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Mucosal Immune Response (mucosal + immune_response)
Selected AbstractsIgG Subclass Responses in Childhood Helicobacter pylori Duodenal Ulcer: Evidence of T-Helper Cell Type 2 ResponsesHELICOBACTER, Issue 4 2004David I. Campbell ABSTRACT Background., Duodenal ulcer in adults chronically infected with Helicobacter pylori is associated with a polarized T-helper cell type 1 (Th1) mucosal immune response, with a predominantly immunoglobulin G2 (IgG2) systemic specific response. It has been suggested that children colonized by H. pylori also produce a mucosal Th1 response, but there are few studies that have measured IgG subclass responses in children with duodenal ulcer. Materials and methods., Seven children with endoscopically proven duodenal ulcer and H. pylori infection and 18 children with biopsy proven H. pylori infection but no duodenal ulcer had relative concentrations of IgG subclass responses (IgGsc) against H. pylori antigens measured by ELISA. Eighteen IgG seropositive adults acted as controls. The range of antigens recognised by IgG1 and IgG2 subclass responses were investigated by Western blots. Results., There were no differences in mean IgGsc responses between children with or without duodenal ulcer. Adults produced an IgG2 predominant response. Western blots showed no qualitative differences in antigens recognised by IgG1 or IgG2. Conclusion., Children with duodenal ulcer, in contrast to adults, produce an IgGsc response consistent with a mucosal Th2 response to H. pylori regardless of the presence of duodenal ulceration. This suggests that disease causation amongst children with H. pylori associated duodenal ulceration may not be dependant upon a mucosal Th1 biased response. [source] Probiotic administration in patients with ileal pouch,anal anastomosis for ulcerative colitis is associated with expansion of mucosal regulatory cellsINFLAMMATORY BOWEL DISEASES, Issue 5 2008Annamaria Pronio MD Abstract Background: Probiotics have anti-inflammatory effects in patients with inflammatory bowel disease and appear to regulate mucosal immune response through reductions in proinflammatory cytokines. The probiotic VSL#3 prevents pouchitis if started within a week of ileostomy closure and maintains remission following antibacterial treatment in patients with refractory or recurrent pouchitis. However, the efficacy of probiotics and their effects on regulatory cells if started at a greater time after surgery in patients undergoing ileal pouch anal anastomosis (IPAA) for ulcerative colitis are unknown. Methods: We conducted an open-label study in which 31 patients at different periods from surgery without signs and symptoms of pouchitis were randomized to 2 sachets of VSL#3 once daily or no treatment for 12 months. Pouchitis disease activity index (PDAI) was evaluated at baseline and after 3, 6, and 12 months. The percentage of CD4+ T lymphocytes expressing CD25 and the inactive form of transforming growth factor-, [latency-associated peptide (LAP)] were evaluated at baseline and after 3 and 6 months in peripheral-blood mononuclear cells and mucosal biopsies. Variation in tissue interleukin-1, and Foxp3 mRNA expression was also evaluated. Results: During the study period, VSL#3-treated patients showed a significant reduction in PDAI score and a significant increase in the percentage of mucosal CD4+CD25high and CD4+ LAP-positive cells compared with baseline values. Tissue samples at different points showed a significant reduction in IL-1, mRNA expression, and a significant increase in Foxp3 mRNA expression. Conclusions: We conclude that VSL#3 administration in patients with IPAA modulates the PDAI and expands the number of mucosal regulatory T cells. (Inflamm Bowel Dis 2008) [source] Epithelial barrier disruption allows nondisease-causing bacteria to initiate and sustain IBD in the IL-10 gene-deficient mouse,INFLAMMATORY BOWEL DISEASES, Issue 8 2007Beate C. Sydora PhD Abstract Background: In the IL-10 gene-deficient mouse model, development of intestinal inflammation is associated with a defect in epithelial barrier integrity that is thought to allow sufficient passage of bacteria or bacterial antigens to initiate a mucosal immune response. Microbial monoassociation experiments into axenic animals have shown that some, but not all, endogenous bacteria will initiate an intestinal inflammatory response. For instance, Bacteroides vulgatus does not initiate intestinal inflammation in axenic IL-10 gene-deficient mice. We investigated whether B. vulgatus requires concomitant disruption of the intestinal epithelial barrier integrity in order to initiate an inflammatory response. Methods: We first identified a dose of the indomethacin that would cause a primary disruption of the epithelial barrier without causing intestinal inflammation. IL-10 axenic mice were then administered this dose of indomethacin in their drinking water for 7 days and concomitantly monoassociated, by oral gavage, with B. vulgatus. Results: Indomethacin treatment (2 ,g/g/d) for 7 days resulted in disruption of epithelial barrier integrity, but it caused neither a systemic inflammatory response nor a mucosal inflammatory response in the colon or cecum. Monoassociation with B. vulgatus alone did not lead to a mucosal inflammatory response, despite a measurable systemic response. In contrast, administration of indomethacin plus B. vulgatus -monoassociation resulted in a marked intestinal inflammatory response in colon and cecum. Conclusions: Our data show that, in a genetically predisposed animal model, the nondisease-causing endogenous bacteria, B. vulgatus, is able to cause an intestinal inflammatory response provided that disruption of the intestinal epithelial barrier has occurred. (Inflamm Bowel Dis 2007) [source] Inflammatory bowel disease: Epidemiology, pathogenesis, and therapeutic opportunitiesINFLAMMATORY BOWEL DISEASES, Issue 5 2006Stephen B Hanauer MD Abstract Ulcerative colitis (UC) and Crohn's disease (CD), the primary constituents of inflammatory bowel disease (IBD), are precipitated by a complex interaction of environmental, genetic, and immunoregulatory factors. Higher rates of IBD are seen in northern, industrialized countries, with greater prevalence among Caucasians and Ashkenazic Jews. Racial gaps are closing, indicating that environmental factors may play a role. IBD is multigenic, with the most clearly established genetic link between certain NOD2 variants and CD. Regardless of the underlying genetic predisposition, a growing body of data implicates a dysfunctional mucosal immune response to commensal bacteria in the pathogenesis of IBD, especially CD. Possible triggers include a chronic inflammatory response precipitated by infection with a particular pathogen or virus or a defective mucosal barrier. The characteristic inflammatory response begins with an infiltration of neutrophils and macrophages, which then release chemokines and cytokines. These in turn exacerbate the dysfunctional immune response and activate either TH1 or TH2 cells in the gut mucosa, respectively associated with CD and, less conclusively, with UC. Elucidation of immunological and genetic factors indicate multiple points at which the inflammatory cascade may be interrupted, yielding the possibility of precise, targeted therapies for IBD. [source] Characterization of colonic and mesenteric lymph node dendritic cell subpopulations in a murine adoptive transfer model of inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 6 2004John Karlis BScHons Abstract Ulcerative colitis and Crohn's disease, collectively termed inflammatory bowel diseases (IBD), are chronic inflammatory diseases of the intestine that afflict more than 4 million people worldwide. Intestinal inflammation is characterized by an abnormal mucosal immune response to normally harmless antigens in the gut flora. In Crohn's disease, the pathogenic mucosal immune response is a typical T helper (TH1) type cell response, whereas ulcerative colitis is predominantly associated with a TH2 response. We are interested in the role of dendritic cells in early immunologic events leading to T cell activation and chronic intestinal inflammation. Using a murine adoptive transfer model of IBD, we found an accumulation of dendritic cells in colon and mesenteric lymph nodes during the early stage of IBD before the appearance of epithelial lesions and tissue degradation. In situ immunostaining and flow-cytometric analysis revealed that approximately 50% of colonic dendritic cells were CD11b+ B220, myeloid dendritic cells and 50% expressed the CD11b, B220+ plasmacytoid phenotype. In corresponding mesenteric lymph nodes, approximately 16% were plasmacytoid dendritic cells. Colonic myeloid dendritic cells were shown to express the co-stimulatory molecule CD40. Both, colonic myeloid and plasmacytoid dendritic cells released interferon-, in situ and stimulated T cell proliferation ex vivo. Our results show that dendritic cells can mature in the intestine without migrating to mesenteric lymph nodes. Mature intestinal dendritic cells may form a nucleation site for a local T cell response and play an important role in the pathogenesis of IBD. [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] An exploration of Glo-3A antibody levels in children at increased risk for type 1 diabetes mellitusPEDIATRIC