (Sweden)

    H. Khorami

    2003-09-01

    Full Text Available Neopterin, apyrazinopyrimidine compound, is produced by macrophages after induction by interferon gamma (IFN-y and serves as a marker of cellular immune system activation followed by oxidative stress. The aim of this study was to determine urinary neopterin to creatinine ratio (UNCR as a surrogate marker of cell-mediated immune activation in multiple sclerosis (MS. Three weekly early morning urine samples were collected from 27 patients with MS and 31 age- and sex-matched apparently healthy subjects. Urinary neopterin and creatinine were determined using reversed phase high-performance liquid chromatography and Jaffe reaction, respectively. UNCR was significantly higher in patients than in healthy controls indicating IFN-y-induced cellular immunity activation and oxidative stress in multiple sclerosis. As a non-invasive method, UNCR determination may be helpful in monitoring disease progression and the effects of therapies, as well.

  19. Cell-mediated immune responses to Malassezia furfur serovars A, B and C in patients with pityriasis versicolor, seborrheic dermatitis and controls.

    Science.gov (United States)

    Ashbee, H R; Ingham, E; Holland, K T; Cunliffe, W J

    1994-06-01

    It has been postulated that patients with Malassezia furfur-associated dermatoses have a deficient cell-mediated immune response to M. furfur. This study examined the cell-mediated immune responses to M. furfur serovars A, B and C of 10 patients with pityriasis versicolor and 10 age- and sex-matched controls; and 10 patients with seborrheic dermatitis and 10 age- and sex-matched controls. The responses to each serovar of M. furfur were assessed using the lymphocyte transformation assay and the leukocyte migration inhibition assay. The lymphocyte transformation responses of the patients with pityriasis versicolor to M. furfur serovars A, B and C (0/10, 6/10 and 5/10 respectively) were not significantly different from those of controls (0/10, 2/10 and 1/10). However, for patients with seborrheic dermatitis, significantly more patients' lymphocytes responded to serovars B and C (6/10 and 6/10 respectively) than those of controls (1/10 and 1/10). No patient or control responded to serovar A. In the leukocyte migration inhibition assay, the leukocytes from a greater proportion of patients with pityriasis versicolor (5/7) responded to serovar B than controls (2/10); and the leukocytes from a greater proportion of patients with seborrheic dermatitis (4/10) responded to serovar C than controls (0/9). Thus, this data did not indicate the presence of any cell-mediated immune deficiency to M. furfur in patients with pityriasis versicolor or seborrheic dermatitis, as measured by the lymphocyte transformation assay or the leukocyte migration inhibition assay. The greater responsiveness of T lymphocytes from patients may indicate that T lymphocytes might be involved in the pathogenesis of these diseases.

  20. Effects of feed supplementation with glycine chelate and iron sulfate on selected parameters of cell-mediated immune response in broiler chickens.

    Science.gov (United States)

    Jarosz, Łukasz; Kwiecień, Małgorzata; Marek, Agnieszka; Grądzki, Zbigniew; Winiarska-Mieczan, Anna; Kalinowski, Marcin; Laskowska, Ewa

    2016-08-01

    Because little is known about the impact of chelated (Fe-Gly, Fe-Gly+F) and inorganic (FeSO4, FeSO4+F) iron products on immune response parameters in broiler chickens, the objective of the study was to determine the effects of inorganic and organic forms of iron on selected parameters of the cell-mediated immune response in broiler chickens by assessing the percentage of CD3(+)CD4(+), CD3(+)CD8(+), CD25(+), and MHC Class II lymphocytes, as well as the CD4(+)/CD8(+) ratio and IL-2 concentration in the peripheral blood. The experiments were conducted using 50day-old Ross 308 roosters. The test material was peripheral blood. Flow cytometry was used to determine selected cell-mediated immune response parameters. The results obtained indicate that the use of iron chelates in the diet of broiler chickens may stimulate cellular defense mechanisms. As a result of the experiment an increase was observed in the percentage of Th1, mainly T CD4(+) and T CD8(+). It was also noted that application of chelated iron can increase production of T CD8(+) cytotoxic cells and IL-2, which promotes the body's natural response to developing inflammation. There were no changes in T CD4(+), T CD8(+), T CD25(+) or MHC II lymphocyte subpopulations in the chickens following application of the inorganic form of iron.

  1. A hypoxia-induced decrease of either MICA/B or Hsp70 on the membrane of tumor cells mediates immune escape from NK cells.

    Science.gov (United States)

    Schilling, Daniela; Tetzlaff, Fabian; Konrad, Sarah; Li, Wei; Multhoff, Gabriele

    2015-01-01

    Recent findings suggest that hypoxia of the tumor microenvironment contributes to immune escape from natural killer (NK) cell-mediated cytotoxicity. Heat shock protein 70 (Hsp70) and the stress-regulated major histocompatibility class I chain-related protein A and B (MICA/B) both serve as ligands for activated NK cells when expressed on the cell surface of tumor cells. Herein, we studied the effects of hypoxia and hypoxia-inducible factor-1α (HIF-1α) on the membrane expression of these NK cell ligands in H1339 with high and MDA-MB-231 tumor cells with low basal HIF-1α levels and its consequences on NK cell-mediated cytotoxicity. We could show that a hypoxia-induced decrease in the membrane expression of MICA/B and Hsp70 on H1339 and MDA-MB-231 cells, respectively, is associated with a reduced sensitivity to NK cell-mediated lysis. A knockdown of HIF-1α revealed that the decreased surface expression of MICA/B under hypoxia is dependent on HIF-1α in H1339 cells with high basal HIF-1α levels. Hypoxia and HIF-1α did not affect the MICA/B expression in MDA-MB-231 cells but reduced the Hsp70 membrane expression which in turn also impaired NK cell recognition. Furthermore, we could show that the hypoxia-induced decrease in membrane Hsp70 is independent of HIF-1α in MDA-MB-231. Our data indicate that hypoxia-induced downregulation of both NK cell ligands MICA/B and Hsp70 impairs NK cell-mediated cytotoxicity, whereby only MICA/B appears to be regulated by HIF-1α.

  2. 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.

  3. [Cell-mediated immunity and delayed hypersensitivity study in splenectomy patients: a comparative evaluation between IFN-gamma and skin tests].

    Science.gov (United States)

    Miniello, S; Jirillo, E; Urgesi, G; D'Abbicco, D; Tomasicchio, N; Bonomo, G M

    1999-01-01

    The authors of this paper attempt to indicate a feasible, easy-to-use and inexpensive instrument for daily assessing and monitoring of splenectomized subjects to see if they are immunocompromised. Skin tests which are considered easy and inexpensive, may be useful for immunological investigation if their effectiveness is considered equal to that of more difficult and expensive methods. They have also assessed the effectiveness of ST in the study of specific cell-mediated immunity in general and also in cases of delayed hypersensibility, comparatively to serum IFN gamma dosage. The latter is produced by Th1 lymphocytes and Natural Killer cells and is considered a reasonable indicator of cell-mediated immunity and Th1-related delayed hypersensibility. The results of this study confirm that ST is effective in 100% of all splenectomized patients compared to positivity of 60% for the compromise of the immunocompetent system revealed by serum IFN gamma dosage in the same sample of patients. In addition, the fundamental role of other cytokines was confirmed. These include IL-2 which is produced by Th1 lymphocytes and whose lack of results in splenectomized patients are immunocompromised. This is revealed not only by IFN gamma dosage but also by ST. PMID:10633837

  4. Chronic active hepatitis induced by Helicobacter hepaticus in the A/JCr mouse is associated with a Th1 cell-mediated immune response.

    Science.gov (United States)

    Whary, M T; Morgan, T J; Dangler, C A; Gaudes, K J; Taylor, N S; Fox, J G

    1998-07-01

    Helicobacter hepaticus infection in A/JCr mice results in chronic active hepatitis characterized by perivascular, periportal, and parenchymal infiltrates of mononuclear and polymorphonuclear cells. This study examined the development of hepatitis and the immune response of A/JCr mice to H. hepaticus infection. The humoral and cell-mediated T helper immune response was profiled by measuring the postinfection (p.i.) antibody response in serum, feces, and bile and by the production of cytokines and proliferative responses by splenic mononuclear cells to H. hepaticus antigens. Secretory immunoglobulin A (IgA) and systemic IgG2a antibody developed by 4 weeks p.i. and persisted through 12 months. Splenocytes from infected mice proliferated and produced more gamma interferon (IFN-gamma) than interleukin-4 (IL-4) or IL-5 when cultured with H. hepaticus outer membrane proteins. The predominantly IgG2a antibody response in serum and the in vitro production of IFN-gamma in excess of IL-4 or IL-5 are consistent with a Th1 immune response reported in humans and mice infected with Helicobacter pylori and Helicobacter felis, respectively. Mice infected with H. hepaticus developed progressively severe perivascular, periportal, and hepatic parenchymal lesions consisting of lymphohistiocytic and plasmacytic cellular infiltrates. In addition, transmural typhlitis was observed at 12 months p.i. The characterization of a cell-mediated Th1 immune response to H. hepaticus infection in the A/JCr mouse should prove valuable as a model for experimental regimens which manipulate the host response to Helicobacter.

  5. Dim light at night interferes with the development of the short-day phenotype and impairs cell-mediated immunity in Siberian hamsters (Phodopus sungorus).

    Science.gov (United States)

    Aubrecht, Taryn G; Weil, Zachary M; Nelson, Randy J

    2014-10-01

    Winter is a challenging time to survive and breed outside of the tropics. Animals use day length (photoperiod) to regulate seasonally appropriate adaptations in anticipation of challenging winter conditions. The net result of these photoperiod-mediated adjustments is enhanced immune function and increased survival. Thus, the ability to discriminate day length information is critical for survival and reproduction in small animals. However, during the past century, urban and suburban development has rapidly expanded and filled the night sky with light from various sources, obscuring crucial light-dark signals, which alters physiological interpretation of day lengths. Furthermore, reduced space, increased proximity to people, and the presence of light at night may act as stressors for small animals. Whereas acute stressors typically enhance immune responses, chronic exposure to stressors often impairs immune responses. Therefore, we hypothesized that the combination of dim light at night and chronic stress interferes with enhanced cell-mediated immunity observed during short days. Siberian hamsters (Phodopus sungorus) were assigned to short or long days with dark nights (0 lux) or dim (5 lux) light at night for 10 weeks. Following 2 weeks of chronic restraint (6 hr/day), a model of chronic stress, delayed type hypersensitivity (DTH) responses were assessed. Both dim light at night and restraint reduced the DTH response. Dim light at night during long nights produced an intermediate short day phenotype. These results suggest the constant presence of light at night could negatively affect survival of photoperiodic rodents by disrupting the timing of breeding and immune responses.

  6. 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.

  7. Aspects of T Cell-Mediated Immunity Induced in Mice by a DNA Vaccine Based on the Dengue-NS1 Antigen after Challenge by the Intracerebral Route.

    Science.gov (United States)

    Oliveira, Edson R A; Gonçalves, Antônio J S; Costa, Simone M; Azevedo, Adriana S; Mantuano-Barradas, Marcio; Nogueira, Ana Cristina M A; Alves, Ada M B

    2016-01-01

    Dengue disease has emerged as a major public health issue across tropical and subtropical countries. Infections caused by dengue virus (DENV) can evolve to life-threatening forms, resulting in about 20,000 deaths every year worldwide. Several animal models have been described concerning pre-clinical stages in vaccine development against dengue, each of them presenting limitations and advantages. Among these models, a traditional approach is the inoculation of a mouse-brain adapted DENV variant in immunocompetent animals by the intracerebral (i.c.) route. Despite the historical usage and relevance of this model for vaccine testing, little is known about the mechanisms by which the protection is developed upon vaccination. To cover this topic, a DNA vaccine based on the DENV non-structural protein 1 (pcTPANS1) was considered and investigations were focused on the induced T cell-mediated immunity against i.c.-DENV infection. Immunophenotyping assays by flow cytometry revealed that immunization with pcTPANS1 promotes a sustained T cell activation in spleen of i.c.-infected mice. Moreover, we found that the downregulation of CD45RB on T cells, as an indicator of cell activation, correlated with absence of morbidity upon virus challenge. Adoptive transfer procedures supported by CFSE-labeled cell tracking showed that NS1-specific T cells induced by vaccination, proliferate and migrate to peripheral organs of infected mice, such as the liver. Additionally, in late stages of infection (from the 7th day onwards), vaccinated mice also presented reduced levels of circulating IFN-γ and IL-12p70 in comparison to non-vaccinated animals. In conclusion, this work presented new aspects about the T cell-mediated immunity concerning DNA vaccination with pcTPANS1 and the i.c. infection model. These insights can be explored in further studies of anti-dengue vaccine efficacy. PMID:27631083

  8. Aspects of T Cell-Mediated Immunity Induced in Mice by a DNA Vaccine Based on the Dengue-NS1 Antigen after Challenge by the Intracerebral Route

    Science.gov (United States)

    Oliveira, Edson R. A.; Gonçalves, Antônio J. S.; Costa, Simone M.; Azevedo, Adriana S.; Mantuano-Barradas, Marcio; Nogueira, Ana Cristina M. A.

    2016-01-01

    Dengue disease has emerged as a major public health issue across tropical and subtropical countries. Infections caused by dengue virus (DENV) can evolve to life-threatening forms, resulting in about 20,000 deaths every year worldwide. Several animal models have been described concerning pre-clinical stages in vaccine development against dengue, each of them presenting limitations and advantages. Among these models, a traditional approach is the inoculation of a mouse-brain adapted DENV variant in immunocompetent animals by the intracerebral (i.c.) route. Despite the historical usage and relevance of this model for vaccine testing, little is known about the mechanisms by which the protection is developed upon vaccination. To cover this topic, a DNA vaccine based on the DENV non-structural protein 1 (pcTPANS1) was considered and investigations were focused on the induced T cell-mediated immunity against i.c.-DENV infection. Immunophenotyping assays by flow cytometry revealed that immunization with pcTPANS1 promotes a sustained T cell activation in spleen of i.c.-infected mice. Moreover, we found that the downregulation of CD45RB on T cells, as an indicator of cell activation, correlated with absence of morbidity upon virus challenge. Adoptive transfer procedures supported by CFSE-labeled cell tracking showed that NS1-specific T cells induced by vaccination, proliferate and migrate to peripheral organs of infected mice, such as the liver. Additionally, in late stages of infection (from the 7th day onwards), vaccinated mice also presented reduced levels of circulating IFN-γ and IL-12p70 in comparison to non-vaccinated animals. In conclusion, this work presented new aspects about the T cell-mediated immunity concerning DNA vaccination with pcTPANS1 and the i.c. infection model. These insights can be explored in further studies of anti-dengue vaccine efficacy. PMID:27631083

  9. 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.

  10. 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

    Acute renal failure (ARF) is a common morbidity factor among patients in the intensive care unit, reaching an incidence from 3% to 30% depending on the definition of ARF and the population. Although the majority of the patients with ARF are treated with continuous renal replacement therapy......, the 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...... the inflammatory response, we measured myeloperoxidase (MPO) in the organs, and CD 11b and major histocompatibility complex (MHC) II-positive cells in the blood. Non-renal I/R elicited the most elevated levels of MPO in extra-renal tissue such as the lungs. There was a trend toward higher MPO levels in the kidney...

  11. 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;

    2011-01-01

    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......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...

  12. The critical role of the tumor microenvironment in shaping natural killer cell-mediated anti-tumor immunity

    Directory of Open Access Journals (Sweden)

    Joanna eBaginska

    2013-12-01

    Full Text Available Considerable evidence has been gathered over the last 10 years showing that the tumor microenvironment (TME is not simply a passive recipient of immune cells, but an active participant in the establishment of immunosuppressive conditions. It is now well documented that hypoxia, within the TME, affects the functions of immune effectors including natural killer (NK cells by multiple overlapping mechanisms. Indeed, each cell in the TME, irrespective of its transformation status, has the capacity to adapt to the hostile TME and produce immune modulatory signals or mediators affecting the function of immune cells either directly or through the stimulation of other cells present in the tumor site. This observation has led to intense research efforts focused mainly on tumor-derived factors. Notably, it has become increasingly clear that tumor cells secrete a number of environmental factors such as cytokines, growth factors, exosomes, and microRNAs impacting the immune cell response. Moreover, tumor cells in hostile microenvironments may activate their own intrinsic resistance mechanisms, such as autophagy, to escape the effective immune response. Such adaptive mechanisms may also include the ability of tumor cells to modify their metabolism and release several metabolites to impair the function of immune cells. In this review, we summarize the different mechanisms involved in the TME that affect the anti-tumor immune function of NK cells.

  13. IL-18 potentiated whole blood IFN-γ assay can identify cell-mediated immune responses towards Lawsonia intracellularis in experimentally infected pigs

    DEFF Research Database (Denmark)

    Riber, Ulla; Jakobsen, Jeanne Toft; Hvass, Henriette Cordes;

    Lawsonia intracellularis is an obligate intracellular bacteria causing proliferative enteropathy (PE) in pigs. The infection causes diarrhoea, retarded growth and sudden death in pigs and is one of the most economically important diseases in the swine industry worldwide. The infection is one...... indications that cell-mediated immune responses (CMI) are important for the protection against infections with L. intracellularis and in mice models IFN-γ has been shown to play a key role in the host defence against experimental infections . In L. intracellularis infected pigs, IFN-γ is only sparsely...... exhibited a much lower level of IFN-γ response. Thus, age seems to be an important parameter in measurement of IFN-γ in response to L. intracellularis infection. In the young pigs antibiotic treatment (from 3 weeks. p.i.) cleared the L. intracellularis infection. In contrast to the low response observed...

  14. 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.

  15. Study of biomaterial-induced macrophage activation, cell-mediated immune response and molecular oxidative damage in patients with dermal bioimplants.

    Science.gov (United States)

    Sánchez, Olga; Rodríguez-Sureda, Víctor; Domínguez, Carmen; Fernández-Figueras, Teresa; Vilches, Angel; Llurba, Elisa; Alijotas-Reig, Jaume

    2012-01-01

    Several soft-tissue dermal fillers have been reported to provoke immunogenicity and may cause adverse reactions despite claims regarding their safety. This study aimed to assess biomaterial-induced macrophage activation, cell-mediated immune response and oxidative stress in 169 patients with dermal bioimplants. To this end, we analysed plasma concentrations of myeloperoxidase (MPO), the chitinase-like proteins chitotriosidase and YKL-40 and molecular oxidative damage. The present study shows, for the first time, that the components of innate immunity: chitotriosidase and YKL-40, are significantly higher in patients with certain bioimplants and these markers of monocyte/macrophage activation rose progressively as adverse reactions (AR) evolved. Plasma MPO levels increased 4-fold in filler users with AR and 3-fold in those without. Analysis by filler type showed subjects injected with calcium hydroxylapatite, methacrylate, acrylamides and silicone to have values significantly above those of non-filler subjects for at least two plasma biomarkers, probably because the afore-mentioned biomaterials are permanent and prone to trigger AR in the long term. By contrast, hyaluronic acid alone elicited little immune response. Plasma concentrations of markers of oxidative damage to lipids and proteins were found to be significantly higher in users of four of the nine dermal fillers studied. These diffusible products of molecular peroxidation would stem from the reaction catalysed by MPO that generates potent oxidants, leading to cell oxidative damage which, in turn, may exert deleterious effects on the organism. Overall, the results of this study on the effects of a range of dermal fillers point to chronic activation of the immune response mediated by macrophages and PMNs. The increases in plasma of MPO, chitotriosidase and YKL-40 proteins and products of macromolecular peroxidation suggests that these molecules could serve as blood-based biochemical markers and alert to the

  16. DNA prime/Adenovirus boost malaria vaccine encoding P. falciparum CSP and AMA1 induces sterile protection associated with cell-mediated immunity.

    Directory of Open Access Journals (Sweden)

    Ilin Chuang

    Full Text Available BACKGROUND: Gene-based vaccination using prime/boost regimens protects animals and humans against malaria, inducing cell-mediated responses that in animal models target liver stage malaria parasites. We tested a DNA prime/adenovirus boost malaria vaccine in a Phase 1 clinical trial with controlled human malaria infection. METHODOLOGY/PRINCIPAL FINDINGS: The vaccine regimen was three monthly doses of two DNA plasmids (DNA followed four months later by a single boost with two non-replicating human serotype 5 adenovirus vectors (Ad. The constructs encoded genes expressing P. falciparum circumsporozoite protein (CSP and apical membrane antigen-1 (AMA1. The regimen was safe and well-tolerated, with mostly mild adverse events that occurred at the site of injection. Only one AE (diarrhea, possibly related to immunization, was severe (Grade 3, preventing daily activities. Four weeks after the Ad boost, 15 study subjects were challenged with P. falciparum sporozoites by mosquito bite, and four (27% were sterilely protected. Antibody responses by ELISA rose after Ad boost but were low (CSP geometric mean titer 210, range 44-817; AMA1 geometric mean micrograms/milliliter 11.9, range 1.5-102 and were not associated with protection. Ex vivo IFN-γ ELISpot responses after Ad boost were modest (CSP geometric mean spot forming cells/million peripheral blood mononuclear cells 86, range 13-408; AMA1 348, range 88-1270 and were highest in three protected subjects. ELISpot responses to AMA1 were significantly associated with protection (p = 0.019. Flow cytometry identified predominant IFN-γ mono-secreting CD8+ T cell responses in three protected subjects. No subjects with high pre-existing anti-Ad5 neutralizing antibodies were protected but the association was not statistically significant. SIGNIFICANCE: The DNA/Ad regimen provided the highest sterile immunity achieved against malaria following immunization with a gene-based subunit vaccine (27%. Protection

  17. 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.

  18. 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;

    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...

  19. 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.

  20. 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...

  1. 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...

  2. An African horse sickness virus serotype 4 recombinant canarypox virus vaccine elicits specific cell-mediated immune responses in horses.

    Science.gov (United States)

    El Garch, H; Crafford, J E; Amouyal, P; Durand, P Y; Edlund Toulemonde, C; Lemaitre, L; Cozette, V; Guthrie, A; Minke, J M

    2012-09-15

    A recombinant canarypox virus vectored vaccine co-expressing synthetic genes encoding outer capsid proteins, VP2 and VP5, of African horse sickness virus (AHSV) serotype 4 (ALVAC(®)-AHSV4) has been demonstrated to fully protect horses against homologous challenge with virulent field virus. Guthrie et al. (2009) detected weak and variable titres of neutralizing antibody (ranging from horses received two vaccinations twenty-eight days apart and three horses remained unvaccinated. The detection of VP2/VP5 specific IFN-γ responses was assessed by enzyme linked immune spot (ELISpot) assay and clearly demonstrated that all ALVAC(®)-AHSV4 vaccinated horses developed significant IFN-γ production compared to unvaccinated horses. More detailed immune responses obtained by flow cytometry demonstrated that ALVAC(®)-AHSV4 vaccinations induced immune cells, mainly CD8(+) T cells, able to recognize multiple T-epitopes through all VP2 and only the N-terminus sequence of VP5. Neither VP2 nor VP5 specific IFN-γ responses were detected in unvaccinated horses. Overall, our data demonstrated that an experimental recombinant canarypox based vaccine induced significant CMI specific for both VP2 and VP5 proteins of AHSV4.

  3. 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.

  4. 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...

  5. PB1 as a potential target for increasing the breadth of T-cell mediated immunity to Influenza A

    DEFF Research Database (Denmark)

    Uddbäck, Ida E M; Steffensen, Maria A; Pedersen, Sara R;

    2016-01-01

    not as efficiently protected against influenza A challenge as similarly NP-vaccinated animals. The reason for this is not a difference in the quality of the primed cells, nor in functional avidity. However, under similar conditions of immunization fewer PB1-specific cells were recruited to the airways, and surface...... in the dominant NP366 epitope were not efficiently protected. To address this problem, we envision the use of a cocktail of adenovectors targeting different internal proteins of influenza A virus. Consequently, we investigated the possibility of using PB1 as a target for an adenovector-based vaccine against...

  6. 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

  7. 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.

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

    Science.gov (United States)

    Neff, C. Preston; Gibbert, Kathrin; Dietze, Kirsten K.; Werner, Tanja; Liu, Jia; Chen, Lieping; Lang, Karl S.; Palmer, Brent E.; Dittmer, Ulf; Zelinskyy, Gennadiy

    2015-01-01

    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. PMID:26484769

  9. 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.

  10. Thiol dependent NF-κB suppression and inhibition of T-cell mediated adaptive immune responses by a naturally occurring steroidal lactone Withaferin A.

    Science.gov (United States)

    Gambhir, Lokesh; Checker, Rahul; Sharma, Deepak; Thoh, M; Patil, Anand; Degani, M; Gota, Vikram; Sandur, Santosh K

    2015-12-01

    Withaferin A (WA), a steroidal lactone isolated from ayurvedic medicinal plant Withania somnifera, was shown to inhibit tumor growth by inducing oxidative stress and suppressing NF-κB pathway. However, its effect on T-cell mediated adaptive immune responses and the underlying mechanism has not been investigated. Since both T-cell responses and NF-κB pathway are known to be redox sensitive, the present study was undertaken to elucidate the effect of WA on adaptive immune responses in vitro and in vivo. WA inhibited mitogen induced T-cell and B-cell proliferation in vitro without inducing any cell death. It inhibited upregulation of T-cell (CD25, CD69, CD71 and CD54) and B-cell (CD80, CD86 and MHC-II) activation markers and secretion of Th1 and Th2 cytokines. WA induced oxidative stress by increasing the basal ROS levels and the immunosuppressive effects of WA were abrogated only by thiol anti-oxidants. The redox modulatory effects of WA in T-cells were attributed to its ability to directly interact with free thiols. WA inhibited NF-κB nuclear translocation in lymphocytes and prevented the direct binding of nuclear NF-κB to its consensus sequence. MALDI-TOF analysis using a synthetic NF-κB-p50 peptide containing Cys-62 residue suggested that WA can modify the cysteine residue of NF-κB. The pharmacokinetic studies for WA were also carried out and in vivo efficacy of WA was studied using mouse model of Graft-versus-host disease. In conclusion, WA is a potent inhibitor of T-cell responses and acts via a novel thiol dependent mechanism and inhibition of NF-κB pathway.

  11. Transcriptomic Analysis of Persistent Infection with Foot-and-Mouth Disease Virus in Cattle Suggests Impairment of Apoptosis and Cell-Mediated Immunity in the Nasopharynx.

    Science.gov (United States)

    Eschbaumer, Michael; Stenfeldt, Carolina; Smoliga, George R; Pacheco, Juan M; Rodriguez, Luis L; Li, Robert W; Zhu, James; Arzt, Jonathan

    2016-01-01

    In order to investigate the mechanisms of persistent foot-and-mouth disease virus (FMDV) infection in cattle, transcriptome alterations associated with the FMDV carrier state were characterized using a bovine whole-transcriptome microarray. Eighteen cattle (8 vaccinated with a recombinant FMDV A vaccine, 10 non-vaccinated) were challenged with FMDV A24 Cruzeiro, and the gene expression profiles of nasopharyngeal tissues collected between 21 and 35 days after challenge were compared between 11 persistently infected carriers and 7 non-carriers. Carriers and non-carriers were further compared to 2 naïve animals that had been neither vaccinated nor challenged. At a controlled false-discovery rate of 10% and a minimum difference in expression of 50%, 648 genes were differentially expressed between FMDV carriers and non-carriers, and most (467) had higher expression in carriers. Among these, genes associated with cellular proliferation and the immune response-such as chemokines, cytokines and genes regulating T and B cells-were significantly overrepresented. Differential gene expression was significantly correlated between non-vaccinated and vaccinated animals (biological correlation +0.97), indicating a similar transcriptome profile across these groups. Genes related to prostaglandin E2 production and the induction of regulatory T cells were overexpressed in carriers. In contrast, tissues from non-carrier animals expressed higher levels of complement regulators and pro-apoptotic genes that could promote virus clearance. Based on these findings, we propose a working hypothesis for FMDV persistence in nasopharyngeal tissues of cattle, in which the virus may be maintained by an impairment of apoptosis and the local suppression of cell-mediated antiviral immunity by inducible regulatory T cells. PMID:27643611

  12. Dual Pressure from Antiretroviral Therapy and Cell-Mediated Immune Response on the Human Immunodeficiency Virus Type 1 Protease Gene

    Science.gov (United States)

    Karlsson, Annika C.; Deeks, Steven G.; Barbour, Jason D.; Heiken, Brandon D.; Younger, Sophie R.; Hoh, Rebecca; Lane, Meghan; Sällberg, Matti; Ortiz, Gabriel M.; Demarest, James F.; Liegler, Teri; Grant, Robert M.; Martin, Jeffrey N.; Nixon, Douglas F.

    2003-01-01

    Human immunodeficiency virus (HIV)-specific CD8+ T-lymphocyte pressure can lead to the development of viral escape mutants, with consequent loss of immune control. Antiretroviral drugs also exert selection pressures on HIV, leading to the emergence of drug resistance mutations and increased levels of viral replication. We have determined a minimal epitope of HIV protease, amino acids 76 to 84, towards which a CD8+ T-lymphocyte response is directed. This epitope, which is HLA-A2 restricted, includes two amino acids that commonly mutate (V82A and I84V) in the face of protease inhibitor therapy. Among 29 HIV-infected patients who were treated with protease inhibitors and who had developed resistance to these drugs, we show that the wild-type PR82V76-84 epitope is commonly recognized by cytotoxic T lymphocytes (CTL) in HLA-A2-positive patients and that the CTL directed to this epitope are of high avidity. In contrast, the mutant PR82A76-84 epitope is generally not recognized by wild-type-specific CTL, or when recognized it is of low to moderate avidity, suggesting that the protease inhibitor-selected V82A mutation acts both as a CTL and protease inhibitor escape mutant. Paradoxically, the absence of a mutation at position 82 was associated with the presence of a high-avidity CD8+ T-cell response to the wild-type virus sequence. Our results indicate that both HIV type 1-specific CD8+ T cells and antiretroviral drugs provide complex pressures on the same amino acid sequence of the HIV protease gene and, thus, can influence viral sequence evolution. PMID:12767994

  13. Strategy for eliciting antigen-specific CD8+ T cell-mediated immune response against a cryptic CTL epitope of merkel cell polyomavirus large T antigen

    Directory of Open Access Journals (Sweden)

    Gomez Bianca P

    2012-10-01

    Full Text Available Abstract Background Merkel cell carcinoma (MCC is a relatively new addition to the expanding category of oncovirus-induced cancers. Although still comparably rare, the number of cases has risen dramatically in recent years. Further complicating this trend is that MCC is an extremely aggressive neoplasm with poor patient prognosis and limited treatment options for advanced disease. The causative agent of MCC has been identified as the merkel cell polyomavirus (MCPyV. The MCPyV-encoded large T (LT antigen is an oncoprotein that is theorized to be essential for virus-mediated tumorigenesis and is therefore, an excellent MCC antigen for the generation of antitumor immune responses. As a foreign antigen, the LT oncoprotein avoids the obstacle of immune tolerance, which normally impedes the development of antitumor immunity. Ergo, it is an excellent target for anti-MCC immunotherapy. Since tumor-specific CD8+ T cells lead to better prognosis for MCC and numerous other cancers, we have generated a DNA vaccine that is capable of eliciting LT-specific CD8+ T cells. The DNA vaccine (pcDNA3-CRT/LT encodes the LT antigen linked to a damage-associated molecular pattern, calreticulin (CRT, as it has been demonstrated that the linkage of CRT to antigens promotes the induction of antigen-specific CD8+ T cells. Results The present study shows that DNA vaccine-induced generation of LT-specific CD8+ T cells is augmented by linking CRT to the LT antigen. This is relevant since the therapeutic effects of the pcDNA3-CRT/LT DNA vaccine is mediated by LT-specific CD8+ T cells. Mice vaccinated with the DNA vaccine produced demonstrably more LT-specific CD8+ T cells. The DNA vaccine was also able to confer LT-specific CD8+ T cell-mediated protective and therapeutic effects to prolong the survival of mice with LT-expressing tumors. In the interest of determining the LT epitope which most MCC-specific CD8+ T cells recognize, we identified the amino acid sequence of the

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

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    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.

  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. 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

  17. 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

  18. 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 ...

  19. 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...

  20. Improved cell mediated immune responses after successful re-vaccination of non-responders to the hepatitis B virus surface antigen (HBsAg) vaccine using the combined hepatitis A and B vaccine.

    Science.gov (United States)

    Nyström, Jessica; Cardell, Kristina; Björnsdottir, Thora Björg; Fryden, Aril; Hultgren, Catharina; Sällberg, Matti

    2008-11-01

    We successfully re-vaccinated hepatitis B virus (HBV) vaccine non-responders using a double dose of the combined hepatitis A virus (HAV) and HBV vaccine. The hope was to improve priming of hepatitis B surface antigen (HBsAg)-specific cell mediated immune response (CMI) by an increased antigen dose and a theoretical adjuvant-effect from the local presence of a HAV-specific CMI. A few non-responders had a detectable HBsAg-specific CMI before re-vaccination. An in vitro detectable HBsAg-specific CMI was primed equally effective in non-responders (58%) as in first time vaccine recipients (68%). After the third dose a weak, albeit significant, association was observed between the magnitude of HBsAg-specific proliferation and anti-HBs levels. This regimen improves the priming of HBsAg-specific CMIs and antibodies.

  1. Humoral and cell-mediated immunity following vaccination with synthetic Candida cell wall mannan derived heptamannoside-protein conjugate: immunomodulatory properties of heptamannoside-BSA conjugate.

    Science.gov (United States)

    Paulovičová, Lucia; Paulovičová, Ema; Karelin, Alexander A; Tsvetkov, Yury E; Nifantiev, Nikolay E; Bystrický, Slavomír

    2012-10-01

    Chemically defined glycoprotein conjugate composed of synthetically prepared mannan-derived heptamannoside with terminal β-1,2-linked mannose residue attached to the α-1,3-linked mannose residues and BSA as carrier protein (M7-BSA conjugate) was analysed for the capacity to induce protective humoral immunity and appropriate alteration cellular immunity. To identify protective antigenic structure of Candida cell wall mannan M7-BSA conjugate was used for BALB/c mice immunization. The obtained results were compared with placebo group and with heat-inactivated C. albicans whole cells immunization. The administration route of M7-BSA conjugate secondary booster injection significantly affected the intensity of humoral immune response and the specificity of produced antibodies. All prepared sera were able to elevate candidacidal activity of polymorphonuclear leukocytes (PMN) in cooperation with complement. Moreover, polyclonal sera obtained after secondary subcutaneous (s.c.) booster injection of M7-BSA conjugate were able to induce candidacidal activity of PMN also in complement independent manner. M7-BSA conjugate immunization induced increases of phagocytic activity and respiratory burst of granulocytes, caused a raise of the proportion of CD3(+) T lymphocytes and increased the CD4(+)/CD8(+) T lymphocyte ratio. We observed also an increasing proportion of CD4(+)CD25(+) T cells compared to immunization with heat inactivated whole C. albicans cells, which in turn promoted an increase of the CD8(+)CD25(+) cell proportion. Immunization with M7-BSA conjugate induced Th1, Th2 and Th17 immune responses as indicated by the elevation of relevant cytokines levels. These data provide some insights on the immunomodulatory properties of oligomannosides and contribute to the development of synthetic oligosaccharide vaccines against fungal diseases.

  2. 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...

  3. 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.

  4. An oral Salmonella-based vaccine inhibits liver metastases by promoting tumor-specific T cell-mediated immunity in celiac & portal lymph nodes. A preclinical study.

    Directory of Open Access Journals (Sweden)

    Alejandrina eVendrell

    2016-03-01

    Full Text Available Primary tumor excision is one of the therapies of cancer most widely used. 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 source 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 immunized with CVD 915 via o.g. 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 & portal lymph nodes (LDLN 21 days after oral bacterial inoculation. The antitumor immune response inside the liver was associated with increased CD4+ and DC 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 & 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.

  5. 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...

  6. 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...

  7. Effects of inhalation exposure to a binary mixture of benzene and toluene on vitamin a status and humoral and cell-mediated immunity in wild and captive American kestrels.

    Science.gov (United States)

    Olsgard, Mandy L; Bortolotti, Gary R; Trask, Brenda R; Smits, Judit E G

    2008-01-01

    Benzene and toluene are representative volatile organic compounds (VOC) released during production, storage, and transportation associated with the oil and gas industry and are chemicals of concern, as they are released in greater and possibly more biologically significant concentrations than other compounds. Most studies of air pollution in high oil and gas activity areas have neglected to consider risks to birds, including top-level predators. Birds can be used as highly sensitive monitors of air quality and since the avian respiratory tract is physiologically different from a rodent respiratory tract, effects of gases cannot be safely extrapolated from rodent studies. Wild and captive male American kestrels were exposed for approximately 1 h daily for 28 d to high (rodent lowest-observed-adverse-effect level [LOAEL] of 10 ppm and 80 ppm, respectively) or environmentally relevant (0.1 ppm and 0.8 ppm, respectively) levels of benzene and toluene. Altered immune responses characteristic of those seen in mammalian exposures were evident in kestrels. A decreased cell-mediated immunity, measured by delayed-type hypersensitivity testing, was evident in all exposed birds. There was no effect on humoral immunity. Plasma retinol levels as measured by high-performance liquid chromatography (HPLC) analysis were decreased in wild and captive kestrels exposed to the rodent LOAEL for combined benzene and toluene. This study indicates that American kestrels are sensitive to combined benzene and toluene. The study also illustrates the need for reference concentrations for airborne pollutants to be calculated, including sensitive endpoints specific to birds. Based on these findings, future studies need to include immune endpoints to determine the possible increased susceptibility of birds to inhaled toxicants.

  8. 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

  9. 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.

  10. 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

  11. 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

  12. 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+, ...

  13. T-cell-mediated immunity to lymphocytic choriomeningitis virus in beta2-integrin (CD18)- and ICAM-1 (CD54)-deficient mice

    DEFF Research Database (Denmark)

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

    1996-01-01

    The T-cell response to lymphocytic choriomeningitis virus was studied in mice with deficient expression of beta2-integrins or ICAM-1. In such mice, the generation of virus-specific cytotoxic T lymphocytes was only slightly impaired and bystander activation was as extensive as that observed in wild...... the inflammatory reaction, indicating that under conditions of more limited immune activation both molecules do play a role in formation of the inflammatory exudate. Finally, virus control was found to be somewhat impaired in both mutant strains. In conclusion, our results indicate that although LFA-1-ICAM-1...

  14. Induction of humoral and cell-mediated anti-human immunodeficiency virus (HIV) responses in HIV sero-negative volunteers by immunization with recombinant gp160.

    Science.gov (United States)

    Kovacs, J A; Vasudevachari, M B; Easter, M; Davey, R T; Falloon, J; Polis, M A; Metcalf, J A; Salzman, N; Baseler, M; Smith, G E

    1993-01-01

    Development of an effective vaccine for prevention of infection with HIV would provide an important mechanism for controlling the AIDS epidemic. In the current study, the first clinical trial of a candidate HIV-1 vaccine initiated in the United States, the safety and immunogenicity of escalating doses (10-1,280 micrograms) of recombinant gp160 (rgp160), were evaluated in 138 HIV-negative volunteers. Maximal antibody responses, as evaluated by ELISA, were seen after immunization with three doses of 1,280 micrograms rgp160. Responses to some specific epitopes of HIV gp160, including the second conserved domain and the CD4 binding site, were seen more frequently than after natural infection. Neutralizing antibodies to the homologous HIV strain, but not heterologous strains, were induced by this regimen. Blastogenic responses to rgp160 were seen in most volunteers receiving at least two doses of > or = 20 micrograms. These envelope-specific T cell responses were also seen against heterologous strains of HIV. No major adverse reactions were seen after immunization. Thus, rgp160 is a safe and immunogenic candidate HIV vaccine; further studies are needed to determine if it will provide any clinical benefit in preventing HIV infection. Images PMID:7688766

  15. 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;

    2015-01-01

    nomically important diseases in modern pig production worldwide. The Enterisol®Ileitis vaccine havebeen shown to reduce clinical disease and to increase weight gain, however, while the natural infectionwith L. intracellularis can provide complete protection against re-infection, this has not been...... achievedby this vaccine. We therefore undertook a detailed characterization of immune responses to L. intracel-lularis infection in vaccinated pigs (VAC) compared to previously infected pigs (RE) in order to pinpointimmunological determinants of protection.Results: The VAC pigs shed L. intracellularis...... 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...

  16. 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

  17. Effects of Bifidobacterium longum BB536 administration on influenza infection, influenza vaccine antibody titer, and cell-mediated immunity in the elderly.

    Science.gov (United States)

    Namba, Kazuyoshi; Hatano, Michiko; Yaeshima, Tomoko; Takase, Mitsunori; Suzuki, Kunihiko

    2010-01-01

    Twenty-seven elderly subjects (mean age 86.7+/-6.6 years) were pre-administered a test food containing 1x10(11) cfu of BB536 daily for 5 weeks (P1), during which they also received influenza vaccination at week 3. The subjects were then randomized to a BB536 group and a placebo group for 14 weeks (P2). The proportion of subjects who contracted influenza was significantly lower in BB536 group than in the to placebo group. The proportion of subjects with fever was also significantly lower in the BB536 group than in the placebo group. In the P1 period, the NK cell activity and the bactericidal activity of the neutrophils were significantly higher at week 5 than to before BB536 administration. In the P2 period, although NK cell activity and neutrophilic activities declined at the end of the study in both the placebo and the BB536 group, neutrophil phagocytic activity and NK cell activity tended to maintain slightly higher levels in the BB536 group than in the placebo group. These results suggest that continuous ingestion of BB536 reduces the incidence of influenza and fever, probably by potentiating innate immunity.

  18. 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

  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. 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

  1. 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.

  2. 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.

  3. 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

  4. 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...

  5. 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

  6. 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

  7. HBsAg及B7-2抗原重组腺病毒载体感染免疫研究%Humoral immunization and cell-mediated immunization evoked by HBsAg and B7-2 Ag coexpression recombinant adenovirus vector

    Institute of Scientific and Technical Information of China (English)

    周智; 张定凤; 任红

    2001-01-01

    regular dose of HBsAg antigen vaccine. The cell-mediated immune response was highly induced by the recombinant adenovirus infection. No clear side effect was observed after immunization. Conclusions This could be a novel strategy for a development of both preventive and therapeutic vaccines against HBV infection. The recombinant adenovirus vector is an effective and safety vector system suitable to the experiments of gene immunization and gene therapy for incurable diseases.

  8. 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, ...

  9. 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

  10. 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...

  11. 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.

  12. Immunity

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008254 Prokaryotic expression and immunogenicity of Fba,a novel fibronectin-binding protein of group A streptococcus.MA Cuiqing(马翠柳),et al.Dept Immunol,Basic Med Coll,Hebei Med Univ,Shijiazhuang 050017.Chin J Infect Dis 2008;26(3):146-150.Objective To express the novel fibronectin-binding protein Fba ofgroupAstreptococcus(GAS)and analyze its immunogenicity,so to evaluate the immune responses to GAS infection.Methods fbagene was amplified by

  13. B-cell-mediated strategies to fight chronic allograft rejection

    Directory of Open Access Journals (Sweden)

    Ali H Dalloul

    2013-12-01

    Full Text Available Solid organs have been transplanted for decades. Since the improvement in graft selection and in medical and surgical procedures, the likelihood of graft function after one year is now close to 90%. Nonetheless even well-matched recipients continue to need medications for the rest of their lives hence adverse side effects and enhanced morbidity. Understanding Immune rejection mechanisms, is of increasing importance since the greater use of living-unrelated donors and genetically unmatched individuals. Chronic rejection is devoted to T-cells, however the role of B-cells in rejection has been appreciated recently by the observation that B-cell depletion improve graft survival. By contrast however, B-cells can be beneficial to the grafted tissue. This protective effect is secondary to either the secretion of protective antibodies or the induction of B-cells that restrain excessive inflammatory responses, chiefly by local provision of IL-10, or inhibit effector T-cells by direct cellular interactions. As a proof of concept B-cell-mediated infectious transplantation tolerance could be achieved in animal models, and evidence emerged that the presence of such B-cells in transplanted patients correlate with a favorable outcome. Among these populations, regulatory B-cells constitute a recently described population. These cells may develop as a feedback mechanism to prevent uncontrolled reactivity to antigens and inflammatory stimuli. The difficult task for the clinician, is to quantify the respective ratios and functions of tolerant vs effector B-cells within a transplanted organ, at a given time point in order to modulate B-cell-directed therapy. Several receptors at the B-cell membrane as well as signaling molecules, can now be targeted for this purpose. Understanding the temporal expansion of regulatory B-cells in grafted patients and the stimuli that activate them will help in the future to implement specific strategies aimed at fighting chronic

  14. Immune effects of probiotics

    OpenAIRE

    Wold, Agnes E.

