Home About us Contact
|
Home About us Contact | ||
|
|
||
Humoral Immunity (humoral + immunity)
Selected AbstractsAmerican Society of Transplantation Symposium on B Cells in Transplantation: Harnessing Humoral Immunity from Rodent Models to Clinical PracticeAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2007A. D. Kirk There is growing awareness that B cells and alloantibodies are important mediators of both acute and chronic allograft injury. Unfortunately, few therapies are clinically available to mitigate the function of B cells or the effects of established alloantibody. As a result, many sensitized people await transplantation without a suitable donor, and several rejection syndromes are emerging that appear to involve B cells either as antibody producers or as antigen-presenting cells. In recognition of this unmet need in transplantation, the American Society of Transplantation organized a Symposium on B cells in Organ Transplantation to foster interest in this topic amongst basic researchers attending the annual meeting of the American Association of Immunologists. This manuscript will give an overview of the presentations from this symposium including the current risks of allosensitization, adaptive accommodation, approaches toward B-cell tolerance for allo- and xenoantigens and clinical application of these concepts in ABO incompatible neonatal cardiac transplantation. [source] Expression of individual immunoglobulin genes occurs in an unusual system consisting of multiple independent lociEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2004Donna Abstract Humoral immunity is effected through the rearrangement of immunoglobulin (Ig) genes in individual somatic cells committed to the B,lymphocyte lineage. Haplotype or allelic exclusion restricts B,lymphocytes to the expression of a single Ig receptor that can sustain further somatic modification. In most species, a specific Ig chain is encoded at a single genetic locus. However, in cartilaginous fish, hundreds of independent Ig heavy- (IgH) and Ig light-chain (IgL) gene loci are present, many of which are joined in the germ line. Ig gene transcripts have been amplified from single peripheral blood lymphocytes isolated from the clearnose skate (Raja eglanteria) using reverse-transcription PCR, and a single productive IgH transcript was detected in the majority of cells analyzed. Similarly, only a single IgL transcript was detected in over half of the individual cells. Taken together, these findings suggest that a mechanism for haplotype exclusion arose early in the evolution of antibody diversity and is independent of a single genetic locus. [source] Humoral immunity in natural infection by tick-borne encephalitis virusJOURNAL OF MEDICAL VIROLOGY, Issue 4 2009Giulietta Venturi Abstract Tick-borne encephalitis (TBE) virus is one of the most important flaviviruses associated with neurological disease in Europe. Cross-reactive antibodies elicited by different flaviviruses can make difficult the interpretation of ELISA and hemagglutination-inhibition (HI) tests for the diagnosis of TBE. Neutralization tests, which are more specific, are not in common use because they are difficult to perform and standardize. A plaque reduction neutralization test (PRNT), optimized previously in vaccinated children, was evaluated in sera from acute cases of TBE, collected for diagnostic purposes, and from healthy human population and wild ruminants, collected for serosurvey purposes. The PRNT results were compared with the results of ELISA and HI tests. In acute TBE disease, most sera were positive for IgM antibodies by ELISA and with high HI antibody titers; neutralizing antibodies were detected in 71.4% of patients, at a very low titer (1:10 NT50) in almost all cases. Seroprevalences of 8% and 6.5% for anti-TBE ELISA antibodies were found in healthy subjects and wild ruminants, respectively. Among anti-TBE positive healthy subjects, a very low 1:10 NT50 titer was detected in 17.4% of cases, while NT80 titers ranging from 1:10 to 1:80 were detected in 65.2% of cases. Among wild ruminants, 90.9% of ELISA and HI positive samples showed a positive, ,1:10 NT80 titer. In conclusion, neutralization assays can be useful for the diagnosis and serosurveys of TBE. J. Med. Virol. 81:665,671, 2009 © 2009 Wiley-Liss, Inc. [source] Humoral immunity to diphtheria, tetanus, measles, and hemophilus influenzae type b in children with acute lymphoblastic leukemia and response to re-vaccinationPEDIATRIC BLOOD & CANCER, Issue 6 2009Emine Zengin Abstract Objective Loss of immunity to previous vaccination and timing of re-vaccination in children receiving chemotherapy remains controversial. The aim of this study was to investigate the immunity to vaccine preventable diseases in children with acute lymphoblastic leukemia (ALL). Procedure Sixty-one patients with ALL and 13 healthy siblings were enrolled. Three study groups included newly diagnosed patients (group 1), patients on maintenance chemotherapy (group 2), and patients that completed chemotherapy (group 3). Blood samples for baseline antibody titers were obtained from all the patients and controls. Patients in group 2 were vaccinated with diphtheria, tetanus, and hemophilus influenzae type b (Hib). Patients in group 3 and controls received the measles vaccine in addition to all the above vaccines. In groups 2 and 3, post-vaccination antibody titers were also obtained. Results Patients and controls had no Hib vaccine during primary vaccination. After chemotherapy median antibody levels against diphtheria, tetanus, measles, and Hib were decreased but tetanus antibodies were still at the protective levels. Proportions of the patients with protective levels were 11.1%, 83.3%, 16.7%, and 16.7% for diphtheria, tetanus, Hib, and measles, respectively. Vaccination achieved protective antibody levels in 81%, 