Connection and communication between the nervous and immune systems

Abstract

Connections between the nervous and immune systems are increasingly recognized as central to brain–body physiology. In this Review, we examine how these systems collaborate to detect and respond to both internal and external stimuli — such as psychological stress, circadian cues, infection, and tissue injury. Rather than operating in isolation, the nervous and immune systems form an integrated network that is more than the sum of its parts. They share a common architecture and vocabulary, enabling bidirectional connection and communication that modulate immune cell characteristics throughout the body. We review immune–nervous interactions within two complementary frameworks: first, a spatial framework that distinguishes communication in the brain, communication within peripheral organs, and communication across distance; and second, a temporal framework that maps nervous system influence across the operational lifespan of the immune system — specifically focusing on how the nervous system impacts immune cell development, distribution, and execution of functions. Finally, we highlight key tools, clinical applications, and questions for future research on how both systems coordinate to respond to somatic and environmental stressors.