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: 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

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

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

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

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

Academic Stress

Academic Stress

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)

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

Results

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

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)

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)

Results: Psychological Data

Results: Immunological Data

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.

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.

Percent Wounds Healed

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

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

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

Caregivers of AD Patients Study

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

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

Three Mile Island

Immune Status: Three Mile Island

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

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

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

Experiment 1 Results

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

Experiment 2 Results

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

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

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

Stress and Infectious Disease: Results

Stress and Infectious Disease: Results

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

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

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

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

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

Results

Is this due to elevated glucocorticoids? STRESS

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