Schedule and magnitude of reproductive investment under immune trade-offs explains sex differences in immunity.

Sex differences in immunity are found in many species. Known immune mechanisms in birds and mammals suggest that pathogen detection may be amplified in females, whereas in males, pathogen killing is amplified. We show that these immunological profiles emerge as distinct peaks on a fitness landscape defined by sensitivity-specificity and infection-immunopathology immune tradeoffs. What selection pressures might drive males and females towards separate peaks? Surprisingly, modeling immune trade-offs alone results in a pattern of sex differences that is the reverse of what is observed. By integrating these trade-offs into a life-history framework, where the schedule and magnitude of reproductive investment differs between the sexes, we find that increased age-specific infection and mortality risks during parental investment can push females towards the peak that aligns with empirical observations. Overall, our model suggests enhanced pathogen detection (in females) versus enhanced pathogen killing (in males) is best explained if shared immune tradeoffs interact with sex-specific reproductive schedules and risks. We suggest ways to test this framework empirically.