(439d) Understanding Adaptive Immunity: A Crossroad of the Physical, Life, and Engineering Sciences

Higher organisms, like humans, have an adaptive immune system that can combat pathogens that have not been encountered before. The adaptive immune system can also go awry, and many autoimmune disorders (e.g., multiple sclerosis, type I diabetes, etc.) are the direct consequence of the adaptive immune system attacking the organism's own tissues. T lymphocytes (T cells) are the orchestrators of the adaptive immune response. They interact with cells, called antigen presenting cells, which display molecular signatures of pathogens on their surface. T cells detect the presence of these molecular signatures of pathogens with great sensitivity. How T cells hunt for antigen, how they discriminate between ?self? and ?non-self? with extraordinary sensitivity, and how their activation is regulated and mis-regulated are central questions in fundamental biology. In spite of some spectacular advances, an understanding of the principles that govern how T cell responses are regulated and misregulated has not emerged. A principal reason for this is that the biology of T cells is an example of ?emergent complexity?; i.e., the pertinent dynamic events cannot be parsed in terms of a linear superposition of the consequences of binary interactions between the relevant components and the cooperative processes span a spectrum of time and length scales. This hierarchical cooperativity, with feedback, makes it difficult to intuit underlying mechanisms from a few observables. I will discuss recent efforts where bringing together approaches from the physical, life, and engineering sciences has shed light on the mechanisms that regulate this complexity. I will especially highlight how stochastic fluctuations and spatial organization of components can influence the behavior of this system in important ways.