IMMUNOCOMPETENT CELLS OF THE UPPER AIRWAY - FUNCTIONS IN NORMAL AND DISEASED MUCOSA

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 immuno globulin (Ig)-producing plasma cells. Locally produced Ig consists mai nly of J-chain-containing dimers and larger polymers of IgA (pIgA) tha t are selectively transported through glandular cells by an epithelial receptor called secretory component or pIgR. Secretory antibodies per form surface protection by immune exclusion of soluble antigens as wel l as infectious agents. Ige can also participate in this primary defen se because it reaches secretions by passive diffusion similar to IgE. However, the inflammatory properties of antibodies belonging to the la tter 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 pr omote persistent inflammation with extravasation and priming of eosino phils. This mechanism appears to occur in the late-phase allergic reac tion, perhaps driven mainly by interleukin-4 (IL-4) released from mast cells subjected to IgE-mediated degranulation. Eosinophils are potent ially 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 l eukocytes into the mucosa. Intercellular adhesion molecule-1 (ICAM-1), which is readily up-regulated by interferon-gamma on airway epitheliu m, is of particular importance for further migration of leukocytes ont o the mucosal surface. However, epithelial ICAM-1 may also provide a c o-signal for overstimulation of CD4(+) T lymphocytes by antigen-presen ting 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 a gainst environmental antigens. Nevertheless, mucosal induction of immu nological tolerance may be possible in the future. Therapeutic control of mucosal expression of adhesion molecules may likewise become an ad junct in the treatment of allergic disease.