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Specific Immune Response (specific + immune_response)
Selected AbstractsCell-surface bound pertussis toxin induces polyclonal T cell responses with high levels of interferon-, in the absence of interleukin-12EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2003Ayako Wakatsuki Abstract Pertussis toxin (PTx), an exotoxin produced by Bordetella pertussis, has long been used as a mucosal adjuvant. We examined the T cell stimulatory properties of PTx in order to dissectits mechanisms of adjuvanticity. PTx or the B-oligomer of PTx (PTxB) failed to activate purified murine CD4+ or CD8+ T cells, as measured by a lack of proliferation or expression of early T cell activation markers. However, these T cells proliferated extensively in response to the toxin in the presence of syngeneic DC, and proliferation was accompanied by a high level of IFN-, production in the absence of IL-12. Interestingly, such responses were independent of signals mediated by MHC,TCR interaction. Both PTx and PTxB were found to bind stably to the surface of DC, and increased the adherence of DC to surrounding cells. These data suggest that polyclonal T cell responses mediated by the toxin are likely to be caused by the toxin bound on the surface of APC, either cross-linking cell surface molecules on T cells, or directly stimulating T cells together with the co-stimulatory molecules expressed on APC. B. pertussis may use this toxin as a mechanism to evade a specific immune response. [source] Construction of a multivalent vaccine strain of Shigella flexneri and evaluation of serotype-specific immunityFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 3 2006Amy V. Jennison Abstract Shigella flexneri causes more fatalities by shigellosis than any other Shigella species. There are 13 different serotypes of S. flexneri and their distribution varies between endemic geographical regions. The immune response against S. flexneri is serotype-specific, so current immunization strategies have required the administration of multiple vaccine strains to provide protection against multiple serotypes. In this study, we report the construction of a multivalent S. flexneri vaccine strain, SFL1425, expressing the O-antigen structure specific for serotypes 2a and 5a. This combination of type antigens has not previously been reported for S. flexneri. The multivalent vaccine strain, SFL1425 was able to induce a specific immune response against both serotypes 2a and 5a in a mouse pulmonary model. [source] Spatiotemporal Control over Molecular Delivery and Cellular Encapsulation from Electropolymerized Micro- and Nanopatterned Surfaces,ADVANCED FUNCTIONAL MATERIALS, Issue 18 2009Eric Stern Abstract Bioactive, patterned micro- and nanoscale surfaces that can be spatially engineered for three-dimensional ligand presentation and sustained release of signaling molecules represent a critical advance for the development of next-generation diagnostic and therapeutic devices. Lithography is ideally suited to patterning such surfaces due to its precise, easily scalable, high-throughput nature; however, to date polymers patterned by these techniques have not demonstrated the capacity for sustained release of bioactive agents. Here a class of lithographically defined, electropolymerized polymers with monodisperse micro- and nanopatterned features capable of sustained release of bioactive drugs and proteins is demonstrated. It is shown that precise control can be achieved over the loading capacity and release rates of encapsulated agents and this aspect is illustrated using a fabricated surface releasing a model antigen (ovalbumin) and a cytokine (interleukin-2) for induction of a specific immune response. Furthermore, the ability of this technique to enable three-dimensional control over cellular encapsulation is demonstrated. The efficacy of the described approach is buttressed by its simplicity, versatility, and reproducibility, rendering it ideally suited for biomaterials engineering. [source] Suppression of allergic airway inflammation in a mouse model by Der p2 recombined BCGIMMUNOLOGY, Issue 1pt2 2009Hai-Feng Ou-Yang Summary Allergic asthma is a chronic inflammatory disease mediated by T helper (Th)2 cell immune responses. Currently, immunotherapies based on both immune deviation and immune suppression, including the development of recombinant mycobacteria as immunoregulatory vaccines, are attractive treatment strategies for asthma. In our previous studies, we created a genetically recombinant form of bacille Calmette,Guerin (rBCG) that expressed Der p2 of house dust mites and established that it induced a shift from a Th2 response to a Th1 response in naive mice. However, it is unclear whether rBCG could suppress allergic airway inflammation in a mouse model. In this article we report that rBCG dramatically inhibited airway inflammation, eosinophilia, mucus