Pressures of life on Earth experienced by our ancestors – as multicellular beings, as hosts to parasites, and as home to microbes – shaped the evolved structure and function of our immune systems. Some of the traits favored by natural selection have conferred resistance against infections while opening vulnerabilities to autoimmune diseases. I will illustrate why analysis of the deep-time origins of mammalian immune systems reveals general principles of optimal defense and helps to explain why hosts are so profoundly variable in their susceptibility to infectious and inflammatory diseases. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Humanities] [Science] [Show ID: 40692]