100%, 89.5%, and 70% of the patients for diphtheria, tetanus, Hib, and measles, respectively. Vaccine responses during maintenance were also satisfying. Conclusion We recommend re-vaccination after 3 months of cessation of chemotherapy. Administration of Hib vaccine may be beneficial after the first 3 months of maintenance chemotherapy especially in children with no primary vaccination followed by a second booster dose after cessation of therapy to increase immunity. Pediatr Blood Cancer 2009;53:967,972. © 2009 Wiley-Liss, Inc. [source] Humoral immunity in renal transplantation: clinical significance and therapeutic approachCLINICAL TRANSPLANTATION, Issue 6 2008Ajda T. Rowshani Abstract:, Donor-specific antibodies (DSA) form a significant barrier in solid organ transplantation of highly pre-sensitized candidates. Although avoiding transplantation over a positive cross-match test can largely prevent the occurrence of hyperacute antibody-mediated rejection, transplantation of highly pre-sensitized candidates is often complicated by the occurrence of acute and chronic antibody-mediated graft rejection leading to diminished graft function and survival. The pre-existent HLA and/or non-HLA-specific antibodies are without any doubt important contributing factors underlying humoral-mediated graft injury. Furthermore, increasing evidence underlines the association of newly formed de novo DSA after transplantation with poor graft function and survival. There is still a need to further develop desensitizing therapies not only to make transplantation of highly pre-sensitized candidates feasible, but also to reduce the new formation of allo-antibodies. Here, we summarize current views on desensitization therapies and the impact of the presence of DSA on the fate of the kidney graft. [source] Immunity against mouse thymus-leukemia antigen (TL) protects against development of lymphomas induced by a chemical carcinogen, N -butyl- N -nitrosoureaCANCER SCIENCE, Issue 11 2004Kunio Tsujimura Mouse thymus-leukemia antigens (TL) are aberrantly expressed on T lymphomas in C57BL/6 (B6) and C3H/He (C3H) mice, while they are not expressed on normal T lymphocytes in these strains. When N -butyl- N -nitrosourea (NBU), a chemical carcinogen, was administered orally to B6 and C3H strains, lymphoma development was slower than in T3b -TL gene-transduced counterpart strains expressing TL ubiquitously as self-antigens, suggesting that anti-TL immunity may play a protective role. In addition, the development of lymphomas was slightly slower in C3H than in B6, which seems to be in accordance with the results of skin graft experiments indicating that both cellular and humoral immunities against TL were stronger in C3H than B6 mice. The interesting finding that B lymphomas derived from a T3b -TL transgenic strain (C3H background) expressing a very high level of TL were rejected in C3H, but not in H-2Kb transgenic mice (C3H background), raises the possibility that TL-specific effector T cell populations are eliminated and/or anergized to a certain extent by interacting with H-2Kb molecules. [source] How B cells shape the immune response against Mycobacterium tuberculosisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2009Paul J. Maglione Abstract Extensive work illustrating the importance of cellular immune mechanisms for protection against Mycobacterium tuberculosis has largely relegated B-cell biology to an afterthought within the tuberculosis (TB) field. However, recent studies have illustrated that B lymphocytes, through a variety of interactions with the cellular immune response, play previously underappreciated roles in shaping host defense against non-viral intracellular pathogens, including M. tuberculosis. Work in our laboratory has recently shown that, by considering these lymphocytes more broadly within their variety of interactions with cellular immunity, B cells have a significant impact on the outcome of airborne challenge with M. tuberculosis as well as the resultant inflammatory response. In this review, we advocate for a revised view of TB immunology in which roles of cellular and humoral immunity are not mutually exclusive. In the context of our current understanding of host defense against non-viral intracellular infections, we review recent data supporting a more significant role of B cells during M. tuberculosis infection than previously thought. [source] Broad T cell immunity to the LcrV virulence protein is induced by targeted delivery to DEC-205/CD205-positive mouse dendritic cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2008Yoonkyung Do Abstract There is a need for a more efficient vaccine against the bacterium Yersinia pestis, the agent of pneumonic plague. The F1-LcrV (F1-V) subunit vaccine in alhydrogel is known to induce humoral immunity. In this study, we utilized DC to investigate cellular immunity. We genetically engineered the LcrV virulence protein into the anti-DEC-205/CD205 mAb and thereby targeted the conjugated protein directly to mouse DEC-205+ DC in situ. We observed antigen-specific CD4+ T cell immunity measured by intracellular staining for IFN-, in three different mouse strains (C57BL/6, BALB/c, and C3H/HeJ), while we could not observe such T cell responses with F1-V vaccine in alhydrogel. Using a peptide library for LcrV protein, we identified two or more distinct CD4+ T cell mimetopes in each MHC haplotype, consistent with the induction of broad immunity. When compared to nontargeted standard protein vaccine, DC targeting greatly increased the efficiency for inducing IFN-,-producing T cells. The targeted LcrV protein induced antibody responses to a similar extent as the F1-V subunit vaccine, but Th1-dependent IgG2a and IgG2c isotypes were observed only after anti-DEC-205:LcrV mAb immunization. This study sets the stage for the analysis of functional roles of