Mucosal Decisions: Tolerance and Responsiveness at Mucosal Surfaces

The primary focus of the entire immune system on protecting the mucosal surfaces – consisting mainly of the oro-gastrointestinal, respiratory, and genital tracts – is now beyond dispute and widely recognized. The evidence is clearly seen in the distribution of lymphoid cells throughout the body, the majority of these cells being found in the intestinal tract and other mucosal surfaces which are exposed to the external environment and subject to colonization by a huge variety of microorganisms (Pabst et al., 2008). In addition, IgA is by far the most abundantly produced immunoglobulin (Ig) isotype in the human body, accounting for approximately two-thirds of all Ig production. Altogether, synthesis of IgA amounts to some 5-10 g/day, of which the majority is secretory IgA (S-IgA; Russell, 2007). Thus the immune system deploys its resources according to where the threats to health mainly arise, and most infections directly afflict or invade through the oral cavity, and the gastrointestinal, respiratory, and genital tracts. However, the mucosal immune system faces a dilemma, because most of the foreign antigenic material present especially in the gastrointestinal tract consists of food as well as a huge number of microorganisms comprising the commensal microbiota amounting to an estimated 1014 cells of probably thousands of different species. Thus, it must distinguish not only between self and non-self, but also between the mass of harmless food antigens, commensals many of which are beneficial, and potentially dangerous pathogens. Considerable strides have been made in recent years in comprehending the mechanisms responsible for responsiveness or conversely non-responsiveness