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Major Advances in Mucosal Immunity

The mammalian mucosal immune system is an integrated network of tissues, lymphoid and constitutive cells, and effector molecules that protect the host from infection of the mucous membrane surfaces. This signifies a major difference from the peripheral immune system, where lymphoid cells and effector molecules are confined to individual lymph nodes, and intercommunication occurs by cell trafficking through the lymphatic and blood circulations. The induction of peripheral immune responses by parenteral vaccination does not result in significant mucosal immunity; however, the reverse is not true. Induction of mucosal immune responses can result in protective immunity in the peripheral immune compartment as well.

The mucosal immune system is anatomically and functionally divided into sites where foreign antigens are encountered and selectively taken up for the initiation of an immune response and the more diffuse collection of B and T lymphocytes, differentiated plasma cells, macrophages, and other antigenpresenting cells, as well as mast cells that comprise effector tissues for mucosal immunity. This network is highly integrated and tightly regulated. The outcome of mucosal tissue encounters with foreign antigens and pathogens can range from mucosal and serum antibody responses and T-cell-mediated immunity to systemic anergy to oral or intranasal antigen, a response that is now termed mucosal tolerance. The separation between the mucosal immune system and the peripheral immune system has evolved as a major host defense mechanism. Mucosal surfaces are enormous, approximately 300 to 400 m2 and as such they require a significant expenditure of lymphoid cell elements for immunity. In this regard, the major antibody isotype in external secretions is IgA, and approximately 40 mg of IgA per kg of body weight is made in mucosal effector tissues each day, especially in the gastrointestinal tract (Conley and Delacroix, 1987). When this output of IgA is combined with its synthesis in bone marrow and peripheral lymphoid tissues, this isotype represents twice the amount of other isotypes combined, including the IgG subclasses, which are produced in higher mammals. Despite this propensity to produce IgA, the major effector cells in the mucosal immune system are T lymphocytes of both CD4+ and CD8+ phenotypes, and in some cases they can represent up to 80% of the entire cell population, clearly indicating their importance in mucosal immunity.

The use of vaccines that induce protective mucosal immunity thus becomes attractive when one considers that most infectious agents come into contact with the host at mucosal surfaces. Induction of mucosal immune responses may not only protect the host from morbidity and mortality due to infection but may possibly prevent infection altogether. The childhood immunization schedule recommended by the Centers for Disease Control and Prevention (CDC, 1999) lists seven vaccines that children should receive: (1) HBV; (2) diphtheria and tetanus toxoids and pertussis (DPT); (3) Hib; (4) poliovirus; (5) measles, mumps, rubella; (6) varicella; and (7) rotavirus. Of those vaccines, OPV and rotavirus are administered by the mucosal route. In fact, of 30 classes of vaccines, toxoids,



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