Diversity of the Immune Repertoire and Immunoregulation

Abstract

Since the midpoint of the 20th century, medical advances in eco- nomically developed countries have exceeded all expectations. In 1950, the year I entered medical school, the average life expectancy in the United States was 68 years. By 2000, it was 77 years (80 years for women). 1 In 1957, when I began my fel- lowship in hematology, there was no combination chemotherapy, the choice of antibi- otics was limited, computed tomography and magnetic resonance imaging did not ex- ist, and most neoplasms were incurable. And in 1958, the year I began my research on immunosuppressive drugs, the role of the lymphocyte was unclear, and successful or- gan and bone marrow transplantation lay in the future. This is not a comprehensive review, but rather a personal reflection on some aspects of immunology with clinical relevance. My main point is that the immune system’s enor- mous repertoire of antigen receptors allows reactivity not only against pathogens, but also against autoantigens. This potential disadvantage is countered, however, by potent regulatory mechanisms that reduce the risk of harm. Research on these mechanisms has changed clinical practice by uncovering new ways of controlling autoimmune dis- eases and preventing graft rejection.