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Psychoneuroimmunology (PNI) investigates the relations between the psychophysiological and immunophysiological dimensions of living beings. PNI brings together researchers in a number of scientific and medical disciplines, including psychology, the neuroscience, immunology, physiology, pharmacology, psychiatry, behavioral medicine, infectious diseases, and rheumatology. Image File history File links Information_icon. ... Psychophysiology is the science of understanding the link between psychology and physiology. ... For the scientific journal named Science, see Science (journal). ... See drugs, medication, and pharmacology for substances that are used to treat patients. ... Psychology (from Greek: ψυχή, psukhē, spirit, soul; and λόγος, logos, knowledge) is an academic/ applied discipline involving the scientific study of mental processes and behavior. ... Drawing of the cells in the chicken cerebellum by S. Ramón y Cajal Neuroscience is a field that is devoted to the scientific study of the nervous system. ... Immunology is a broad branch of biomedical science that covers the study of all aspects of the immune system in all organisms. ... Leonardo da Vincis Vitruvian Man, an important early achievement in the study of physiology. ... Pharmacology (in Greek: pharmacon (φάρμακον) meaning drug, and logos (λόγος) meaning science) is the study of how substances interact with living organisms to produce a change in function. ... Psychiatrist redirects here. ... Behavioral medicine is an interdisciplinary field of medicine concerned with the development and integration of psychosocial, behavioral and biomedical knowledge relevant to health and illness. ... In medicine, infectious disease or communicable disease is disease caused by a biological agent (e. ... Rheumatology, a subspecialty of internal medicine, is devoted to the diagnosis and therapy of rheumatic diseases. ...

The profound interest of PNI is in interactions between the nervous and immune systems, and the relation between behavior and health. Despite the protean approach to research, the outcome common to all research endeavors is the discovery of new information, or novel evidence, which contributes to the continuing and cumulative generation of knowledge. A diagram showing the CNS: 1. ... A request has been made on Wikipedia for this article to be deleted in accordance with the deletion policy. ...

It deals with, among other things, the physiological functioning of the neuroimmune system in states of both health and disease; malfunctions of the neuroimmune system in disorders (autoimmune diseases, hypersensitivities, immune deficiency), the physical, chemical and physiological characteristics of the components of the neuroimmune system in vitro, in situ, and in vivo. Leonardo da Vincis Vitruvian Man, an important early achievement in the study of physiology. ... Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. ... Hypersensitivity refers to undesirable (damaging, discomfort-producing and sometimes fatal) reactions produced by the normal immune system. ... In medicine, immune deficiency (or immunodeficiency) is a state where the immune system is incapable of defending the organism from infectious disease. ... Wiktionary has a definition of: In vitro In vitro (Latin: within glass) means within a test tube, or, more generally, outside a living organism or cell. ... In situ is a Latin phrase meaning in the place. ... In vivo (Latin for (with)in the living). ...

PNI also involves endocrinology and is sometimes referred as psychoendoneuroimmunology (PENI). Endocrinology is a branch of medicine dealing with disorders of the endocrine system and its specific secretions called hormones. ...

History

Interest in the relationship between psychiatric syndromes or symptoms and immune function has been a consistent theme since the beginning of modern medicine.

Walter Cannon, a professor of physiology at Harvard University, looked at the need for mental and physical balance throughout the organism and coined the term, Homeostasis, from the Greek word homoios, meaning similar, and stasis, meaning position. To meet Wikipedias quality standards, this article or section may require cleanup. ... Harvard University (incorporated as The President and Fellows of Harvard College) is a private university in Cambridge, Massachusetts, USA. Founded in 1636,[2] Harvard is the oldest institution of higher learning in the United States. ... Homeostasis is the property of an open system, especially living organisms, to regulate its internal environment to maintain a stable, constant condition, by means of multiple dynamic equilibrium adjustments, controlled by interrelated regulation mechanisms. ...

In his work with animals Cannon observed that any change of emotional state in the animal, such as anxiety, distress, or rage, was accompanied by total cessation of movements of the stomach. These studies into the relationship between the effects of emotions and perceptions on the autonomic nervous system, namely the sympathetic and parasympathetic responses that initiated the recognition of the fight or flight response. His findings were published from time to time in professional journals, then summed up in book form in The Mechanical Factors of Digestion, published in 1911. Dr. Cannon’s seminal work, Bodily Changes in Pain, Hunger, Fear and Rage was published in 1915. This article includes a list of works cited or a list of external links, but its sources remain unclear because it lacks in-text citations. ... This is a disambiguation page — a navigational aid which lists other pages that might otherwise share the same title. ... This article or section is in need of attention from an expert on the subject. ... This article or section should include material from Fight-or-flight The flight or fight response, also called the acute stress response, was first described by Walter Cannon in the 1920s as a theory that animals react to threats with a general discharge of the sympathetic nervous system. ... 1911 (MCMXI) was a common year starting on Sunday (link will display the full calendar). ... 1915 (MCMXV) was a common year starting on Friday (link will display the full calendar). ...

