Immunocompetent cells of the upper airway: Functions in normal and diseased mucosa

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Abstract
Secretory immunity is central in primary defense of the airway mucosa. B cells involved in this local immune system are initially stimulated in mucosa-associated lymphoid tissue, including tonsils and adenoids, and then migrate to secretory effector sites where they become immunoglobulin (Ig)-producing plasma cells. Locally produced Ig consists mainly of J-chain-containing dimers and larger polymers of IgA (pIgA) that are selectively transported through glandular cells by an epithelial receptor called secretory component or pIgR. Secretory antibodies perform surface protection by immune exclusion of soluble antigens as well as infectious agents. IgG can also participate in this primary defense because it reaches secretions by passive diffusion similar to IgE. However, the inflammatory properties of antibodies belonging to the latter two classes explain their involvement in mucosal immunopathology when elimination of penetrating antigens is unsuccessful. T helper (Th) cells activated in this process may by a Th2 profile of cytokines promote persistent inflammation with extravasation and priming of eosinophils. This mechanism appears to occur in the latephase allergic reaction, perhaps driven mainly by interleukin-4 (IL-4) released from mast cells subjected to IgE-mediated degranulation. Eosinophils are potentially tissue-destructive cells, particularly after priming with IL-5. Cytokines also up-regulate adhesion molecules on vascular endothelium and epithelium, thereby enhancing migration of eosinophils and other leukocytes into the mucosa. Intercellular adhesion molecule-1 (ICAM-1), which is readily up-regulated by interferon-γ on airway epithelium, is of particular importance for further migration of leukocytes onto the mucosal surface. However, epithelial ICAM-1 may also provide a co-signal for overstimulation of CD4+ T lymphocytes by antigen-presenting HLA-DR+ epithelium. This latter occurrence could partly explain the airway mucosa appearing less able than gut mucosa to engage CD8+ suppressor cells for down-regulation of hypersensitivity reactions against environmental antigens. Nevertheless, mucosal induction of immunological tolerance may be possible in the future. Therapeutic control of mucosal expression of adhesion molecules may likewise become an adjunct in the treatment of allergic disease.