More than 25% of the population suffer from Type I allergy, an immunoglobulin E (IgE)-mediated hypersensitivity disease. Type I allergy is a disease determined by complex genetic and environmental factors which develops early in infancy, perhaps even in utero. Depending on the site of allergen contact and the operative immunological mechanisms, IgE recognition of allergens can cause a variety of symptoms, ranging from allergic rhinoconjunctivitis, bronchial asthma, manifestations of food allergy, atopic dermatitis and anaphylactic shock. Allergen-induced crosslinking of effector cell- bound IgE antibodies triggers the immediate release of biologically active mediators (e. g., histamine, leukotriens) and thus leads to acute disease manifestations. On the other hand, allergen contact can induce via antigen-presenting cells activation of specific T cells, the release of proinflammatory mediators as well as of cytokines and thus late phase symptoms as well as chronic inflammation.
Therapy of Type I allergy can be achieved by symptomatic pharmacotherapy which reduces the disease symptoms but does not represent a causative treatment. General and more causative treatment strategies for Type I allergy which are based on the neutralization of IgE antibodies or of proinflammatory cytokines are either in an experimental stage or show limited efficacy in clinical trials. Allergen-specific immunotherapy is the only causative therapy approach for Type I allergy. It is based on the administration of the disease-eliciting allergens. Numerous clinical studies performed since the introduction of this treatment form in 1911 document clinical efficacy of immunotherapy but the immunological mechanisms operative have not been definitively clarified. Modulation of allergen-specific T cell responses, effector cell responsiveness, induction of protective antibodies and tolerance have been discussed. In the recent past rapid progress has been made regarding the characterization of the disease-eliciting allergens and the development of adjuvants and vaccination/tolerance induction protocols. The current SFB proposal represents a research network which should lead to the development of allergen-specific strategies for the diagnosis, prevention and treatment of Type I allergy based on detailed studies of the disease-eliciting allergens and their interaction with the immune system. The project program put forward by basic scientists and clinical investigators will focus on the molecular characterization of important allergens, use defined allergen molecules to investigate allergen-specific immune responses, and, ultimately, will develop and evaluate molecular and immunological treatment strategies in the affected patients.
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- Larché M, Akdis CA, Valenta R. Immunological mechanisms of allergen-specific immunotherapy. Nat Rev Immunol. 2006 Oct;6(10):761-71.