Survival of vertebrate hosts against infections depends on important natural or innate resistance mechanisms combined with adaptive immune responses of T and B cells. Infectious agents probe the limit of immune responses and help to characterize three basic parameters of immunity specificity, tolerance and memory. Specificity: the specificity repertoire of T and B cells is probably in the order of 104 - 105 specificities expressed by protective T cells, or by protective neutralizing antibodies. Tolerance is best defined by rules of reactivity to eliminate infections while avoiding destruction of normal cells; this is achieved by complete elimination of T cells that are specific for antigens persisting within the lymphohemopoietic system. In contrast, T and B cells specific for self- or foreign antigens, limited to extralymphatic tissues are not induced but potentially can be activated to react. Thus antigen staying outside of lymphatic tissues are immunologically ignored. Induction of a T cell response is the result of antigens newly and temporarily entering lymph-nodes or spleen, initially in a local fashion and exhibiting an optimal distribution kinetics within the lymphohemopoietic system. Memory is the fact that a host is resistant against disease caused by re-infection with the same agent. Protection correlates best with an antigen-driven activation of B cells/plasmocytes to maintain protective antibody levels and 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 offspring, activated memory T cells cannot be transmitted for several reasons incl. rejection. Attenuation of infections in infants by maternal antibodies is the physiological correlate of man-made vaccines, therefore infections against which antibody-dependent protection is key work. T cells play an essential role in maintaining T help-dependent memory antibody titers, but also in controlling the many infections that persist in a host at rather low levels (including tuberculosis, HIV). We cannot yet imitate this subtle equilibrium between infection and host, therefore we do not have these vaccines. This explains why all efficient vaccines protect via antibodies whereas vaccination against variable antigens or to maintain macrophage activation or protective T cell responses have so far been unsuccessful.