Immune-Driven Pathogen Evolution
© 2016 Elsevier Ltd All rights reserved. The development of immunity places pressure on pathogens to find ways to evade or subvert it, through mechanisms such as clonal antigenic variation or the downregulation of major histocompatibility complex (MHC) molecules. It also sets up competition between different pathogen strains, as a previously infected host may no longer be available for infection due to the establishment of immune responses that are also effective against the newly invading strain. Competition between strains is particularly acute when the principal targets of immunity are conserved epitopes: in these cases, each individual can only sustain a single infection by a particular pathogen species and may thereafter enjoy lifelong protection, such as for many common childhood infections like measles, mumps, and whooping cough (pertussis). Pathogens in this category typically evolve toward a state of very limited diversity dominated by genotypes of optimal virulence (i.e., that which maximizes transmissibility). When the principal targets of immunity are variable, the same principles of competitive exclusion lead to the coexistence of antigenic types (here referred to as strains), which differ as widely as possible in the immune responses they provoke. Immunological competition between pathogen strains may lead to the stable establishment of discrete antigenic types with nonoverlapping variant repertoires or cause cyclical, or even chaotic, fluctuations to occur in the frequencies of different antigenic types. The structuring of pathogen populations through immune selection can in turn induce nonrandom associations among host genes involved in pathogen recognition such as MHC loci.