Protective and Damaging Effects of Stress Mediators

(Stress and the Immune System)Chapter Four

Caitlin Cleary

June 13, 2007

http://www.kf6nvr.net/blog/archives/images/computing_stress.jpg

Psychoneuroimmunology

• Scientific field investigating the link between bidirectional communications among the nervous system, endocrine and immune systems

– What are the implications of these linkages for physical and mental health?

- Stress!!!

What is stress?

• A specific response by the body to a stimulus that disturbs or interferes with normal physiological equilibrium/homeostasis

• Stressors: can be real, imagined, internal or external– Physical/environmental– Natural disasters– Major life changes (good and bad)– Hassles/day-to-day aggravations– Personality related

Stress - cross talk between CNS and immune system

• The brain is the master controller of the nervous, endocrine, and immune system

– However, the brain is also a target for these systems

– Subject to both protection and damage

New Terms

• Allostasis: superordinate system by which stability is achieved through change – Primary mediators: HPA axis, catecholamines, and

cytokines– When set homeostatic points are out of boundaries, it

is referred to as allostatic states (ex. hypertension, cytokines increasing risk for autoimmune/inflammatory disorder)

• Allostatic load and allostatic overload: the cumulative wear and tear on the regulatory systems of the brain and body from the cumulative result of an allostatic state

Peripheral Limbs of the Stress System: Part One

HPA axis: hypothalamic-pituitary-adrenal axis which regulates body processes including digestion, immune system, mood/sexuality, energy usage

Regulates hormone levels and maintains homeostasis

http://cti.itc.virginia.edu/~psyc220/kalat/JK367.fig12.6.HPA_axis.jpg

Peripheral Limbs of the Stress System: Part Two, Autonomic Nervous System

• Involuntary activities that maintain homeostasis – i.e., cardiovascular, respiratory, and digestive functions, etc.

• Sympathetic and Parasympathetic branches that work complementary to each other

http://www.buteyko.co.nz/asthma/facts/images/nervous.jpg

Normal Stress Response

Prey sees a predator

The event initiates stress response

The prey is able to escape predation

Stress response dissipates and body returns to homeostasis

“Fight or Flight” or “Tend and Befriend”

Complicated Stress Interactions

Stress induces change for adaptation

• Behavioral/Psychological (changes to eating, sleeping patterns, mood, etc.)

• Physiological (increased blood pressure, heart rate, dry throat, etc.)

• Immunological (suppression of immune system)

“The General Adaptation Syndrome”

Hans Selye (1936)/ Cannon (1932) : the general adaptation syndrome, a classic, stereotyped theory of stress

1) Alarm reaction: adrenal medulla releases epinephrine, and the adrenal cortex produces glucocorticoids, promoting adaptation and restoring homeostasis (allostasis)

2) Resistance: defense and adaptation are optimal (allostatic load)

3) Exhaustion: persistence of stress response – which may lead to illness or death (allostatic overload)

Chronic Stress Effects

• Consistently elevated cortisol and catecholamine levels (Stress response chronically activated)

• Non immune related: Diabetes, insomnia, myocardial infarction

• Stressful events predispose to disease and immune deregulation – infection, cancer, autoimmune diseases (ms)

• Impaired learning – atrophy in hippocampus• Depression (resulting from altered immune

function)

Non-immune related allostatic overload

Glucocorticoids regulate behaviors that control energy input and expenditure - energy conversion serves the body well in the short term- elevated insulin levels (glucose uptake) and glucocorticoids promotes deposition of body fat and the formation of atherosclerotic plaques in the coronary arteries in the long term

Immune related allostatic overload• These glucocorticoids can modulate the immune system

by lowering the Th1 response and increasing the Th2 response (diminishing cell mediated immune response)

• Cortisol, a specific glucocorticoid, and catecholamines can cause changes in proliferation, cytokine secretion, antibody production, cellular trafficking, and cytolytic processes

• It has been shown that adding CRH in vivo causes NK cell cytotoxicity to go down

• Clinical administration of glucocorticoids, such as cortisol, cause eosinophil and lymphocyte numbers to decrease

• Products of the Immune system also can react with the HPA axis. IL-1, a cytokine produced by the immune system to mediate inflammation, causes ACTH release indirectly by increasing CRH

QUESTIONS?