The central nervous system has always been considered an "immunologically privileged" site because the gatekeeper, the blood-brain-barrier (BBB), prevents even macromolecules from entering. In fact, as in other tissues, effector (but not naive) lymphocytes readily cross the BBB as part of normal immune surveillance and these cells participate in the control or elimination of invading pathogens. Thus, under normal circumstances, lymphocyte trafficking through the brain benefits the organism. However,in individuals with multiple sclerosis (MS), myelin-reactive CD4+ T cells enter the CNS, become activated and mediate an inflammatory response culminating in breakdown of the BBB, edema, inflammation and demyelination. The purpose of this section is toreview mechanisms of CD4+ lymphocyte priming (afferent response), homing to the CNS and activation (efferent response). MS and the murine model, experimental allergic encephalomyelitis (EAE) will be used to illustrate this process.
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