production and mast cell degranulation in allergic mice. Analysis of interferon-, (IFN-,) and interleukin-4 (IL-4) levels in bronchoalveolar lavage fluid (BALF) and lung tissue revealed that the suppression was associated with a shift from a Th2 response to a Th1 response. At the same time, rBCG induced a CD4+ CD25+ Foxp3+ T-cell subtype that could suppress the proliferation of Th2 effector cells in vitro in an antigen-specific manner. Moreover, suppression of CD4+ CD25+ T cells could be adoptively transferred. Thus, our results demonstrate that rBCG induces both generic and specific immune responses. The generic immune response is associated with a shift from a Th2 to a Th1 cytokine response, whereas the specific immune response against Der p2 appears to be related to the expansion of transforming growth factor-, (TGF-,)-producing CD4+ CD25+ Foxp3+ regulatory T cells. rBCG can suppress asthmatic airway inflammation through both immune deviation and immune suppression and may be a feasible, efficient immunotherapy for asthma. [source] BALB/c mice resistant to Toxoplasma gondii infection proved to be highly susceptible when previously infected with Myocoptes musculinus fur mitesINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 5 2007Áurea Welter Summary The immune response induced by Toxoplasma gondii is characterized by Th1 immune mechanisms. We previously demonstrated that C57BL/6 mice infested with Myocoptes musculinus and infected with T. gondii by intraperitoneal route undergo accelerated mortality according to Th2 immune mechanisms induced by the acarian. To evaluate whether infection with M. musculinus influences T. gondii -induced Th1 response in a resistant mouse lineage, BALB/c, which develops latent chronic toxoplasmosis in a way similar to that observed in immunocompetent humans, this study was done. The animals were infected with T. gondii ME-49 strain 1 month after M. musculinus infestation, being the survival and the immune response monitored. The double-infected displayed higher mortality rate if compared with the mono-infected mice. In addition, infection with M. musculinus changed the T. gondii -specific immune response, converting BALB/c host to a susceptible phenotype. Spleen cells had increased the levels of IL-4 in double-infected mice. This alteration was associated with severe pneumonia, encephalitis and wasting condition. In addition, a higher tissue parasitism was observed in double-infected animals. It can be concluded that infection with these two contrasting parasites, M. musculinus and T. gondii, may convert an immunocompetent host into a susceptible one, and such a host will develop severe toxoplasmosis. [source] Adverse drug reactions to biologicsJOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 6 2010Kathrin Scherer Summary The use of biologics has rapidly expanded since the introduction of the first diagnostic antibodies; they are now widely employed in oncology, autoimmune disorders, inflammatory diseases and transplantation medicine. Their widespread use has resulted in an increase in adverse drug reactions. Adverse effects result from both direct pharmacological actions and immunological actions, as well as through induction of a specific immune response. The nomenclature, particularly of the monoclonal antibodies, identifies the target structure and organ as well as the species of origin, which then helps predict their effects and antigenic properties. Depending on the extent of foreign protein, anti-allotypic or anti-idiotypic antibodies with or without neutralizing properties may be induced. Adverse drug reactions from biologics often depend on the target and may be explained by activation or inhibition of particular cytokine pathways. Adverse drug reactions are classified by their pathomechanism, which enhances understanding of the pathogenesis and facilitates both allergologic diagnostic measures and planning of premedication in future treatments. This review emphasizes immunostimulatory and hypersensitivity reactions. [source] Lyme borreliosis , an updateJOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 5 2007Elisabeth Aberer Summary Lyme borreliosis is the most common tick-borne, infectious disease in the northern hemisphere. Disease manifestations in the United States and Europe vary as a result of geographic distribution of different species within the genospecies Borrelia burgdorferi sensu lato, which in turn are host-specific. Certain toxigenic B. burgdorferi strains cause early disseminated disease. The ability of Borrelial organisms to break down the extracellular matrix also promotes dissemination. B. burgdorferi are eliminated by complement-mediated lysis and by T and B cell activity of the specific immune response. Yet, B. burgdorferi can evade humoral immunity by means of type of protective mechanism by which it adheres to the proteoglycan decorin in