Inter-réactions lymphoépithéliales chez le sujet normal et dans les maladies inflammatoires intestinales aspects morphologiques de la présentation antigénique (original) (raw)
Related papers
Le système immunitaire muqueux dans les maladies inflammatoires intestinales
Acta Endoscopica, 1991
Ľimmunité sécrétaire est la partie la mieux définie du système immunitaire muqueux. Ce mécanisme de défense humorale adapté dépend ďune coopération étroite entre ľépithélium sécrétoire et les plasmocytes locaux. Ces immunocytes produisent de préférence des diméres et de plus larges polyméres ďIgA. Les IgA polymériques (poly-IgA) et les pentaméres IgM, contiennent des chaînes J et peuvent pour cette raison, être liés au composant sécrétoire épithélial (CS). Son fonctionnement en tant que récepteur de transport poly-Ig est nécessaire à la production ďIgA sécrétoire (SIgA) et ďIgM sécrétoire (SIgM). Des faits multiples montrent que les anticorps SIgA et SIgM assurent ľexclusion immunitaire, ’opposant ainsi à la colonisation microbienne de la muqueuse et à la pénétration ďantigènes solubles. La production muqueuse de poly-IgA est déréglée de façon significative dans les maladies inflammatoires intestinales (Mil), ce dont témoigne la réduction drastique de ľexpression chaîne-J au niveau des immunocytes IgA muqueux. En outre, on observe une déviation significative des sous-classes IgA2 vers les IgAl, moins résistantes à la dégradation protéolytique. Ces modifications, associées à une activation des lymphocytes T et des macrophages, et à une augmentation importante des cellules productrices ďIgG, altèrent ľhoméostase immunitaire locale et menacent la défense muqueuse. Bien qu’un accroissement de la totalité de la population immunocytaire muqueuse puisse compenser la production relativement réduite de poly-IgA, la diminution de ľexpression CS au niveau de ľépithélium régénératif ou dysplasique, montre que le système SIgA n’est en aucun cas intact dans les Mil. Ľactivation du complément observée en relation avec des dépôts d'IgGl épithéliaux chez les patients atteints de recto-colite ulcéreuse, suggère que ľépithélium de surface est soumis à une agression immunitaire. Ces dépôts épithéliaux contiennent réguliérement des complexes terminaux du complément (CTC) et trés souvent du C3b, témoins ďune activation persistante. La comparaison entre des jumeaux univitellins mais différents du point de vue colite ulcéreuse, suggère qu’une réponse IgGl locale prononcée pourrait, en partie, être génétiquement déterminée ; une possibilité intéressante serait que ce phénomène représente une réponse autoimmune (anti-épithéliale). Néanmoins, ľévénement initial, déclenchant le mécanisme immunopathologique des MII demeure inconnu. La suppression de la tolérance orale aux antigènes endoluminaux a été suggérée comme un mécanisme ďautoentretien possible, probablement par interaction entre les lymphocytes T CD4b+ activés et les cellules épithéliales avec une expression HLA classe II exagérément intense. Secretory immunity is the best defined part of the mucosal immune system. This adaptive humoral defence mechanism depends on a fascinating cooperation between the secretory epithelium and the local plasma cells. These immunocytes produce preferentially dimers and larger polymers of IgA. Such polymeric IgA (poly-IgA), and also pentameric IgM, contain J chain and can therefore become bound to the epithelial secretory component (SC). Its function as a poly-Ig transport receptor is necessary for the generation of secretory IgA (SIgA) and secretory IgM (SIgM). There is abundant evidence that SIgA and SIgM antibodies perform immune exclusion, thereby counteracting microbial colonization and mucosal penetration of soluble antigens. The mucosal poly-IgA production is significantly down-regulated in inflammatory bowel disease (IBD), as revealed by a strikingly decreased J-chain expression in mucosal IgA immunocytes. There is moreover a significant shift from the IgA2 to the IgAl subclass, which is less resistant to proteolytic degradation. These changes, along with activation of T cells and macrophages and a dramatic increase of IgG-producing cells, will alter the local immunological homeostasis and jeopardize mucosal defence. Although the overall increase of the total mucosal immuno- cyte population may compensate for the relatively reduced poly-IgA production, decreased SC expression in regenerat- ing and dysplastic epithelium shows that the SIgA system is by no means intact in IBD. Complement activation observed in relation to epithelial IgGl deposits in
The mucosal immune system at the gastrointestinal barrier
Best Practice & Research Clinical Gastroenterology, 2008
The immune system faces a considerable challenge in its efforts to maintain tissue homeostasis in the intestinal mucosa. It is constantly confronted with a large array of antigens, and has to prevent the dissemination and proliferation of potentially harmful agents while sparing the vital structures of the intestine from immune-mediated destruction. Complex interactions between the highly adapted effector cells and mechanisms of the innate and adaptive immune system generally prevent the luminal microflora from penetrating the intestinal mucosa and from spreading systemically. Non-haematopoietic cells critically contribute to the maintenance of local tissue homeostasis in an antigen-rich environment by producing protective factors (e.g. production of mucus by goblet cells, or secretion of microbicidal defensins by Paneth cells) and also through interactions with the adaptive and innate immune system (such as the production of chemotactic factors that lead to the selective recruitment of immune cell subsets). The complexity of the regulatory mechanisms that control the local immune response to luminal antigens is also reflected in the observation that mutations in immunologically relevant genes often lead to the development of uncontrolled inflammatory reactions in the microbially colonized intestine of experimental animals.
