The evolution of powerful yet perilous immune systems

Area of Science:

• Evolutionary biology
• Immunology
• Human health

Background:

• The mammalian immune system demonstrates both protective and harmful capabilities, as exemplified by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections.
• Natural selection theoretically optimizes immune responses to balance defense benefits against costs like immunopathology and resource expenditure.

Purpose of the Study:

• To apply evolutionary biology principles to predict optimal immune responses.
• To explain the occurrence of maladaptive immunopathological responses.
• To elucidate the evolutionary factors contributing to human susceptibility to excessive immune reactions.

Main Methods:

• Conceptual analysis integrating evolutionary biology with immunology.
• Examination of evolutionary legacies such as multicellularity and life-history strategies.
• Consideration of coevolution with symbionts and demographic history.

Main Results:

• Evolutionary biology can predict optimal immune response levels.
• Evolutionary frameworks help explain why individuals exhibit seemingly maladaptive immunopathology.
• Human susceptibility to overzealous, pathology-inducing cytokine responses is linked to evolutionary factors.

Conclusions:

• Evolutionary insights complement molecular and cellular mechanisms in understanding immunopathology.
• Multicellularity, life-history strategy, symbiont coevolution, and demographic history shape human immune responses.
• Understanding these evolutionary drivers is crucial for managing immune-mediated diseases.