Generation of diversity is a stochastic post germ line encoded event. The ability to discern btw harmful and innocuous antigens is learned in the neonatal period. Auto reactive lymphocytes recognize self antigens and are deleted. Foreign antigens introduced during that period would also induce tolerance. Horror autotoxicus would result from a break down of tolerance to self (ex: diabetes i attacks islet cells) Old view: self-nonself / antigen driven / developmentally determined. New view: context model/ circumstance driven/ determined by milieu. Immune system activated by pamps (ex: lps on pathogens) triggering prrs (ex: toll receptor) Ag presented in presence of danger productive immune response. Ex of danger signals: molecules released during injury and necrotic cell death (heat shock proteins) Decision of tolerance or productive response by state of apc. When activated b/c of infection, inflammation, papmps or danger, d apc upregulates: Signal one: presentation of antigen to t cells. Note: apc doesn"t need costimulation once it is activated!