Revisiting the Mechanisms of CNS Immune Privilege

Abstract

Whereas the study of the interactions between the immune system and the central nervous system (CNS) has often focused on pathological conditions, the importance of neuroimmune communication in CNS homeostasis and function has become clear over that last two decades. Here we discuss the progression of our understanding of the interaction between the peripheral immune system and the CNS. We examine the notion of immune privilege of the CNS in light of both earlier findings and recent studies revealing a functional meningeal lymphatic system that drains cerebrospinal fluid (CSF) to the deep cervical lymph nodes, and consider the implications of a revised perspective on the immune privilege of the CNS on the etiology and pathology of different neurological disorders.

Figure 1. Paths of CSF fluid drainage

The CSF, flowing between the arachnoid and the pia matter of the meninges, can drain into the blood stream through the arachnoid granulations located along the superior sagittal sinus and the transverse sinuses, or reach the lymphatic vasculature of the nasal mucosa by crossing the cribriform plate, localized under the olfactory bulbs, along the olfactory nerves.

Figure 2. The meningeal lymphatics enable the drainage of macromolecules and immune cells

While the CSF fluid drains back to the bloodstream, the macromolecules and immune cells localized within the CSF drain primarily through the meningeal lymphatic vessels to reach the deep cervical lymph nodes.