Infections as Adjuvants for Autoimmunity: The Adjuvant Effect

In 1796, Edward Jenner introduced vaccination, in which prior inoculation with cowpox (vaccinia) protected against a subsequent infection with smallpox in humans. Recent understanding of innate immune pattern recognition of pathogens has helped explain the "adjuvant effect". The term "adjuvant effect" was first applied to the critical role of mycobacteria in the Freund's adjuvant used to induce experimental thyroiditis. While adjuvants are often empirical microbial components, possessing potent bioactivities, infectious agents naturally generate their own adjuvant effect and can induce autoimmunity. Briefly, human Toll-like receptors (TLRs) play crucial roles in the innate immune responses against potentially harmful microorganisms, in addition to being biosensors of tissue damage. The nonclonal augmentation of autoimmunity by the adjuvant effect can be harnessed to boost anticancer immune responses. Adjuvants and natural infections can exert potent immunostimulatory activities through the adjuvant effect, which can lead to autoimmune disease.