Springer Semin Immunopathol (1989) 11:439-456 Springer Seminars in Immunopathology © Springer-Verlag 1989 Autoreactive Mechanisms in Infective Endocarditis Bernhard Maisch Department of Internal Medicine-Cardiology, Philipps-University Marburg, Postfach 2360, Baldinger Strasse, D-3550 Marburg, Federal Republic of Germany Summary. Infective endocarditis is not a simple interaction between a microbial agent and a cardiac valve. For the infection of a non-bacterial thrombotic vegeta- tion, predisposition is required which is at least partially operative by a decreased suppressor T cell activity. During infection, peripheral blood natural killer cell activity is decreased, but normalizes under anti-microbial therapy. Non-major histocompatibility complex-restricted lymphocytotoxicity to isolated heart cells can be present in one third of patients. Circulating immune complexes normalize during therapy. They may be the cause of many clinical symptoms of infective endocarditis. Anti-bacterial and also anti-sarcolemmal antibodies which are cross- reactive to the bacterium are secreted in a polyclonal immune response. Anti-sar- colemmal antibodies which are cytolytic in vitro in the presence of complement may partly explain the myocardial factor of heart failure in patients with only marginal valve incompetence due to the endocarditic vegetation. Introduction Neither the systemic manifestations nor the clinical signs and symptoms in infec- tive endocarditis can be simply explained by the hemodynamic consequences of the valvular lesion. Nor can the pathogenesis be elucidated by the bacterial vegeta- tion or the simple immune response to an invading microorganism [39, 71, 72, 75, 76, 80, 81, 93, 100, 101]. The immune response in infective endocarditis, as in any form of inflammation [56], is part of a "network" that has systemic and cardiac sites of action, and which comprises anti-microbial and autoreactive components. It involves predisposition and genetic factors of the individual and has to take into account the tropism and virulence of the infective agent [21, 22, 71, 72, 74, 76, 79-81]. Pathogenetic Concept of the Non-bacterial Thrombotic Vegetation (NBTV) Our current pathogenetic concept of one hallmark of infective endocarditis [32], the NBTV, can be derived from Fig. la [75]. Local [66, 106], or constitutional factors, genetics, permanently or temporarily altered immuno-regulatory proper- ties of the host [43, 51, 65, 107, 120] may facilitate the infection by the NBTV. The NBTV itself develops much more easily on a heart valve which has been predamaged by rheumatic fever, senescence and calcification of the valve ap- paratus, or on "loci minoris resistentiae", as in mitral valve prolapse, or in ar-