Home About us Contact
|
Home About us Contact | ||
|
|
||
Mucosal Immune System (mucosal + immune_system)
Selected AbstractsNeonatal exposure to staphylococcal superantigen improves induction of oral tolerance in a mouse model of airway allergyEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2009Anna Lönnqvist Abstract The hygiene hypothesis suggests that lack of microbial stimulation in early infancy may lead to allergy, but it has been difficult to identify particular protective microbial exposures. We have observed that infants colonised in the first week(s) of life with Staphylococcus aureus have lower risk of developing food allergy. As many S. aureus strains produce superantigens with T-cell stimulating properties, we here investigate whether neonatal mucosal exposure to superantigen could influence the capacity to develop oral tolerance and reduce sensitisation and allergy. BALB/c mice were exposed to staphylococcal enterotoxin A (SEA) as neonates and fed with OVA as adults, prior to sensitisation and i.n. OVA challenge. Our results show that SEA pre-treated mice are more efficiently tolerised by OVA feeding, as shown by lower lung-cell infiltration and antigen-specific IgE response in the SEA pre-treated mice, compared with sham-treated mice. This was not due to deletion or anergy of lymphocytes by SEA treatment, because the SEA pre-treated mice that were fed with PBS showed similar inflammatory response as the sham-treated PBS-fed mice. Our results suggest that strong T-cell activation in infancy conditions the mucosal immune system and promotes development of oral tolerance. [source] Lamina propria dendritic cells: For whom the bell TOLLs?EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2008Maria Rescigno PhD. Abstract One of the major tasks of the mucosal immune system is to discriminate between dangerous and harmless antigens that are encountered daily at mucosal sites. In the gastrointestinal tract, immune cells have to tolerate food antigens and commensal microbes but at the same time have to induce a prompt response against invasive pathogens, when needed. In this issue of the European Journal of Immunology, it is shown that intestinal dendritic cell (DC) populations can be distinguished based on the expression level of Toll-like receptors (TLR) and on the response of these TLR to their microbial ligands. DC either do not express TLR or they express them but respond in a non-inflammatory mode. In this commentary, these findings are discussed in the context of available knowledge on lamina propria DC. See accompanying article http://dx.doi.org/10.1002/eji.200737909 [source] Site-specific expression of CD11b and SIRP, (CD172a) on dendritic cells: implications for their migration patterns in the gut immune systemEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2005Diane Bimczok Abstract Dendritic cells (DC) in the intestinal tract play a major role in directing the mucosal immune system towards tolerance or immunity. We analyzed whether different mucosal DC subsets in pigs have specific functions, localizations, or migration patterns in vivo. Therefore, we collected physiologically migrating DC by pseudo-afferent cannulation of the intestinal duct in eight Göttingen minipigs. Lymph DC were phenotypically and functionally characterized and compared to DC found on histological sections of porcine small intestine and mesenteric lymph nodes (MLN). Four different DC subpopulations were detected. Lamina propria (LP) DC were mainly CD11b+ signal regulatory protein,, (SIRP,)+, DC in Peyer's patches were mainly CD11b,/SIRP,+ in subepithelial domes and CD11b,/SIRP,, in interfollicular regions, whereas MLN DC were largely CD11b+/SIRP,,. Of these four subsets, only the CD11b+/SIRP,+ DC and the CD11b+/SIRP,, DC were present in lymph. This suggests that DC migration to MLN largely originates from the LP. Lymph DC expressed high levels of MHC class,II and costimulatory molecules and had a low capacity for FITC-dextran uptake, indicating a mature phenotype. However, lymph DC did not induce PBMC proliferation in MLR, and migration was not significantly influenced by mucosal antigen application. [source] In vitro reconstructed mucosa-integrating Langerhans' cellsEXPERIMENTAL DERMATOLOGY, Issue 4 2003P. Sivard Abstract:, All three-dimensional in vitro mucosal models constructed, thus far, have only been reconstituted by epithelial cells. We have developed a reconstructed oral and vaginal epithelium that integrates Langerhans' cells (LC), the dendritic cells (DC) of malpighian epithelia. The epithelium was composed of gingival or vaginal keratinocytes seeded on a de-epidermized dermis (DED) and grown in submerged culture for 2 weeks. LC precursors, obtained after differentiation of cord blood-derived CD34+ hematopoietic progenitor cells (CD34+HPC) by granulocyte macrophage-colony stimulating factor (GM-CSF), tumor necrosis factor-, (TNF-,), transforming growth factor-, (TGF-,) and Flt3-ligand (Flt3-L), were introduced after 6,8 days of culture into