INFECTIONS AND THE DEVELOPMENT OF ALLERGY

The development of resistance or sensitivity to environmental antigens depends to a large extent on the nature of immunological memory which is generated during early antigen encounters in infancy and early chi ldhood. The latter involves antigen-driven selection for specific Th-l -like versus Th-2-like memory cells within individual immune responses to inhaled allergens, a process which occurs in the regional lymph no des (RLN) draining the conducting airways and which is regulated by a variety of cytokines produced by antigen-specific CD4(+) and CD8(+) T- cells. In addition, this T-cell selection process can theoretically be influenced by infectious agents, at two distinct levels. Firstly, inf ections in the airway mucosa may mobilise and activate local tissue ma crophages, which migrate to RLN and secrete Th-2-inhibitory cytokines such as IL-12 and IFN alpha, and also add to IFN gamma levels in the m ilieu via stimulation of NK cells. Secondly, microbial stimulation via gastrointestinal tract (GIT) commensals and pathogens is recognised a s the principal trigger for postnatal maturation of overall immune com petence in mammals. Recent studies indicate that the speed with which the immune system in human infants attains adult-equivalent competence postnatally is inversely related to 'risk' for primary allergic sensi tisation to environmental antigens. Factors which affect qualitative/q uantitative aspects of microbial colonisation of the GIT during early postnatal life may accordingly have unexpected downstream effects on s eemingly unrelated processes such as development of T cell memory to a llergens.