DIABETES, Issue 8 2009M Simpson Aims: To determine whether Glo-3A, (formerly referred to as homologue of Glb1 or Glb1) antibodies are associated with islet autoimmunity (IA) in children at increased risk for type 1 diabetes (T1D) and to investigate their relation with environmental correlates of T1D. Methods: We selected a sample from the Diabetes Autoimmunity Study in the Young (DAISY), a prospective study of children at increased risk for T1D. Cases were positive for insulin, glutamic acid decarboxylase (GAD), or insulinoma-associated antigen-2 (IA-2) autoantibodies on two consecutive visits and either diagnosed with diabetes mellitus or still autoantibody positive when selected. Controls were from the same increased risk group, of similar age as the cases but negative for autoantibodies. Sera from 91 IA cases and 82 controls were analyzed in a blinded manner for immunoglobulin G (IgG) antibodies to Glo-3A by ELISA. Results: Adjusting for family history of T1D and human leukocyte antigen (HLA)-DR4 positivity, Glo-3A antibodies were not associated with IA case status (OR: 1.01, 95% CI: 0.99,1.03). Adjusting for age, family history of T1D, and HLA-DR4 positivity, Glo-3A antibody levels were inversely associated with breast-feeding duration (beta = ,0.08, p = 0.001) and directly associated with current intake of foods containing gluten (beta = 0.24, p = 0.007) in IA cases but not in controls. Zonulin, a biomarker of gut permeability, was directly associated with Glo-3A antibody levels in cases (beta = 0.73, p = 0.003) but not in controls. Conclusion: Differing correlates of Glo-3A antibodies in IA cases and controls suggest an underlying difference in mucosal immune response. [source] Increased production of serum IgA-class antibody to lipid A in Kawasaki diseasePEDIATRICS INTERNATIONAL, Issue 1 2002Seiichiro Takeshita Abstract Background:,The etiology of Kawasaki disease (KD) remains unknown. To investigate whether a conventional bacterial antigen is involved in the pathogenesis of KD, we studied the serum response to lipopolysaccharide (LPS). Methods:,We measured the serum levels of IgG-, IgM- and IgA-class antibodies (Ab) to lipid A, a toxic site of LPS, using enzyme-linked immunosorbent assay in 20 patients with KD, 11 patients with Gram-negative bacterial infection (GNBI), 27 healthy children and 12 healthy adults. Results:,The serum levels of anti-lipid A IgG, IgM and IgA tended to increase with advancing age in healthy children older than 6 months of age. The mean level of anti-lipid A IgM in the acute phase of GNBI and the mean levels of anti-lipid A IgM and IgA in the acute phase of KD were found to increase significantly, in comparison to the age-matched controls. Furthermore, the mean level of anti-lipid A IgA also showed a significant increase from the acute to the subacute phases of KD. Regarding the IgA-subclass response, higher titers of anti-lipid A specific Ab were seen in the IgA2 subclass than in the IgA1 subclass. Conclusion:,These findings indicate that KD patients demonstrate an intense response to lipid A in the IgA, especially IgA2-subclass, thus suggesting that an unusual activation of the mucosal immune response to a ubiquitous antigen derived from Gram-negative bacteria may be involved in the pathogenesis of KD. [source] Boost of mucosal secretory immunoglobulin A response by clarithromycin in paediatric influenzaRESPIROLOGY, Issue 8 2009Takako SAWABUCHI ABSTRACT Background and objective: The antiviral neuraminidase inhibitor oseltamivir (OSV) is used to treat influenza. The macrolide clarithromycin (CAM) is used to treat bacterial infections and has anti-inflammatory and immunomodulatory activities. This retrospective study investigated the immunomodulatory effects of CAM in children presenting with influenza A. Methods: The study recruited 40 children with acute influenza, and grouped them according to the treatment received: 5-day treatment with OSV (n = 14), CAM (n = 8), OSV + CAM (n = 12) and untreated (n = 6). The before and after treatment comparisons were made of the level of secretory IgA (sIgA) against influenza A virus (H3N2) and (H1N1), total sIgA, viral RNA copy numbers in nasopharyngeal aspirates and disease symptoms. Results: Infection induced anti-viral mucosal sIgA in the nasopharyngeal aspirates of most patients of all treatment groups. Particularly prominent increases in the levels were found in the CAM and OSV + CAM groups. Low induction of anti-viral sIgA was observed in the OSV group, but the addition of CAM to OSV augmented sIgA production and restored local mucosal sIgA levels. The frequency of residual cough in the OSV + CAM group was significantly lower than in the other