the reconstituted epithelium. The in vitro reconstituted mucosal epithelium formed a multilayered, well-differentiated epithelial structure, confirmed by the immunohistochemical expression of cytokeratins 4, 6, 10, 13, 14, 16 and involucrin. LC were identified in the basal and suprabasal epithelial layers by CD1a antigen, S100 protein and Langerin/CD207 expression, and by transmission electron microscopy. Type IV collagen was expressed at the chorio,epithelial junction, and most ultrastructural features of this junction were visualized by electron microscopy. This in vitro reconstructed gingiva or vagina integrating LC represents interesting models very similar to native tissues. Because LC play an important role in the mucosal immune system, our models could be useful for conducting studies on interactions with pathogenic agents (viruses, bacteria etc.), as well as in pharmacological, toxicological and clinical research. [source] Characterization of cells of the B lineage in the human adult greater omentumIMMUNOLOGY, Issue 1 2006Laurent Boursier Summary Peritoneal B cells and their omental precursors play an important role in the immune response of the peritoneal cavity and mucosal surfaces in mice. We have previously shown that peritoneal and mucosal B lineage cells are unlikely to be significantly linked in humans. However, the status of the omentum remains unknown. Here, using immunohistochemistry, we observed that sparse, quiescent B cells and occasional clusters of B cells were present in the omentum and that plasma cells, predominantly with cytoplasmic immunoglobulin G (IgG), were present. We analysed sequences of immunoglobulin genes amplified using reverse transcriptase,polymerase chain reaction (RT-PCR) from the normal human greater omentum, and describe the characteristics of variable region genes used by IgG, IgA and IgM. We focused on the properties of IgVH4 and IgVH5 families to allow comparisons of like with like between different Ig isotypes and cells from different immune compartments. We observed that the IgM genes were derived from a mixed population with mutated and unmutated immunoglobulin sequences. All IgVH4 and IgVH5 genes used by IgA and IgG from omental cells showed evidence of somatic hypermutation but the load of mutations was not significantly different to that seen in either the systemic or the mucosal compartments. The trends observed, including the dominance of IgG plasma cells, the IgA1/IgA2 ratio being biased towards IgA1, JH1 usage, and a moderate level of somatic mutations, link omental B lineage cells with the systemic compartment. These observations reinforce previous studies highlighting the difference between human and murine B-cell compartments and their relationship to the mucosal immune system. [source] Improving M cell mediated transport across mucosal barriers: do certain bacteria hold the keys?IMMUNOLOGY, Issue 1 2004Angela L. Man Summary Specialized microfold (M) cells of the follicle-associated epithelium (FAE) of the mucosal-associated lymphoid tissue (MALT) in gut and the respiratory system play an important role in the genesis of both mucosal and systemic immune responses by delivering antigenic substrate to the underlying lymphoid tissue where immune responses start. Although it has been shown that dendritic cells (DC) also have the ability to sample antigens directly from the gut lumen, M cells certainly remain the most important antigen-sampling cell to be investigated in order to devise novel methods to improve mucosal delivery of biologically active compounds. Recently, novel information on the interactions between bacteria and FAE have come to light that unveil further the complex cross-talk taking place at mucosal interfaces between bacteria, epithelial cells and the immune system and which are central to the formation and function of M cells. In particular, it has been shown that M cell mediated transport of antigen across the FAE is improved rapidly by exposure to certain bacteria, thus opening the way to identify new means to achieve a more effective mucosal delivery. Here, these novel findings and their potential in mucosal immunity are analysed and discussed, and new approaches to improve antigen delivery to the mucosal immune system are also proposed. [source] Mechanisms of natural tolerance in the intestine.INFLAMMATORY BOWEL DISEASES, Issue 4 2004Implications for inflammatory bowel disease Abstract Tolerance, the regulated inability to respond to a specific immunologic stimulant, is a physiological event important to normal immune function. Just as loss of tolerance to self-proteins results in autoimmune diseases, we assert that loss of tolerance to commensal flora in the intestinal lumen leads to inflammatory bowel disease (IBD). Mechanisms through which the mucosal immune system establishes and remains hyporesponsive toward the presence of food proteins and commensal flora, which we define as natural tolerance, are discussed. In addition to the contributions by commensal flora, the innate