Picking up on Cannon's work was Hans Selye. Selye experimented with animals putting them under different physical and mental adverse conditions and noted that under these conditions the body consistently adapted to heal and recover. Several years of experimentation that formed the empiric foundation of Dr. Selye's concept of the General Adaptation Syndrome. This syndrome consists of an enlargement of the adrenal gland, atrophy of the thymus, spleen and other lymphoid tissue, and gastric ulcerations. Hans Hugo Bruno Selye, CC (Selye János, 1907 - 1982), was a Canadian endocrinologist of Austrian-Hungarian origin. ... Stress (roughly the opposite of relaxation) is a medical term for a wide range of strong external stimuli, both physiological and psychological, which can cause a physiological response called the general adaptation syndrome, first described in 1936 by Hans Selye in the journal Nature. ... In mammals, the adrenal glands are the triangle-shaped endocrine glands that sit atop the kidneys. ... Thymus, see Thyme. ... The spleen is an organ of the lower abdomen, where it functions in the destruction of old red blood cells and holding a reservoir of blood. ... Wikipedia does not have an article with this exact name. ... Endoscopic images of a duodenal ulcer. ...

Selye describes three stages of adaptation, including an initial brief alarm reaction, followed by a prolonged period of resistance and a terminal stage of exhaustion and death. This foundational work led to a rich line of research on the biological functioning of glucocorticoids.^[1] The name glucocorticoid derives from early observations that these hormones were involved in glucose metabolism. ...

Mid 20th century studies of psychiatric patients reported immune alterations in psychotic patients, including numbers of lymphocytes ^{[2] [3]} and poorer antibody response to pertussis vaccination, compared with nonpsychiatric control subjects.^[4] In 1964 George F. Solomon et all. coined the term "psychoimmunology" and published a landmark paper: "Emotions, immunity, and disease: a speculative theoretical integration."^[5] A lymphocyte is a type of white blood cell involved in the human bodys immune system. ... Each antibody binds to a specific antigen; an interaction similar to a lock and key. ... 1964 (MCMLXIV) was a leap year starting on Wednesday (the link is to a full 1964 calendar). ...

Birth of Psychoneuroimmunology

In 1975 Robert Ader and Nicholas Cohen at the University of Rochester advanced PNI with their demonstration of classic conditioning of immune function, and coined the term "psychoneuroimmunology".^[6][7] Ader had discovered that the immune system of rats can be conditioned to respond to external stimuli unrelated to immune function. Ader was investigating how long conditioned responses (in the sense of Pavlov's conditioning of dogs to drool when they heard a bell ring) might last in laboratory rats. To condition the rats, he used a combination of saccharine-laced water and the drug Cytoxan which induces nausea and suppresses the immune system. Ader was surprised to discover that after conditioning, just feeding the rats saccharine-laced water was sufficient to suppress the immune system of the rats. In other words, a signal via the nervous system (taste) was affecting immune function. This was one of the first scientific experiments that demonstrated that the nervous system can affect the immune system. 1975 (MCMLXXV) was a common year starting on Wednesday. ... The University of Rochester is a private, coeducational and nonsectarian research institution located in Rochester, New York. ... Ivan Petrovich Pavlov (Russian: ) (September 14, 1849 – February 27, 1936) was a Russian physiologist, psychologist, and physician. ... Saccharin is the oldest artificial sweetener; it was discovered in 1879 by Ira Remsen and Constantine Fahlberg of Johns Hopkins University. ... Cyclophosphamide (the generic name for Cytoxan, Neosar) is a nitrogen mustard alkylating agent, used to treat various types of cancer and some autoimmune disorders. ... For the Beck song, see Nausea (song). ...

