Aging in the immune system is a loss of balance

The innate and adaptive arms of the vertebrate immune system work in close collaboration to protect organisms from harmful pathogens. As an organism ages its immune system undergoes immunosenescence, characterized by degraded performance or malfunction, in either arm, that leads to diseases and even death. However, a system-level mechanism of immunosenescence is not understood.
In this talk, I introduce a mathematical model of immune response that integrates the innate and adaptive components, which enables studies of their mutual modulation over an individual’s lifetime. Our results capture the clinically-observed chronic inflammation associated with aging, demonstrating that this “inflamm-aging” could be of protective origin by compensating for weakened adaptive immunity. We show that the timing of onset of persistent inflammatory response depends strongly on the temporal pattern of pathogen encounter and uncover potential determinants of the timing. Finally we examine the bipartite role of adaptive immunity in a balance between removing pathogens and mitigating inflammation. In all, our work suggests that aging in the immune system exemplifies a failure of coordination between adaptive and innate immunity and the timing of failure is strongly shaped by the infection history.