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

4. 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

7. 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

8. 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

9. 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

10. Academic Stress

11. Academic Stress

12. 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)

13. 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

14. Results

15. 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

16. 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)

17. 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)

18. Results: Psychological Data

19. Results: Immunological Data

20. 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.

21. 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.

22. Percent Wounds Healed

23. 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

24. 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

25. Caregivers of AD Patients Study
Current Caregivers
Former Caregivers
Controls
Perceived Social Stress
16.73
10.46
9.61
Social Support
29.82
37.85
36.57

26. Caregivers of AD Patients Study

27. 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

28. 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

29. Three Mile Island

30. Immune Status: Three Mile Island

31. 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

32. 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

33. 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
No Stress Test for NK cell cytotoxicity
Control

34. Experiment 1 Results

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

36. Experiment 2 Results

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

38. 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

39. 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

40. Stress and Infectious Disease: Results

41. Stress and Infectious Disease: Results

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

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

44. 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

45. 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

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

47. Results

48. Is this due to elevated glucocorticoids?
STRESS

49. 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