IFN-,-producing T cells in Y.,pestis infection. [source] To switch or not to switch , the opposing roles of TACI in terminal B cell differentiationEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2007Ulrich Salzer MD Abstract The TNF superfamily ligands BAFF and APRIL and their three receptors BAFFR, BCMA, and TACI comprise a network that is critically involved in the development and function of humoral immunity. Failure of this complex system is associated with autoimmune disease, B lymphocyte tumours, and antibody deficiency. While BAFF:BAFFR interactions control peripheral B cell survival and homeostasis, BCMA function seems limited to the survival of long-lived bone marrow plasma cells. The functional activity of the third receptor TACI is, however, ambiguous: while TACI,/, mice predominantly develop autoimmunity and lymphoproliferation, TACI deficiency in humans primarily manifests itself as an antibody deficiency syndrome. An article in this issue of the European Journal of Immunology demonstrates a negative regulation via TACI in human B cells by using TACI specific antibodies. B cell proliferation, class switch recombination, and Ig production induced by various stimuli were inhibited via TACI. Within the BAFF/APRIL network, the expression of the receptors and ligands is spatially, as well as temporally, highly regulated at various stages of B cell development and function. Defining the exact contribution of TACI stimulation by specific triggers in vitro enables us to better understand the complex, context-dependent responses initiated by TACI in vivo. See accompanying article http://dx.doi.org/10.1002/eji.200636623 [source] Carotenoid and melanin-based ornaments signal similar aspects of male quality in two populations of the common yellowthroatFUNCTIONAL ECOLOGY, Issue 1 2010Peter O. Dunn Summary 1.,Female preferences for particular male ornaments may shift between populations as a consequence of ecological differences that change the reliability and detectability of the ornament, but few studies have examined how ornaments function in different populations. 2.,We examined the signalling function of male plumage ornaments in a warbler, the common yellowthroat (Geothlypis trichas), breeding in New York (NY) and Wisconsin (WI), USA. Males have two prominent ornaments: a black facial mask pigmented with melanin and a yellow bib pigmented by carotenoids. Previous studies in WI indicate that the size of the mask, and not the bib, is primarily related to female choice and male reproductive success. In NY, however, the pattern is reversed and attributes of the bib (size and colour), and not the mask, are the target of sexual selection. 3.,We found that brightness of the yellow bib was the best signal of humoral immunity (immunoglobulin G) in NY and mask size was the best signal in WI, after controlling for breeding experience and capture date. Thus, similar aspects of male quality appeared to be signalled by different ornaments in different populations. 4.,There was no difference between populations in the level of plasma carotenoids or the prevalence of malarial parasites, which may affect the costs and benefits of choosing males with particular ornaments in each location. 5.,Even though females in different populations prefer different ornaments produced by different types of pigments, these ornaments appear to be signalling similar aspects of male quality. Our results caution against inferring the function of particular ornaments based simply on their type of pigment. [source] Deficiency in OGG1 Protects against Inflammation and Mutagenic Effects Associated with H. pylori Infection in MouseHELICOBACTER, Issue 5 2006Eliette Touati Abstract Background:,Helicobacter pylori infection is associated with gastric cancer. Study with the Big Blue mouse model has reported a mutagenic effect associated with the H. pylori infection, as a result in part of oxidative DNA damage. The present work investigates the consequences of a deficiency in the OGG1 DNA glycosylase, responsible for the excision of 8-oxo guanine, on the inflammatory and genotoxic host response to the infection. Materials and Methods:, Big Blue Ogg1,/, C57BL/6 mice were orally inoculated with H. pylori strain SS1 or vehicle only, and sacrificed after 1, 3, or 6 months. The serologic response, histologic lesions, mutant frequency, and spectra of mutations were assessed in the stomach and compared to what observed in the wild-type (Wt) context. Results:, Inflammatory lesions induced in the gastric mucosa of H. pylori -infected mice, corresponding to a moderate gastritis, were less severe in Ogg1,/, than in Wt Big Blue mice. Analysis of antimicrobial humoral immunity exhibited a lower IgG2a serum level (Th1 response) after 6 months of infection in Ogg1,/, than in the Wt mice. In these conditions, the H. pylori -SS1 infection in the Ogg1,/, mice did not induce a mutagenic effect at the gastric epithelial cells level, either after 3 or 6 months. Conclusions:, The inactivation of the OGG1 DNA glycosylase in mouse leads to less severe inflammatory lesions and abolished the mutagenic effect at the gastric epithelial cells level, induced by the H. pylori infection. These data suggest for the OGG1deficiency a protective role against inflammation and genotoxicity associated to the H. pylori infection. [source] Quantitative analysis of anti,hepatitis C virus antibody,secreting B cells in patients with chronic hepatitis C,HEPATOLOGY, Issue 1 2006Takeji Umemura To investigate the quantitative characteristics of humoral immunity in patients with hepatitis C, we established an enzyme-linked immunosorbent spot (ELISpot) assay for detection of anti,hepatitis C virus (HCV)-secreting B cells. Receiver operating characteristic curve analysis demonstrated 100% specificity and 58% to 92% sensitivity for detecting B-cell responses to NS5b, NS3, E2, and