'ABC' of mucosal immunology.

Abstract

Two adaptive homeostatic mechanisms normally preserve mucosal integrity: (i) immune exclusion mediated by secretory antibodies to inhibit penetration of potentially dangerous microorganisms and proteins, and (ii) immunosuppression to counteract hypersensitivity against innocuous antigens. The latter mechanism is called 'oral tolerance' when induced via the gut. Similar mechanisms are suppressive against commensal bacteria. Such two-layered anti-inflammatory defense explains why persistent allergy to dietary proteins is not more common, with the exception of gluten intolerance (celiac disease) where abrogation of mucosal homeostasis is overt. Thus, mucosally induced tolerance is generally a robust adaptive mechanism in view of the fact that a ton of food may pass annually through the gut of an adult - regularly giving rise to uptake of intact dietary antigens in the nanogram range after a meal. However, the immunoregulatory network and the epithelial barrier are poorly developed in the neonatal period, which therefore is critical with regard to priming for allergy. Notably, the postnatal development of mucosal immune homeostasis depends on appropriate microbial colonization. In this process, antigen-presenting cells are 'decision makers', linking innate and adaptive immunity. Their microbe-sensing function is influenced by both microbial products and dietary constituents, including vitamin A and lipids such as polyunsaturated n-3 fatty acids.