The immunologic basis of autoimmunization

Abstract

Autoimmunization is today so readily accepted as established fact that it is easy to forget its turbulent history. There was a time when a few stubborn physicians had to insist against informed opinion that autoimmune diseases really existed. The answer they received was, “… I'll never believe there is such a thing as an autoantibody.” 1 Now the tables are turned. Today immunochemists are presenting schemes that require the formation of autoantibodies during the normal immune response. 2 Between these two extremes there is an evolution of thought that began with horror autotoxicus, 3 continued with the demonstration of experimental autoimmunization in laboratory animals, 4 entered the clinic with the realization that certain forms of hemolytic anemia were due to autoantibodies, 5 crystallized as a biologic problem with the advent of immunologic tolerance, 6 advanced into the rarefied theory of forbidden clones, 7 progressed immeasurably when spontaneous autoimmunity was found in the mouse, 8 and reached its present state of complexity with the discoveries of immunoglobulin receptors on lymphocytes, 9 idiotypes, 10 and suppressor cells. 11 Perhaps the most important advance was the realization, spontaneously arrived at by almost the entire immunologic community, that the production of autoantibodies can be understood only in the context of the general rules of antibody formation.