When T-helper cells don't help: immunopathology during XXXX .

@entity1 @entity410 @entity66 @entity19 @entity383 @entity281 @entity56 @entity380 @entity3204
Disease directly caused by immune system action is known as immunopathology. Many factors may lead the immune system to cause rather than cure disease, and autoimmune, @entity56 , and infection-related @entity66 affect millions of @entity1 worldwide. This review presents an analysis of T-helper cell mediated, infection-related immunopathology within the framework of evolutionary ecology. A proximate cause of infection-related immunopathology is an error in the type of T-helper response induced. Distinct subsets of T-helper cells enable different effector mechanisms and therefore work optimally against different types of parasites (e.g., extracellular versus intracellular parasites). Immune responses that cure rather than cause disease require that the T-helper subset be tailored to the parasite. It is thus critical for the immunophenotype to match the "environment" of the @entity281 . As in other cases of adaptive plasticity, a mismatch between an organism's phenotype and the selective environment can decrease @entity410 . T-helper response induction may be confounded by coinfection of a single host by multiple parasite species. Because of normally adaptive feedback loops that lend to polarize T-helper responses, it can become impossible for the immune system to mount effective, conflicting responses concurrently. Immunophenotype-environment mismatches may thus be inevitable when simultaneous, conflicting immune responses are required. An ultimate cause of infection-related immunopathology in a multiparasite selection regime is the T-helper response polarization that can propagate response errors and constrain the ability of the immune system to resolve conflicting response requirements. A case study is used to illustrate how coinfection can exacerbate immunopathology and to frame testable predictions about optimal responses to coinfection (e.g., is the observed joint response to coinfection accurately predicted by the average of the component single-infection optimal responses, where the single-infection optima are weighted by the contribution of each to @entity410 ). The case study includes immunological and pathological data from @entity19 infected by @entity380 alone and by @entity383 in combination with @entity3204 . Such data can inform hypothesis tests of evolutionary ecological principles, and ecological analysis can in turn clarify assumptions about responses to coinfection for a greater understanding of the immune system. The synthesis of evolutionary ecology and immunology could therefore be of mutual benefit to the two disciplines.