In 1981 David Felten, then working at the Indiana University of Medicine, discovered a network of nerves leading to blood vessels as well as cells of the immune system. The researchers also found nerves in the thymus and spleen terminating near clusters of lymphocytes, macrophages and mast cells, all of which help control immune function. This discovery provided one of the first indications of how neuro-immune interaction occurs. 1981 (MCMLXXXI) was a common year starting on Thursday of the Gregorian calendar. ... Indiana University, founded in 1820, is a nine-campus university system in the state of Indiana. ... Thymus, see Thyme. ... The spleen is an organ of the lower abdomen, where it functions in the destruction of old red blood cells and holding a reservoir of blood. ... A scanning electron microscope (SEM) image of a single human lymphocyte. ... A macrophage of a mouse stretching its arms to engulf two particles, possibly pathogens Macrophages (Greek: big eaters, makros = long, phagein = eat) are white blood cells, more specifically phagocytes, acting in the nonspecific defense as well as the specific defense system of vertebrate animals. ... Mast cells A mast cell (or mastocyte) is a resident cell of areolar connective tissue (loose connective tissue) that contains many granules rich in histamine and heparin. ...

Ader, Cohen and Felton went on to write the groundbreaking two-volume book Psychoneuroimmunology in 1981, which laid out the underlying premise that the brain and immune system represent a single, integrated system of defense. An updated fourth edition was released in 2006.

In 1985 Research by neuropharmacologist, Candace Pert, revealed that neuropeptides are present on both the cell walls of the brain and in the immune system.^[8][9] The discovery by Pert, et all. that neuropeptides and neurotransmitters are also on cell walls of the immune system shows a close association with emotions and suggests that emotions and health are deeply interdependent. Showing that the immune and endocrine systems are modulated not only by the brain but by the central nervous system itself has had an enormous impact on how we understand disease. 1985 (MCMLXXXV) was a common year starting on Tuesday of the Gregorian calendar. ... Candace Beebe Pert (born 26th July 1946) is a neuroscientist who discovered the opiate receptor, the cellular bonding site for endorphins in the brain. ... A Neuropeptide is any of the variety of peptides found in neural tissue; e. ... In psychology and common terminology, emotion is the language of a persons internal state of being, normally based in or tied to their internal (physical) and external (social) sensory feeling. ... The endocrine system is a control system of ductless endocrine glands that secrete chemical messengers called hormones that circulate within the body via the bloodstream to affect distant organs. ...

Contemporary advances in psychiatry, immunology, neurology and other integrated disciplines of medicine has fostered enormous growth for PNI. The mechanisms underlying behaviorally induced alterations of immune function, and immune alterations inducing behavioral changes, is likely to have clinical and therapeutic implications that will not be fully appreciated until more is known about the extent of these interrelationships in normal and pathophysiological states.

The Immune-Brain Loop

Further information: Cell signaling networks and Signal transduction

While the lay person can believe in a mind-body connection, the PNI researcher is looking for the exact mechanisms by which specific brainimmunity effects are achieved. Evidence for nervous system–immune system interactions exists at several biological levels. Cell signaling pathways interact with one another to form networks in natural systems. ... This article or section does not cite its references or sources. ... The seperation of the mind from the body is of relatively recent origin. ...

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. During an immune response the brain and the immune system "talk to each other" and this process is essential for maintaining homeostasis. Two major pathway systems are involved in this cross-talk: the Hypothalamic-pituitary-adrenal axis (HPA axis) and the sympathetic nervous system (SNS). The activation of SNS during an immune response might be aimed to localize the inflammatory response. The hypothalamic-pituitary-adrenal axis (HPA axis) is a major part of the neuroendocrine system that controls reactions to stress and has important functions in regulating various body processes such as digestion, the immune system and energy usage. ... Grays FIG. 838– The right sympathetic chain and its connections with the thoracic, abdominal, and pelvic plexuses. ...

The body's primary stress management system is the HPA axis. The HPA axis responds to physical and mental challenge to maintain homeostasis in part by controlling the body's cortisol level. Dysregulation of the HPA axis is implicated in numerous stress-related diseases. HPA axis activity and cytokines are intrinsically intertwined: inflammatory cytokines stimulate adrenocorticotropic hormone (ACTH) and cortisol secretion, while, in turn, glucocorticoids suppress the synthesis of proinflammatory cytokines. Cortisol is a corticosteroid hormone produced by the adrenal cortex that is involved in the response to stress; it increases blood pressure, blood sugar levels, may cause infertility in women, and suppresses the immune system. ... Adrenocorticotropic hormone (ACTH or corticotropin) is a polypeptide hormone produced and secreted by the pituitary gland. ... The name glucocorticoid derives from early observations that these hormones were involved in glucose metabolism. ...