groups including the group treated with OSV. Conclusions: CAM boosted the nasopharyngeal mucosal immune response in children presenting with influenza A, even in those treated with OSV who had low production of mucosal anti-viral sIgA, and alleviated the symptoms of influenza. [source] Correlation of Local Interleukin-1beta Levels with Specific IgA Response Against Gardnerella vaginalis Cytolysin in Women with Bacterial VaginosisAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2002SABINA CAUCI PROBLEM:,Mucosal immune system activation may represent a critical determinant of adverse sequelae correlated with bacterial vaginosis, as HIV sexual transmission, upper genital tract infections, cervicitis, endometritis, postsurgical infections, and adverse pregnancy outcomes as preterm delivery (PTD), low birth weight (LBW). METHOD OF STUDY:,Levels of interleukin-1beta (IL-1beta), anti- Gardnerella vaginalis hemolysin (Gvh) IgA, pH, Nugent score, and number of leukocytes were measured in vaginal fluids of 60 fertile women with bacterial vaginosis and of 64 healthy controls. RESULTS:,Vaginal IL-1beta levels were nearly 13-fold higher in women with bacterial vaginosis (BV) and were associated with anti-Gvh IgA response. IL-1beta was positively correlated with leukocyte counts in the smear both in healthy and bacterial vaginosis positive women. CONCLUSIONS:,Induction of the proinflammatory cytokine IL-1beta may be a necessary event to elicit an innate immune response to control anaerobic genital tract infections. High levels of vaginal IL-1beta are associated with mounting of an antigen-specific mucosal immune response in women with bacterial vaginosis. Parallel induction of innate and adaptive immune response may be associated with protection from ascent of micro-organisms to the upper genital tract, and from acquiring viral infection through the vaginal tract. [source] Mediastinal lymph node CD8,, DC initiate antigen presentation following intranasal coadministration of ,-GalCerEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2007Sung-Youl Ko Abstract Our previous study revealed that ,-galactosylceramide (,-GalCer) is a potent nasal vaccine adjuvant inducing both potent humoral and cellular immune responses and affording complete protection against viral infections and tumors. However, the antigen-presenting cells (APC) that are activated by NKT cells and thereby initiate the immune responses following intranasal coadministration of protein antigen and ,-GalCer are poorly understood. We assessed here where antigen presentation occurs and which APC subset mediates the early stages of immune responses when protein antigen and ,-GalCer are intranasally administered. We show that dendritic cells (DC), but not B cells, initiated the mucosal immune responses at mediastinal lymph nodes. Of the DC subsets, the CD8,,B220,CD11c+ DC subset played the most prominent role in the direct and cross-presentation of protein antigen to naive T cells and in triggering the naive T cells to differentiate into effector T cells. This might be mainly caused by a relatively larger population of CD1dhigh cells of CD8,,B220,CD11c+ DC subset than those of other DC subsets. These results indicate that CD8,,B220,CD11c+ DC is the principal subset becoming immunogenic after interaction with NKT cells and abrogating tolerance to intranasally administered protein antigen when ,-GalCer is coadministered as a nasal vaccine adjuvant. [source] Effect of mucosal and systemic immunization with virus-like particles of severe acute respiratory syndrome coronavirus in miceIMMUNOLOGY, Issue 2 2010Baojing Lu Summary Nasal administration has emerged as a promising and attractive route for vaccination, especially for the prophylaxis of respiratory diseases. Our previous studies have shown that severe acute respiratory syndrome coronavirus (SARS-CoV) virus-like particles (VLPs) can be assembled using a recombinant baculovirus (rBV) expression system and such VLPs induce specific humoral and cellular immune responses in mice after subcutaneous injection. Here, we investigated mucosal immune responses to SARS-CoV VLPs in a mouse model. Mice were immunized in parallel, intraperitoneally or intranasally, with VLPs alone or with VLPs plus cytosine,phosphate,guanosine (CpG). Immune responses, including the production of SARS-CoV-specific serum immunoglobulin G (IgG) and secretory immunoglobulin A (sIgA), were determined in mucosal secretions and tissues. Both immunizations induced SARS-CoV-specific IgG, although the levels of IgG in groups immunized via the intraperitoneal (i.p.) route were higher. sIgA was detected in saliva in groups immunized intranasally but not in groups