ON THE MYSTIQUE OF THE IMMUNOLOGICAL SELF

Since the time of Paul Ehrlich 100 years ago, we have known that the i mmunological apparatus somehow inhibits most damaging autoimmune respo nses while permitting a response to exogenous immunogens. With the dis covery of tolerance, the concept of immunological surveillance, and es pecially with the discovery of HLA restriction of T-cell recognition, the term ''the immunological self'' and the phrase ''self-non-self dis crimination'' have gained wide currency. Immunology has been called '' The Science of Self'', and self-nonself discrimination has been assign ed as the driving force for its complex evolution. The concept of self has thus been given such mystical trappings since the time of Macfarl ane Burnet that recent workers have felt free to pronounce it the cent ral paradigm of modern immunology, and to claim to overthrow it! In th is article, we challenge some of the more egregious claims about the i mmunological self by recalling important historical findings, by revie wing the mechanisms of Darwinian evolution, and by remembering that th e general pathology of immunogenic inflammation shows that the immune response cannot discriminate between the benign and the noxious.