Immunologic mechanisms of allergen-specific immunotherapy

  • C. A. Akdis
  • K. Blaser
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 495)

Abstract

Allergic diseases basically are immunological disorders, related to activation of a distinct cytokine pattern in T cells, including increased secretion of certain allergic inflammatory cytokines, in particular of IL-4, IL-5 and/or IL-13. (1-3). Whereas the symptoms of immediate and late type allergic reactions can be ameliorated by various pharmacological treatments, the allergen-specific immunotherapy (SIT) represents the only curative approach for specific Type I allergy (4-9). SIT is most efficient in allergy to insect venoms and allergic rhinitis (6 9). However, the mechanism by which SIT achieves clinical improvement remained unclear until recent time. A rise in allergen-blocking IgG antibodies particularly of the IgG4 class (10-12), the generation of IgE-modulating CD8+T cells and a reduction in the number of mast cells and eosinophils and release of mediators (13-14), were fund to be associated with successful SIT. Furthermore, SIT was found to be associated with a decrease in IL-4 and IL-5 production by CD4+T cells, and in some cases with a shift towards increased IFN-y production (9 15-22). However, it appeared, that the induction of an unresponsive or anergic state in peripheral T cells and the reactivation of the response by cytokines from the tissue microenvironment are basic intermediate key steps in the mechanism of SIT (15-17). Thus, conditions of the immunological microenvironment and production of cytokines by tissue cells may finally determine, whether a SIT develops towards a successful or unsuccessful treatment. Therefore, for successful and safe SIT, allergen variants should be created, of which recognition sites for the T cells remained intact, whereas binding sites for IgE antibodies were removed. Intact T cell-epitopes are required in order to enable the induction of specific T cell tolerance or anergy against the antigen/allergen. The antibody-or B cell-epitopes are not only prerequisites for elicitation of adverse reactions, IgE antibodies also focus the allergen efficiently onto antigen-presenting B cells which present it to T cells in a way that favors development of a Th2 dominated cytokine pattern (18 23 24)

Keywords

Dust Tyrosine Interferon Histamine Dermatitis 

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© Springer Science+Business Media New York 2001

Authors and Affiliations

  • C. A. Akdis
    • 1
  • K. Blaser
    • 1
  1. 1.Swiss Institute of Allergy and Asthma Research (S1AF)DavosSwitzerland

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