immunized intraperitoneally. CpG had an adjuvant effect on IgA production in genital tract washes when administered intranasally but only affected IgA production in faeces samples when administered intraperitoneally. In addition, IgA was also detected in mucosal tissues from the lung and intestine, while CpG induced an increased level of IgA in the intestine. Most importantly, neutralization antibodies were detected in sera after i.p. and intranasal (i.n.) immunizations. Secretions in genital tract washes from the i.n. group also showed neutralization activity. Furthermore, VLPs that were administered intraperitoneally elicited cellular immune responses as demonstrated by enzyme-linked immunospot (ELISPOT) assay analyses. In summary, our study indicates that mucosal immunization with rBV SARS-CoV VLPs represent an effective means for eliciting protective systemic and mucosal immune responses against SARS-CoV, providing important information for vaccine design. [source] Prebiotics in chronic intestinal inflammationINFLAMMATORY BOWEL DISEASES, Issue 3 2009Mirjam A.C. Looijer, Van Langen MD Abstract Prebiotics are nondigestible fermentable fibers that are reported to have health benefits for the host. Older as well as more recent studies show beneficial effects in experimental colitis and lately also in human inflammatory bowel diseases (IBD), such as Crohn's disease, ulcerative colitis, and chronic pouchitis. In this review we give an overview of the benefits of prebiotics in rodent IBD models and in IBD patients and discuss their possible protective mechanisms. Commensal intestinal bacteria induce and perpetuate chronic intestinal inflammation, whereas others are protective. However, most of the current medications are directed against the exaggerated proinflammatory immune response of the host, some of them toxic and costly. Feeding prebiotics changes the composition of the intestinal microflora toward more protective intestinal bacteria and alters systemic and mucosal immune responses of the host. Therapy for IBD targeting intestinal bacteria and their function is just emerging. Prebiotics have the promise to be relatively safe, inexpensive, and easy to administer. Unraveling their protective mechanisms will help to develop rational applications of prebiotics. However, the initial promising results with dietary prebiotics in preclinical trials as well as small studies in human IBD will need to be confirmed in large randomized controlled clinical trials. (Inflamm Bowel Dis 2008) [source] Protection against influenza virus infection by intranasal vaccine with surf clam microparticles (SMP) as an adjuvantJOURNAL OF MEDICAL VIROLOGY, Issue 7 2006Takeshi Ichinohe Abstract A safe and effective adjuvant is necessary to enhance mucosal immune responses for the development of an inactivated intranasal influenza vaccine. The present study demonstrated the effectiveness of surf clam microparticles (SMP) derived from natural surf clams as an adjuvant for an intranasal influenza vaccine. The adjuvant effect of SMP was examined when co-administered intranasally with inactivated A/PR8 (H1N1) influenza virus hemagglutinin vaccine in BALB/c mice. Administration of the vaccine with SMP induced a high anti-PR8 haemagglutinin (HA)-specific immunoglobulin A (IgA) response in the nasal wash and immunoglobulin G (IgG) response in the serum, resulting in protection against both nasal-restricted infection and lethal lung infection by A/PR8 virus. In addition, administration of SMP with A/Yamagata (H1N1), A/Beijing (H1N1), or A/Guizhou (H3N2) vaccine conferred complete protection against A/PR8 virus challenge in the nasal infection model, suggesting that SMP adjuvanted vaccine can confer cross-protection against variant influenza viruses. The use of SMP is suggested as a new safe and effective mucosal adjuvant for nasal vaccination against influenza virus infection. J. Med. Virol. 78:954,963, 2006. © 2006 Wiley-Liss, Inc. [source] The mucosal immune systemPARASITE IMMUNOLOGY, Issue 5 2003Thomas T. MacDonald SUMMARY This article outlines the lymphoid structures and cell types important in the intestinal immune response. Particular attention is paid to differences between rodents and man where there appears to be fundamental differences in the sources of the T and B cells which populate the mucosa. The majority of the data still suggest that Peyer's patches are the inductive site of mucosal immunity and the mucosa (lamina propria and epithelium) is the effector site, but there is growing realization that mucosal immune responses can occur in the absence of Peyer's patches and that antigen sampling may also occur in the lamina propria. [source] | ||||||||||