3. Stress and the immune system

stress

“Nonspecific response of the body to any demand” - Selye 

• Selye was an endocrinologist 

• Found that BLANK affected the immune response of rats 

• Placed rats in challenging social environments 

How we appraise and respond to challenging/threatening events 

• Do they exceed our current ability to cope? 

stressors

demanding situations that require adjustment for us to cope 

• Things that are ambiguous, uncertain, uncontrollable 

• Events that seem central to our values/goals  

eustress

• Planning a fun event (wedding, birthday) 

• A change in your life 

• Having a baby 

• Moving in with your partner 

distress

• negative, overwhelming, impairs functioning 

• Stressor is perceived as difficult 

• Exceeds our ability to cope 

levels of stress

• Low stress – feel no pressure, not very productive  

• Moderate level of stress – we get the most work done 

• High stress – we feel like we cannot cope, cannot be productive 

GAS- General Adaptation Syndrome 

• Continuous stress leads to death 

• Reach a point of exhaustion  

• Damages the body 

• Medical therapy can improve well-being  

Stages  

Alarm phase 

1. Initial shock Slight reduction in resistance to stress 

2. Countershock Stress resistance begins to peak 

Adaptation 

3. Resistance phase Resistant to stress 

2. If stress continues to be elevated, we reach exhaustion 

Exhaustion 

4. Exhaustion 

1. Body shuts down 

   1. Stress damages the body – physiological complications 

5. Effective medical therapy 

   1. Return to normal levels of stress 

6. OR DEATH 

fight or flight

Sympathetic nervous system prepares to respond (fight or flee) 

• Evolutionarily hard-wired into us 

• Racing thoughts, tunnel vision, dry mouth (digestion shuts down), heart beats faster, quicker and shallow breathing, adrenal glands release adrenaline (aka epinephrine), nausea, sweaty palms 

• Shallow and quick breathing can make us dizzy or lightheaded 

• Blood goes towards muscles 

• muscles tense/shake 

• cold extremities 

tend and befriend

Common for women 

• Nurturing relationships 

• Seeking out others (social support) when under stress 

• Oxytocin can ease stress 

SAM – sympatho-adreno-medullary axis 

1. Stressor  

2. Hypothalamus secretes CRH (corticotropin releasing hormone) 

3. CRH stimulates pituitary gland 

4. Pituitary releases ACTH (adrenocorticotrophic hormone) 

5. SNS (sympathetic nervous system) activation 

   1. Adrenal medulla secretes epinephrine and norepinephrine (adrenaline)

   2. Epi/norepi trigger fight or flight 

      1. Increased HR, BP, respiration, sweating, etc. 

HPA - Hypothalamic pituitary adrenal axis

1. Hypothalamus secretes CRH 

2. CRH stimulates pituitary 

3. Pituitary releases ACTH 

4. Adrenal cortex releases glucocorticoids (incl. Cortisol) 

   1. Aka corticoid steroids 

   2. Return to baseline, promote healing, reduce inflammation 

5. Ideally, blood levels of ACTH decrease, and cortisol production shuts off 

HPA axis dysfunction

occurs when SAM is repeatedly activated by stressors

• Cortisol is constantly secreted by BLANK

• Cortisol can suppress immune function 

• Inflammatory diseases 

• Inability to respond/recover from stress 

• Physical and psychological problems 

HPA axis suppression

Chronic stress – BLANK can be underactive 

• No cortisol response 

• Autoimmune diseases 

  • Asthma 

  • Multiple sclerosis 

  • Rheumatoid arthritis 

Blunted cortisol (hypocortisolism) response is associated with higher levels of estrogen 

• More common in women 

• Estrogen lowers cortisol response 

exercise activates SAM

Brief periods of sympathetic nervous system activation is protective 

• Does NOT activate HPA 

• Can recover from BLANK more quickly 

• BLANK has an end point 

VS stressor/trauma – flashbacks reactivate response 

• Experienced long after it initially occurs 

allostatic load

Chronic activation of SAM due to stressors can create a new (altered) set point for homeostasis 

