Infectious Triggers of T Cell Autoimmunity

Autoimmunity is a significant health concern with diseases like type 1 diabetes (T1D) rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and multiple sclerosis (MS) drastically increasing in prevalence. The precise trigger for autoimmunity is unknown, although genetics clearly plays a significant role. However, low concordance rates in monozygotic twins as well as geographical distribution patterns suggest that the development of autoimmunity is the culmination of multiple factors, with genetic predisposition being only one component. Retrospective epidemiological and animal studies have shown that infection is an important factor in the generation of autoimmune disease. Traditionally, cross-reactive T cell recognition, known as molecular mimicry, as well as bystander T cell activation culminating in epitope spreading, have been the predominant mechanisms through which infection may culminate in an autoimmune response. Notwithstanding, recent studies suggest other avenues, including microbial toxins and virus-induced decoy of the immune system, may also play a role. In this chapter the relationship between the antimicrobial immune response and development of autoimmune disease will be reviewed.