host defense and the adaptive immune systems promote natural tolerance to sustain normal mucosal homeostasis. Understanding the molecular and cellular events that mediate natural tolerance will lead to more advanced insights into IBD pathogenesis and improved therapeutic options. [source] A viewpoint of mucosal immunity in relation to early feeding methodINTERNATIONAL JOURNAL OF FOOD SCIENCE & TECHNOLOGY, Issue 4 2001Michael Oladipo Ogundele Summary Atopic diseases are common health problems in society and their incidence is increasing unabated. A number of studies in animal models have shown that antigen-specific IgE suppression could be induced for the treatment of allergic disorders. Many of the present therapeutic strategies in children have not been entirely successful and early breastfeeding could provide a practicable means of helping the affected children. An overview of the mucosal immune system is hereby presented to explain the natural mechanisms involved in protecting organisms from allergic reactions to food and other non-harmful antigens presented at the mucosal surfaces. The protective role of early breastfeeding in modulating this natural phenomenon is emphasized. The undeniable limitations of breastfeeding in the management of some peculiar cases of childhood dietary protein intolerance are also highlighted. [source] Ultrastructural characteristics and lectin-binding properties of M cells in the follicle-associated epithelium of chicken caecal tonsilsJOURNAL OF ANATOMY, Issue 4 2000HIROSHI KITAGAWA To clarify the nature of M cells, the detailed ultrastructural characteristics and lectin-binding properties of M cells were investigated in follicle-associated epithelium (FAE) of chicken caecal tonsils. M cells presented various outlines from columnar to dome shaped. Their polymorphism was dependent on the number of harboured intraepithelial migrating cells. The lighter and larger nuclei of M cells were situated at more apical levels in the epithelial lining compared with those of neighbouring microvillous epithelial cells. The microvilli, which were significantly shorter and thicker than those of adjacent microvillous epithelial cells, were sparsely distributed or completely absent on the apical surfaces of M cells. In general, the apical cytoplasm of M cells without microvilli protruded slightly into the intestinal lumen. Numerous small vesicles were often contained in the apical cytoplasm. The numerous small invaginations of the apical and lateral cell surfaces suggested active transportation of luminal substances. No canaliculi existed in the apical cytoplasm of M cells whereas they were often detected in the neighbouring microvillous epithelial cells. A noteworthy finding was the frequent detection of multivesicular bodies in the apical cytoplasm of M cells. These multivesicular bodies suggest some degradation of ingested luminal substances during transcytoplasmic transportation. WGA and 4 other lectins strongly reacted with all epithelial cells except for M cells, this negativity suggesting a means of detecting M cells in chicken caecal tonsils. Three lectins, DSL, ConA and Jacalin, reacted weakly with the glycocalyx on M cells. The positive reactivity might allow chicken M cells to be utilised for specific antigen delivery into the mucosal immune system in some parenteral vaccinations. [source] Role of viability of probiotic strains in their persistence in the gut and in mucosal immune stimulationJOURNAL OF APPLIED MICROBIOLOGY, Issue 4 2004C. Maldonado Galdeano Abstract Aims:, To determine how probiotic bacteria contact with intestinal epithelial and immune cells and the conditions to induce a good mucosal immune stimulation. Methods and Results:,Lactobacillus casei was studied by transmission electron microscopy (TEM) to determine its interaction with the gut. We compared the influence of viable and nonviable lactic acid bacteria on the intestinal mucosal immune system (IMIS) and their persistence in the gut of mice. TEM showed whole Lact. casei adhered to the villi; the bacterial antigen was found in the cytoplasm of the enterocytes. Viable bacteria stimulated the IMIS to a greater extent than nonviable bacteria with the exception of Lact. delbrueckii subsp. bulgaricus. For all the strains assayed at 72 h no antigenic particles were found in the intestine. Conclusion:, Antigenic particles but not the whole bacteria can enter to epithelial cells and contact with the immune cells. Bacterial viability is a condition for a better stimulation of the IMIS. Significance and Impact of the Study:, We demonstrated that only antigenic particle interact with the immune cells and their fast clearance from the gut agrees with those described for the particulate antigens. The regular consumption of probiotics should not adversely affect the host. [source] Comparison of intranasal with targeted lymph node immunization using PR8-Flu ISCOM adjuvanted HIV antigens in macaquesJOURNAL OF MEDICAL VIROLOGY, Issue 5 2007G. Koopman Abstract The rapidly