• difference between baseline and altered set point

• wear and tear

effects of allostatic load

• more visceral fat

• lower heart rate variability

• difficulty lowering cortisol HPA axis dysfunction

• decreased hippocampal volume

  stress is neurotoxic

coping

how a person manages internal and external demands 

negative affect

people with depression, hostility…

more likely to cope by

• avoidance

• alcohol or drug use

• being sedentary

positive emotional states

promote better mental & physical health 

• Lower levels of stress-related biomarkers 

• More likely to engage in approach-oriented coping 

• Instead of avoidance 

optimism

better psychological stress profiles 

• Better heart rate variability 

• Less reactivity to stress 

• Wound healing is faster 

effective coping

linked to

• religiosity/spirituality

• intelligence

• conscientiousness

• sense of control

• high self-esteem

mindfulness training

stress reduction

• Downregulate emotional centers (limbic area) 

• Boost self-compassion 

• focus on present 

expressive writing

• Daily journaling practice 

• Writing about our feelings can help us cope 

• Writing a letter to others, but not giving it to the person 

• Emotional disclosure 

relaxation training

• Deep breathing 

• Visual imaging practice 

• Going to a safe place 

• Progressive muscle relaxation 

Structured stress management program 

• Self-monitoring 

• Identifying stressors and their antecedents 

• Eliminating negative self-talk 

• Reappraise events 

• At-home practice 

social support

Had been linked to 

• Reduced cortisol responses to stress 

• Less accumulated wear and tear (allostatic load) 

• Less cellular aging 

• Lower likelihood of illness 

• Faster recovery from illness, surgery 

• Have better health habits 

• Report less pain and other adverse symptoms 

caregiver stress

linked to poor immune functioning  

• Higher self-reported stress levels 

• Abnormalities in daily cortisol production 

  • Normally highest in morning 

  • Should decrease and allow you to wind down for sleep 

Family members caring for loved ones with Alzheimer’s disease 

• Reported more depression and less life satisfaction 

• Were found to have lower % of T-cells and other immunosuppressive measures 

• Overproduced pro-inflammatory cytokines 

natural immunity

• Inflammatory response triggered by both psychological and physical stress 

• Releases proinflammatory cytokines into blood stream 

• IL-1, IL-6, TNF-alpha 

specific immunity

T-cells, B-cells, antibodies 

Psychoneuroimmunology (PNI)

Study of interactions between nervous, endocrine, and immune systems  

• Both physical and psychological stress can trigger inflammatory response  

indirect measure of immune functioning

measure how quickly wound heals

• Punch biopsy 

• Take a small sample of tissue 

• See how quickly the wound heals 

• Group under chronic stress vs control group 

Psychological distress slows down wound healing due to impairment of inflammatory response 

direct effects of stress on immunity

• Stress activates SAM, HPA responds 

Immune cells have receptors for glucocorticoids (cortisol) and norepinephrine/epinephrine 

• T-cells, B-cells, lymphocytes 

• Suppress the immune response 

indirect effect of stress on immunity

Stress alters immune function by encouraging maladaptive health (coping) behaviors 

smoking

• Weakens production of macrophages at wound sites 

• Slows down natural immunity 

• Reduces blood flow by constricting blood vessels (vasoconstriction) 

• Nicotine and other toxins suppress white blood cell activity 

fragmented sleep

• secretion of growth hormone happens in slow-wave (deep) sleep 

• Time for repair and healing  

substance abuse

a common maladaptive way to cope with stress

short term acute stressors

• up regulation of natural immunity (inflammation)  

• down regulation of specific immunity 

chronic stressors

• constant low level inflammatory response 

• chronic immune response problems 

reduced immune functioning

• smoking

• stress

• sleep disorders

• age - more proinflammatory cytokines

• fat tissue secretes inflammatory cytokines

glucocorticoid resistance model

1. If glucocorticoids (cortisol) can no longer suppress the production of proinflammatory cytokines 

2. Overproduction of cytokines 

3. Chronic inflammatory conditions 

   1. Arthritis- Red, warm, swollen joints 

   2. CVD 

   3. T2D 

chronic stress → HPA dysregulation → cortisol released → cortisol resistance

recall that cortisol is normally anti-inflammatory