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 mucosa-associated lymphoid tissue, apparently including the tonsils and adenoid. From these inductive sites, memory cells migrate to secretory 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 selectively transported through glandular cells by an epithelial receptor called secretory component or the pIg receptor. IgG can participate in immune exclusion because it reaches the secretions by passive diffusion. However, its proinflammatory properties render IgG antibodies of local immunopathological importance when elimination of penetrating antigens is unsuccessful. T helper (Th) cells activated in this process may by a Th2 cytokine profile promote persistent inflammation with extravasation 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 IgE-mediated activation, and subsequently also by Th2 cell activation. Eosinophils are potentially tissue-damaging, particularly after priming with IL-5. Various cytokines up-regulate adhesion molecules on endothelial and epithelial cells, thereby enhancing migration of eosinophils into the mucosa, and perhaps in addition causing aberrant immune regulation within the epithelium. Soluble antigens bombarding the epithelial surfaces normally seem to induce several immunosuppressive mechanisms, but mucosal homeostasis appears less patent in the airways than oral tolerance to dietary antigens operating in the gut.
Brandtzaeg
P
P
Laboratory for Immunohistochemistry and Immunopathology (LIIPAT), University of Oslo, National Hospital, Rikshospitalet, Norway.
Jahnsen
F L
FL
Farstad
I N
IN
D001402:B-Lymphocytes / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D002448:Cell Adhesion; D016207:Cytokines / Q000276:immunology; D004804:Eosinophils / Q000276:immunology; D006706:Homeostasis; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D008407:Mast Cells / Q000276:immunology; D009297:Nasal Mucosa / Q000276:immunology*; D012137:Respiratory System / Q000276:immunology*
D015704:CD4 Antigens; D016827:CD8 Antigens; D016207:Cytokines; D007070:Immunoglobulin A; D007074:Immunoglobulin G