Psychoneuroimmunology is the study of interactions between behavior, the brain, and the immune system. It also connects the fields of psychiatry, endocrinology, physiology, and the biomedical research community. Robert Ader and Nicholas Cohen (1981) introduced the term psychoneuroimmunogy as the title for their landmark book, which included reviews of the role of the central nervous system (CNS) in the complicated interplay of behavior and the immune system.

Let us first see how the brain is actually connected to the immune system. That is how the brain can actually control the immune system, which was once thought of a discrete closed system. It was assumed that the immune system takes its own route of functions. However, it was recently observed that various psychological conditions affect the immune system. So let’s begin with the way the CNS is connected to the Immune system.

Connections of Central Nervous System to Immune System

The brain is connected to the immune system like every other system of the body. The brain regulates the immune system by two different means. First through direct   Physical contact (between brain and immune system) and indirectly through certain factors released by nervous system (e.g. endocrine gland)

  1. Physical contact of brain with the immune system

The brain connects and controls other peripheral processes through peripheral nervous system. The autonomic nervous system, composed of sympathetic and parasympathetic branches. The sympathetic nervous system innervates immune organs such as the thymus, bone marrow, spleen, lymph nodes and gut associated lymphoid tissue. By having nerves connected to these important immune organs, the brain is able to directly regulate immune system activities. Sympathetic nerve terminals release the catecholamine (neurotransmitters) named norepinephrine. Immune organs and cells contain catecholamine receptors. The terminals of sympathetic nerves in these immune organs make contacts with lymphocytes themselves, and these contacts have the ultrastructural features of synaptic contacts.

  1. Released factors

In the 1950’s, biologists discovered that most of the hormones influence the immune system. The hormones secreted by hypothalamus, thyroid, the pituitary and the ovaries and testes influence immune cells. The brain and peripheral nerves release numerous neurotransmitters and other chemicals called neuropeptides. Neurotransmitters and neuropeptides are also chemical messengers. Most neurotransmitters and neuropeptides influence immune cell activities. There are many hormones, neurotransmitters and neuropeptides released by the brain or by structures controlled by the brain which regulate the immune system

The brain can communicate with the peripheral organs by releasing factors that cause endocrine glands to secrete hormones into the circulation, thereby enabling the hormones to reach the various organs and bind to hormone receptors on the organs.


(also called hydrocortisone) is the best-known example of hormonal control of the immune system. It is an anti-inflammatory and immunosuppressive hormone made by the adrenal cortex. The production of cortisol is governed by the pituitary and the pituitary is controlled by the hypothalamus. Hence the brain, via its control over cortisol and other hormone secretions, helps regulate the immune system indirectly.

Mechanism: After the brain is exposed to cytokines, the hypothalamus begins secreting more of a key hormone called corticotrophin releasing factor (CRF). CRF stimulates the pituitary to release adrenocorticotropic hormone (ACTH). The adrenals are stimulated by ACTH to release more cortisol. CRF, ACTH and cortisol are three of the main hormones released in response to cytokine exposure. They are called stress hormones because they are elevated during biologically stressful conditions like infection, trauma, cancer and ischemic events. Psychologically stressful conditions also raise stress hormone levels. T and B cells have receptors for many hormones, including the stress hormones.


Activation of the sympathetic nervous system by stressors also leads to the release of catecholamines (i.e., norepinephrine and epinephrine) (neurotransmitters as well as hormones) from the inner portion (medulla) of the adrenal gland into the blood; lymphocytes have catecholamine receptors as well. Immune cell function is altered by the action of these hormones and transmitters at receptors on the lymphocytes. Therefore, the brain controls immune cells and organs in the same ways as other peripheral structures.


  • Evidences:

The brain lesions and stimulation at some brain sites affects some aspect(s) of immune responses. The indirect control of the brain over the immune response through hormones can be exhibited through the blocking of their receptors on the immune cells like lymphocytes.

  1. Brain lesions

Lesions of the hypothalamus alter the course of a variety of immune processes. Lesions of hypothalamus also alters in vivo measures of immune function such as antibody production and rejection of tissue transplants and in vitro measures such as stimulated lymphocyte proliferation. Lesions in other regions of brain can also alter immune function.

  1. Brain stimulation/Destruction

Electrical stimulation of hypothalamic regions augment several immune parameters. With regard to the autonomic nervous system, chemical destruction with 6- hydroxydopamine can impair some aspects of immune function. Destruction or stimulation of neural pathways that are connected to the immune system alter the function of the immune system, and so the connection between the CNS is of real significance.

  1. Blocking the hormone receptors

The blocking of the hormone receptors on lymphocytes alters the course of immunity, proving the effect of the hormones on the immune response, which in turn are controlled by the brain (hypothalamus).


  • The Brain to Immune System Paradigm

The human brain has an ability to consciously and unconsciously control the immune system. Therefore it is concluded that thoughts effect immune response Happy, positive thoughts result in a healthier, more effective immune system. Similarly, negative, depressing thoughts result in a hobbled and less effective immune system. The high incidence of serious physical illness in patients diagnosed with depression appears to support the theory that thoughts and emotions can affect physical health. Depressed persons not only have more physical illnesses than happy people, but their illnesses are more serious, with more complications and higher death rates.

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Maier et al (1994) Psychoneuroimmunology, The Interface Between Behavior, Brain, and Immunity. American Psychologist. Vol. 49. No. 12, 1004-1017.