spreading HIV epidemic requires a vaccine that elicits potent mucosal immunity to halt or slow transmission. Induction of these responses will depend on the use of appropriate adjuvants and targeting of the mucosal immune system. Previously, immune stimulating complexes (ISCOM) have shown great potency as adjuvant in the induction of mucosal responses in mice and systemic responses in non-human primates. In this study, HIV formulated in PR8-Flu ISCOM adjuvant was applied to immunize rhesus macaques against HIV; targeting the mucosa either via intranasal (IN) application or via targeted lymph node immunization (TLNI). While, strong systemic, HIV specific, cytokine, lymphoproliferative, and antibody responses were induced via the TLNI route, the IN application generated only low responses. Furthermore, all four animals immunized via TLNI developed vaginal IgA antibodies against gp120. In conclusion, in contrast to what has been demonstrated in mice, the IN application of PR8-Flu ISCOM did not induce strong immune responses in rhesus macaques unlike those immunized by the TLNI route. J. Med. Virol. 79:474,482, 2007. © 2007 Wiley-Liss, Inc. [source] Abnormalities of IgA1 production in IgA nephropathyNEPHROLOGY, Issue 2002John FEEHALLY SUMMARY: IgA nephropathy (IgAN) is characterized by the mesangial deposition of polymeric IgA1 (plgA1). the original view that this plgA1 is derived from the mucosal immune system can no longer be sustained. Studies of duodenal mucosa and marrow indicate increased production of plgA1 in the marrow and decreased production in the mucosa. These changes are consistent with immunization studies showing exaggerated and prolonged plgA responses to systemic immunization, and reduced mucosal responses to mucosal neoantigens. However, the IgA1 and IgG systemic responses to mucosal antigen are increased in IgAN, a finding consistent with impairment in oral tolerance, the process by which systemic immune responses, to mucosal antigen challenge are normally suppressed. Both IgA1 production and the induction of oral tolerance are under T-cell control. T-cell populations involved in these processes include ,, T cells, Tr cells and T-helper (Th)3 cells; cytokines with a key role in the control of IgA production include interleukin (IL)-10 and transforming growth factor (TGF)-,. There is evidence of abnormal ,, T-cell V region usage in both mucosa and marrow in IgAN. Increased expression of relevant cytokines has also been reported in circulating T cells in IgAN. the increased O-glycosylation of circulating IgA1 in IgAN may also be further evidence of a shift in the production of mucosal-type plgA1 from the mucosa to marrow. These findings suggest that the specific lymphocyte homing mechanisms that normally maintain oral tolerance and control the site of IgA production require further study in IgAN. [source] Immune-mediated alteration in gut physiology and its role in host defence in nematode infectionPARASITE IMMUNOLOGY, Issue 8-9 2004W. I. Khan SUMMARY Activation of the mucosal immune system of the gastrointestinal tract in nematode infection results in altered intestinal physiology, which includes changes in intestinal motility and mucus production. These changes are considered to be under direct immunological control rather than a non-specific consequence of the inflammatory reaction to the infective agent. However, little is known about the immunological basis for the changes in intestinal physiology accompanying nematode infection, or the precise role of these changes in host defence, which remains an important area to explore. In this review we describe the mechanisms by which the immune response to nematode infection influences the changes in two major cells of intestinal physiology, namely smooth muscle and goblet cells, and how these changes in intestinal physiology contribute to the host defence. Data clearly demonstrate that the T helper (Th) 2 type immune response generated by nematode infection plays an important role in the development of infection-induced intestinal muscle hypercontractility and goblet cell hyperplasia and that these immune-mediated changes in intestinal physiology are associated with worm expulsion. These observations strongly suggest that intestinal muscle contractility, goblet cell hyperplasia and worm expulsion share a common immunological basis and may be causally related. These data not only provide insights into host defence in nematode infection in the context of muscle function and goblet cell response, but also have broad implications in elucidating the pathophysiology of a wide range of gastrointestinal disorders associated with altered gut physiology. [source] Immunization for Protection of the Reproductive Tract: A ReviewAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2002MICHAEL W. RUSSELL PROBLEM: Local application of non-replicating antigens to the female reproductive tract is ineffective in stimulating the common mucosal immune system, and induces only weak genital antibody responses. Studies of