the joints and skin. A further factor in the persistence of the pathogen is altered antigen expression. Re-infection usually occurs with a different strain, although repeated infection with the same strain is also possible after a certain period of latency. New developments in serologic testing include the use of recombinant native antigen as well as antigens produced in vivo such as VlsE (variable major protein-like sequence, expressed) or decorin-binding protein A. Diagnosis continues to be complicated by seropositivity of healthy individuals, the persistence of antibodies after therapy, and a lacking humoral immune response in patients with erythema migrans. [source] Influence of dietary ß-glucan on growth performance, lymphocyte proliferation, specific immune response and haptoglobin plasma concentrations in pigsJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 1-2 2003S. Hiss Summary Immunomodulatory feed additives might offer alternatives to anti-microbial growth promoters in swine production. The present study was conducted to assess the effects of ,-1,3/1,6 glucans, i.e. of specific yeast cell wall components, on immune function and growth performance in pigs. After weaning at 4 weeks of age, 75 piglets were allocated to 3 different groups for 4 weeks, the diet was supplemented with 0, 0.015 or 0.03% of ,-glucan, respectively. All animals were vaccinated against porcine reproductive and respiratory syndrome (PRRS). After 4 weeks, average daily gains (ADG) of ,-glucan treated pigs were not different from the controls. Feed intake was tendentiously (p < 0.1) increased at 0.03%,-glucan, without alteration of feed efficiency. Serum haptoglobin concentrations at the end of the 4 week treatment were increased in all groups when compared to the initial levels (p < 0.001), without differences between the groups (p > 0.05). Haptoglobin levels were inversely related to ADG. Lymphocyte proliferation indices were not different in control and treatment groups. Specific vaccination responses, as quantified by the PRRS antibody titres occurred in all animals, but no relation with ,-glucan feeding was observed. Our results indicate marginal benefits of ,-glucan supplements for growth performance and no effect on the immune parameters tested. The observed trend towards increased feed intake needs further elucidation. [source] Specific bronchoalveolar lavage fluid T cells associate with disease in a pair of monozygotic twins discordant for sarcoidosisJOURNAL OF INTERNAL MEDICINE, Issue 6 2001J. Grunewald Abstract.,Grunewald J, Eklund A (Karolinska Hospital, Stockholm, Sweden). Specific bronchoalveolar lavage fluid T cells associate with disease in a pair of monozygotic twins discordant for sarcoidosis (Case report). J Intern Med 2001; 250: 535,539. A 49-year-old Caucasian woman had an acute onset of sarcoidosis. Bronchoscopy with bronchoalveolar lavage (BAL) showed a pronounced accumulation of BAL fluid CD4+ T cells expressing the T-cell receptor (TCR) AV2S3 gene. In line with this observation, the patient was HLA-DR17 positive, previously shown to strongly correlate with lung compartmentalized AV2S3+ T cells. At follow-up after recovery, reduced numbers of BAL fluid AV2S3+ T cells were found. Interestingly, BAL fluid of a healthy monozygotic twin sister contained normal numbers of AV2S3+ lung T cells. This report shows the T-cell repertoire of BAL fluid T cells to correlate with the disease (sarcoidosis), indicating a local and specific immune response triggered by an unknown antigen in sarcoidosis. [source] Fifteen years of Env C2V3C3 evolution in six individuals infected clonally with human immunodeficiency virus type 1JOURNAL OF MEDICAL VIROLOGY, Issue 11 2007Bernd Kupfer Abstract The study of the evolution of human immunodeficiency virus type 1 (HIV-1) requires blood samples collected longitudinally and data on the approximate time point of infection. Although these requirements were fulfilled in several previous studies, the infectious sources were either unknown or heterogeneous genetically. In the present study, HIV-1 env C2V3C3 (nt 7029-7315) evolution was examined retrospectively in a cohort of hemophiliacs. Compared to other cohorts, the area of interest here was the infection of six hemophiliacs by the same virus strain, that is, the infecting viruses shared an identical genome. As expected, divergence from the founder sequence as well as interpatient divergence of the predominant virus strains increased significantly over time. Based on the V3 nucleotide sequences, CCR5 usage was predicted exclusively throughout the whole period of infection in all patients. Interestingly, common patterns of viral evolution were detected in the patients of the cohort. Four amino acid substitutions within the V3 loop emerged and persisted subsequently in five (positions 305 and 308 of the HXB2 gp120 reference sequence) and six patients (positions 325 and 328 in HXB2 gp120), respectively. These common changes within the V3 loop are likely to be enforced by HIV-1 specific immune response. J. Med. Virol. 