The common mucosal immune system

Studies in humans have also shown that orally administered antigen results in the presence of S-IgA antibodies in remote external secretions. For example, studies have shown that ingestion of killed bacterial vaccines, i.e. Streptococcus mutans or Vibrio cholerae plus cholera toxin B subunit (CT-B), induce specific S-IgA antibodies in external secretions but not in serum. Mitogen stimulation of human peripheral blood lymphocytes results in the synthesis of polymeric IgA (serum IgA is mostly monomeric) and in the induction of both IgAl and IgA2 plasma cells. Further, the peripheral blood B cells of human volunteers ingesting bacterial vaccines produced specific IgA antibodies, suggesting that they were in a mucosal homing pathway. In fact, studies with several viral and other bacterial vaccines have clearly shown the subsequent presence of S-IgA antibodies in various human external secretions.

Equally compelling work in experimental animals is providing evidence that intranasal immunization is a particularly effective way to induce mucosal S-lgA as well as serum antibody responses. In these studies, less vaccine antigen and mucosal adjuvant is required for induction of effective mucosal immunity. Further, intranasal immunization appears to be particularly effective for induction of S-IgA antibodies in nasal washes, saliva, tears and in general nongastrointest-inal external secretions. It is intriguing that this route of immunization is particularly effective in priming for genitourinary tract responses, and offers promise for development of vaccines to prevent sexually transmitted diseases.

In summary, mammals possess a common mucosal immune system, in which antigen stimulation of MALT induces an exodus of specific lymphocytes which home to the various mucosal effector sites (Figures 1 and 2). These responses are finely regulated and T cells and cytokines are of central importance for ultimate plasma cell differentiation and production of S-IgA antibodies in external secretions. The current need for vaccines, including the universal efforts to develop immunity to human immunodeficiency virus (HIV), compels us to increase our understanding of how we can use the common mucosal immune system to advantage for the ultimate prevention of infectious diseases at mucosal sites.

See also: B lymphocyte activation; Cytokines; Gastrointestinal tract infections; Helper T lymphocytes; IgA; Immunoglobulin class switching; Joining J chain; Lymphocyte trafficking; Oral immunity; Oral tolerance; Secretory component (the polymeric Ig receptor); Vaccines.

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