The Scientific Journals

By : Esther M. Sternberg and Philip W. Gold

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. Indeed, the brain is  perhaps the most prolific endocrine organ in the body and produces many hormones that act both on the   brain and on tissues throughout the body.

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 causes 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.

Cortisol is a steroid hormone that increases the rate and strength of heart contractions, sensitizes blood vessels to the actions of norepinephrine (an adrenalinelike hormone) and affects many metabolic functions —actions that help to prepare the body to meet a stressful situation. In addition, cortisol is a potent  immunoregulator and antiinflammatory agent. It plays a crucial role in preventing the immune system from overreacting to injuries and damaging tissues. Furthermore, cortisol inhibits the release of CRH by the  hypothalamus—a simple feedback loop that keeps this component of the stress response under control. Thus, CRH and cortisol directly link the body’s brainregulated stress response and its immune response.

CRH-secreting neurons of the hypothalamus send fibers to regions in the brain stem that help to regulate the sympathetic nervous system, as well as to another brain stem area called the locus ceruleus. The sympathetic nervous system, which mobilizes the body during stress, also innervates immune organs, such as the thymus,  lymph nodes and spleen, and helps to control inflammatory responses throughout the body. Stimulation of the  locus ceruleus leads to behavioral arousal, fear and enhanced vigilance.

Perhaps even more important for the induction of fear-related behaviors is the amygdala, where inputs from  the sensory regions of the brain are charged as stressful or not. CRH-secreting neurons in the central nucleus  of the amygdala send fibers to the hypothalamus and the locus ceruleus, as well as to other parts of the brain  stem. These CRH-secreting neurons are targets of messengers released by immune cells during an immune response. By recruiting the CRH-secreting neurons, the immune signals not only activate cortisolmediated restraint of the immune response but also induce behaviors that assist in recovery from illness or injury. CRH-secreting neurons also have connections with hypothalamic regions that regulate food intake and  reproductive behavior. In addition, there are other hormonal and nerve systems, such as the thyroid, growth and female sex hormones, and the sympathomedullary pathways, that influence brain–immune system  interactions.

Next : The Immune System’s Signals