WHY ARE WE NOT ALL ALLERGIC - BASIC MECHANISMS FOR TOLERANCE DEVELOPMENT

Harmless antigens encountered on the mucosal surface are normally tole rated in the sense that they do not induce inflammatory immune respons es. Oral tolerance is the type of mucosal immune regulation that preve nts inflammatory reactions to food proteins. However, parasites and in vasive microorganisms at the mucosal surfaces must be recognised and d ealt with in a proper manner. The immune system does so by cross-regul ating the response where it either produces IgA to exclude invasion, I gE to fight parasites, or IgG to destroy the invasive organisms. Aller gy is an anti-parasitic reaction to a misinterpreted but harmless anti gen. This lack of tolerance induction is influenced by genetic factors controlling the amount of interleukin (IL)-4 produced initially in th e immune response. IL-4 directs B-cells to produce IgE, induces naive T-cells to become IL-4 producing T-helper cells (Th2 cells) and preven t other T-cells from entering into the IFN-gamma-producing Th1 pathway . Long lasting Th2 clones lose their IL-12 responsiveness and can no l onger be induced to produce IFN-gamma thus they are locked in an aller gy inducing Th2 phenotype. Environmental factors play on the genetic b ackground and influence the outcome of the immune response. Mucosal to lerance depends on an intact mucosal surface, is influenced by the age of the subject, and can be manipulated through antigen dose and place of entry. Immune-manipulating therapy may be more successful in prima ry than in secondary prevention of allergy. (C) 1997 Elsevier Science B.V.