Current Concepts of Autoimmunization: An Interpretive Review

W HEN an animal of one species is injected with the serum, tissues or blood cells of another, it forms antibodies against the injected material; this is known as heteroimmunization. Likewise, animals of one species, when injected with cells or tissues of animals of the same species, usually react immunologically; thus is isoimmunization. Thus, Ehrlich and Morgenroth,’ when they injected red cells of goats into other goats, were able to produce antibodies ( i.e., isohemolysins, isoagglutinins ) . However, Ehrlich was never able to induce the formation of antibodies by injecting the cells or tissues of one animal back into the same animal; i.e.. he was unable to induce autoimmunization. From these negative experiments, Ehrlich formulated his famous concept of horror autotoxicus, which indicated that the body could not-perhaps would not-produce antibodies against itself, since this would lead to self-destruction. Nevertheless, within a few years of this formulation, Donath and Landsteiner2 demonstrated, in a patient with paroxysmal cold hemoglobulinuria, an autohemolysin-a substance which had the property of attacking and destroying the patient’s own red blood cells under appropriate conditions of body temperature. The validity of these observations, reported at the turn of the century, has been maintained over the ensuing years. In the early years of the 20th century, the French physicians Chauffard and Troisi& and \\Tidal, Abrami and Brul#{233}4demonstrated autohemolysins and autoagglutinins in various forms of acquired hemolytic anemia. This work was forgotten or dismissed as of no significance for a generation and then rediscovered.5 Since then, with the development of newer technics for the demonstration of antibodies either within the blood or adherent to cells or tissues, the label of autoirnmunization has gradually been applied to a number of dinical conditions. Thus, an ever-increasing number of workers are convinced that many cases of acquired hemolytic anemia, idiopathic thrombocytopenic ptirpura ( ITP ) , systemic lupus and rheumatoid arthritis develop as the result of a process of autoimmunization. On the other hand, this view has been attacked on two grounds: ( 1 ) The antigen for the presumed antibody has ordinarily not been found, and ( 2 ) experimental autoimmunization has notuntil recently-been demonstrated. Witebskv, for many years one of the foremost o )ponents of the concept of autoimmunization, consistently stressed these two features : ( 1 ) Know the antigen, and ( 2 ) reproduce the autoimmune process experimentally! By a