core antigens. The median sum of anti-HCV,secreting B cells to all HCV antigens tested was significantly higher in 39 patients with chronic hepatitis C (47.3 spot forming cells [SFCs]/106 peripheral blood mononuclear cells [PBMCs]) than in 9 recovered subjects (15.3 SFCs/106 PBMCs; P = .05) or 11 uninfected controls (5.3 SFCs/106 PBMCs; P < .001); the significant difference (P = .018) in chronic versus recovered patients was in reactivity to nonstructural antigens NS3 and NS5b. Anti-HCV immunoglubulin M (IgM),secreting B cells were also readily detected and persisted decades into HCV infection; there was no difference in IgM-positive cells between chronic and recovered patients. ELISpot reactivity to genotype 1,derived antigens was equivalent in patients of genotypes 1, 2, and 3. There was significant correlation between the numbers of anti-HCV IgG-secreting B cells and serum aminotransferase and to the level of circulating antibody. In conclusion, ELISpot assays can be adapted to study B-cell as well as T-cell responses to HCV. Measurement at the single-cell level suggests that humoral immunity plays a minor role in recovery from HCV infection and that B-cell immunity is strongest in those with persistent infection. (HEPATOLOGY 2005.) [source] Long-term follow-up after successful interferon therapy of acute hepatitis CHEPATOLOGY, Issue 1 2004Johannes Wiegand Early treatment of acute hepatitis C infection with interferon alfa-2b (IFN-,-2b) prevents chronicity in almost all patients. So far, no data are available on the long-term outcome after interferon (IFN) therapy of acute hepatitis C. The aim of this study was to assess the clinical, virological, and immunological long-term outcome of 31 successfully treated patients with acute hepatitis C infection who were followed for a median of 135 weeks (52-224 weeks) after end of therapy. None of the individuals had clinical evidence of liver disease. Alanine aminotransferase (ALT) levels were normal in all but 1 patient. Serum hepatitis C virus (HCV) RNA was negative throughout follow-up, even when investigated with the highly sensitive transcription-mediated amplification (TMA) assay (cutoff 5-10 IU/mL). In addition, no HCV RNA was detected in peripheral blood mononuclear cells (PBMC) of 15 cases tested. The patients' overall quality-of-life scores as determined by the SF-36 questionnaire did not differ from the German reference control cohort. Ex vivo interferon gamma (IFN-,) ELISPOT analysis detected HCV-specific CD4+ T-helper cell reactivity in only 35% of cases, whereas HCV-specific CD8+ T-cell responses were found in 4 of 5 HLA -A2,positive individuals. Anti-HCV antibody levels decreased significantly during and after therapy in all individuals. In conclusion, early treatment of symptomatic acute hepatitis C with IFN-,-2b leads to a long-term virological, biochemical, and clinical response. Waning of anti-HCV humoral immunity and presence of HCV-specific CD8+ (but not CD4+) T cells highlights the complexity of T-cell and B-cell memory to HCV, which might be significantly altered by IFN treatment. (HEPATOLOGY 2004;40:98,107.) [source] Antibodies Against Hepatitis C Virus,Like Particles and Viral Clearance in Acute and Chronic Hepatitis CHEPATOLOGY, Issue 3 2000Thomas F. Baumert M.D. We recently described the efficient assembly of hepatitis C virus (HCV) structural proteins into HCV-like particles (HCV-LPs) in insect cells. These noninfectious HCV-LPs have similar morphologic and biophysical properties as putative virions isolated from HCV-infected humans and can induce a broadly directed immune response in animal models. The HCV envelope proteins of HCV-LPs are presumably presented in a native, virion-like conformation and may therefore interact with antienvelope antibodies directed against conformational epitopes. In this study, HCV-LPs were used as capture antigens in an enzyme-linked immunosorbent assay (ELISA) to detect and quantify antibodies against HCV structural proteins in patients with acute and chronic hepatitis C. High titers of anti,HCV-LP antibodies were detected in patients chronically infected with HCV genotypes 1 to 6. In contrast to individuals with chronic hepatitis C, patients with acute self-limited hepatitis C displayed only a transient and weak seroreactivity against HCV-LPs. Patients with chronic HCV infection successfully treated with interferon demonstrated a gradual decline of anti,HCV-LP titers during or subsequent to viral clearance. Sustained interferon responders were characterized by significantly higher pretreatment levels of anti,HCV-LP antibodies as compared with nonresponders (P = .0001). In conclusion, HCV infection is associated with limited humoral immunity against the envelope proteins present on the HCV-LPs. An HCV-LP,based ELISA may be a useful diagnostic tool to distinguish acute hepatitis C from chronic HCV infection with exacerbation, and to predict viral clearance in response to interferon. [source] The fundamental contribution of Robert A. Good to the discovery of the crucial role of thymus in mammalian immunityIMMUNOLOGY, Issue 3 2006Domenico Ribatti Summary Robert Alan Good was a pioneer in the field of immunodeficiency diseases. He and his colleagues defined the cellular basis and functional consequences of many of the inherited immunodeficiency diseases. His was one of the groups that discovered the pivotal role of the thymus in the immune system development and defined the separate development of the thymus-dependent and bursa-dependent lymphoid cell lineages and their responsibilities in cell-mediated and humoral immunity. [source] The CD1d-binding glycolipid ,-galactosylceramide enhances humoral immunity to T-dependent and T-independent antigen in a CD1d-dependent mannerIMMUNOLOGY, Issue 1 2006Gillian A. Lang Summary Specific interaction of class II/peptide with the T-cell