Download The effect of acute and chronic stress on the Immune System as

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
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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: hypothalamicpituitary-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?