    2001-01-01

    Twenty papers concerning the effects on the immune system of ingestion of probiotic bacteria in humans have been reviewed. Several studies report that intake of probiotics stimulate cell-mediated immune effector functions. Thus, enhanced production of interferon-y by blood cells, enhanced phagocytosis by polymorphonuclear leukocytes (PMN) and to a lesser extent monocytes, and enhanced expression of complement receptors on PMNs are effects quite consistently seen in subjects consuming probioti...

  15. 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

  16. The Role of Antioxidation and Immunomodulation in Postnatal Multipotent Stem Cell-Mediated Cardiac Repair

    Directory of Open Access Journals (Sweden)

    Johnny Huard

    2013-08-01

    Full Text Available Oxidative stress and inflammation play major roles in the pathogenesis of coronary heart disease including myocardial infarction (MI. The pathological progression following MI is very complex and involves a number of cell populations including cells localized within the heart, as well as cells recruited from the circulation and other tissues that participate in inflammatory and reparative processes. These cells, with their secretory factors, have pleiotropic effects that depend on the stage of inflammation and regeneration. Excessive inflammation leads to enlargement of the infarction site, pathological remodeling and eventually, heart dysfunction. Stem cell therapy represents a unique and innovative approach to ameliorate oxidative stress and inflammation caused by ischemic heart disease. Consequently, it is crucial to understand the crosstalk between stem cells and other cells involved in post-MI cardiac tissue repair, especially immune cells, in order to harness the beneficial effects of the immune response following MI and further improve stem cell-mediated cardiac regeneration. This paper reviews the recent findings on the role of antioxidation and immunomodulation in postnatal multipotent stem cell-mediated cardiac repair following ischemic heart disease, particularly acute MI and focuses specifically on mesenchymal, muscle and blood-vessel-derived stem cells due to their antioxidant and immunomodulatory properties.

  17. Mesenchymal stem cell-mediated functional tooth regeneration in swine.

    Directory of Open Access Journals (Sweden)

    Wataru Sonoyama

    Full Text Available Mesenchymal stem cell-mediated tissue regeneration is a promising approach for regenerative medicine for a wide range of applications. Here we report a new population of stem cells isolated from the root apical papilla of human teeth (SCAP, stem cells from apical papilla. Using a minipig model, we transplanted both human SCAP and periodontal ligament stem cells (PDLSCs to generate a root/periodontal complex capable of supporting a porcelain crown, resulting in normal tooth function. This work integrates a stem cell-mediated tissue regeneration strategy, engineered materials for structure, and current dental crown technologies. This hybridized tissue engineering approach led to recovery of tooth strength and appearance.

  18. 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

  19. 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

  20. 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...

  1. 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.

  2. Bone marrow stromal cell: mediated neuroprotection for spinal cord repair

    OpenAIRE

    Ritfeld, Gaby Jane

    2014-01-01

    Currently, there is no treatment available that restores anatomy and function after spinal cord injury. This thesis explores transplantation of bone marrow-derived mesenchymal stem cells (bone marrow stromal cells; BMSCs) as a therapeutic approach for spinal cord repair. BMSCs secrete neurotrophic factors, enabling neuroprotection/tissue sparing in a rat model of spinal cord injury. In this model system, bone marrow stromal cell-mediated tissue sparing leads to motor and sensory function impr...

  3. Mesenchymal Stem Cell-Mediated Functional Tooth Regeneration in Swine

    OpenAIRE

    Wataru Sonoyama; Yi Liu; Dianji Fang; Takayoshi Yamaza; Byoung-Moo Seo; Chunmei Zhang; He Liu; Stan Gronthos; Cun-Yu Wang; Songlin Wang; Songtao Shi

    2006-01-01

    Mesenchymal stem cell-mediated tissue regeneration is a promising approach for regenerative medicine for a wide range of applications. Here we report a new population of stem cells isolated from the root apical papilla of human teeth (SCAP, stem cells from apical papilla). Using a minipig model, we transplanted both human SCAP and periodontal ligament stem cells (PDLSCs) to generate a root/periodontal complex capable of supporting a porcelain crown, resulting in normal tooth function. This wo...

  4. 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......60)-specific immunoglobulin G (IgG) antibodies were analysed using enzyme-linked immunosorbent assay (ELISA) kits. Proliferative reactivity of peripheral blood mononuclear cells was studied in vitro against Chlamydia elementary body (EB) and recombinant CHSP60 antigens. RESULTS: C. trachomatis-specific...

  5. 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 double......-deficient mice were more susceptible to intracerebral infection than CXCR3-deficient mice. Analysis of effector T cell generation revealed an accelerated antiviral CD8+ T cell response in CXCR3/CCR5 double-deficient mice. Furthermore, while the accumulation of CD8+ T cells in the neural parenchyma...

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

    Directory of Open Access Journals (Sweden)

    Yoseph A. Mekori

    2012-01-01

    Full Text Available 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 cytokine release. The signaling events associated with this pathway of mast cell activation have also been elucidated confirming the activation of the Ras MAPK systems. More recently, we hypothesized and demonstrated that mast cells may also be activated by microparticles released from activated T cells that are considered as miniature version of a cell. By extension, microparticles might affect the activity of mast cells, which are usually not in direct contact with T cells at the inflammatory site. Recent works have also focused on the effects of regulatory T cells on mast cells. These reports highlighted the importance of the cytokines IL-2 and IL-9, produced by mast cells and T cells, respectively, in obtaining optimal immune suppression. Finally, physical contact, associated by OX40-OX40L engagement has been found to underlie the down-regulatory effects exerted by regulatory T cells on mast cell function.

  7. T cell-mediated modulation of mast cell function: heterotypic adhesion-induced stimulatory or inhibitory effects.

    Science.gov (United States)

    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 cytokine release. The signaling events associated with this pathway of mast cell activation have also been elucidated confirming the activation of the Ras mitogen-activated protein kinase systems. More recently, we hypothesized and demonstrated that mast cells may also be activated by microparticles released from activated T cells that are considered as miniature version of a cell. By extension, microparticles might affect the activity of mast cells, which are usually not in direct contact with T cells at the inflammatory site. Recent works have also focused on the effects of regulatory T cells (Treg) on mast cells. These reports highlighted the importance of the cytokines IL-2 and IL-9, produced by mast cells and T cells, respectively, in obtaining optimal immune suppression. Finally, physical contact, associated by OX40-OX40L engagement has been found to underlie the down-regulatory effects exerted by Treg on mast cell function. PMID:22566892

  8. 葎草花粉变应原核酸疫苗通过诱导Foxp3+Treg细胞分化介导对哮喘模型小鼠的免疫保护作用%Foxp3+Treg cells mediate immune protection of humulus pollen allergy DNA vaccine pcD-NA3.1-Hum in asthmatic mice

    Institute of Scientific and Technical Information of China (English)

    卢家美; 李满祥; 孙秀珍; 张永红; 刘昀; 徐晶; 张苏梅

    2014-01-01

    Objective To construct a humulus pollen allergy DNA vaccine pcDNA3.1-Hum and investigate its effect for immune protection mediated by Foxp3+Treg cells in asthmatic mice. Methods The target humulus gene obtained from pTripIEx2-Hum plasmid by double enzyme digestion was inserted sequentially into pcDNA3.1(-) vector to generate the recombinant plasmid pcDNA3.1-Hum, which was validated by sequencing. The pcDNA3.1-Hum plasmid was transfected into COS-7 cells and the expression of the ectopic protein was analyzed using Western blotting. Co-cultured dendritic cells and CD4+CD25-T cells were stimulated with the expressed protein to test its efficacy in inducing Foxp3+Treg cells. The levels of humulus-specific IgE and IgG2a were assayed to evaluate the allergenicity and immunogenicity of pcDNA3.1-Hum in mice. The immunoprotective effect of pcDNA3.1-Hum was assessed in a mouse model of humulus-specific asthma. Results The constructed pcDNA3.1-Hum plasmid was validated by sequencing and Western blotting, and the expressed protein was shown to induce Foxp3+Treg cells in the co-culture. In normal mice, pcDNA3.1-Hum induced a significant increase of humulus-specific IgG2a but had no effect on IgE. In the asthmatic mice, pcDNA3.1-Hum significantly decreased inflammatory cell counts and eosinophil percentages in the BALF, ameliorated lung inflammation, and lowered AHR and IL-4 levels; immunization of the mice with pcDNA3.1-Hum reversed humulus-induced reduction of serum IFN-γ and prevented the humulus-triggered reduction of Foxp3+Treg cell percentage in the spleen. Conclusion We have successfully constructed a highly immunogenic pcDNA3.1-Hum DNA vaccine that can mediate immune protection by inducing Foxp3+Treg cells.%目的:构建葎草花粉变应原核酸疫苗pcDNA3.1-Hum,并探讨其是否通过诱导Foxp3+Treg细胞分化介导对哮喘模型小鼠的免疫保护作用。方法双酶切pTripIEx2-Hum质粒以获取目的基因,定向插入pcDNA3.1(-)载

  9. Narcolepsy-Associated HLA Class I Alleles Implicate Cell-Mediated Cytotoxicity

    Science.gov (United States)

    Tafti, Mehdi; Lammers, Gert J.; Dauvilliers, Yves; Overeem, Sebastiaan; Mayer, Geert; Nowak, Jacek; Pfister, Corinne; Dubois, Valérie; Eliaou, Jean-François; Eberhard, Hans-Peter; Liblau, Roland; Wierzbicka, Aleksandra; Geisler, Peter; Bassetti, Claudio L.; Mathis, Johannes; Lecendreux, Michel; Khatami, Ramin; Heinzer, Raphaël; Haba-Rubio, José; Feketeova, Eva; Baumann, Christian R.; Kutalik, Zoltán; Tiercy, Jean-Marie

    2016-01-01

    Study Objectives: Narcolepsy with cataplexy is tightly associated with the HLA class II allele DQB1*06:02. Evidence indicates a complex contribution of HLA class II genes to narcolepsy susceptibility with a recent independent association with HLA-DPB1. The cause of narcolepsy is supposed be an autoimmune attack against hypocretin-producing neurons. Despite the strong association with HLA class II, there is no evidence for CD4+ T-cell-mediated mechanism in narcolepsy. Since neurons express class I and not class II molecules, the final effector immune cells involved might include class I-restricted CD8+ T-cells. Methods: HLA class I (A, B, and C) and II (DQB1) genotypes were analyzed in 944 European narcolepsy with cataplexy patients and in 4,043 control subjects matched by country of origin. All patients and controls were DQB1*06:02 positive and class I associations were conditioned on DQB1 alleles. Results: HLA-A*11:01 (OR = 1.49 [1.18–1.87] P = 7.0*10−4), C*04:01 (OR = 1.34 [1.10–1.63] P = 3.23*10−3), and B*35:01 (OR = 1.46 [1.13–1.89] P = 3.64*10−3) were associated with susceptibility to narcolepsy. Analysis of polymorphic class I amino-acids revealed even stronger associations with key antigen-binding residues HLA-A-Tyr9 (OR = 1.32 [1.15–1.52] P = 6.95*10−5) and HLA-C-Ser11 (OR = 1.34 [1.15–1.57] P = 2.43*10−4). Conclusions: Our findings provide a genetic basis for increased susceptibility to infectious factors or an immune cytotoxic mechanism in narcolepsy, potentially targeting hypocretin neurons. Citation: Tafti M, Lammers GJ, Dauvilliers Y, Overeem S, Mayer G, Nowak J, Pfister C, Dubois V, Eliaou JF, Eberhard HP, Liblau R, Wierzbicka A, Geisler P, Bassetti CL, Mathis J, Lecendreux M, Khatami R, Heinzer R, Haba-Rubio J, Feketeova E, Baumann CR, Kutalik Z, Tiercy JM. Narcolepsy-associated HLA class I alleles implicate cell-mediated cytotoxicity. SLEEP 2016;39(3):581–587. PMID:26518595

  10. The effect and mechanism of Astragaloside IV on immune function of regulatory T cell mediated by high mobility group box 1 protein in vitro%黄芪甲苷对体外高迁移率族蛋白B1介导小鼠调节性T细胞免疫功能的影响

    Institute of Scientific and Technical Information of China (English)

    黄立锋; 李金凤; 姚咏明; 张淑文; 李文雄

    2014-01-01

    Objective Based the previous studies, the present study was performed to investigate the antagonistic effects of different doses of Astragaloside IV on the immune function of Treg mediated by HMGB1 in vitro and its potential mechanism.Methods CD4+CD25-T cells isolated from the spleens of male BABL/c mice by magnetic beads were seeded on 48-well cell culture plates and were randomly divided into four groups as follows(12 holes per group). Normal control group: CD4+CD25-T cells were cultured merely. Treg group: Tregs(100μl) and CD4+CD25-T cells were co-cultured in ratio of 1:10. HMGB1+Treg group: Tregs(100μl) stimulated by HMGB1(1μg/ml) for 72 h and CD4+CD25-T cells were co-cultured in ratio of 1∶10. HMGB1+AST IV+Treg group: Tregs(100μl) stimulated by HMGB1(1μg/ml) and AST IV(100μg/ml)for 72 h were co-cultured with CD4+CD25-T cells in ratio of 1:10. CD4+CD25-T cells and supernatants were again collected on post-culture 72 hour. The proliferation of CD4+CD25- T cells was analyzed by MTT test, the activity of NFAT and the contents of cytokines of IL-2 released into supernatants were also determined by means of ELISA. Results When CD4+CD25-T cells were co-cultured with Tregs, the cell proliferation(0.166±0.039) and the levels of NFAT(0.156±0.035) and IL-2(2.38±0.58) in supernatant were markedly decreased as compared with those in the control group(P<0.01). However, the contrary results were found when CD4+CD25-T cells were co-cultured with Treg stimulated by HMGB1. Compared with those in the(HMGB1+Treg) group, the contrary results were showed with a dose-dependent in the(HMGB1+ASTⅣ+Treg) group.Conclusion ASTⅣcan rivalry the effects of HMGB1 on immune function of Treg in vitro, this result indicate that ASTⅣhas the therapeutic action on inflammation promoted by HMGB1.%目的:观察高迁移率族蛋白B1(HMGB1)刺激的小鼠调节性T细胞(CD4+CD25+Treg)对CD4+CD25-T细胞免疫功能的影响及黄芪甲苷(AST Ⅳ)对HMGB1介

  11. 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

  12. Mast cell mediator tryptase levels after inhalation or intravenous administration of high doses pharmaceutically prepared heroin

    NARCIS (Netherlands)

    E.J. Rook; A.P. van Zanten; W. van den Brink; J.M. van Ree; J.H. Beijnen

    2006-01-01

    Background: Opioids like morphine and heroin induce mast cell degranulation in vitro. The release of mast cell mediators like histamine and tryptase may lead to allergic symptoms. In this study it was investigated whether mast cell mediator release also occurs in vivo in addicted patients who partic

  13. First line of defense: Innate cell-mediated control of pulmonary Aspergillosis

    Directory of Open Access Journals (Sweden)

    Vanessa eEspinosa

    2016-03-01

    Full Text Available Mycotic infections and their effect on the human condition have been widely overlooked and poorly surveilled by many health organizations even though mortality rates have increased in recent years. The increased usage of immunosuppressive and myeloablative therapies for the treatment of malignant as well as non-malignant diseases has contributed significantly to the increased incidence of fungal infections. Invasive fungal infections have been found to be responsible for at least 1.5 million deaths worldwide. About 90% of these deaths can be attributed to Cryptococcus, Candida, Aspergillus, and Pneumocystis. A better understanding of how the host immune system contains fungal infection is likely to facilitate the development of much needed novel antifungal therapies. Innate cells are responsible for the rapid recognition and containment of fungal infections and have been found to play essential roles in defense against multiple fungal pathogens. In this review we summarize our current understanding of host-fungi interactions with a focus on mechanisms of innate cell-mediated recognition and control of pulmonary aspergillosis.

  14. Loss of STAT3 in Lymphoma Relaxes NK Cell-Mediated Tumor Surveillance

    Directory of Open Access Journals (Sweden)

    Eva Maria Putz

    2014-01-01

    Full Text Available The transcription factors and proto-oncogenes STAT3 and STAT5 are highly activated in hematological malignancies and represent promising therapeutic targets. Whereas the importance of STAT5 as tumor promoter is beyond doubt, the role of STAT3 in hematological cancers is less well understood. Both, enforced as well as attenuated expression of STAT3 were reported in hematopoietic malignancies. Recent evidence implicates STAT3 as key player for tumor immune surveillance as it both mediates the production of and response to inflammatory cytokines. Here we investigated the effects of STAT3 deletion in a BCR/ABL-induced lymphoma model, which is tightly controlled by natural killer (NK cells in vivo. Upon STAT3 deletion tumor growth is significantly enhanced when compared to STAT3-expressing controls. The increased tumor size upon loss of STAT3 was accompanied by reduced NK cell infiltration and decreased levels of the cytokine IFN-γ and the chemokine RANTES. Upon transplantation into NK cell-deficient mice differences in lymphoma size were abolished indicating that STAT3 expression in the tumor cells controls NK cell-dependent tumor surveillance. Our findings indicate that STAT3 inhibition in lymphoma patients will impair NK cell-mediated tumor surveillance, which needs to be taken into account when testing STAT3 inhibitors in preclinical or clinical trials.

  15. Loss of STAT3 in Lymphoma Relaxes NK Cell-Mediated Tumor Surveillance

    Energy Technology Data Exchange (ETDEWEB)

    Putz, Eva Maria [Institute of Pharmacology and Toxicology, University of Veterinary Medicine, Veterinaerplatz 1, Vienna 1210 (Austria); Hoelzl, Maria Agnes [Institute of Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna (MUV), Waehringer Strasse 13A, Vienna 1090 (Austria); Baeck, Julia [Institute of Pharmacology and Toxicology, University of Veterinary Medicine, Veterinaerplatz 1, Vienna 1210 (Austria); Bago-Horvath, Zsuzsanna [Institute of Pharmacology and Toxicology, University of Veterinary Medicine, Veterinaerplatz 1, Vienna 1210 (Austria); Clinical Institute of Pathology, Medical University of Vienna (MUV), Waehringer Gürtel 18-20, Vienna 1090 (Austria); Schuster, Christian [Institute of Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna (MUV), Waehringer Strasse 13A, Vienna 1090 (Austria); Reichholf, Brian [Institute of Pharmacology and Toxicology, University of Veterinary Medicine, Veterinaerplatz 1, Vienna 1210 (Austria); Kern, Daniela; Aberger, Fritz [Department of Molecular Biology, University of Salzburg, Hellbrunnerstrasse 34, Salzburg 5020 (Austria); Sexl, Veronika; Hoelbl-Kovacic, Andrea, E-mail: andrea.hoelbl@vetmeduni.ac.at [Institute of Pharmacology and Toxicology, University of Veterinary Medicine, Veterinaerplatz 1, Vienna 1210 (Austria)

    2014-01-27

    The transcription factors and proto-oncogenes STAT3 and STAT5 are highly activated in hematological malignancies and represent promising therapeutic targets. Whereas the importance of STAT5 as tumor promoter is beyond doubt, the role of STAT3 in hematological cancers is less well understood. Both, enforced as well as attenuated expression of STAT3 were reported in hematopoietic malignancies. Recent evidence implicates STAT3 as key player for tumor immune surveillance as it both mediates the production of and response to inflammatory cytokines. Here we investigated the effects of STAT3 deletion in a BCR/ABL-induced lymphoma model, which is tightly controlled by natural killer (NK) cells in vivo. Upon STAT3 deletion tumor growth is significantly enhanced when compared to STAT3-expressing controls. The increased tumor size upon loss of STAT3 was accompanied by reduced NK cell infiltration and decreased levels of the cytokine IFN-γ and the chemokine RANTES. Upon transplantation into NK cell-deficient mice differences in lymphoma size were abolished indicating that STAT3 expression in the tumor cells controls NK cell-dependent tumor surveillance. Our findings indicate that STAT3 inhibition in lymphoma patients will impair NK cell-mediated tumor surveillance, which needs to be taken into account when testing STAT3 inhibitors in preclinical or clinical trials.

  16. Endogenous n-3 Polyunsaturated Fatty Acids Attenuate T Cell-Mediated Hepatitis via Autophagy Activation

    Science.gov (United States)

    Li, Yanli; Tang, Yuan; Wang, Shoujie; Zhou, Jing; Zhou, Jia; Lu, Xiao; Bai, Xiaochun; Wang, Xiang-Yang; Chen, Zhengliang; Zuo, Daming

    2016-01-01

    Omega-3 polyunsaturated fatty acids (n-3 PUFAs) exert anti-inflammatory effects in several liver disorders, including cirrhosis, acute liver failure, and fatty liver disease. To date, little is known about their role in immune-mediated liver diseases. In this study, we used fat-1 transgenic mice rich in endogenous n-3 PUFAs to examine the role of n-3 PUFAs in immune-mediated liver injury. Concanavalin A (Con A) was administered intravenously to wild-type (WT) and fat-1 transgenic mice to induce T cell-mediated hepatitis. Reduced liver damage was shown in Con A-administrated fat-1 transgenic mice, as evidenced by decreased mortality, attenuated hepatic necrosis, lessened serum alanine aminotransferase activity, and inhibited production of pro-inflammatory cytokines (e.g., TNF-α, IL-6, IL-17A, and IFN-γ). In vivo and in vitro studies demonstrated that n-3 PUFAs significantly inhibited the activation of hepatic T cells and the differentiation of Th1 cells after Con A challenge. Further studies showed that n-3 PUFAs markedly increased autophagy level in Con A-treated fat-1 T cells compared with the WT counterparts. Blocking hepatic autophagy activity with chloroquine diminished the differences in T cell activation and liver injury between Con A-injected WT and fat-1 transgenic mice. We conclude that n-3 PUFAs limit Con A-induced hepatitis via an autophagy-dependent mechanism and could be exploited as a new therapeutic approach for autoimmune hepatitis. PMID:27679638

  17. Lung Regeneration: Endogenous and Exogenous Stem Cell Mediated Therapeutic Approaches

    Directory of Open Access Journals (Sweden)

    Khondoker M. Akram

    2016-01-01

    Full Text Available The tissue turnover of unperturbed adult lung is remarkably slow. However, after injury or insult, a specialised group of facultative lung progenitors become activated to replenish damaged tissue through a reparative process called regeneration. Disruption in this process results in healing by fibrosis causing aberrant lung remodelling and organ dysfunction. Post-insult failure of regeneration leads to various incurable lung diseases including chronic obstructive pulmonary disease (COPD and idiopathic pulmonary fibrosis. Therefore, identification of true endogenous lung progenitors/stem cells, and their regenerative pathway are crucial for next-generation therapeutic development. Recent studies provide exciting and novel insights into postnatal lung development and post-injury lung regeneration by native lung progenitors. Furthermore, exogenous application of bone marrow stem cells, embryonic stem cells and inducible pluripotent stem cells (iPSC show evidences of their regenerative capacity in the repair of injured and diseased lungs. With the advent of modern tissue engineering techniques, whole lung regeneration in the lab using de-cellularised tissue scaffold and stem cells is now becoming reality. In this review, we will highlight the advancement of our understanding in lung regeneration and development of stem cell mediated therapeutic strategies in combating incurable lung diseases.

  18. 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

    Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown...... that 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 greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture...

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

    Science.gov (United States)

    Sawcer, Stephen; Hellenthal, Garrett; Pirinen, Matti; Spencer, Chris C.A.; Patsopoulos, Nikolaos A.; Moutsianas, Loukas; Dilthey, Alexander; Su, Zhan; Freeman, Colin; Hunt, Sarah E.; Edkins, Sarah; Gray, Emma; Booth, David R.; Potter, Simon C.; Goris, An; Band, Gavin; Oturai, Annette Bang; Strange, Amy; Saarela, Janna; Bellenguez, Céline; Fontaine, Bertrand; Gillman, Matthew; Hemmer, Bernhard; Gwilliam, Rhian; Zipp, Frauke; Jayakumar, Alagurevathi; Martin, Roland; Leslie, Stephen; Hawkins, Stanley; Giannoulatou, Eleni; D’alfonso, Sandra; Blackburn, Hannah; Boneschi, Filippo Martinelli; Liddle, Jennifer; Harbo, Hanne F.; Perez, Marc L.; Spurkland, Anne; Waller, Matthew J; Mycko, Marcin P.; Ricketts, Michelle; Comabella, Manuel; Hammond, Naomi; Kockum, Ingrid; McCann, Owen T.; Ban, Maria; Whittaker, Pamela; Kemppinen, Anu; Weston, Paul; Hawkins, Clive; Widaa, Sara; Zajicek, John; Dronov, Serge; Robertson, Neil; Bumpstead, Suzannah J.; Barcellos, Lisa F.; Ravindrarajah, Rathi; Abraham, Roby; Alfredsson, Lars; Ardlie, Kristin; Aubin, Cristin; Baker, Amie; Baker, Katharine; Baranzini, Sergio E.; Bergamaschi, Laura; Bergamaschi, Roberto; Bernstein, Allan; Berthele, Achim; Boggild, Mike; Bradfield, Jonathan P.; Brassat, David; Broadley, Simon A.; Buck, Dorothea; Butzkueven, Helmut; Capra, Ruggero; Carroll, William M.; Cavalla, Paola; Celius, Elisabeth G.; Cepok, Sabine; Chiavacci, Rosetta; Clerget-Darpoux, Françoise; Clysters, Katleen; Comi, Giancarlo; Cossburn, Mark; Cournu-Rebeix, Isabelle; Cox, Mathew B.; Cozen, Wendy; Cree, Bruce A.C.; Cross, Anne H.; Cusi, Daniele; Daly, Mark J.; Davis, Emma; de Bakker, Paul I.W.; Debouverie, Marc; D’hooghe, Marie Beatrice; Dixon, Katherine; Dobosi, Rita; Dubois, Bénédicte; Ellinghaus, David; Elovaara, Irina; Esposito, Federica; Fontenille, Claire; Foote, Simon; Franke, Andre; Galimberti, Daniela; Ghezzi, Angelo; Glessner, Joseph; Gomez, Refujia; Gout, Olivier; Graham, Colin; Grant, Struan F.A.; Guerini, Franca Rosa; Hakonarson, Hakon; Hall, Per; Hamsten, Anders; Hartung, Hans-Peter; Heard, Rob N.; Heath, Simon; Hobart, Jeremy; Hoshi, Muna; Infante-Duarte, Carmen; Ingram, Gillian; Ingram, Wendy; Islam, Talat; Jagodic, Maja; Kabesch, Michael; Kermode, Allan G.; Kilpatrick, Trevor J.; Kim, Cecilia; Klopp, Norman; Koivisto, Keijo; Larsson, Malin; Lathrop, Mark; Lechner-Scott, Jeannette S.; Leone, Maurizio A.; Leppä, Virpi; Liljedahl, Ulrika; Bomfim, Izaura Lima; Lincoln, Robin R.; Link, Jenny; Liu, Jianjun; Lorentzen, Åslaug R.; Lupoli, Sara; Macciardi, Fabio; Mack, Thomas; Marriott, Mark; Martinelli, Vittorio; Mason, Deborah; McCauley, Jacob L.; Mentch, Frank; Mero, Inger-Lise; Mihalova, Tania; Montalban, Xavier; Mottershead, John; Myhr, Kjell-Morten; Naldi, Paola; Ollier, William; Page, Alison; Palotie, Aarno; Pelletier, Jean; Piccio, Laura; Pickersgill, Trevor; Piehl, Fredrik; Pobywajlo, Susan; Quach, Hong L.; Ramsay, Patricia P.; Reunanen, Mauri; Reynolds, Richard; Rioux, John D.; Rodegher, Mariaemma; Roesner, Sabine; Rubio, Justin P.; Rückert, Ina-Maria; Salvetti, Marco; Salvi, Erika; Santaniello, Adam; Schaefer, Catherine A.; Schreiber, Stefan; Schulze, Christian; Scott, Rodney J.; Sellebjerg, Finn; Selmaj, Krzysztof W.; Sexton, David; Shen, Ling; Simms-Acuna, Brigid; Skidmore, Sheila; Sleiman, Patrick M.A.; Smestad, Cathrine; Sørensen, Per Soelberg; Søndergaard, Helle Bach; Stankovich, Jim; Strange, Richard C.; Sulonen, Anna-Maija; Sundqvist, Emilie; Syvänen, Ann-Christine; Taddeo, Francesca; Taylor, Bruce; Blackwell, Jenefer M.; Tienari, Pentti; Bramon, Elvira; Tourbah, Ayman; Brown, Matthew A.; Tronczynska, Ewa; Casas, Juan P.; Tubridy, Niall; Corvin, Aiden; Vickery, Jane; Jankowski, Janusz; Villoslada, Pablo; Markus, Hugh S.; Wang, Kai; Mathew, Christopher G.; Wason, James; Palmer, Colin N.A.; Wichmann, H-Erich; Plomin, Robert; Willoughby, Ernest; Rautanen, Anna; Winkelmann, Juliane; Wittig, Michael; Trembath, Richard C.; Yaouanq, Jacqueline; Viswanathan, Ananth C.; Zhang, Haitao; Wood, Nicholas W.; Zuvich, Rebecca; Deloukas, Panos; Langford, Cordelia; Duncanson, Audrey; Oksenberg, Jorge R.; Pericak-Vance, Margaret A.; Haines, Jonathan L.; Olsson, Tomas; Hillert, Jan; Ivinson, Adrian J.; De Jager, Philip L.; Peltonen, Leena; Stewart, Graeme J.; Hafler, David A.; Hauser, Stephen L.; McVean, Gil; Donnelly, Peter; Compston, Alastair

    2011-01-01

    Multiple sclerosis (OMIM 126200) is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability.1 Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals;2,3 and systematic attempts to identify linkage in multiplex families have confirmed that variation within the Major Histocompatibility Complex (MHC) exerts the greatest individual effect on risk.4 Modestly powered Genome-Wide Association Studies (GWAS)5-10 have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects play a key role in disease susceptibility.11 Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9772 cases of European descent collected by 23 research groups working in 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 DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the Class I region. Immunologically relevant genes are significantly over-represented amongst those mapping close to the identified loci and particularly implicate T helper cell differentiation in the pathogenesis of multiple sclerosis. PMID:21833088

  20. 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.

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

    OpenAIRE

    Sedigheh Bahrami Mahne; Seyed Alireza Mahdaviani; Nima Rezaei

    2014-01-01

    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 t...

  2. 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

  3. 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.

  4. 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.

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

    OpenAIRE

    Sawcer, Stephen; Hellenthal, Garrett; Pirinen, Matti; Spencer, Chris C A; Patsopoulos, Nikolaos A; Moutsianas, Loukas; Dilthey, Alexander; Su, Zhan; Freeman, Colin; Hunt, Sarah E.; Edkins, Sarah; Gray, Emma; Booth, David R; Potter, Simon C.; Goris, An

    2011-01-01

    Multiple sclerosis (OMIM 126200) is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. 1 Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals; 2,3 and systematic attempts to identify...

  6. Altered cell-mediated immunity to group A haemolytic streptococcal antigens in chronic plaque psoriasis.

    Science.gov (United States)

    Baker, B S; Powles, A V; Malkani, A K; Lewis, H; Valdimarsson, H; Fry, L

    1991-07-01

    The proliferative lymphocyte response to sonicated group A, beta-haemolytic streptococci (Strep-A) was measured by thymidine incorporation in 78 patients with psoriasis (guttate, chronic plaque or both). Lymphocytes from 72 of these patients were also cultured with streptokinase/streptodornase (SK/SD), and 20 of the patients with chronic plaque psoriasis were further tested with PPD, Candida albicans and sonicated Streptococcus mutans, a bacterial type not associated clinically with psoriasis. The median stimulation index (SI) of the psoriasis group to the Strep-A preparation was significantly higher than that of a group of 27 non-psoriatic individuals (P less than 0.05). Within this group, only the patients with chronic plaque psoriasis (n = 42) showed a significantly increased proliferative response compared to the non-psoriatic controls (median SI = 123.8 and 31.9, respectively, P less than 0.01). Although the lymphocyte response of the chronic plaque group to SK/SD was also markedly higher than that of the control group, this difference did not reach statistical significance. In addition, these patients did not show significantly increased responses to any of the other antigens tested, including S. mutans. No correlation was observed between the degree of proliferation to Strep-A and disease extent or activity. Similarly, ASO titres, which were raised in 11 out of 23 guttate and three out of nine chronic plaque psoriasis patients tested, did not correlate with the proliferative responses observed.

  7. 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

    Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that g...

  8. The role of cytokines and chemokines in the T-cell-mediated autoimmune process in alopecia areata.

    Science.gov (United States)

    Ito, Taisuke; Tokura, Yoshiki

    2014-11-01

    The aetiology of alopecia areata (AA) is still not fully understood. However, recent clinical and experimental studies have provided insights into the pathomechanisms of AA and revealed that it is an organ-specific and cell-mediated autoimmune disease. Some triggers, such as viral infections, trauma, hormones and emotional/physical stressors, may cause activation of autoreactive T cells that target hair follicle (HF) autoantigens. In these immunological responses, cytokines and chemokines are regarded as key players that mediate the autoimmune inflammation. This results in the collapse of HF immune privilege, which is central to the pathogenesis of AA. This essay will focus on how cytokines and chemokines contribute to the immunological aspects of AA. The management of AA often remains difficult in a number of cases. Our review suggests that novel therapies for AA may involve targeting cytokines and chemokines. PMID:25040075

  9. The role of cytokines and chemokines in the T-cell-mediated autoimmune process in alopecia areata.

    Science.gov (United States)

    Ito, Taisuke; Tokura, Yoshiki

    2014-11-01

    The aetiology of alopecia areata (AA) is still not fully understood. However, recent clinical and experimental studies have provided insights into the pathomechanisms of AA and revealed that it is an organ-specific and cell-mediated autoimmune disease. Some triggers, such as viral infections, trauma, hormones and emotional/physical stressors, may cause activation of autoreactive T cells that target hair follicle (HF) autoantigens. In these immunological responses, cytokines and chemokines are regarded as key players that mediate the autoimmune inflammation. This results in the collapse of HF immune privilege, which is central to the pathogenesis of AA. This essay will focus on how cytokines and chemokines contribute to the immunological aspects of AA. The management of AA often remains difficult in a number of cases. Our review suggests that novel therapies for AA may involve targeting cytokines and chemokines.

  10. 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

  11. 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...

  12. Community Immunity (Herd Immunity)

    Science.gov (United States)

    ... Read more information on enabling JavaScript. Skip Content Marketing Share this: Main Content Area ​Community Immunity ("Herd" ... population is immunized, protecting most community members. The principle of community immunity applies to control of a ...

  13. 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 ...

  14. Effector cell mediated cytotoxicity measured by intracellular Granzyme B release in HIV infected subjects

    Directory of Open Access Journals (Sweden)

    Mahajan Supriya D.

    2003-01-01

    Full Text Available CD8+ cytotoxic T lymphocyte (CTL activity is currently believed to be one of the key immunologic mechanisms responsible for the prevention or attenuation of HIV-1 infection. The induction of CD8+ T cell activation may also result in the production of soluble or non-classical lytic factors that are associated with protection from infection or slower disease progression. Traditionally, CD8+ CTL responses have been measured by the classic chromium release assay, monitoring the ability of T cells (Effector cells to lyse radiolabelled HLA – matched “target cells” that express the appropriate antigen-MHC complex. This method is not only labor intensive, semi quantitative assay at best, but also needs fresh, non-cryopreserved cells. Recently, cytokine specific ELISPOT assays or tetrameric MHC-I/ peptide complexes have utilized to directly quantitate circulating CD8+ effector cells, and these assays are more sensitive, quantitative and reproducible than the traditional CTL lysis assay and can also be performed on cryopreserved cells. Although these are reproducible assays for the assessment of soluble antiviral activity secreted by activated T cell populations they can be extremely expensive to perform. We have used FACS Analysis to measure Granzyme B release as a function of cell mediated cytotoxicity. This method helps quantitate the CTL activity and also identifies the phenotype of the cells elucidating this immune response. The method described not only monitors immunological response but also is also simple to perform, precise and extremely time efficient and is ideal for screening a large number of samples.

  15. Immunity to Fish Rhabdoviruses

    Directory of Open Access Journals (Sweden)

    Maureen K. Purcell

    2012-01-01

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

  16. Antibody-Dependent Cell-Mediated Cytotoxicity to Hemagglutinin of Influenza A Viruses After Influenza Vaccination in Humans

    Science.gov (United States)

    Zhong, Weimin; Liu, Feng; Wilson, Jason R.; Holiday, Crystal; Li, Zhu-Nan; Bai, Yaohui; Tzeng, Wen-Pin; Stevens, James; York, Ian A.; Levine, Min Z.

    2016-01-01

    Background. Detection of neutralizing antibodies (nAbs) to influenza A virus hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However, current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred. Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection. Methods. Virus neutralization and ADCC activities of serum samples from individuals who received either seasonal or a stock-piled H5N1 avian influenza vaccine were evaluated by hemagglutination inhibition assay, microneutralization assay, and an improved ADCC natural killer (NK) cell activation assay. Results. Immunization with inactivated seasonal influenza vaccine led to strong expansion of both nAbs and ADCC-mediating antibodies (adccAbs) to H3 antigen of the vaccine virus in 24 postvaccination human sera. In sharp contrast, 18 individuals vaccinated with the adjuvanted H5N1 avian influenza vaccine mounted H5-specific antibodies with strong ADCC activities despite moderate virus neutralization capacity. Strength of HA-specific ADCC activities is largely associated with the titers of HA-binding antibodies and not with the fine antigenic specificity of anti-HA nAbs. Conclusions. Detection of both nAbs and adccAbs may better reflect protective capacity of HA-specific antibodies induced by avian influenza vaccines.

  17. 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.

  18. Towards Future T Cell-Mediated Influenza Vaccines

    Directory of Open Access Journals (Sweden)

    Thi H. O. Nguyen

    2016-04-01

    Full Text Available Influenza A virus (IAVs infections impact significantly on global health, being particularly problematic in children, the elderly, pregnant women, indigenous populations and people with co-morbidities. Antibody-based vaccines require annual administration to combat rapidly acquired mutations modifying the surface haemagglutinin (HA and neuraminidase (NA glycoproteins. Conversely, influenza-specific CD8+ T cell responses directed at peptides derived from the more conserved internal virus proteins are known to be protective, suggesting that T cell-based vaccines may provide long-lasting cross-protection. This review outlines the importance of CD8+ T cell immunity to seasonal influenza and pandemic IAVs and summarises current vaccination strategies for inducing durable CD8+ T cell memory. Aspects of future IAV vaccine design and the use of live virus challenge in humans to establish proof of principle are also discussed.

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

    Science.gov (United States)

    Meissonnier, Guylaine M; Pinton, Philippe; Laffitte, Joëlle; Cossalter, Anne-Marie; Gong, Yun Yun; Wild, Christopher P; Bertin, Gérard; Galtier, Pierre; Oswald, Isabelle P

    2008-09-01

    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 microg 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-alpha, IL-1beta, IL-6, IFN-gamma) 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-gamma 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.

  20. 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

  1. 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....

  2. Effect of plasmapheresis on the immune system in endotoxin-induced sepsis

    DEFF Research Database (Denmark)

    Toft, P; Schmidt, R; Broechner, A C;

    2008-01-01

    BACKGROUND: It has been proposed that plasmapheresis is most effective when applied early in Gram-negative sepsis. We therefore studied the effect of early plasmapheresis on immunity in experimental Escherichia coli endotoxin-induced sepsis. METHODS: 20 pigs received 30 microg/kg of E. coli...... infusion, it only temporarily attenuated a part of the activated cell-mediated immunity....

  3. CD4+ T cell-mediated presentation of non-infectious HIV-1virion antigens to HIV-specific CD8+ T cells

    Institute of Scientific and Technical Information of China (English)

    XU Jian-qing; Franco Lori; Julianna Lisziewicz

    2006-01-01

    Background The mechanism of chronic immune activation and impairment of HIV-specific immune responses during chronic infection is not fully understood. However, it is known that high immune activation leads to more rapid progression to AIDS. We hypothesize that CD4+ T cell-mediated viral antigen presentation contributes to this pathologic immune activation in HIV-infected individuals.Methods HIV-specific T cells, responding to noninfectious HIV-1 virions as antigen, were measured by flow cytometric assays. These experimental conditions reflect the in vivo condition where noninfectious HIV-1 represents more than 99% of the antigens.Results CD4+ T cells purified from HIV-infected individuals were capable of cross presenting exogenous noninfectious HIV-1 virions to HIV-1-specific CD8+ T cells. Cross presentation required the entry of HIV-1 to CD4+ T cells and antigen translocation from endoplasmic reticulum to the Golgi complex. Blocking CD4+mediated activation of HIV-specific CD8+ T cells and redirecting the viral antigens to antigen presenting cells improved HIV-specific T cell responses.Conclusions One possible cause of chronic immune activation and impairment of HIV-1 specific T cell responses is represented by HIV-1 harboring CD4+ T cells cross presenting HIV-1 antigen to activate CD8+ T cells. This new mechanism provides the first evidence that cross presentation of noninfectious HIV-1. Virions play a role in the immunopathogenesis of HIV-1 infection.

  4. Cell mediated therapeutics for cancer treatment: Tumor homing cells as therapeutic delivery vehicles

    Science.gov (United States)

    Balivada, Sivasai

    Many cell types were known to have migratory properties towards tumors and different research groups have shown reliable results regarding cells as delivery vehicles of therapeutics for targeted cancer treatment. Present report discusses proof of concept for 1. Cell mediated delivery of Magnetic nanoparticles (MNPs) and targeted Magnetic hyperthermia (MHT) as a cancer treatment by using in vivo mouse cancer models, 2. Cells surface engineering with chimeric proteins for targeted cancer treatment by using in vitro models. 1. Tumor homing cells can carry MNPs specifically to the tumor site and tumor burden will decrease after alternating magnetic field (AMF) exposure. To test this hypothesis, first we loaded Fe/Fe3O4 bi-magnetic NPs into neural progenitor cells (NPCs), which were previously shown to migrate towards melanoma tumors. We observed that NPCs loaded with MNPs travel to subcutaneous melanoma tumors. After alternating magnetic field (AMF) exposure, the targeted delivery of MNPs by the NPCs resulted in a mild decrease in tumor size (Chapter-2). Monocytes/macrophages (Mo/Ma) are known to infiltrate tumor sites, and also have phagocytic activity which can increase their uptake of MNPs. To test Mo/Ma-mediated MHT we transplanted Mo/Ma loaded with MNPs into a mouse model of pancreatic peritoneal carcinomatosis. We observed that MNP-loaded Mo/Ma infiltrated pancreatic tumors and, after AMF treatment, significantly prolonged the lives of mice bearing disseminated intraperitoneal pancreatic tumors (Chapter-3). 2. Targeted cancer treatment could be achieved by engineering tumor homing cell surfaces with tumor proteases cleavable, cancer cell specific recombinant therapeutic proteins. To test this, Urokinase and Calpain (tumor specific proteases) cleavable; prostate cancer cell (CaP) specific (CaP1 targeting peptide); apoptosis inducible (Caspase3 V266ED3)- rCasp3V266ED3 chimeric protein was designed in silico. Hypothesized membrane anchored chimeric protein (rCasp3V

  5. Insect immune resistance to parasitoids

    Institute of Scientific and Technical Information of China (English)

    Yves Carton; Marylène Poirié; Anthony J. Nappi

    2008-01-01

    Insect host-parasitoid interactions involve complex physiological, biochemical and genetic interactions. Against endoparasitoids, immune-competent hosts initiate a blood cell-mediated response that quickly destroys the intruders and envelops them in a multilayered melanotic capsule. During the past decade, considerable progress has been made in identifying some of the critical components of the host response, mainly because of the use of efficient molecular tools. This review examines some of the components of the innate immune response of Drosophila, an insect that has served as an exceptionally good experimental model for studying non-self recognition processes and immune cell signaling mechanisms. Topics considered in this review include hematopoiesis, proliferation and adhesion of hemocytes, melanogenesis and associated cytotoxic molecules, and the genetic aspects of the host-parasitoid interaction.

