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42.2F: Regulating Immune Tolerance

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  • Immune tolerance of self and harmless antigens occurs by deleting B and T cells that recognize those antigens, often near mucosal surfaces.


    Describe the process by which immune tolerance is acquired


    Key Points

    • Mucosal surfaces are those that are in contact with air, but, unlike the skin, allow fluid to flow in and out of them.
    • Due to the location of mucosal surfaces, they are often the first sites to encounter new antigens.
    • The immune system has to be regulated to prevent wasteful, unnecessary responses to harmless substances and, more importantly, so that it does not attack “self”.
    • Mucosal-associated lymphoid tissue, or MALT, is involved in immune tolerance to harmless, foreign antigens.

    Key Terms

    • self-antigen: antigens (substances that bind to antibodies) that are usually well tolerated by the immune system, which has been educated to non-reactivity against the structures
    • mucous membrane: a membrane which secretes mucus; it forms the lining of body passages that contact the air, such as the respiratory and genitourinary tracts including the mouth, nasal passages, vagina and urethra

    Mucosal surfaces

    The innate and adaptive immune responses discussed thus far comprise the systemic immune system (affecting the whole body), which is distinct from the mucosal immune system. Mucosa are another name for mucous membranes. Mucosal immunity is formed by mucosa-associated lymphoid tissue, or MALT, which functions independently of the systemic immune system; it has its own innate and adaptive components. MALT is a collection of lymphatic tissue that combines with epithelial tissue lining the mucosa throughout the body. This tissue functions as the immune barrier and immune response in areas of the body in direct contact to the external environment. The systemic and mucosal immune systems use many of the same cell types. Foreign particles that make their way to MALT are taken up by absorptive epithelial cells called M cells and delivered to APCs (antigen-presenting cells) located directly below the mucosal tissue. M cells are located in the Peyer’s patch, which is a lymphoid nodule. APCs of the mucosal immune system are primarily dendritic cells, with B cells and macrophages playing minor roles. Processed antigens displayed on APCs are detected by T cells in the MALT and at various mucosal induction sites, such as the tonsils, adenoids, appendix, or the mesenteric lymph nodes of the intestine. Activated T cells then migrate through the lymphatic system and into the circulatory system to mucosal sites of infection.


    MALT tissue: The topology and function of intestinal MALT is shown. Pathogens are taken up by M cells in the intestinal epithelium and excreted into a pocket formed by the inner surface of the cell. The pocket contains antigen-presenting cells, such as dendritic cells, which engulf the antigens, then present them with MHC II molecules on the cell surface. The dendritic cells migrate to an underlying tissue called a Peyer’s patch. Antigen-presenting cells, T cells, and B cells aggregate within the Peyer’s patch, forming organized lymphoid follicles. There, some T cells and B cells are activated. Other antigen-loaded dendritic cells migrate through the lymphatic system where they activate B cells, T cells, and plasma cells in the lymph nodes. The activated cells then return to MALT tissue effector sites. IgA and other antibodies are secreted into the intestinal lumen.

    MALT is a crucial component of a functional immune system because mucosal surfaces, such as the nasal passages, are the first tissues onto which inhaled or ingested pathogens are deposited. This allows the immune system to detect and deal with pathogens very quickly after they enter the body through various mucous membranes. The mucosal tissue includes the mouth, pharynx, and esophagus, along with the gastrointestinal, respiratory, and urogenital tracts.

    Immune tolerance

    The immune system has to be regulated to prevent wasteful, unnecessary responses to harmless substances and, more importantly, so that it does not attack “self.” The acquired ability to prevent an unnecessary or harmful immune response to a detected foreign substance known not to cause disease or to self-antigens is described as immune tolerance. The primary mechanism for developing immune tolerance to self-antigens occurs during the selection for weakly, self-binding cells during T and B lymphocyte maturation. Any T or B lymphocytes that recognize harmless foreign or “self” antigens are deleted before they can fully mature into immunocompetent cells.

    There are populations of T cells that suppress the immune response to self-antigens. They also suppress the immune response after the infection has cleared to minimize host cell damage induced by inflammation and cell lysis. Immune tolerance is especially well developed in the mucosa of the upper digestive system because of the tremendous number of foreign substances (such as food proteins) that APCs of the oral cavity, pharynx, and gastrointestinal mucosa encounter. Immune tolerance is brought about by specialized APCs in the liver, lymph nodes, small intestine, and lung that present harmless antigens to a diverse population of regulatory T (Treg) cells: specialized lymphocytes that suppress local inflammation and inhibit the secretion of stimulatory immune factors. The combined result of Treg cells is to prevent immunologic activation and inflammation in undesired tissue compartments, allowing the immune system to focus on hazardous pathogens instead.



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