Immunoperoxidase demonstration of the cellular composition of the normal and coeliac small bowel
Clinical and experimental immunology, 1987
Immunohistological analysis of the cellular composition of the small intestinal mucosa in a group of untreated and treated coeliac patients and non-coeliac control subjects was performed using monoclonal antibodies and an immunoperoxidase technique. A characteristic cellular distribution was observed within the normal mucosa. The intraepithelial and lamina propria compartments were occupied mainly by T suppressor/cytotoxic and T helper/inducer cells respectively. Further subdivision of lamina propria T helper/inducer cells with the Leu 8 antibody revealed that these were of the Leu 3a+ Leu 8- phenotype. Macrophages, defined by the RFD7 antibody, were seen to occupy the same microenvironment as T helper/inducer cells. T cells expressing the T cell activation antigen defined by anti-Ta1 were found with the normal lamina propria, although few cells were identified by the anti-Tac antibody. HLA-Dr antigens were expressed by stellate cells within the lamina propria, and also by the epith...
Gastroenterology, 1989
Abbreviations used in this paper: AX, antigen-presenting cell; BALT, bronchus-associated lymphoid tissue; C, complement; FAE, follicle-associated epithelium; GALT, gut-associated lymphoid tissue; IBD, inflammatory bowel disease; IEL, intraepithelial lymphocyte: IL-Z, interleukin 2; MHC, major histocompatibility complex; pig, polymeric immunoglobulin; pIgA, polymeric (or dimeric) immunoglobulin A; pIgh4, polymeric immunoglobulin M; PP, Peyer's patch: SC, secretory component; SIgA, secretory immunoglobulin A; SIgM, secretory immunoglobulin M
The role of enterocytes in the intestinal barrier function and antigen uptake
Microbes and Infection, 2005
The intestinal epithelium is a critical interface between the organism and its environment. The cell polarity and structural properties of the enterocytes, limiting the amount of antigen reaching the epithelial surface, form the basis of the integrity of the epithelium. However, apart from their participation in digestive processes, the enterocytes perform more than just a passive barrier function. The resistance of the tight junctions regulates the paracellular transport of antigens. Furthermore, the enterocytes take up and process antigens, involving two functional pathways. In the major pathway, enzymes in the lysosomes degrade the antigens. In the minor direct transcytotic pathway, the antigens are not degraded and are released into the interstitial space. Moreover, the enterocytes can present processed antigens directly to T cells and are often directly involved in immune processes. In inflammatory conditions, the properties of the epithelial barrier and the outcome of the immune response to luminal antigens can be changed.
European Journal of Immunology, 1999
In pigs the lymphocytes emigrating from the intestinal wall were collected by cannulating the lymphatics, labeled in vitro using a fluorescent dye and retransfused. The injection of 6.6 ± 4.2 × 10 8 cells resulted in a labeling index between 1.5 % in intestinal lymph, 0.2 % in the spleen and lymph nodes,˚0.1 % in the intestinal lamina propria and 0.003 % in intraepithelial lymphocytes. About 25 % of the injected cells were present in the blood and 1 % was recovered in the lymph. T cells were found in similar proportions in the injected and the recovered cells in the organs (70-80 %). The proportion of IgA + cells among the immigrated cells in the intestinal lamina propria ranged from 5 to 8 %, which in absolute numbers was up to 60 % of the injected IgA + cells. T and IgM + cells did not show a higher accumulation in any organ. These experiments in conventional, unrestrained animals revealed that (1) T cells immigrate into the intestinal lamina propria, (2) preferential migration of IgA + cells from gut lymph to the intestinal lamina propria is obvious under in vivo conditions and (3) the immigrated IgA + cells represent a very small population which is difficult to detect when analyzed in relative numbers.