Molecules called pro-inflammatory cytokines, which include interleukin-1 (IL-1), Interleukin-2 (IL-2), interleukin-6 (IL-6), Interleukin-10 (IL-10), Interleukin-12 (IL-12), Interferon-gamma (IFN-Gamma) and tumor necrosis factor alpha (TNF-alpha) can affect the brain. Immune cells called macrophages, which are the first on the scene of any infection, create these molecules and experiments showed that they can act directly inside the brain by creation of microglia and astrocytes (both types of glial cells) to trigger a sickness response. Cytokines are also locally produced in the brain, especially in the hypothalamus, thus contributing to the development of behavioural effects.^[10] Interleukin-1 (IL-1) is a cytokine that is secreted by macrophages, monocytes and dendritic cells. ... Interleukin-2 (IL2) is an interleukin, a type of biological response modifier that can improve the bodys natural response to disease. ... Interleukin-6 (IL-6) is a pro-inflammatory cytokine secreted by T cells and macrophages to stimulate immune response to trauma, especially burns or other tissue damage leading to inflammation. ... Interleukin-10 (IL-10 or IL10), also known as human cytokine synthesis inhibitory factor (CSIF), is an anti-inflammatory cytokine, capable of inhibiting synthesis of pro-inflammatory cytokines like IFN-gamma, IL-2, IL-3, TNFα and GM-CSF by cells such as macrophages and Th1 cells. ... Interleukin 12 (IL-12) is an interleukin that are naturally produced by macrophages and human B-lymphoblastoid cells (NC-37)in response to antigenic stimulation. ... Interferon-gamma or IFN-g is a dimerized soluble cytokine which is a Type II Interferon. ... Tumor necrosis factors (or the TNF-family) refers to a group of cytokines family which can cause apoptosis. ... Macrophages (Greek: big eaters) are cells found in tissues that are responsible for phagocytosis of pathogens, dead cells and cellular debris. ... Microglia are a type of glial cell that act as the immune cells of the Central nervous system (CNS). ... Astrocytes, also known as astroglia, are characteristic star-shaped cells in the brain. ... Neuroglia cells of the brain shown by Golgis method. ...

Cytokines mediate and control immune and inflammatory responses. Complex interactions exist between cytokines, inflammation and the adaptive responses in maintaining homeostasis. Like the stress response, the inflammatory reaction is crucial for survival. Systemic inflammatory reaction results in stimulation of four major programs^[11]: A request has been made on Wikipedia for this article to be deleted in accordance with the deletion policy. ... Inflammation is the first response of the immune system to infection or irritation and may be referred to as the innate cascade. ... Homeostasis is the property of an open system, especially living organisms, to regulate its internal environment to maintain a stable, constant condition, by means of multiple dynamic equilibrium adjustments, controlled by interrelated regulation mechanisms. ...

• the acute-phase reaction
• the sickness syndrome
• the pain program
• the stress response

These are mediated by the HPA axis and the SNS. Common human diseases such as allergy, autoimmunity, chronic infections and sepsis are characterized by a dysregulation of the pro-inflammatory versus anti-inflammatory and T helper (Th1) versus (Th2) cytokine balance. This article deals specifically with IgE-mediated hypersensitivity. ... Sepsis (in Greek Σήψις, putrefaction) is a serious medical condition, resulting from the immune response to a severe infection. ... This article or section does not adequately cite its references or sources. ...

Recent studies show pro-inflammatory cytokine processes take place during depression, mania and bipolar disease, in addition to autoimmune hypersensativity and chronic infections. Cytokines are a group of proteins and peptides that are used in organisms as signaling compounds. ... Clinical depression (also called major depressive disorder, or sometimes unipolar when compared with bipolar disorder, which is sometimes called manic depression) is a state of intense sadness, melancholia or despair that has advanced to the point of being disruptive to an individuals social functioning and/or activities of daily... Mania is a severe medical condition characterized by extremely elevated mood, energy, and thought patterns. ... For other uses, see Bipolar. ...

Chronic secretion of stress hormones, glucocorticoids (GCs) and catecholamines (CAs), as a result of disease, may reduce the affect of neurotransmitters, including serotonin, norepinephrine and dopamine, or other receptors in the brain, thereby leading to the dysregulation of neurohormones. Under stimulation, norepinephrine is released from the sympathetic nerve terminals in organs, and the target immune cells express adrenoreceptors. Through stimulation of these receptors, locally released norepinephrine, or circulating catecholamines such as epinephrine, affect lymphocyte traffic, circulation, and proliferation, and modulate cytokine production and the functional activity of different lymphoid cells. In medical terms, stress is a physical or psychological stimulus that can produce mental or physiological reactions that may lead to illness. ... Hormone is also the NATO reporting name for the Soviet/Russian Kamov Ka-25 military helicopter. ... The name glucocorticoid derives from early observations that these hormones were involved in glucose metabolism. ... Catecholamines are chemical compounds derived from the amino acid tyrosine that act as hormones or neurotransmitters. ... Neurotransmitters are chemicals that are used to relay, amplify and modulate electrical signals between a presynaptic and a postsynaptic neuron. ... Serotonin (5-hydroxytryptamine, or 5-HT) is a monoamine neurotransmitter synthesized in serotonergic neurons in the central nervous system (CNS) and enterochromaffin cells in the gastrointestinal tract of animals including humans. ... Norepinephrine (INN) or noradrenaline (BAN) is a catecholamine and a phenethylamine with chemical formula C8H11NO3. ... Dopamine is a phenethylamine naturally produced by the human body. ... The adrenergic receptors (or adrenoceptors) are a class of G_protein coupled receptors that is the target of catecholamines. ... Adrenaline redirects here. ... A scanning electron microscope (SEM) image of a single human lymphocyte. ... Wikipedia does not have an article with this exact name. ...

