CROSS-TALK & SIGNALING PATHWAYS

The immune system and the brain talk to each other through signaling pathways. The brain and the immune system are the two major adaptive systems of the body, & the two most complex. Two major pathways are involved in this cross-talk: the hypothalamic-pituitary-adrenal axis (HPA axis) and the sympathetic nervous sytem (SNS).

Both systems also rely on chemical mediators for communication. Electrical signals along nerve pathways, for instance, are converted to chemical signals at the synapses between neurons. The chemical messengers produced by immune cells communicate not only with other parts of the immune system but also with the brain and nerves, and chemicals released by nerve cells can act as signals to immune cells. Hormones from the body travel to the brain in the bloodstream, and the brain itself makes hormones.

A key hormone shared by the central nervous and immune systems is corticotropin-releasing hormone (CRH); produced in the hypothalamus and several other brain regions, it unites the stress and immune responses. The hypothalamus releases CRH into a specialized bloodstream circuit that conveys the hormone to the pituitary gland, which is just beneath the brain. CRH caused the pituitary to release adrenocorticotropin hormone (ACTH) into the bloodstream, which in turn stimulates the adrenal glands to produce cortisol, the best-known hormone of the stress response.

Brain and immune system can either stimulate or inhibit each other. Immune cells produce cytokines (chemical signals) that stimulate the hypothalamus through the bloodstream or via nerves elsewhere in the body. The hormone CRH, produced in the hypothalamus, activates the HPA axis. The release of cortisol tunes down the immune system. CRH, acting on the brain stem, stimulates the sympathetic nervous system, which activates immune organs and regulates inflammatory responses throughout the body. Disruption of these communications in any way leads to greater susceptibility to disease and immune complications.