Psychoneuroimmunology

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 T-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 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 LymphoidOrgans Lymph nodes • Small, round or ovoid structures • Found at specific points along the lymph vessels • They clean the 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 • They are the first to encounter pathogens that enter the body by the nose or mouth

7. The LymphoidOrgans 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 whichaids the maturation of T-cells Spleen • Upper left region of the abdomen • Cleans blood, disposes of worn-out blood cells • Removes bacteria

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 leukocyte, found in lymph Several types of lymphocytes: • T-lymphocytes or T-cells • B-lymphocytes or B-cells • Natural killer (NK) cells

10. Antigens & Infection Antigens • invading microbes such as bacteria, viruses, parasites, or 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 expectorated • Stomach has acid pH that kills bacteria • Bacteria in the intestine prevent the development of pathogens

12. Nonspecific Immunity (cont’d) Inflammatory reaction • Injured tissue releases inflammatory chemicals • Capillaries dilate and become more permeable • This 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

15. Nonspecific Immunity Natural Killer Cells • Large granular lymphocytes • Kill virus-infected cells and tumour cells by cell to cell contact (next slide)

17. Specific Immunity • Protection against particular antigens • Results from prior exposure to a specific antigen • Acquired sometime after birth Results from the action of: • B lymphocytes or B-cells • These 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 • Regulate the immune response

18. Specific Immunity Memory • 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 • This allows water and salts to enter • The cell swells and bursts

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

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

25. Humoral Immunity T-lymphocytes(T-cells) Helper T-cells (CD4) • produce substances called interleukins that speed the division of B-cells and T-cells 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 • Occurs much faster

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

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 (e.g., Cohen et al. 1991) • 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

35. Stress & Immune Functioning (2) Longitudinal studies (e.g., Irwin et al 1987) • 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

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)

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

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

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)

45. Conditioning and Immunity Ader & Cohen (1975) • Study paradigm • Pairing of saccharine with cyclophosphamide (CY) • CY is a drug with immunosuppressive properties • 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