Glucocorticoids also inhibit the further secretion of corticotropin-releasing hormone from the hypothalamus and ACTH from the pituitary (negative feedback). Under certain conditions stress hormones may facilitate inflammation through induction of signaling pathways and through activation of the Corticotropin-releasing hormone. The hypothalamus (from Greek ὑποθαλαμος = under the thalamus) is a region of the mammalian brain located below the thalamus, forming the major portion of the ventral region of the diencephalon and functioning to regulate certain metabolic processes and other autonomic activities. ... Located at the base of the skull, the pituitary gland is protected by a bony structure called the sella turcica. ... Negative feedback is a type of feedback in which the system responds in an opposite direction to the perturbation. ... Corticotropin-releasing hormone (CRH), also called corticotropin-releasing factor (CRF) or corticoliberin, is a polypeptide hormone involved in the stress response. ...

These abnormalities and the failure of the adaptive systems to resolve inflammation affect the well-being of the individual, including behavioral parameters, quality of life and sleep, as well as indices of metabolic and cardiovascular health, developing into a "systemic anti-inflammatory feedback" and/or "hyperactivity" of the local pro-inflammatory factors which may contribute to the pathogenesis of disease. Santorio Santorio (1561-1636) in his steelyard balance, from Ars de statica medecina, first published 1614 Metabolism (from μεταβολισμος(metavallo), the Greek word for change), in the most general sense, is the ingestion and breakdown of complex compounds, coupled...

This systemic or neuro-inflammation and neuroimmune activation have been shown to play a role in the etiology of a variety of neurodegenerative disorders such as Parkinson's and Alzheimer's disease, multiple sclerosis, pain, and AIDS-associated dementia. However, cytokines and chemokines also modulate central nervous system (CNS) function in the absence of overt immunological, physiological, or psychological challenges.^[12] Etiology (alternately aetiology, aitiology) is the study of causation. ... Parkinsons disease (PD; paralysis agitans) is a neurodegenerative disease of the substantia nigra (an area in the basal ganglia of the brain). ... Acquired Immune Deficiency Syndrome or acquired immunodeficiency syndrome (AIDS or Aids) is a collection of symptoms and infections resulting from the specific damage to the immune system caused by the human immunodeficiency virus (HIV). ... Cytokines are a group of proteins and peptides that are used in organisms as signaling compounds. ... Chemokines are a family of pro-inflammatory activation-inducible cytokines, or small protein signals secreted by cells. ...

Psychoneuroimmunological effects

There is now sufficient data to conclude that immune modulation by psychosocial stressors and/or interventions can lead to actual health changes. Although changes related to infectious disease and wound healing have provided the strongest evidence to date, the clinical importance of immunological disregulation is highlighted by increased risks across diverse conditions and diseases. This false-colored electron micrograph shows a malaria sporozoite migrating through the midgut epithelia. ... Superficial bullet wounds In medicine, a wound is a type of physical trauma wherein the skin is torn, cut or punctured (an open wound), or where blunt force trauma causes a contusion (a closed wound). ...

Link between stress and disease

Stressors can produce profound health consequences. In one epidemiological study, for example, all-cause mortality increased in the month following a severe stressor – the death of a spouse.^[13] Theorists propose that stressful events trigger cognitive and affective responses which, in turn, induce sympathetic nervous system and endocrine changes, and these ultimately impair immune function ^{[14] [15]}. Potential health consequences are broad, but include rates of infection ^{[16] [17]} HIV progression ^{[18] [19]} and cancer incidence and progression ^{[20] [21] [22]}

