Immune protection of the brain--efficient and delicate.

Abstract

The brain is in general considered the body's noblest organ. Its parenchyma is densely packed with electrically active neurons and glial cells that constantly undergo spatial rearrangements, but there is little connective tissue. The brain is vulnerable; it requires a particular degree of protection. Quite obviously, the brain is protected against external physical forces by a robust capsule formed by skull bones and meninges. Less obvious and by no means trivial is how the body protects its brain from endogenous danger, for example microbial infection. In fact, there has been a longstanding debate concerning the existence of immune reactivity within the central nervous system (CNS). In 1986, my colleagues and I reviewed the traditional concept of neuroimmunology?that the CNS was an immunoprivileged site, excluded from immune surveillance, and inaccessible to immunocompetent migratory cells [1]. The evidence supporting the concept of immunologic privilege rested on three structural peculiarities that distinguish the CNS from other tissues. First, there is a specialized endothelial bloodbrain barrier (BBB) that secludes the CNS parenchyma from the circulating blood and prevents most blood components from entering the tissue. Second, the CNS lacks fully organized drainage via lymphatic vessels. These are of crucial importance for the transport of antigen-presenting (dendritic) cells to travel from peripheral tissues to immune organs, where they trigger a full immune response. Third, major histocompatibility complex (MHC) determinants are conspicuously absent in the mature CNS. Without MHC proteins expressed on cell membranes, there is no presentation of antigenic peptide to specific T lymphocytes. Perhaps of even more importance, professional antigen-presenting cells, the cells specialized for the transport of peripheral antigen to immune organs and for activation of antigen-inexperienced naive T cells, are missing in the CNS. A wealth of recent information indicates that the BBB, lack of lymphatic drainage, and the lack of MHC antigens by no means reflect an absolute absence of immune reactivity within