79:1729,1739, 2007. © 2007 Wiley-Liss, Inc. [source] HLA-restricted specific tumor cytolysis by autologous T-lymphocytes infiltrating metastatic bone malignant fibrous histiocytoma of lymph nodeJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 1 2006Tomohide Tsukahara Abstract Malignant fibrous histiocytoma (MFH) of the bone is a high-grade sarcoma characterized histologically by the composition of fibroblasts and pleomorphic cells with a prominent storiform pattern. Despite institution of multi-modality treatments, the prognosis for patients with this tumor remains unsatisfactory. In the present study, towards the goal of developing active immunotherapy for those affected, we established four cell lines from a 53-year-old woman who suffered from MFH of the humerus with lymph node metastases. MFH2003 and MFH2003-B7.1 were the primary lesion-derived cell line and its B7.1-transfectant, respectively. B2003-EBV and TIL2003 were a B cell line established from peripheral blood lymphocytes and a T cell line established from tumor-invaded lymph nodes, respectively. MFH2003 cells could be maintained over a period of 1 year in vitro, and could be xenotransplanted into nude mice. The phenotype of cells analyzed by immunostaining was similar to the original tumor. TIL2003 cells were all CD8+ and specifically recognized MFH2003 cells and MFH2003-B7.1 cells, but not B2003-EBV cells. An anti-HLA-class I monoclonal antibody completely blocked the anti-MFH2003 response of TILs2003. These findings indicate the existence of an anti-MFH specific immune response in the microenvironment of metastatic lymph nodes. The present autologous cell lines provide the basis for identification of novel tumor-associated antigens and may be helpful in the establishment of immunotherapy for patients with MFH of the bone. © 2005 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res [source] Influence of a cocoa-enriched diet on specific immune response in ovalbumin-sensitized ratsMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 3 2009Teresa Pérez-Berezo Abstract Previous studies in young rats have reported the impact of 3 weeks of high cocoa intake on healthy immune status. The present article describes the effects of a longer-term cocoa-enriched diet (9 weeks) on the specific immune response to ovalbumin (OVA) in adult Wistar rats. At 4 weeks after immunization, control rats produced anti-OVA antibodies, which, according their amount and isotype, were arranged as follows: IgG1 > IgG2a > IgM > IgG2b > IgG2c. Both cocoa diets studied (4% and 10%) down-modulated OVA-specific antibody levels of IgG1 (main subclass associated with the Th2 immune response in rats), IgG2a, IgG2c and IgM isotypes. Conversely, cocoa-fed rats presented equal or higher levels of anti-OVA IgG2b antibodies (subclass linked to the Th1 response). Spleen and lymph node cells from OVA-immunized control and cocoa-fed animals proliferated similarly under OVA stimulation. However, spleen cells from cocoa-fed animals showed decreased interleukin-4 secretion (main Th2 cytokine), and lymph node cells from the same rats displayed higher interferon-, secretion (main Th1 cytokine). These changes were accompanied by a reduction in the number of anti-OVA IgG-secreting cells in spleen. In conclusion, cocoa diets induced attenuation of antibody synthesis that may be attributable to specific down-regulation of the Th2 immune response. [source] Inflammation, heat shock proteins and periodontal pathogens in atherosclerosis: an immunohistologic studyMOLECULAR ORAL MICROBIOLOGY, Issue 4 2006P. J. Ford Background:, Inflammation is a significant component of atherosclerosis lesions. Bacteria, including periodontopathogens, have been demonstrated in atherosclerotic plaques and cross-reactivity of the immune response to bacterial GroEL with human heat shock protein 60 has been suggested as a link between infections and atherosclerosis. Methods:, In this study, the nature of the inflammatory infiltrate and the presence of human heat shock protein 60 and GroEL were examined in 31 carotid endarterectomy specimens. Additionally, monoclonal antibodies were used to detect the presence of six bacteria, including those implicated in periodontal disease. Results:, The inflammatory cell infiltrate of the lesions was dominated by CD14+ macrophages and CD4+ T cells. Most cells of the infiltrate as well as the endothelium were HLA-DR+, indicating activation; however, there was an absence of CD25 expression, demonstrating that the activated T cells were not proliferating. Few CD1a+ and CD83+ cells were noted. Human heat shock protein 60 expression was evident on endothelial cells and cells with the appearance of smooth muscle cells and lymphocytes. GroEL and bacteria were