receptor (TCR) expressed by class II-restricted CD4+ T helper (Th) cells is essential for in vivo production of antibodies reactive with T-dependent antigen. In response to stimulation with CD1d-binding glycolipid, V,14+ TCR-expressing, CD1d-restricted natural killer T (NKT) cells may provide additional help for antibody production. We tested the hypothesis that the CD1d-binding glycolipid ,-galactosylceramide (,-GC) enhances production of antibodies reactive with T-dependent antigen in vivo. ,-GC enhanced antibody production in vivo in a CD1d-dependent manner in the presence of class II-restricted Th cells and induced a limited antibody response in Th-deficient mice. ,-GC also led to alterations in isotype switch, selectively increasing production of immunoglobulin G2b. Further analysis revealed that ,-GC led to priming of class II-restricted Th cells in vivo. Additionally, we observed that ,-GC enhanced production of antibodies reactive with T-independent antigen, showing the effects of NKT cells on B cells independently of Th cells. Our data show that NKT cells have multiple effects on the induction of a humoral immune response. We propose that NKT cells could be exploited for the development of novel vaccines where protective antibody is required. [source] Interleukin-21 is a T-helper cytokine that regulates humoral immunity and cell-mediated anti-tumour responsesIMMUNOLOGY, Issue 2 2004Pallavur V. Sivakumar Summary Cytokines and their receptors represent key targets for therapeutic intervention. Ligands are being used to supplement cell numbers that become depleted as a result of disease (organ failure, infection) or subsequent disease treatments (i.e. chemotherapy). Conversely, the inhibition of target cell binding by cytokines is an established strategy for abrogating pathologic cellular activities common to many immunological diseases. Considerable effort in biomedical research is being focused on the cytokine families that play a dominant role in regulating immunity and then prioritizing each member for its therapeutic potential. Currently, the interleukin-2 (IL-2) family of cytokines is widely recognized for its central involvement in controlling lymphocyte function and is the most explored for medical utility. Collectively, these proteins (or their antagonists) are either marketed drugs or have received advanced testing for an impressive array of indications including cancer, infectious disease, transplantation, inflammation and allergic asthma. Here we review the current understanding of IL-21, the most recent member of this cytokine family to be discovered. As will be discussed, IL-21 shares many of the same attributes as its relatives in that it has broad immunoregulatory activity and can modulate both humoral and cell-mediated responses. Its ability to stimulate durable anti-tumour responses in mice defines one therapeutic indication that merits clinical development. [source] Rhesus macaque antibody molecules: sequences and heterogeneity of alpha and gamma constant regionsIMMUNOLOGY, Issue 1 2004Franco Scinicariello Summary Rhesus macaques (Macaca mulatta) are extensively used in vaccine development. Macaques infected with simian immunodeficiency viruses (SIV) or simian-human immunodeficiency viruses (SHIV) are the best animal model currently available for acquired-immune-deficiency-syndrome-related studies. Recent results emphasize the importance of antibody responses in controlling HIV and SIV infection. Despite the increasing attention placed on humoral immunity in these models, very limited information is available on rhesus macaque antibody molecules. Therefore, we sequenced, cloned and characterized immunoglobulin gamma (IGHG) and alpha (IGHA) chain constant region genes from rhesus macaques of Indian and Chinese origin. Although it is currently thought that rhesus macaques express three IgG subclasses, we identified four IGHG genes, which were designated IGHG1, IGHG2, IGHG3 and IGHG4 on the basis of sequence similarities with the four human genes encoding the IgG1, IgG2, IgG3 and IgG4 subclasses. The four genes were expressed at least at the messenger RNA level, as demonstrated by real-time reverse transcription polymerase chain reaction (RT-PCR). The level of intraspecies heterogeneity was very high for IGHA genes, whereas IGHG genes were remarkably similar in all animals examined. However, single amino acid substitutions were present in IGHG2 and IGHG4 genes, indicating the presence of IgG polymorphism possibly resulting in the expression of different allotypes. Two IgA alleles were identified in several animals and RT-PCR showed that both alleles may be expressed. Presence of immunoglobulin gene polymorphism appears to reflect the unusually high levels of intraspecies heterogeneity already demonstrated for major histocompatibility complex genes in this non-human primate species. [source] Partial tolerance of subcutaneously transplanted xenogeneic tumour cell graft by Fas-mediated immunosuppressionIMMUNOLOGY, Issue 1 2001Takahiro Sawada Summary Certain anti-Fas antibodies, such as RMF2, induce apoptosis of Fas-expressing cells. We applied the Fas/anti-Fas system to induce killing of Fas-expressing immunocytes with resultant immunosuppression. W7TM-1 tumour cells, a rat T-cell line, were inoculated subcutaneously in BALB/c mice and tumour growth was monitored in untreated mice and in mice treated with RMF2. Prior to treatment with RMF2, we examined the expression of Fas in isolated splenocytes and in tumour-infiltrating lymphocytes by flow cytometry and immunohistochemistry, respectively. There was a remarkable increase in Fas-positive lymphocytes, including natural killer (NK) cells, among splenocytes at day 5 after tumour cell inoculation. The number of Fas-positive infiltrating lymphocytes also increased markedly, from day 5 to day 10. We then examined whether