Learning and memory ... and the immune system

Abstract

The nervous system and the immune system are two main regulators of homeostasis in the body. Communication between them ensures normal functioning of the organism. Immune cells and molecules are required for sculpting the circuitry and determining the activity of the nervous system. Within the parenchyma of the central nervous system (CNS), microglia constantly monitor synapses and participate in their pruning during development and possibly also throughout life. Classical inflammatory cytokines, such as interleukin (IL)-1β and tumor necrosis factor (TNF), are released during neuronal activity and play a crucial role in regulating the strength of synaptic transmission. Systemically, proper functioning of the immune system is critical for maintaining normal nervous system function. Disruption of the immune system functioning leads to impairments in cognition and in neurogenesis. In this review we provide examples of the communication between the nervous and the immune systems in the interest of normal CNS development and function.

Figure 1.

Working model of the immune response during a cognitive task. Under homeostatic conditions, the meningeal spaces are surveyed for potential disturbances by resident myeloid cells, as well as circulating white blood cells (including monocytes and T cells). During an acute cognitive task performance, such as Morris water maze, circulating immune cells can be activated by peripheral danger signals (the identity of which is yet to be determined, but potentially corticosterone and catecholamines), which are released in response to the stress that the task involves. In a wild-type mouse, activated T cells and monocytes infiltrate the meninges and mount a homeostatic type-2 immune response, releasing tissue-building cytokines such as IL-4 and IL-10. In SCID mice that lack the adaptive branch of the immune system (no mature T and B cells), nonregulated inflammatory monocytes initiate a type 1 inflammatory response, with the release of inflammatory cytokines such as TNFα. Although the cellular and molecular pathways are yet to be elucidated, the inflammatory type-1 response contributes to impaired cognition, whereas an alternative type-2 immune response is more “procognitive.”