immune responses to genital infections such as gonorrhea also support the concept that, lacking mucosal immune inductive sites, the reproductive tract is ill-equipped to mount effective immune responses. METHOD OF STUDY: Intranasal (i.n.) and intravaginal (i.vag.) routes of immunization of mice with a protein antigen coupled to cholera toxin (CT) B subunit, or genetically engineered as chimeric proteins with the A2/B sunbunits of CT or type II heat-labile enterotoxin, were compared for their ability to induce specific antibody responses in vaginal fluids, saliva, and serum. RESULTS: Mice immunized i.n. developed substantially stronger vaginal immunoglobulin A (IgA) and immunoglobulin G (IgG) and serum IgG and IgA antibodies, than those immunized i.vag. which also failed to develop salivary antibodies. Vaginal antibody responses induced i.n. persisted for at least 1 year, and were recallable by booster immunization after a prolonged period. CONCLUSIONS: Such alternative strategies for inducing potent genital antibody responses offer the prospect of prophylactic immunization against genital infections. Further studies are required to evaluate their applicability to humans, and to comprehend the cellular and molecular mechanisms involved in delivering effective immune responses to the reproductive tracts. [source] Characterization of a QTL region affecting clinical mastitis and protein yield on BTA6ANIMAL GENETICS, Issue 5 2009H. Nilsen Summary Quantitative trait loci affecting clinical mastitis were detected and fine mapped to a narrow region on bovine chromosome 6 in the Norwegian Red cattle population. The region includes the casein gene cluster and several candidate genes thought to influence clinical mastitis. The most significant results were found for SNPs within the Mucin 7 gene. This gene encodes an antimicrobial peptide and constitutes part of the first line of defence for the mucosal immune system. Detection of long haplotypes extending several Mb may indicate that artificial selection has influenced the haplotype structures in the region. A search for selection sweeps supports this observation and coincides with association results found both by single SNP and haplotype analyses. Our analyses identified haplotypes carrying quantitative trait loci alleles associated with high protein yield and simultaneously fewer incidences of clinical mastitis. The fact that such haplotypes are found in relative high frequencies in Norwegian Red may reflect the combined breeding goal that is characterized by selection for both milk production and disease resistance. The identification of these haplotypes raises the possibility of overcoming the unfavourable genetic correlation between these traits through haplotype-assisted selection. [source] Dendritic cells in the recognition of intestinal microbiotaCELLULAR MICROBIOLOGY, Issue 4 2006Jan Hendrik Niess Summary Mucosal dendritic cells (DCs) constantly survey the luminal microenvironment which contains commensal microbiota and potentially harmful organisms regulating pathogen recognition and adaptive as well as innate defense activation. Distinct mechanisms are beginning to emerge by which intestinal antigen sampling and handling is achieved ensuring specificity and contributing to redundancy in pathogen detection. Distinct DC subsets are associated with these mechanisms and regulate specific innate or adaptive immune responses to help distinguish between commensal microbiota, pathogens and self antigens. Understanding DC biology in the mucosal immune system may contribute to the unraveling of infection routes of intestinal pathogens and may aid in developing novel vaccines and therapeutic strategies for the treatment of infectious and inflammatory diseases. [source] Cytokine gene polymorphisms and sudden infant death syndromeACTA PAEDIATRICA, Issue 3 2010L Ferrante Abstract Aim:, Several studies indicate that the mucosal immune system is stimulated in cases of sudden infant death syndrome (SIDS), and our hypothesis is that this immune reaction is because of an unfavourable combination of functional polymorphisms in the cytokine genes. Methods:, Thus, in this study, single nucleotide polymorphisms (SNPs) in the genes encoding IL-6, IL-8, IL-12, IL-13, IL-16, IL-18 and IFN, were investigated in 148 SIDS cases, 56 borderline SIDS cases, 41 cases of infectious death and 131 controls. Results:, Regarding genotype distribution, no differences between the investigated groups were found. However, in the SIDS group, the genotypes IL-8 ,251AA/AT and IL-8 ,781CT/TT were significantly more frequent in the SIDS cases found dead in a prone sleeping position, compared with SIDS cases found dead in other sleeping positions. In addition, there was an association between fever prior to death and the genotype IL-13 +4464GG in the cases of infectious death. Conclusion:, This study indicates that specific interleukin genotypes are a part of a genetic make up that make infants sleeping prone at risk for SIDS. [source] | |||||||||||||