Immunological Changes Induced By Allergen Immunotherapy

The commonly recognized immunological changes that occur secondary to successful allergen immunotherapy (Table 2) include: (1) a rise in serum IgG-"blocking" antibody; (2) blunting of the usual seasonal rise of IgE followed by a slow decline of IgE over the course of immunotherapy; (3) increase in IgG- and IgA-blocking antibodies in the respiratory secretions; (4) reduction in basophil reactivity and sensitivity to specific allergens; (5) reduced production of inflammatory mediators during both early- and late-phase responses to allergen exposure; (6) decreased mast cell numbers and eosinophil recruitment; and (7) reduced lymphocyte responsiveness (proliferation and cytokine production) to specific allergens and a shift of T-cell subsets away from a TH2 type (producing IL-4 and IL-5) in favor of a THl-type T-lymphocyte response (interferon [IFN-y]).

The hallmark of asthma and allergic rhinitis is allergic inflammation of the mucosa and submucosa, predominantly caused by eosinophils. TH2 lymphocytes amplify and prolong allergic inflammation and late-phase reactions. TH1 cytokines, i.e., IFN-y and IL-2, inhibit production of TH2 cytokines. Successful immunotherapy is associated with a shift in IL-4/IFN-y production (from IL-4 to IFN-y) either as a consequence of downregulation of the TH2 response or increase in the TH1 response by regulatory T cells screting interleukin (IL)-10 and transforming growth factor (TGF)-p.

Not all immunological changes associated with effective immunotherapy occur in all subjects, although there is general correlation between clinical improvement and favorable alterations from baseline immunological parameters. Reduction in biological sensitivity to specific allergens has been demonstrated in allergen immunotherapy trials to such allergens as ragweed, mixed grasses, birch and mountain cedar pollen vaccines; the molds, Alternaria spp and Cladosporium spp; and cat dander and house dust mites. Successful allergen immunotherapy ameliorates, but usually does not completely eliminate, the respiratory symptoms of allergic rhinitis and allergic asthma.

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