Benefits of Being Big: How a T cell response can occur as rapidly in a human as a mouse

Abstract The adaptive immune response must be fast in order to protect against exponentially growing novel pathogens. A remarkable property of the immune system is that despite a human which is approximately 2500 times larger than a mouse, the human immune response is initiated as fast as that of mice. This is in contrast to most biological processes slowing systematically with body mass. We have now collected data comparing the sizes of immune organs including spleen and lymph nodes across a large number of species including mice, rat, rabbit, macques, human, pigs, camels, cattle, and elephants. We mathematically demonstrate that while spleens scale similarly to other organs such as the hearts and kidneys, the size and number of lymph nodes scale differently than typical organ size. Using a novel computational modeling approach to predict the time that the first T cell is likely to encounter a dendritic cell presenting cognate antigen after infection, we show that the size and number of lymph nodes determine the timing of the adaptive immune response and enable even very large animals to respond quickly to pathogen infection. Combined with empirical scaling of lymph node volume, this suggests that the initiation of T cell adaptive immunity in lymph nodes occurs faster in larger animals like humans, compared to small laboratory animals which are the focus of many immunological and vaccine studies. UNM Center for Advanced Research Computing, supported in part by NSF, for high performance computing resources, as well as the James S. McDonnell Foundation and NSF awards 2030037 and 2020247 for funding.