Why Do Immune Systems Harm Their Bearers?

Immune-mediated diseases ranging from septic shock to multiple sclerosis exact a huge toll on human health.  Many of the molecular and cellular mechanisms by which the immune system can harm a host’s own tissues or even cause death are well understood.  However, evolutionary explanations for self-harm have received less attention.  What forces of natural selection have generated such a remarkable immune system – capable of feats like memory responses that protect against particular influenza strains decades after first exposure – that also is capable of causing such tremendous damage to our own bodies?

This talk will focus on our emerging understanding of the evolutionary causes of immune-mediated disease, including important roles for susceptibility trade-offs and for long-term co-evolution with parasites such as gastrointestinal worms.  For example, in wild sheep, autoimmunity is associated with enhanced resistance to infectious diseases.  Hosts may thus experience a trade-off: a host could be susceptible to autoimmune diseases OR infections, but not both.  Such a trade-off could help to explain the persistence of diseases like lupus.  Recent tests suggest that this trade-off is borne out in human populations.  Furthermore, the clearance of our co-evolved gastrointestinal worms can alter immune system balance in a way that exacerbates autoimmune disease.  Will the future of medicine entail “restoration ecology” of the human gut, reinstating worms to rein in diseases like ulcerative colitis? These and other clinical implications of an evolutionary understanding of immune-mediated disease will be discussed.