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The immune system's function is to protect against microorganisms, but infection is nonetheless the most frequent cause of death in human history. Until the last century, life expectancy was only ∼25 years. Recent increases in human life span primarily reflect the development of hygiene, vaccines, and anti-infectious drugs, rather than the adjustment of our immune system to coevolving microbes by natural selection. We argue here that most individuals retain a natural vulnerability to infectious diseases, reflecting a great diversity of inborn errors of immunity.

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