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)


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)


Cell Epitope Cell Tolerance Cytokine Pattern Cell Anergy Altered Peptide Ligand 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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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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