Psychoneuroimmunology

1. Psychoneuroimmunology Margot Shields December 2006 Core References: Cohen S, Herbert TB. Health psychology: Psychological factors and physical disease from the perspective of human psychoneuroimmunology. Annual Review of Psychology 1996; 47: 113-42. Kiecolt-Glaser J, McGuire L, Robles TF, Glaser R. Psychoneuroimmunology: Psychological influences on the immune function and health. Journal of Consulting and Clinical Psychology 2002; 70: 537-47

2. Psychoneuroimmunology • Definition - the study of interrelations between the central nervous system and the immune system. • Interrelations→ association is bidirectional. • Animal studies advanced the understanding of PNI • showed evidence for nerves connecting the CNS and the immune system • existence if chemicals called cytokines that are produced by the immune system, cross the blood-brain barrier and alter how the CNS functions.

3. Psychoneuroimmunology • Term first coined in 1964 by George F. Solomon (suggested that personality factors and emotions played a role in autoimmune disease). • There were only a handful of human studies prior to the 80’s. • The main focus of PNI human studies is to see if psychological factors affect states of immunity, and whether or not psychologically induced changes in immunity alter susceptibility to immune system-mediated disease. • 1981 book by Ader, Felten and Cohen called Psychoneuroimmunology reviewed the role of the CNS in the relationship between behaviour and the immune system. • In 2001 the third edition of the book used two volumes to cover the growing number of research contributions.

4. Tests of Immune Function • Most immune system cells are located in bone marrow, thymus, lymph node, spleen, tonsils and appendix. • Because there is no easy way to access the cells of these organs, PNI work with humans is primarily limited to the study of immune components in circulating peripheral blood. • Circulating blood transports immune components between the organs of the immune system and sites of inflammation. • Components of the immune system that circulate in the blood (e.g., some types of white blood cells and antibodies) work to combat against invading antigens.

5. Tests of Immune Function (1) Enumerative tests • Enumerative tests count the number or percentages of different kinds of white blood cells in the peripheral blood (neutrophils, monocytes and lymphocytes). • The body cannot respond adequately to invading antigens without a minimum number of each type of immune cell. An optimum response requires a proper balance of the various types of cells. • However, changes found in the PNI literature are usually quite small and whether these changes indicate compromised immune function is theoretically unclear.

6. Tests of Immune Function (2) Functional tests In vitro tests • Cells are removed from the body and their function is studied in the lab. • Lymphocyte proliferation • test of cellular immunity that examines how effectively stimulated lymphocytes divide. • It is assumed greater proliferation indicates more effective cell function. • Lymphocytes are the key cells controlling the immune response. • The ability of these cells to proliferate rapidly in the fact of an antigenic challenge is essential to an adequate response. • NK (natural killer) cell cytotoxic activity test • used to determine how effectively NK cells kill transformed cells • NK cells can be thought of as serving a surveillance function (NK natural killer cells).

7. Tests of Immune function (3) Functional tests In vivo tests - asses the function of cells in living organisms • Quantification of antibodies (Ab) to herpes viruses • used to indirectly assess cellular immune competence. • almost everyone has been exposed to common herpes viruses. • these viruses differ from most other known viruses in that after exposure, they are present in the body all the time, although often in latent states. • when the immune system is suppressed, the latent virus replicates. • Ab is produced in response to the herpes viral replication and the amount of Ab produced fluctuates in relation to the amount of the virus produced. • therefore higher levels of herpes virus Ab are interpreted as indirect evidence of compromised cellular immune function.

8. Tests of Immune function In vivo tests - Continued • Delayed-type hypersensitivity response • a more direct test of cellular immunity. • small amounts of an antigen are introduced by injection into the skin. • a hypersensitivity response is one in which swelling and redness occurs at the site of injection. • inflammation is expected in response to the antigens and the larger the inflammation, the more competent the cellular immune system is assumed to be. • Competence of the humoral arm of the immune system • assessed by measuring the amount of Ab produced in response to inoculation by an antigen. • the more Ab produced in response to the antigen the more competent the humoral system is assumed to be. • can be measured in the blood, saliva or nasal discharge.

9. Immunity and disease • other pathways by which psychological states could have impact on the immune system and susceptibility to disease.

10. Stress Laboratory studies • Assess the effects of acute stressors (5-20 minutes) on immune response. • Associated with declines in the functional aspects of immunity. • Immune changes in both cell numbers and functions occur as soon as 5 minutes after the onset of a stressor. • Most immune indicators return to baseline measures by one hour following cessation of the stressor, but there is some evidence that NK activity remains depressed for as long as 48 hours. • High SNS activation in face of acute stressors is associated with larger immune changes.

11. Stress Short-term or acute stressors • Series of studies looked at the impact of exams on cellular immune function among medical students. • During exams, students showed a decrease in the function of a range of indicators of cellular immune response (decreased NK activity, lymphocyte proliferation, increases in production of antibody to herpes virus). • Immune response to a vaccination (Hep B) was associated with stress levels. Those experiencing stress were less likely to produce and antibody after the first vaccination. • It was also found that exam stress was related to delays in healing of wounds.

12. Stress Chronic stress • Caregivers of Alzheimer’s patients found to have prolonged endocrine and immune dysregulation, alterations in vaccine response and delayed wound healing. • Immunological changes have been documented for weeks or months following natural disasters such as hurricanes or earthquakes. Intrusive thoughts among victims of a hurricane were found to be associated with lower levels of natural killer cells (NK). • Studies were conducted to assess stress effects on residents of the area surrounding the Three Mile Island nuclear power plant. Almost 10 years after the accident higher levels of the antibody to herpes virus was found in TMI residents compared with marched control group residents.

13. Affect and personality • Findings from a daily diary study showed that antibodies to an orally ingested antigen were higher in saliva on days when participants reported more positive moods. • Negative mood has been shown to be associated with reduced NK cells. • Among healthy older adults, a sense of coherence moderated the association between anticipation of moving and reduced levels of NK cells. • In a sample of HIV-infected men, situational optimism about health outcomes was liked to a slower immune decline, later symptom onset and longer survival.

14. Interpersonal Relationships • Among women whose husbands were undergoing cancer treatment, those reporting higher levels of social support had higher NK cell activity and higher levels of lymphocyte proliferation. • Medical students who reported higher levels of social support had a stronger immune response to a Hep B vaccination. • People with fewer social ties are more susceptible to respiratory viruses. • Spousal caregivers of dementia patients who had lower levels of social support had the greatest negative changes in the immune function one year later. • However, relationships that are negative are also associated with immune dysregulation. Marital conflict is associated with lower levels of endocrine and immune function.

15. Health consequences • Studies have shown that psychosocial factors are associated with immune related health outcomes including infectious disease, cancer, wound healing, autoimmune disease and HIV. • However there is limited evidence for direct immune pathways for these links, and the studies have methodological problems. • Currently PNI studies use a battery of vitro tests and for humans these tests are limited to peripheral blood samples. • This likely does not reflect important immunological processes occurring in lymphoid organs or other regions such as the skin.