Innate Immune Induction of the Adaptive Immune Response

Ten years ago, nearly to the day, one of us (C.A.J.) wasasked by Jim Watson and John Inglis to write the introductory essay to the 54th annual Cold Spring HarborSymposium in Quantitative Biology. He agreed, with theproviso that he could write about anything he wanted to.That is how he came to write a paper called "Approaching the Asymptote: Revolution and Evolution in Immunology (Janeway 1989). It was the best lecture henever gave! In it, he predicted that there would bemolecules that were encoded in the germ line whichwould recognize the presence of molecules produced bybroad classes of pathogens, which he termed patternrecognition receptors (PRRs). He postulated that thesePRRs would recognize what are now called pathogen-associated molecular patterns (PAMPs) and that the binding of the pathogen product to these PRRs would induceexpression of molecules that control the decision by naivelymphocytes to respond to antigen. These molecules arecalled costimulators and their induction is essential forinitiating an adaptive immune response. Expression ofthese molecules was proposed to be regulated by innateimmunity. This paper updates the original hypothesisproposed at the time of the 54th Cold Spring Harbormeeting with the progress made during the past 10 yearsin this area...