  6. Psychoneuroimmunology in pregnancy: immune pathways linking stress with maternal health, adverse birth outcomes, and fetal development.

    Science.gov (United States)

    Christian, Lisa M

    2012-01-01

    It is well-established that psychological stress promotes immune dysregulation in nonpregnant humans and animals. Stress promotes inflammation, impairs antibody responses to vaccination, slows wound healing, and suppresses cell-mediated immune function. Importantly, the immune system changes substantially to support healthy pregnancy, with attenuation of inflammatory responses and impairment of cell-mediated immunity. This adaptation is postulated to protect the fetus from rejection by the maternal immune system. Thus, stress-induced immune dysregulation during pregnancy has unique implications for both maternal and fetal health, particularly preterm birth. However, very limited research has examined stress-immune relationships in pregnancy. The application of psychoneuroimmunology research models to the perinatal period holds great promise for elucidating biological pathways by which stress may affect adverse pregnancy outcomes, maternal health, and fetal development.

  7. A Possible Role for CD8+ T Lymphocytes in the Cell-Mediated Pathogenesis of Pemphigus Vulgaris

    Directory of Open Access Journals (Sweden)

    Federica Giurdanella

    2013-01-01

    Full Text Available Pemphigus vulgaris (PV is an autoimmune blistering disease whose pathogenesis involves both humoral and cell-mediated immune response. Though the pathogenetic role of autoantibodies directed against desmoglein 3 is certain, a number of other factors have been suggested to determine acantholysis in PV. In this study we examined the possible role of CD8+ T cells in the development of acantholysis by a passive transfer of PV autoantibodies using CD8 deficient mice, and we also studied the inflammatory infiltrate of PV skin lesions by immunohistochemical staining. The results of the immunohistochemical staining to study the expression of CD3, CD4, and CD8 in PV skin lesions showed that CD4+ are more expressed than CD8+ in the inflammatory infiltrate of PV lesions, confirming the data of the previous literature. The passive transfer study showed a lower incidence of pemphigus in the group of CD8 deficient mice compared to the control one of wild-type mice. These results suggest that CD8+ T cells may play a role in the pathogenesis of PV, perhaps through the Fas/FasL pathway.

  8. The role of CC chemokine receptor 5 in antiviral immunity

    DEFF Research Database (Denmark)

    Nansen, Anneline; Christensen, Jan Pravsgaard; Andreasen, Susanne Ørding;

    2002-01-01

    that the virus-induced clonal expansion of antigen-specific T cells was augmented in CCR5(-/-) mice especially with regard to the CD4(+) subset. Despite absence of CCR5, intracerebral infection invariably resulted in lethal T cell-mediated meningitis, and quantitative and qualitative analysis of the inflammatory...... influence of CCR5 was found, not even when viral peptide was used as local trigger instead of live virus. Finally, long-term CD8(+) T cell-mediated immune surveillance was efficiently sustained in CCR5(-/-) mice. Taken together, these results indicate that expression of CCR5 is not critical for T cell...

  9. Oxaliplatin regulates expression of stress ligands in ovarian cancer cells and modulates their susceptibility to natural killer cell-mediated cytotoxicity.

    Science.gov (United States)

    Siew, Yin-Yin; Neo, Soek-Ying; Yew, Hui-Chuing; Lim, Shun-Wei; Ng, Yi-Cheng; Lew, Si-Min; Seetoh, Wei-Guang; Seow, See-Voon; Koh, Hwee-Ling

    2015-12-01

    Selected cytotoxic chemicals can provoke the immune system to recognize and destroy malignant tumors. Most of the studies on immunogenic cell death are focused on the signals that operate on a series of receptors expressed by dendritic cells to induce tumor antigen-specific T-cell responses. Here, we explored the effects of oxaliplatin, an immunogenic cell death inducer, on the induction of stress ligands and promotion of natural killer (NK) cell-mediated cytotoxicity in human ovarian cancer cells. The results indicated that treatment of tumor cells with oxaliplatin induced the production of type I interferons and chemokines and enhanced the expression of major histocompatibility complex class I-related chains (MIC) A/B, UL16-binding protein (ULBP)-3, CD155 and TNF-related apoptosis-inducing ligand (TRAIL)-R1/R2. Furthermore, oxaliplatin but not cisplatin treatment enhanced susceptibility of ovarian cancer cells to NK cell-mediated cytolysis. In addition, activated NK cells completely abrogated the growth of cancer cells that were pretreated with oxaliplatin. However, cancer cells pretreated with the same concentration of oxaliplatin alone were capable of potentiating regrowth over a period of time. These results suggest an advantage in combining oxaliplatin and NK cell-based therapy in the treatment of ovarian cancer. Further investigation on such potential combination therapy is warranted.

  10. Antibody-Dependent Cell-Mediated Cytotoxicity to Hemagglutinin of Influenza A Viruses After Influenza Vaccination in Humans.

    Science.gov (United States)

    Zhong, Weimin; Liu, Feng; Wilson, Jason R; Holiday, Crystal; Li, Zhu-Nan; Bai, Yaohui; Tzeng, Wen-Pin; Stevens, James; York, Ian A; Levine, Min Z

    2016-04-01

    Background.  Detection of neutralizing antibodies (nAbs) to influenza A virus hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However, current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred. Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection. Methods.  Virus neutralization and ADCC activities of serum samples from individuals who received either seasonal or a stock-piled H5N1 avian influenza vaccine were evaluated by hemagglutination inhibition assay, microneutralization assay, and an improved ADCC natural killer (NK) cell activation assay. Results.  Immunization with inactivated seasonal influenza vaccine led to strong expansion of both nAbs and ADCC-mediating antibodies (adccAbs) to H3 antigen of the vaccine virus in 24 postvaccination human sera. In sharp contrast, 18 individuals vaccinated with the adjuvanted H5N1 avian influenza vaccine mounted H5-specific antibodies with strong ADCC activities despite moderate virus neutralization capacity. Strength of HA-specific ADCC activities is largely associated with the titers of HA-binding antibodies and not with the fine antigenic specificity of anti-HA nAbs. Conclusions.  Detection of both nAbs and adccAbs may better reflect protective capacity of HA-specific antibodies induced by avian influenza vaccines. PMID:27419174

  11. Immune System

    Science.gov (United States)

    ... Can I Help a Friend Who Cuts? Immune System KidsHealth > For Teens > Immune System Print A A ... put us out of commission. What the Immune System Does The immune (pronounced: ih-MYOON) system, which ...

  12. Immune response to fungal infections.

    Science.gov (United States)

    Blanco, Jose L; Garcia, Marta E

    2008-09-15

    The immune mechanisms of defence against fungal infections are numerous, and range from protective mechanisms that were present early in evolution (innate immunity) to sophisticated adaptive mechanisms that are induced specifically during infection and disease (adaptive immunity). The first-line innate mechanism is the presence of physical barriers in the form of skin and mucous membranes, which is complemented by cell membranes, cellular receptors and humoral factors. There has been a debate about the relative contribution of humoral and cellular immunity to host defence against fungal infections. For a long time it was considered that cell-mediated immunity (CMI) was important, but humoral immunity had little or no role. However, it is accepted now that CMI is the main mechanism of defence, but that certain types of antibody response are protective. In general, Th1-type CMI is required for clearance of a fungal infection, while Th2 immunity usually results in susceptibility to infection. Aspergillosis, which is a disease caused by the fungus Aspergillus, has been the subject of many studies, including details of the immune response. Attempts to relate aspergillosis to some form of immunosuppression in animals, as is the case with humans, have not been successful to date. The defence against Aspergillus is based on recognition of the pathogen, a rapidly deployed and highly effective innate effector phase, and a delayed but robust adaptive effector phase. Candida albicans, part of the normal microbial flora associated with mucous surfaces, can be present as congenital candidiasis or as acquired defects of cell-mediated immunity. Resistance to this yeast is associated with Th1 CMI, whereas Th2 immunity is associated with susceptibility to systemic infection. Dermatophytes produce skin alterations in humans and other animals, and the essential role of the CMI response is to destroy the fungi and produce an immunoprotective status against re-infection. The resolution

  13. Vaccines and immunization against human papillomavirus.

    Science.gov (United States)

    Christensen, Neil D; Budgeon, Lynn R

    2014-01-01

    Prophylactic and therapeutic immunization strategies are an effective method to control human papillomavirus (HPV)-associated diseases and cancers. Current protective virus-like particle and capsid-based vaccines are highly protective against vaccine-matched HPV types, and continued improvements in second-generation vaccines will lead to broader protection and cross-protection against the cancer-associated types. Increasing the effectiveness of broadly cross-protective L2-based immunogens will require adjuvants that activate innate immunity to thus enhance adaptive immunity. Therapeutic immunization strategies are needed to control and cure clinical disease and HPV-associated cancers. Significant advances in strategies to improve induction of cell-mediated immunity to HPV early (and capsid) proteins have been pretested in preclinical animal papillomavirus models. Several of these effective protocols have translated into successful therapeutic immune-mediated clearance of clinical lesions. Nevertheless, there are significant challenges in activating immunity to cancer-associated lesions due to various immune downregulatory events that are triggered by persistent HPV infections. A better understanding of immune responses to HPV lesions in situ is needed to optimize immune effector T cells that efficiently locate to sites of infection and which should lead to an effective immunotherapeutic management of this important human viral pathogen. The most effective immunization strategy may well require combination antiviral and immunotherapeutic treatments to achieve complete clearance of HPV infections and associated cancers. PMID:24643192

  14. 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

  15. CD4+ type II NKT cells mediate ICOS and programmed death-1-dependent regulation of type 1 diabetes

    DEFF Research Database (Denmark)

    Kadri, Nadir; Korpos, Eva; Gupta, Shashank;

    2012-01-01

    Type 1 diabetes (T1D) is a chronic autoimmune disease that results from T cell-mediated destruction of pancreatic ß cells. CD1d-restricted NKT lymphocytes have the ability to regulate immunity, including autoimmunity. We previously demonstrated that CD1d-restricted type II NKT cells, which carry...... diverse TCRs, prevented T1D in the NOD mouse model for the human disease. In this study, we show that CD4(+) 24aß type II NKT cells, but not CD4/CD8 double-negative NKT cells, were sufficient to downregulate diabetogenic CD4(+) BDC2.5 NOD T cells in adoptive transfer experiments. CD4(+) 24aß NKT cells...... in the pancreas draining lymph nodes. To our knowledge, these results provide for the first time cellular and molecular information on how type II CD1d-restricted NKT cells regulate T1D....

  16. Angiogenesis in patients with psoriasis and psoriatic arthritis: cell-mediated and humoral mechanisms, its role in pathogenesis, and searching for promising therapeutic targets

    Directory of Open Access Journals (Sweden)

    T.V. Korotaeva

    2014-01-01

    Full Text Available Modern concepts of the role of angiogenesis in pathogenesis of psoriasis and psoriatic arthritis (PsA are analyzed. The features of cell-mediated and humoral immune responses resulting in proliferation of synovial membrane and vessel overgrowth in patients with this pathology are discussed. A number of angiogenesis mediators, pro-angiogenic cytokines, growth factors, matrix metalloproteinases, etc. are shown to be involved in progression of neovascularization. The role of tumor necrosis factor α as a key therapeutic target for treatment of psoriasis and PsA is emphasized. Drugs inhibiting some stages of angiogenesis, which are either used in clinical practice or are being developed, are discussed. 

  17. Hope-Simpsons Progressive Immunity Hypothesis as a Possible Explanation for Herpes Zoster Incidence Data

    OpenAIRE

    Guzzetta, Giorgio; Poletti, Piero; del Fava, Emanuele; Ajelli, Marco; Tomba, Gian Paolo Scalia; Merler, Stefano; Manfredi, Piero

    2013-01-01

    Varicella-zoster virus (VZV) is the causative agent of both varicella (chickenpox) and herpes zoster (HZ) (shingles). After varicella infection, the virus remains dormant in the hosts dorsal ganglia and can reactivate due to waning cell-mediated immunity, causing HZ. Exposure of varicella-immune persons to VZV may boost the hosts immune response, resulting in a protective effect against HZ. In this study, we used mathematical models of VZV transmission and HZ development to test the biologica...

  18. 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.

  19. Effect of disodium cromoglycate on mast cell-mediated immediate-type allergic reactions.

    Science.gov (United States)

    Shin, Hye-Young; Kim, Jung-Sook; An, Nyeon-Hyoung; Park, Rae-Kil; Kim, Hyung-Min

    2004-04-23

    We investigated the effect of disodium cromoglycate (DSCG) on mast cell-mediated immediate-type hypersensitivity. DSCG inhibited systemic allergic reaction induced by compound 48/80 dose-dependently. Passive cutaneous anaphylaxis was inhibited by 71.6% by oral administration of DSCG (1 g/kg). When DSCG was pretreated at concentration rang from 0.01-1000 g/kg, the serum histamine levels were reduced in a dose dependent manner. DSCG also significantly inhibited histamine release from rat peritoneal mast cell (RPMC) by compound 48/80. We confirmed that DSCG inhibited compound 48/80-induced degranulation of RPMC by alcian blue/nuclear fast red staining. In addition, DSCG showed a significant inhibitory effect on anti-dinitrophenyl IgE-mediated tumor necrosis factor-alpha production. These results indicate that DSCG inhibits mast cell-mediated immediate-type allergic reaction. PMID:15050425

  20. Mannose 6-, fructose 1-, and fructose 6-phosphates inhibit human natural cell-mediated cytotoxicity.

    OpenAIRE

    Forbes, J T; Bretthauer, R. K.; Oeltmann, T N

    1981-01-01

    In vitro human natural cell-mediated cytotoxicity (NCMC) to K-562, Molt-4, and F-265 cells is inhibited in a dose-dependent manner by mannose 6-phosphate, fructose 1-phosphate and fructose 6-phosphate. This inhibition is not observed with mannose, glucose, fucose, glucose 6-phosphate, mannose 1-phosphate, galactose 1-phosphate, or galactose 6-phosphate. Preincubation of the effector cells, obtained from fresh whole blood, with mannose-6-phosphate, fructose-1-phosphate, or fructose-6-phosphate...

  1. Effects of intravenous immunoglobulins on T-cell mediated, concanavalin A-induced hepatitis in mice.

    Science.gov (United States)

    Shirin, H; Bruck, R; Aeed, H; Hershkoviz, R; Lider, O; Kenet, G; Avni, Y; Halpern, Z

    1997-12-01

    Concanavalin A (ConA) activates T lymphocytes and causes T-cell mediated hepatic injury in mice. The intravenous administration of human immunoglobulins has beneficial effects in T-cell mediated diseases such as experimental autoimmune encephalomyelitis and adjuvant arthritis. In the present study, we examined the effects of intravenous immunoglobulins in a mouse model of T-cell mediated, acute liver injury induced by concanavalin A. Balb/c mice were inoculated with 12 mg/kg concanavalin A with or without intravenous immunoglobulins at doses of 0.4, 0.6, 0.8 g/kg body wt. The serum levels of liver enzymes, tumor necrosis factor-alpha, interferon-gamma and interleukin-6 were assayed 2, 6 and 24 h after concanavalin A administration. Intravenous immunoglobulins did not prevent concanavalin A-induced hepatitis, as manifested by elevation of serum aminotransferases and histopathological evaluation. The serum levels of tumor necrosis factor-alpha in mice pretreated with immunoglobulins, measured 2 h after ConA treatment were reduced, while interferon-gamma levels measured 6 h after ConA inoculation were 5-fold higher than control levels. There was no effect of intravenous immunoglobulins on the release of interleukin 6. In conclusion, these results indicate that intravenous immunoglobulin is not effective in preventing T-cell mediated concanavalin A-induced hepatitis. The increased secretion of interferon-gamma and the incomplete suppression of tumor necrosis factor-alpha release may explain the lack of efficacy of intravenous immunoglobulin in this experimental model. PMID:9455732

  2. Role of T-cell-mediated inflammation in psoriasis: pathogenesis and targeted therapy

    OpenAIRE

    Conrad, Curdin

    2013-01-01

    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 pathogen...

  3. 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)

  4. Defence mechanisms and immune evasion in the interplay between the humane immune system and Plasmodium falciparum

    DEFF Research Database (Denmark)

    Theander, T G

    1992-01-01

    in the liver and the spleen are avoided by sequestration of the mature parasites to the vascular endothelium. The interplay between the human defence system and the malaria parasite governs the symptomatology, the pathology and the development of immunity to the disease. These interactions are extremely......Immunity to P. falciparum malaria is developed as a result of long term exposure to the parasite and depends on immunological memory. The key directors in immune recognition and regulation of the immunological responses are the T-cells. It seems reasonable to propose that immunity is acquired when...... a critical mass of T-cells, recognizing relevant malaria antigens, has been developed. These T-cells mediate immunity by regulating macrophage and B-cell activity, but they may also act directly as cytotoxic cells on infected hepatocytes and through production of parasite-toxic cytokines. The potential...

  5. 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)

  6. Chronically Elevated Levels of Short-Chain Fatty Acids Induce T Cell-Mediated Ureteritis and Hydronephrosis.

    Science.gov (United States)

    Park, Jeongho; Goergen, Craig J; HogenEsch, Harm; Kim, Chang H

    2016-03-01

    Short-chain fatty acids (SCFAs) are major products of gut microbial fermentation and profoundly affect host health and disease. SCFAs generate IL-10(+) regulatory T cells, which may promote immune tolerance. However, SCFAs can also induce Th1 and Th17 cells upon immunological challenges and, therefore, also have the potential to induce inflammatory responses. Because of the seemingly paradoxical SCFA activities in regulating T cells, we investigated, in depth, the impact of elevated SCFA levels on T cells and tissue inflammation in mice. Orally administered SCFAs induced effector (Th1 and Th17) and regulatory T cells in ureter and kidney tissues, and they induced T cell-mediated ureteritis, leading to kidney hydronephrosis (hereafter called acetate-induced renal disease, or C2RD). Kidney hydronephrosis in C2RD was caused by ureteral obstruction, which was, in turn, induced by SCFA-induced inflammation in the ureteropelvic junction and proximal ureter. Oral administration of all major SCFAs, such as acetate, propionate, and butyrate, induced the disease. We found that C2RD development is dependent on mammalian target of rapamycin activation, T cell-derived inflammatory cytokines such as IFN-γ and IL-17, and gut microbiota. Young or male animals were more susceptible than old or female animals, respectively. However, SCFA receptor (GPR41 or GPR43) deficiency did not affect C2RD development. Thus, SCFAs, when systemically administered at levels higher than physiological levels, cause dysregulated T cell responses and tissue inflammation in the renal system. The results provide insights into the immunological and pathological effects of chronically elevated SCFAs. PMID:26819206

  7. Colonic immune stimulation by targeted oral vaccine.

    Directory of Open Access Journals (Sweden)

    Mahesh Kathania

    Full Text Available BACKGROUND: Currently, sufficient data exist to support the use of lactobacilli as candidates for the development of new oral targeted vaccines. To this end, we have previously shown that Lactobacillus gasseri expressing the protective antigen (PA component of anthrax toxin genetically fused to a dendritic cell (DC-binding peptide (DCpep induced efficacious humoral and T cell-mediated immune responses against Bacillus anthracis Sterne challenge. METHODOLOGY/PRINCIPAL FINDING: In the present study, we investigated the effects of a dose dependent treatment of mice with L. gasseri expressing the PA-DCpep fusion protein on intestinal and systemic immune responses and confirmed its safety. Treatment of mice with different doses of L. gasseri expressing PA-DCpep stimulated colonic immune responses, resulting in the activation of innate immune cells, including dendritic cells, which induced robust Th1, Th17, CD4(+Foxp3(+ and CD8(+Foxp3(+ T cell immune responses. Notably, high doses of L. gasseri expressing PA-DCpep (10(12 CFU were not toxic to the mice. Treatment of mice with L. gasseri expressing PA-DCpep triggered phenotypic maturation and the release of proinflammatory cytokines by dendritic cells and macrophages. Moreover, treatment of mice with L. gasseri expressing PA-DCpep enhanced antibody immune responses, including IgA, IgG(1, IgG(2b, IgG(2c and IgG(3. L. gasseri expressing PA-DCpep also increased the gene expression of numerous pattern recognition receptors, including Toll-like receptors, C-type lectin receptors and NOD-like receptors. CONCLUSION/SIGNIFICANCE: These findings suggest that L. gasseri expressing PA-DCpep has substantial immunopotentiating properties, as it can induce humoral and T cell-mediated immune responses upon oral administration and may be used as a safe oral vaccine against anthrax challenge.

  8. 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.

  9. Stem cell mediation of functional recovery after stroke in the rat.

    Directory of Open Access Journals (Sweden)

    Pedro Ramos-Cabrer

    Full Text Available BACKGROUND: Regenerative strategies of stem cell grafting have been demonstrated to be effective in animal models of stroke. In those studies, the effectiveness of stem cells promoting functional recovery was assessed by behavioral testing. These behavioral studies do, however, not provide access to the understanding of the mechanisms underlying the observed functional outcome improvement. METHODOLOGY/PRINCIPAL FINDINGS: In order to address the underlying mechanisms of stem cell mediated functional improvement, this functional improvement after stroke in the rat was investigated for six months after stroke by use of fMRI, somatosensory evoked potentials by electrophysiology, and sensorimotor behavior testing. Stem cells were grafted ipsilateral to the ischemic lesion. Rigorous exclusion of spontaneous recovery as confounding factor permitted to observe graft-related functional improvement beginning after 7 weeks and continuously increasing during the 6-month observation period. The major findings were i functional improvement causally related to the stem cells grafting; ii tissue replacement can be excluded as dominant factor for stem cell mediated functional improvement; iii functional improvement occurs by exclusive restitution of the function in the original representation field, without clear contributions from reorganization processes, and iv stem cells were not detectable any longer after six months. CONCLUSIONS/SIGNIFICANCE: A delayed functional improvement due to stem cell implantation has been documented by electrophysiology, fMRI and behavioral testing. This functional improvement occurred without cells acting as a tissue replacement for the necrotic tissue after the ischemic event. Combination of disappearance of grafted cells after six months on histological sections with persistent functional recovery was interpreted as paracrine effects by the grafted stem cells being the dominant mechanism of cell activity underlying the observed

  10. Dehydroeffusol effectively inhibits human gastric cancer cell-mediated vasculogenic mimicry with low toxicity

    International Nuclear Information System (INIS)

    Accumulated data has shown that various vasculogenic tumor cells, including gastric cancer cells, are able to directly form tumor blood vessels via vasculogenic mimicry, supplying oxygen and nutrients to tumors, and facilitating progression and metastasis of malignant tumors. Therefore, tumor vasculogenic mimicry is a rational target for developing novel anticancer therapeutics. However, effective antitumor vasculogenic mimicry-targeting drugs are not clinically available. In this study, we purified 2,7-dihydroxyl-1-methyl-5-vinyl-phenanthrene, termed dehydroeffusol, from the traditional Chinese medicinal herb Juncus effusus L., and found that dehydroeffusol effectively inhibited gastric cancer cell-mediated vasculogenic mimicry in vitro and in vivo with very low toxicity. Dehydroeffusol significantly suppressed gastric cancer cell adhesion, migration, and invasion. Molecular mechanistic studies revealed that dehydroeffusol markedly inhibited the expression of a vasculogenic mimicry master gene VE-cadherin and reduced adherent protein exposure on the cell surface by inhibiting gene promoter activity. In addition, dehydroeffusol significantly decreased the expression of a key vasculogenic gene matrix metalloproteinase 2 (MMP2) in gastric cancer cells, and diminished MMP2 protease activity. Together, our results showed that dehydroeffusol effectively inhibited gastric cancer cell-mediated vasculogenic mimicry with very low toxicity, suggesting that dehydroeffusol is a potential drug candidate for anti-gastric cancer neovascularization and anti-gastric cancer therapy. - Highlights: • Dehydroeffusol markedly inhibits gastric cancer cell-mediated vasculogenic mimicry. • Dehydroeffusol suppresses the expression of vasculogenic mimicry key gene VE-cadherin. • Dehydroeffusol decreases the MMP2 expression and activity in gastric cancer cells. • Dehydroeffusol is a potential anti-cancer drug candidate with very low toxicity

  11. Dehydroeffusol effectively inhibits human gastric cancer cell-mediated vasculogenic mimicry with low toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Wenming; Meng, Mei; Zhang, Bin; Du, Longsheng; Pan, Yanyan; Yang, Ping; Gu, Zhenlun; Zhou, Quansheng, E-mail: quanshengzhou@yahoo.com; Cao, Zhifei, E-mail: hunancao@163.com

    2015-09-01

    Accumulated data has shown that various vasculogenic tumor cells, including gastric cancer cells, are able to directly form tumor blood vessels via vasculogenic mimicry, supplying oxygen and nutrients to tumors, and facilitating progression and metastasis of malignant tumors. Therefore, tumor vasculogenic mimicry is a rational target for developing novel anticancer therapeutics. However, effective antitumor vasculogenic mimicry-targeting drugs are not clinically available. In this study, we purified 2,7-dihydroxyl-1-methyl-5-vinyl-phenanthrene, termed dehydroeffusol, from the traditional Chinese medicinal herb Juncus effusus L., and found that dehydroeffusol effectively inhibited gastric cancer cell-mediated vasculogenic mimicry in vitro and in vivo with very low toxicity. Dehydroeffusol significantly suppressed gastric cancer cell adhesion, migration, and invasion. Molecular mechanistic studies revealed that dehydroeffusol markedly inhibited the expression of a vasculogenic mimicry master gene VE-cadherin and reduced adherent protein exposure on the cell surface by inhibiting gene promoter activity. In addition, dehydroeffusol significantly decreased the expression of a key vasculogenic gene matrix metalloproteinase 2 (MMP2) in gastric cancer cells, and diminished MMP2 protease activity. Together, our results showed that dehydroeffusol effectively inhibited gastric cancer cell-mediated vasculogenic mimicry with very low toxicity, suggesting that dehydroeffusol is a potential drug candidate for anti-gastric cancer neovascularization and anti-gastric cancer therapy. - Highlights: • Dehydroeffusol markedly inhibits gastric cancer cell-mediated vasculogenic mimicry. • Dehydroeffusol suppresses the expression of vasculogenic mimicry key gene VE-cadherin. • Dehydroeffusol decreases the MMP2 expression and activity in gastric cancer cells. • Dehydroeffusol is a potential anti-cancer drug candidate with very low toxicity.

  12. Development of cell mediated immunity to flagellar antigens and acquired resistance to infection by Trypanosoma cruzi in mice

    Directory of Open Access Journals (Sweden)

    S. C. Gonçalves da Costa

    1981-12-01

    Full Text Available Modulation by BCG and/or cyclophosphamide of sensitization of mice with flagellar fraction (a tubulin-enriched fraction prevented death of mice challenged with T. cruzi CL strain trypomastigotes recovered from Vero cells. A methodology was ceveloped to assay specific antigens and to determine optimal doses for sensitization and elicitation of DTH in mice. CL strain is predominantly myotropic strain which does not produce important parasitism of mononuclear phagocyte cells; these cells appear to control infection when activated in vivo. Maximum protection was seen in this study when BCG and cyclophosphamide were associated, but protection was observed also when cyclophosphamide, that prevents supressor T cells, was applied 2 days before flagellar fraction sensitization in normal mice. These experiments suggested that the macrophage may have an important role in the early phases of infection particularly when nonspecific stimulation is associated with specific sensitization. A correlation betwen delayed hypersensitivity to parasite antigens and protection was observed.Camundongos sensibilizados com a Fração Flagelar de formas epimastigotas, desenvolvem um estado de hipersensibilidade retardada medida pelo teste do "Footpad" que pode ser elicitado seis dias após quando se empregam doses ótimas de sensibilização e elicitação. Esta hipersensibilidade retardada pode ser ampliada quando se empregam camundongos pré-tratados por formas vivas de Mycobacterium bovis e a ciclofosfamida ou ambos. O melhor resultado obtido foi registrado quando o BCG e a ciclofosfamida foram empregados em associação, sugerindo que efeitos independentes foram somados. Quando a dose de elicitação da Fração Flagelar foi substituída por uma dose de 10*4 trypomastigotas vivas, esta elicitou a hipersensibilidade retardada de intensidade correlata àquela observada quando a Fração Flagelar foi empregada. Nos diferentes grupos sensibilizados com Fração Flagelar apenas ou modulados pelo BCG ou ciclofosfamida ou ambos, constatou-se um estado de resistência cujo nível avaliado pela parasitemia e mortalidade estava relacionado com o nível de hipersensibilidade retardada medida 24 horas após no local da dose infecção. A transferência adotiva da hipersensibilidade retardada foi obtida quando células do linfo-nodo de doadores imunes foram injetadas com a Fração Flagelar em camundongos normais. A correlação entre o nível de hipersensibilidade retardada e o grau de resistência à infecção experimental pelo T. cruzi poderá ampliar os fenômenos imunológicos envolvidos nos mecanismos de imunoproteção à tripanosomiase americana.

  13. Development of cell mediated immunity to flagellar antigens and acquired resistance to infection by Trypanosoma cruzi in mice

    OpenAIRE

    S. C. Gonçalves da Costa; P. H. Lagrande

    1981-01-01

    Modulation by BCG and/or cyclophosphamide of sensitization of mice with flagellar fraction (a tubulin-enriched fraction) prevented death of mice challenged with T. cruzi CL strain trypomastigotes recovered from Vero cells. A methodology was ceveloped to assay specific antigens and to determine optimal doses for sensitization and elicitation of DTH in mice. CL strain is predominantly myotropic strain which does not produce important parasitism of mononuclear phagocyte cells; these cells appear...

  14. Humoral and cell-mediated immunity to Porcine Circovirus type 2 (PCV2) vaccination and natural infection

    OpenAIRE

    Morganti, Marina

    2012-01-01

    Porcine circovirus type 2 (PCV2) has been identified as the main causative agent of the postweaning multisystemic wasting syndrome (PMWS), one of the major swine diseases worldwide that is commonly referred, together with other relevant porcine diseases related to PCV2, as belonging to the porcine circovirus associated diseases (PCVD). The most important strategy to prevent and control PCV2 associated diseases, apart from management procedures and control of coinfections, is the vaccinatio...

  15. 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.

  16. 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

  17. Enhanced killing of chordoma cells by antibody-dependent cell-mediated cytotoxicity employing the novel anti-PD-L1 antibody avelumab.

    Science.gov (United States)

    Fujii, Rika; Friedman, Eitan R; Richards, Jacob; Tsang, Kwong Y; Heery, Christopher R; Schlom, Jeffrey; Hodge, James W

    2016-06-01

    Chordoma, a rare bone tumor derived from the notochord, has been shown to be resistant to conventional therapies. Checkpoint inhibition has shown great promise in immune-mediated therapy of diverse cancers. The anti-PD-L1 mAb avelumab is unique among checkpoint inhibitors in that it is a fully human IgG1 capable of mediating antibody-dependent cell-mediated cytotoxicity (ADCC) of PD-L1-expressing tumor cells. Here, we investigated avelumab as a potential therapy for chordoma. We examined 4 chordoma cell lines, first for expression of PD-L1, and in vitro for ADCC killing using NK cells and avelumab. PD-L1 expression was markedly upregulated by IFN-γ in all 4 chordoma cell lines, which significantly increased sensitivity to ADCC. Brachyury is a transcription factor that is uniformly expressed in chordoma. Clinical trials are ongoing in which chordoma patients are treated with brachyury-specific vaccines. Co-incubating chordoma cells with brachyury-specific CD8+ T cells resulted in significant upregulation of PD-L1 on the tumor cells, mediated by the CD8+ T cells' IFN-γ production, and increased sensitivity of chordoma cells to avelumab-mediated ADCC. Residential cancer stem cell subpopulations of chordoma cells were also killed by avelumab-mediated ADCC to the same degree as non-cancer stem cell populations. These findings suggest that as a monotherapy for chordoma, avelumab may enable endogenous NK cells, while in combination with T-cell immunotherapy, such as a vaccine, avelumab may enhance NK-cell killing of chordoma cells via ADCC.

  18. Protein-Energy Malnutrition (PEM) is Believed to Lead to an Increased Susceptibility to Infection, or cause Impaired Immunity

    OpenAIRE

    Mellova Amir Masrizal

    2003-01-01

    Infection, occurring with malnutrition, is a major cause of morbidity in all age groups and is responsible for two-thirds of all death under 5 yr of age in developing countries. Many cells of the immune system are known to depend for their function on metabolic pathways that employ various nutrients as critical factors. The most consistent changes in immune competence in PEM are in cell-mediated immunity, the bactericidal function of neutrophils, the complement system, the secretory immunoglo...

  19. Cutting edge: membrane lymphotoxin regulates CD8(+) T cell-mediated intestinal allograft rejection.

    Science.gov (United States)

    Guo, Z; Wang, J; Meng, L; Wu, Q; Kim, O; Hart, J; He, G; Zhou, P; Thistlethwaite, J R; Alegre, M L; Fu, Y X; Newell, K A

    2001-11-01

    Blocking the CD28/B7 and/or CD154/CD40 costimulatory pathways promotes long-term allograft survival in many transplant models where CD4(+) T cells are necessary for rejection. When CD8(+) T cells are sufficient to mediate rejection, these approaches fail, resulting in costimulation blockade-resistant rejection. To address this problem we examined the role of lymphotoxin-related molecules in CD8(+) T cell-mediated rejection of murine intestinal allografts. Targeting membrane lymphotoxin by means of a fusion protein, mAb, or genetic mutation inhibited rejection of intestinal allografts by CD8(+) T cells. This effect was associated with decreased monokine induced by IFN-gamma (Mig) and secondary lymphoid chemokine (SLC) gene expression within allografts and spleens respectively. Blocking membrane lymphotoxin did not inhibit rejection mediated by CD4(+) T cells. Combining disruption of membrane lymphotoxin and treatment with CTLA4-Ig inhibited rejection in wild-type mice. These data demonstrate that membrane lymphotoxin is an important regulatory molecule for CD8(+) T cells mediating rejection and suggest a strategy to avoid costimulation blockade-resistant rejection. PMID:11673481

  20. Cell-mediated BMP-2 liberation promotes bone formation in a mechanically unstable implant environment.

    Science.gov (United States)

    Hägi, Tobias T; Wu, Gang; Liu, Yuelian; Hunziker, Ernst B

    2010-05-01

    The flexible alloplastic materials that are used in bone-reconstruction surgery lack the mechanical stability that is necessary for sustained bone formation, even if this process is promoted by the application of an osteogenic agent, such as BMP-2. We hypothesize that if BMP-2 is delivered gradually, in a cell-mediated manner, to the surgical site, then the scaffolding material's lack of mechanical stability becomes a matter of indifference. Flexible discs of Ethisorb were functionalized with BMP-2, which was either adsorbed directly onto the material (rapid release kinetics) or incorporated into a calcium-phosphate coating (slow release kinetics). Unstabilized and titanium-plate-stabilized samples were implanted subcutaneously in rats and retrieved up to 14 days later for a histomorphometric analysis of bone and cartilage volumes. On day 14, the bone volume associated with titanium-plate-stabilized discs bearing an adsorbed depot of BMP-2 was 10-fold higher than that associated with their mechanically unstabilized counterparts. The bone volume associated with discs bearing a coating-incorporated depot of BMP-2 was similar in the mechanically unstabilized and titanium-plate-stabilized groups, and comparable to that associated with the titanium-plate-stabilized discs bearing an adsorbed depot of BMP-2. Hence, if an osteogenic agent is delivered in a cell-mediated manner (via coating degradation), ossification can be promoted even within a mechanically unstable environment.

  1. Role of the spleen in cell-mediated cardiac allograft rejection

    Energy Technology Data Exchange (ETDEWEB)

    Hall, B.M.

    1982-04-01

    A quantitative adoptive transfer assay was used to investigate the role of the spleen in cell-mediated rejection of directly vascularized heart grafts. In this assay, the cell-mediated rejection response can be examined directly by testing the capacity of inocula of T cells to effect rejection of DA heart grafts in PVG rats whose own lymphocytes have been destroyed by whole body irradiation. The capacity of a variety of inocula, including lymph node cells (LNCs), spleen cells, and T cells from lymph node and spleen, to restore rejection were compared in groups of splenectomized and nonsplenectomized hosts. In both groups all inocula restored rejection toward normal. Only in experiments testing inocula equivalent to a small fraction of the naive peripheral lymphocyte pool was rejection delayed in the splenectomized hosts, and this was only a delay of a few days. These results showed that in the absence of the spleen, the primary rejection responses can be generated. In addition, it was demonstrated that the normal spleen contains only a small fraction of the T cell pool with the capacity to effect rejection. Memory T cells were also shown to mediate rejection in splenectomized hosts. It is concluded that with strongly incompatible grafts, splenectomy has only a trivial immunosuppressive effect; it removes neither a sigificant proportion of the alloreactive T cell pool nor the essential site for activation of proliferation of these cells.

  2. NK cell-mediated killing of AML blasts. Role of histamine, monocytes and reactive oxygen metabolites

    International Nuclear Information System (INIS)

    Blasts recovered from patients with acute myelogenous leukaemia (AML) were lysed by heterologeous natural killer (NK) cells treated with NK cell-activating cytokine-induced killing of AML blasts was inhibited by monocytes, recovered from peripheral blood by counterflow centrifugal elutriation. Histamine, at concentrations exceeding 0.1 μM, abrogated the monocyte-induced inhibition of NK cells; thereby, histamine and IL-2 or histamine and IFN-α synergistically induced NK cell-mediated destruction of AML blasts. The effect of histamine was completely blocked by the histamine H2-receptor (H2R) antagonist ranitidine but not by its chemical control AH20399AA. Catalase, a scavenger of reactive oxygen metabolites (ROM), reversed the monocyte-induced inhibition of NK cell-mediated killing of blast cells, indicating that the inhibitory signal was mediated by products of the respiratory burst of monocytes. It is concluded that (i) monocytes inhibit anti-leukemic properties of NK cells, (ii) the inhibition is conveyed by monocyte-derived ROM, and (iii) histamine reverses the inhibitory signal and, thereby, synergizes with NK cell-activating cytokines to induce killing of AML blasts. (au) 19 refs

  3. The Qa-1 Dependent CD8+ T Cell Mediated Regulatory Pathway

    Institute of Scientific and Technical Information of China (English)

    Hong Jiang

    2005-01-01

    The immune system has evolved a variety of regulatory mechanisms to ensure the peripheral self-tolerance as well as the optimal capacity to elicit effective anti-infection immunity. At present, there is no satisfactory conceptual framework to explain how the peripheral immunity is regulated at a biological system level, which enables the immune system to perform its essential functions to mount effective immunity to virtually any foreign antigens but avoid harmful immune responses to self. In this regard, during the past few years, an "affinity/avidity model of peripheral T cell regulation" has been proposed and tested, which opens up a new paradigm to understand how the peripheral immunity, to both self and foreign antigens, is regulated. The paradigm is based on the discovery of a subset CD8+ T cells with TCRs which specifically recognize a unique set of self-peptides presented by the MHC class Ib molecule Qa-1 differentially expressed on T cells as a function of the affinity/avidity of T cell activation.These Qa-1 restricted CD8+ T cells represent an example of how the immune system utilizes a unified mechanism to regulate adaptive immunity to both self and foreign antigens. Thus, by selectively down-regulating T cells of intermediate affinity/avidity, to any antigens, the immune system controls the adaptive immunity without the necessity to distinguish self from non-self in the periphery at the level of T cell regulation.

  4. 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...

  5. Role of immunity in age-related resistance to paralysis after murine leukemia virus infection.

    OpenAIRE

    Hoffman, P M; Robbins, D S; Morse, H C

    1984-01-01

    Resistance to the paralytic effects of a wild mouse (Cas-Br-M) murine leukemia virus infection develops with age and is complete by 10 days of age in susceptible NFS mice. The possibility that cell-mediated immunity plays a significant role in this resistance was suggested by the observation that treatment of 10-day-old mice with antithymocyte serum rendered them susceptible to paralysis. By comparison, mice rendered incapable of generating a humoral immune response by treatment from birth to...

  6. 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

  7. Remarkable heterogeneity displayed by oval cells in rat and mouse models of stem cell-mediated liver regeneration

    DEFF Research Database (Denmark)

    Jelnes, Peter; Santoni-Rugiu, Eric; Rasmussen, Morten;

    2007-01-01

    the molecular phenotypes of oval cells in several of the most commonly used protocols of stem cell-mediated liver regeneration-namely, treatment with 2-acetylaminofluorene and partial (70%) hepatectomy (AAF/PHx); a choline-deficient, ethionine-supplemented (CDE) diet; a 3,5-diethoxycarbonyl-1,4-dihydro......The experimental protocols used in the investigation of stem cell-mediated liver regeneration in rodents are characterized by activation of the hepatic stem cell compartment in the canals of Hering followed by transit amplification of oval cells and their subsequent differentiation along hepatic...... remarkable phenotypic discrepancies exhibited by oval cells in stem cell-mediated liver regeneration between rats and mice and underline the importance of careful extrapolation between individual species....

  8. 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)

  9. Cell-mediated mutagenesis and cell transformation of mammalian cells by chemical carcinogens

    International Nuclear Information System (INIS)

    We have developed a cell-mediated mutagenesis assay in which cells with the appropriate markers for mutagenesis are co-cultivated with either lethally irradiated rodent embryonic cells that can metabolize carcinogenic hydrocarbons or with primary rat liver cells that can metabolize chemicals carcinogenic to the liver. During co-cultivation, the reactive metabolites of the procarcinogen appear to be transmitted to the mutable cells and induce mutations in them. Assays of this type make it possible to demonstrate a relationship between carcinogenic potency of the chemicals and their ability to induce mutations in mammalian cells. In addition, by simultaneously comparing the frequencies of transformation and mutation induced in normal diploid hamster cells by benzo(a)pyrene (BP) and one of its metabolites, it is possible to estimate the genetic target size for cell transformation in vitro

  10. A non-surgical approach for male germ cell mediated gene transmission through transgenesis.

    Science.gov (United States)

    Usmani, Abul; Ganguli, Nirmalya; Sarkar, Hironmoy; Dhup, Suveera; Batta, Suryaprakash R; Vimal, Manoj; Ganguli, Nilanjana; Basu, Sayon; Nagarajan, P; Majumdar, Subeer S

    2013-01-01

    Microinjection of foreign DNA in male pronucleus by in-vitro embryo manipulation is difficult but remains the method of choice for generating transgenic animals. Other procedures, including retroviral and embryonic stem cell mediated transgenesis are equally complicated and have limitations. Although our previously reported technique of testicular transgenesis circumvented several limitations, it involved many steps, including surgery and hemicastration, which carried risk of infection and impotency. We improved this technique further, into a two step non-surgical electroporation procedure, for making transgenic mice. In this approach, transgene was delivered inside both testes by injection and modified parameters of electroporation were used for in-vivo gene integration in germ cells. Using variety of constructs, germ cell integration of the gene and its transmission in progeny was confirmed by PCR, slot blot and immunohistochemical analysis. This improved technique is efficient, requires substantially less time and can be easily adopted by various biomedical researchers.

