Mechanisms of specific immunotherapy of allergic diseases

The clinical effectiveness of specific immunotherapy (SIT) in the management of IgE-mediated diseases of the respiratory tract and venom allergy has been well established (1 -3). However, the exact mechanisms of the treatment effect remain obscure. So far, the putative mechanisms have largely been deduced from observations of fluctuations in various immunologic parameters during allergen desensitization with reference to the clinical course of the diseases. Thus, elucidation of the mechanisms of SIT has followed closely the progress in understanding of the mechanisms of allergic disorders, reflecting currently available laboratory techniques. In 1911, the original report of Noon (4) suggested that grass-pollen extracts, used for immunotherapy of hay fever, induced a toxin, causing allergic symptoms. In response to injection of pollen extract, a patient developed antitoxins that prevented the development of disease. Later authors considered that generation of neutralizing antibodies occurred during SIT (5, 6). With the progress in understanding the mechanisms of allergy, subsequent variants of the yin-yang hypothesis (e.g., T helper/T suppressor-cell balance or T helper 2-/T helper 1 -cell subsets balance) have been proposed. Since most studies employed immunologic parameters in peripheral blood or, at best, in tissue fluids (e.g., in nasal or bronchial lavages), the relevance of these data for the situation in both the primary or secondary lymphatic and the effector tissue is often not clear. However, current technology. including hybridization in situ, provides a much improved insight into local tissue responses.