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Evolution of self/non-self discrimination strategies within the innate immune system

Our group studies innate immunity with the goal of understanding strategies of pathogen recognition and self/non-self discrimination. The innate immune system represents the ideal vehicle to pursue these questions because it has evolved under constant selective pressure from microbial pathogens. While adaptive immunity utilizes millions of clonally expressed receptors, the innate immune system uses an alternative strategy: a limited number of receptors with fixed specificities that are expressed non-clonally. The benefit of this strategy is speed; the cost is that the system is critically dependent on the selection of appropriate microbial targets. If the target is easily mutated, then the immune response will fail. If the target is not unique to microbes, then the immune response may attack the host. The solutions to this problem represent a fascinating set of compromises by both the host and microbes. We believe that studying this balance between innate immunity and microbial pathogens will reveal critical balance points in self/non-self discrimination with fundamental implications for our understanding of mammalian immunity. To tackle these issues the lab focuses on the function and regulation of Toll-like receptors (TLRs). TLRs are the prototypical innate immune receptor family. They participate in innate immunity, adaptive immunity, and, in some instances, autoimmunity. This central role makes TLRs an ideal system to address the conceptual issues discussed above.

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