  11. Role of paracrine factors in stem and progenitor cell mediated cardiac repair and tissue fibrosis

    Directory of Open Access Journals (Sweden)

    Burchfield Jana S

    2008-10-01

    Full Text Available Abstract A new era has begun in the treatment of ischemic disease and heart failure. With the discovery that stem cells from diverse organs and tissues, including bone marrow, adipose tissue, umbilical cord blood, and vessel wall, have the potential to improve cardiac function beyond that of conventional pharmacological therapy comes a new field of research aiming at understanding the precise mechanisms of stem cell-mediated cardiac repair. Not only will it be important to determine the most efficacious cell population for cardiac repair, but also whether overlapping, common mechanisms exist. Increasing evidence suggests that one mechanism of action by which cells provide tissue protection and repair may involve paracrine factors, including cytokines and growth factors, released from transplanted stem cells into the surrounding tissue. These paracrine factors have the potential to directly modify the healing process in the heart, including neovascularization, cardiac myocyte apoptosis, inflammation, fibrosis, contractility, bioenergetics, and endogenous repair.

  12. Susceptibility to T cell-mediated liver injury is enhanced in asialoglycoprotein receptor-deficient mice.

    Science.gov (United States)

    McVicker, Benita L; Thiele, Geoffrey M; Casey, Carol A; Osna, Natalia A; Tuma, Dean J

    2013-05-01

    T cell activation and associated pro-inflammatory cytokine production is a pathological feature of inflammatory liver disease. It is also known that liver injury is associated with marked impairments in the function of many hepatic proteins including a hepatocyte-specific binding protein, the asialoglycoprotein receptor (ASGPR). Recently, it has been suggested that hepatic ASGPRs may play an important role in the physiological regulation of T lymphocytes, leading to our hypothesis that ASGPR defects correlate with inflammatory-mediated events in liver diseases. Therefore, in this study we investigated whether changes in hepatocellular ASGPR expression were related to the dysregulation of intrahepatic T lymphocytes and correlate with the development of T-cell mediated hepatitis. Mice lacking functional ASGPRs (receptor-deficient, RD), and wild-type (WT) controls were intravenously injected with T-cell mitogens, Concanavalin A (Con A) or anti-CD3 antibody. As a result of T cell mitogen treatment, RD mice lacking hepatic ASGPRs displayed enhancements in liver pathology, transaminase activities, proinflammatory cytokine expression, and caspase activation compared to that observed in normal WT mice. Furthermore, FACS analysis demonstrated that T-cell mitogen administration resulted in a significant rise in the percentage of CD8+ lymphocytes present in the livers of RD animals versus WT mice. Since these two mouse strains differ only in whether they express the hepatic ASGPR, it can be concluded that proper ASGPR function exerts a protective effect against T cell mediated hepatitis and that impairments to this hepatic receptor could be related to the accumulation of cytotoxic T cells that are observed in inflammatory liver diseases.

  13. 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...

  14. Echinoderm immunity.

    Science.gov (United States)

    Smith, L Courtney; Ghosh, Julie; Buckley, Katherine M; Clow, Lori A; Dheilly, Nolwenn M; Haug, Tor; Henson, John H; Li, Chun; Lun, Cheng Man; Majeske, Audrey J; Matranga, Valeria; Nair, Sham V; Rast, Jonathan P; Raftos, David A; Roth, Mattias; Sacchi, Sandro; Schrankel, Catherine S; Stensvåg, Klara

    2010-01-01

    A survey for immune genes in the genome for the purple sea urchin has shown that the immune system is complex and sophisticated. By inference, immune responses of all echinoderms maybe similar. The immune system is mediated by several types of coelomocytes that are also useful as sensors of environmental stresses. There are a number of large gene families in the purple sea urchin genome that function in immunity and of which at least one appears to employ novel approaches for sequence diversification. Echinoderms have a simpler complement system, a large set of lectin genes and a number of antimicrobial peptides. Profiling the immune genes expressed by coelomocytes and the proteins in the coelomic fluid provide detailed information about immune functions in the sea urchin. The importance of echinoderms in maintaining marine ecosystem stability and the disastrous effects of their removal due to disease will require future collaborations between ecologists and immunologists working towards understanding and preserving marine habitats. PMID:21528703

  15. Effect of centchroman on cellular and humoral immunity.

    Science.gov (United States)

    Thomas, Licto; Asad, Mohammad; Hrishikeshavan, Heremaglur Jagannath; Chandrakala, Gowda Kallenahalli

    2007-01-01

    Centchroman (Ormeloxifene) is a nonsteroidal selective estrogen receptor modulator that is used as once a week oral contraceptive agent. The effect of centchroman on the immune system was evaluated by using different experimental models such as carbon clearance test, cyclophosphamide induced neutropenia, neutrophil adhesion test, effect on serum immunoglobulins, mice lethality test and indirect haemagglutination test. The first three models namely carbon clearance test, cyclophosphamide induced neutropenia and neutrophil adhesion test were used to study cell mediated immunity while the latter three models were used to see the effect on humoral immunity. Centchroman was administered orally at a dose of 5 mg/kg and levamisole (2.5 mg/kg/ p.o) was used as standard drug. Centchroman significantly increased the levels of serum immunoglobulins and also prevented the mortality induced by bovine Pasteurella multocida in mice. It also increased significantly the circulating antibody litre in indirect haemagglunation test. However, it did not show any significant effect on phagocytic index in carbon clearance assay and nor did influence the adhesion of neutrophils in the neutrophil adhesion test. Centchroman was also not effective in preventing the cyclophosphamde induced neutropenia. Hence, it was concluded that centchroman increases humoral immunity with no significant effect on cell mediated immunity. PMID:18476393

  16. The influence of the swine major histocompatibility genes on antibody and cell-mediated immune responses to immunization with an aromatic-dependent mutant of Salmonella typhimurium.

    Science.gov (United States)

    Lumsden, J S; Kennedy, B W; Mallard, B A; Wilkie, B N

    1993-01-01

    Eighty-two major histocompatibility complex (MHC) swine leukocyte antigen (SLA) defined miniature pigs from 16 litters were examined for serum agglutinating antibody titer and O-polysaccharide (O-ps) specific peripheral blood lymphocyte blastogenesis following two parenteral vaccinations with 1 x 10(8) aromatic-dependent (aroA) Salmonella typhimurium and following oral challenge with 1 x 10(12) virulent parent S. typhimurium. Least mean squares analysis allowed separate determinations of the effects of MHC genotype, dam, sire and litter. In most cases only litter significantly influenced both lymphocyte blastogenesis and antibody titer before and after vaccination and following challenge. However, pig SLA haplotype significantly influenced the degree of O-ps specific lymphocyte proliferation six days after the second vaccination (p < 0.004). Lymphocyte proliferation and serum agglutinating antibody response six days after primary vaccination were negatively correlated (r2 = -0.68, p < 0.001). In most cases, "dd" and "gg" homozygous and "dg" heterozygous pigs, having the same MHC class II region, behaved immunologically as a group distinct from the other genotypes. PMID:8431799

  17. The influence of the swine major histocompatibility genes on antibody and cell-mediated immune responses to immunization with an aromatic-dependent mutant of Salmonella typhimurium.

    OpenAIRE

    Lumsden, J S; Kennedy, B. W.; Mallard, B A; Wilkie, B. N.

    1993-01-01

    Eighty-two major histocompatibility complex (MHC) swine leukocyte antigen (SLA) defined miniature pigs from 16 litters were examined for serum agglutinating antibody titer and O-polysaccharide (O-ps) specific peripheral blood lymphocyte blastogenesis following two parenteral vaccinations with 1 x 10(8) aromatic-dependent (aroA) Salmonella typhimurium and following oral challenge with 1 x 10(12) virulent parent S. typhimurium. Least mean squares analysis allowed separate determinations of the ...

  18. 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

  19. Intratumoral Interleukin-21 Increases Antitumor Immunity, Tumor-infiltrating CD8(+) T-cell Density and Activity, and Enlarges Draining Lymph Nodes

    DEFF Research Database (Denmark)

    Sondergaard, H.; Galsgaard, E.D.; Bartholomaeussen, M.;

    2010-01-01

    generally benefits the tumor microenvironment and activates tumor-draining LNs. Overall, our data suggest that IL-21 augments CD8(+) T-cell-mediated antitumor immunity through increased proliferation and effector function and acts both on tumor-infiltrating CD8(+) T cells as well as on the draining LNs......, and investigated the mechanisms by which IL-21 enhances CD8(+) T-cell-mediated antitumor immunity. We found that in comparison to subcutaneous administration, IT administration of IL-21 more potently inhibited tumor growth and increased survival. This correlated with increased densities of tumor-infiltrating CD8...

  20. 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.

  1. Echinoderm immunity

    OpenAIRE

    JE García-Arrarás; F Ramírez-Gómez

    2010-01-01

    Echinoderms are exclusively marine animals that, after the chordates, represent the second largest group of deuterostomes. Their diverse species composition and singular ecological niches provide at the same time challenges and rewards when studying the broad range of responses that make up their immune mechanisms. Two types of responses comprise the immune system of echinoderms: a cellular response and a humoral one. Cell-based immunity is carried by the celomocytes, a morphologically hetero...

  2. Immune Thrombocytopenia

    OpenAIRE

    Kistanguri, Gaurav; McCrae, Keith R

    2013-01-01

    Immune thrombocytopenia (ITP) is a common hematologic disorder characterized by isolated thrombocytopenia. ITP presents as a primary form characterized by isolated thrombocytopenia (platelet count < 100 × 109/L) in the absence of other causes or disorders that may be associated with thrombocytopenia, or a secondary form in which immune thrombocytopenia develops in association with another disorder that is usually immune or infectious. ITP may affect individuals of all ages, with peaks during ...

  3. Immunomodulatory effects of dietary non-digestible oligosaccharides in T cell-mediated autoimmune arthritis

    NARCIS (Netherlands)

    Rogier, R.; Ederveen, T.; Hartog, A.; Walgreen, B.; Van Den Bersselaar, L.; Helsen, M.; Vos, P.; Garssen, J.; Willemsen, L.; Van Den Berg, W.; Koenders, M.; Abdollahi-Roodsaz, S.

    2015-01-01

    Background: Accumulating evidence indicates the relevance of intestinal microbiota in shaping the immune response and supports its contribution to the development of autoimmune diseases. Prebiotic non-digestible oligosaccharides are known to selectively support growth of commensal Bifidobacteria and

  4. Immune System

    Science.gov (United States)

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

  5. Cell-mediated cytotoxicity-supporting activity of various human gammaglobulin preparations.

    Directory of Open Access Journals (Sweden)

    Wakiguchi,Hiroshi

    1987-04-01

    Full Text Available Antibody activity, especially that involved in the reaction of antibody-dependent cell-mediated cytotoxicity (ADCC, of five commercially available human gammaglobulin preparations (standard, pepsin-treated, plasmin-treated, polyethylene glycol-fractionated and S-sulfonated gammaglobulin was measured. All these gammaglobulin preparations had high titers of hemagglutination inhibition and neutralizing antibody against measles virus. In ADCC reaction, the pepsin-treated gammaglobulin preparation showed no antibody activity. The standard gammaglobulin preparation showed weak activity only when highly diluted. The remaining three preparations showed high activity. Though the S-sulfonated gammaglobulin preparation showed no activity in ADCC reaction, it showed high activity after reconversion by means of oxidation and reduction in vitro. The plasmin-treated gammaglobulin preparation showed greater activity than the polyethylene glycol-fractionated preparation of the optimal concentration. In ADCC tests using the plasmin-treated gammaglobulin preparation, K cell activity was strongly inhibited by Hg (thimerosal, while, in those using the standard gammaglobulin preparation, the activity was hardly influenced by Hg, suggesting that the low ADCC activity of the standard gammaglobulin preparation of high concentrations was due to the inhibitory effect of aggregated immunoglobulin G molecules.

  6. Measurement of cell mediated cytotoxicity by post-labeling surviving target cells

    International Nuclear Information System (INIS)

    The 51Cr release assay (CRA) is the commonly accepted technique for measurement of cell mediated cytotoxicity. This assay shows some disadvantages when mononucleated cells of human peripheral blood (MNC) are used as effector and target cells. The uptake of 51Cr by PHA stimulated lymphocytes is low compared to the spontaneous release. In an attempt to develop a cytotoxicity assay suitable for human lymphocytes we used 14C-TdR to label target cells surviving after contact with effector cells. Cytotoxic lymphocytes were generated by incubation of MNC with irradiated allogeneic MNC for 6 days. On day 6 the effector cells are irradiated and cocultured with PHA stimulated target cells. Twenty-four hours later 14C-TdR is added. After an additional 24 h the cultures are harvested and 14C-TdR taken up by target cells is measured. It is shown that the effector cells are still cytotoxic after irradiation. These cells do not take up 14C-TdR. Cell-free supernatants do not influence the uptake of 14C-TdR by target cells. The results obtained with this assay correlate very well those obtained by the CRA, if the spontaneous release does not exceed 30%. (author)

  7. Hepatic non-parenchymal cells and extracellular matrix participate in oval cell-mediated liver regeneration

    Institute of Scientific and Technical Information of China (English)

    Wei Zhang; Xiao-Ping Chen; Wan-Guang Zhang; Feng Zhang; Shuai Xiang; Han-Hua Dong; Lei Zhang

    2009-01-01

    AIM: To elucidate the interaction between nonparenchymal cells, extracellular matrix and oval cells during the restituting process of liver injury induced by partial hepatectomy (PH). METHODS: We examined the localization of oval cells, non-parenchymal cells, and the extracellular matrix components using immunohistochemical and double immunofluorescent analysis during the proliferation and differentiation of oval cells in N-2-acetylaminofluorene (2-AAF)/PH rat model. RESULTS: By day 2 after PH, small oval cells began to proliferate around the portal area. Most of stellate cells and laminin were present along the hepatic sinusoids in the periportal area. Kupffer cells and fibronectin markedly increased in the whole hepatic lobule. From day 4 to 9, oval cells spread further into hepatic parenchyma, closely associated with stellate cells, fibronectin and laminin. Kupffer cells admixed with oval cells by day 6 and then decreased in the periportal zone. From day 12 to 15, most of hepatic stellate cells (HSCs), laminin and fibronectin located around the small hepatocyte nodus, and minority of them appeared in the nodus. Kupffer cells were mainly limited in the pericentral sinusoids. After day 18, the normal liver lobule structures began to recover.CONCLUSION: Local hepatic microenvironment may participate in the oval cell-mediated liver regeneration through the cell-cell and cell-matrix interactions.

  8. Cell-mediated retraction versus hemodynamic loading - A delicate balance in tissue-engineered heart valves.

    Science.gov (United States)

    van Loosdregt, Inge A E W; Argento, Giulia; Driessen-Mol, Anita; Oomens, Cees W J; Baaijens, Frank P T

    2014-06-27

    Preclinical studies of tissue-engineered heart valves (TEHVs) showed retraction of the heart valve leaflets as major failure of function mechanism. This retraction is caused by both passive and active cell stress and passive matrix stress. Cell-mediated retraction induces leaflet shortening that may be counteracted by the hemodynamic loading of the leaflets during diastole. To get insight into this stress balance, the amount and duration of stress generation in engineered heart valve tissue and the stress imposed by physiological hemodynamic loading are quantified via an experimental and a computational approach, respectively. Stress generation by cells was measured using an earlier described in vitro model system, mimicking the culture process of TEHVs. The stress imposed by the blood pressure during diastole on a valve leaflet was determined using finite element modeling. Results show that for both pulmonary and systemic pressure, the stress imposed on the TEHV leaflets is comparable to the stress generated in the leaflets. As the stresses are of similar magnitude, it is likely that the imposed stress cannot counteract the generated stress, in particular when taking into account that hemodynamic loading is only imposed during diastole. This study provides a rational explanation for the retraction found in preclinical studies of TEHVs and represents an important step towards understanding the retraction process seen in TEHVs by a combined experimental and computational approach. PMID:24268314

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

    Directory of Open Access Journals (Sweden)

    Yuan Li

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

  10. The Role of Non-specific and Specific Immune Systems in Poultry against Newcastle Disease

    Directory of Open Access Journals (Sweden)

    Dyah Ayu Hewajuli

    2015-09-01

    Full Text Available Newcastle disease (ND is caused by avian paramyxovirus-1 which belong to Avulavirus genus and Paramyxoviridae family. The birds have abnormalities in humoral (bursa fabricius and cellular (thymus and spleen lymphoid organs. Lesions decrease the immune system. Immune system consists of non-specific and specific immune systems. The main components of non-specific immunity are physical and chemical barrier (feather and skin or mucosa, phagocytic cells (macrophages and natural killer, protein complement and the mediator of inflammation and cytokines. Interferons (IFNs belong to a group of cytokines that play a major role in the nonspecific or innate (natural immunity. The virulent ND virus encodes protein of V gene can be suppressed IFN type I. This leads to non-specific immune system fail to respond to the virulent strains resulting in severe pathogenicity. The defense mechanism of the host is replaced by specific immunity (adaptive immunity when natural immunity fails to overcome the infection. The specific immune system consists of humoral mediated immunity (HMI and cell-mediated immunity (CMI. The cells of immune system that react specifically with the antigen are B lymphocytes producing the antibodies, T lymphocytes that regulate the synthesis of antibodies and T cells as effector or the direct cytotoxic cells. Both non-specific and specific immunities are complementary against the invasion of ND virus in the birds. The objective of this article is to discuss the role of non specific and specific immune system in ND.

  11. 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

  12. 5-Azacytidine Promotes an Inhibitory T-Cell Phenotype and Impairs Immune Mediated Antileukemic Activity

    OpenAIRE

    Thomas Stübig; Anita Badbaran; Tim Luetkens; York Hildebrandt; Djordje Atanackovic; Binder, Thomas M. C.; Boris Fehse; Nicolaus Kröger

    2014-01-01

    Demethylating agent, 5-Azacytidine (5-Aza), has been shown to be active in treatment of myeloid malignancies. 5-Aza enhances anticancer immunity, by increasing expression of tumor-associated antigens. However, the impact of 5-Aza immune responses remains poorly understood. Here, T-cell mediated tumor immunity effects of 5-Aza, are investigated in vitro and in vivo. T-cells from healthy donors were treated with 5-Aza and analyzed by qRT-PCR and flow cytometry for changes in gene expression and...

  13. Echinoderm immunity

    Directory of Open Access Journals (Sweden)

    JE García-Arrarás

    2010-09-01

    Full Text Available Echinoderms are exclusively marine animals that, after the chordates, represent the second largest group of deuterostomes. Their diverse species composition and singular ecological niches provide at the same time challenges and rewards when studying the broad range of responses that make up their immune mechanisms. Two types of responses comprise the immune system of echinoderms: a cellular response and a humoral one. Cell-based immunity is carried by the celomocytes, a morphologically heterogeneous population of free roaming cells that are capable of recognizing and neutralizing pathogens. Celomocytes present diverse morphologies and functions, which include phagocytosis, encapsulation, clotting, cytotoxicity, wound healing among others. Humoral immunity is mediated by a wide variety of secreted compounds that can be found in the celomic fluid and play important roles in defense against infection. Compounds such as lectins, agglutinins, perforins, complement and some cytokines make up some of the humoral responses of echinoderms. Recent advances in the field of molecular biology, genomics and transcriptomics have allowed for the discovery of new immune genes and their products. These discoveries have expanded our knowledge of echinoderm immunity and are setting up the stage for future experiments to better understand the evolution of the immune mechanisms of deuterostomes

  14. Immunity booster

    International Nuclear Information System (INIS)

    The immunity booster is, according to its patent description, microbiologically pure water with an D/(D+H) isotopic concentration of 100 ppm, with physical-chemical characteristics similar to those of distilled water. It is obtained by sterilization of a mixture of deuterium depleted water, with a 25 ppm isotopic concentration, with distilled water in a volume ratio of 4:6. Unlike natural immunity boosters (bacterial agents as Bacillus Chalmette-Guerin, Corynebacterium parvum; lipopolysaccharides; human immunoglobulin) or synthetical products (levamysol; isoprinosyne with immunostimulating action), which cause hypersensitivity and shocks, thrill, fever, sickness and the immunity complex disease, the water of 100 ppm D/(D + H) isotopic concentration is a toxicity free product. The testing for immune reaction of the immunity booster led to the following results: - an increase of cell action capacity in the first immunity shielding stage (macrophages), as evidenced by stimulation of a number of essential characterizing parameters, as well as of the phagocytosis capacity, bactericide capacity, and opsonic capacity of serum; - an increase of the number of leucocyte particularly of the granulocyte in peripheral blood, produced especially when medullar toxic agents like caryolysine are used; - it hinders the effect of lowering the number of erythrocytes in peripheral blood produced by experimentally induced chronic inflammation; - an increase of nonspecific immunity defence capacity against specific bacterial aggression of both Gram-positive bacteria (Streptococcus pneumoniae558) and of the Gram-negative ones (Klebsiella pneumoniae 507); - an increase of immunity - stimulating activity (proinflamatory), like that of levamisole as evidenced by the test of stimulation of experimentally induced inflammation by means of carrageenan. The following advantages of the immunity booster are stressed: - it is toxicity free and side effect free; - can be orally administrated as food

  15. Immunity challenge.

    Science.gov (United States)

    Davenport, R John

    2003-06-11

    As people get older, their immune systems falter. The elderly are more susceptible to infections than youngsters are, and hyperactive inflammatory responses appear to contribute to some age-associated illnesses, including Alzheimer's disease and atherosclerosis. Investigating the effect of aging on the immune system was once a scientific stepchild, but card-carrying immunologists are now tackling the problem head-on. Despite the immune system's complexity, researchers have started to make sense of how its components change with age. As the research progresses, scientists hope to bolster elderly people's response to infectious diseases and quiet the inflammation that can make aging a painful experience. PMID:12844525

  16. Immune modulation with sulfasalazine attenuates immunopathogenesis but enhances macrophage-mediated fungal clearance during Pneumocystis pneumonia.

    Directory of Open Access Journals (Sweden)

    Jing Wang

    Full Text Available Although T cells are critical for host defense against respiratory fungal infections, they also contribute to the immunopathogenesis of Pneumocystis pneumonia (PcP. However, the precise downstream effector mechanisms by which T cells mediate these diverse processes are undefined. In the current study the effects of immune modulation with sulfasalazine were evaluated in a mouse model of PcP-related Immune Reconstitution Inflammatory Syndrome (PcP-IRIS. Recovery of T cell-mediated immunity in Pneumocystis-infected immunodeficient mice restored host defense, but also initiated the marked pulmonary inflammation and severe pulmonary function deficits characteristic of IRIS. Sulfasalazine produced a profound attenuation of IRIS, with the unexpected consequence of accelerated fungal clearance. To determine whether macrophage phagocytosis is an effector mechanism of T cell-mediated Pneumocystis clearance and whether sulfasalazine enhances clearance by altering alveolar macrophage phagocytic activity, a novel multispectral imaging flow cytometer-based method was developed to quantify the phagocytosis of Pneumocystis in vivo. Following immune reconstitution, alveolar macrophages from PcP-IRIS mice exhibited a dramatic increase in their ability to actively phagocytose Pneumocystis. Increased phagocytosis correlated temporally with fungal clearance, and required the presence of CD4(+ T cells. Sulfasalazine accelerated the onset of the CD4(+ T cell-dependent alveolar macrophage phagocytic response in PcP-IRIS mice, resulting in enhanced fungal clearance. Furthermore, sulfasalazine promoted a TH2-polarized cytokine environment in the lung, and sulfasalazine-enhanced phagocytosis of Pneumocystis was associated with an alternatively activated alveolar macrophage phenotype. These results provide evidence that macrophage phagocytosis is an important in vivo effector mechanism for T cell-mediated Pneumocystis clearance, and that macrophage phenotype can be altered

  17. Two sides of one coin: massive hepatic necrosis and progenitor cell-mediated regeneration in acute liver failure.

    Science.gov (United States)

    Weng, Hong-Lei; Cai, Xiaobo; Yuan, Xiaodong; Liebe, Roman; Dooley, Steven; Li, Hai; Wang, Tai-Ling

    2015-01-01

    Massive hepatic necrosis is a key event underlying acute liver failure, a serious clinical syndrome with high mortality. Massive hepatic necrosis in acute liver failure has unique pathophysiological characteristics including extremely rapid parenchymal cell death and removal. On the other hand, massive necrosis rapidly induces the activation of liver progenitor cells, the so-called "second pathway of liver regeneration." The final clinical outcome of acute liver failure depends on whether liver progenitor cell-mediated regeneration can efficiently restore parenchymal mass and function within a short time. This review summarizes the current knowledge regarding massive hepatic necrosis and liver progenitor cell-mediated regeneration in patients with acute liver failure, the two sides of one coin. PMID:26136687

  18. Two sides of one coin: massive hepatic necrosis and progenitor cell-mediated regeneration in acute liver failure.

    Science.gov (United States)

    Weng, Hong-Lei; Cai, Xiaobo; Yuan, Xiaodong; Liebe, Roman; Dooley, Steven; Li, Hai; Wang, Tai-Ling

    2015-01-01

    Massive hepatic necrosis is a key event underlying acute liver failure, a serious clinical syndrome with high mortality. Massive hepatic necrosis in acute liver failure has unique pathophysiological characteristics including extremely rapid parenchymal cell death and removal. On the other hand, massive necrosis rapidly induces the activation of liver progenitor cells, the so-called "second pathway of liver regeneration." The final clinical outcome of acute liver failure depends on whether liver progenitor cell-mediated regeneration can efficiently restore parenchymal mass and function within a short time. This review summarizes the current knowledge regarding massive hepatic necrosis and liver progenitor cell-mediated regeneration in patients with acute liver failure, the two sides of one coin.

  19. Bystander CD8 T-Cell-Mediated Demyelination is Interferon-γ-Dependent in a Coronavirus Model of Multiple Sclerosis

    OpenAIRE

    Dandekar, Ajai A.; Anghelina, Daniela; Perlman, Stanley

    2004-01-01

    Mice infected with the coronavirus mouse hepatitis virus, strain JHM (JHM) develop a disease that shares many histological characteristics with multiple sclerosis. We previously demonstrated that JHM-infected mice that only have CD8 T cells specific for an epitope not in the virus develop demyelination on specific activation of these cells. Herein we show that this process of bystander T-cell-mediated demyelination is interferon-γ (IFN-γ)-dependent. The absence of IFN-γ abrogated demyelinatio...

  20. Regulatory T cell-mediated suppression of Th9 cell development and effector function

    OpenAIRE

    Hoffmann, Markus

    2014-01-01

    T helper (Th) 9 cells are an important subpopulation of the CD4+ T helper cells. Due to their ability to secrete Interleukin-(IL-)9, Th9 cells essentially contribute to the expulsion of parasitic helminths from the intestinal tract but they play also an immunopathological role in the course of asthma. Recently, a beneficial function of Th9 cells in anti-tumor immune responses was published. In a murine melanoma tumor model Th9 cells were shown to enhance the anti-melanoma immune response via ...

  1. Roscovitine suppresses CD4+ T cells and T cell-mediated experimental uveitis.

    Directory of Open Access Journals (Sweden)

    Zili Zhang

    Full Text Available BACKGROUND: T cells are essential for the development of uveitis and other autoimmune diseases. After initial activation, CD4+ lymphocytes express the co-stimulatory molecule OX40 that plays an important role in T cell proliferation. Cyclin dependent kinase 2 (CdK2 plays a pivotal role in the cell cycle transition from G1 to S phase. In addition, recent research has implicated CdK2 in T cell activation. Thus, we sought to test the immunosuppressive effect of roscovitine, a potent CdK2 inhibitor, on CD4+ T cell activation, proliferation, and function. DESIGN AND METHODS: Mouse CD4+ T cells were activated by anti-CD3 and anti-CD28 antibodies. The expression of OX40, CD44, and CdK2 were analyzed by flow cytometry. In addition, cell cycle progression and apoptosis of control and roscovitine-treated T lymphocytes were measured by BrdU incorporation and annexin V assay, respectively. Furthermore, the immunoregulatory effect of roscovitine was evaluated in both ovalbumin-induced uveitis and experimental autoimmune uveitis (EAU models. RESULTS: In this study, we found that T cell activation induced OX40 expression. Cell cycle analysis showed that more CD4+OX40+ cells entered S phase than OX40- T cells. Concurrently, CD4+OX40+ cells had a higher level of CdK2 expression. Roscovitine treatment blocked activated CD4+ cells from entering S phase. In addition, roscovitine not only reduced the viability of CD4+ lymphocytes but also suppressed T cell activation and cytokine production. Finally, roscovitine significantly attenuated the severity of T cell-dependent, OX40-enhanced uveitis. CONCLUSION: These results implicate CdK2 in OX40-augmented T cell response and expansion. Furthermore, this study suggests that roscovitine is a novel, promising, therapeutic agent for treating T cell-mediated diseases such as uveitis.

  2. Curcuma oil reduces endothelial cell-mediated inflammation in postmyocardial ischemia/reperfusion in rats.

    Science.gov (United States)

    Manhas, Amit; Khanna, Vivek; Prakash, Prem; Goyal, Dipika; Malasoni, Richa; Naqvi, Arshi; Dwivedi, Anil K; Dikshit, Madhu; Jagavelu, Kumaravelu

    2014-09-01

    Endothelial cells initiated inflammation persisting in postmyocardial infarction needs to be controlled and moderated for avoiding fatal complications. Curcuma oil (C.oil, Herbal Medicament), a standardized hexane soluble fraction of Curcuma longa has possessed neuroprotective effect. However, its effect on myocardial ischemia/reperfusion (MI/RP) and endothelial cells remains incompletely defined. Here, using in vivo rat MI/RP injury model and in vitro cellular approaches using EA.hy926 endothelial cells, enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and myograph, we provide evidence that with effective regimen and preconditioning of rats with C.oil (250 mg/kg, PO), before and after MI/RP surgery protects rats from MI/RP-induced injury. C.oil treatment reduces left ventricular ischemic area and endothelial cell-induced inflammation, specifically in the ischemic region (*P < 0.0001) and improved endothelial function by reducing the expression of proinflammatory genes and adhesion factors on endothelial cells both in vitro and in vivo. Furthermore, mechanistic studies have revealed that C.oil reduced the expression of adhesion factors like E-selectin (#P = 0.0016) and ICAM-1 ($P = 0.0069) in initiating endothelial cells-induced inflammation. In line to the real-time polymerase chain reaction expression data, C.oil reduced the adhesion of inflammatory cells to endothelial cells as assessed by the interaction of THP-1 monocytes with the endothelial cells using flow-based adhesion and under inflammatory conditions. These studies provide evidence that salutary effect of C.oil on MI/RP could be achieved with pretreatment and posttreatment of rats, C.oil reduced MI/RP-induced injury by reducing the endothelial cell-mediated inflammation, specifically in the ischemic zone of MI/RP rat heart.

  3. A Neutralizing Antibody Assay Based on a Reporter of Antibody-Dependent Cell-Mediated Cytotoxicity.

    Science.gov (United States)

    Wu, Yuling; Li, Jia J; Kim, Hyun Jun; Liu, Xu; Liu, Weiyi; Akhgar, Ahmad; Bowen, Michael A; Spitz, Susan; Jiang, Xu-Rong; Roskos, Lorin K; White, Wendy I

    2015-11-01

    Benralizumab is a humanized anti-IL5 receptor α (IL5Rα) monoclonal antibody (mAb) with enhanced (afucosylation) antibody-dependent cell-mediated cytotoxicity (ADCC) function. An ADCC reporter cell-based neutralizing antibody (NAb) assay was developed and characterized to detect NAb against benralizumab in human serum to support the clinical development of benralizumab. The optimal ratio of target cells to effector cells was 3:1. Neither parental benralizumab (fucosylated) nor benralizumab Fab resulted in ADCC activity, confirming the requirement for ADCC activity in the NAb assay. The serum tolerance of the cells was determined to be 2.5%. The cut point derived from normal and asthma serum samples was comparable. The effective range of benralizumab was determined, and 35 ng/mL [80% maximal effective concentration (EC80)] was chosen as the standard concentration to run in the assessment of NAb. An affinity purified goat anti-benralizumab polyclonal idiotype antibody preparation was shown to have NAb since it inhibited ADCC activity in a dose-dependent fashion. The low endogenous concentrations of IL5 and soluble IL5 receptor (sIL5R) did not demonstrate to interfere with the assay. The estimated assay sensitivities at the cut point were 1.02 and 1.10 μg/mL as determined by the surrogate neutralizing goat polyclonal and mouse monoclonal anti-drug antibody (ADA) controls, respectively. The assay can detect NAb (at 2.5 μg/mL) in the presence of 0.78 μg/mL benralizumab. The assay was not susceptible to non-specific matrix effects. This study provides an approach and feasibility of developing an ADCC cell-based NAb assay to support biopharmaceuticals with an ADCC function. PMID:26205082

  4. Effect of Chicoric Acid on Mast Cell-Mediated Allergic Inflammation in Vitro and in Vivo.

    Science.gov (United States)

    Lee, Na Young; Chung, Kyung-Sook; Jin, Jong Sik; Bang, Keuk Soo; Eom, Ye-Jin; Hong, Chul-Hee; Nugroho, Agung; Park, Hee-Jun; An, Hyo-Jin

    2015-12-24

    Chicoric acid (dicaffeoyl-tartaric acid), is a natural phenolic compound found in a number of plants, such as chicory (Cichorium intybus) and Echinacea (Echinacea purpurea), which possesses antioxidant, anti-inflammatory, antiviral, and analgesic activities. Although these biological effects of chicoric acid have been investigated, there are no reports of its antiallergic-related anti-inflammatory effects in human mast cells (HMC)-1 or anaphylactic activity in a mouse model. Therefore, we investigated the antiallergic-related anti-inflammatory effect of chicoric acid and its underlying mechanisms of action using phorbol-12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated HMC-1 cells. Chicoric acid decreased the mRNA expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β. We studied the inhibitory effects of chicoric acid on the nuclear translocation of nuclear factor kappa B (NF-κB) and activation of caspase-1. However, mitogen-activated protein kinase (MAPK) activation was not sufficient to abrogate the stimulus. In addition, we investigated the ability of chicoric acid to inhibit compound 48/80-induced systemic anaphylaxis in vivo. Oral administration of chicoric acid at 20 mg/kg inhibited histamine release and protected mice against compound 48/80-induced anaphylactic mortality. These results suggest that chicoric acid has an antiallergic-related anti-inflammatory effect that involves modulating mast cell-mediated allergic responses. Therefore, chicoric acid could be an efficacious agent for allergy-related inflammatory disorders. PMID:26593037

  5. Adult Immunization

    OpenAIRE

    Omer Coskun

    2008-01-01

    Despite the many advances in modern medicine, each year thousands of people in the world die from diseases that are easily prevented by safe and effective vaccines. Few measures in preventive medicine are of such proven value and as easy to implement as routine immunization against infectious diseases. Prevention of infection by immunization is a lifelong process. There are a number of vaccines that all adults (¡I18 years) require. There are also other vaccines that need to be tailored t...

  6. MHC class II-dependent basophil-CD4(+) T cell interactions promote T(H)2 cytokine-dependent immunity

    NARCIS (Netherlands)

    Perrigoue, J.G.; Saenz, S.A.; Siracusa, M.C.; Allenspach, E.J.; Taylor, B.C.; Giacomin, P.; Nair, M.G.; Du, Y.R.; Zaph, C.; Rooijen, van N.; Comeau, M.R.; Pearce, E.J.; Laufer, T.M.; Artis, D.

    2009-01-01

    Dendritic cells can prime naive CD4(+) T cells; however, here we demonstrate that dendritic cell-mediated priming was insufficient for the development of T helper type 2 cell-dependent immunity. We identify basophils as a dominant cell population that coexpressed major histocompatibility complex cla

  7. Tetherin does not significantly restrict dendritic cell-mediated HIV-1 transmission and its expression is upregulated by newly synthesized HIV-1 Nef

    Directory of Open Access Journals (Sweden)

    Wu Li

    2011-04-01

    Full Text Available Abstract Background Dendritic cells (DCs are among the first cells to encounter HIV-1 and play important roles in viral transmission and pathogenesis. Immature DCs allow productive HIV-1 replication and long-term viral dissemination. The pro-inflammatory factor lipopolysaccharide (LPS induces DC maturation and enhances the efficiency of DC-mediated HIV-1 transmission. Type I interferon (IFN partially inhibits HIV-1 replication and cell-cell transmission in CD4+ T cells and macrophages. Tetherin is a type I IFN-inducible restriction factor that blocks HIV-1 release and modulates CD4+ T cell-mediated cell-to-cell transmission of HIV-1. However, the role of type I IFN and tetherin in HIV-1 infection of DCs and DC-mediated viral transmission remains unknown. Results We demonstrated that IFN-alpha (IFNα-induced mature DCs restricted HIV-1 replication and trans-infection of CD4+ T cells. Tetherin expression in monocyte-derived immature DCs was undetectable or very low. High levels of tetherin were transiently expressed in LPS- and IFNα-induced mature DCs, while HIV-1 localized into distinct patches in these DCs. Knockdown of induced tetherin in LPS- or IFNα-matured DCs modestly enhanced HIV-1 transmission to CD4+ T cells, but had no significant effect on wild-type HIV-1 replication in mature DCs. Intriguingly, we found that HIV-1 replication in immature DCs induced significant tetherin expression in a Nef-dependent manner. Conclusions The restriction of HIV-1 replication and transmission in IFNα-induced mature DCs indicates a potent anti-HIV-1 response; however, high levels of tetherin induced in mature DCs cannot significantly restrict wild-type HIV-1 release and DC-mediated HIV-1 transmission. Nef-dependent tetherin induction in HIV-1-infected immature DCs suggests an innate immune response of DCs to HIV-1 infection.

  8. Prenatal immune challenge alters the hypothalamic-pituitary-adrenocortical axis in adult rats.

    OpenAIRE

    Reul, J M; Stec, I; Wiegers, G J; Labeur, M S; Linthorst, A C; Arzt, E; Holsboer, F

    1994-01-01

    We investigated whether non-abortive maternal infections would compromise fetal brain development and alter hypothalamic-pituitary-adrenocortical (HPA) axis functioning when adult. To study putative teratogenic effects of a T cell-mediated immune response versus an endotoxic challenge, 10-d-pregnant rats received a single intraperitoneal injection of 5 x 10(8) human red blood cells (HRBC) or gram-negative bacterial endotoxin (Escherichia coli LPS: 30 micrograms/kg). The adult male progeny (3 ...

  9. Candida Immunity

    Directory of Open Access Journals (Sweden)

    Julian R. Naglik

    2014-01-01

    Full Text Available The human pathogenic fungus Candida albicans is the predominant cause of both superficial and invasive forms of candidiasis. C. albicans primarily infects immunocompromised individuals as a result of either immunodeficiency or intervention therapy, which highlights the importance of host immune defences in preventing fungal infections. The host defence system utilises a vast communication network of cells, proteins, and chemical signals distributed in blood and tissues, which constitute innate and adaptive immunity. Over the last decade the identity of many key molecules mediating host defence against C. albicans has been identified. This review will discuss how the host recognises this fungus, the events induced by fungal cells, and the host innate and adaptive immune defences that ultimately resolve C. albicans infections during health.

  10. Fasting-Mimicking Diet Reduces HO-1 to Promote T Cell-Mediated Tumor Cytotoxicity.

    Science.gov (United States)

    Di Biase, Stefano; Lee, Changhan; Brandhorst, Sebastian; Manes, Brianna; Buono, Roberta; Cheng, Chia-Wei; Cacciottolo, Mafalda; Martin-Montalvo, Alejandro; de Cabo, Rafael; Wei, Min; Morgan, Todd E; Longo, Valter D

    2016-07-11

    Immune-based interventions are promising strategies to achieve long-term cancer-free survival. Fasting was previously shown to differentially sensitize tumors to chemotherapy while protecting normal cells, including hematopoietic stem and immune cells, from its toxic side effects. Here, we show that the combination of chemotherapy and a fasting-mimicking diet (FMD) increases the levels of bone marrow common lymphoid progenitor cells and cytotoxic CD8(+) tumor-infiltrating lymphocytes (TILs), leading to a major delay in breast cancer and melanoma progression. In breast tumors, this effect is partially mediated by the downregulation of the stress-responsive enzyme heme oxygenase-1 (HO-1). These data indicate that FMD cycles combined with chemotherapy can enhance T cell-dependent targeted killing of cancer cells both by stimulating the hematopoietic system and by enhancing CD8(+)-dependent tumor cytotoxicity. PMID:27411588

  11. 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...... in their ability to induce DC-dependent IFN-gamma production by NK cells. This suggests that DCs stimulated by gut LAB may expand the pool of NK cells and increase their cytotoxic potential. Specific LAB, inducing high levels of IL-12 in DCs, may promote amplification of a type-1 response via potent stimulation...... of IFN-gamma production in NK cells. Combining IFN-gamma-inducing and non-inducing LAB completely abrogates DC-mediated IFN-gamma production by NK cells, and therefore LAB modulating IFN-gamma production in NK cells may be important regulators of the immune response....

  12. Low-Dose IL-2 Induces Regulatory T Cell-Mediated Control of Experimental Food Allergy.

    Science.gov (United States)

    Bonnet, Benjamin; Vigneron, James; Levacher, Béatrice; Vazquez, Thomas; Pitoiset, Fabien; Brimaud, Faustine; Churlaud, Guillaume; Klatzmann, David; Bellier, Bertrand

    2016-07-01

    Regulatory T cells (Tregs) are pivotal for maintenance of immune self-tolerance and also regulate immune responses to exogenous Ags, including allergens. Both decreased Treg number and function have been reported in allergic patients, offering new therapeutic perspectives. We previously demonstrated that Tregs can be selectively expanded and activated by low doses of IL-2 (ld-IL-2) inducing immunoregulation without immunosuppression and established its protective effect in autoimmune diseases. In this study, we evaluated the ability of ld-IL-2 to control allergy in an experimental model of food allergy. Ld-IL-2 induced Treg expansion and activation that elicited protection against clinical manifestations of food allergy in two mouse models with OVA and peanut. This clinical effect was lost in Treg-depleted mice, demonstrating the major contribution of Tregs in ld-IL-2 efficacy. Mechanistic studies further indicated that protection from allergy could be explained by a Treg-dependent local modification of the Th1/Th2 balance and an inhibition of mast cell recruitment and activation. Preventive and therapeutic effects of ld-IL-2 were observed over a 7-mo-period, highlighting its long-term efficacy. This study demonstrated that ld-IL-2 is efficient to prevent and to treat allergic immune responses, and thus represents a promising therapeutic strategy for managing allergic diseases. PMID:27259854

  13. Immune thrombocytopenia.

    Science.gov (United States)

    Kistangari, Gaurav; McCrae, Keith R

    2013-06-01

    Immune thrombocytopenia (ITP) is a common hematologic disorder characterized by isolated thrombocytopenia. ITP presents as a primary or a secondary form. ITP may affect individuals of all ages, with peaks during childhood and in the elderly, in whom the age-specific incidence of ITP is greatest. Bleeding is the most common clinical manifestation of ITP. The pathogenesis of ITP is complex, involving alterations in humoral and cellular immunity. Corticosteroids remain the most common first line therapy for ITP. This article summarizes the classification and diagnosis of primary and secondary ITP, as well as the pathogenesis and options for treatment. PMID:23714309

  14. Feline infectious peritonitis. An immune-mediated coronaviral vasculitis.

    Science.gov (United States)

    August, J R

    1984-09-01

    Mainly through studies inducing experimental infection of susceptible cats, significant advances have recently been made in our understanding of the pathogenesis of FIP. Much of this knowledge should not presently be directly extrapolated to field cases of FIP, because the route of infection and challenge dose and strain of virus may be significantly different. Advances in the prevention and treatment of FIP will depend greatly on clarification of the exact nature of the several coronaviruses affecting cats and the role of cell-mediated immunity in resistance to FIPV.

