The clinical picture of an infectious disease, the character of its course, the outcomes depend on the mode of entry. When infection occurs naturally there happens an adequate immune response, the disease manifests typical symptoms, proceeds cyclically and ends with the recovery with formation of a full-fledged sterile immunity. In the case of hematogenous infection these is no full mode of entry and there may develop fulminant forms of the disease or a chronic course with the involvement of visceral organs in the process. Sterilizing immunity is not formed in this case. Complete sanogenesis requires the presence of the pathogen or its mediators in the primary site of infection. HIV, hepatitis C and B, tetanus, rabies should be treated as infectious diseases occurring due to the mechanisms of tropism's change. It provides the emergence of new tropism substrates with subsequent involvement in the process of visceral organs. The challenge for the future is to search for specific mediators of the immune response, triggering and controlling all stages of a germ and macroorganism interaction.