Why the regeneration of immunological tolerance by vaccination is difficult

Autoimmunity, including that involved in chronic inflammatory rheumatic diseases, seems to be the price we have to pay for our efficient immune system. It has the ability to precisely recognize pathogens and tumor cells, to efficiently fight them, to adapt to their alterations and provide specific immunity for a lifetime. "Inoculation", and more specifically "vaccination" takes advantage of this, either by transfer of protective antibodies (passive vaccination) or by using attenuated pathogens or parts of them by which a specific protective immunity is induced (active vaccination). The idea to use vaccination to reduce undesired (auto)immunity and chronic inflammation is nothing new in rheumatology. Many biologicals are antibodies, which specifically block the mediators of inflammation and in the broader sense are similar to a passive vaccination. The active vaccination with autoantigens using the recent mRNA/liposome technology, has shown in experimental animal models that they can prevent the formation of chronic inflammatory immune reactions, in that they strengthen the physiological tolerance and deviate the immune system to noninflammatory immune reactions against the antigen; however, there is still a long way to go to achieve the actual goals of a permanent suppression of established undesired immune reactions and the regeneration of immunological tolerance.