Stress is thought to affect immune function through emotional and/or behavioral manifestations such as anxiety, fear, tension, anger and sadness and physiological changes heart rate, blood pressure. sweating. Researchers have suggested that these changes are beneficial if they are of limited duration^[23], but when stress is chronic, the system is unable to maintain equilibrium or homeostasis. In medical terms, stress is a physical or psychological stimulus that can produce mental or physiological reactions that may lead to illness. ... This article includes a list of works cited or a list of external links, but its sources remain unclear because it lacks in-text citations. ... Fear is a powerful, unpleasant feeling of risk or danger, either real or imagined. ... Tension may mean: In physics, tension is a force related to the stretching of a string or a similar object. ... This article is about the emotion. ... In everyday language depression refers to any downturn in mood, which may be relatively transitory and perhaps due to something trivial. ... Heart Rate is a term used to describe the frequency of the cardiac cycle. ... A sphygmomanometer, a device used for measuring blood pressure. ... Sweating (also called perspiration or sometimes transpiration) is the production and evaporation of a fluid, consisting primarily of water as well as a smaller amount of sodium chloride (the main constituent of table salt), that is excreted by the sweat glands in the skin of mammals. ... Homeostasis is the property of an open system, especially living organisms, to regulate its internal environment to maintain a stable, constant condition, by means of multiple dynamic equilibrium adjustments, controlled by interrelated regulation mechanisms. ...

Immune changes in response to very brief stressors have been a central theme in the last decade of PNI research, but older literature also provides early illustrations. In a study published in 1960, subjects were led to believe that they had accidentally caused serious injury to a companion through misuse of explosives.^[24]

Two meta-analyses of the literature show a consistent reduction of immune function in healthy people who are experiencing stress.

In the first meta-analysis by Herbert and Cohen in 1993,^[25] they examined 38 studies of stressful events and immune function in healthy adults. They included studies of acute laboratory stressors (e.g. a speech task), short-term naturalistic stressors (e.g. medical examinations), and long-term naturalistic stressors (e.g. divorce, bereavement, caregiving, unemployment). They found consistent stress-related increases in numbers of total white blood cells, as well as decreases in the numbers of helper T cells, suppressor T cells, and cytotoxic T cells, B cells, and Natural killer cells (NK). They also reported stress-related decreases in NK and T cell function, and T cell proliferative responses to phytohemaglutinin [PHA] and concanavalin A [Con A]. These effects were consistent for short-term and long-term naturalistic stressors, but not laboratory stressors. White Blood Cells is also the name of a White Stripes album. ... A T helpered cell (or TH) cell, is a T cell (a type of white blood cell or leukocyte) which has on its surface antigen receptors that can bind to fragments of antigens displayed by the Class II MHC molecules found on professional antigen-presenting cells (APCs). ... Regulatory T cells (also known as suppressor T cells) are a specialized subpopulation of T cells that act to suppress activation of the immune system and thereby maintain immune system homeostasis and tolerance to self. ... A cytotoxic (or TC) T cell is a T cell (a type of white blood cell) which has on its surface antigen receptors that can bind to fragments of antigens displayed by the Class I MHC molecules of virus (or other intracellular pathogen) infected somatic cells and tumor cells. ... B cells are lymphocytes that play a large role in the humoral immune response (as opposed to the cell-mediated immune response). ... Natural killer (NK) cells are a form of cytotoxic lymphocyte which constitute a major component of the innate immune system. ...

In the second meta-analysis by Zorrilla et al in 2001,^[26] they replicated Herbert and Cohen’s meta-analysis. Using the same study selection procedures, they analyzed 75 studies of stressors and human immunity. Naturalistic stressors were associated with increases in number of circulating neutrophils, decreases in number and percentages of total T cells and helper T cells, and decreases in percentages of Natural killer cell (NK) cells and cytotoxic T cell lymphocytes. They also replicated Herbert and Cohen’s finding of stress-related decreases in NKCC and T cell mitogen proliferation to Phytohaemagglutinin (PHA) and Concanavalin A (Con A). Neutrophil granulocytes (commonly referred to as neutrophils) are a class of white blood cells and are part of the immune system. ... T cells are a subset of lymphocytes that play a large role in the immune response. ... A T helpered cell (or TH) cell, is a T cell (a type of white blood cell or leukocyte) which has on its surface antigen receptors that can bind to fragments of antigens displayed by the Class II MHC molecules found on professional antigen-presenting cells (APCs). ... Natural NK cells are cytotoxic; small granules in their cytoplasm contain special proteins such as perforin and proteases known as granzymes. ... A cytotoxic T cell (also known as TC, CTL or killer T cell) belongs to a sub-group of T lymphocytes (a type of white blood cell) which are capable of inducing the death of infected somatic or tumor cells; they kill cells that are infected with viruses (or other... A mitogen is a substance that causes a cell to begin dividing. ... Phytohaemagglutinin (PHA, or phytohemagglutinin) is a lectin found in plants, especially beans, in the highest concentrations in the red kidney bean (Phaseolus vulgaris). ... Concanavalin A is a lectin protein from Jackbean (Canavalia ensiformis). ...