detected within intimal cells. Chlamydia pneumoniae, Porphyromonas gingivalis, Fusobacterium nucleatum, Tannerella forsythia, Prevotella intermedia, and Actinobacillus actinomycetemcomitans were found in 21%, 52%, 34%, 34%, 41%, and 17% of arteries, respectively. Conclusion:, These results give evidence for a specific immune response associated with atherosclerosis. Whether bacteria initiate the observed inflammation in atherosclerotic lesions is not clear; however, the present study shows that maintenance of inflammation may be enhanced by the presence of periodontopathic bacteria. [source] Localization of antigen-presenting cells in Helicobacter pylori -infected gastric mucosaPATHOLOGY INTERNATIONAL, Issue 4 2002Tatsuhiko Suzuki Helicobacter pylori (HP) infection is known to induce the specific immune response in the gastric mucosa. The immune response is triggered by presentation of antigen peptides on the major histocompatibility assembly of the antigen-presenting cells (APC) with the assistance of costimulatory molecules such as B7-1 (CD80) and B7-2 (CD86). Their counter-receptors or ligands on T cells are CD28 or cytotoxic lymphocyte-associated molecule-4. The aim of the present study was to clarify the localization of APC and their relation with T cells in HP-infected human gastric mucosa. Our findings suggest that the macrophages in the lamina propria may mainly act as APC in the HP-infected gastric mucosa, and the triggered immune response might be involved in the mucosal immune response in the inflamed gastric mucosa to invasive antigens related to HP organisms. [source] Beryllium-stimulated neopterin as a diagnostic adjunct in chronic beryllium diseaseAMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 6 2003Lisa A. Maier MD, MSPH Abstract Background The diagnosis of chronic beryllium disease (CBD) relies on the beryllium lymphocyte proliferation test (BeLPT) to demonstrate a Be specific immune response. This test has improved early diagnosis, but cannot discriminate beryllium sensitization (BeS) from CBD. We previously found high neopterin levels in CBD patients' serum and questioned whether Be-stimulated neopterin production by peripheral blood cells in vitro might be useful in the diagnosis of CBD. Methods CBD, BeS, Be exposed workers without disease (Be-exp) normal controls and sarcoidosis subjects were enrolled. Peripheral blood mononuclear cells (PBMN) were cultured in the presence and absence of beryllium sulfate. Neopterin levels were determined from cell supernatants by enzyme linked immunosorbent assay (ELISA). Clinical evaluation of CBD subjects included chest radiography, pulmonary function testing, exercise testing, and the BeLPT. Results CBD patients produced higher levels of neopterin in both unstimulated and Be-stimulated conditions compared to all other subjects (P,<,0.0001). Unstimulated neopterin mononuclear cell levels overlapped among groups, however, Be-stimulated neopterin levels in CBD showed little overlap. Using a neopterin concentration of 2.5 ng/ml as a cutoff, Be-stimulated neopterin had a sensitivity of 80% and specificity of 100% for CBD and was able to differentiate CBD from BeS. Be-stimulated neopterin was inversely related to measures of pulmonary function, exercise capacity, and gas exchange. Conclusions Neopterin may be a useful diagnostic adjunct in the non-invasive assessment of CBD, differentiating CBD from BeS. Further studies will be required to determine how it performs in workplace screening. Am. J. Ind. Med. 43:592,601, 2003. © 2003 Wiley-Liss, Inc. [source] Immunoglobulins and complement in postmortem multiple sclerosis tissue,ANNALS OF NEUROLOGY, Issue 1 2009Michael H. Barnett MBBS Objective To identify evidence of a discrete, specific immune response in multiple sclerosis (MS) by analyzing the distribution of immunoglobulins and complement in tissue derived from cases of MS, and from control inflammatory white matter diseases known to express viral and autoantigens in the brain and spinal cord. Methods Autopsy tissue from 25 MS patients and 24 patients with other neurological diseases was examined immunohistochemically for immunoglobulins and activated complement (C3d and C9neo). Results In tissue remote from focal lesions in MS and other neurological diseases, IgG was detected in many normal structures but not in myelin or ramified microglia. Disrupted myelin in areas of active myelin breakdown and in phagocytes stained positively for C3d and C9neo, and equivocally for IgG in MS and all other neurological diseases examined, including ischemic infarcts. Disease-specific deposits of IgG or complement were detected in virus-infected cells in progressive multifocal leukoencephalopathy, subacute sclerosing panencephalitis, and cytomegalovirus encephalitis; in glial-limiting membranes in neuromyelitis optica; and in senile plaques in Alzheimer's dementia. Specific to MS were unusual