IMMUNOLOGY AND THE NERVOUS SYSTEM

The immune system participates in both physiologic and pathologic processes that occur within the peripheral and central nervous systems (PNS and CNS). Physiologic responses include immune surveillance by resident (microglia in CNS) and circulating (monocytes/macrophages, dendritic cells) innate immune system cells, that then support subsequent cellular (T cell) and humoral (antibody) adaptive immune responses. Immune responses in the nervous system are essential for clearance of injured tissue and supporting repair processes. Although regarded as a site of relative immune privilege the nervous system, both peripheral and central, can be the selective target of immune mediated disease. In contrast to most animal models, human immune mediated neurologic diseases are occurring spontaneously in an outbred population living in a “dirty environment”. Development of a target directed “autoimmune disease” is dependent on a cascade of events that include initiation of the process response within the immune system, migration of the relevant cells and molecules across the blood-nervous system barrier, persistence of the immune response within the target, and interaction of immune mediators with their target. Environmental and genetic factors influencing these events are important determinants both of disease incidence and disease course. Environmental factors include exposure to pathogens that express antigens that mimic endogenous ones (molecular mimicry) or that express ligands interacting with pattern receptors (eg toll like receptors (TLRs)) expressed by innate immune cells, resulting in enhanced support for an ensuing immune response. Genetic factors regulate properties of the immune system (eg MHC antigen haplotype), blood-nerve barrier, and neural cell susceptibility to injury. Criteria needed to establish the immuno-pathogenic basis of specific neurologic disorders include presence of a specific immune mediator only in affected individuals including at the target site, capacity to adoptively transfer the disease with the mediator, and evidence that its removal is of therapeutic benefit.