Psychoneuroimmunology. Josée L. Jarry, Ph.D. Health Psychology, psy333 Department of Psychology University of Toronto September 30, 2002

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1 Psychoneuroimmunology Josée L. Jarry, Ph.D. Health Psychology, psy333 Department of Psychology University of Toronto September 30, 2002

2 Psychoneuroimmunology - Definition The study of the link between psychological states and the functioning of the immune system The link between the two is provided by the Central Nervous System (CNS) Our psychology affects our nervous system which in turn affects our immunity

3 The Immune System Designed to monitor the invasion of microorganisms in the body Prevent their spread and growth by eliminating them Prevents infection: the growth of cells associated with disease Also patrols for mutant cells Made of specific and nonspecific immunity It is spread throughout the body in the form of the lymphatic system

4 The Lymphatic System Consists of lymphatic vessels and lymphatic organs Closely associated with the cardiovascular system Contributes to the body s immune response One way system that begins with with lymphatic capillaries Ends with a return of the lymph to the blood circulation

5 Lymphatic Capillaries & Vessels Take up fluid that has diffused from and has not been absorbed by the blood capillaries Once fluid has entered the lymphatic vessels, it is called lymph The lymphatic capillaries join to form the lymphatic vessels

6 The Lymphoid Organs Lymph nodes Small, ovoid or round structures Found at specific points along the lymph vessels Clean lymph Antigens leaking into the lymph nodes activate lymphocytes to mount an immune response Tonsils Located in a ring around the pharynx Functions similar to that of lymph nodes The first to encounter pathogens that enter the body by the nose or mouth

7 The Lymphoid Organs Bone marrow The site of origin of all types of blood cells Including all white blood cells Thymus Located in the upper thoracic cavity A site of lymphocyte maturation Secretes thymosin which aids the maturation of T-cells Spleen Upper left region of the abdomen Cleans blood, disposes of worn-out blood cells Removes bacteria

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9 Lymph Called lymph because it contains lymphocytes Comes from capillary diffusion & fluids secreted from the body cells Lymphocytes A type of white blood cell or leukocytes found in lymph Several types of lymphocytes: T-lymphocytes or T-cells B-lymphocytes or B-cells Natural killer cells (NK)

10 Antigens & Infection Antigens invading microbes such as bacteria, viruses, parasites, and fungi any microorganism that is foreign to our physiology Pathogens antigens that have the potential to cause disease Localized infection the infection is confined to a defined site Focal infection the infection remains localized but sends toxins to other parts of the body Systemic infection the infection spreads to a number of areas of the body at once

11 Nonspecific Immunity Barriers to entry Skin secretes oil that kills bacteria on skin Upper respiratory tract is lined with ciliated cells that sweep mucus and trapped particles up into the throat to be swallowed or expectorate Stomach has acid ph that kills bacteria Bacteria in the intestine prevent the development of pathogens

12 Non-specific Immunity Inflammatory reaction Injured tissue releases inflammatory chemicals Capillaries dilate and become more permeable Allows proteins and fluids to escape The rise in temperature increases phagocytosis by white blood cells Results in redness, heat, swelling The swelling stimulates free nerve endings, pain Blood vessel rupture results in the formation of a clot that seals the break

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15 Nonspecific Immunity Natural Killer Cells Large granular lymphocytes Kill virus infected cells and tumour cells by cell to cell contact

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17 Specific Immunity Protection against specific antigens Results from prior exposure to a specific antigen Acquired sometime after birth Results from the action of: B lymphocytes or B cells Mature in bone marrow Produce antibodies that combine with, and neutralize antigens T lymphocytes or T cells Mature in the thymus gland Directly attack antigen bearing cells Regulates the immune response

18 Memory Specific Immunity certain immune system cells adapt to an antigen also remember it when they encounter it again the immune system cells react to antigens more strongly when they encounter it again Specificity specific immune system cells respond to specific antigens only Tolerance the immune system cells do not react to the body s own cells, or self

19 Cell-mediated Immunity T-lymphocytes (T cells) Cytotoxic T cells Responsible for cell-mediated immunity Destroy specific antigen-bearing cells such as virus infected or cancer cells Contain perforin molecules Form a pore in the membrane of the infected cell Allows water and salts to enter The cell swells and bursts

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21 Cell-mediated Immunity Activation of T cells T cells have receptors macrophages present fragments of broken down pathogens to T cells through a HLA antigen this sensitizes the T-cell which acquires specific receptors on its surface that enables them to recognize the invader The T-cell undergoes clonal expansion Cytotoxic T-cells secrete chemicals that kill infected cells Helper T cells produce cytokines that stimulate B cells Some T cells become memory T cells

