The evolution of powerful yet perilous immune systems

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9 Scopus citations


The mammalian immune system packs serious punch against infection but can also cause harm: for example, coronavirus disease 2019 (COVID-19) made headline news of the simultaneous power and peril of human immune responses. In principle, natural selection leads to exquisite adaptation and therefore cytokine responsiveness that optimally balances the benefits of defense against its costs (e.g., immunopathology suffered and resources expended). Here, we illustrate how evolutionary biology can predict such optima and also help to explain when/why individuals exhibit apparently maladaptive immunopathological responses. Ultimately, we argue that the evolutionary legacies of multicellularity and life-history strategy, in addition to our coevolution with symbionts and our demographic history, together explain human susceptibility to overzealous, pathology-inducing cytokine responses. Evolutionary insight thereby complements molecular/cellular mechanistic insights into immunopathology.

Original languageEnglish (US)
Pages (from-to)117-131
Number of pages15
JournalTrends in Immunology
Issue number2
StatePublished - Feb 2022

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


  • Goldilocks
  • cytokines
  • evolutionary biology
  • immunopathology
  • optimality


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