On immunity against infections and vaccines: credo 2004.

Resistance of vertebrate hosts against infections comprises important natural or innate resistance combined with adaptive immune responses of T and B cells. Viruses, bacteria or classical parasites all probe the limit of immune responses and of immunity. They, therefore, offer an excellent opportunity to assess the biology, physiology and molecular aspects of immune responses and help in characterizing the three basic parameters of immunology-- specificity, tolerance and memory. Various experiments are summarized that indicate that the rules of antiviral, antitumour, antiorgan graft and of autoimmune responses are basically the same. The practical specificity repertoire of T and B cells is probably in the order of 10(4)-10(5) specificities expressed by T cells or by neutralizing antibodies. Tolerance is best defined by rules of reactivity to eliminate infections while avoiding destruction of normal cells by complete elimination of T cells that are specific for antigens persisting within the blood and lymphatic (lymphohaemopoietic) system. Induction of a T-cell response is the result of antigens newly entering lymph nodes or spleen, initially in a local fashion and exhibiting an optimal distribution kinetics within the lymphohaemopoietic system. Antigen staying outside lymphatic tissues are immunologically ignored (e.g. are non-events). Thus immune reactivity is regulated by antigen dose, time and relative distribution kinetics. Memory is the fact that a host is resistant against disease caused by reinfection with the same agent. Memory correlates best with antigen-dependent maintenance of elevated antibody titres in serum and mucosal secretions, or with an antigen-driven activation of T cells, such that they are protective immediately against peripheral reinfections in solid tissues. While antibodies transferred from mother to offspring are a prerequisite for the survival of otherwise unprotected immuno-incompetent offsprings, activated memory T cells cannot be transmitted. Thus, attenuation of infections in newborns and babies by maternal antibodies is the physiological correlate of man-made vaccines. T cells not only play an essential role in maintaining T-help-dependent memory antibody titres, but also in controlling the many infections that persist in a host at rather low levels (such as tuberculosis, measles and HIV).