IMMUNE FUNCTIONS AND IMMUNOPATHOLOGY OF THE MUCOSA OF THE UPPER RESPIRATORY PATHWAYS

The specific defence of airway mucosae depends primarily on secretory immunity. The B cells involved are initially stimulated in organized m ucosa-associated lymphoid tissue, apparently including the tonsils and adenoid. From these inductive sites, memory cells migrate to secretor y effector sites where they differentiate terminally to immunoglobulin (Ig)-producing plasma cells. Locally produced Ig consists mainly of J chain-containing dimers and larger polymers of IgA (pIgA) that are se lectively transported through glandular cells by an epithelial recepto r called secretory component or the pig receptor. IgG can participate in immune exclusion because it reaches the secretions by passive diffu sion. However, its proinflammatory properties render IgG antibodies of local immunopathological importance when elimination of penetrating a ntigens is unsuccessful. T helper (Th) cells activated in this process may by a Th2 cytokine profile promote persistent inflammation with ex travasation and priming of eosinophils. This development appears to be part of the late-phase allergic reaction, perhaps initially driven by interleukin-4 (IL-4) released from mast cells that are subjected to I gE-mediated activation, and subsequently also by Th2 cell activation. Eosinophils are potentially tissue-damaging, particularly after primin g with IL-5. Various cytokines up-regulate adhesion molecules on endot helial and epithelial cells, thereby enhancing migration of eosinophil s into the mucosa, and perhaps in addition causing aberrant immune reg ulation within the epithelium. Soluble antigens bombarding the epithel ial surfaces normally seem to induce several immunosuppressive mechani sms, but mucosal homeostasis appears less patent in the airways than o ral tolerance to dietary antigens operating in the gut.