The blood-brain barrier and the immune privilege of the central nervous system

Collectively known as “immune privilege”, various factors regulate the generation of immune responses in the central nervous system (CNS) and suppress inflammation that would otherwise damage neuronal tissue where cell regeneration processes are severely limited. Recently it has become clear that immune privilege is not absolute but is relative to other organs, varies with age, and varies between the different anatomical compartments of the CNS, with the parenchyma proper exhibiting the highest immune privilege (Galea et al. 2007). Although there are multiple mechanisms that contribute to the immune-privileged nature of the CNS, including the lack of lymphatic vessels, the relative absence of antigen-presenting cells, and the low level of expression of major histocompatibility molecules in the CNS parenchyma (reviewed by Engelhardt and Coisne 2011, Ransohoff and Brown 2012, Shechter et al. 2013a), in this chapter we will focus our attention on the contribution of the blood-brain barrier (BBB) in maintaining immune privilege in the CNS. While there is substantial variability among the physical barriers of the CNS, the BBB generally consists of endothelial cells (ECs), pericytes, astrocytes, neurons, glial cells, and their associated basement membranes, which comprise a complex multilayer, multicellular structure known as the neurovascular unit (NVU).