Mucosal immunity--mucosal tolerance. A strategy for treatment of allergic diseases

The mucosal surfaces of the respiratory, the gastrointestinal and the urogenital tract, covering a total of 300 m2, are the largest areas within the body in contact with the external environment and thus are major sites of antigen exposure. Discriminating between pathogenic antigens, towards which a protective immune response has to be established, and harmless antigens--such as food, airborne antigens or the commensal bacterial flora--that should be ignored is the most challenging task of the mucosal immune system. In order to handle these challenges the mucosal immune system has generated two arms of adaptive defenses: (1) antigen exclusion performed by secretory IgA and secretory IgM antibodies to modulate or inhibit adherence or colonization of microorganisms and prevent penetration of potentially dangerous antigens (toxins, etc.), and (2) suppressive mechanisms to avoid local and peripheral overreaction against innocuous substances contacting the mucosal surfaces. The latter arm is referred to as oral or mucosal tolerance. A breakdown or a failure of induction of long-lasting tolerance to environmental and food antigens or components of the indigenous microflora is believed to lead to allergic diseases or food enteropathies. Based on the physiological situation to prevent hypersensitivity reactions, tolerance induction via the mucosa has been proposed as a treatment strategy against human inflammatory diseases, such as allergies.