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23 Humoral Immunity B-lymphocytes (B-cells) Have antigen specific receptors on their surface Antigen binds with receptor This stimulates the B cell to undergo clonal expansion B cells divide into plasma cells Plasma cells mass produce antibodies Antibodies circulate, find antigens, bind to them, and mark them for latter destruction The destruction is then carried out by phagocytes Some B cells become memory cells Memory cells are responsible for long-term immunity

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25 Humoral Immunity T-lymphocytes (T-cells) Helper T-cells (CD4) produce substances called interleukins that speed the division of B-lymphocytes Suppressor T-cells (CD8) suppress the production of antibodies after the antigen has been destroyed

26 Primary & Secondary Immune Response Primary immune response occurs during the initial exposure to an invader some of the sensitized B-cells and T-cells replicate but do not go into action they become memory lymphocytes Memory B and T cells become activated only if the antigen reappears Secondary immune response occurs during subsequent exposure to antigen memory lymphocytes initiate the immune response direct and indirect attack on the antigen only much faster

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29 Immunocompetence (1) the degree to which an antigen is identified, destroyed, and disposed of by the immune system processes Measuring immunocompetence Enumerative assay consists of counting NK, T-cells, and B-cells cannot count them directly in bone marrow or the spleen therefore, count them in the bloodstream and mucous secretions (often saliva) Competence is determined by: a minimum number of cells for adequate immune function a balance between various cell types in general, the higher the count, the better the immune system functions

30 Immunocompetence (2) Functional tests of immunocompetence consists of combining blood sample with a mitogen then measure the production of lymphocytes Mitogens a mitogen stimulates immune cell activity like an antigen concanavalin (Con A) phytohemagglutinin (PHA) pokeweed mitogen (PWM) For NK cells: NK cell cytotoxic activity assay Cell count after introduction of tumour cells Measuring the destruction of the tumour cells or NK cell lysis

31 The effects of psychological factors on the immune system: Stress, Mood, Personality, and Social Support

32 Stress & Immune Functioning (1) The nervous system and the immune system interact closely the nervous system affects the endocrine system by controlling the secretion of hormones via the pituitary gland it also affects the immune system via the autonomic nervous system s action on the thymus gland, the spleen and bone marrow hormones from the pituitary and adrenal gland modulate the immune system cells immune cells secrete cytokines and antibodies that fight foreign invaders cytokines are blood born messengers that regulate the development of immune cells and also influence the central nervous system

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34 Stress & Immune Functioning (1) aversive condition in which the demands of a situation are perceived to be greater than our ability to cope with them (Lazarus & Folkman, 1984) Laboratory studies volunteers are exposed to acute, short-term stressors (e.g. making speeches) immune functioning is simultaneously measured shows that it takes as little as five minutes for a stressor to inhibit the ability of the immune system to respond effectively also exposure to antigens record illness occurrences Ex: Cohen et al. (1991)

35 Stress & Immune Functioning (2) Longitudinal studies involves following-up individuals who have suffered significant stresses at one point over long period of time after the stressful event or time period shows that strong stresses lead to significantly more illness over time this effect remains after controlling for factors that may account for increased illness such as smoking and substance abuse also shows that the immune system can remain suppressed in the long term Ex: Irwin et al (1987)

36 Stress & Immune Functioning (3) Field studies involves measuring immune functions following stress occurring in a natural setting not necessarily long term Main effect versus interaction stress is often investigated in the spirit of being a main effect in fact, it may interact with other factors to produce immunosuppression and illness studies have shown that stress combines with factors such as personality style to affect illness Ex: Tice and Baumeister (1997)

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39 Mood and Immunity stressful life events often induce significant negative emotions such sadness, grief and helplessness stress often brings on depression depression has a strong impact on illness and death sick people with depression are three times as likely to die from their illness as those who are not depressed studies also show that negative mood suppresses immune function

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41 Mood and Cancer Two ways of measuring the impact of mood on cancer Both are longitudinal Begin with cancer free people measure their mood then monitor for cancer onset Begin with people who have cancer assess their mood then monitor cancer progression Cancer mediated by suppressed immunity? depressed people have lower natural killer cell activity (NKCA) than non-depressed matched people Antidepressants increase NKCA

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43 Personality, Social Support, and Immunity Personality a person s collection of attributes and behavioural tendencies that are consistent over time and across a variety of situations Ex: Esterling et al., 1993 Social support interpersonal resources that help avoid or cope with difficult times. Can be emotional support or instrumental support (tangible) Ex: Theorell et al (1995)

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45 Conditioning and Immunity Ader & Cohen (1975) Study paradigm paring of saccharine with cyclophosphamide (CY) CY is a drug with immunosuppressive CY is the unconditioned stimulus to suppress immune functions saccharine is the conditioned stimulus exposure to antigen measurement of antibodies after exposure to saccharine alone Reduced production of antibodies after saccharine alone

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