RMF2 could induce apoptosis of Fas-positive activated lymphocytes isolated from the spleen at day 5 in vitro. Terminal deoxy (d) -UTP nick end labelling (TUNEL) and Annexin V staining methods showed apoptosis of isolated cells when incubated with RMF2, and typical apoptotic features were confirmed by 4,,6-diamidino-2-phenylindole dihydrochloride (DAPI) staining. Furthermore, suppression of cellular and humoral immunity was noted in RMF2-treated mice by mixed lymphocyte reaction and assay of serum levels of immunoglobulin G, respectively. Finally, treatment of animals with RMF2 daily from day 5 to day 9 could maintain the tumour size, while the tumour mass began to diminish in untreated mice immediately after reaching a maximum size. We confirmed the enhancing effects of long-term treatment with RMF2, through the induction of immunosuppression, on the growth of unvascularized xenogeneic tumour cell grafts. [source] Selective expression of inhibitory Fc, receptor by metastatic melanoma impairs tumor susceptibility to IgG-dependent cellular responseINTERNATIONAL JOURNAL OF CANCER, Issue 12 2008Lydie Cassard Abstract During melanoma progression, patients develop anti-tumor immunity including the production of anti-tumor antibodies. Although the strategies developed by malignant cells to escape anti-tumor cellular immunity have been extensively investigated, little is known about tumor resistance to humoral immunity. The main effect of IgG antibodies is to activate the immune response by binding to host Fc gamma receptors (Fc,R) expressed by immune cells. We previously reported in a limited study that some human metastatic melanoma cells ectopically express the Fc,RIIB1, an inhibitory isoform of Fc,R. By analyzing a large panel of different types of human primary and metastatic solid tumors, we report herein that expression of Fc,RIIB is restricted to melanoma and is acquired during tumor progression. We show that Fc,RIIB expression prevents the lysis of human metastatic melanoma cells by NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) in vitro, independently of the intracytoplasmic region of Fc,RIIB. Using experimental mouse models, we demonstrate that expression of Fc,RIIB protects B16F0 melanoma tumors from the ADCC induced by monoclonal and polyclonal anti-tumor IgG in vivo. Thus, our results identify Fc,RIIB as a marker of human metastatic melanoma that impairs the tumor susceptibility to Fc,R-dependent innate effector responses. © 2008 Wiley-Liss, Inc. [source] Antibody response against NY-ESO-1 in CHP-NY-ESO-1 vaccinated patientsINTERNATIONAL JOURNAL OF CANCER, Issue 10 2007Ryohei Kawabata Abstract NY-ESO-1 specific humoral responses are frequently observed in patients with various types of NY-ESO-1 antigen expressing tumors. In a large proportion of NY-ESO-1 antibody-positive patients of NY-ESO-1-specific CD8 T-cells can also be detected suggesting that monitoring of the NY-ESO-1 specific humoral immune response may be a relevant and more practical surrogate for estimating the overall immune response against NY-ESO-1 in clinical vaccine studies. We have immunized 9 cancer patients with full length NY-ESO-1 protein formulated with cholesterol-bearing hydrophobized pullulan (CHP-NY-ESO-1) and investigated the humoral immune responses against NY-ESO-1. Seven patients were NY-ESO-1 antibody-negative and 2 patients were positive prior to vaccination. Vaccination with CHP-NY-ESO-1 resulted in the induction or increase of NY-ESO-1 antibody responses in all 9 patients immunized. Epitope analysis revealed 5 regions in the NY-ESO-1 protein molecule that were recognized by antibodies induced after vaccination. The 5 regions were also recognized by antibodies present in nonvaccinated, NY-ESO-1 antibody-positive cancer patients. A peptide spanning amino acids 91,108 was recognized in 6 out of 9 vaccinated patients and in 8 out of 9 nonvaccinated, sero-positive patients, being the most dominant antigenic epitope in NY-ESO-1 for antibody recognition in cancer patients. In conclusion, we showed that CHP-NY-ESO-1 protein vaccination had a potent activity for inducing humoral immune responses against NY-ESO-1 antigen in cancer patients. The antigenic epitopes recognized by antibodies in the vaccinated patients were similar to those recognized in cancer patients with spontaneous humoral immunity against NY-ESO-1. © 2007 Wiley-Liss, Inc. [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] Carotenoid and protein supplementation have differential effects on pheasant ornamentation and immunityJOURNAL OF EVOLUTIONARY BIOLOGY, Issue 1 2007H. G. SMITH Abstract A currently popular hypothesis states that the expression of carotenoid-dependent sexual ornaments and immune function may be correlated because both traits are positively affected by carotenoids. However, such a correlation may arise for another reason: it is well known that immune function is dependent on nutritional condition. A recent study has suggested that the expression of ornaments may too depend on nutritional condition, as males in good nutritional condition are better at assimilating and/or modulating carotenoids. Thus, carotenoid-dependent ornaments and immune function may be correlated because both are dependent on nutritional condition. To elucidate if, and how, ornamentation and immune function are linked, pheasant diets were supplemented with carotenoid and/or protein in a fully factorial experiment. Carotenoid treatment affected wattle coloration and tail growth, but not cellular or humoral immunity. Immunity was unrelated to males' initial ornamentation including wattle colour. Males in better body condition, measured as residual mass, increased their wattle coloration more when carotenoid supplemented. Protein positively affected humoral but not cellular immunity, but had no effect on ornaments. Cellular, but not