Evolution Of The Autoimmunity Concept

Paul Ehrlich was the first to coin the term autoimmunity [11] with regard to the harmful aspects of immunity, namely—the emergence of autoantibodies directed against the organism's own antigens. However, the expression used ('horror autotoxicus') has served to denote a mechanism avoiding autoimmunization, exemplified in goat models (producing alloantibodies but not autoantibodies).

The revolutionary ideas expressed by Ehrlich were subsequently abandoned for a century although anecdotal works confirming his notions were sporadically reported. The turning point, leading to the general acceptance of the autoimmunity concept was the experiments by Witebski & Rose (reviewed in Reference [12]) showing that rabbits immunized with rabbit thy-roglobulin developed thyroiditis following production of anti-thyroglobulin autoantibodies. These observations were supported by the models of autoimmune hemolytic anemia and thrombocytopenia in which anti-red blood cell antibodies were detected and had been shown to be associated with bouts of hemolysis and thrombocytopenia [13].

The discovery of the NZB mouse (a strain which develops spontaneous autoimmune disease) provided a new tool for the study of autoimmmunity, con firming the previous evolving notions regarding the ability of the immune system to attack its own inherent constituents.

Further progress towards better understanding of autoimmunity has been achieved by the realization that the ability to distinguish between self and non-self during fetal life is a prerequisite for normal function of the immune system.

The term tolerance was introduced to signify the lack of autoreactivity. These ideas were later extended by Burnet [14], assuming that autoimmunization results from the emergence of 'forbidden' clones (lymphocytes possessing receptors for autoantigens escaping 'normal' deletion by the thymus during fetal life). Although this idea was later neglected, it represents the basis for the modern approach regarding autoimmunity as failure of the immune system to recognize its intrinsic components as its own.

Different methods of classification have been proposed for autoimmune diseases. An accepted method is based upon the organs afflicted (Table 3). Accordingly, diseases involving multiple organs include: SLE, rheumatoid arthritis, Sjogren's syndrome and scleroderma, whereas examples of organ-specific diseases encompass: Graves' disease, Hashimoto's thyroiditis, myasthenia gravis, polymyositis, pernicious anemia, Addison's disease, IDDM, primary billiary cirrhosis, autoimmune hemolytic anemia and pemphigus.

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