Intraepithelial TCRαβ T Cells in Health and Disease
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The mucosal surfaces of the body are protected against pathogens and other environmental antigens by the mucosal immune system. This is functionally separate from the circulatory immune system, and represents by far the largest part of the entire immune system. Components include innate and adaptive immune cells and molecules. Specific T and B cells induced by antigens in the major immune inductive sites located in the gastrointestinal and upper respiratory tract are programmed to relocate in remote mucosal effector sites where secretory IgA antibodies and effector T cells are generated. Regulatory mechanisms including regulatory T cells and cytokines maintain a hypo‐responsive, non‐inflammatory state that prevents over‐reaction to the large mass of antigenic material consisting of food and other environmental antigens as well as the commensal microbiota. However, the mucosal immune system can respond vigorously with localised and disseminated responses when stimulated by aggressive pathogens. Key Concepts The mucosal immune system protects the large surface areas of the oro‐gastrointestinal, respiratory and genital tracts, the conjunctivae, their associated glands and the mammary glands. The mucosal immune system discriminates between pathogens that elicit a vigorous response, commensals that are regulated but not eliminated and harmless antigens such as food components that are tolerated. Innate components of mucosal immunity include physicochemical barriers such as mucus and low pH, and an array of antimicrobial molecules and cells that defend the mucosae against pathogenic attack and initiate recognition by the adaptive immune system. Adaptive components of mucosal immunity include locally produced secretory IgA antibodies, and both effector and regulatory T cells. Mucosal immune inductive sites such as intestinal Peyer's patches and other mucosa‐associated lymphoid tissues take up luminal antigens and disseminate induced, antigen‐specific T and B cells to remote effector sites in the ‘common’ mucosal immune system. Dendritic cells and other antigen‐presenting cells are located within the mucosal immune inductive sites and in the lamina propria underlying the epithelium. Mucosal trafficking of antigen‐induced T and B cells is determined by a set of vascular addressins, mucosal chemokines and receptors imprinted on lymphocytes during their induction. Mucosal epithelial cells have an integral role in antigen recognition and uptake, interaction with the cells of the immune system and delivery of the cells and molecules involved in immune defence. Innate defence cells including mast cells, macrophages, neutrophils and eosinophils are recruited to the mucosae, and display phenotypic profiles distinct from equivalent cells in systemic locations or the circulation.
The mucosal surfaces of the body are protected against pathogens and other environmental antigens by the mucosal immune system. This is functionally separate from the circulatory immune system, and represents by far the largest part of the entire immune system. Components include innate and adaptive immune cells and molecules. Specific T and B cells induced by antigens in the major immune inductive sites located in the gastrointestinal and upper respiratory tract are programmed to relocate in remote mucosal effector sites where secretory IgA antibodies and effector T cells are generated. Regulatory mechanisms including regulatory T cells and cytokines maintain a hypo‐responsive, non‐inflammatory state that prevents over‐reaction to the large mass of antigenic material consisting of food and other environmental antigens as well as the commensal microbiota. However, the mucosal immune system can respond vigorously with localised and disseminated responses when stimulated by aggressive pathogens. Key Concepts The mucosal immune system protects the large surface areas of the oro‐gastrointestinal, respiratory and genital tracts, the conjunctivae, their associated glands and the mammary glands. The mucosal immune system discriminates between pathogens that elicit a vigorous response, commensals that are regulated but not eliminated and harmless antigens such as food components that are tolerated. Innate components of mucosal immunity include physicochemical barriers such as mucus and low pH, and an array of antimicrobial molecules and cells that defend the mucosae against pathogenic attack and initiate recognition by the adaptive immune system. Adaptive components of mucosal immunity include locally produced secretory IgA antibodies, and both effector and regulatory T cells. Mucosal immune inductive sites such as intestinal Peyer's patches and other mucosa‐associated lymphoid tissues take up luminal antigens and disseminate induced, antigen‐specific T and B cells to remote effector sites in the ‘common’ mucosal immune system. Dendritic cells and other antigen‐presenting cells are located within the mucosal immune inductive sites and in the lamina propria underlying the epithelium. Mucosal trafficking of antigen‐induced T and B cells is determined by a set of vascular addressins, mucosal chemokines and receptors imprinted on lymphocytes during their induction. Mucosal epithelial cells have an integral role in antigen recognition and uptake, interaction with the cells of the immune system and delivery of the cells and molecules involved in immune defence. Innate defence cells including mast cells, macrophages, neutrophils and eosinophils are recruited to the mucosae, and display phenotypic profiles distinct from equivalent cells in systemic locations or the circulation.
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