Fig. 2.

A simplified scheme that divides organisms into categories based on whether or not they co-evolved with humans and needed to be tolerated, and so developed immunoregulatory roles within the immune system. The ‘old’ infections were able to persist in isolated hunter-gatherer groups as carrier states and latent infections, and so evolved the ability to modulate the immune system. The microbiotas also needed to be tolerated, and an unknown subset of organisms within the commensal microbiotas is derived from the environment, including animal sources. The crowd infections evolved relatively recently and either kill the host or immunize, and constitute the only category that is increased rather than decreased in high-income settings. Epidemiological studies show that the crowd infections are not immunoregulatory.