The self-nonself concept as a basis for immune complex to replace "autoimmune diseases".

The remarkable history of the 1951 pp 66 year old woman with gastric adenocarcinoma is reviewed. After subtotal gastrectomy she survived for 22 years without any metastases. Presumably the artificially induced high titer IgG, anti-P1 proved to be cytotoxic in two stages: (1) binding of anti-P1 to the terminal fifth sugar, galactose, and (2) the action of cellular immunity in the form of killer T derived lymphocytes containing receptors for IgG molecules. An identical mechanism may be operative in inducing abortions in the pp pregnant woman with a P1 fetus. P1 illegitimate glycolipid (GL) red cell antigen and Forssman (Fs) tissue in adenocarcinoma suggest the self-nonself concept because these are genetically foreign to the host. This concept applies also to numerous "autoimmune" diseases such as RA, lupus, glomerulonephritis, Coombs positive hemolytic anemia and other diseases with immune complexes (ICs) of 20--22 Svedberg units deposited as lesions with tissue damage. In the presence of the GL antigens (ABO, P, Fs), the normal serum contains antibodies for the missing antigen(s). The predicted anti-Fs was present in about 80% of normal employees of ages 18--70. In cancer sera the incidence was 35--40%. On testing normal sera by age in terms of decades anti-Fs was present in 93% in the youngest, and only 55% in the oldest group. This may be associated with the gradual loss of protein synthesis with aging and/or the accumulation of soluble ICs which bind the C1q portion of the C added to the test mixture of heat-inactivated serum (1 : 8) g.p. C (1 : 30) and srbc. In "autoimmune" diseases there is an active immune response to viral or bacterial infections or infestations or drugs which attach to rbc and/or tissue cell membranes. This results in the deposition in selected organs of ICs of 20--22 S units with lesions and tissue damage. For therapy plasma (from young donors) exchange has been recommended to compensate for the loss of IgG antibodies and C.