One of the biggest threats to survival is infection, so that the immune system is under permanent and strong evolutionary pressure to be highly responsive. By tracing the evolution of the invertebrate immune system, it can be seen that it largely followed the classical model based on bi-directional predator-prey relationships. Similarly, the evolutionary emergence of MHC system and the mechanisms of immune recognition in vertebrates came as a direct result of a microbe-exerted selection pressure. The new possibilities gave rise to new conveniences and brought about certain risks in the new forms, like auto-immunity, allo-immunity and reproductive efficacy. To that effect, the evolutionary emergence of the MHC has enabled a more effective defence from intracellular parasites, such as viruses. However, the whole complex of processing/presenting/recognizing of antigens could be closely related to the auto-immunity as a by-product of the evolution of MHC system and adoptive immunity. On the other hand, tumor development is frequently accompanied by the immune response against self and altered antigens expressed by tumor cells, because these antigens are the most prevalent molecules recognized by the immune system. The activation of the auto-immune process in parallel with an effective anti-tumor response could mean the failure of protective control mechanisms of the immune reaction that may be responsible for the prevention of auto-immune diseases. At the same time, the activation of suppressor/modulatory mechanisms possibly accompanied by the activation of anti-tumor auto-immune-like immune response could be a factor of anti-tumor immunity failure in all vertebrates.