IMMUNOLOGY - Roitt I. - Mir 2000

Chapter 23. Hypersensitivity - Type I

DESENSITIZATION

Desensitization therapy involves administering progressively increasing doses of an allergen. Although clinical improvement is frequently achieved, the precise mechanism remains unclear. Following such injections, serum levels of allergen-specific IgG and suppressor T-Cell activity increase, whereas specific IgE levels decline (Fig. 23.28). However, in most cases, no clear correlation has been established between any of these changes and the amelioration of patients' clinical condition. At the same time, it has been shown that successful desensitization in ragweed allergy is accompanied by the appearance of allergen-specific suppressor T Cells in the serum. This may lead to several consequences, such as the potential suppression of the IgE response and T-cell-dependent mast cell mobilization. The observed effect could also be explained by the predominance of Th1 rather than Th2 cell activity in the Immune Response to the allergen. In the case of bee venom allergy, where desensitization is accompanied by IgG production, the level of specific venom-blocking IgG Antibodies correlates well with the clinical protective effect.

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Fig. 23.28. Classical desensitization therapy consists of repeated administration of increasing doses of an allergen. This results in elevated levels of antigen-specific IgG and reduced content of antigen-specific IgE. The decrease in IgE levels is attributed to increased suppressor T-cell activity, which manifests as an attenuation of antigen-induced lymphocyte transformation (LT) in vitro. Desensitization may also be related to a shift in the Th1/Th2 cell balance involved in the immune response to the allergen.

Tolerance can be induced by modifying the allergen Structure

Recent studies on allergen structure have demonstrated that their T-cell epitopes can be identified through in vitro lymphocyte proliferation. Immunotherapy using these Peptides induces T-cell tolerance and holds clinical potential. Another approach to limiting the IgE response in mice involves The Use of glutaraldehyde-modified allergens; this shifts the ratio between Th2 and Th1 cells in favor of the latter, thereby switching the humoral response from the IgE type to IgG2a (see Fig. 23.6). In both cases, IL-4 production is diminished. The feasibility of employing this type of specific immunotherapy (using modified allergens) in humans remains to be determined. Modified allergens (so-called allergoids) were already used in the 1950s and yielded some clinical efficacy.

Tolerance induction suppresses the IgE response without eliminating the B cells that produce this immunoglobulin

Current reliable data indicate that animals possess very long-lived suppressor T cells and radiation-resistant (non-dividing) immunological memory B cells capable of producing IgE. For example, in normal rats and mice, repeated inhalation of an antigen (egg albumin) induces tolerance accompanied by suppression of the IgE response.

Research led by Holt established that in animals with a high IgE response, IgE memory cells and IgE plasma cells are highly resistant to the effects of Ovalbumin-specific suppressor T cells, which fail to alter the IgE response of these animals to egg albumin. However, The transfer of such suppressor T cells to non-immunized animals with a high IgE response prevents them from developing a strong IgE response to egg albumin. These findings are undoubtedly significant, given that human allergies are diagnosed after sensitization has already occurred, which may account for the relative inefficacy of desensitization therapy in many cases. Further investigation into the mechanism(s) responsible for the long-term persistence of these memory B cells (such as prolonged antigen presentation by dendritic cells or idiotype network systems) should make a substantial contribution to The Development of novel therapeutic strategies.

Interestingly, inhalation of noxious agents (nitrogen oxides or histamine), According to the same Holt group, prior to antigen exposure can provoke a pronounced IgE response even in low-responder animals. This further underscores The Role of environmental factors in inducing the IgE response (see above).