microglial nodules containing short, linear deposits of activated complement (C3d) on partly demyelinated axons located in normal-appearing periplaque white matter. Interpretation IgG and complement immunostaining of disrupted myelin in MS lesions, frequently cited as an indication of pathogenic anti-myelin antibodies, is a nonspecific feature that cannot be interpreted as evidence of a distinct pathogenesis or serve to define particular variants of the disease. The unusual microglial nodules described in this study may constitute a specific biomarker with pathogenetic significance in MS. Ann Neurol 2009;65:32,46 [source] Novel CD8+ Treg suppress EAE by TGF-,- and IFN-,-dependent mechanismsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2009Mei-Ling Chen Abstract Although CD8+ Treg-mediated suppression has been described, CD8+ Treg remain poorly characterized. Here we identify a novel subset of CD8+ Treg that express latency-associated peptide (LAP) on their cell surface (CD8+LAP+ cells) and exhibit regulatory activity in vitro and in vivo. Only a small fraction of CD8+LAP+ cells express Foxp3 or CD25, although the expression levels of Foxp3 for these cells are higher than their LAP, counterparts. In addition to TGF-,, CD8+LAP+ cells produce IFN-,, and these cells suppress EAE that is dependent on both TGF-, and IFN-,. In an adoptive co-transfer model, CD8+LAP+ cells suppress myelin oligodendrocyte glycoprotein (MOG)-specific immune responses by inducing or expanding Foxp3+ cells and by inhibiting proliferation and IFN-, production in vivo. Furthermore, in vivo neutralization of IFN-, and studies with IFN-,-deficient mice demonstrate an important role for IFN-, production in the function of CD8+LAP+ cells. Our findings identify the underlying mechanisms that account for the immunoregulatory activity of CD8+ T cells and suggest that induction or amplification of CD8+LAP+ cells may be a therapeutic strategy to help control autoimmune processes. [source] Testosterone and innate immune function inversely covary in a wild population of breeding Dark-Eyed Juncos (Junco hyemalis)FUNCTIONAL ECOLOGY, Issue 5 2006T. J. GREIVES Summary 1Innate immunity refers to the non-specific components of the primary immune response, which act broadly to destroy pathogens. Effective innate immune responses may save an individual the energetic costs associated with activating subsequent specific immune responses. 2Testosterone can suppress immune function in vitro and in vivo. Most studies examining testosterone's effects on immunity have focused on experimentally elevated testosterone and acquired immune responses (e.g. humoral and cell-mediated responses to foreign antigens). Few studies have investigated the relationship between endogenous levels of testosterone and innate immunity. 3In a wild breeding population of Dark-Eyed Juncos (Junco hyemalis Linnaeus), we asked whether endogenous levels of testosterone measured at several points during the breeding season covaried with two components of innate immunity: total levels of non-specific immunoglobulin-G (IgG), and complement levels. 4Testosterone levels were significantly negatively correlated with both total IgG and complement activity. Both immune measures were also positively correlated with body mass. Taken together with experimental results from the same species, these results suggest that elevated testosterone levels may compromise innate as well as acquired immune function. [source] Peripheral tolerance limits CNS accumulation of CD8 T cells specific for an antigen shared by tumor cells and normal astrocytesGLIA, Issue 15 2008Thomas Calzascia Abstract T cell mediated immunotherapies are proposed for many cancers including malignant astrocytoma. As such therapies become more potent, but not necessarily more tumor-specific, the risk of collateral autoimmune damage to normal tissue increases. Tumors of the brain present significant challenges in this respect, as autoimmune destruction of brain tissue could have severe consequences. To investigate local immune reactivity toward a tumor-associated antigen in the brain, transgenic mice were generated that express a defined antigen (CW3170,179) in astroglial cells. The resulting six transgenic mouse lines expressed the transgenic self-antigen in cells of the gastrointestinal tract and CNS compartments, or in the CNS alone. By challenging transgenic mice with tumor cells that express CW3, self/tumor-specific immune responses were visualized within a normal polyclonal T cell repertoire. A large expansion of the endogenous CW3170,179 -specific CD8 T cell population was observed in nontransgenic mice after both subcutaneous and intracerebral implantation of tumor cells. In contrast, CW3170,179 -specific immune responses were not observed in transgenic mice that exhibited extracerebral transgene expression. Importantly, in certain groups of mice in which