Communication between the brain and immune system

• Stimulation of brain sites alters immunity (stressed animals have altered immune systems).
• Immune cells produce cytokines that act on the CNS.
• Immune cells respond to signals from the CNS.

Communication between neuroendocrine and immune system

• Glucocorticoids and catecholamines influence immune cells.^[27]
• Endorphins from pituitary & adrenal medulla act on immune system.
• Activity of the immune system is correlated with neurochemical/neuroendocrine activity of brain cells.

Located at the base of the skull, the pituitary gland is protected by a bony structure called the sella turcica. ... Medulla in general means the inner part, and derives from the Latin word for marrow. In medicine it is contrasted to the cortex. ...

Connections between glucocorticoids and immune system

• Anti-inflammatory hormones that enhance the organisms response to a stressor.
• Prevent the overreaction of the body own defense system.
• Regulators of the immune system.
• Affect cell growth, proliferation & differentiation.
• Cause immunosuppression.
• Suppress cell adhesion, antigen presentation, chemotaxis & cytotoxicity.
• Increase apoptosis.

Schematic of cell adhesion The study of cell adhesion is part of cell biology. ... An antigen is a substance that stimulates an immune response, especially the production of antibodies. ... A cell undergoing apoptosis. ...

Corticotropin-releasing hormone (CRH)

Release of corticotropin-releasing hormone (CRH) from the hypothalamus is influenced by stress. Corticotropin-releasing hormone (CRH), also called corticotropin-releasing factor (CRF) or corticoliberin, is a polypeptide hormone involved in the stress response. ... The hypothalamus (from Greek ὑποθαλαμος = under the thalamus) is a region of the mammalian brain located below the thalamus, forming the major portion of the ventral region of the diencephalon and functioning to regulate certain metabolic processes and other autonomic activities. ...

• CRH is a major regulator of the HPA axis/stress axis.
• CRH Regulates secretion of Adrenocorticotropic hormone (ACTH).
• CRH is widely distributed in the brain and periphery
• CRH also regulates the actions of the Autonomic nervous system ANS and immune system.

Furthermore, stressors that enhance the release of CRH suppress the function of the immune system; conversely, stressors that depress CRH release potentiate immunity. Adrenocorticotropic hormone (ACTH or corticotropin) is a polypeptide hormone produced and secreted by the pituitary gland. ... This article or section is in need of attention from an expert on the subject. ...

• Central mediated since peripheral administration of CRH antagonist does not affect immunosuppression.

Pharmaceutical Advances

Further information: Neuropsychopharmacology

Glutamate agonists, cytokine inhibitors, vanilloid-receptor agonists, catecholamine modulators, ion-channel blockers, anticonvulsants, GABA agonists (including opioids and cannabinoids), COX inhibitors, acetylcholine modulators, melatonin analogs (such as Ramelton), adenosine receptor antagonists and several miscellaneous drugs (including biologics like Passiflora edulis) are being studied for their psychoneuroimmunological effects. Technical advancements in recent years have allowed progress toward the understanding of the brain and how drugs can be made to affect it. ... Glutamate is the anion of glutamic acid. ... The vanilloid receptor subtype 1 (TRPV1) is a nonselective ligand-gated cation channel that may be activated by a wide variety of exogenous and endogenous stimuli, including heat greater than 43°C, low pH, anandamide, and capsaicin. ... Ion channels are pore-forming proteins that help to establish and control the small voltage gradient that exists across the plasma membrane of all living cells (see cell potential) by allowing the flow of ions down their electrochemical gradient. ... The anticonvulsants, sometimes also called antiepileptics, belong to a diverse group of pharmaceuticals used in prevention of the occurrence of epileptic seizures. ... Gaba may refer to: Gabâ or gabaa (Philippines), the concept of negative karma of the Cebuano people GABA, the gamma-amino-butyric acid neurotransmitter GABA receptor, in biology, receptors with GABA as their endogenous ligand Gaba 1 to 1, an English conversational school in Japan Marianne Gaba, a US model... An opioid is any agent that binds to opioid receptors found principally in the central nervous system and gastrointestinal tract. ... Cannabinoids are a group of chemicals which activate the bodys cannabinoid receptors. ... Cyclooxygenase (COX) is an enzyme (EC 1. ... The chemical compound acetylcholine, often abbreviated as ACh, was the first neurotransmitter to be identified. ... Melatonin, 5-methoxy-N-acetyltryptamine, is a hormone found in all living creatures from algae[1] to humans, at levels that vary in a diurnal cycle. ... Ramelteon, marketed as Rozerem by Takeda Pharmaceuticals North America, is the first in a new class of sleep agents that selectively binds to the MT1 and MT2 receptors in the suprachiasmatic nucleus (SCN), versus binding to GABA-A receptors, such as with drugs like Ambien CR, Lunesta, and Sonata. ... To meet Wikipedias quality standards, this article or section may require cleanup. ... Passion fruit (Portuguese: Maracujá) comes from passion flower vines, plants of the genus Passiflora, native to tropical and sub-tropical America. ...

