This document discusses the relationship between stress and the immune system. It provides three main theories on how psychological stress can impact immunity. The first theory proposed by Hans Selye suggested that stress globally suppresses the immune system. The second theory proposed by Robert Ader found that immune responses could be classically conditioned. The third theory discussed how stress activates the HPA axis and increases cortisol levels, which can impair immune function. The document also describes the components and functions of the innate and adaptive immune system, and how different types of stressors like acute and chronic stress can influence immune cells and cytokines. Research evidence is presented showing that stress can reduce resistance to illness by suppressing immunity.

1. Effect of stress on Immune System
By :TANUSHREE BHARGAVA
Clinical psychologist Shimla
tanushree4help@gmail.com

2. Content
1. Stress
2. Stressors
3. Theories: Relation b/w stress and immune system.
4. Immune system :Functions & components
5. Effect of type of stress on immune system

3. • Psychoneuroimmunology is a discipline that
studies the relationship between psychologic
states and the immune response(Mosby’s
medical dictionary,8th edition,2009,Elsevier)

4. What is Stress
• Stress is simply a reaction to a stimulus that disturbs our
physical or mental equilibrium.
• A stressful event can trigger the “fight-or-flight” response,
causing hormones such as adrenaline and cortisol to surge
through the body.
• According to Hans Selye “Stress is the physiological response
of the body to external stressors.”

5. Stressors
• Stressors: It Is a chemical or biological agent, environmental
condition, external stimulus or an event that causes stress to an
organism.
• This stressor can be real, imagined, internal or external.
• Examples:
• Physical/environmental, Natural disasters, Major life changes
(good and bad),Hassles/day-to-day aggravations etc.

6. Types Of stressors(Elliot & Eisdorfer
1982)
• Acute Stressors: Time limited stressors.
Ex: Public Speaking, Mental Arithmetic etc. (within minutes of
stressor onset); the “fight/flight” response
• Chronic Stressors: Long lasting stressors such as traumatic
injury leading to physical illness. (that last for months or
years)
Ex.: caregiving for a family member with Alzheimer’s Disease,
marital discord, poverty.

7. Theories suggesting link between
stress and immune system
How can psychological events affect
the immune system?

8. Theory 1
• One of the first proponents to study the relationship between
stress,immune system and disease was Hans Selye.
• Selye (1975) suggested that stress globally suppresses the immune system
and provided first model relating stress and immune response.
• He described three stages of general adaptation syndrome in response to
stress:
• Alarm stage :is the first stage where body prepares for fight-or-flight in
response to a threat. If the stressful situation persists
• Resistance: At this stage body channelizes all its resources by secreting
further hormones and blood sugar to sustain energy to fight.
• exhaustion: When the stressor remains for a long time. In this stage,
body has run out of its reserve energy and immunity. At this juncture, due
to heavy depletion of body resources, one may fall ill or die.
• Studies support this model by reporting association of chronic stress with
decrease in natural killer cell, suppression of lymphocyte responses
(Herbert & Cohen, 1993).

9. Hans Selye's research suggested a link between the exhaustion stage of the
general adaptation syndrome and weak immune system and physical illness.

10. Theory 2:
The term psychoneuroimmunology was coined by Robert Ader,
who accidentally found that immune system could be classically conditioned.

11. In an experiment of classical conditioning of rats, Ader and Cohen
(1975).
• They fed rats with saccharin while injecting a drug that caused
stomach upset.
• As a result, mice learned to avoid the saccharin.
• An additional side effect of the drug was that it suppressed immune
system.
• When the experiment was repeated without the injection of drug to
reverse the aversion, they found high proportion of the rats died
when receiving saccharin alone.
•
This led them to hypothesize that, by classical conditioning saccharin
alone suppressed the immune system enough to kill the rats.
This experiment indicated that signals from nervous system can affect
immune system.

12. THEORY 3: Stress and immune system are activated by HPA axis and
Cortisol (anti-inflammation) theory: Overview of the hypothalamic-
pituitary-adrenal (HPA) axis and its bi-directional communication with the
immune system. The complex regulatory interactions between the HPA axis and the
immune/inflammatory network are shown

13. Stress causes Dysregulated Cortisol response:Recent research suggests that it
is hormones that are responsible for the negative effects of stress, their secretion
being increased by activation of the hypothalamic-pituitary axis and the
sympathetic branch of the autonomic nervous system.
• Short term stressor – raises it
• Long term and long past stresses might result in too low of Cortisol –
Flattens out the diurnal cycle of Cortisol production.

14. High Cortisol levels are related to :
• impairs the body’s ability to control inflammation, so inflammatory diseases
develop.
• Inversely related to Lymphocytes in blood.
• Impairs Immune function by :Killing WBC,
• Effects leukocytes(wbc production and production of antibody).
• Which effect production of b cells and t cells
Low levels of Cortisol:
• In patients with autoimmune disease, despite the higher levels of systemic
inflammation.

