Convergence and divergence of individual immune responses over the life course

Three ingredients create the strikingly variable immune trajectories observed across human populations: (i) genetic variation, (ii) individual-scale generation of additional genetic diversity solely in lymphocytes, and (iii) collision of these processes with a changing environment through life, triggering plastic responses that can have lasting effects. We explore what generates or reduces immune variation, integrating recent empirical advances with potential overarching evolutionary principles. We posit that the multiple components of the immune system each present trade-offs (such as self-defense–self-harm, and investments in memory–retaining flexibility for future responses) that vary through life, and that variation in how immune components balance these trade-offs increases homeostasis to external and internal threats. Disentangling the mechanisms that shape immune diversity could inform effective strategies to manage microbial interactions and mitigate the burden of immune-mediated chronic diseases.