Evolutionary Causes and Consequences of Immunopathology

Immune responses can cause severe disease, despite the role immunity plays in defending against parasitism. Indeed, immunopathology is a remarkably common cause of disease and has strong impacts upon both host and parasite fitness. Why has immune-mediated disease not been eliminated by natural selection? What constraints might immunopathology impose upon the evolution of resistance? In this review, we explore two major mechanistic causes of immunopathology in mammals and consider how such disease may have influenced immune system design. We then propose hypotheses that could explain the failure of natural selection to eliminate immunopathology. Finally, we suggest how the evolution of strategies for parasite virulence and host resistance may be shaped by this “double-edged sword” of immunity. Future work may reveal whether immunopathology constrains the evolution of resistance in all host taxa.