The Role of Microglia and Astrocytes in Cns Immune Surveillance and Immunopathology

Abstract

Efficient immune surveillance and tissue repair within the central nervous system (CNS) are achieved through a complex and highly regulated network of interactions between resident brain cells and the immune system. Due to its unique structure and environment, the CNS exerts a strict control on the development of inflammatory and immune reactions that can be extremely injurious (Cserr and Knopf, 1992). Major features that contribute to the immune privilege of the CNS include: the presence of structural barriers such as the tight endothelial junctions of the brain vasculature restricting the passage of circulating immune cells and molecules; the lack of a lymphatic drainage; the absence of potent antigen presenting cells (APC) such as dendritic cells that capture potential antigens in the tissues and transport them to regional lymph nodes to initiate immune responses. Several other local mechanisms have been recently proposed which may actively limit immunogenic inflammation and tissue damage within the CNS. These include: the presence of mediators, such as transforming growth factor-β (TGF-β) (Cserr and Knopf, 1992) or brain lipids (Irani et al., 1997) with an immunosuppressive role; a strict downregulatory control exerted by neurons on major histocompatibility complex (MHC) antigen expression within the CNS parenchyma, thereby limiting the potential for local antigen presentation (Neumann et al., 1996); apoptotic elimination of T cells as a mean to terminate cell-mediated immune responses once they have been initiated within the CNS (Bauer et al., 1995).