Autoimmune Disease: Pathogenesis

Autoimmune diseases are the result of specific immune responses directed against structures of the self (Burnet and Fenner, 1949). The organism possesses powerful mechanisms to avoid immune autoaggression. The acquired ability of the immune system to avoid responsiveness to self antigens is defined as ‘tolerance’, and is obtained by the cooperative efforts of central and peripheral mechanisms, which allow a rapid and efficient removal of pathogens (e.g. viruses or bacteria) in the absence of self-recognition. Occasionally, autoreactive cells may be activated, probably because of molecular mimicry (see below) between structures of the invading microorganism and the self. These autoreactive immune responses, however, are rapidly controlled and shut off by several immunoregulatory mechanisms. Autoimmune diseases, on the other hand, originate from a sustained and persistent immune response against self-constituents, and require a breakdown in tolerance. The mechanisms responsible for this breakdown are so far poorly defined. See also: Autoimmune disease; Immunological tolerance: mechanisms; Molecular mimicry An autoimmune response, usually induced by a triggering event, may be primarily Tor B-cell-mediated, or both. It might, however, be simplistic to define an autoimmune response as B-cell-mediated only. Indeed, whenever immunoglobulin (Ig) G antibody production is initiated, help from CD4+ T cells is provided. In some diseases the autoimmune aggression results in the complete and irreversible loss of function of the targeted tissue (e.g. Hashimoto thyroiditis or insulin-dependent diabetes). In others, the tissue is chronically damaged by the autoimmune reaction, resulting in either hyperstimulation or inhibition of its function (e.g. Graves–Basedow disease or myasthenia gravis). Finally, in other situations, the pathogenic events aremultiple and complex, leading to impairment or destruction of several tissues at the same time (e.g. systemic lupus erythematosus (SLE). See also: Autoimmune disease aetiology and pathogenesis Once the autoimmune reaction is initiated, it is usually self-sustained, leading to the chronic or definitive impairment of the target tissue. The mechanisms underlying the perpetuation of an autoimmune reaction are still obscure, and this makes the treatment of autoimmune diseases even more complicated.