  15. Ibrutinib interferes with the cell-mediated anti-tumor activities of therapeutic CD20 antibodies: implications for combination therapy

    DEFF Research Database (Denmark)

    Da Roit, F.; Engelberts, P. J.; Taylor, R. P.;

    2015-01-01

    the possible positive or negative impact of these drugs on all known mechanisms of action of both type I and type II anti-CD20 antibodies. Pretreatment with ibrutinib for 1 hour did not increase direct cell death of cell lines or chronic lymphocytic leukemia samples mediated by anti-CD20 antibodies. Pre......-treatment with ibrutinib did not inhibit complement activation or complement-mediated lysis. In contrast, ibrutinib strongly inhibited all cell-mediated mechanisms induced by anti-CD20 antibodies rituximab, ofatumumab or obinutuzumab, either in purified systems or whole blood assays. Activation of natural killer cells...

  16. Integrin Receptors on Tumor Cells Facilitate NK cell-mediated Antibody-dependent Cytotoxicity

    OpenAIRE

    Anikeeva, Nadia; Steblyanko, Maria; Fayngerts, Svetlana; Kopylova, Natalya; Marshall, Deborah J.; Powers, Gordon D.; Sato, Takami; Campbell, Kerry S.; Sykulev, Yuri

    2014-01-01

    NK cells that mediate ADCC play an important role in tumor-specific immunity. We have examined factors limiting specific lysis of tumor cells by CD16.NK-92 cells induced by CNTO 95LF antibodies recognizing αV integrins that are overexpressed on many tumor cells. Although all tested tumor cells were killed by CD16.NK-92 effectors in the presence of the antibodies, the killing of target cells with a low level of ICAM-1 expression revealed a dramatic decrease in their specific lysis at high anti...

  17. Adoptively Transferred Dendritic Cells Restore Primary Cell-Mediated Inflammatory Competence to Acutely Malnourished Weanling Mice

    OpenAIRE

    Hillyer, Lyn; Whitley, Charlene; Olver, Amy; Webster, Michelle; Steevels, Tessa; Woodward, Bill

    2008-01-01

    Immune depression associated with prepubescent malnutrition underlies a staggering burden of infection-related morbidity. This investigation centered on dendritic cells as potentially decisive in this phenomenon. C57BL/6J mice, initially 19 days old, had free access for 14 days to a complete diet or to a low-protein formulation that induced wasting deficits of protein and energy. Mice were sensitized by i.p. injection of sheep red blood cells on day 9, at which time one-half of the animals in...

  18. Protein-Energy Malnutrition (PEM is Believed to Lead to an Increased Susceptibility to Infection, or cause Impaired Immunity

    Directory of Open Access Journals (Sweden)

    Mellova Amir Masrizal

    2003-08-01

    Full Text Available Infection, occurring with malnutrition, is a major cause of morbidity in all age groups and is responsible for two-thirds of all death under 5 yr of age in developing countries. Many cells of the immune system are known to depend for their function on metabolic pathways that employ various nutrients as critical factors. The most consistent changes in immune competence in PEM are in cell-mediated immunity, the bactericidal function of neutrophils, the complement system, the secretory immunoglobin A, and antibody response.

  19. Langerhans Cells Suppress CD49a+ NK Cell-Mediated Skin Inflammation.

    Science.gov (United States)

    Scholz, Felix; Naik, Shruti; Sutterwala, Fayyaz S; Kaplan, Daniel H

    2015-09-01

    Recruitment of innate immune effector cells into sites of infection is a critical component of resistance to pathogen infection. Using a model of intradermal footpad injection of Candida albicans, we observed that inflammation as measured by footpad thickness and neutrophil recruitment occurred independent of adoptive immunity but was significantly reduced in MyD88(-/-) and IL-6(-/-) mice. Unexpectedly, huLangerin-DTA mice (ΔLC) that lack Langerhans cells (LC) developed increased skin inflammation and expressed higher amounts of IL-6, suggesting a suppressive role for LC. Increased inflammation also occurred in Rag1(-/-) ΔLC mice but was reversed by Ab-mediated ablation of NK cells. CXCR6(+)CD49a(+) NK cells are a liver-resident subset that can mediate inflammatory skin responses. We found that exaggerated skin inflammation was absent in ΔLC × CXCR6(-/-) mice. Moreover, the exaggerated response in ΔLC mice could be adoptively transferred with liver CD49a(+) NK cells. Finally, CD49a(+) NK cells in ΔLC but not control mice were recruited to the skin, and inhibition of their recruitment prevented the exaggerated response. Thus, in the absence of LC, CD49a(+) liver NK cells display an inappropriately proinflammatory phenotype that results in increased local skin inflammation. These data reveal a novel function for LC in the regulation of this recently described subset of skin tropic NK cells. PMID:26209621

  20. Integrin receptors on tumor cells facilitate NK cell-mediated antibody-dependent cytotoxicity.

    Science.gov (United States)

    Anikeeva, Nadia; Steblyanko, Maria; Fayngerts, Svetlana; Kopylova, Natalya; Marshall, Deborah J; Powers, Gordon D; Sato, Takami; Campbell, Kerry S; Sykulev, Yuri

    2014-08-01

    NK cells that mediate ADCC play an important role in tumor-specific immunity. We have examined factors limiting specific lysis of tumor cells by CD16.NK-92 cells induced by CNTO 95LF antibodies recognizing αV integrins that are overexpressed on many tumor cells. Although all tested tumor cells were killed by CD16.NK-92 effectors in the presence of the antibodies, the killing of target cells with a low level of ICAM-1 expression revealed a dramatic decrease in their specific lysis at high antibody concentration, revealing a dose limiting effect. A similar effect was also observed with primary human NK cells. The effect was erased after IFN-γ treatment of tumor cells resulting in upregulation of ICAM-1. Furthermore, killing of the same tumor cells induced by Herceptin antibody was significantly impaired in the presence of CNTO 95Ala-Ala antibody variant that blocks αV integrins but is incapable of binding to CD16. These data suggest that αV integrins on tumor cells could compensate for the loss of ICAM-1 molecules, thereby facilitating ADCC by NK cells. Thus, NK cells could exercise cytolytic activity against ICAM-1 deficient tumor cells in the absence of proinflammatory cytokines, emphasizing the importance of NK cells in tumor-specific immunity at early stages of cancer. PMID:24810893

  1. Predictors of immune function in space flight

    Science.gov (United States)

    Shearer, William T.; Zhang, Shaojie; Reuben, James M.; Lee, Bang-Ning; Butel, Janet S.

    2007-02-01

    Of all of the environmental conditions of space flight that might have an adverse effect upon human immunity and the incidence of infection, space radiation stands out as the single-most important threat. As important as this would be on humans engaged in long and deep space flight, it obviously is not possible to plan Earth-bound radiation and infection studies in humans. Therefore, we propose to develop a murine model that could predict the adverse effects of space flight radiation and reactivation of latent virus infection for humans. Recent observations on the effects of gamma and latent virus infection demonstrate latent virus reactivation and loss of T cell mediated immune responses in a murine model. We conclude that using this small animal method of quantitating the amounts of radiation and latent virus infection and resulting alterations in immune responses, it may be possible to predict the degree of immunosuppression in interplanetary space travel for humans. Moreover, this model could be extended to include other space flight conditions, such as microgravity, sleep deprivation, and isolation, to obtain a more complete assessment of space flight risks for humans.

  2. Adult Immunization

    Directory of Open Access Journals (Sweden)

    Omer Coskun

    2008-04-01

    Full Text Available Despite the many advances in modern medicine, each year thousands of people in the world die from diseases that are easily prevented by safe and effective vaccines. Few measures in preventive medicine are of such proven value and as easy to implement as routine immunization against infectious diseases. Prevention of infection by immunization is a lifelong process. There are a number of vaccines that all adults (¡I18 years require. There are also other vaccines that need to be tailored to meet individual variations in risk resulting from occupation, foreign travel, underlying illness, lifestyle and age. In this study, we tried to review this important subject. [TAF Prev Med Bull. 2008; 7(2: 159-166

  3. Adult Immunization

    Directory of Open Access Journals (Sweden)

    Omer Coskun

    2008-04-01

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

  4. Antagonizing Arachidonic Acid-Derived Eicosanoids Reduces Inflammatory Th17 and Th1 Cell-Mediated Inflammation and Colitis Severity

    Directory of Open Access Journals (Sweden)

    Jennifer M. Monk

    2014-01-01

    Full Text Available During colitis, activation of two inflammatory T cell subsets, Th17 and Th1 cells, promotes ongoing intestinal inflammatory responses. n-6 polyunsaturated fatty acid- (PUFA- derived eicosanoids, such as prostaglandin E2 (PGE2, promote Th17 cell-mediated inflammation, while n-3 PUFA antagonize both Th17 and Th1 cells and suppress PGE2 levels. We utilized two genetic mouse models, which differentially antagonize PGE2 levels, to examine the effect on Th17 cells and disease outcomes in trinitrobenzene sulfonic acid- (TNBS- induced colitis. Fat-1 mice contain the ω3 desaturase gene from C. elegans and synthesize n-3 PUFA de novo, thereby reducing the biosynthesis of n-6 PUFA-derived eicosanoids. In contrast, Fads1 Null mice contain a disrupted Δ5 desaturase gene and produce lower levels of n-6 PUFA-derived eicosanoids. Compared to Wt littermates, Fat-1 and Fads1 Null mice exhibited a similar colitic phenotype characterized by reduced colonic mucosal inflammatory eicosanoid levels and mRNA expression of Th17 cell markers (IL-17A, RORγτ, and IL-23, decreased percentages of Th17 cells and, improved colon injury scores (P≤0.05. Thus, during colitis, similar outcomes were obtained in two genetically distinct models, both of which antagonize PGE2 levels via different mechanisms. Our data highlight the critical impact of n-6 PUFA-derived eicosanoids in the promotion of Th17 cell-mediated colonic inflammation.

  5. Effect of chronic, low-level whole-body irradiation on canine immune status

    International Nuclear Information System (INIS)

    A whole blood lectin-induced lymphocyte stimulation test using Con-A and PHA was used to assess the cell-mediated immune status of 52 beagle dogs over a period of 16 months. These dogs included 38 controls 4 exposed to 0.06 R/d, 3 to 0.3 R/d, 4 to 1.0 R/d, and 3 to 2.0 R/d. The data indicated the presence of seasonal variation in immunity with a peak in July and a trough in January

  6. Induced Th2 dominant immune response in APPswe, PSEN1dE9 transgenic mice after nasal immunization with an adenoviral vector encoding 10 tandem repeats of beta-amyloid 3-10

    Institute of Scientific and Technical Information of China (English)

    Rong Guo; Kui Huang; Tongzi Jiang; Jian Li; Yu Li; Xiaona Xing; Yunpeng Cao

    2011-01-01

    Immunotherapy for Alzheimer's disease (AD) is effective in improving cognitive function in transgenic mouse models of AD. Because the AN1792 [beta-amyloid (Aβ) 1-42] vaccine was halted because of T cell mediated meningoencephalitis, many scientists are searching for a novel vaccine to avoid the T cell mediated immune response caused by the Aβ1-42. Importantly, the time when the immunization is begun can influence the immune effect. In this study, an adenovirus vaccine was constructed containing 10 × Aβ3-10 repeats and gene adjuvant CpG DNA. Transgenic AD mice were immunized intranasally for 3 months. After 10 × Aβ3-10 vaccine immunization, high titers of anti-Aβ42 IgG1 predominant antibodies were induced. In spatial learning ability and probe tests, the 10 × Aβ3-10 immunized mice showed significantly improved memories compared to control mice. The 10 × Aβ3-10 vaccine resulted in a robust Th2 dominant humoral immune response and reduced learning deficits in AD mice. In addition, the 10 × Aβ3-10 vaccine might be more efficient if administered before Aβ aggregation at an early stage in the AD mouse brain. Thus, the adenovirus vector encoding 10 × Aβ3-10 is a promising vaccine for AD.

  7. The Immune System of HIV-Exposed Uninfected Infants

    Science.gov (United States)

    Abu-Raya, Bahaa; Kollmann, Tobias R.; Marchant, Arnaud; MacGillivray, Duncan M.

    2016-01-01

    Infants born to human immunodeficiency virus (HIV) infected women are HIV-exposed but the majority remains uninfected [i.e., HIV-exposed uninfected (HEU)]. HEU infants suffer greater morbidity and mortality from infections compared to HIV-unexposed (HU) peers. The reason(s) for these worse outcomes are uncertain, but could be related to an altered immune system state. This review comprehensively summarizes the current literature investigating the adaptive and innate immune system of HEU infants. HEU infants have altered cell-mediated immunity, including impaired T-cell maturation with documented hypo- as well as hyper-responsiveness to T-cell activation. And although prevaccination vaccine-specific antibody levels are often lower in HEU than HU, most HEU infants mount adequate humoral immune response following primary vaccination with diphtheria toxoid, haemophilus influenzae type b, whole cell pertussis, measles, hepatitis B, tetanus toxoid, and pneumococcal conjugate vaccines. However, HEU infants are often found to have lower absolute neutrophil counts as compared to HU infants. On the other hand, an increase of innate immune cytokine production and expression of co-stimulatory markers has been noted in HEU infants, but this increase appears to be restricted to the first few weeks of life. The immune system of HEU children beyond infancy remains largely unexplored. PMID:27733852

  8. 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

  9. From Space to the Patient: A New Cytokine Release Assay to Monitor the Immune Status of HIV Infected Patients and Sepsis Patients

    Science.gov (United States)

    Kaufmann, I.; Draenert, R.; Gruber, M.; Feuerecker, M.; Crucian, B. E.; Mehta, S. L.; Roider, J.; Pierson, D. L.; Briegel, J. M.; Schelling, G.; Sams, C. F.; Chouker, A.

    2013-01-01

    Monitoring of humans either in the healthy men under extreme environmental stress like space flight, in human immunodeficiency virus (HIV) infected patients or in sepsis is of critical importance with regard to the timing of adequate therapeutic (counter-)measures. The in vivo skin delayed-type hypersensitivity test (DTH) served for many years as a tool to evaluate cell mediated immunity. However, this standardised in vivo test was removed from the market in 2002 due to the risk of antigen stabilization. To the best of our knowledge an alternative test as monitoring tool to determine cell mediated immunity is not available so far. For this purpose we tested a new alternative assay using elements of the skin DTH which is based on an ex vivo cytokine release from whole blood and asked if it is suitable and applicable to monitor immune changes in HIV infected patients and in patients with septic shock.

  10. 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.

  11. [Circulating immune complexes in the pathogenesis of recurrent erysipelas].

    Science.gov (United States)

    Frolov, A F; Rychnev, V E; Frolov, V M; Bala, M A

    1985-11-01

    The dynamics of circulating immune complexes (CIC) in comparison with the level of SH-groups of serum deproteinate and other characteristics of cell-mediated and humoral immunity (the reaction of the inhibition of antibodies, the levels of T-cells and their main subpopulations) was studied in 103 erysipelas patients and in 46 persons having had the disease at the acute period of this infection and at the periods between relapses. The elevated levels of CIC and SH-groups of serum deproteinate were found to be directly correlated with the inhibition index. The study showed that, as a rule, in patients with the elevated level of CIC the frequently relapsing form of erysipelas, accompanied by the formation of relative hypersuppressor-type secondary immunodeficiency and by a decrease in the functional activity of dermal macrophages, was observed. PMID:2936048

  12. MFG-E8 Is Critical for Embryonic Stem Cell-Mediated T Cell Immunomodulation

    Directory of Open Access Journals (Sweden)

    Yuan Tan

    2015-11-01

    Full Text Available The molecules and mechanisms pertinent to the low immunogenicity of undifferentiated embryonic stem cells (ESCs remain poorly understood. Here, we provide evidence that milk fat globule epidermal growth factor 8 (MFG-E8 is a vital mediator in this phenomenon and directly suppresses T cell immune responses. MFG-E8 is enriched in undifferentiated ESCs but diminished in differentiated ESCs. Upregulation of MFG-E8 in ESCs increases the successful engraftment of both undifferentiated and differentiated ESCs across major histocompatibility complex barriers. MFG-E8 suppresses T cell activation/proliferation and inhibits Th1, Th2, and Th17 subpopulations while increasing regulatory T cell subsets. Neutralizing MFG-E8 substantially abrogates these effects, whereas addition of recombinant MFG-E8 to differentiated ESCs restores immunosuppression. Furthermore, we provide the evidence that MFG-E8 suppresses T cell activation and regulates T cell polarization by inhibiting PKCθ phosphorylation through the α3/5βV integrin receptor. Our findings offer an approach to facilitate transplantation acceptance.

  13. NKT cells mediate the recruitment of neutrophils by stimulating epithelial chemokine secretion during colitis.

    Science.gov (United States)

    Huang, Enyu; Liu, Ronghua; Lu, Zhou; Liu, Jiajing; Liu, Xiaoming; Zhang, Dan; Chu, Yiwei

    2016-05-27

    Ulcerative colitis (UC) is a kind of inflammatory bowel diseases characterized by chronic inflammation and ulcer in colon, and UC patients have increased risk of getting colorectal cancer. NKT cells are cells that express both NK cell markers and semi-invariant CD1d-restricted TCRs, can regulate immune responses via secreting a variety of cytokines upon activation. In our research, we found that the NKT cell-deficient CD1d(-/-) mice had relieved colitis in the DSS-induced colitis model. Further investigations revealed that the colon of CD1d(-/-) mice expressed less neutrophil-attracting chemokine CXCL 1, 2 and 3, and had decreased neutrophil infiltration. Infiltrated neutrophils also produced less reactive oxygen species (ROS) and TNF-α, indicating they may cause less epithelial damage. In addition, colitis-associated colorectal cancer was also relieved in CD1d(-/-) mice. During colitis, NKT cells strongly expressed TNF-α, which could stimulate CXCL 1, 2, 3 expressions by the epithelium. In conclusion, NKT cells can regulate colitis via the NKT cell-epithelium-neutrophil axis. Targeting this mechanism may help to improve the therapy of UC and prevent colitis-associated colorectal cancer. PMID:27063801

  14. Characterization and mesenteric lymph node cells-mediated immunomodulatory activity of litchi pulp polysaccharide fractions.

    Science.gov (United States)

    Huang, Fei; Zhang, Ruifen; Liu, Yang; Xiao, Juan; Su, Dongxiao; Yi, Yang; Wang, Guangjin; Wei, Zhencheng; Zhang, Mingwei

    2016-11-01

    Three water-soluble hetero-polysaccharides, designated LP1-3, were isolated from litchi pulp. Their structures, solution properties and immunomodulatory activities were evaluated. LP1 contained (1→4,6)-β-d-Glc and (1→4)-α-l-Gal, while LP2 contained (1→3)-α-l-Ara and (l→2)-β-d-Gal, and LP3 contained α-l-Ara and (l→4)-β-Rha. Their molecular weights ranged from 105,880 to 986,470g/mol. LP1 had a spherical conformation with hyper-branched structure and LP2 was semi-flexible chain, while the polysaccharide chains of LP3 were cross linked to form network-like conformation in solution. In addition, all fractions strongly stimulated mesenteric lymph node cell proliferation, IFN-γ and IL-6 secretion in the dose range of 25-100μg/mL compared with untreated control group (pcell proliferation and cytokine secretion, which may be attributed to its unique chemical structure and chain conformation. This is the first report on the solution properties and intestinal immunity activities of polysaccharides from litchi pulp. PMID:27516297

  15. Non-specific protection against pulmonary Legionella pneumophila infection in guinea-pigs immunized and challenged with mycobacteria.

    OpenAIRE

    Gibson, D. H.; Baskerville, A.; Ashworth, L. A.; Fitzgeorge, R. B.

    1985-01-01

    Experiments were designed to test the ability of the non-specific efferent limb of cell mediated immunity (CMI) to protect guinea-pigs against a lethal L. pneumophila challenge. A secondary CMI response was generated in the lungs of guinea-pigs using an established protocol which consisted of intraperitoneal infection with Mycobacterium bovis BCG followed by intravenous infection with Mycobacterium tuberculosis H37Ra. The animals were challenged with L. pneumophila (100 LD50) by the aerosol r...

  16. Dynamics of Regulatory T-Cells during Pregnancy: Effect of HIV Infection and Correlations with Other Immune Parameters

    OpenAIRE

    Kelly Richardson; Adriana Weinberg

    2011-01-01

    OBJECTIVES: Regulatory T cells (Treg) increase in the context of HIV infection and pregnancy. We studied Treg subpopulations in HIV-infected and uninfected women during pregnancy and their relationship with inflammation, activation and cell-mediated immunity (CMI). DESIGN AND METHODS: Blood obtained from 20 HIV-infected and 18 uninfected women during early and late gestation was used to measure Treg and activated T cells (Tact) by flow cytometry; plasma cytokines and inflammatory markers by E...

  17. Immunization of Mice with Recombinant Protein CobB or AsnC Confers Protection against Brucella abortus Infection

    OpenAIRE

    Simei Fu; Jie Xu; Xianbo Li; Yongfei Xie; Yefeng Qiu; Xinying Du; Shuang Yu; Yaoxia Bai; Yanfen Chen; Tongkun Wang; Zhoujia Wang; Yaqing Yu; Guangneng Peng; Kehe Huang; Liuyu Huang

    2012-01-01

    Due to drawbacks of live attenuated vaccines, much more attention has been focused on screening of Brucella protective antigens as subunit vaccine candidates. Brucella is a facultative intracellular bacterium and cell mediated immunity plays essential roles for protection against Brucella infection. Identification of Brucella antigens that present T-cell epitopes to the host could enable development of such vaccines. In this study, 45 proven or putative pathogenesis-associated factors of Bruc...

  18. Intracellular protease activation in apoptosis and cell-mediated cytotoxicity characterized by cell-permeable fluorogenic protease substrates

    Institute of Scientific and Technical Information of China (English)

    Beverly Z Packard; Akira Komoriya

    2008-01-01

    Over the past decade the importance of signaling from reporter molecules inside live cells and tissues has been clearly established. Biochemical events related to inflammation, tumor metastasis and proliferation, and viral infectivity and replication are examples of processes being further defined as more molecular tools for live cell measurements become available. Moreover, in addition to quantitating parameters related to physiologic processes, real-time imaging of molecular interactions that compose basic cellular activities are providing insights into understanding disease mechanisms as well as extending clinical efficacy of therapeutic regimens. In this review the use of highly cell-permeable fluorogenic substrates that report protease activities inside live cells is described; applications to defining the molecular events of two cellular processes, i.e., apoptosis and cell-mediated cytotoxicity, are then illustrated.

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

    Science.gov (United States)

    Wozniak, Karen L; Ravi, Sailatha; Macias, Sandra; Young, Mattie L; Olszewski, Michal A; Steele, Chad; Wormley, Floyd L

    2009-09-03

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

  20. Cytomegalovirus-Infected Cells Resist T Cell Mediated Killing in an HLA-Recognition Independent Manner.

    Science.gov (United States)

    Proff, Julia; Walterskirchen, Christian; Brey, Charlotte; Geyeregger, Rene; Full, Florian; Ensser, Armin; Lehner, Manfred; Holter, Wolfgang

    2016-01-01

    In order to explore the potential of HLA-independent T cell therapy for human cytomegalovirus (HCMV) infections, we developed a chimeric antigen receptor (CAR) directed against the HCMV encoded glycoprotein B (gB), which is expressed at high levels on the surface of infected cells. T cells engineered with this anti-gB CAR recognized HCMV-infected cells and released cytokines and cytotoxic granules. Unexpectedly, and in contrast to analogous approaches for HIV, Hepatitis B or Hepatitis C virus, we found that HCMV-infected cells were resistant to killing by the CAR-modified T cells. In order to elucidate whether this phenomenon was restricted to the use of CARs, we extended our experiments to T cell receptor (TCR)-mediated recognition of infected cells. To this end we infected fibroblasts with HCMV-strains deficient in viral inhibitors of antigenic peptide presentation and targeted these HLA-class I expressing peptide-loaded infected cells with peptide-specific cytotoxic T cells (CTLs). Despite strong degranulation and cytokine production by the T cells, we again found significant inhibition of lysis of HCMV-infected cells. Impairment of cell lysis became detectable 1 day after HCMV infection and gradually increased during the following 3 days. We thus postulate that viral anti-apoptotic factors, known to inhibit suicide of infected host cells, have evolved additional functions to directly abrogate T cell cytotoxicity. In line with this hypothesis, CAR-T cell cytotoxicity was strongly inhibited in non-infected fibroblasts by expression of the HCMV-protein UL37x1, and even more so by additional expression of UL36. Our data extend the current knowledge on Betaherpesviral evasion from T cell immunity and show for the first time that, beyond impaired antigen presentation, infected cells are efficiently protected by direct blockade of cytotoxic effector functions through viral proteins.

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

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    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.

  2. Gene expression profiles of human liver cells mediated by hepatitis B virus X protein

    Institute of Scientific and Technical Information of China (English)

    Wei-ying ZHANG; Fu-qing XU; Chang-liang SHAN; Rong XIANG; Li-hong YE; Xiao-dong ZHANG

    2009-01-01

    Aim: To demonstrate the gene expression profiles mediated by hepatitis B virus X protein (HBx), we characterized the molecular features of pathogenesis associated with HBx in a human liver cell model.Methods: We examined gene expression profiles in L-O2-X cells, an engineered L-O2 cell line that constitutively expresses HBx, relative to L-O2 cells using an Agilent 22 K human 70-mer oligonucleotide microarray representing more than 21,329 unique, well-characterized Homo sapiens genes, Western blot analysis and RNA interference (RNAi) targeting HBx mRNA validated the overexpression of proliferating cell nuclear antigen (PCNA) and Bcl-2 in L-O2-X cells. Meanwhile, the BrdU incorporation assay was used to test cell proliferation mediated by upregulated cyclooxygenase-2 (COX-2).Results: The microarray showed that the expression levels of 152 genes were remarkably altered; 82 of the genes were upregulated and 70 genes were downregulated in L-O2-X cells. The altered genes were associated with signal transduction pathways, cell cycle, metastasis, transcriptional regulation, immune response, metabolism, and other processes. PCNA and Bcl-2 were upregulated in L-O2-X cells. Furthermore, we found that COX-2 upregulation in L-O2-X cells enhanced proliferation using the BrdU incorporation assay, whereas indomethacin (an inhibitor of COX-2) abolished the promotion.Conclusion: Our findings provide new evidence that HBx is able to regulate many genes that may be involved in the car-cinogenesis. These regulated genes mediated by HBx may serve as molecular targets for the prevention and treatment of hepatocellular carcinoma.

  3. mTOR regulation of lymphoid cells in immunity to pathogens

    Directory of Open Access Journals (Sweden)

    Rachael eKeating

    2016-05-01

    Full Text Available Immunity to pathogens exists as a fine balance between promoting activation and expansion of effector cells, while simultaneously limiting normal and aberrant responses. These seemingly opposing functions are kept in check by immune regulators. The mechanistic target of rapamycin (mTOR is a serine/threonine kinase that senses nutrient availability and in turn, regulates cell metabolism, growth, and survival accordingly. mTOR plays a pivotal role in facilitating immune defense against invading pathogens by regulating the differentiation, activation, and effector functions of lymphoid cells. Here we focus on the emerging and sometimes contradictory roles of mTOR in orchestrating lymphoid cell-mediated host immune responses to pathogens. A thorough understanding of how mTOR impacts lymphoid cells in pathogen defense will provide the necessary base for developing therapeutic interventions for infectious diseases.

  4. mTOR Regulation of Lymphoid Cells in Immunity to Pathogens.

    Science.gov (United States)

    Keating, Rachael; McGargill, Maureen Ann

    2016-01-01

    Immunity to pathogens exists as a fine balance between promoting activation and expansion of effector cells, while simultaneously limiting normal and aberrant responses. These seemingly opposing functions are kept in check by immune regulators. The mechanistic target of rapamycin (mTOR) is a serine/threonine kinase that senses nutrient availability and, in turn, regulates cell metabolism, growth, and survival accordingly. mTOR plays a pivotal role in facilitating immune defense against invading pathogens by regulating the differentiation, activation, and effector functions of lymphoid cells. Here, we focus on the emerging and sometimes contradictory roles of mTOR in orchestrating lymphoid cell-mediated host immune responses to pathogens. A thorough understanding of how mTOR impacts lymphoid cells in pathogen defense will provide the necessary base for developing therapeutic interventions for infectious diseases. PMID:27242787

  5. Immune thrombocytopenia.

    Science.gov (United States)

    Maher, George M

    2014-10-01

    Immune thrombocytopenia (ITP) in children is a relatively uncommon and generally benign condition presenting as abrupt onset of bruising, petechiae and thrombocytopenia in an otherwise healthy child due to production of anti-platelet autoantibodies. Diagnosis is largely clinical and laboratory investigation should be kept to a minimum. Indications for treatment have not been standardized and include bleeding, parental anxiety and quality of life. Multiple treatments are available that have been proven to increase the platelet count; the most commonly employed include IVIG, steroids and WinRho (anti-D). Intracranial hemorrhage is the most serious potential complication but is extremely rare and splenectomy is reserved for chronically symptomatic patients who have not responded to other modalities. Identification of molecular targets may be a promising avenue for future research. PMID:25423768

  6. 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

  7. Effects of the space flight environment on the immune system

    Science.gov (United States)

    Sonnenfeld, Gerald; Butel, Janet S.; Shearer, William T.

    2003-01-01

    Space flight conditions have a dramatic effect on a variety of physiologic functions of mammals, including muscle, bone, and neurovestibular function. Among the physiological functions that are affected when humans or animals are exposed to space flight conditions is the immune response. The focus of this review is on the function of the immune system in space flight conditions during actual space flights, as well as in models of space flight conditions on the earth. The experiments were carried out in tissue culture systems, in animal models, and in human subjects. The results indicate that space flight conditions alter cell-mediated immune responses, including lymphocyte proliferation and subset distribution, and cytokine production. The mechanism(s) of space flight-induced alterations in immune system function remain(s) to be established. It is likely, however, that multiple factors, including microgravity, stress, neuroendocrine factors, sleep disruption, and nutritional factors, are involved in altering certain functions of the immune system. Such alterations could lead to compromised defenses against infections and tumors.

  8. Immune Memory to Sudan Virus: Comparison between Two Separate Disease Outbreaks

    Directory of Open Access Journals (Sweden)

    Ariel Sobarzo

    2015-01-01

    Full Text Available Recovery from ebolavirus infection in humans is associated with the development of both cell-mediated and humoral immune responses. According to recent studies, individuals that did not survive infection with ebolaviruses appear to have lacked a robust adaptive immune response and the expression of several early innate response markers. However, a comprehensive protective immune profile has yet to be described. Here, we examine cellular memory immune responses among survivors of two separate Ebolavirus outbreaks (EVDs due to Sudan virus (SUDV infection in Uganda—Gulu 2000–2001 and Kibaale 2012. Freshly collected blood samples were stimulated with inactivated SUDV, as well as with recombinant SUDV or Ebola virus (EBOV GP (GP1–649. In addition, ELISA and plaque reduction neutralization assays were performed to determine anti-SUDV IgG titers and neutralization capacity. Cytokine expression was measured in whole blood cultures in response to SUDV and SUDV GP stimulation in both survivor pools, demonstrating recall responses that indicate immune memory. Cytokine responses between groups were similar but had distinct differences. Neutralizing, SUDV-specific IgG activity against irradiated SUDV and SUDV recombinant proteins were detected in both survivor cohorts. Furthermore, humoral and cell-mediated crossreactivity to EBOV and EBOV recombinant GP1–649 was observed in both cohorts. In conclusion, immune responses in both groups of survivors demonstrate persistent recognition of relevant antigens, albeit larger cohorts are required in order to reach greater statistical significance. The differing cytokine responses between Gulu and Kibaale outbreak survivors suggests that each outbreak may not yield identical memory responses and promotes the merits of studying the immune responses among outbreaks of the same virus. Finally, our demonstration of cross-reactive immune recognition suggests that there is potential for developing cross

  9. Immune memory to Sudan virus: comparison between two separate disease outbreaks.

    Science.gov (United States)

    Sobarzo, Ariel; Eskira, Yael; Herbert, Andrew S; Kuehne, Ana I; Stonier, Spencer W; Ochayon, David E; Fedida-Metula, Shlomit; Balinandi, Steven; Kislev, Yaara; Tali, Neta; Lewis, Eli C; Lutwama, Julius Julian; Dye, John M; Yavelsky, Victoria; Lobel, Leslie

    2015-01-01

    Recovery from ebolavirus infection in humans is associated with the development of both cell-mediated and humoral immune responses. According to recent studies, individuals that did not survive infection with ebolaviruses appear to have lacked a robust adaptive immune response and the expression of several early innate response markers. However, a comprehensive protective immune profile has yet to be described. Here, we examine cellular memory immune responses among survivors of two separate Ebolavirus outbreaks (EVDs) due to Sudan virus (SUDV) infection in Uganda-Gulu 2000-2001 and Kibaale 2012. Freshly collected blood samples were stimulated with inactivated SUDV, as well as with recombinant SUDV or Ebola virus (EBOV) GP (GP1-649). In addition, ELISA and plaque reduction neutralization assays were performed to determine anti-SUDV IgG titers and neutralization capacity. Cytokine expression was measured in whole blood cultures in response to SUDV and SUDV GP stimulation in both survivor pools, demonstrating recall responses that indicate immune memory. Cytokine responses between groups were similar but had distinct differences. Neutralizing, SUDV-specific IgG activity against irradiated SUDV and SUDV recombinant proteins were detected in both survivor cohorts. Furthermore, humoral and cell-mediated crossreactivity to EBOV and EBOV recombinant GP1-649 was observed in both cohorts. In conclusion, immune responses in both groups of survivors demonstrate persistent recognition of relevant antigens, albeit larger cohorts are required in order to reach greater statistical significance. The differing cytokine responses between Gulu and Kibaale outbreak survivors suggests that each outbreak may not yield identical memory responses and promotes the merits of studying the immune responses among outbreaks of the same virus. Finally, our demonstration of cross-reactive immune recognition suggests that there is potential for developing cross-protective vaccines for ebolaviruses

  10. 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

    OpenAIRE

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

    2011-01-01

    Abstract 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 hy...

  11. Transcriptomic analysis of persistent infection with foot-and-mouth disease virus in cattle suggests impairment of cell-mediated immunity in the nasopharynx

    Science.gov (United States)

    In order to investigate the mechanisms of persistent foot-and-mouth disease virus (FMDV) infection in cattle, transcriptome alterations associated with the FMDV carrier state were characterized using a bovine whole-transcriptome microarray. Eighteen cattle (8 vaccinated with a recombinant FMDV A vac...

  12. In Vivo Expression of and Cell-Mediated Immune Responses to the Plasmid-Encoded Virulence-Associated Proteins of Rhodococcus equi in Foals▿

    OpenAIRE

    Jacks, Stephanie; Giguère, Steeve; Prescott, John F.

    2007-01-01

    Rhodococcus equi is a facultative intracellular pathogen that causes pneumonia in foals but does not induce disease in adult horses. Virulence of R. equi depends on the presence of a large plasmid, which encodes a family of seven virulence-associated proteins (VapA and VapC to VapH). Eradication of R. equi from the lungs depends on gamma interferon (IFN-γ) production by T lymphocytes. The objectives of the present study were to determine the relative in vivo expression of the vap genes of R. ...

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

    DEFF Research Database (Denmark)

    Pleidrup, Janne; Dalgaard, Tina S.; Norup, Liselotte 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...

  14. 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...

  15. Immunity and immunization in elderly.

    Science.gov (United States)

    Bourée, Patrice

    2003-12-01

    As the average life expectancy increases, retired people want to travel. Five to 8% of travellers in tropical areas are old persons. Immune system suffers of old age as the other organs. The number and the functions of the T-lymphocytes decrease, but the B-lymphocytes are not altered. So, the response to the vaccinations is slower and lower in the elderly. Influenza is a great cause of death rate in old people. The seroconversion, after vaccine, is 50% from 60 to 70 years old, 31% from 70 to 80 years old, and only 11% after 80 years old. But in public health, the vaccination reduced the morbidity by 25%, admission to hospital by 20%, pneumonia by 50%, and mortality by 70%. Antipoliomyelitis vaccine is useful for travellers, as the vaccines against hepatitis and typhoid fever. Pneumococcal vaccine is effective in 60%. Tetanus is fatal in at last 32% of the people above 80 years, therefore this vaccine is very important.

  16. Immune System Involvement

    Science.gov (United States)

    ... to find out more! Email * Zipcode The Immune System and Psoriatic Disease What is an autoimmune disease? ... and painful joints and tendons. Treating the immune system The immune system is not only the key ...

  17. Immune System Quiz

    Science.gov (United States)

    ... Here's Help White House Lunch Recipes Quiz: Immune System KidsHealth > For Kids > Quiz: Immune System Print A A A Text Size How much do you know about your immune system? Find out by taking this quiz! View Survey ...

  18. Childhood Immunization Schedule

    Science.gov (United States)

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

  19. Effects of benzene inhalation on lymphocyte subpopulations and immune response in mice.

    Science.gov (United States)

    Aoyama, K

    1986-08-01

    To clarify the immunotoxicity of benzene, the effects of benzene inhalation on T and B lymphocytes and immune responses in mice were examined. BALB/c male mice were exposed to 50 or 200 ppm benzene vapor, 6 hr/day for 7 or 14 consecutive days. T and B lymphocytes, in blood and spleen, were detected by the cytotoxicity assay with anti-Thy-1.2 monoclonal antibody and the membrane immunofluorescence test with anti-immunoglobulin antibody, respectively. Humoral immune response to sheep red blood cells was determined by the hemolytic plaque-forming cell assay. Cell-mediated immune response was measured by contact sensitivity (CS) to picryl chloride. The activity of suppressor cells was evaluated in spleen by the suppressive effect on passive transfer of CS. The ratio and absolute number of T and B lymphocytes in blood and spleen were depressed after a 7-day exposure at 50 ppm benzene. The depression of B lymphocytes was dose dependent and more intense than that of T lymphocytes. The ability to form antibodies was suppressed by benzene at all exposure levels, but the CS response was resistant to benzene inhalation and rather enhanced at 200 ppm exposure for 14 days. The activity of suppressor cells could not be detected at this dose level. These data show that benzene inhalation effects on humoral and cell-mediated immune responses are a result of the selective toxicity of benzene to B lymphocytes and suppressor T cells.

  20. Role of Bacterial Exopolysaccharides as Agents in Counteracting Immune Disorders Induced by Herpes Virus

    Directory of Open Access Journals (Sweden)

    Concetta Gugliandolo

    2015-08-01

    Full Text Available Extreme marine environments, such as the submarine shallow vents of the Eolian Islands (Italy, offer an almost unexplored source of microorganisms producing unexploited and promising biomolecules for pharmaceutical applications. Thermophilic and thermotolerant bacilli isolated from Eolian vents are able to produce exopolysaccharides (EPSs with antiviral and immunomodulatory effects against Herpes simplex virus type 2 (HSV-2. HSV-2 is responsible for the most common and continuously increasing viral infections in humans. Due to the appearance of resistance to the available treatments, new biomolecules exhibiting different mechanisms of action could provide novel agents for treating viral infections. The EPSs hinder the HSV-2 replication in human peripheral blood mononuclear cells (PBMC but not in WISH (Wistar Institute Susan Hayflic cells line, indicating that cell-mediated immunity was involved in the antiviral activity. High levels of Th1-type cytokines were detected in PBMC treated with all EPSs, while Th2-type cytokines were not induced. These EPSs are water soluble exopolymers able to stimulate the immune response and thus contribute to the antiviral immune defense, acting as immunomodulators. As stimulants of Th1 cell-mediated immunity, they could lead to the development of novel drugs as alternative in the treatment of herpes virus infections, as well as in immunocompromised host.

  1. Ag85A DNA Vaccine Delivery by Nanoparticles: Influence of the Formulation Characteristics on Immune Responses.

    Science.gov (United States)

    Poecheim, Johanna; Barnier-Quer, Christophe; Collin, Nicolas; Borchard, Gerrit

    2016-01-01

    The influence of DNA vaccine formulations on immune responses in combination with adjuvants was investigated with the aim to increase cell-mediated immunity against plasmid DNA (pDNA) encoding Mycobacterium tuberculosis antigen 85A. Different ratios of pDNA with cationic trimethyl chitosan (TMC) nanoparticles were characterized for their morphology and physicochemical characteristics (size, zeta potential, loading efficiency and pDNA release profile) applied in vitro for cellular uptake studies and in vivo, to determine the dose-dependent effects of pDNA on immune responses. A selected pDNA/TMC nanoparticle formulation was optimized by the incorporation of muramyl dipeptide (MDP) as an immunostimulatory agent. Cellular uptake investigations in vitro showed saturation to a maximum level upon the increase in the pDNA/TMC nanoparticle ratio, correlating with increasing Th1-related antibody responses up to a definite pDNA dose applied. Moreover, TMC nanoparticles induced clear polarization towards a Th1 response, indicated by IgG2c/IgG1 ratios above unity and enhanced numbers of antigen-specific IFN-γ producing T-cells in the spleen. Remarkably, the incorporation of MDP in TMC nanoparticles provoked a significant additional increase in T-cell-mediated responses induced by pDNA. In conclusion, pDNA-loaded TMC nanoparticles are capable of provoking strong Th1-type cellular and humoral immune responses, with the potential to be further optimized by the incorporation of MDP. PMID:27626449

  2. 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...

  3. Recording information about immunizations

    OpenAIRE

    Gadsby, Roger

    1980-01-01

    The recording of information on triple plus polio and rubella immunizations is reviewed and immunization rates determined for patients in a single-handed practice. Rates of triple plus polio immunizations are satisfactory but rates for rubella immunization are very poor. Immunization information is not exchanged between different sections of the Health Service in Stoke-on-Trent and so the general practitioner has no reliable immunization record for his patients.

  4. Immunization with chlamydial plasmid protein pORF5 DNA vaccine induces protective immunity against genital chlamydial infection in mice

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    To validate the immune protective efficacy of pORF5 DNA vaccine and to analyze potential mechanisms related to this protection. In this study, pORF5 DNA vaccine was constructed and evaluated for its protective immunity in a mouse model of genital chlamydial infection. Groups of BALB/c mice were immunized intranasally with pORF5 DNA vaccine. Humoral and cell mediated immune responses were evaluated. The clearance ability of chlamydial challenge from the genital tract and the chlamy- dia-induced upper genital tract gross pathology and histopathological characterization were also de- tected. The results showed that the total and the IgG2a anti-pORF5 antibody levels in serum were sig- nificantly elevated after pcDNA3.1-pORF5 vaccination, as were the total antibody and IgA levels in vaginal fluids. pcDNA3.1-pORF5 induced a significantly high level of Th1 response as measured by robust gamma interferon (IFN-γ). Minimal IL-4 was produced by immune T cells in response to the re-stimulation with pORF5 protein or the inactive elementary body in vitro. pcDNA3.1-pORF5-vacci- nated mice displayed significantly reduced bacterial shedding upon a chlamydial challenge and an accelerated resolution of infection. 100% of pcDNA3.1-pORF5 vaccinated mice successfully resolved the infection by day 24. pcDNA3.1-pORF5-immunized mice also exhibited protection against patho- logical consequences of chlamydial infection. The stimulated index was significantly higher than that of mice immunized with pcDNA3.1 and PBS (P<0.05). Together, these results demonstrated that immu- nization with pORF5 DNA vaccine is a promising approach for eliciting a protective immunity against a genital chlamydial challenge.

