Immune surveillance and autoantigen recognition in the central nervous system

The central nervous system (CNS) is considered to be a severely disadvantaged site for the elicitation of immune responses. First, there is no specialised lymphatic drainage. Second, both glia and neuronal cells normally do not express appreciable levels of major histocompatibility complex molecules. Third, the vasculature of the CNS is, at least in most places, lined by endothelial cells that have tight junctions and form a barrier (the blood-brain barrier) against most molecules and cells present in the circulation. Fourth, the cells most important in the initiation of immune response, the leucocyte dendritic cell, are not present. Nevertheless, the existence of inflammatory diseases of this tissue, occurring naturally as in multiple sclerosis or in animals after peripheral immunisation with CNS autoantigens, indicates that the immune system can access and recognise antigens in this site. How this is achieved has become clearer in recent years and primarily seems to involve extravasation of activated but not resting T cells across the blood-brain barrier, and recognition of antigen on macrophage-like perivascular cells, rather than cells within the CNS parenchyme such as astrocytes or microglia. The processes involved in immunological patrolling of the CNS and development of autoimmune inflammatory disease are reviewed.