MECHANISMS OF IMMUNOLOGICAL TOLERANCE DISRUPTION

Abstract

Autoimmune diseases belong to disorders with an unclear etiology. The spectrum of autoimmune diseases is wide, the most well known of them are type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, Crohn’s disease, vitiligo, and others. The key role in the development of autoimmune reactions is played by disturbances of immunological homeostasis. Despite numerous researches, the exact mechanisms of autoimmunity still remain unclear. The analysis of data provided by the literature on the mechanisms of disorders of immunological tolerance is presented in the review. The most discussed theories of pathological autoimmune processes development are described: the theory of hereditary predisposition, the theory of immunological dysregulation and regulatory T-cell dysfunction, the theory of network regulation, the infectious theory of autoimmune diseases development (molecular mimicry, polyclonal activation of lymphocytes). The theory of hereditary predisposition reflects the critical role of hereditary factors in the development of autoimmunity, in particular, the data on relations of autoimmune disorders to human major histocompatibility complex are provided. In addition, the data indicating that the development of autoimmune processes in an organism can be associated with changes in the content and function of regulatory T-lymphocytes are provided in the work. These cells are directly involved in the mechanisms of cellular immune responses in autoimmune diseases and may explain the disorders of immunological tolerance, subsequently leading to the development and progression of immunopathology. The idea of idiotype-anti-idiotype interactions, which can serve as a mechanism ensuring normal autoimmune reactions or lead to the activation of autoreactive clones, is revealed in the description of network regulation theory. The infectious theory of development of autoimmune pathologies presented in the review is based on the results of numerous researches and suggests that the viruses can provoke failures of immunity and lead to autoimmunity.