  5. Mechanisms of immunological eradication of a syngeneic guinea pig tumor. II. Effect of methotrexate treatment and T cell depletion of the recipient on adoptive immunity

    International Nuclear Information System (INIS)

    The influence of methotrexate on the development of immunity to the line 10 hepatoma was studied in guinea pigs. Chronic methotrexate treatment had no apparent effect on the ability of immune guinea pigs to suppress the growth of inoculated tumor cells. In contrast, the same methotrexate regimen inhibited the development of tumor immunity if started before the 8th day after immunization with a vaccine containing viable line 10 cells admixed with Bacillus Calmette-Guerin (BCG) cell walls. Thus, methotrexate selectively inhibited the afferent limb of the immune response. In adoptive transfer experiments, methotrexate-treated recipient guinea pigs were capable of being passively sensitized with immune spleen cells, indicating that the primary cell-mediated immune response of the recipient was not required for adoptive immunity. The contribution of recipient T cells in adoptive immunity was further investigated in guinea pigs deleted of T cells by thymectomy, irradiation, and bone marrow reconstitution. Despite demonstrable deficiency in T lymphocyte reactions, B animals were fully capable of rejecting tumors after transfer of immune cells. These results suggest that the expression of adoptive immunity was independent of recipient T cell participation. In addition, sublethal irradiation of immune spleen cells prior to adoptive transfer abolished their efficacy. Proliferation of transferred immune cells in the recipient may be essential for expression of adoptive immunity

  6. DNA vaccine encoding L7/L12-P39 of Brucella abortus induces protective immunity in BALB/c mice

    Institute of Scientific and Technical Information of China (English)

    LUO De-yan; LI Peng; XING Li; ZHAO Guang-yu; SHI Wei; ZHANG Song-le; WANG Xi-liang

    2006-01-01

    @@ Brucella abortus is a gram-negative, facultative, intracellular bacterium that infects both cattle and humans, causing abortion and infertility in the former and undulant fever, endocarditis, arthritis, and osteomyelitis. Resistance to Brucella depends on acquired cell-mediated immunity (CMI).1 Live attenuated vaccines can stimulate strong CMI response, which are usually very effective against brucellosis and are used to control brucellosis in domestic animals. However, there is no safe and effective vaccine available for human because the vaccine strains used for animals are considered too virulent for humans. A vaccine that will be noninfectious to humans but effective in stimulating a broad protective immune response is needed.2

  7. Short communication: Variation in production parameters among Canadian Holstein cows classified as high, average, and low immune responders.

    Science.gov (United States)

    Stoop, C L; Thompson-Crispi, K A; Cartwright, S L; Mallard, B A

    2016-06-01

    Dairy cattle evaluated for immune responses and identified as high responders are known to have a lower occurrence of economically important diseases, including mastitis, metritis, ketosis, and retained placenta. These high immune responders have also been shown to make more antibody following vaccination and to have improved milk and colostrum quality. Therefore, breeding for improved immune response is expected to have several benefits in the dairy industry. However, a concern of such an approach to improve animal health is the potential cost of lost production due to an allocation of host resources to mount a robust immune response. The objective of this study was to evaluate early- and late-lactation production parameters in cattle classified as having high, average, or low estimated breeding values (EBV) for cell-mediated (CMIR), antibody-mediated (AMIR), and overall immune responses. A total of 561 cows from 6 herds were phenotyped for immune response and ranked based on EBV for CMIR and AMIR. A linear animal model was used to evaluate differences in milk, fat, and protein yields among immune response groups, and a regression analysis was conducted based on immune response EBV. Overall, no difference in production parameters was found based on immune response rank; however, some positive relationships with immune response EBV were found, suggesting that breeding for enhanced immune responsiveness as a prophylactic approach to improve animal health would not come at the cost of lost production. PMID:27060821

  8. 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.

  9. 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

  10. Antimicrobial peptide LL-37 promotes antigen-specific immune responses in mice by enhancing Th17-skewed mucosal and systemic immunities.

    Science.gov (United States)

    Kim, Sae-Hae; Yang, In-Young; Kim, Ju; Lee, Kyung-Yeol; Jang, Yong-Suk

    2015-05-01

    The human antimicrobial peptide LL-37 is known to have chemotactic and modulatory activities on various cells including monocytes, T cells, and epithelial cells. Given that LL-37 enhances chemotactic attraction and modulates the activity of DCs, it is conceivable that it might play a role as an immune adjuvant by skewing the immune environment toward immunostimulatory conditions. In this study, we characterized the mucosal adjuvant activity of LL-37 using model and pathogenic Ags. When LL-37-conjugated Ag was administered orally to mice, a tolerogenic Peyer's patch environment was altered to cell populations containing IL-6-secreting CD11c(+), CD11c(+) CD70(+), and Th17 cells capable of evoking a subsequent LL-37-conjugated Ag-specific immune response in both systemic and mucosal immune compartments. In addition, we showed presentation of formyl peptide receptor, an LL-37 receptor, on M cells, which may aid the initiation of an LL-37-mediated enhanced immune response through targeting and transcytosis of the conjugated Ag. Based on our findings, we conclude that LL-37 has potential as an oral mucosal adjuvant, not only by enhancing the delivery of LL-37-conjugated Ag to M cells, but also by triggering T-cell-mediated Ag-specific immune responses through modulation of the mucosal immune environment.

  11. Our Immune System

    Science.gov (United States)

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

  12. The Ameliorative Effect of Sophoricoside on Mast Cell-Mediated Allergic Inflammation in Vivo and in Vitro

    Directory of Open Access Journals (Sweden)

    Jae-Young Um

    2013-05-01

    Full Text Available Sophoricoside exhibits numerous pharmacological effects, including anti- inflammatory and anti-cancer actions, yet the exact mechanism that accounts for the anti-allergic effects of sophoricoside is not completely understood. The aim of the present study was to elucidate whether and how sophoricoside modulates the mast cell-mediated allergic inflammation in vitro and in vivo. We investigated the pharmacological effects of sophoricoside on both compound 48/80 or histamine-induced scratching behaviors and 2,4-dinitrochlorobenzene (DNCB-induced atopic dermatitis in mice. Additionally, to find a possible explanation for the anti-inflammatory effects of sophoricoside, we evaluated the effects of sophoricoside on the production of histamine and inflammatory cytokines and activation of nuclear factor-κB (NF-κB and caspase-1 in phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI-stimulated human mast cells (HMC-1. The finding of this study demonstrated that sophoricoside reduced compound 48/80 or histamine-induced scratching behaviors and DNCB-induced atopic dermatitis in mice. Additionally, sophoricoside inhibited the production of inflammatory cytokines as well as the activation of NF-κB and caspase-1 in stimulated HMC-1. Collectively, the findings of this study provide us with novel insights into the pharmacological actions of sophoricoside as a potential molecule for use in the treatment of allergic inflammation diseases.

  13. Pig but not Human Interferon-γ Initiates Human Cell-Mediated Rejection of Pig Tissue in vivo

    Science.gov (United States)

    Sultan, Parvez; Murray, Allan G.; McNiff, Jennifer M.; Lorber, Marc I.; Askenase, Philip W.; Bothwell, Alfred L. M.; Pober, Jordan S.

    1997-08-01

    Split-thickness pig skin was transplanted on severe combined immunodeficient mice so that pig dermal microvessels spontaneously inosculated with mouse microvessels and functioned to perfuse the grafts. Pig endothelial cells in the healed grafts constitutively expressed class I and class II major histocompatibility complex molecules. Major histocompatibility complex molecule expression could be further increased by intradermal injection of pig interferon-γ (IFN-γ ) but not human IFN-γ or tumor necrosis factor. Grafts injected with pig IFN-γ also developed a sparse infiltrate of mouse neutrophils and eosinophils without evidence of injury. Introduction of human peripheral blood mononuclear cells into the animals by intraperitoneal inoculation resulted in sparse perivascular mononuclear cell infiltrates in the grafts confined to the pig dermis. Injection of pig skin grafts on mice that received human peripheral blood mononuclear cells with pig IFN-γ (but not human IFN-γ or heat-inactivated pig IFN-γ ) induced human CD4+ and CD8+ T cells and macrophages to more extensively infiltrate the pig skin grafts and injure pig dermal microvessels. These findings suggest that human T cell-mediated rejection of xenotransplanted pig organs may be prevented if cellular sources of pig interferon (e.g., passenger lymphocytes) are eliminated from the graft.

  14. Comparison of Th1- and Th2-associated immune reactivities stimulated by single versus multiple vaccination of mice with irradiated Schistosoma mansoni cercariae

    Energy Technology Data Exchange (ETDEWEB)

    Caulada-Benedetti, Z.; Al-Zamel, F.; Sher, A.; James, S. (NIAID, Bethesda, MD (USA))

    1991-03-01

    Mice immunized against Schistosoma mansoni by a single percutaneous exposure to radiation-attenuated parasite larvae demonstrate partial resistance to challenge infection that has been shown to correlate with development of cell-mediated immunity, whereas mice hyperimmunized by multiple exposure to attenuated larvae produce antibodies capable of transferring partial protection to naive recipients. Measurement of Ag-specific lymphokine responses in these animals suggested that the difference in resistance mechanisms may be due to the differential induction of Th subset response by the two immunization protocols. Thus, upon Ag stimulation, singly immunized mice predominantly demonstrated responses associated with Th1 reactivity, including IL-2 and IFN-gamma production, whereas multiply immunized animals showed increased IL-5, IL-4, and IgG1 antibody production associated with enhanced Th2 response. These responses demonstrated some degree of organ compartmentalization, with splenocytes demonstrating higher Th1-related lymphokine production and cells from draining lymph nodes showing stronger proliferation and Th2 type reactivity. However, hyperimmunized mice also continued to demonstrate substantial Th1-associated immune reactivity. Moreover, in vivo Ag challenge elicited activated larvacidal macrophages in hyperimmunized animals. These observations indicate that protective cell-mediated mechanisms associated with induction of CD4+ Th1 cell reactivity predominate in singly vaccinated mice. Further vaccination stimulates Th2 responses, such as enhanced IgG1 production, that may also contribute to protective immunity.

  15. 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.

  16. Understanding Herd Immunity.

    Science.gov (United States)

    Metcalf, C J E; Ferrari, M; Graham, A L; Grenfell, B T

    2015-12-01

    Individual immunity is a powerful force affecting host health and pathogen evolution. Importantly, the effects of individual immunity also scale up to affect pathogen transmission dynamics and the success of vaccination campaigns for entire host populations. Population-scale immunity is often termed 'herd immunity'. Here we outline how individual immunity maps to population outcomes and discuss implications for control of infectious diseases. Particular immunological characteristics may be more or less likely to result in a population level signature of herd immunity; we detail this and also discuss other population-level outcomes that might emerge from individual-level immunity.

  17. 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.

  18. The Xs and Y of immune responses to viral vaccines.

    Science.gov (United States)

    Klein, Sabra L; Jedlicka, Anne; Pekosz, Andrew

    2010-05-01

    The biological differences associated with the sex of an individual are a major source of variation, affecting immune responses to vaccination. Compelling clinical data illustrate that men and women differ in their innate, humoral, and cell-mediated responses to viral vaccines. Sex affects the frequency and severity of adverse effects of vaccination, including fever, pain, and inflammation. Pregnancy can also substantially alter immune responses to vaccines. Data from clinical trials and animal models of vaccine efficacy lay the groundwork for future studies aimed at identifying the biological mechanisms that underlie sex-specific responses to vaccines, including genetic and hormonal factors. An understanding and appreciation of the effect of sex and pregnancy on immune responses might change the strategies used by public health officials to start efficient vaccination programmes (optimising the timing and dose of the vaccine so that the maximum number of people are immunised), ensure sufficient levels of immune responses, minimise adverse effects, and allow for more efficient protection of populations that are high priority (eg, pregnant women and individuals with comorbid conditions).

  19. Intratumoral interleukin-21 increases antitumor immunity, tumor-infiltrating CD8+ T-cell density and activity, and enlarges draining lymph nodes

    DEFF Research Database (Denmark)

    Søndergaard, Henrik; Galsgaard, Elisabeth D; Bartholomaeussen, Monica;

    2010-01-01

    , and investigated the mechanisms by which IL-21 enhances CD8 T-cell-mediated antitumor immunity. We found that in comparison to subcutaneous administration, IT administration of IL-21 more potently inhibited tumor growth and increased survival. This correlated with increased densities of tumor-infiltrating CD8...... of IT administration of IL-21 was due to a local rather than systemic effect. IT administration of IL-21 led to enlarged tumor-draining lymph nodes (LNs), with increased naive lymphocyte numbers and proliferation of activated lymphocytes, suggesting that local administration of IL-21 generally benefits the tumor...... microenvironment and activates tumor-draining LNs. Overall, our data suggest that IL-21 augments CD8 T-cell-mediated antitumor immunity through increased proliferation and effector function and acts both on tumor-infiltrating CD8 T cells as well as on the draining LNs. IT administration led to superior CD8 T...

  20. 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

  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 appropr......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. 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.

  3. Effects of Probiotic and Prebiotic on Average Daily Gain, Fecal Shedding of Escherichia Coli, and Immune System Status in Newborn Female Calves

    OpenAIRE

    Roodposhti, Pezhman Mohamadi; Dabiri, Najafgholi

    2012-01-01

    Thirty two Holstein female calves (initial body weight = 40±3.0 kg) were used to investigate the effects of probiotic and prebiotic on average daily gain (ADG), fecal E. coli count, white blood cell count, plasma IgG1 level and cell-mediated immune response to injection of phytohemagglutinin in suckling female calves. Calves were assigned randomly to one of the four treatments, including whole milk without additives (control), whole milk containing probiotic, whole milk containing prebiotic a...

  4. Tomatine Adjuvantation of Protective Immunity to a Major Pre-erythrocytic Vaccine Candidate of Malaria is Mediated via CD8+ T Cell Release of IFN-γ

    OpenAIRE

    Heal, Karen G.; Taylor-Robinson, Andrew W.

    2010-01-01

    The glycoalkaloid tomatine, derived from the wild tomato, can act as a powerful adjuvant to elicit an antigen-specific cell-mediated immune response to the circumsporozoite (CS) protein, a major pre-erythrocytic stage malaria vaccine candidate antigen. Using a defined MHC-class-I-restricted CS epitope in a Plasmodium berghei rodent model, antigen-specific cytotoxic T lymphocyte activity and IFN-γ secretion ex vivo were both significantly enhanced compared to responses detected from similarly ...

  5. 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, ...

  6. Separation of effector cells mediating antibody-dependent cellular cytotoxicity (ADC) to erythrocyte targets from those mediating ADC to tumor targets.

    Science.gov (United States)

    Pollack, S B; Nelson, K; Grausz, J D

    1976-04-01

    Murine spleen cells mediate antibody-dependent cellular cytotoxicity (ADC) both to erythrocyte targets in a 51Cr release assay and to syngeneic tumor targets in a microcytotoxicity assay. The effector cells active in the two ADC assays can be separated by passage of the spleen cells through columns of Sephadex G-10 at 37 degrees C. Cells mediating ADC to sarcoma cells did not adhere to the G-10 and were recovered in the column effluent. These nonadherent cells were not cytotoxic to antibody-coated chicken red blood cells. Spleen cells which mediated ADC in a 51Cr release assay to the red cell targets adhered to G-10. Adherent effector cells could subsequently be recovered from the columns by elution with 5 X 10(-4) M EDTA. PMID:815438

  7. [The cellular immunity indices of patients with malignant melanoma using the viral immunomodulator rigvir].

    Science.gov (United States)

    Glinkina, L S; Bruvere, R Zh; Venskus, D R; Garklava, R R; Muceniece, A J

    1992-01-01

    The effect of rigvir, an immunomodulator of the viral origin, on cell-mediated immunity was studied in patients with skin malignant melanoma. Rosette formation and monoclonal antibody techniques were used to measure blood immunocompetent cell levels in patients with the above pathology, cases of benign skin tumors and healthy subjects. Rigvir was shown to influence natural resistance by raising blood monocyte and large granule-containing lymphocyte levels. It potentiated recruitment of pre-T-lymphocytes and young active T-lymphocytes to the peripheral blood. PMID:1300752

  8. Antibody-dependent cell-mediated cytotoxicity (ADCC) toward human O+ red cells coated with anti-D antibody: comparison between lymphocyte and monocyte ADCC activity.

    OpenAIRE

    Sunada,Mitsutoshi; Suzuki, Shinya; Ota, Zensuke

    1985-01-01

    We investigated the antibody dependent cell-mediated cytotoxicity (ADCC) of lymphocytes and monocytes toward human O+ red cells coated with anti-D antibody using a 51Cr release assay. Lysis of sensitized red cells by lymphocytes occurred rapidly, but monocyte-mediated lysis occurred slowly. This difference might be due to postphagocytic 51Cr release by monocytes. ADCC of lymphocytes increased in proportion to the effector cell number, but large amounts of antibodies were required. In contrast...

  9. Development of IgG Mediated Antibody Dependent Cell-mediated Cytotoxicity (ADCC) in the Serum and Genital Mucosa of HIV Seroconverters

    OpenAIRE

    Aziz, Mariam; Mahmood, Fareeha; Mata, Mariana; Durkin, Helen G.; Liu, Chenglong; Greenblatt, Ruth M.; Nowicki, Marek; Elizabeth T Golub; Anastos, Kathryn; French, Audrey L.; Baum, Linda L.

    2015-01-01

    Background We measured antibody-dependent cell mediated cytotoxicity (ADCC) activity in serum and genital fluids of heterosexually exposed women during HIV seroconversion. Methods Plasma and cervico-vaginal lavage (CVL) fluid from 11 seroconverters (SC) were analyzed biannually from one year pre- to 6 year post-seroconversion using a 51Cr-release assay to measure HIV-1 gp120 specific ADCC. Results No SC had significant HIV specific CVL ADCC activity before seroconversion or until 1.5 yr after...

  10. 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

  11. An impedance-based cytotoxicity assay for real-time and label-free assessment of T-cell-mediated killing of adherent cells.

    Science.gov (United States)

    Peper, Janet Kerstin; Schuster, Heiko; Löffler, Markus W; Schmid-Horch, Barbara; Rammensee, Hans-Georg; Stevanović, Stefan

    2014-03-01

    The in vitro assessment of T-cell-mediated cytotoxicity plays an important and increasingly relevant role both in preclinical target evaluation and during immunomonitoring to accompany clinical trials employing targeted immunotherapies. For a long time, the gold standard for this purpose has been the chromium release assay (CRA). This end point assay, however, shows several disadvantages including the inevitable use of radioactivity. Based on electrical impedance measurements (using the xCELLigence system), we have established a label-free assay, facilitating the real-time monitoring of T-cell-mediated cytotoxicity. The coculture of peptide-specific T-cell lines with peptide-loaded target cells reproducibly led to a decrease in impedance due to induced apoptosis and detachment of target cells. Comparing our results to the standard CRA assay, we could demonstrate that impedance-based measurements show comparable results after short incubation periods (6h) but outperform the CRA both in reproducibility and sensitivity after prolonged incubation (24h), enabling the detection of target cell lysis with an effector to target ratio as low as 0.05:1. The impedance-based assay represents a valuable and highly sensitive tool for label-free real-time high throughput analysis of T-cell-mediated cytotoxicity.

  12. Immune Responses Following Mouse Peripheral Nerve Xenotransplantation in Rats

    Directory of Open Access Journals (Sweden)

    Lai-Jin Lu

    2009-01-01

    Full Text Available Xenotransplantation offers a potentially unlimited source for tissues and organs for transplantation, but the strong xenoimmune responses pose a major obstacle to its application in the clinic. In this study, we investigate the rejection of mouse peripheral nerve xenografts in rats. Severe intragraft mononuclear cell infiltration, graft distension, and necrosis were detected in the recipients as early as 2 weeks after mouse nerve xenotransplantation. The number of axons in xenografts reduced progressively and became almost undetectable at week 8. However, mouse nerve xenotransplantation only led to a transient and moderate increase in the production of Th1 cytokines, including IL-2, IFN-γ, and TNF-α. The data implicate that cellular immune responses play a critical role in nerve xenograft rejection but that further identification of the major effector cells mediating the rejection is required for developing effective means to prevent peripheral nerve xenograft rejection.

  13. H. pylori exploits and manipulates innate and adaptive immune cell signaling pathways to establish persistent infection

    Directory of Open Access Journals (Sweden)

    Arnold Isabelle C

    2011-11-01

    Full Text Available Abstract Persistent infection with the gastric bacterial pathogen Helicobacter pylori causes gastritis and predisposes carriers to a high gastric cancer risk, but has also been linked to protection from allergic, chronic inflammatory and autoimmune diseases. In the course of tens of thousands of years of co-existence with its human host, H. pylori has evolved elaborate adaptations that allow it to persist in the hostile environment of the stomach in the face of a vigorous innate and adaptive immune response. For this review, we have identified several key immune cell types and signaling pathways that appear to be preferentially targeted by the bacteria to establish and maintain persistent infection. We explore the mechanisms that allow the bacteria to avoid detection by innate immune cells via their pattern recognition receptors, to escape T-cell mediated adaptive immunity, and to reprogram the immune system towards tolerance rather than immunity. The implications of the immunomodulatory properties of the bacteria for the prevention of allergic and auto-immune diseases in chronically infected individuals are also discussed.

  14. [Exploration of novel therapeutic targets for neuropathic pain based on the regulation of immune cells].

    Science.gov (United States)

    Kobayashi, Yuka; Kiguchi, Norikazu; Saika, Fumihiro; Kishioka, Shiroh

    2015-06-01

    The pathogenesis of neuropathic pain is quite complicated and diverse. Because pre-existing analgesics, such as opioid analgesics and nonsteroidal anti-inflammatory drugs, are not sufficient to treat it, it is a serious task to establish a strategy of remedy for neuropathic pain. Recently, increasing evidence suggests that immune cell-mediated neuroinflammation in the nervous system induces central and peripheral sensitization, resulting in chronic pain. Initially, the immune system plays an important role in host defense. Although intravital homeostasis is kept constant by innate and adaptive immunity, the immune system is activated excessively due to infection, stress and tissue injury. Activated immune cells produce and release several kinds of inflammatory mediators, which act directly on sensory neurons and promote a recruitment of immune cells, developing the feedback loop of inflammatory exacerbation. We've focused on the role of crosstalk between immune cells and neurons in peripheral neuroinflammation, and explored a novel candidate for a remedy of neuropathic pain. In this review, we will introduce recent reports and our research work that suggest the functional significance of neuroinflammation in neuropathic pain, and survey possibilities of new strategies for chronic pain from the point of view of basic research. PMID:26281298

  15. 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 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 responses and correlates of immunity for scrub typhus. PMID:25601925

  16. Imbalanced immune homeostasis in immune thrombocytopenia.

    Science.gov (United States)

    Yazdanbakhsh, Karina

    2016-04-01

    Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder resulting from low platelet counts caused by inadequate production as well as increased destruction by autoimmune mechanisms. As with other autoimmune disorders, chronic ITP is characterized by perturbations of immune homeostasis with hyperactivated effector cells as well as defective regulatory arm of the adaptive immune system, which will be reviewed here. Interestingly, some ITP treatments are associated with restoring the regulatory imbalance, although it remains unclear whether the immune system is redirected to a state of tolerance once treatment is discontinued. Understanding the mechanisms that result in breakdown of immune homeostasis in ITP will help to identify novel pathways for restoring tolerance and inhibiting effector cell responses. This information can then be translated into developing therapies for averting autoimmunity not only in ITP but also many autoimmune disorders. PMID:27312156

  17. Conditional PDK1 Ablation Promotes Epidermal and T-Cell-Mediated Dysfunctions Leading to Inflammatory Skin Disease.

    Science.gov (United States)

    Yu, Minjun; Owens, David M; Ghosh, Sankar; Farber, Donna L

    2015-11-01

    Phosphoinositide-dependent kinase-1 (PDK1) is a key signaling molecule downstream of the phosphatidylinositol 3-kinase pathway and is a master regulator of multiple kinases in cells of epithelial and hematopoietic lineages. The physiological role of PDK1 in regulating skin and immune homeostasis is not known. Here we developed a mouse model in which PDK1 is conditionally ablated in activated CD4 T cells, regulatory T cells, and mature keratinocytes through OX40-Cre recombinase expression. The resultant mice (PDK1-CKO) spontaneously developed severe dermatitis, skin fibrosis, and systemic T helper type 2 immunity, succumbing by 11 weeks of age. Through a series of T-cell transfers, bone marrow reconstitutions, and crossing to lymphocyte-deficient backgrounds, we demonstrate that ablation of PDK1 in keratinocytes is the major driver of disease pathogenesis. PDK1-deficient keratinocytes exhibit intrinsic defects in the expression of key structural proteins including cytokeratin-10 and loricrin, resulting in increased keratinocyte turnover, which in turn triggers inflammation, T-cell recruitment, and immune-mediated destruction. Our results reveal PDK1 as a central regulator of keratinocyte homeostasis that prevents skin immune infiltration and inflammation. PMID:26099023

  18. Immune System and Disorders

    Science.gov (United States)

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

  19. 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.

  20. Innate immunity and adjuvants

    OpenAIRE

    Akira, Shizuo

    2011-01-01

    Innate immunity was for a long time considered to be non-specific because the major function of this system is to digest pathogens and present antigens to the cells involved in acquired immunity. However, recent studies have shown that innate immunity is not non-specific, but is instead sufficiently specific to discriminate self from pathogens through evolutionarily conserved receptors, designated Toll-like receptors (TLRs). Indeed, innate immunity has a crucial role in early host defence aga...

  1. Immunizations for foreign travel.

    OpenAIRE

    Hill, D. R.

    1992-01-01

    One of the most important aspects of preparing travelers for destinations throughout the world is providing them with immunizations. Before administering any vaccines, however, a careful health and immunization history and travel itinerary should be obtained in order to determine vaccine indications and contraindications. There are three categories of immunizations for foreign travel. The first category includes immunizations which are routinely recommended whether or not the individual is tr...

  2. Biomarkers for immune thrombocytopenia

    OpenAIRE

    Yu, Lingjia; Zhang, Chunmei; Zhang, Liping; Shi, Yongyu; Ji, Xuebin

    2015-01-01

    Immune thrombocytopenia is an autoimmune disease with abnormal biomarkers. Immune thrombocytopenia pathogenesis is a complicated process in which the patient’s immune system is activated by platelet autoantigens resulting in immune mediated platelet destruction or suppression of platelet production. The autoantibodies produced by autoreactive B cells against self antigens are considered to play a crucial role. In addition, biomarkers such as transforming growth factor-beta1,Toll-like receptor...

  3. Aging changes in immunity

    Science.gov (United States)

    ... keeps your immune system strong. DO NOT smoke. Smoking weakens your immune system. Limit your intake of alcohol . Ask your provider how much alcohol is safe for you. Look into safety measures to prevent falls and injuries. A weak immune system can ...

  4. The Immune System Game

    Science.gov (United States)

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

    2015-01-01

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

  5. Immune Disorder HSCT Protocol

    Science.gov (United States)

    2016-01-09

    Immune Deficiency Disorders:; Severe Combined Immunodeficiency; Chronic Granulomatous Disease; X-linked Agammaglobulinemia; Wiskott-Aldrich Syndrome; Hyper-IgM; DiGeorge Syndrome; Chediak-Higashi Syndrome; Common Variable Immune Deficiency; Immune Dysregulatory Disorder:; Hemophagocytic Lymphohistiocytosis; IPEX; Autoimmune Lymphoproliferative Syndrome; X-linked Lymphoproliferative Syndrome

  6. A mathematical model of tumor–immune interactions

    KAUST Repository

    Robertson-Tessi, Mark

    2012-02-01

    A mathematical model of the interactions between a growing tumor and the immune system is presented. The equations and parameters of the model are based on experimental and clinical results from published studies. The model includes the primary cell populations involved in effector T-cell mediated tumor killing: regulatory T cells, helper T cells, and dendritic cells. A key feature is the inclusion of multiple mechanisms of immunosuppression through the main cytokines and growth factors mediating the interactions between the cell populations. Decreased access of effector cells to the tumor interior with increasing tumor size is accounted for. The model is applied to tumors with different growth rates and antigenicities to gauge the relative importance of various immunosuppressive mechanisms. The most important factors leading to tumor escape are TGF-Β-induced immunosuppression, conversion of helper T cells into regulatory T cells, and the limitation of immune cell access to the full tumor at large tumor sizes. The results suggest that for a given tumor growth rate, there is an optimal antigenicity maximizing the response of the immune system. Further increases in antigenicity result in increased immunosuppression, and therefore a decrease in tumor killing rate. This result may have implications for immunotherapies which modulate the effective antigenicity. Simulation of dendritic cell therapy with the model suggests that for some tumors, there is an optimal dose of transfused dendritic cells. © 2011 Elsevier Ltd.

  7. Inflammatory Bowel Disease: Autoimmune or Immune-mediated Pathogenesis?

    Directory of Open Access Journals (Sweden)

    Zhonghui Wen

    2004-01-01

    Full Text Available The pathogenesis of Crohn's disease (CD and ulcerative colitis (UC, the two main forms of inflammatory bowel disease (IBD, is still unclear, but both autoimmune and immune-mediated phenomena are involved. Autoimmune phenomena include the presence of serum and mucosal autoantibodies against intestinal epithelial cells in either form of IBD, and against human tropomyosin fraction five selectively in UC. In addition, perinuclear antineutrophil cytoplasmic antibodies (pANCA are common in UC, whereas antibodies against Saccharomyces cerevisiae (ASCA are frequently found in CD. Immune-mediate phenomena include a variety of abnormalities of humoral and cell-mediated immunity, and a generalized enhanced reactivity against intestinal bacterial antigens in both CD and UC. It is currently believed that loss of tolerance against the indigenous enteric flora is the central event in IBD pathogenesis. Various complementary factors probably contribute to the loss of tolerance to commensal bacteria in IBD. They include defects in regulatory T-cell function, excessive stimulation of mucosal dendritic cells, infections or variants of proteins critically involved in bacterial antigen recognition, such as the products of CD-associated NOD2/CARD15 mutations.

  8. Aryl Hydrocarbon Receptor-Dependent Pathways in Immune Regulation.

    Science.gov (United States)

    Gargaro, M; Pirro, M; Romani, R; Zelante, T; Fallarino, F

    2016-08-01

    The idea of possible involvement of the aryl hydrocarbon receptor (AhR) in transplant tolerance can be traced back >30 years, when very low doses of dioxin-the most potent AhR ligand-were found to markedly reduce the generation of cytotoxic T lymphocytes in response to alloantigen challenge in vivo. AhR is a ligand-activated transcription factor that is activated by dioxins and other environmental pollutants. We now know that AhR can bind a broad variety of activating ligands that are disparate in nature, including endogenous molecules and those formed in the gut from food and bacterial products. Consequently, in addition to its classical role as a toxicological signal mediator, AhR is emerging as a transcription factor involved in the regulation of both innate and adaptive immune responses in various immune cell types, including lymphocytes and antigen-presenting cells (APCs). Allograft rejection is mostly a T cell-mediated alloimmune response initiated by the recognition of alloantigens presented by donor and recipient APCs to recipient CD4(+) and CD8(+) T cells. Based on those findings, AhR may function as a critical sensor of outside and inside environments, leading to changes in the immune system that may have relevance in transplantation. PMID:26751261

  9. 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

  10. IL-13-induced proliferation of airway epithelial cells: mediation by intracellular growth factor mobilization and ADAM17

    Directory of Open Access Journals (Sweden)

    Sandifer Tracy

    2007-07-01

    Full Text Available Abstract Background The pleiotrophic cytokine interleukin (IL-13 features prominently in allergic and inflammatory diseases. In allergic asthma, IL-13 is well established as an inducer of airway inflammation and tissue remodeling. We demonstrated previously that IL-13 induces release of transforming growth factor-α (TGFα from human bronchial epithelial cells, with proliferation of these cells mediated by the autocrine/paracrine action of this growth factor. TGFα exists as an integral membrane protein and requires proteolytic processing to its mature form, with a disintegrin and metalloproteinase (ADAM17 responsible for this processing in a variety of tissues. Methods In this study, normal human bronchial epithelial (NHBE cells grown in air/liquid interface (ALI culture were used to examine the mechanisms whereby IL-13 induces release of TGFα and cellular proliferation. Inhibitors and antisense RNA were used to examine the role of ADAM17 in these processes, while IL-13-induced changes in the intracellular expression of TGFα and ADAM17 were visualized by confocal microscopy. Results IL-13 was found to induce proliferation of NHBE cells, and release of TGFα, in an ADAM17-dependent manner; however, this IL-13-induced proliferation did not appear to result solely from ADAM17 activation. Rather, IL-13 induced a change in the location of TGFα expression from intracellular to apical regions of the NHBE cells. The apical region was also found to be a site of significant ADAM17 expression, even prior to IL-13 stimulation. Conclusion Results from this study indicate that ADAM17 mediates IL-13-induced proliferation and TGFα shedding in NHBE cells. Furthermore, they provide the first example wherein a cytokine (IL-13 induces a change in the intracellular expression pattern of a growth factor, apparently inducing redistribution of intracellular stores of TGFα to the apical region of NHBE cells where expression of ADAM17 is prominent. Thus, IL-13

  11. Immune tolerance induction using fetal directed placental injection in rodent models: a murine model.

    Directory of Open Access Journals (Sweden)

    Kei Takahashi

    Full Text Available Induction of the immune response is a major problem in replacement therapies for inherited protein deficiencies. Tolerance created in utero can facilitate postnatal treatment. In this study, we aimed to induce immune tolerance towards a foreign protein with early gestational cell transplantation into the chorionic villi under ultrasound guidance in the murine model.Pregnant C57BL/6 (B6 mice on day 10 of gestation were anesthetized and imaged by high resolution ultrasound. Murine embryos and their placenta were positioned to get a clear view in B-mode with power mode of the labyrinth, which is the equivalent of chorionic villi in the human. Bone marrow cells (BMCs from B6-Green Fluorescence Protein (B6GFP transgenic mice were injected into the fetal side of the placenta which includes the labyrinth with glass microcapillary pipettes. Each fetal mouse received 2 x 105 viable GFP-BMCs. After birth, we evaluated the humoral and cell-mediated immune response against GFP.Bone marrow transfer into fetal side of placenta efficiently distributed donor cells to the fetal mice. The survival rate of this procedure was 13.5%(5 out of 37. Successful engraftment of the B6-GFP donor skin grafts was observed in all recipient (5 out of 5 mice 6 weeks after birth. Induction of anti-GFP antibodies was completely inhibited. Cytotoxic immune reactivity of thymic cells against cells harboring GFP was suppressed by ELISPOT assay.In this study, we utilized early gestational placental injection targeting the murine fetus, to transfer donor cells carrying a foreign protein into the fetal circulation. This approach is sufficient to induce both humoral and cell-mediated immune tolerance against the foreign protein.

  12. Activation of Toll-like Receptor-2 by Endogenous Matrix Metalloproteinase-2 Modulates Dendritic-Cell-Mediated Inflammatory Responses

    Directory of Open Access Journals (Sweden)

    Emmanuelle Godefroy

    2014-12-01

    Full Text Available Matrix metalloproteinase-2 (MMP-2 is involved in several physiological mechanisms, including wound healing and tumor progression. We show that MMP-2 directly stimulates dendritic cells (DCs to both upregulate OX40L on the cell surface and secrete inflammatory cytokines. The mechanism underlying DC activation includes physical association with Toll-like receptor-2 (TLR2, leading to NF-κB activation, OX40L upregulation on DCs, and ensuing TH2 differentiation. Significantly, MMP-2 polarizes T cells toward type 2 responses in vivo, in a TLR2-dependent manner. MMP-2-dependent type 2 polarization may represent a key immune regulatory mechanism for protection against a broad array of disorders, such as inflammatory, infectious, and autoimmune diseases, which can be hijacked by tumors to evade immunity.

  13. Activation of toll-like receptor-2 by endogenous matrix metalloproteinase-2 modulates dendritic-cell-mediated inflammatory responses.

    Science.gov (United States)

    Godefroy, Emmanuelle; Gallois, Anne; Idoyaga, Juliana; Merad, Miriam; Tung, Navpreet; Monu, Ngozi; Saenger, Yvonne; Fu, Yichun; Ravindran, Rajesh; Pulendran, Bali; Jotereau, Francine; Trombetta, Sergio; Bhardwaj, Nina

    2014-12-11

    Matrix metalloproteinase-2 (MMP-2) is involved in several physiological mechanisms, including wound healing and tumor progression. We show that MMP-2 directly stimulates dendritic cells (DCs) to both upregulate OX40L on the cell surface and secrete inflammatory cytokines. The mechanism underlying DC activation includes physical association with Toll-like receptor-2 (TLR2), leading to NF-κB activation, OX40L upregulation on DCs, and ensuing TH2 differentiation. Significantly, MMP-2 polarizes T cells toward type 2 responses in vivo, in a TLR2-dependent manner. MMP-2-dependent type 2 polarization may represent a key immune regulatory mechanism for protection against a broad array of disorders, such as inflammatory, infectious, and autoimmune diseases, which can be hijacked by tumors to evade immunity.

  14. Activation of Toll-like receptor-2 by endogenous matrix metalloproteinase-2 modulates dendritic cell-mediated inflammatory responses

    Science.gov (United States)

    Godefroy, Emmanuelle; Gallois, Anne; Idoyaga, Juliana; Merad, Miriam; Tung, Navpreet; Monu, Ngozi; Saenger, Yvonne; Fu, Yichun; Nair, Rajesh; Pulendran, Bali; Jotereau, Francine; Trombetta, Sergio; Bhardwaj, Nina

    2015-01-01

    SUMMARY Matrix metalloproteinase-2 (MMP-2) is involved in several physiological mechanisms, including wound healing and tumor progression. We show that MMP-2 directly stimulates dendritic cells (DCs) to both up-regulate OX40L on the cell surface and secrete inflammatory cytokines. The mechanism underlying DC activation includes physical association with Toll-like receptor-2 (TLR2), leading to NF-κB activation, OX40L up-regulation on DCs and ensuing TH2 differentiation. Significantly, MMP-2 polarizes T cells towards type-2 responses in vivo, in a TLR2-dependent manner. MMP-2-dependent type-2 polarization may represent a key immune regulatory mechanism to protect against a broad array of disorders, such as inflammatory, infectious and autoimmune diseases, which can be hijacked by tumors to evade immunity. PMID:25466255

  15. Virus-Specific Antibody, in the Absence of T Cells, Mediates Demyelination in Mice Infected with a Neurotropic Coronavirus

    OpenAIRE

    Kim, Taeg S.; Perlman, Stanley

    2005-01-01

    Mice infected with mouse hepatitis virus strain JHM develop an inflammatory demyelinating disease in the central nervous system with many similarities to human multiple sclerosis. The mouse disease is primarily immune-mediated because demyelination is not detected in JHM-infected mice lacking T or B cells but does occur after transfer of JHM-specific T cells. Although less is known about the ability of antibodies to mediate demyelination, the presence of oligoclonally expanded B cells and hig...

  16. 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...

  17. Interruption of dendritic cell-mediated TIM-4 signaling induces regulatory T cells and promotes skin allograft survival.

    Science.gov (United States)

    Yeung, Melissa Y; McGrath, Martina M; Nakayama, Masafumi; Shimizu, Tetsunosuke; Boenisch, Olaf; Magee, Ciara N; Abdoli, Rozita; Akiba, Hisaya; Ueno, Takuya; Turka, Laurence A; Najafian, Nader

    2013-10-15

    Dendritic cells (DCs) are the central architects of the immune response, inducing inflammatory or tolerogenic immunity, dependent on their activation status. As such, DCs are highly attractive therapeutic targets and may hold the potential to control detrimental immune responses. TIM-4, expressed on APCs, has complex functions in vivo, acting both as a costimulatory molecule and a phosphatidylserine receptor. The effect of TIM-4 costimulation on T cell activation remains unclear. In this study, we demonstrate that Ab blockade of DC-expressed TIM-4 leads to increased induction of induced regulatory T cells (iTregs) from naive CD4(+) T cells, both in vitro and in vivo. iTreg induction occurs through suppression of IL-4/STAT6/Gata3-induced Th2 differentiation. In addition, blockade of TIM-4 on previously activated DCs still leads to increased iTreg induction. iTregs induced under TIM-4 blockade have equivalent potency to control and, upon adoptive transfer, significantly prolong skin allograft survival in vivo. In RAG(-/-) recipients of skin allografts adoptively transferred with CD4(+) T cells, we show that TIM-4 blockade in vivo is associated with a 3-fold prolongation in allograft survival. Furthermore, in this mouse model of skin transplantation, increased induction of allospecific iTregs and a reduction in T effector responses were observed, with decreased Th1 and Th2 responses. This enhanced allograft survival and protolerogenic skewing of the alloresponse is critically dependent on conversion of naive CD4(+) to Tregs in vivo. Collectively, these studies identify blockade of DC-expressed TIM-4 as a novel strategy that holds the capacity to induce regulatory immunity in vivo.

  18. Conditional PDK1 ablation promotes epidermal and T cell-mediated dysfunctions leading to inflammatory skin disease

    OpenAIRE

    Yu, Minjun; Owens, David M.; Ghosh, Sankar; Farber, Donna L.

    2015-01-01

    Phosphoinositide dependent kinase-1 (PDK1) is a key signaling molecule downstream of the phosphatidylinositol 3-kinase (PI-3 kinase) pathway and is a master regulator of multiple kinases in cells of epithelial and hematopoietic lineages. The physiological role of PDK1 in regulating skin and immune homeostasis is not known. Here we developed a mouse model in which PDK1 is conditionally ablated in activated CD4 T cells, regulatory T cells and mature keratinocytes, through OX40-Cre recombinase e...

  19. Costs and benefits of experimentally induced changes in the allocation of growth versus immune function under differential exposure to ectoparasites.

    Directory of Open Access Journals (Sweden)

    Natalia Pitala

    Full Text Available BACKGROUND: Ecological immunology has focused on the costs of investment in immunocompetence. However, understanding optimal resource allocation to immune defence requires also identification of its benefits, which are likely to occur only when parasites are abundant. METHODOLOGY: We manipulated the abundance of parasitic hen fleas in blue tit (Cyanistes caeruleus nests, and supplemented their hosts, the nestlings, with methionine (a sulphur amino acid enhancing cell-mediated immunity during day 3-6. We found a significant interaction between these two experimental factors on the development of immune defences and growth rates. Only in parasitized nests did methionine supplementation boost immune (PHA response, and did nestling with experimentally increased immunocompetence show a relatively faster growth rate than control nestlings between days 6-9. Hence, the allocation of resources into immune defence and its growth-benefits are apparent only in presence of parasites. The main cost of methionine-induced increased allocation to the immune system was an increase in mortality, independently of ectoparasites. Nestlings in all treatments compensated initial growth reduction and all reached equal body size at day 16 (just prior to fledging, indicating a lack of long-term benefits. In addition, methionine treatment tended (P = 0.09 to lower circulating plasma immunoglobulin levels, possibly indicating a trade-off between the cell-mediated and humoral components of the immune system. CONCLUSIONS: We found no strong benefits of an increased investment in immunocompetence in a parasite-rich environment. Any deviation from the growth trajectory (due to changes in allocation induced by methionine is largely detrimental for survival. Hence, while costs are apparent identifying the benefits of investment in immunocompetence during ontogeny is challenging.

  20. 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

  1. Dendritic Cells in Innate and Adaptive Immune Responses against Influenza Virus

    Directory of Open Access Journals (Sweden)

    Artur Summerfield

    2009-11-01

    Full Text Available Dendritic cells (DC are major players in both innate and adaptive immune responses against influenza virus. These immune responses, as well as the important interface between the innate and adaptive systems, are orchestrated by specialized subsets of DC, including conventional steady-state DC, migratory DC and plasmacytoid DC. The characteristics and efficacy of the responses are dependent on the relative activity of these DC subsets, rendering DC crucial for the development of both naïve and memory immune responses. However, due to their critical role, DC also contribute to the immunopathological processes observed during acute influenza, such as that caused by the pathogenic H5N1 viruses. Therein, the role of different DC subsets in the induction of interferon type I, proinflammatory cytokine and chemokine responses is important for the outcome of interaction between the virus and host immune defences. The present review will present current knowledge on this area, relating to the importance of DC activity for the induction of efficacious humoral and cell-mediated immune responses. This will include the main viral elements associated with the triggering or inhibition of DC activation. Finally, the current knowledge on understanding how differences in various vaccines influence the manner of immune defence induction will be presented.

