The innate and adaptive immune responses compose the systemic immune system (affecting the whole body), which is distinct from the mucosal immune system. Mucosa associated lymphoid tissue (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. The mucosal tissue includes the mouth, pharynx, and esophagus, and the gastrointestinal, respiratory, and urogenital tracts.

Mucosal immunity is formed by MALT, which functions independently of the systemic immune system, and which 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 response in areas of the body with 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 and delivered to APCs located directly below the mucosal tissue. APCs of the mucosal immune system are primarily dendritic cells, with B cells and macrophages having minor roles. Processed antigens displayed on APCs are detected by T cells in the MALT and at 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.

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 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. There are populations of T cells that suppress the immune response to self-antigens and that 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 (T_reg) cells, specialized lymphocytes that suppress local inflammation and inhibit the secretion of stimulatory immune factors. The combined result of T_reg cells is to prevent immunologic activation and inflammation in undesired tissue compartments and to allow the immune system to focus on pathogens instead.

The adaptive immune response is a slower-acting, longer-lasting, and more specific response than the innate response. However, the adaptive response requires information from the innate immune system to function. APCs display antigens on MHC molecules to naïve T cells. T cells with cell-surface receptors that bind a specific antigen will bind to that APC. In response, the T cells differentiate and proliferate, becoming T_H cells or T_C cells. T_H cells stimulate B cells that have engulfed and presented pathogen-derived antigens. B cells differentiate into plasma cells that secrete antibodies, whereas T_C cells destroy infected or cancerous cells. Memory cells are produced by activated and proliferating B and T cells and persist after a primary exposure to a pathogen. If re-exposure occurs, memory cells differentiate into effector cells without input from the innate immune system. The mucosal immune system is largely independent of the systemic immune system but functions in parallel to protect the extensive mucosal surfaces of the body. Immune tolerance is brought about by T_reg cells to limit reactions to harmless antigens and the body’s own molecules.