humoral, immunity increased with male body condition. Thus, there was no evidence that an immune-stimulatory effect of carotenoids resulted in wattle coloration honestly signalling immune function, but wattle coloration may still signal male body condition. [source] Maternal circulating interferon-, and interleukin-6 as biomarkers of Th1/Th2 immune status throughout pregnancyJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 1 2008Aziz Aris Abstract Aim:, T cells may be classified as T helper type 1 (Th1) cells, which synthesize cytokines inducing cellular immunity, or T helper type 2 (Th2), which synthesize cytokines inducing humoral immunity. According to the Th1/Th2 paradigm, it has been postulated that successful pregnancy induces an immune Th2 bias, but it is not yet clear how Th1 and Th2 systems vary simultaneously throughout the pregnancy. Methods:, Using maternal circulating interferon-, (IFN-,) and interleukin-6 (IL-6) as biomarkers of Th1 and Th2 cytokines, respectively, we examined the variation of circulating Th1/Th2 ratio in 35 healthy pregnant women from 10 to 40 weeks of pregnancy. Results:, With increasing gestational age, maternal circulating levels of IFN-, decrease, whereas those of IL-6 increase. The IFN-,/IL-6 ratio switches around the 19th week of pregnancy. Conclusions:, Our results suggest that maternal systemic IFN-, and IL-6 concentrations may be biomarkers of Th1/Th2 immune status during pregnancy. Moreover, our findings showed that contrary to the Th1/Th2 paradigm, the Th1 bias may be prevailing at the beginning of pregnancy, balanced in the middle of pregnancy and supplanted by the Th2 bias at the end of pregnancy. [source] Quantitative mouse model of implant-associated osteomyelitis and the kinetics of microbial growth, osteolysis, and humoral immunity,JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 1 2008Dan Li Abstract Although osteomyelitis (OM) remains a serious problem in orthopedics, progress has been limited by the absence of an in vivo model that can quantify the bacterial load, metabolic activity of the bacteria over time, immunity, and osteolysis. To overcome these obstacles, we developed a murine model of implant-associated OM in which a stainless steel pin is coated with Staphylococcus aureus and implanted transcortically through the tibial metaphysis. X-ray and micro-CT demonstrated concomitant osteolysis and reactive bone formation, which was evident by day 7. Histology confirmed all the hallmarks of implant-associated OM, namely: osteolysis, sequestrum formation, and involucrum of Gram-positive bacteria inside a biofilm within necrotic bone. Serology revealed that mice mount a protective humoral response that commences with an IgM response after 1 week, and converts to a specific IgG2b response against specific S. aureus proteins by day 11 postinfection. Real-time quantitative PCR (RTQ-PCR) for the S. aureus specific nuc gene determined that the peak bacterial load occurs 11 days postinfection. This coincidence of decreasing bacterial load with the generation of specific antibodies is suggestive of protective humoral immunity. Longitudinal in vivo bioluminescent imaging (BLI) of luxA-E transformed S. aureus (Xen29) combined with nuc RTQ-PCR demonstrated the exponential growth phase of the bacteria immediately following infection that peaks on day 4, and is followed by the biofilm growth phase at a significantly lower metabolic rate (p,<,0.05). Collectively, these studies demonstrate the first quantitative model of implant-associated OM that defines the kinetics of microbial growth, osteolysis, and humoral immunity following infection. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J. Orthop Res 26:96,105, 2008 [source] Depressed humoral immunity after weight reduction in competitive judoistsLUMINESCENCE: THE JOURNAL OF BIOLOGICAL AND CHEMICAL LUMINESCENCE, Issue 3 2002Seikou Ohta Abstract We studied changes in serum opsonic activity (SOA) in male judoists who were engaged in active weight reduction. Serum immunoglobulins, complements and SOA, measured by neutrophil-associated chemiluminescence responses, were investigated 20 days, 7 days and 1 day before a competition and 5 days after the competition. In addition, muscle strength and anaerobic work capacity, as well as body composition, were also determined. A dietary survey was conducted daily during the observation period. Body weight decreased by 4.2 kg over 19 days. SOA significantly decreased 5 days after the competition, as well as the concentrations of serum immunoglobulins, complements and total proteins. These trends were noted in the marked weight reduction group (i.e. reduction weight of body fat/body fat weight before weight reduction ,25%) more than the slight reduction group (<25%). Depressed SOA was closely correlated with the decreased concentrations of immunoglobulins and complements. These results suggest that the decrease in immunoglobulins and complements following weight reduction is associated with reduced SOA, which might cause susceptibility to infections. This study demonstrated that such immunosuppression appeared in the recovery period after the competition rather than immediately before the competition. Copyright © 2002 John Wiley & Sons, Ltd. [source] Female house wrens (Troglodytes aedon) increase the size, but not immunocompetence, of their offspring through extra-pair matingMOLECULAR ECOLOGY, Issue 16 2008ANNA M. FORSMAN Abstract House wrens are typically socially monogamous, but frequently engage in extra-pair matings leading to multisired broods. Because females do not appear to acquire direct material benefits from their extra-pair mates, we tested the hypothesis that female house wrens derive indirect genetic benefits, such as enhanced immunocompetence (cutaneous immune activity, humoral immunity, and plasma bactericidal activity) and