  2. Signatures of T cells as correlates of immunity to Francisella tularensis.

    Directory of Open Access Journals (Sweden)

    Kjell Eneslätt

    Full Text Available Tularemia or vaccination with the live vaccine strain (LVS of Francisella tularensis confers long-lived cell-mediated immunity. We hypothesized that this immunity depends on polyfunctional memory T cells, i.e., CD4(+ and/or CD8(+ T cells with the capability to simultaneously express several functional markers. Multiparametric flow cytometry, measurement of secreted cytokines, and analysis of lymphocyte proliferation were used to characterize in vitro recall responses of peripheral blood mononuclear cells (PBMC to killed F. tularensis antigens from the LVS or Schu S4 strains. PBMC responses were compared between individuals who had contracted tularemia, had been vaccinated, or had not been exposed to F. tularensis (naïve. Significant differences were detected between either of the immune donor groups and naïve individuals for secreted levels of IL-5, IL-6, IL-10, IL-12, IL-13, IFN-γ, MCP-1, and MIP-1β. Expression of IFN-γ, MIP-1β, and CD107a by CD4(+CD45RO(+ or CD8(+CD45RO(+ T cells correlated to antigen concentrations. In particular, IFN-γ and MIP-1β strongly discriminated between immune and naïve individuals. Only one cytokine, IL-6, discriminated between the two groups of immune individuals. Notably, IL-2- or TNF-α-secretion was low. Our results identify functional signatures of T cells that may serve as correlates of immunity and protection against F. tularensis.

  3. Effect of high mobility group box-1 protein on immune cells and its regulatory mechanism

    Institute of Scientific and Technical Information of China (English)

    Ying-yi LUAN; Feng-huaYAO; Qing-hong ZHANG; Xiao-mei ZHU; Ning DONG; Yong-ming YAO

    2012-01-01

    High mobility group box-1 protein (HMGB1),which is a nuclear protein,participates in chromatin architecture and transcriptional regulation.When released from cells,HMGB1 also plays a well-established role as a pro-inflammatory mediator during innate immune responses to injury.In the initial stage of injury,there is a release of large quantities of early pro-inflammatory mediators to initiate or perpetuate immune responses against pathogens,but this pro-inflammatory period is transient,and it is followed by a prolonged period of immune suppression.At present,several lines of evidences have suggested that HMGB1 is a late cytokine provoking delayed endotoxin morbidity,which may enhance the production of early proinflammatory mediators,and it can contribute potently to the activation of different immune cells and play a role in the development of host cell-mediated immunity.The biology of HMGB1 has been extensively studied as a pro-inflammatory cytokine of systemic inflammation,however,this review will attempt to provide a summary of the effects of HMGB1 on different immune cells and its regulatory mechanism in acute insults.

  4. Immune Adjuvant Effect of Molecularly-defined Toll-Like Receptor Ligands

    Directory of Open Access Journals (Sweden)

    Deana N. Toussi

    2014-04-01

    Full Text Available Vaccine efficacy is optimized by addition of immune adjuvants. However, although adjuvants have been used for over a century, to date, only few adjuvants are approved for human use, mostly aimed at improving vaccine efficacy and antigen-specific protective antibody production. The mechanism of action of immune adjuvants is diverse, depending on their chemical and molecular nature, ranging from non-specific effects (i.e., antigen depot at the immunization site to specific activation of immune cells leading to improved host innate and adaptive responses. Although the detailed molecular mechanism of action of many adjuvants is still elusive, the discovery of Toll-like receptors (TLRs has provided new critical information on immunostimulatory effect of numerous bacterial components that engage TLRs. These ligands have been shown to improve both the quality and the quantity of host adaptive immune responses when used in vaccine formulations targeted to infectious diseases and cancer that require both humoral and cell-mediated immunity. The potential of such TLR adjuvants in improving the design and the outcomes of several vaccines is continuously evolving, as new agonists are discovered and tested in experimental and clinical models of vaccination. In this review, a summary of the recent progress in development of TLR adjuvants is presented.

  5. 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

  6. Simultaneous immunization against tuberculosis.

    Directory of Open Access Journals (Sweden)

    Elma Z Tchilian

    Full Text Available BACKGROUND: BCG, the only licensed vaccine against tuberculosis, provides some protection against disseminated disease in infants but has little effect on prevention of adult pulmonary disease. Newer parenteral immunization prime boost regimes may provide improved protection in experimental animal models but are unproven in man so that there remains a need for new and improved immunization strategies. METHODS AND FINDINGS: Mice were immunized parenterally, intranasally or simultaneously by both routes with BCG or recombinant mycobacterial antigens plus appropriate adjuvants. They were challenged with Mycobacterium tuberculosis (Mtb and the kinetics of Mtb growth in the lungs measured. We show that simultaneous immunization (SIM of mice by the intranasal and parenteral routes is highly effective in increasing protection over parenteral BCG administration alone. Intranasal immunization induces local pulmonary immunity capable of inhibiting the growth of Mtb in the early phase (the first week of infection, while parenteral immunization has a later effect on Mtb growth. Importantly, these two effects are additive and do not depend on priming and boosting the immune response. The best SIM regimes reduce lung Mtb load by up to 2 logs more than BCG given by either route alone. CONCLUSIONS: These data establish SIM as a novel and highly effective immunization strategy for Mtb that could be carried out at a single clinic visit. The efficacy of SIM does not depend on priming and boosting an immune response, but SIM is complementary to prime boost strategies and might be combined with them.

  7. Participation of CD45, NKR-P1A and ANK61 antigen in rat hepatic NK cell (pit cell)-mediated target cell cytotoxicity

    Institute of Scientific and Technical Information of China (English)

    Dian Zhong Luo; David Vermijlen; B lent Ahishali; Vasilis Triantis; Eddie Wisse; Karin Vanderkerken; Peter J.K. Kuppen

    2000-01-01

    AIM Several triggering receptors have been described to be involved in natural killer (NK) cellmediated target cytotoxicity. In these studies, NK cells derived from blood or spleen were used. Pit cells are liver-specific NK cells that possess a higher level of natural cytotoxicity and a different morphology when compared to blood NK cells. The aim of this study was to characterize the role of the NK-triggering molecules NKR-P1A, ANK61 antigen, and CD45 in pit cell-mediated killing of target cells. METHODS 51 Cr-release and DNA fragmentation were used to quantify target cell lysis and apoptosis, respectively. RESULTS Flow cytometric analysis showed that pit cells expressed CD45, NKR-P1A, and ANK61 antigen. Treatment of pit cells with monoclonal antibody ( mAb ) to CD45 ( ANK74 ) not only inhibited CC531s or YAC-1 target lysis but also apoptosis induced by pit cells. The mAbs to NKRP1A (3.2.3) and ANK61 antigen (ANK61) had no effect on pit cell-mediated CC531s or YAC-1 target cytolysis or apoptosis, while they did increase the Fcγ receptor positive (FcγR+) P815 cytolysis and apoptosis. This enhanced cytotoxicity could he inhibited by 3,4-dichloroisocoumarin, an inhibitor of granzymes. CONCLUSION These results indicate that CD45 participates in pit cell-mediated CC531s and YAC-1 target cytolysis and apoptosis. NKR-P1A and ANK61 antigen on pit cells function as activation structures against FcγR+ P815 cells, which was mediated by the perforin/granzyme pathway.

  8. 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

  9. Commensal-induced regulatory T cells mediate protection against pathogen-stimulated NF-kappaB activation.

    Directory of Open Access Journals (Sweden)

    Caitlin O'Mahony

    Full Text Available Host defence against infection requires a range of innate and adaptive immune responses that may lead to tissue damage. Such immune-mediated pathologies can be controlled with appropriate T regulatory (Treg activity. The aim of the present study was to determine the influence of gut microbiota composition on Treg cellular activity and NF-kappaB activation associated with infection. Mice consumed the commensal microbe Bifidobacterium infantis 35624 followed by infection with Salmonella typhimurium or injection with LPS. In vivo NF-kappaB activation was quantified using biophotonic imaging. CD4+CD25+Foxp3+ T cell phenotypes and cytokine levels were assessed using flow cytometry while CD4+ T cells were isolated using magnetic beads for adoptive transfer to naïve animals. In vivo imaging revealed profound inhibition of infection and LPS induced NF-kappaB activity that preceded a reduction in S. typhimurium numbers and murine sickness behaviour scores in B. infantis-fed mice. In addition, pro-inflammatory cytokine secretion, T cell proliferation, and dendritic cell co-stimulatory molecule expression were significantly reduced. In contrast, CD4+CD25+Foxp3+ T cell numbers were significantly increased in the mucosa and spleen of mice fed B. infantis. Adoptive transfer of CD4+CD25+ T cells transferred the NF-kappaB inhibitory activity. Consumption of a single commensal micro-organism drives the generation and function of Treg cells which control excessive NF-kappaB activation in vivo. These cellular interactions provide the basis for a more complete understanding of the commensal-host-pathogen trilogue that contribute to host homeostatic mechanisms underpinning protection against aberrant activation of the innate immune system in response to a translocating pathogen or systemic LPS.

  10. Effect of Green Tea Extract on T cell Mediated Hypersensitivity Reaction in BALB/c Mice Exposed to Gamma Irradiation

    International Nuclear Information System (INIS)

    Gamma radiation is widely used in the treatment of malignant neoplasms. However, it deprives the host immune function which may retard tumor rejection by the immune response. The main purpose of the present study is to test the ability of green tea dry extract to restore the T cell hypersensitivity reaction in gamma irradiated BALB/c mice. It aims also to elucidate the possible mechanism of action of ionizing radiation and green tea dry extract in the immune function. Four groups of BALB/c mice, each of ten, have been used in each experiment. The first group served as a control, the second group received green tea dry extract and the third group was exposed to 2 Gy gamma irradiation, while the fourth group received green tea dry extract before and after gamma irradiation. The following parameters were determined, the contact sensitivity reaction by the mouse ear swelling response, local dendritic cell migration, local lymph node weight, lymphocyte proliferation, spleen and thymus weight with their lymphocyte count. The effect of gamma irradiation and green tea dry extract on the elicitation phase of contact sensitivity was also determined. Data from the present study showed that gamma irradiation caused a significant decrease of the mouse ear swelling response and retarded dendritic cell migration. They also showed a significant decline in the lymphocytes proliferation in lymph node draining the contact sensitizer application. Total body exposure to 2 Gy gamma irradiation induced marked decline of thymus weight and thymocyte count, while it reduced spleen weight and spleenocyte count to a lesser extent. Exposure to gamma irradiation enhanced the elicitation phase of contact sensitivity. Administration of green tea dry extract partially preserved the contact sensitivity response to oxazolone in gamma irradiated BALB/c mice. It markedly minimized the enhancement of the elicitation phase of ear swelling. In conclusion, the present study heralds a beneficial role of

  11. Sarcomas as a mise en abyme of mesenchymal stem cells: exploiting interrelationships for cell mediated anticancer therapy

    DEFF Research Database (Denmark)

    Burns, Jorge S; Safwat, Akmal; Grisendi, Giulia;

    2012-01-01

    Mise en abyme meaning "placed into abyss or infinite recurrence" is an apt paradigm for the relentless growth of sarcoma cells. Its alternative meaning, "self-reflexive embedding" fits the central role attributed to cancer stem cells (CSCs). Diversely sourced and defined, mesenchymal stem cells...... (MSCs) may be the cells of sarcoma origin, evolve a CSC phenotype and/or contribute to tumor growth through inherent qualities for homing, neovascularization, paracrine cross-feeding, microvesicle secretion, cell fusion, entosis and immune modulation. Exploiting these qualities, MSC expressing modified...

  12. Proteomics and insect immunity

    Directory of Open Access Journals (Sweden)

    L Shi

    2006-01-01

    Full Text Available Insect innate immunity is both a model for vertebrate immunity as well as a key system that impactsmedically important pathogens that are transmitted by insects. Recent developments in proteomics andprotein identification techniques combined with the completion of genome sequences for Anophelesgambiae and Drosophila melanogaster provided the tools for examining insect immunity at a new level ofmolecular detail. Application of proteomics to insect immunity resulted in predictions of new roles inimmunity for proteins already known in other contexts (e.g. ferritin, transferrin, Chi-lectins and helped totarget specific members of multi-gene families that respond to different pathogens (e.g. serine proteases,thioester proteins. In addition, proteomics studies verify that post-translational modifications play a keyrole in insect immunity since many of the identified proteins are modified in some way. These studiescomplement recent work on insect transcriptomes and provide new directions for further investigation ofinnate immunity.

  13. 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

  14. 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.

  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. 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.

  17. 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.

  18. T cell metabolism. The protein LEM promotes CD8⁺ T cell immunity through effects on mitochondrial respiration.

    Science.gov (United States)

    Okoye, Isobel; Wang, Lihui; Pallmer, Katharina; Richter, Kirsten; Ichimura, Takahuru; Haas, Robert; Crouse, Josh; Choi, Onjee; Heathcote, Dean; Lovo, Elena; Mauro, Claudio; Abdi, Reza; Oxenius, Annette; Rutschmann, Sophie; Ashton-Rickardt, Philip G

    2015-05-29

    Protective CD8(+) T cell-mediated immunity requires a massive expansion in cell number and the development of long-lived memory cells. Using forward genetics in mice, we identified an orphan protein named lymphocyte expansion molecule (LEM) that promoted antigen-dependent CD8(+) T cell proliferation, effector function, and memory cell generation in response to infection with lymphocytic choriomeningitis virus. Generation of LEM-deficient mice confirmed these results. Through interaction with CR6 interacting factor (CRIF1), LEM controlled the levels of oxidative phosphorylation (OXPHOS) complexes and respiration, resulting in the production of pro-proliferative mitochondrial reactive oxygen species (mROS). LEM provides a link between immune activation and the expansion of protective CD8(+) T cells driven by OXPHOS and represents a pathway for the restoration of long-term protective immunity based on metabolically modified cytotoxic CD8(+) T cells.

  19. Update on the use of intravenous immune globulin in the treatment of patients with inflammatory muscle disease.

    Science.gov (United States)

    Dalakas, M C

    1995-11-01

    The inflammatory myopathies consist of three distinct groups: dermatomyositis, polymyositis, and inclusion body myositis. Dermatomyositis is distinguished by its characteristic rash, while polymyositis is a diagnosis of exclusion. Inclusion body myositis is characterized by early involvement of distal muscle groups and the quadriceps. Definitive diagnosis is made by muscle biopsy, which demonstrates histological features characteristic for each disorder. Immune mechanisms play a role in the pathogenesis of the inflammatory myopathies. A complement-mediated microangiopathy is seen in dermatomyositis, while there is evidence for a T cell-mediated process in polymyositis and inclusion body myositis. Treatment with prednisone is helpful to a majority of patients for a period of time. Immunosuppressive drugs have met with limited success. We describe a group of patients with dermatomyositis, resistant to available therapies, whose muscle strength, skin changes, and muscle biopsies improved significantly during treatment with intravenous immune globulin. The treatment of polymyositis and inclusion body myositis with intravenous immune globulin is currently under study.

  20. A Fractal Immune Network

    OpenAIRE

    Bentley, Peter J.; Timmis, Jon

    2004-01-01

    Proteins are the driving force in development (embryogenesis) and the immune system. Here we describe how a model of proteins designed for evolutionary development in computers can be combined with a model of immune systems. Full details of a prototype system are provided, and preliminary experiments presented. Results show that evolution is able to adjust the mapping between input data and antigens and cause useful changes to the subnetworks formed by the immune algorithm.

  1. Immunomodulatory properties of medicinal mushrooms: differential effects of water and ethanol extracts on NK cell-mediated cytotoxicity.

    Science.gov (United States)

    Lu, Chia-Chen; Hsu, Ya-Jing; Chang, Chih-Jung; Lin, Chuan-Sheng; Martel, Jan; Ojcius, David M; Ko, Yun-Fei; Lai, Hsin-Chih; Young, John D

    2016-10-01

    Medicinal mushrooms have been used for centuries in Asian countries owing to their beneficial effects on health and longevity. Previous studies have reported that a single medicinal mushroom may produce both stimulatory and inhibitory effects on immune cells, depending on conditions, but the factors responsible for this apparent dichotomy remain obscure. We show here that water and ethanol extracts of cultured mycelium from various species (Agaricus blazei Murrill, Antrodia cinnamomea, Ganoderma lucidum and Hirsutella sinensis) produce opposite effects on NK cells. Water extracts enhance NK cell cytotoxic activity against cancer cells, whereas ethanol extracts inhibit cytotoxicity. Water extracts stimulate the expression and production of cytolytic proteins (perforin and granulysin) and NKG2D/NCR cell surface receptors, and activate intracellular signaling kinases (ERK, JNK and p38). In contrast, ethanol extracts inhibit expression of cytolytic and cell surface receptors. Our results suggest that the mode of extraction of medicinal mushrooms may determine the nature of the immunomodulatory effects produced on immune cells, presumably owing to the differential solubility of stimulatory and inhibitory mediators. These findings have important implications for the preparation of medicinal mushrooms to prevent and treat human diseases. PMID:27469258

  2. Evaluation of Chosen Cytokine Levels among Patients with Herpes Zoster as Ability to Provide Immune Response

    Science.gov (United States)

    Zajkowska, Agata; Garkowski, Adam; Świerzbińska, Renata; Kułakowska, Alina; Król, Monika Emilia; Ptaszyńska-Sarosiek, Iwona; Nowicka-Ciełuszecka, Anna; Pancewicz, Sławomir; Czupryna, Piotr; Moniuszko, Anna; Zajkowska, Joanna

    2016-01-01

    Aim and Background Herpes zoster is a viral disease caused by the reactivation of varicella–zoster virus (VZV) which remained latent in the cranial nerve or dorsal root ganglia. Cell-mediated immunity is known to decline with age as part of immunosenescence and can lead to the reactivation of VZV. Whereas herpes zoster is usually mild in healthy young persons, older patients are at increased risk for complications. In the present study we investigated the serum cytokine profile (IL-17, IL-23, IL-21, IL-4, IL-12), representing cellular and humoral immunity and assessed the level of VZV IgG antibodies in patients with herpes zoster. Methods We investigated the serum concentrations of IL-17, IL-23, IL-21, IL-4, IL-12 and the level of VZV IgG antibodies in 23 patients with herpes zoster who did not develop superinfection. The control group was represented by 21 individuals in similar age with no inflammatory and infectious diseases. Cytokine and antibodies levels were measured by ELISA method. Statistical analysis was performed using the ROC curve (receiver operating characteristic), t-test, Welch’s t-test, and nonparametric tests with STATISTICA 10 software. Results In patients with herpes zoster, the serum level of IL-17, IL-23, IL-21, IL-4 and IL-12 as well as VZV IgG antibodies titer were statistically significantly increased compared to control group. Conclusion Our results confirm the broad activation of the immune system involving humoral and cell-mediated immunity. PMID:26934574

  3. 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)

  4. Innate immunity and adjuvants.

    Science.gov (United States)

    Akira, Shizuo

    2011-10-12

    Innate immunity was for a long time considered to be non-specific because the major function of this system is to digest pathogens and present antigens to the cells involved in acquired immunity. However, recent studies have shown that innate immunity is not non-specific, but is instead sufficiently specific to discriminate self from pathogens through evolutionarily conserved receptors, designated Toll-like receptors (TLRs). Indeed, innate immunity has a crucial role in early host defence against invading pathogens. Furthermore, TLRs were found to act as adjuvant receptors that create a bridge between innate and adaptive immunity, and to have important roles in the induction of adaptive immunity. This paradigm shift is now changing our thinking on the pathogenesis and treatment of infectious, immune and allergic diseases, as well as cancers. Besides TLRs, recent findings have revealed the presence of a cytosolic detector system for invading pathogens. I will review the mechanisms of pathogen recognition by TLRs and cytoplasmic receptors, and then discuss the roles of these receptors in the development of adaptive immunity in response to viral infection. PMID:21893536

  5. Immunity and skin cancer

    Energy Technology Data Exchange (ETDEWEB)

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

    1981-01-01

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

  6. Local hyperthermia treatment of tumors induces CD8+ T cell-mediated resistance against distal and secondary tumors

    Science.gov (United States)

    Zhang, Peisheng; Chen, Lei; Baird, Jason R.; Demidenko, Eugene; Turk, Mary Jo; Hoopes, P. Jack; Conejo-Garcia, Jose R.; Fiering, Steven

    2014-01-01

    Combinatorial use of iron oxide nanoparticles (IONPs) and an alternating magnetic filed (AMF) can induce local hyperthermia in tumors in a controlled and uniform manner. Heating B16 primary tumors at 43°C for 30 minutes activated dendritic cells (DCs) and subsequently CD8+ T cells in the draining lymph node (dLN) and conferred resistance against rechallenge with B16 (but not unrelated Lewis Lung carcinoma) given 7 days post hyperthermia on both the primary tumor side and the contralateral side in a CD8+ T cell-dependent manner. Mice with heated primary tumors also resisted rechallenge given 30 days post hyperthermia. Mice with larger heated primary tumors had greater resistance to secondary tumors. No rechallenge resistance occurred when tumors were heated at 45°C. Our results demonstrate the promising potential of local hyperthermia treatment applied to identified tumors in inducing anti-tumor immune responses that reduce the risk of recurrence and metastasis. PMID:24566274

  7. Adaptive immunity to fungi.

    Science.gov (United States)

    Verma, Akash; Wüthrich, Marcel; Deepe, George; Klein, Bruce

    2014-11-06

    Life-threatening fungal infections have risen sharply in recent years, owing to the advances and intensity of medical care that may blunt immunity in patients. This emerging crisis has created the growing need to clarify immune defense mechanisms against fungi with the ultimate goal of therapeutic intervention. We describe recent insights in understanding the mammalian immune defenses that are deployed against pathogenic fungi. We focus on adaptive immunity to the major medically important fungi and emphasize three elements that coordinate the response: (1) dendritic cells and subsets that are mobilized against fungi in various anatomical compartments; (2) fungal molecular patterns and their corresponding receptors that signal responses and shape the differentiation of T-cell subsets and B cells; and, ultimately (3) the effector and regulatory mechanisms that eliminate these invaders while constraining collateral damage to vital tissue. These insights create a foundation for the development of new, immune-based strategies for prevention or enhanced clearance of systemic fungal diseases.

  8. Behavioral Immunity in Insects

    Directory of Open Access Journals (Sweden)

    Thierry Lefèvre

    2012-08-01

    Full Text Available Parasites can dramatically reduce the fitness of their hosts, and natural selection should favor defense mechanisms that can protect hosts against disease. Much work has focused on understanding genetic and physiological immunity against parasites, but hosts can also use behaviors to avoid infection, reduce parasite growth or alleviate disease symptoms. It is increasingly recognized that such behaviors are common in insects, providing strong protection against parasites and parasitoids. We review the current evidence for behavioral immunity in insects, present a framework for investigating such behavior, and emphasize that behavioral immunity may act through indirect rather than direct fitness benefits. We also discuss the implications for host-parasite co-evolution, local adaptation, and the evolution of non-behavioral physiological immune systems. Finally, we argue that the study of behavioral immunity in insects has much to offer for investigations in vertebrates, in which this topic has traditionally been studied.

  9. Artificial Immune Systems (2010)

    CERN Document Server

    Greensmith, Julie; Aickelin, Uwe

    2010-01-01

    The human immune system has numerous properties that make it ripe for exploitation in the computational domain, such as robustness and fault tolerance, and many different algorithms, collectively termed Artificial Immune Systems (AIS), have been inspired by it. Two generations of AIS are currently in use, with the first generation relying on simplified immune models and the second generation utilising interdisciplinary collaboration to develop a deeper understanding of the immune system and hence produce more complex models. Both generations of algorithms have been successfully applied to a variety of problems, including anomaly detection, pattern recognition, optimisation and robotics. In this chapter an overview of AIS is presented, its evolution is discussed, and it is shown that the diversification of the field is linked to the diversity of the immune system itself, leading to a number of algorithms as opposed to one archetypal system. Two case studies are also presented to help provide insight into the m...

  10. Skin scarification with Plasmodium falciparum peptide vaccine using synthetic TLR agonists as adjuvants elicits malaria sporozoite neutralizing immunity

    Science.gov (United States)

    Mitchell, Robert A.; Altszuler, Rita; Frevert, Ute; Nardin, Elizabeth H.

    2016-01-01

    Malaria eradication will require a combination of vector control, chemotherapy and an easily administered vaccine. Sterile immunity can be elicited in humans by immunization with sporozoites, the infective stage injected by bite of the mosquito vector, however, whole parasite vaccines present formidable logistical challenges for production, storage and administration. The “gold standard” for infectious disease eradiation, the Smallpox Eradication Programme, utilized mass immunization using the skin scarification (SS) route. SS may more closely mimic the natural route of malaria infection initiated by sporozoites injected by mosquito bite which elicits both neutralizing antibodies and protective cell mediated immunity. We investigated the potential of SS immunization using a malaria repeat peptide containing a protective B cell epitope of Plasmodium falciparum, the most lethal human species, and delivery vehicles containing TLR agonists as adjuvants. In a murine model, SS immunization with peptide in combination with TLR-7/8 and -9 agonists elicited high levels of systemic sporozoite neutralizing antibody, Th1- type CD4+ T cells and resistance to challenge by bites of infected mosquitoes. SS provides the potential to elicit humoral immunity to target Plasmodium at multiple stages of its complex life cycle. PMID:27624667

  11. Skin scarification with Plasmodium falciparum peptide vaccine using synthetic TLR agonists as adjuvants elicits malaria sporozoite neutralizing immunity.

    Science.gov (United States)

    Mitchell, Robert A; Altszuler, Rita; Frevert, Ute; Nardin, Elizabeth H

    2016-01-01

    Malaria eradication will require a combination of vector control, chemotherapy and an easily administered vaccine. Sterile immunity can be elicited in humans by immunization with sporozoites, the infective stage injected by bite of the mosquito vector, however, whole parasite vaccines present formidable logistical challenges for production, storage and administration. The "gold standard" for infectious disease eradiation, the Smallpox Eradication Programme, utilized mass immunization using the skin scarification (SS) route. SS may more closely mimic the natural route of malaria infection initiated by sporozoites injected by mosquito bite which elicits both neutralizing antibodies and protective cell mediated immunity. We investigated the potential of SS immunization using a malaria repeat peptide containing a protective B cell epitope of Plasmodium falciparum, the most lethal human species, and delivery vehicles containing TLR agonists as adjuvants. In a murine model, SS immunization with peptide in combination with TLR-7/8 and -9 agonists elicited high levels of systemic sporozoite neutralizing antibody, Th1- type CD4+ T cells and resistance to challenge by bites of infected mosquitoes. SS provides the potential to elicit humoral immunity to target Plasmodium at multiple stages of its complex life cycle. PMID:27624667

  12. Regulatory mechanisms of immune tolerance in type 1 diabetes and their failures.

    Science.gov (United States)

    Kuhn, Chantal; Besançon, Alix; Lemoine, Sébastien; You, Sylvaine; Marquet, Cindy; Candon, Sophie; Chatenoud, Lucienne

    2016-07-01

    In this brief review we propose to discuss salient data showing the importance of immune regulatory mechanisms, and in particular of Treg, for the control of pathogenic anti-β-cell response in autoimmune diabetes. Disease progression that culminates with the massive destruction of insulin-secreting β-cells and advent of hyperglycemia and glycosuria tightly correlates with a functional deficit in immune regulation. Better dissection of the cellular and molecular mechanisms through which the immune system normally sustains tolerance to "self", and which become defective when autoimmune aggression is overt, is the only direct and robust way to learn how to harness these effectively, so as to restore immune tolerance in patients with insulin-dependent type 1 diabetes. No doubt that regulatory T cells are a privileged mechanism underlying this self-tolerance in the periphery. The discovery of the key role of the transcription factor FoxP3, represented the cornerstone leading to the great advances in the field we are witnessing today. Type 1 diabetes is certainly one of the prototypic T cell-mediated autoimmune diseases where immune regulatory mechanisms relying on specialized subsets of T cells have been the most thoroughly analyzed from the fundamental point of view and also largely exploited in a translational therapeutic perspective. PMID:27216249

  13. Effect of dose and source of supplemental zinc on immune response and oxidative enzymes in lambs.

    Science.gov (United States)

    Nagalakshmi, D; Dhanalakshmi, K; Himabindu, D

    2009-10-01

    An experiment of 150 days was conducted on 42 male Nellore lambs (28.3 +/- 0.64 kg) to determine the effect of zinc (Zn) supplementation (0,15, 30 and 45 ppm) in diet from inorganic (ZnSO(4)) and organic (Zn proteinate) sources on immune response and antioxidant enzyme activities by allotting them randomly to 7 groups in completely randomized design. The basal diet (BD) contained 29.28 ppm Zn. The humoral immune response assessed at 75 d against B. abortus was higher (Peffect on titres against chicken RBC antigen. The cell mediated immune response assessed as delayed type hypersensitivity (DTH) response against phytohaemagglutinin-P and in vitro lymphocyte proliferative response against concanavalin A at 150 d was higher (Peffect on immune response. The DTH response and antibody titres against B.abortus were higher (Pconcentration and alkaline phosphatase (ALP) activity (75 d of experiment) was higher in Zn supplemented lambs. The ALP activity increased (P enzyme activities and immune response compared to ZnSO(4).

  14. 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

  15. Mindfulness meditation and the immune system: a systematic review of randomized controlled trials.

    Science.gov (United States)

    Black, David S; Slavich, George M

    2016-06-01

    Mindfulness meditation represents a mental training framework for cultivating the state of mindful awareness in daily life. Recently, there has been a surge of interest in how mindfulness meditation improves human health and well-being. Although studies have shown that mindfulness meditation can improve self-reported measures of disease symptomatology, the effect that mindfulness meditation has on biological mechanisms underlying human aging and disease is less clear. To address this issue, we conducted the first comprehensive review of randomized controlled trials examining the effects of mindfulness meditation on immune system parameters, with a specific focus on five outcomes: (1) circulating and stimulated inflammatory proteins, (2) cellular transcription factors and gene expression, (3) immune cell count, (4) immune cell aging, and (5) antibody response. This analysis revealed substantial heterogeneity across studies with respect to patient population, study design, and assay procedures. The findings suggest possible effects of mindfulness meditation on specific markers of inflammation, cell-mediated immunity, and biological aging, but these results are tentative and require further replication. On the basis of this analysis, we describe the limitations of existing work and suggest possible avenues for future research. Mindfulness meditation may be salutogenic for immune system dynamics, but additional work is needed to examine these effects. PMID:26799456

  16. Expanding roles for CD4 T cells and their subpopulations in tumor immunity and therapy

    Directory of Open Access Journals (Sweden)

    Mark J Dobrzanski

    2013-03-01

    Full Text Available The importance of CD4 T cells in orchestrating the immune system and their role in inducing effective T cell-mediated therapies for the treatment of patients with select established malignancies are undisputable. Through a complex and balanced array of direct and indirect mechanisms of cellular activation and regulation, this functionally diverse family of lymphocytes can potentially promote tumor eradication, long-term tumor immunity and aid in establishing and/or rebalancing immune cell homeostasis through interaction with other immune cell populations within the highly dynamic tumor environment. However, recent studies have uncovered additional functions and roles for CD4 T cells, some of which are independent of other lymphocytes, that can not only influence and contribute to tumor immunity but paradoxically promote tumor growth and progression. Here, we review the recent advances in our understanding of the various CD4 T cell lineages and their signature cytokines in disease progression and/or regression. We discuss their direct and indirect mechanistic interplay among themselves and with other responding cells of the antitumor response, their potential roles and abilities for "plasticity" and memory cell generation within the hostile tumor environment and their potentials in cancer treatment and adoptive immunotherapies.

  17. Regulatory mechanisms of immune tolerance in type 1 diabetes and their failures.

    Science.gov (United States)

    Kuhn, Chantal; Besançon, Alix; Lemoine, Sébastien; You, Sylvaine; Marquet, Cindy; Candon, Sophie; Chatenoud, Lucienne

    2016-07-01

    In this brief review we propose to discuss salient data showing the importance of immune regulatory mechanisms, and in particular of Treg, for the control of pathogenic anti-β-cell response in autoimmune diabetes. Disease progression that culminates with the massive destruction of insulin-secreting β-cells and advent of hyperglycemia and glycosuria tightly correlates with a functional deficit in immune regulation. Better dissection of the cellular and molecular mechanisms through which the immune system normally sustains tolerance to "self", and which become defective when autoimmune aggression is overt, is the only direct and robust way to learn how to harness these effectively, so as to restore immune tolerance in patients with insulin-dependent type 1 diabetes. No doubt that regulatory T cells are a privileged mechanism underlying this self-tolerance in the periphery. The discovery of the key role of the transcription factor FoxP3, represented the cornerstone leading to the great advances in the field we are witnessing today. Type 1 diabetes is certainly one of the prototypic T cell-mediated autoimmune diseases where immune regulatory mechanisms relying on specialized subsets of T cells have been the most thoroughly analyzed from the fundamental point of view and also largely exploited in a translational therapeutic perspective.

  18. 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

  19. 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.

  20. Novel immune modulators used in hematology: impact on NK cells.

    Science.gov (United States)

    Krieg, Stephanie; Ullrich, Evelyn

    2012-01-01

    There is a wide range of important pharmaceuticals used in treatment of cancer. Besides their known effects on tumor cells, there is growing evidence for modulation of the immune system. Immunomodulatory drugs (IMiDs(®)) play an important role in the treatment of patients with multiple myeloma or myelodysplastic syndrome and have already demonstrated antitumor, anti-angiogenic, and immunostimulating effects, in particular on natural killer (NK) cells. Tyrosine kinase inhibitors are directly targeting different kinases and are known to regulate effector NK cells and expression of NKG2D ligands (NKG2DLs) on tumor cells. Demethylating agents, histone deacetylases, and proteasome inhibitors interfere with the epigenetic regulation and protein degradation of malignant cells. There are first hints that these drugs also sensitize tumor cells to chemotherapy, radiation, and NK cell-mediated cytotoxicity by enhanced expression of TRAIL and NKG2DLs. However, these pharmaceuticals may also impair NK cell function in a dose- and time-dependent manner. In summary, this review provides an update on the effects of different novel molecules on the immune system focusing NK cells. PMID:23316191

  1. Immune-Modulation by Epidermal Growth Factor Receptor Inhibitors: Implication on Anti-Tumor Immunity in Lung Cancer

    Science.gov (United States)

    Herrmann, Amanda C.; Bernatchez, Chantale; Haymaker, Cara; Molldrem, Jeffrey J.; Hong, Waun Ki; Perez-Soler, Roman

    2016-01-01

    Skin toxicity is the most common toxicity caused by Epidermal Growth Factor Receptor (EGFR) inhibitors, and has been associated with clinical efficacy. As EGFR inhibitors enhance the expression of antigen presenting molecules in affected skin keratinocytes, they may concurrently facilitate neo-antigen presentation in lung cancer tumor cells contributing to anti-tumor immunity. Here, we investigated the modulatory effect of the EGFR inhibitor, erlotinib on antigen presenting molecules and PD-L1, prominent immune checkpoint protein, of skin keratinocytes and lung cancer cell lines to delineate the link between EGFR signaling pathway inhibition and potential anti-tumor immunity. Erlotinib up-regulated MHC-I and MHC-II proteins on IFNγ treated keratinocytes but abrogated IFNγ-induced expression of PD-L1, suggesting the potential role of infiltrating autoreactive T cells in the damage of keratinocytes in affected skin. Interestingly, the surface expression of MHC-I, MHC-II, and PD-L1 was up-regulated in response to IFNγ more often in lung cancer cell lines sensitive to erlotinib, but only expression of PD-L1 was inhibited by erlotinib. Further, erlotinib significantly increased T cell mediated cytotoxicity on lung cancer cells. Lastly, the analysis of gene expression dataset of 186 lung cancer cell lines from Cancer Cell Line Encyclopedia demonstrated that overexpression of PD-L1 was associated with sensitivity to erlotinib and higher expression of genes related to antigen presenting pathways and IFNγ signaling pathway. Our findings suggest that the EGFR inhibitors can facilitate anti-tumor adaptive immune responses by breaking tolerance especially in EGFR driven lung cancer that are associated with overexpression of PD-L1 and genes related to antigen presentation and inflammation. PMID:27467256

  2. Unexpected role for IL-17 in protective immunity against hypervirulent Mycobacterium tuberculosis HN878 infection.

    Directory of Open Access Journals (Sweden)

    Radha Gopal

    2014-05-01

    Full Text Available Mycobacterium tuberculosis (Mtb, the causative agent of tuberculosis (TB, infects one third of the world's population. Among these infections, clinical isolates belonging to the W-Beijing appear to be emerging, representing about 50% of Mtb isolates in East Asia, and about 13% of all Mtb isolates worldwide. In animal models, infection with W-Beijing strain, Mtb HN878, is considered "hypervirulent" as it results in increased mortality and causes exacerbated immunopathology in infected animals. We had previously shown the Interleukin (IL -17 pathway is dispensable for primary immunity against infection with the lab adapted Mtb H37Rv strain. However, it is not known whether IL-17 has any role to play in protective immunity against infection with clinical Mtb isolates. We report here that lab adapted Mtb strains, such as H37Rv, or less virulent Mtb clinical isolates, such as Mtb CDC1551, do not require IL-17 for protective immunity against infection while infection with Mtb HN878 requires IL-17 for early protective immunity. Unexpectedly, Mtb HN878 induces robust production of IL-1β through a TLR-2-dependent mechanism, which supports potent IL-17 responses. We also show that the role for IL-17 in mediating protective immunity against Mtb HN878 is through IL-17 Receptor signaling in non-hematopoietic cells, mediating the induction of the chemokine, CXCL-13, which is required for localization of T cells within lung lymphoid follicles. Correct T cell localization within lymphoid follicles in the lung is required for maximal macrophage activation and Mtb control. Since IL-17 has a critical role in vaccine-induced immunity against TB, our results have far reaching implications for the design of vaccines and therapies to prevent and treat emerging Mtb strains. In addition, our data changes the existing paradigm that IL-17 is dispensable for primary immunity against Mtb infection, and instead suggests a differential role for IL-17 in early protective

  3. Unexpected Role for IL-17 in Protective Immunity against Hypervirulent Mycobacterium tuberculosis HN878 Infection

    Science.gov (United States)

    Gopal, Radha; Monin, Leticia; Slight, Samantha; Uche, Uzodinma; Blanchard, Emmeline; A. Fallert Junecko, Beth; Ramos-Payan, Rosalio; Stallings, Christina L.; Reinhart, Todd A.; Kolls, Jay K.; Kaushal, Deepak; Nagarajan, Uma; Rangel-Moreno, Javier; Khader, Shabaana A.

    2014-01-01

    Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), infects one third of the world's population. Among these infections, clinical isolates belonging to the W-Beijing appear to be emerging, representing about 50% of Mtb isolates in East Asia, and about 13% of all Mtb isolates worldwide. In animal models, infection with W-Beijing strain, Mtb HN878, is considered “hypervirulent” as it results in increased mortality and causes exacerbated immunopathology in infected animals. We had previously shown the Interleukin (IL) -17 pathway is dispensable for primary immunity against infection with the lab adapted Mtb H37Rv strain. However, it is not known whether IL-17 has any role to play in protective immunity against infection with clinical Mtb isolates. We report here that lab adapted Mtb strains, such as H37Rv, or less virulent Mtb clinical isolates, such as Mtb CDC1551, do not require IL-17 for protective immunity against infection while infection with Mtb HN878 requires IL-17 for early protective immunity. Unexpectedly, Mtb HN878 induces robust production of IL-1β through a TLR-2-dependent mechanism, which supports potent IL-17 responses. We also show that the role for IL-17 in mediating protective immunity against Mtb HN878 is through IL-17 Receptor signaling in non-hematopoietic cells, mediating the induction of the chemokine, CXCL-13, which is required for localization of T cells within lung lymphoid follicles. Correct T cell localization within lymphoid follicles in the lung is required for maximal macrophage activation and Mtb control. Since IL-17 has a critical role in vaccine-induced immunity against TB, our results have far reaching implications for the design of vaccines and therapies to prevent and treat emerging Mtb strains. In addition, our data changes the existing paradigm that IL-17 is dispensable for primary immunity against Mtb infection, and instead suggests a differential role for IL-17 in early protective immunity against

  4. Innate immune recognition and regulation in liver injury: A brief report from a series of studies

    Institute of Scientific and Technical Information of China (English)

    TIAN ZhiGang

    2009-01-01

    The discovery of innate immune receptors and the emergence of liver Immunology (high content of NK and NKT cells in liver) led to the second research summit in innate immunity since the finding of NK cells in the middle 1970s. Liver disease is one of the most dangerous threats to humans, and the pro-gress in innate immunology and liver immunology made it possible to re-explain the cellular end too-lecular immune mechanisms of liver disease. In the past ten years, we have found that innate recogni-tion of hepatic NK and NKT subsets were involved in murine liver injury. We established a novel NK cell-dependent acute murine hepatitis model by activating Toll-like receptor-3 (TLR-3) with an injection of poly I:C, which may mimic mild viral hepatitis (such as Chronic Hepatitis B). We observed that a network of innate immune cells including NK, NKT and Kupffer cells is involved in liver immune injury in our established NK cell-dependent murine model. We noted that TLR-3 on Kupffer ceils activated by pretreatment with poly I:C might protect against bacterial toxin (LPS)-induced fuIminant hepatitis by down-regulating TLR-4 function, while TLR-3 pre-activation of NK cells might reduce Con A-induced NKT cell-mediated fulminant hepatitis by blocking NKT cell recruitment to the liver. We also found that the oversensitivity to injury by immune stimulation in HBV (hepatitis B virus) transgenic mice (full HBV gene-tg or HBs-tg) correlated to the over-expression of Real, an NKG2D (natural killer cell group 2D) ligand of NK cells or CDld, a ligand of TCR-V14 of NKT cells, on HBV+ hepatocytes, which leads to an innate immune response against hepatocytes and is critical in liver immune injury and regeneration.

  5. Immunity in urogenital protozoa.

    Science.gov (United States)

    Malla, N; Goyal, K; Dhanda, R S; Yadav, M

    2014-09-01

    Innate and adaptive immunity play a significant role in urogenital infections. Innate immunity is provided by the epithelial cells and mucus lining along with acidic pH, which forms a strong physical barrier against the pathogens in female reproductive tract. Cells of innate immune system, antimicrobial peptides, cytokines, chemokines and adaptive immunity in the reproductive tract are evolved during infection, and a pro-inflammatory response is generated to fight against the invading pathogen Trichomonas vaginalis, a primary urogenital protozoa, the etiological agent of human trichomoniasis, a curable sexually transmitted infection. The involvement of the urogenital tract by other protozoal infections such as P. falciparum, Trypanosoma, Leishmania, Toxoplasma, Entamoeba histolytica and Acanthamoeba infection is rarely reported. Trichomonas induce pro-inflammatory and immunosuppressive responses in infected subjects. Multifactorial pathogenic mechanisms including parasite adherence, cysteine proteases, lipophosphoglycan, free radical, cytokine generation and Toll-like receptors appear to interplay with the induction of local and systemic immune responses that ultimately determine the outcome of the infection. However, the involvement of urogenital pathogen-specific immune mechanisms and effect of normal local resident flora on the outcome (symptomatic vs. asymptomatic) of infection are poorly understood. Moreover, immune interactions in trichomoniasis subjects co-infected with bacterial and viral pathogens need to be elucidated.

  6. Intracellular haemolytic agents of Heterocapsa circularisquama exhibit toxic effects on H. circularisquama cells themselves and suppress both cell-mediated haemolytic activity and toxicity to rotifers (Brachionus plicatilis).

