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Stress and Infections

Stress and Infections. Antigens ~ proteins on the surface of cells that identify microorganisms as native or foreign. Lymphocytes ~ specialized white blood cells that play important roles in immune reaction. Immune System Barriers. Nonspecific Immune System Barriers:

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Stress and Infections

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  1. Stress and Infections • Antigens ~ proteins on the surface of cells that identify microorganisms as native or foreign. • Lymphocytes ~ specialized white blood cells that play important roles in immune reaction.

  2. Immune System Barriers • Nonspecific Immune System Barriers: • Mucus Membranes: destroy foreign organisms • Phagocytosis: process where foreign organisms and debris are consumed and destroyed by phagocytes • Natural Killer Cells (NK Cells): able to kill foreign organisms

  3. Specific Immune System Cell Mediated Immunity: T lymphocytes • Develop in the bone marrow • Mature in the Thymus gland • macrophage ingests a foreign micororganism and displays the antigen which attracts T cells • helper T cells: cytokines • killer T cells

  4. Specific Immune System Antibody-Mediated Immunity • Directed by B lymphocytes • Develop and mature in the Bone marrow • Once T cells are helping the macrophage, they secrete a protein to cause B cell proliferation • B cells produce antibodies for the specific antigen • memory B cells

  5. Academic Stress: Kiecolt-Glaser, et al. 1984 • First year medical students • Baseline immune response • 1 month before final exams • Exam immune response • first day of final exams • Self report measures of distress • UCLA loneliness scale

  6. Academic Stress Results: • Self-report data: greater distress during finals week • Immune function: • significant decrease in NK cell activity during finals week • students with higher distress scores had lower NK cell activity

  7. Academic Stress

  8. Academic Stress

  9. Marital Stress: Kiecolt-Glaser, et al., 1987 • 38 married women • 38 separated/divorced women • Immunological data • helper T cells • NK cell activity • Epstein-Barr Virus: higher in patients on immunosuppressive drugs • indicates increase in amount of infectious virus (reactivation)

  10. Epstein-Barr Virus (EBV) Epstein-Barr Virus (EBV) Mononucleosis Immunosuppressive Drugs Increase in Antibodies to EBV Why the Increase? Drug Suppress Immune System Increase Virus Activity Increased Antibody Production to EBV

  11. Results

  12. Chronic Stress Caregivers of AD Patients Study: Keicolt-Glaser et al., 1987 • 34 Caregivers of Alzheimer’s Disease Patients • 34 Age Matched Controls • Psychological Data • Blood Samples

  13. Caregivers of AD Patients Study Psychological Data 1. Self-Report Data a. Life Satisfaction b. Degree of Loneliness c. Physical Health d. Mental Health 2. Depression Inventory (Beck Depression Inventory)

  14. Caregivers of AD Patients Study Blood Samples (Immunological Data) 1. Total T Lymphocytes 2. Helper T Lymphocytes 3. Natural Killer (NK) Cells 4. Antibody levels to EBV • Epstein-Barr Virus: Higher in patients on immunosuppressive drugs • Indicates increase in amount of infectious virus (reactivation)

  15. Results: Psychological Data

  16. Results: Immunological Data

  17. Conclusion • Caregivers of Alzheimer’s Disease patients are more distressed • They have poorer immune function • Despite all of this, there were no health differences between the two groups.

  18. More Results • Caregivers of Alzheimer’s Disease patients showed slower healing of wounds as a result of an arm biopsy used to test recuperative function.

  19. Percent Wounds Healed

  20. Caregivers of AD Patients Study • Glaser, et al., 1999: 3 groups: • 11 current spousal caregivers • 13 former caregivers • 28 non-caregivers • all groups matched on age, health, education, etc • examined immune response to a pneumonia vaccine

  21. Caregivers of AD Patients Study • Psychological measures: • Perceived Stress Scale • Interpersonal Support Evaluation List • Immune measures: • obtain blood sample prior to pneumonia vaccine • additional blood samples at 2 weeks, 1 month, 3 months, and 6 months after the vaccine

  22. Caregivers of AD Patients Study

  23. Caregivers of AD Patients Study

  24. Conclusions • Current caregivers were able to process the pneumonia vaccine initially, but were not able to maintain it over time • Former caregivers did not demonstrate a deficit in immune function

  25. More Chronic Stress: Davidson and Baum, 1986 Three Mile Island: 1979 • 58 months after the accident • Two groups of subjects: • 5 mile radius • 80 miles away • Measured self-reported symptoms of distress • Measured physiological variables • Measured immune status

  26. Three Mile Island

  27. Immune Status: Three Mile Island

  28. Are we likely to get into trouble because stress suppresses our immune system? S. Ben-Eliyahu rt al., 1991 Relationship between: • Acute stress • NK cell cytotoxic activity • Metastatic spread of lung tumor

  29. Acute Stress and Tumor Growth • Tumor: MADB106 cell line • NK cell cytotoxicity: • NK cells from the spleen • incubate with MADB106 tumor cells • Induction of tumor metastasis: • inject tumor cells into tail vein on Day 0 • euthanize Day 12 • count the number of lung tumors

  30. Acute Stress and Tumor Growth • Stress Procedure: • attach a weight to the tail of a rat • place the rat in a water tank for three minutes • repeat 5 times with a 3 minute rest interval • Experiment 1 design: 1 hour Stress Test for NK cell cytotoxicity 1 hour No Stress Test for NK cell cytotoxicity Control

  31. Experiment 1 Results

  32. Acute Stress and Tumor Growth • Experiment 2 Design: 1 hour 12 days Stress inject tumor lung cells tumor growth 1 hour 12 days No Stress inject tumor lung Control cells tumor growth

  33. Experiment 2 Results

  34. Conclusions • Acute stress reduces NK cell cytotoxicity • Acute stress increases lung tumor growth Does this apply to humans?

  35. Stress and Infectious Disease Cohen et al., 1991 • Common Cold Unit, England • 394 healthy adult subjects • questionnaires first day at unit • psychological stress • health habits • personality

  36. Stress and Infectious Disease • Nasal Drops • saline control group • viruses (n=5 different respiratory viruses) • concentration similar to person-to-person contact (20 to 60% illness rate) • measured levels of virus in nasal washings for 6 days after

  37. Stress and Infectious Disease: Results

  38. Stress and Infectious Disease: Results

  39. What causes stress-induced immunosuppression? Glucocorticoids • Halt formation of new lymphocytes in Thymus • Kill lymphocytes • Remove lymphocytes from circulation • Inhibit communication

  40. Keller, 1985 • Removed adrenal glands from rats (ADX) • stress the rat with inescapable shock • measure number of lymphocytes in the blood

  41. Stress-Induced tumor growth increases with age Sapolsky and Donnelly, 1985 • aged rats during stress secrete higher levels of glucocorticoids than young rats • determine if chronic stress increases tumor growth in aged rats

  42. Sapolsky and Donnelly, 1985 • Tumor: Fujinami sarcoma • Stress sessions: • vibration • cold exposure • immobilzation • 4 groups of rats: • young-stressed • young-no stress • old-stressed • old-no stress

  43. Sapolsky and Donnelly, 1985 • Design: 1 week 1week Inject Measure tumor cells tumor growth daily stress rest

  44. Results

  45. Is this due to elevated glucocorticoids? STRESS

  46. What is the adaptive value of inhibiting the immune system during stress? • Immune system activation leads to sickness behaviors • lethargy, weakness • increased sleep • This is not conducive to confronting acute/chronic stress • Stress causes a brief increase in immune function, followed by a decrease

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