Mucosal immunity and allergic responses: lack of regulation and/or lack of microbial stimulation?

Allergic hyperreactivity is defined as an exaggerated immune response [typically immunoglobulin E (IgE) but also non-IgE mediated] toward harmless antigenic stimuli. The prevalence of allergic disease has increased dramatically during the last 20 years, especially in developed countries. Both genetic and environmental factors contribute to susceptibility to allergy. Evidence has emerged supporting the hypothesis that a reduction in antigenic stimulation brought about by widespread vaccination, improvements in standards of hygiene, and extensive use of antibiotics has contributed to the dysregulation of T-helper 2 cell (Th2) type responsiveness that typifies allergy. Regulation of the inherently Th2-biased mucosal immune response is crucial both to the maintenance of homeostasis at this strategic defensive barrier and to the prevention of allergic disease. The ability of Th1 responses to counter-regulate Th2 reactivity is well characterized. More recently, interest has centered on regulatory T cells, which can suppress both Th1 and Th2 cells through the secretion of immunosuppressive cytokines such as interleukin-10 and transforming growth factor-beta. In this review, we discuss the basic cellular mechanisms of allergic diseases at mucosal surfaces, focusing on allergic responses to food, before examining newer work that suggests the induction of allergic hyperreactivity is due to a deficient immunoregulatory network, a lack of microbial stimulation, or both.