STRESS AND IMMUNE

SYSTEM

C. SINGGIH WAHONO
Divisi Reumatologi-Imunologi
Lab/SMF IPD RSSA/FK UB
email: singgih_wahono@yahoo.com
Psychoneuroimmunology (PNI)

the interaction between psychological

processes and the nervous and
immune systems

PNI takes an interdisciplinary

approach,: psychology, neuroscience,
immunology, endocrinoogy,
physiology, infectious disease,
rheumatology, etc.
 9

Definition of Stressors

Stressors:
environmental or internal
demands which tax or exceed a
persons resources
 10

Stressor Time Windows

Immediate acute phase (within minutes of

stressor onset); the fight/flight response

Short-term stressors (that last for days or

weeks)
Ex.: exams*, moving, being fired

Chronic stressors (that last for months or years)

Ex.: caregiving for a family member with
Alzheimers Disease, marital discord, poverty
Innate and adaptive immunity
 Soluble antigen

B cell Plasma cell Antibodies

help
Antigen phagocytosed Macrophage
Th1
by APC

T helper
APC MHC 2

CD4+
Th2
help
Intracellular microbes/ B cell
virus
T cytolytic
Plasma cell

MHC 1
Virus infected cell CD8+ Effector T cytolytic
BIRDVIEW OF ADAPTIVE IMMUNITY
Th1 and Th2 cytokines
 1
How Can Stress Contribute
to Disease?
 Communication systems include:
HPA
Sympathetic nervous system (SNS)
Noradrenergic innervate immune
system
Cytokines induce symptoms of
illness

 7
MODERATING VARIABLES
STRESSOR Genetic predisposition
Previous life experiences
Coping
Social support

NO Psychological Stress? YES

HYPOTHALAMIC
ACTIVATION

CRH
PITUITARY FACTORS SYMPATHETIC ACTIVATION
ACTH Norepinephrine

Medulla
EPINEPHRINE

GLUCOCORTICOIDS Cortex

Adrenal Glands

IMMUNE SYSTEM
HPA Axis

GOODMAN & GILMAN'S,2006

 5
NE and epinephrine can alter
lymphocyte migration:

Immediate exposure (30 min)

lymphocytes,
natural killer cells

Longer exposure (days)

NK cells
 6
NE can alter innate and adaptive
immune function in organs and in
circulation:

Fine tunes immune responses,

allowing for quick adjustments
(within minutes)

Shift from Th1 to Th2

 8

Leukocytes express glucocorticoid receptors:

cortisol acts on glucocorticoid receptors to have the

following effects
inhibit lymphocyte proliferation

inhibit production of pro-inflammatory cytokines

Shift from Th1 to Th2 cell activity by stimulating

synthesis of IL-10, IL-4
 11

Innate Immune System Mobilization in

the Immediate Acute Phase of a Stressor

Redistribution of immune cells

(increase in leukocytes in blood)

Increase in innate, non-specific

immunity (increased NK cell activity)

Decrease in specific immunity

 1
2
Alterations in Specific Immunity following
Exposure to Short-term Stressors:

Decrease in Th1 cellular immune

response (e.g., proliferative response
of lymphocytes)

Increase in Th2 humoral immunity

(e.g., Th2 cytokine production)
 13
Alterations in Non-specific and Specific Immunity
following Exposure to Chronic Stressors:

Decrease in both Th1 cellular and Th2

humoral immune response (e.g., lower
antibody titers to hepatitis B vaccines*)

Decrease in innate, non-specific immune

responses (except inflammatory activity)

Persistent inflammatory activity (e.g.,

increased pro-inflammatory cytokine
production)
 14
Effects of Stress on the Immune
System Depend not Only on Timing
but Characteristics of the Person

Immune effects are stronger in

those who:
Are older
More depressed
Less supported
 20
Hypothalamus
Stressors
CRH immediate-acute
phase
Short-term-days/weeks
Chronic-months/years
Anterior Pituitary

ACTH

Adrenal Cortex

Cortisol
 21
Cortisol suppresses
Hypothalamus
immune functions
such as pro-
CRH
inflammatory cytokine
production via the
glucocorticoid
receptor (GCR).
Anterior Pituitary

ACTH

Adrenal Cortex

Cortisol GCR Immune Cell

 2
Hypothalamus But stress-> INCREASES pro-2
inflammatory cytokine
production
CRH
One mechanism: Glucocorticoid
Resistance: stress induced
downregulation of GCR; cortisol
cannot restrain pro-
inflammatory cytokine
Anterior Pituitary production so cytokine
production increases
(animal/human studies)
ACTH

Adrenal Cortex

Cortisol GCR
Immune
Cell
 24

Are these stress-induced

immunologic changes
clinically significant?

Do they contribute to disease

onset or accelerate disease
course?
2
6
 28

Mediators of Stress-related Changes

in Wound Healing

diminished mononuclear cell

trafficking to the wound site

reduced expression of cytokine,

chemokine, growth factor genes

decreased production of pro-

inflammatory cytokines in wound
environment*
Effect of stress on Cancer
Decrease cellular immune response
(innate & adaptive) against cancer
Decreased DNA repair capacity
Inhibit cancer cells apoptosis
Behavioral therapy can increase
immune response against cancer
 Effect of Stress on
Autoimmune disease

Flare of some autoimmune

diseases, e,g. : SLE, RA, SSA, etc.
Effect of Stress on Infection
Prolonged the course of TB
Streptococcal and stapyloccal
infection is increased
Associated with respiratory
infection, recurrent of genital
herpes, common cold.
 Interventions to enhance
immunocompetence
AIDS patients who benefited from
exercise and stress reduction
intervention, :
improvement in T CD4+ /TCD8+
ratios,
CD4+ T cell counts,
NK-cell cytotoxicity.
 Interventions to enhance
immunocompetence
Relaxation may mute effects of
stress:

higher NK cellactivity after

relaxation intervention
Reduces pro-inflammatory
cytokines
Cellular immunity enhanced
 Interventions to enhance
immunocompetence
Better NK cell activity in breast
cancer patients was related to:
High quality emotional support
from a spouse,
Perceived psychosocial support
from the patients physician
Actively seeking social support
 29
How Might Information From the Field
of Psychoneuroimmunology Influence
Your Clinical Practice?

Ask about life stressors (short

term and chronic), impact on
functioning
Ask about how a patient is coping,
social supports. Does it help?
Recognize that vaccinations may
be less protective during stressful
times (consider other
precautions)
 How Might Information From the
Field of Psychoneuroimmunology
Influence Your Clinical Practice?

Recognize that wound healing may be

influenced by stress
Recognize that immune functions may
be affected by the use of drugs that
influence the ANS or glucocorticoids
(e.g., -blockers).
Ask about therapy and make
recommendations and/or referrals as
needed (know what is available in the
community).
recognize the limitations in knowledge
when patients ask about whether a
given therapy (visualization, etc) can
 Conclusions

There is a significant relationship

between Psychology, neurologic
system, immune system and health/
diseases.
Hopefully, it will provide a better
improvement promoting health,
preventing disease, and improving
the results of conventional therapies