To understand the intriguing story of how the nervous system, endocrine system, and immune system interact, we need to examine some of the main features of the immune system. In your blood are different classes of white blood cells (leukocytes). The phagocytes (“eating” cells) are specialized to engulf and destroy invading germs. But phagocytes rely on other white blood cells (the lymphocytes) to tell them what to attack. B lymphocytes (or B cells, because they form in the bone marrow), produce proteins called antibodies (or immunoglobulins). Antibodies latch onto foreign molecules such as viruses or bacteria and summon phagocytes and circulating proteins to destroy the invaders. T lymphocytes (T cells), so called because they form in the thymus gland, can act as killer cells, forming a strong part of the body’s attack against foreign substances. In addition, special T lymphocytes called helper T cells secrete cytokines, cell signaling proteins that regulate the activity of B lymphocytes and phagocytes.

These immune system cells form in the thymus gland, bone marrow, spleen, and lymph nodes (see Figure 1), which release the cells into the bloodstream.

Figure 1  Main Components of the Human Immune System
(a) The various components of the immune system protect us by means of three classes of white blood cells: (b) B lymphocytes produce antibodies to attack invading microbes. (c) T lymphocytes form helper cells that release cytokines to regulate B cells to divide or die. (d) T cells also form killer cells that, together with phagocytes (“eating” cells), directly attack foreign tissues or microbes.

Communication among the Nervous, Immune, and Endocrine Systems

The brain affects the immune system through autonomic nerve fibers that innervate immune system organs such as the spleen and thymus gland. These fibers are usually noradrenergic, sympathetic postganglionic axons that affect antibody production and immune cell proliferation (Bellinger et al., 1992).

The brain also carefully monitors immune reactions to make sure they are not too extreme and ultimately harmful to the body. For example, peripheral axons of the vagus nerve have receptors to detect high levels of cytokines and relay the information to the brain. Then, brainstem neurons with axons that lead back out the vagus nerve release acetylcholine, which inhibits cytokine release from immune cells (Wang et al., 2003). Hypothalamic neurons and neurons located in the walls of cerebral ventricles also monitor cytokines in circulation (Bartfai, 2001; Dantzer et al., 2008; Samad et al., 2001). Thus, the brain is directly informed about the actions of the immune system, which serves as an early-warning sensory system to alert the brain when microbes invade the body (Besedovsky and del Rey, 1992).

There is an interesting theory about why our brains monitor the immune system so closely. Although that achy, lethargic feeling that we have with the flu is unpleasant, it is also adaptive because it forces us to rest and keep out of trouble until we recover (Hart, 1988). Perhaps high levels of cytokines are what cause the brain to enforce that sick feeling. This suggestion has given rise to the idea that some people’s depression may be due to a broad set of physiological changes in the brain, including large alterations in the availability of several neurotransmitters, that are brought about by excessive quantities of cytokines in circulation and penetrating the brain. Indeed, one action of antidepressant drugs is to reduce cytokine production (Dantzer et al., 2008; Kenis and Maes, 2002; Maes et al., 1991).

The immune system and nervous system also interact extensively with the endocrine system. Figure 2 shows some examples of these relationships. All three systems interact reciprocally, so there is a constant state of flux, carefully tuning the immune system so that it vigorously attacks foreign cells but leaves the body’s own cells alone.

Several lines of evidence indicate that the immune system is compromised during depression (M. Stein et al., 1991)—a situation that, if sustained, could increase susceptibility to infectious diseases, cancer, and autoimmune disorders. Altered immune function is also observed in people who are grieving the death of a relative, especially a spouse (M. Stein and Miller, 1993).


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