Optimal immune specificity at the intersection of host life history and parasite epidemiology.

Hosts diverge widely in how, and how well, they defend themselves against infection and immunopathology. Why are hosts so heterogeneous? Both epidemiology and life history are commonly hypothesized to influence host immune strategy, but the relationship between immune strategy and each factor has commonly been investigated in isolation. Here, we show that interactions between life history and epidemiology are crucial for determining optimal immune specificity and sensitivity. We propose a demographically-structured population dynamics model, in which we explore sensitivity and specificity of immune responses when epidemiological risks vary with age. We find that variation in life history traits associated with both reproduction and longevity alters optimal immune strategies–but the magnitude and sometimes even direction of these effects depends on how epidemiological risks vary across life. An especially compelling example that explains previously-puzzling empirical observations is that depending on whether infection risk declines or rises at reproductive maturity, later reproductive maturity can select for either greater or lower immune specificity, potentially illustrating why studies of lifespan and immune variation across taxa have been inconclusive. Thus, the sign of selection on the life history-immune specificity relationship can be reversed in different epidemiological contexts. Drawing on published life history data from a variety of chordate taxa, we generate testable predictions for this facet of the optimal immune strategy. Our results shed light on the causes of the heterogeneity found in immune defenses both within and among species and the ultimate variability of the relationship between life history and immune specificity. Author summary: Organisms must use their immune defenses to counter infections, and their particular immune needs and optimal strategy for defense are likely to depend on the infection threats they face and their reproductive and survival schedules. Yet little is known about how these factors might interact together to influence immune strategy. We used a population dynamics model to examine how optimal immune specificity in host recognition of parasites depends simultaneously upon reproduction, survival, and parasite threats across life. We find that the strength and direction of the association between immune specificity and reproduction or survival depends on parasite threats and how they vary with age. For example, a highly specific immune response is favored for long-lived, slow-reproducing organisms when infection risk declines with age but is also favored for short-lived, fast-reproducing organisms when infection risk rises with age. Thus organisms with very different schedules may have identical specificities depending on their particular circumstances. Our research highlights how the immune strategies needed to "live fast and die young" or "live long and prosper" are not fixed but rather will depend on the interplay of different pathogen risks at different stages of life with when, during their lives, organisms reproduce. [ABSTRACT FROM AUTHOR]