Basic Aspects of the Immunology of Neuroinflammation

Neuroinflammation is used to describe an immune-related process that occurs within the central nervous system (CNS). The objective of this chapter is to introduce basic aspects of neuroinflammation in the context of psychiatric disorders. Inflammatory processes are evident in the CNS with a myriad of stimuli including neurological disease, CNS injury or infection, peripheral infection, and psychological stress. Because the CNS maintains a degree of immune privilege, endothelial cells of the blood-brain barrier (BBB) and resident CNS innate immune cells are integral to the interpretation and propagation of inflammatory signals. For instance, activated CNS immune cells and the BBB coordinate production of cytokines and secondary messengers that act directly to influence neurophysiology. Another key concept is that there is bidirectional communication between the immune system and CNS. Afferent neuro-immune pathways relay the peripheral inflammatory profile to the CNS by secretion of cytokines and direct neuronal activation. Communication through afferent neuro-immune pathways promotes physiological and behavioral responses that are aimed to help clear pathogens from the host. For example, peripheral infection increases circulating IL-1β that induces production of prostaglandins and IL-1β by CNS immune cells that initiate fever and the behavioral symptoms of sickness. Although transient cytokine responses in the brain may be beneficial to the host, prolonged neuroinflammation associated with chronic illness, neurodegenerative disease, stress, and aging impair neuroimmune regulation and negatively affect normal cognitive and behavioral processes. Thus, understanding neuroimmune regulation and mechanisms that mediate neuroinflammation is important because these pathways likely contribute to the pathophysiology of several mental health disorders.