The Adjuvant Effect in Infection and Autoimmunity

Infections are widely believed to serve as a trigger for initiating autoimmune disease in humans. An infectious agent may activate lymphocytes in an antigen-specific manner and can also provide the nonantigen-specific second signal necessary to induce a pathogenic adaptive immune response. Collectively, the secondary signaling necessary for induction of an autoimmune disease has been referred to as the adjuvant effect. Examples of an adjuvant effect have been described in the induction of experimental thyroiditis where the administration with thyroglobulin of muramyl dipeptide of mycobacteria or lipopolysaccaride of Gram-negative bacilli provide the necessary adjuvant effect. Other commonly used adjuvants fail to induce disease, although they may elicit autoantibody formation. Myocarditis can be induced in susceptible mice by infection with cardiotrophic coxsackievirus B3 and even induced in resistant mice if an additional adjuvant effect is provided through proinflammatory cytokines like interleukin-1β and tumor necrosis factor-α. The adjuvant effect is usually exerted early after infection during the innate immune response, operating at least in part through toll-like receptors and mast cells to direct the subsequent pathogenic adaptive immune response.