transgene expression was restricted to the CNS, antigen-specific immune responses occurred when tumor was implanted subcutaneously, but not intracerebrally. This local immune tolerance in the brain was induced via peripheral (extrathymic) rather than central (thymic) tolerance mechanisms. Thus, this study highlights the role of regional immune regulation in the prevention of autoimmunity in the brain, and the potential impact of these mechanisms for brain tumor immunotherapy. © 2008 Wiley-Liss, Inc. [source] Suppression of allergic airway inflammation in a mouse model by Der p2 recombined BCGIMMUNOLOGY, Issue 1pt2 2009Hai-Feng Ou-Yang Summary Allergic asthma is a chronic inflammatory disease mediated by T helper (Th)2 cell immune responses. Currently, immunotherapies based on both immune deviation and immune suppression, including the development of recombinant mycobacteria as immunoregulatory vaccines, are attractive treatment strategies for asthma. In our previous studies, we created a genetically recombinant form of bacille Calmette,Guerin (rBCG) that expressed Der p2 of house dust mites and established that it induced a shift from a Th2 response to a Th1 response in naive mice. However, it is unclear whether rBCG could suppress allergic airway inflammation in a mouse model. In this article we report that rBCG dramatically inhibited airway inflammation, eosinophilia, mucus production and mast cell degranulation in allergic mice. Analysis of interferon-, (IFN-,) and interleukin-4 (IL-4) levels in bronchoalveolar lavage fluid (BALF) and lung tissue revealed that the suppression was associated with a shift from a Th2 response to a Th1 response. At the same time, rBCG induced a CD4+ CD25+ Foxp3+ T-cell subtype that could suppress the proliferation of Th2 effector cells in vitro in an antigen-specific manner. Moreover, suppression of CD4+ CD25+ T cells could be adoptively transferred. Thus, our results demonstrate that rBCG induces both generic and specific immune responses. The generic immune response is associated with a shift from a Th2 to a Th1 cytokine response, whereas the specific immune response against Der p2 appears to be related to the expansion of transforming growth factor-, (TGF-,)-producing CD4+ CD25+ Foxp3+ regulatory T cells. rBCG can suppress asthmatic airway inflammation through both immune deviation and immune suppression and may be a feasible, efficient immunotherapy for asthma. [source] A novel synthetic adjuvant enhances dendritic cell functionIMMUNOLOGY, Issue 1pt2 2009Karen S. M. Phillipps Summary The lipid core peptide (LCP) is a novel, synthetic, self-adjuvanted vaccine delivery system that neatly incorporates the adjuvant, carrier and antigenic peptides of a vaccine into a single molecular entity. This system has been previously shown to efficiently deliver vaccines and induce immunity. Because adjuvants target sentinels of the immune response, such as dendritic cells (DCs), that are widely distributed throughout the body to initiate specific immune responses, we investigated the effects of the adjuvant on DCs. Here we show that LCP targets vaccines to DCs and induces their activation. [source] TCRBV3S1 and TCRBV18 gene segment polymorphisms in Brazilian Caucasoid and Black populationsINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 1 2002C. Dresch Summary The T-cell receptor (TCR) repertoire plays an important role in shaping specific immune responses. Genetic polymorphisms at the TCR locus, in both constant and variable regions, seem to represent an important mechanism for generating inter-individual and inter-population differences. Considering the scarcity of immune parameters characterized for normal human populations, we decided to determine the frequency of two TCRBV polymorphisms (located in the TCRBV3S1 and TCRBV18 gene segments) in two ethnically distinct groups of the general Brazilian population. Both polymorphisms are related to the expression of these segments at the T-cell surface and can consequently modulate the T-cell repertoire, potentially modifying the capacity of a given individual to develop an immune response. These DNA polymorphisms were analysed in material obtained from adult, normal South-American Caucasoid and Black individuals. A total of 139 individuals were analysed for the TCRBV3S1 and 141 for the TCRBV18 gene segment polymorphisms. The data indicated statistically significant differences in allelic frequencies for the two ethnic groups analysed, suggesting that any correlation between TCR usage or T-cell repertoire and development of a given disease should take in account the ethnic origin of the population studied. [source] Gill disease of marine fish caused by infection with Neoparamoeba pemaquidensisJOURNAL OF FISH DISEASES, Issue 9 2001B L Munday Amoebic gill disease (AGD) of maricultured salmonids, turbot, Scophthalmus maximus (L.), European seabass, Dicentrarchus labrax (L.), and sharpsnout seabream, Diplodus puntazzo (Cetti), caused by Neoparamoeba pemaquidensis has been reported from Australia (Tasmania), Ireland, France, Chile, North America (Washington State and California) and Spain. Of the salmonids, Atlantic salmon, Salmo salar L., appears to be the most susceptible with rainbow trout, Oncorhynchus mykiss (Walbaum), also suffering significant disease. Only minor outbreaks have been reported in coho, O. kisutch (Walbaum), and chinook salmon, O. tshawytscha (Walbaum). The disease now accounts for 10,20% of production costs of Atlantic salmon in Tasmania and has lead to temporary abandonment of culture of this species in parts of Spain. It is of lesser, but still significant, importance in other countries. Much is known about the pathology of AGD but the pathophysiology of the disease is poorly understood. There is evidence that non-specific immunity is involved in fish acquiring resistance to AGD, but no unequivocal evidence exists for protection as a result of specific immune responses. To date, for salmonids, the only effective treatment for AGD is a freshwater bath. Control procedures based on modification of management strategies have been minimal and virtually unresearched. [source] Effects of graded levels of dietary myo -inositol on non-specific immune and specific immune parameters in juvenile Jian carp (Cyprinus carpio var. Jian)AQUACULTURE RESEARCH, Issue 10 2010Wei-Dan Jiang Abstract The aim of this study was to evaluate the effects of myo -inositol (MI) on non-specific immune and specific immune defence in fish. A total of 1050 Jian carp (Cyprinus carpio var. Jian) (22.28±0.07 g) were randomly distributed into seven groups, of three replicates each, of feeding diets containing graded levels of MI (163.5, 232.7, 384.2, 535.8, 687.3, 838.8 and 990.3 mg MI kg,1 diet). After a 60-day growth trial, an infectious trial was conducted by injection of Aeromonas hydrophila for 17 days. Results showed that the red blood cell (RBC) and the white blood cell count were significantly increased with increasing MI levels up to 535.8 mg kg,1 diet (P<0.05). The spleen index showed a tendency similar to RBC, whereas the head kidney index showed the inverse pattern (P<0.05). The phagocytic activity of leucocytes, haemagglutination titre, lysozyme activity, anti- A. hydrophila antibody titre and immunoglobulin M, after being injected with A. hydrophila, were all improved with an increase in the MI levels up to 232.7,687.3 mg kg,1 diet respectively (P<0.05). Myo -inositol did not influence serum acid phosphatase activity and total iron-binding capacity (P>0.05). These results suggested that MI could enhance non-specific immune and specific immune responses in fish. [source] Photodynamic therapy-generated tumor cell lysates with CpG-oligodeoxynucleotide enhance immunotherapy efficacy in human papillomavirus 16 (E6/E7) immortalized tumor cellsCANCER SCIENCE, Issue 5 2007Su-Mi Bae Immunotherapy with photodynamic therapy (PDT) offers great promise as a new alternative for cancer treatment; however, its use remains experimental. In this study, we examined the immunotherapeutic significance of human papillomavirus (HPV)-immortalized tumor cell lysates induced by PDT with CpG-oligodeoxynucleotide (ODN). PDT-cell lysates were generated by irradiating Radachlorin (5 µg/mL) preloaded TC-1 cells carrying HPV 16 E7. PDT-cell lysates plus ODN coinjection for protection against E7-expressing tumors as well as specific immune responses were evaluated with the following tests: heat shock protein 70 (HSP70) enzyme-linked immunosorbent assay, in vitro and in vivo tumor growth inhibition, interferon-, (IFN-,) and tumor necrosis factor-, (TNF-,) assay, cytotoxic T-lymphocyte assay, and fluorescence activated cell sorting (FACS) analysis. PDT-cell lysates plus ODN coinjection showed a significant suppression of tumor growth at both prophylactic and therapeutic levels, compared to PDT (or F/T)-cell lysates or ODN alone. In addition, we evaluated the level of the immune response with the coinjection. HSP70, an important regulator of inflammatory and immune response, was observed in abundance in the PDT-cell lysates. IFN-, production and cytotoxic T lymphocytes (CTL) responses were induced by PDT-cell lysates plus ODN injection. The coinjection resulted in PDT-cell lysate-specific antibodies (IgG1, IgG2a, IgG2b, and IgG3) and T-helper cell responses significantly higher than PDT-cell lysates alone. Moreover, IFN-, production and CTL responses were significantly induced in the PDT-cell lysate plus ODN immunized groups. These enhanced immune responses appeared to be mediated by CD8+ T cells only. These data suggest that PDT-cell lysates plus ODN injection may be an effective approach to induce CTL immune responses as a possible immunotherapeutic strategy for cancer therapy. (Cancer Sci 2007; 98: 747,752) [source] | ||||||||||||||||