Mechanisms of brain protection against autoimmune inflammation

Abstract

A significant number of unique antigens expressed in the brain can activate an adaptive immune response, increasing the risk of autoimmune inflammation in the central nervous system (CNS). As a result, a complex protection system exists in the CNS to prevent autoimmune reactions. In addition to the blood-brain- and blood-cerebrospinal fluid-barriers, we discuss complex systems of antigen drainage and circulation of antigen-presenting cells in the CNS. Moreover, the interaction of the CNS with the peripheral immune system typically occurs in specific areas (choroid plexuses, perivascular spaces, and brain meninges), and resident cells of the innate immune system (macrophages, microglia, astrocytes) have limited opportunities for antigen presentation and do not migrate to regional lymph nodes. There are signs of activation of adaptive immunity against CNS antigens in normal conditions, which, however, do not lead to autoimmune diseases. The review covers the mechanisms of maintaining natural immune self-tolerance in the CNS and their failure in autoimmune CNS pathology.