condition (size and haematoserological traits) for their offspring, by mating polyandrously. We predicted that extra-pair young (EPY) should show greater immune responsiveness and better body condition than their within-pair maternal half-siblings (WPY). Contrary to our prediction, WPY had higher cutaneous immune activity than their EPY brood-mates in two of three years, and EPY and WPY did not differ in measures of innate and humoral immunity. WPY also had higher albumin to ,-globulin ratios than EPY; however, they were not in better condition based on other measures. EPY had consistently longer tarsi (a measure of long-bone size) than their WPY half-siblings, suggesting that females engage in extra-pair copulations with larger males. The benefits of large structural size in the study population is unknown, but based on evidence from other passerines, we suggest that structural size may be an important fitness-related trait in house wrens. We conclude that our results are not consistent with the hypothesis that females gain immune-related benefits for their offspring by engaging in extra-pair matings. Further study of the fitness consequences of differences in tarsus length is needed to determine whether females acquire size-related benefits for their offspring from extra-pair mates. [source] Identification of an ospC operator critical for immune evasion of Borrelia burgdorferiMOLECULAR MICROBIOLOGY, Issue 1 2007Qilong Xu Summary Timely expression of the outer surface protein C (OspC) is crucial for the pathogenic strategy of the Lyme disease spirochete Borrelia burgdorferi. The pathogen abundantly expresses OspC during initial infection when the antigen is required, but downregulates when its presence poses a threat to the spirochetes once the anti-OspC humoral response has developed. Here, we show that a large palindromic sequence immediately upstream of the ospC promoter is essential for the repression of ospC expression during murine infection and for the ability of B. burgdorferi to evade specific OspC humoral immunity. Deletion of the sequence completely diminished the ability of B. burgdorferi to avoid clearance by transferred OspC antibody in SCID mice. B. burgdorferi lacking the regulatory element was able to initiate infection but unable to persist in immunocompetent mice. Taken together, the regulatory element immediately upstream of the ospC promoter serves as an operator that may interact with an unidentified repressor(s) to negatively regulate ospC expression and is essential for the immune evasion of B. burgdorferi. [source] Ghrelin and leptin modulate immunity and liver function in overweight childrenPEDIATRICS INTERNATIONAL, Issue 1 2009Yuki Okamatsu Abstract Background:, The rising prevalence of obesity represents a growing worldwide public health problem. Interactions of adipocytokines and low-grade systemic inflammation presently are considered important in the development of obesity, as well as associated chronic disease including bronchial asthma, obesity-related liver disease and type 2 diabetes mellitus. The purpose of the present study was to investigate metabolic, hormonal, immunologic and inflammatory factors in overweight children and to further clarify possible immunomodulatory effects of obesity-related hormones and cytokines. Methods:, Forty-nine prepubertal overweight children and 49 age-matched controls of normal weight without underlying disease were enrolled. Levels of plasma ghrelin and serum leptin, cytokines (interleukin [IL]-4, IL-10, IL-12, 1L-13), C-reactive protein, immunoglobulin, and insulin were measured, and liver function tests were done to better understand their status in the setting of obesity. Results:, Overweight subjects had significantly higher measures of adiposity (body mass indexI, % body fat) and had significantly higher serum levels of IgG, IgA and IgE than non-obese children (P = 0.038, 0.0043, 0.0034, respectively); the opposite was true for IgM (P = 0.025). The incidence of presumed non-alcoholic fatty liver disease was 28.6% in overweight children. In overweight children, serum leptin levels were associated with liver function index (aspartate aminotransferase/alanine aminotransferase ratio) and serum insulin levels. Some elevated immunoglobulin levels significantly correlated with plasma ghrelin levels and liver function index. Conclusions:, It is possible that appetite-regulating hormones modulate both humoral immunity and liver function. Further studies with a larger number of subjects are needed to clarify the precise mechanisms of this association. [source] Gonadal steroids and salivary IgA in healthy young women and menAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 3 2010Sari M. Van Anders Empirical evidence from clinical, nonhuman animal, and in vitro studies point to links between immune function and gonadal steroids, including potential androgenic immunosuppression and estrogenic immunoenhancement. This study was designed to test links between steroids and one marker of mucosal humoral immunity,immunoglobulin A (IgA) in healthy individuals, to facilitate comparisons with other species and clinical populations, as there are few existing studies with healthy humans that also allow gender/sex investigations. Participants (86 women, 91 men) provided a saliva sample for measurement of testosterone (T), estradiol (E2), and IgA. Results showed that E2 was significantly and positively correlated with IgA in women, and group analyses by E2 quartile showed that this association was linear. No significant correlations or nonlinear associations were seen between T and IgA in men or women, or E2 and IgA in men. Evidence from this study indicates that IgA and E2 are significantly associated in healthy premenopausal women. Am. J. Hum. Biol. 2010. © 2009 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||||||||||||||