For example, SSRI's, SNRI's and tricyclic antidepressants acting on serotonin, norepinephrine and dopamine receptors have been shown to be immunomodulatory and anti-inflammatory against pro-inflammatory cytokine processes, specifically on the regulation of IFN-gamma and IL-10, as well as TNF-alpha and IL-6 through a pyschoneuroimmunological process.^[28][29][30] Antidepressants have also been shown to suppress TH1 upregulation.^{[31][32][33][34][35]} SSRI is an acronym that stands for several things: It is a class of antidepressants called selective serotonin reuptake inhibitor SSRI also is used as the stock symbol for Silver Standard Resources Inc. ... Serotonin norepinephrine reuptake inhibitors (SNRIs) are a class of antidepressant used in the treatment of clinical depression and other affective disorders. ... Chemical structure of the tricyclic antidepressant amitriptyline. ... An antidepressant is a medication used primarily in the treatment of clinical depression. ... Serotonin (5-hydroxytryptamine, or 5-HT) is a monoamine neurotransmitter synthesized in serotonergic neurons in the central nervous system (CNS) and enterochromaffin cells in the gastrointestinal tract of animals including humans. ... Norepinephrine (INN) or noradrenaline (BAN) is a catecholamine and a phenethylamine with chemical formula C8H11NO3. ... Dopamine is a phenethylamine naturally produced by the human body. ...

Tricyclic and dual serotonergic-noradrenergic reuptake inhibition by SNRIs (or SSRI-NRI combinations), have also shown analgesic properties additionally.^[36][37] According to recent evidences antidepressants also seem to exert beneficial effects in experimental autoimmune neuritis in rats by decreasing Interferon-beta (IFN-beta) release or augmenting NK activity in depressed patients.^[38] This article or section does not adequately cite its references or sources. ... Inflammation is the first response of the immune system to infection or irritation and may be referred to as the innate cascade. ... Interferons (IFNs) are natural proteins produced by the cells of the immune systems of most animals in response to a challenge by a foreign agents such as viruses, bacteria, parasites and tumour cells. ...

These studies warrant investigation for antidepressants for use in both psychiatric and non-psychiatric illness and that a psychoneuroimmunological approach may be required for optimal pharmacotherapy in many diseases.^[39] Future antidepressants may be made to specifically target the immune system by either blocking the actions of pro-inflammatory cytokines or increasing the production of anti-inflammatory cytokines.^[40] Pharmacotherapy is the practice of treating diseases with medication. ...

References

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Recommended Reading

• Berczi and Szentivanyi (2003) NeuroImmune Biology, Elsevier, ISBN 0-444-50851-1 (Written for the highly technical reader)
• Goodkin, Karl, and Adriaan P. Visser, (eds), Psychoneuroimmunology: Stress, Mental Disorders , and Health, American Psychiatric Press, 2000, ISBN 0-88048-171-4, technical.
• Ransohoff, Richard, et al (eds), Universes in Delicate Balance: Chemokines and the Nervous System, Elsevier, 2002, ISBN 0-444-51002-8
• Robert Ader, David L. Felten, Nicholas Cohen , Psychoneuroimmunology, 4th edition, 2 volumes, Academic Press, (2006), ISBN 0-12-088576-X

See also

This article or section is in need of attention from an expert on the subject. ... The fight-or-flight response, also called the acute stress response, was first described by Walter Cannon in 1929. ... Post-traumatic stress disorder (PTSD) is a term for certain severe psychological consequences of exposure to, or confrontation with, stressful events that the person experiences as highly traumatic. ... A cluttered environment with too many tasks can lead to stress. ...

External Links

• Psychoneuroimmunology Research Society
• Home page of Robert Ader - University of Rochester
• UCLA-NPI Cousins Center for Psychoneuroimmunology
• Biochemical Aspects of Anxiety