Psychoimmunology 1 Psychology 415; Social Basis of Health Behavior Natural v. Acquired / Specific immune parameters  Natural immunity  Genetic, species-wide antigen compliment  Quick acting, general cellular immune components Macrophages Compliment Natural Killer  Acquired / specific immunity  Vaccines, immune memory  Slow, highly targeted T helper cells T cytotoxic cells (“T cells”) β cells Cytokine release Inflammation  Recognize antigen on cells Antibodies  “lock on” expressed antigen & lyse cells Recognize & kill “free” (plasma) antigen 

Psychoimmunology 2 Psychology 415; Social Basis of Health Behavior Cytokine pathway  Stress or physical trauma  cytokine pathway Trauma / infection Pro-inflammatory cytokines IL6, tumor necrosis factor NK Pro-inflammatory cytokines IL6, tumor necrosis factor NK Inflammation Acute stress “Sickness behavior” Lethargy Withdrawal Responsiveness to pain Energy conservation Stress reduction Avoid pathogens “Sickness behavior” Lethargy Withdrawal Responsiveness to pain Energy conservation Stress reduction Avoid pathogens Clear / avoid infection Up-regulation of natural / cellular immunity  NK proliferation & cytotoxicity Up-regulation of natural / cellular immunity  NK proliferation & cytotoxicity

Psychoimmunology 3 Psychology 415; Social Basis of Health Behavior Cytokine pathway  Affect-driven alterations in cytokine pathway Trauma / infection Pro-inflammatory cytokines IL6, tumor necrosis factor Pro-inflammatory cytokines IL6, tumor necrosis factor Chronic Inflammation Plaque Lipids Plaque Lipids Inadequate wound healing Chronic Stress, Negative affect “Sickness behavior” Lethargy Withdrawal Responsiveness to pain Energy conservation Stress reduction Avoid pathogens “Sickness behavior” Lethargy Withdrawal Responsiveness to pain Energy conservation Stress reduction Avoid pathogens C-reactive protein, Il6, etc. Clear / avoid infection Down-regulation of acquired / specific immunity  NK  Antibody titers Down-regulation of acquired / specific immunity  NK  Antibody titers Morbidity, CHD Morbidity, CHD

Psychoimmunology 4 Psychology 415; Social Basis of Health Behavior HPA pathway  Hypothalamic – pituitary – adrenocortical pathway Stress, ψTrauma, chronic arousal Catecholamine, cortisol secretion Catecholamine, cortisol secretion Inflammation Decreasing threshold for HPA activation Morbidity Immune activation

Psychoimmunology 5 Psychology 415; Social Basis of Health Behavior HPA pathway  Linkage of HPA axis, immune products, and affect Stress, ψTrauma, chronic arousal Catecholamine, cortisol secretion Catecholamine, cortisol secretion Inflammation Negative affect, Anxiety, Insomnia, memory deficits Negative affect, Anxiety, Insomnia, memory deficits Morbidity Immune activation

Psychoimmunology 6 Psychology 415; Social Basis of Health Behavior Bi-directional effects  Bi-directional: immune competence and affect  Depression, stress, arousal  HPA activation  inflammation & NK depletion HIV:  Depression, concealment of MSM status  mortality  ART treatment  lessened depressive affect  Cytokine stimulation  depressed affect, lethargy.

Psychoimmunology 7 Psychology 415; Social Basis of Health Behavior Bi-directional process of immune system & ψ Affect: Depression Anger & anxiety Stress Affect: Depression Anger & anxiety Stress Morbidity & mortality: URI CHD Cancer Morbidity & mortality: URI CHD Cancer Ψ Mediators: Diet Alcohol / drug use Exercise / activity Ψ Mediators: Diet Alcohol / drug use Exercise / activity Immune Mediators: NK / Il6 / cytokine production C-reactive protein HPA pathway Inflammation Immune Mediators: NK / Il6 / cytokine production C-reactive protein HPA pathway Inflammation

Psychoimmunology 8 Psychology 415; Social Basis of Health Behavior Cytokine / immune system effects on depression  Inflammation / “sickness” behavior may interfere with hippocampal-mediated learning  Similar mechanism as cognitive load  Interference with avoidance learning

Psychoimmunology 9 Psychology 415; Social Basis of Health Behavior Chronic disease, “illness behavior” and depression

Psychoimmunology 10 Psychology 415; Social Basis of Health Behavior Key Immunological moderators  Gender;  Mediated by threshold for negative affect or depression Dx  Race;  SES; strong main effect on all health parameters  Neuroticism (type “D” or “C” personality)  Acute Stress  Bereavement Increase in cortisol, norepinephrine consistent decrease in NK proliferation  Trauma / environmental change Decrease in cortisol Increase in cellular immunity?  Social / marital conflict [“high anger” couples] >> social / marital support  Exams (x age…)  Chronic stress  Caregiving burden  [distress]  decrements in humoral & cellular systems  (Non)marriage in men  Non-disclosure among MSM  HIV mortality Biphasic model: Immune enhancement (?) Immune suppression Biphasic model: Immune enhancement (?) Immune suppression