Genes, Environments, and Phenotypic Plasticity in Immunology

For most of its history, immunology has sought to control environmental variation to establish genetic causality. As with all biological traits though, variation among individuals arises by three broad pathways: genetic (G), environmental (E), and the interactive between the two (GxE); and immunity is no different. Here, we review the value of applying the evolutionary frameworks of phenotypic plasticity and reaction norms to immunology. Because standardized laboratory environments are vastly different from the conditions under which populations evolved, we hypothesize that immunology might presently be missing important phenotypic variation and even focusing on dysregulated molecular and cellular processes. Modest adjustments to study designs could make model organism immunology more productive, reproducible, and reflective of human physiology.