    Science.gov (United States)

    Nishiguchi, Tomoki; Cho, Kichul; Yasutomi, Masumi; Ueno, Mikinori; Yamaguchi, Kenichi; Basti, Leila; Yamasaki, Yasuhiro; Takeshita, Satoshi; Kim, Daekyung; Oda, Tatsuya

    2016-10-01

    A harmful dinoflagellate, Heterocapsa circularisquama, is highly toxic to shellfish and the zooplankton rotifer Brachionus plicatilis. A previous study found that H. circularisquama has both light-dependent and -independent haemolytic agents, which might be responsible for its toxicity. Detailed analysis of the haemolytic activity of H. circularisquama suggested that light-independent haemolytic activity was mediated mainly through intact cells, whereas light-dependent haemolytic activity was mediated by intracellular agents which can be discharged from ruptured cells. Because H. circularisquama showed similar toxicity to rotifers regardless of the light conditions, and because ultrasonic ruptured H. circularisquama cells showed no significant toxicity to rotifers, it was suggested that live cell-mediated light-independent haemolytic activity is a major factor responsible for the observed toxicity to rotifers. Interestingly, the ultrasonic-ruptured cells of H. circularisquama suppressed their own lethal effect on the rotifers. Analysis of samples of the cell contents (supernatant) and cell fragments (precipitate) prepared from the ruptured H. circularisquama cells indicated that the cell contents contain inhibitors for the light-independent cell-mediated haemolytic activity, toxins affecting H. circularisquama cells themselves, as well as light-dependent haemolytic agents. Ethanol extract prepared from H. circularisquama, which is supposed to contain a porphyrin derivative that displays photosensitising haemolytic activity, showed potent toxicity to Chattonella marina, Chattonella antiqua, and Karenia mikimotoi, as well as to H. circularisquama at the concentration range at which no significant toxicity to rotifers was observed. Analysis on a column of Sephadex LH-20 revealed that light-dependent haemolytic activity and inhibitory activity on cell-mediated light-independent haemolytic activity existed in two separate fractions (f-2 and f-3), suggesting that both

  7. AAV2-mediated in vivo immune gene therapy of solid tumours

    LENUS (Irish Health Repository)

    Collins, Sara A

    2010-12-20

    Abstract Background Many strategies have been adopted to unleash the potential of gene therapy for cancer, involving a wide range of therapeutic genes delivered by various methods. Immune therapy has become one of the major strategies adopted for cancer gene therapy and seeks to stimulate the immune system to target tumour antigens. In this study, the feasibility of AAV2 mediated immunotherapy of growing tumours was examined, in isolation and combined with anti-angiogenic therapy. Methods Immune-competent Balb\\/C or C57 mice bearing subcutaneous JBS fibrosarcoma or Lewis Lung Carcinoma (LLC) tumour xenografts respectively were treated by intra-tumoural administration of AAV2 vector encoding the immune up-regulating cytokine granulocyte macrophage-colony stimulating factor (GM-CSF) and the co-stimulatory molecule B7-1 to subcutaneous tumours, either alone or in combination with intra-muscular (IM) delivery of AAV2 vector encoding Nk4 14 days prior to tumour induction. Tumour growth and survival was monitored for all animals. Cured animals were re-challenged with tumourigenic doses of the original tumour type. In vivo cytotoxicity assays were used to investigate establishment of cell-mediated responses in treated animals. Results AAV2-mediated GM-CSF, B7-1 treatment resulted in a significant reduction in tumour growth and an increase in survival in both tumour models. Cured animals were resistant to re-challenge, and induction of T cell mediated anti-tumour responses were demonstrated. Adoptive transfer of splenocytes to naïve animals prevented tumour establishment. Systemic production of Nk4 induced by intra-muscular (IM) delivery of Nk4 significantly reduced subcutaneous tumour growth. However, combination of Nk4 treatment with GM-CSF, B7-1 therapy reduced the efficacy of the immune therapy. Conclusions Overall, this study demonstrates the potential for in vivo AAV2 mediated immune gene therapy, and provides data on the inter-relationship between tumour

  8. Human monocytes undergo functional re-programming during differentiation to dendritic cell mediated by human extravillous trophoblasts

    Science.gov (United States)

    Zhao, Lei; Shao, Qianqian; Zhang, Yun; Zhang, Lin; He, Ying; Wang, Lijie; Kong, Beihua; Qu, Xun

    2016-01-01

    Maternal immune adaptation is required for a successful pregnancy to avoid rejection of the fetal–placental unit. Dendritic cells within the decidual microenvironment lock in a tolerogenic profile. However, how these tolerogenic DCs are induced and the underlying mechanisms are largely unknown. In this study, we show that human extravillous trophoblasts redirect the monocyte-to-DC transition and induce regulatory dendritic cells. DCs differentiated from blood monocytes in the presence of human extravillous trophoblast cell line HTR-8/SVneo displayed a DC-SIGN+CD14+CD1a− phenotype, similar with decidual DCs. HTR8-conditioned DCs were unable to develop a fully mature phenotype in response to LPS, and altered the cytokine secretory profile significantly. Functionally, conditioned DCs poorly induced the proliferation and activation of allogeneic T cells, whereas promoted CD4+CD25+Foxp3+ Treg cells generation. Furthermore, the supernatant from DC and HTR-8/SVneo coculture system contained significant high amount of M-CSF and MCP-1. Using neutralizing antibodies, we discussed the role of M-CSF and MCP-1 during monocyte-to-DCs differentiation mediated by extravillous trophoblasts. Our data indicate that human extravillous trophoblasts play an important role in modulating the monocyte-to-DC differentiation through M-CSF and MCP-1, which facilitate the establishment of a tolerogenic microenvironment at the maternal–fetal interface. PMID:26857012

  9. Human monocytes undergo functional re-programming during differentiation to dendritic cell mediated by human extravillous trophoblasts.

    Science.gov (United States)

    Zhao, Lei; Shao, Qianqian; Zhang, Yun; Zhang, Lin; He, Ying; Wang, Lijie; Kong, Beihua; Qu, Xun

    2016-01-01

    Maternal immune adaptation is required for a successful pregnancy to avoid rejection of the fetal-placental unit. Dendritic cells within the decidual microenvironment lock in a tolerogenic profile. However, how these tolerogenic DCs are induced and the underlying mechanisms are largely unknown. In this study, we show that human extravillous trophoblasts redirect the monocyte-to-DC transition and induce regulatory dendritic cells. DCs differentiated from blood monocytes in the presence of human extravillous trophoblast cell line HTR-8/SVneo displayed a DC-SIGN(+)CD14(+)CD1a(-) phenotype, similar with decidual DCs. HTR8-conditioned DCs were unable to develop a fully mature phenotype in response to LPS, and altered the cytokine secretory profile significantly. Functionally, conditioned DCs poorly induced the proliferation and activation of allogeneic T cells, whereas promoted CD4(+)CD25(+)Foxp3(+) Treg cells generation. Furthermore, the supernatant from DC and HTR-8/SVneo coculture system contained significant high amount of M-CSF and MCP-1. Using neutralizing antibodies, we discussed the role of M-CSF and MCP-1 during monocyte-to-DCs differentiation mediated by extravillous trophoblasts. Our data indicate that human extravillous trophoblasts play an important role in modulating the monocyte-to-DC differentiation through M-CSF and MCP-1, which facilitate the establishment of a tolerogenic microenvironment at the maternal-fetal interface. PMID:26857012

  10. Nanobody-based chimeric receptor gene integration in Jurkat cells mediated by PhiC31 integrase

    International Nuclear Information System (INIS)

    The crucial role of T lymphocytes in anti-tumor immunity has led to the development of novel strategies that can target and activate T cells against tumor cells. Recombinant DNA technology has been used to generate non-MHC-restricted chimeric antigen receptors (CARs). Here, we constructed a panel of recombinant CAR that harbors the anti-MUC1 nanobody and the signaling and co-signaling moieties (CD3ζ/CD28) with different spacer regions derived from human IgG3 with one or two repeats of the hinge sequence or the hinge region of FcγRII. The PhiC31 integrase system was employed to investigate if the recombination efficiency could be recruited for high and stable expression of T cell chimeric receptor genes. The effect of nuclear localization signal (NLS) and two different promoters (CMV and CAG) on efficacy of PhiC31 integrase in human T cell lines was evaluated. The presence of integrase in combination with NLS, mediated up to 7.6 and 8.5 fold increases in CAR expression in ZCHN-attB and ZCHHN-attB cassette integrated T cells, respectively. Our results showed that highly efficient and stable transduction of the Jurkat cell line by PhiC31 integrase is a feasible modality for generating anti-cancer chimeric T cells for use in cancer immunotherapy.

  11. A Critical Role of IL-21-Induced BATF in Sustaining CD8-T-Cell-Mediated Chronic Viral Control

    Directory of Open Access Journals (Sweden)

    Gang Xin

    2015-11-01

    Full Text Available Control of chronic viral infections by CD8 T cells is critically dependent on CD4 help. In particular, helper-derived IL-21 plays a key role in sustaining the CD8 T cell response; however, the molecular pathways by which IL-21 sustains CD8 T cell immunity remain unclear. We demonstrate that IL-21 causes a phenotypic switch of transcription factor expression in CD8 T cells during chronic viral infection characterized by sustained BATF expression. Importantly, BATF expression during chronic infection is both required for optimal CD8 T cell persistence and anti-viral effector function and sufficient to rescue “unhelped” CD8 T cells. Mechanistically, BATF sustains the response by cooperating with IRF4, an antigen-induced transcription factor that is also critically required for CD8 T cell maintenance, to preserve Blimp-1 expression and thereby sustain CD8 T cell effector function. Collectively, these data suggest that CD4 T cells “help” the CD8 response during chronic infection via IL-21-induced BATF expression.

  12. CD8 T cell-mediated protection against liver-stage malaria: Lessons from a mouse model

    Directory of Open Access Journals (Sweden)

    John eHarty

    2014-06-01

    Full Text Available Malaria is a major global health problem, with severe mortality in children living is Sub-Saharan Africa, and there is currently no licensed effective vaccine. However, vaccine-induced protection from Plasmodium infection, the causative agent of malaria, was established for humans in small clinical trials and for rodents in the 1960’s. Soon after, a critical role for memory CD8 T cells in vaccine induced protection against Plasmodium liver-stage infection was established in rodent models and is assumed to apply to humans. However, these seminal early studies have led to only modest advances over the ensuing years in our understanding the basic features of memory CD8 T cells required for protection against liver-stage Plasmodium infection, an issue which has likely impeded the development of effective vaccines for humans. Given the ethical and practical limitations in gaining mechanistic insight from human vaccine and challenge studies, animal models still have an important role in dissecting the basic parameters underlying memory CD8 T cell immunity to Plasmodium. Here, we will highlight recent data from our own work in the mouse model of Plasmodium infection that identify quantitative and qualitative features of protective memory CD8 T cell responses. Finally, these lessons will be discussed in the context of recent findings from clinical trials of vaccine–induced protection in controlled human challenge models.

  13. CD8 T-cell-mediated protection against liver-stage malaria: lessons from a mouse model

    Science.gov (United States)

    Van Braeckel-Budimir, Natalija; Harty, John T.

    2014-01-01

    Malaria is a major global health problem, with severe mortality in children living in sub-Saharan Africa, and there is currently no licensed, effective vaccine. However, vaccine-induced protection from Plasmodium infection, the causative agent of malaria, was established for humans in small clinical trials and for rodents in the 1960s. Soon after, a critical role for memory CD8 T cells in vaccine-induced protection against Plasmodium liver-stage infection was established in rodent models and is assumed to apply to humans. However, these seminal early studies have led to only modest advances over the ensuing years in our understanding the basic features of memory CD8 T cells required for protection against liver-stage Plasmodium infection, an issue which has likely impeded the development of effective vaccines for humans. Given the ethical and practical limitations in gaining mechanistic insight from human vaccine and challenge studies, animal models still have an important role in dissecting the basic parameters underlying memory CD8 T-cell immunity to Plasmodium. Here, we will highlight recent data from our own work in the mouse model of Plasmodium infection that identify quantitative and qualitative features of protective memory CD8 T-cell responses. Finally, these lessons will be discussed in the context of recent findings from clinical trials of vaccine-induced protection in controlled human challenge models. PMID:24936199

  14. Nanobody-based chimeric receptor gene integration in Jurkat cells mediated by PhiC31 integrase

    Energy Technology Data Exchange (ETDEWEB)

    Iri-Sofla, Farnoush Jafari [Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Rahbarizadeh, Fatemeh, E-mail: rahbarif@modares.ac.ir [Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Ahmadvand, Davoud [Center of Pharmaceutical Nanotechnology and Nanotoxicology, Department of Pharmaceutics and Analytical Chemistry, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen O (Denmark); Rasaee, Mohammad J. [Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran (Iran, Islamic Republic of)

    2011-11-01

    The crucial role of T lymphocytes in anti-tumor immunity has led to the development of novel strategies that can target and activate T cells against tumor cells. Recombinant DNA technology has been used to generate non-MHC-restricted chimeric antigen receptors (CARs). Here, we constructed a panel of recombinant CAR that harbors the anti-MUC1 nanobody and the signaling and co-signaling moieties (CD3{zeta}/CD28) with different spacer regions derived from human IgG3 with one or two repeats of the hinge sequence or the hinge region of Fc{gamma}RII. The PhiC31 integrase system was employed to investigate if the recombination efficiency could be recruited for high and stable expression of T cell chimeric receptor genes. The effect of nuclear localization signal (NLS) and two different promoters (CMV and CAG) on efficacy of PhiC31 integrase in human T cell lines was evaluated. The presence of integrase in combination with NLS, mediated up to 7.6 and 8.5 fold increases in CAR expression in ZCHN-attB and ZCHHN-attB cassette integrated T cells, respectively. Our results showed that highly efficient and stable transduction of the Jurkat cell line by PhiC31 integrase is a feasible modality for generating anti-cancer chimeric T cells for use in cancer immunotherapy.

  15. Trace metals, melanin-based pigmentation and their interaction influence immune parameters in feral pigeons (Columba livia).

    Science.gov (United States)

    Chatelain, M; Gasparini, J; Frantz, A

    2016-04-01

    Understanding the effects of trace metals emitted by anthropogenic activities on wildlife is of great concern in urban ecology; yet, information on how they affect individuals, populations, communities and ecosystems remains scarce. In particular, trace metals may impact survival by altering the immune system response to parasites. Plumage melanin is assumed to influence the effects of trace metals on immunity owing to its ability to bind metal ions in feathers and its synthesis being coded by a pleiotropic gene. We thus hypothesized that trace metal exposure would interact with plumage colouration in shaping immune response. We experimentally investigated the interactive effect between exposure to an environmentally relevant range of zinc and/or lead and melanin-based plumage colouration on components of the immune system in feral pigeons (Columba livia). We found that zinc increased anti-keyhole limpet hemocyanin (KLH) IgY primary response maintenance, buffered the negative effect of lead on anti-KLH IgY secondary response maintenance and tended to increase T-cell mediated phytohaemagglutinin (PHA) skin response. Lead decreased the peak of the anti-KLH IgY secondary response. In addition, pheomelanic pigeons exhibited a higher secondary anti-KLH IgY response than did eumelanic ones. Finally, T-cell mediated PHA skin response decreased with increasing plumage eumelanin level of birds exposed to lead. Neither treatments nor plumage colouration correlated with endoparasite intensity. Overall, our study points out the effects of trace metals on some parameters of birds' immunity, independently from other confounding urbanization factors, and underlines the need to investigate their impacts on other life history traits and their consequences in the ecology and evolution of host-parasite interactions. PMID:26809976

  16. Trace metals, melanin-based pigmentation and their interaction influence immune parameters in feral pigeons (Columba livia).

    Science.gov (United States)

    Chatelain, M; Gasparini, J; Frantz, A

    2016-04-01

    Understanding the effects of trace metals emitted by anthropogenic activities on wildlife is of great concern in urban ecology; yet, information on how they affect individuals, populations, communities and ecosystems remains scarce. In particular, trace metals may impact survival by altering the immune system response to parasites. Plumage melanin is assumed to influence the effects of trace metals on immunity owing to its ability to bind metal ions in feathers and its synthesis being coded by a pleiotropic gene. We thus hypothesized that trace metal exposure would interact with plumage colouration in shaping immune response. We experimentally investigated the interactive effect between exposure to an environmentally relevant range of zinc and/or lead and melanin-based plumage colouration on components of the immune system in feral pigeons (Columba livia). We found that zinc increased anti-keyhole limpet hemocyanin (KLH) IgY primary response maintenance, buffered the negative effect of lead on anti-KLH IgY secondary response maintenance and tended to increase T-cell mediated phytohaemagglutinin (PHA) skin response. Lead decreased the peak of the anti-KLH IgY secondary response. In addition, pheomelanic pigeons exhibited a higher secondary anti-KLH IgY response than did eumelanic ones. Finally, T-cell mediated PHA skin response decreased with increasing plumage eumelanin level of birds exposed to lead. Neither treatments nor plumage colouration correlated with endoparasite intensity. Overall, our study points out the effects of trace metals on some parameters of birds' immunity, independently from other confounding urbanization factors, and underlines the need to investigate their impacts on other life history traits and their consequences in the ecology and evolution of host-parasite interactions.

  17. 5-Azacytidine treatment sensitizes tumor cells to T-cell mediated cytotoxicity and modulates NK cells in patients with myeloid malignancies

    DEFF Research Database (Denmark)

    Gang, A O; Frøsig, T M; Brimnes, M K;

    2014-01-01

    Treatment with the demethylating agent 5-Azacytidine leads to prolonged survival for patients with myelodysplastic syndrome, and the demethylation induces upregulation of cancer-testis antigens. Cancer-testis antigens are well-known targets for immune recognition in cancer, and the immune system ...... no effects could be detected. Together, these data support a strategy for combining 5-Azacytidine treatment with immune therapy for potential clinical benefit....

  18. Susceptibility of adherent versus suspension target cells derived from adherent tissue culture lines to cell-mediated cytotoxicity in rapid 51Cr-release assays

    International Nuclear Information System (INIS)

    Preparation of target cells from tissue culture lines which grow adherent to tissue culture vessels is often desirable for tests of cell-mediated cytotoxicity (CMC). In the present study the authors used cells derived from adherent tissue culture lines to compare the merits of suspension vs. adherent target cells in short-term 51Cr-release assays. Cytotoxic activity of murine spleen cells sensitized in vitro against allogeneic spleen cells or syngeneic sarcoma cells was tested with fibroblast or sarcoma target cells. In parallel tests, aliquots of tissue culture lines were detached and used as either suspension or adherent target cells in CMC assays, matching the concentrations of suspension and adherent target cells. In both allogeneic and syngeneic combinations adherent target cells released less 51Cr spontaneously and were more susceptible to CMC than their suspension counterparts. (Auth.)

  19. Immunization for Women

    Science.gov (United States)

    ... Immunization History Vaccine Safety Articles Resources Personal Stories Vaccine Education Videos Research Articles ACOG Resources Resources & Links ACOG Update on Zika Virus Pregnancy Attention pregnant women! Pregnant women, their ...

  20. HIV and Immunizations

    Science.gov (United States)

    HIV Treatment HIV and Immunizations (Last updated 3/1/2016; last reviewed 3/1/2016) Key Points Vaccines are products that ... a disease outbreak. Is there a vaccine against HIV? Testing is underway on experimental vaccines to prevent ...

  1. Immune System (For Parents)

    Science.gov (United States)

    ... lock onto them. T cells are like the soldiers, destroying the invaders that the intelligence system has ... can't be prevented, you can help your child's immune system stay stronger and fight illnesses by ...

  2. Antiviral immunity in amphibians.

    Science.gov (United States)

    Chen, Guangchun; Robert, Jacques

    2011-11-01

    Although a variety of virus species can infect amphibians, diseases caused by ranaviruses ([RVs]; Iridoviridae) have become prominent, and are a major concern for biodiversity, agriculture and international trade. The relatively recent and rapid increase in prevalence of RV infections, the wide range of host species infected by RVs, the variability in host resistance among population of the same species and among different developmental stages, all suggest an important involvement of the amphibian immune system. Nevertheless, the roles of the immune system in the etiology of viral diseases in amphibians are still poorly investigated. We review here the current knowledge of antiviral immunity in amphibians, focusing on model species such as the frog Xenopus and the salamander (Ambystoma tigrinum), and on recent progress in generating tools to better understand how host immune defenses control RV infections, pathogenicity, and transmission.

  3. Immunity of international organizations

    CERN Document Server

    Schrijver, Nico

    2015-01-01

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

  4. Depression of Complement Regulatory Factors in Rat and Human Renal Grafts Is Associated with the Progress of Acute T-Cell Mediated Rejection.

    Directory of Open Access Journals (Sweden)

    Kazuaki Yamanaka

    Full Text Available The association of complement with the progression of acute T cell mediated rejection (ATCMR is not well understood. We investigated the production of complement components and the expression of complement regulatory proteins (Cregs in acute T-cell mediated rejection using rat and human renal allografts.We prepared rat allograft and syngeneic graft models of renal transplantation. The expression of Complement components and Cregs was assessed in the rat grafts using quantitative real-time PCR (qRT-PCR and immunofluorescent staining. We also administered anti-Crry and anti-CD59 antibodies to the rat allograft model. Further, we assessed the relationship between the expression of membrane cofactor protein (MCP by immunohistochemical staining in human renal grafts and their clinical course.qRT-PCR results showed that the expression of Cregs, CD59 and rodent-specific complement regulator complement receptor 1-related gene/protein-y (Crry, was diminished in the rat allograft model especially on day 5 after transplantation in comparison with the syngeneic model. In contrast, the expression of complement components and receptors: C3, C3a receptor, C5a receptor, Factor B, C9, C1q, was increased, but not the expression of C4 and C5, indicating a possible activation of the alternative pathway. When anti-Crry and anti-CD59 mAbs were administered to the allograft, the survival period for each group was shortened. In the human ATCMR cases, the group with higher MCP expression in the grafts showed improved serum creatinine levels after the ATCMR treatment as well as a better 5-year graft survival rate.We conclude that the expression of Cregs in allografts is connected with ATCMR. Our results suggest that controlling complement activation in renal grafts can be a new strategy for the treatment of ATCMR.

  5. Immune dysfunction in cirrhosis

    OpenAIRE

    Sipeki Nóra; Antal-Szalmás Péter (1968-) (laboratóriumi szakorvos, laboratóriumi hematológus és immunológus, klinikai farmakológus szakorvos); Lakatos Péter László; Papp Mária (1975-) (belgyógyász, gasztroenterológus)

    2014-01-01

    Innate and adaptive immune dysfunction, also referred to as cirrhosis-associated immune dysfunction syndrome, is a major component of cirrhosis, and plays a pivotal role in the pathogenesis of both the acute and chronic worsening of liver function. During the evolution of the disease, acute decompensation events associated with organ failure(s), so-called acute-on chronic liver failure, and chronic decompensation with progression of liver fibrosis and also development of disease specific comp...

  6. Adults Need Immunizations, Too!

    Centers for Disease Control (CDC) Podcasts

    2012-03-19

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

  7. Artificial Immune Systems Tutorial

    CERN Document Server

    Aickelin, Uwe

    2008-01-01

    The biological immune system is a robust, complex, adaptive system that defends the body from foreign pathogens. It is able to categorize all cells (or molecules) within the body as self-cells or non-self cells. It does this with the help of a distributed task force that has the intelligence to take action from a local and also a global perspective using its network of chemical messengers for communication. There are two major branches of the immune system. The innate immune system is an unchanging mechanism that detects and destroys certain invading organisms, whilst the adaptive immune system responds to previously unknown foreign cells and builds a response to them that can remain in the body over a long period of time. This remarkable information processing biological system has caught the attention of computer science in recent years. A novel computational intelligence technique, inspired by immunology, has emerged, called Artificial Immune Systems. Several concepts from the immune have been extracted an...

  8. Artificial Immune Systems

    CERN Document Server

    Aickelin, Uwe

    2009-01-01

    The biological immune system is a robust, complex, adaptive system that defends the body from foreign pathogens. It is able to categorize all cells (or molecules) within the body as self-cells or non-self cells. It does this with the help of a distributed task force that has the intelligence to take action from a local and also a global perspective using its network of chemical messengers for communication. There are two major branches of the immune system. The innate immune system is an unchanging mechanism that detects and destroys certain invading organisms, whilst the adaptive immune system responds to previously unknown foreign cells and builds a response to them that can remain in the body over a long period of time. This remarkable information processing biological system has caught the attention of computer science in recent years. A novel computational intelligence technique, inspired by immunology, has emerged, called Artificial Immune Systems. Several concepts from the immune have been extracted an...

  9. Apoptotic-like Leishmania exploit the host´s autophagy machinery to reduce T-cell-mediated parasite elimination

    Science.gov (United States)

    Crauwels, Peter; Bohn, Rebecca; Thomas, Meike; Gottwalt, Stefan; Jäckel, Florian; Krämer, Susi; Bank, Elena; Tenzer, Stefan; Walther, Paul; Bastian, Max; van Zandbergen, Ger

    2015-01-01

    Apoptosis is a well-defined cellular process in which a cell dies, characterized by cell shrinkage and DNA fragmentation. In parasites like Leishmania, the process of apoptosis-like cell death has been described. Moreover upon infection, the apoptotic-like population is essential for disease development, in part by silencing host phagocytes. Nevertheless, the exact mechanism of how apoptosis in unicellular organisms may support infectivity remains unclear. Therefore we investigated the fate of apoptotic-like Leishmania parasites in human host macrophages. Our data showed—in contrast to viable parasites—that apoptotic-like parasites enter an LC3+, autophagy-like compartment. The compartment was found to consist of a single lipid bilayer, typical for LC3-associated phagocytosis (LAP). As LAP can provoke anti-inflammatory responses and autophagy modulates antigen presentation, we analyzed how the presence of apoptotic-like parasites affected the adaptive immune response. Macrophages infected with viable Leishmania induced proliferation of CD4+ T-cells, leading to a reduced intracellular parasite survival. Remarkably, the presence of apoptotic-like parasites in the inoculum significantly reduced T-cell proliferation. Chemical induction of autophagy in human monocyte-derived macrophage (hMDM), infected with viable parasites only, had an even stronger proliferation-reducing effect, indicating that host cell autophagy and not parasite viability limits the T-cell response and enhances parasite survival. Concluding, our data suggest that apoptotic-like Leishmania hijack the host cells´ autophagy machinery to reduce T-cell proliferation. Furthermore, the overall population survival is guaranteed, explaining the benefit of apoptosis-like cell death in a single-celled parasite and defining the host autophagy pathway as a potential therapeutic target in treating Leishmaniasis. PMID:25801301

  10. Betamethasone, but Not Tacrolimus, Suppresses the Development of Th2 Cells Mediated by Langerhans Cell-Like Dendritic Cells.

    Science.gov (United States)

    Matsui, Katsuhiko; Tamai, Saki; Ikeda, Reiko

    2016-01-01

    It is well known that Langerhans cells (LCs) work as the primary orchestrators in the polarization of the immune milieu towards a T helper type 1 (Th1) or T helper type 2 (Th2) response. In this study, we investigated the effects of tacrolimus and betamethasone, each used as topical applications in atopic dermatitis (AD), on Th2 cell development mediated by LCs. LC-like dendritic cells (LDCs) were generated from mouse bone marrow cells and used as substitutes for LCs. Mice were primed with ovalbumin (OVA) peptide-pulsed LDCs, which had been treated with tacrolimus or betamethasone, via the hind footpad. After 5 d, the cytokine response in the popliteal lymph nodes was investigated by enzyme-linked immunosorbent assay. The expression of cell surface molecules on LDCs was investigated via reverse transcriptase polymerase chain reaction. Administration of OVA peptide-pulsed LDCs, which had been treated with betamethasone, inhibited Th2 cell development, as represented by the down-regulation of interleukin-4 production, and also inhibited Th1 cell development, represented by the down-regulation of interferon-γ production. However, tacrolimus-treated LDCs did not induce such inhibition of the development of Th1 and Th2 cells. The inhibition of Th1 and Th2 cell development was associated with the suppression of CD40 and T-cell immunoglobulin, and mucin domain-containing protein (TIM)-4 expression, respectively, in LDCs. These results suggest that the topical application of betamethasone to skin lesions of patients with AD acts on epidermal LCs, and may inhibit the development of Th2 cells, thus being of benefit for the control of AD. PMID:27374298

  11. CD8 T cell-mediated killing of orexinergic neurons induces a narcolepsy-like phenotype in mice.

    Science.gov (United States)

    Bernard-Valnet, Raphaël; Yshii, Lidia; Quériault, Clémence; Nguyen, Xuan-Hung; Arthaud, Sébastien; Rodrigues, Magda; Canivet, Astrid; Morel, Anne-Laure; Matthys, Arthur; Bauer, Jan; Pignolet, Béatrice; Dauvilliers, Yves; Peyron, Christelle; Liblau, Roland S

    2016-09-27

    Narcolepsy with cataplexy is a rare and severe sleep disorder caused by the destruction of orexinergic neurons in the lateral hypothalamus. The genetic and environmental factors associated with narcolepsy, together with serologic data, collectively point to an autoimmune origin. The current animal models of narcolepsy, based on either disruption of the orexinergic neurotransmission or neurons, do not allow study of the potential autoimmune etiology. Here, we sought to generate a mouse model that allows deciphering of the immune mechanisms leading to orexin(+) neuron loss and narcolepsy development. We generated mice expressing the hemagglutinin (HA) as a "neo-self-antigen" specifically in hypothalamic orexin(+) neurons (called Orex-HA), which were transferred with effector neo-self-antigen-specific T cells to assess whether an autoimmune process could be at play in narcolepsy. Given the tight association of narcolepsy with the human leukocyte antigen (HLA) HLA-DQB1*06:02 allele, we first tested the pathogenic contribution of CD4 Th1 cells. Although these T cells readily infiltrated the hypothalamus and triggered local inflammation, they did not elicit the loss of orexin(+) neurons or clinical manifestations of narcolepsy. In contrast, the transfer of cytotoxic CD8 T cells (CTLs) led to both T-cell infiltration and specific destruction of orexin(+) neurons. This phenotype was further aggravated upon repeated injections of CTLs. In situ, CTLs interacted directly with MHC class I-expressing orexin(+) neurons, resulting in cytolytic granule polarization toward neurons. Finally, drastic neuronal loss caused manifestations mimicking human narcolepsy, such as cataplexy and sleep attacks. This work demonstrates the potential role of CTLs as final effectors of the immunopathological process in narcolepsy.

  12. Parenteral is more efficient than mucosal immunization to induce regression of human papillomavirus-associated genital tumors.

    Science.gov (United States)

    Decrausaz, Loane; Domingos-Pereira, Sonia; Duc, Mélanie; Bobst, Martine; Romero, Pedro; Schiller, John T; Jichlinski, Patrice; Nardelli-Haefliger, Denise

    2011-08-01

    Cervical cancer is a public health concern as it represents the second cause of cancer death in women worldwide. High-risk human papillomaviruses (HPV) are the etiologic agents, and HPV E6 and/or E7 oncogene-specific therapeutic vaccines are under development to treat HPV-related lesions in women. Whether the use of mucosal routes of immunization may be preferable for inducing cell-mediated immune responses able to eradicate genital tumors is still debated because of the uniqueness of the female genital mucosa (GM) and the limited experimentation. Here, we compared the protective activity resulting from immunization of mice via intranasal (i.n.), intravaginal (IVAG) or subcutaneous (s.c.) routes with an adjuvanted HPV type 16 E7 polypeptide vaccine. Our data show that s.c. and i.n. immunizations elicited similar frequencies and avidity of TetE71CD81 and E7-specific Interferon-gamma-secreting cells in the GM, whereas slightly lower immune responses were induced by IVAG immunization. In a novel orthotopic murine model, both s.c. and i.n. immunizations allowed for complete long-term protection against genital E7-expressing tumor challenge. However, only s.c. immunization induced complete regression of already established genital tumors. This suggests that the higher E7-specific systemic response observed after s.c. immunization may contribute to the regression of growing genital tumors, whereas local immune responses may be sufficient to impede genital challenges. Thus, our data show that for an efficiently adjuvanted protein-based vaccine, parenteral vaccination route is superior to mucosal vaccination route for inducing regression of established genital tumors in a murine model of HPV-associated genital cancer.

  13. Innate and adaptive immune responses in male and female reproductive tracts in homeostasis and following HIV infection

    Science.gov (United States)

    Nguyen, Philip V; Kafka, Jessica K; Ferreira, Victor H; Roth, Kristy; Kaushic, Charu

    2014-01-01

    The male and female reproductive tracts are complex microenvironments that have diverse functional demands. The immune system in the reproductive tract has the demanding task of providing a protective environment for a fetal allograft while simultaneously conferring protection against potential pathogens. As such, it has evolved a unique set of adaptations, primarily under the influence of sex hormones, which make it distinct from other mucosal sites. Here, we discuss the various components of the immune system that are present in both the male and female reproductive tracts, including innate soluble factors and cells and humoral and cell-mediated adaptive immunity under homeostatic conditions. We review the evidence showing unique phenotypic and functional characteristics of immune cells and responses in the male and female reproductive tracts that exhibit compartmentalization from systemic immunity and discuss how these features are influenced by sex hormones. We also examine the interactions among the reproductive tract, sex hormones and immune responses following HIV-1 infection. An improved understanding of the unique characteristics of the male and female reproductive tracts will provide insights into improving clinical treatments of the immunological causes of infertility and the design of prophylactic interventions for the prevention of sexually transmitted infections. PMID:24976268

  14. Genetically defined race, but not sex, is associated with higher humoral and cellular immune responses to measles vaccination.

    Science.gov (United States)

    Voigt, Emily A; Ovsyannikova, Inna G; Haralambieva, Iana H; Kennedy, Richard B; Larrabee, Beth R; Schaid, Daniel J; Poland, Gregory A

    2016-09-22

    In addition to host genetic and environmental factors, variations in immune responses to vaccination are influenced by demographic variables, such as race and sex. The influence of genetic race and sex on measles vaccine responses is not well understood, yet important for the development of much-needed improved measles vaccines with lower failure rates. We assessed associations between genetically defined race and sex with measles humoral and cellular immunity after measles vaccination in three independent and geographically distinct cohorts totaling 2872 healthy racially diverse children, older adolescents, and young adults. We found no associations between biological sex and either humoral or cellular immunity to measles vaccine, and no correlation between humoral and cellular immunity in these study subjects. Genetically defined race was, however, significantly associated with both measles vaccine-induced humoral and cellular immune responses, with subjects genetically classified as having African-American ancestry demonstrating significantly higher antibody and cell-mediated immune responses relative to subjects of Caucasian ancestry. This information may be useful in designing novel measles vaccines that are optimally effective across human genetic backgrounds. PMID:27591105

  15. Regulation of immune suppression induced by UV radiation

    International Nuclear Information System (INIS)

    Full text: Exposure of the skin of mice and men to increasing doses of UV radiation causes erythema, blistering, accelerated photoageing, DNA lesions and photocarcinogenesis. Moderate exposure also suppresses T cell-mediated immune function, a defect which is a prerequisite for the promotion or outgrowth phase of the UV-initiated tumour, and which is accompanied by dysregulated cutaneous cytokine patterns. A major cutaneous photoreceptor for the immunosuppression is epidermal urocanic acid (UCA). Naturally occurring trans-UCA photoisomerises in the stratum corneum and epidermis to cis-UCA, in a direct reaction. Cis-UCA has been found to have local and systemic immunosuppressive properties. The action spectrum for the photoimmuno-suppression is maximal in the UVB (280 320nm) waveband. However longer wavelength UVA (320-400nm), which interacts with skin predominantly via oxidative reactions, is not immunosuppressive at environmental exposure doses, and unexpectedly can provide protection from UVB-immunosuppression. We find that UVA protective exposure prevents the major UVB-alterations to the cytokine array. In addition, UVA (but not UVB) exposure induces cutaneous haem oxygenase (HO) activity, an endogenous antioxidant enzyme. HO is known to be redox-regulated, and to be the major stress protein induced in cultured fibroblasts by UVA. We find that UVA-immune protection is dependent on the induced HO; that enhanced HO activity following UVA is cytokine-dependent; and that the induced HO acts by inhibiting the immunosuppressive potential of cis-UCA. Thus oxidant states resulting predominantly from UVA irradiation, while apparently immunologically innocuous, seem to actively upregulate this defensive HO response. These studies have therefore revealed interactions between different UV wavebands important for immune regulation both in the skin and systemically, which may have a critical bearing on the carcinogenic outcome in chronically exposed skin, and offer the

  16. Complex Adaptive Immunity to enteric fevers in humans: Lessons learned and the path forward

    Directory of Open Access Journals (Sweden)

    Marcelo B. Sztein

    2014-10-01

    Full Text Available Salmonella enterica serovar Typhi (S. Typhi, the causative agent of typhoid fever, and S. Paratyphi A and B, causative agents of paratyphoid fever, are major public health threats throughout the world. Although two licensed typhoid vaccines are currently available, they are only moderately protective and immunogenic necessitating the development of novel vaccines. A major obstacle in the development of improved typhoid, as well as paratyphoid vaccines is the lack of known immunological correlates of protection in humans. Considerable progress has been made in recent years in understanding the complex adaptive host responses against S. Typhi. Although the induction of S. Typhi-specific antibodies (including their functional properties and memory B cells, as well as their cross-reactivity with S. Paratyphi A and S. Paratyphi B has been shown, the role of humoral immunity in protection remains undefined. Cell mediated immunity (CMI is likely to play a dominant role in protection against enteric fever pathogens. Detailed measurements of CMI performed in volunteers immunized with attenuated strains of S. Typhi have shown, among others, the induction of lymphoproliferation, multifunctional type 1 cytokine production and CD8+ cytotoxic T cell responses. In addition to systemic responses, the local microenvironment of the gut is likely to be of paramount importance in protection from these infections. In this review we will critically assess current knowledge regarding the role of CMI and humoral immunity following natural S. Typhi and S. Paratyphi infections, experimental challenge, and immunization in humans. We will also address recent advances regarding cross-talk between the host’s gut microbiota and immunization with attenuated S. Typhi, mechanisms of systemic immune responses, and the homing potential of S. Typhi-specific B and T cells to the gut and other tissues.

  17. Exercise, immune function and respiratory infection: An update on the influence of training and environmental stress.

    Science.gov (United States)

    Walsh, Neil P; Oliver, Samuel J

    2016-02-01

    This review outlines recent advancements in the understanding of athlete immune health. Controversies discussed include whether high levels of athletic training and environmental stress (for example, heat acclimation, cryotherapy and hypoxic training) compromise immunity and increase upper respiratory tract infection (URTI). Recent findings challenge early exercise immunology doctrine by showing that international athletes performing high-volume training suffer fewer, not greater, URTI episodes than lower-level performers and URTI incidence decreases, not increases, around the time of competition compared with heavy training. Herein we raise the possibility of host genetic influences on URTI and modifiable behavioural and training-related factors underpinning these recent observations. Continued controversy concerns the proportion of URTI symptoms reported by athletes that are due to infectious pathogens, airway inflammation or as yet unknown causes and indeed whether the proportion differs in athletes and non-athletes. Irrespective of the cause of URTI symptoms (infectious or non-infectious), experts broadly agree that self-reported URTI hinders high-volume athletic training but, somewhat surprisingly, less is known about the influence on athletic performance. In athletes under heavy training, both innate and acquired immunity are often observed to decrease, typically 15-25%, but whether relatively modest changes in immunity increase URTI susceptibility remains a major gap in knowledge. With the exception of cell-mediated immunity that tends to be decreased, exercising in environmental extremes does not provide an additional threat to immunity and host defence. Recent evidence suggests that immune health may actually be enhanced by regular intermittent exposures to environmental stress (for example, intermittent hypoxia training).

  18. Immunizations climb, then falter.

    Science.gov (United States)

    Kane, H

    1994-01-01

    The extended immunization campaign began in the mid 1980s and contributed to immunization of 4 out of every 5 infants worldwide, or 80% by the end of the 1980s. There was a slight relaxation of effort around 1990 and 1991, and declines occurred in 28 developing countries. In developing countries, 101 countries maintained or increased immunization in 1991. Rates dropped in Brazil and Venezuela and sub-Saharan Africa. Rates remained constant in 1992, except for the declines in women's tetanus immunization. Distribution is 4-5 times a year to 100 million infants. The savings in lives amounted to 3 million 1992, and further extension could have saved another 1.7 million. The cost in low income countries is $6 to $20, with an average of $15. Five visits are required for complete immunization into one dose; costs could then be reduced by 70%. Total annual costs amount to $2.2 to $2.4 billion for the United Nations Expanded Programme on Immunization. This sum amounts to 2% of public health expenditures in developing countries. The benefits are in reduction in health care costs and expanded productive potential of people. The measles vaccine alone reduced the death rate from 2.5 million in 1980 to 900,000 in 1990. Nonfatal measles morbidity was reduced from 75 million to 25 million for the same period. From averted measles incidents, the savings in treatment costs and productive potential are immeasurable. The first smallpox vaccine was developed in 1796 by Edward Jenner, but it took nearly two for final smallpox eradication in 1979 worldwide. Over the past 10 years, polio eradication has cost $1.4 billion, but without polio vaccines, the cost would reach $500 million annually. Refrigeration and transportation to remote areas has made immunization difficult. The development of low-dose vaccines that would maintain potency in tropical temperatures would be a welcome contribution.

  19. Basophil-derived amphiregulin is essential for UVB irradiation-induced immune suppression.

    Science.gov (United States)

    Meulenbroeks, Chantal; van Weelden, Huib; Schwartz, Christian; Voehringer, David; Redegeld, Frank A M; Rutten, Victor P M G; Willemse, Ton; Sijts, Alice J A M; Zaiss, Dietmar M W

    2015-01-01

    UVB irradiation (290-320 nm) is used to treat skin diseases like psoriasis and atopic dermatitis, and is known to suppress contact hypersensitivity (CHS) reactions in mouse models. Regulatory T cells (Treg cells) have been shown to be responsible for this UVB-induced suppression of CHS. The epidermal growth factor (EGF)-like growth factor amphiregulin (AREG) engages EGFR on Treg cells and, in different disease models, it was shown that mast cell-derived AREG is essential for optimal Treg cell function in vivo. Here we determined whether AREG has a role in UVB-induced, Treg cell-mediated suppression of CHS reactions in the skin. Our data show that AREG is essential for UVB-induced CHS suppression. In contrast to the general assumption, however, mast cells were dispensable for UVB-induced immune suppression, whereas basophil-derived AREG was essential. These data reveal, to our knowledge, a previously unreported function for basophils in the homeostasis of immune responses in the skin. Basophils thus fulfill a dual function: they contribute to the initiation of effective type 2 immune responses and, by enhancing the suppressive capacity of local Treg cell populations, also to local immune regulation in the skin. PMID:25089660

  20. Induction of the immune response suppression in mice inoculated with Candida albicans.

    Science.gov (United States)

    Valdez, J C; Mesón, D E; Sirena, A; de Petrino, S F; Eugenia, M; de Jorrat, B B; de Valdex, M G

    1986-03-01

    There is a controversy in respect to the immunological response (humoral or cellular) concerning the defense against Candida albicans. Candidosis would induce sub-populations of suppressor cells in the host cell-immune response. This report tries to show the effect of different doses of C. albicans (alive or heat-killed) on the expression of cell-mediated and humoral immunity. The effect upon cell immunity was determined by inoculating different lots of singeneic mice, doses of varied concentration of C. albicans and checking for delayed-type hipersensitivity (D.T.H.). D.T.H. was also controlled in syngeneic normal mice which had previously been injected with inoculated mice spleen cells. Humoral immunity was assayed by measuring the induced blastogenesis by Pokeweed Mitogen on spleen mononuclear cells with different doses of C. albicans. Results obtained show that the different doses gave origin to: Suppression of humoral and cell response (10(8) alive); Suppression of only humoral response (10(6) alive); Suppression of cell response and increase of humoral response (10(9) dead); Increase of both responses (10(8) dead).