15. Immune system
• Immune system :
• The system of biological structures and processes within
an organism that protects against disease(Beck and
Gregory,2007)
• To function properly, an immune system must detect a
wide variety of agents known as pathogens , from viruses
to parasitic worms and distinguish them from the
organism’s own healthy tissue(Beck & Gregory 2007)

16. • Research shows that stress can decrease the
efficacy of immune system.

17. Immune System

18. Structure of Immune System
• Lymphatic system: consist of bone marrow, spleen,thymus and lymph
nodes)
• Leukocytes

19. Structure of Immune System
• Leukocytes(WBC):It has 2 pathways
– Lymphocytes: Produced by bone marrow
• T Cells
• B Cells
Leukocytes(WBC)
Phagocytic cells
(Innate Immunity)
Lymphocytes
(Adaptive Immunity)

20. Immunity System
• In human body there are two types of immune system : Song
and Leonard 2000;hofmyer 2005)
• First Line Defence: Innate Immunity(non specific)
• Second Line Defence: Adaptive Immunity(specific)
• Both systems work together to prevent foreign organisms to
enter and destroy them even if they enter.

21. Immune System
Leukocytes(WBC)
Innate
Immunity
Phagocytic
Cells
NK Cells
Adaptive
Immunity
B cells
T cells
Th1
Th2
Cytoxines

22. Effect of stress on immune system?

23. Effect of stress
• Leukocytes(WBC):
• Acute stress: It causes an increase in circulating white blood
cells.
• Chronic stress: When cortisol remains high, however, white
blood cell numbers are reduced

24. First Pathway
Innate Immunity
(First Line Immune Defence)
Phagocytic Cells NK Cells

25. • First line immune Defense
1.Phagocytes: (Non Specific):
• Engulfs and digests foreign organisms.
• Short Lived.
• Present in both circulation and the tissue.
• This signals other cells of invasion
– Activates T- cells to duplicate
– Produce IL-1 that promotes other cell activity
Long term stress: Decrease in innate, non-specific immune responses
(except inflammatory activity)

26. 2. Natural Killing Cells(Non Specific):
• Kills virally infected cells and tumor cells by release of toxic substances
into the cells
• Enhance killing and inhibits viral production
• In vitro, NK kills tumor cells in 3 hrs.
• Research Suggests:
 NK cells taken from stressed animals are less effective than from non-
stressed animals.
 Cohen et al. (2007) – Being unemployed reduced natural killer cell
cytotoxicity. Getting a job recovers function

27. Short Term effects:
• Causes NE surges : Increases NK activity.
• Redistribution of immune cells (increase in leukocytes in
blood)
• Increase in innate, non-specific immunity (increased NK cell
activity)
Long term Stressors:
• Suppresses NK cells production.
• Reactivate latent viruses ,lower antibody response to
vaccination.

28. Adaptive Immunity
B cells
(Responsible for producing
antibody molecule)
T (Th cells )
Helper T(Assist)
Regular T cells
(Suppress other cell
Immune Response
Cytoxic T cells ((Kill
infected or foreign
eukaryotic cells)
Lymphocytes(produced by
bone marrow)

29. Second Line Of Defense: (Specific)
Require specificity or fit between immune cell receptor and antigen – pre-programmed.
• T-cells : are Cytotoxic injects toxins to kill foreigners. recognize foreign antigens
on the surface of cells, organisms, or tissues:
• Helper – T cells: “brains” of the bunch but don’t kill anything themselves.
TYPES:
Th1 AND Th 2:
• These two are intended to be balanced as they coordinate other immune system
activity.
• Th1 cells are great against viruses and bacteria among other things.
If Th2 numbers get too high too long, conditions like allergy, inflammation,
autoimmune disorders, cancer and pain are more likely to exist and Th1 is
depressed.
T cells regulate proliferation and activity of other cells of the immune system:
B cells, macrophages, etc.

30. The “choice” between Th1 and Th2 is influenced by CYTOKINES
– T-killer cells(Cytotoxic T cells):Kill the viruses
– T-suppressor cells: stop the attack, when there is no virus. Turns off the
attack
Inactivity of T-suppressor cells is implicated in autoimmune diseases

31. Short term effect:
• Decrease in specific immunity. Decrease in Th1 cellular immune
response (e.g., proliferative response of lymphocytes)
• Increase in Th2 humoral immunity (e.g., Th2 cytokine production)
Long term effect:
• Suppresses lymphocyte production cells production.
• Decrease in both Th1 cellular and Th2 humoral immune response
(e.g., lower antibody titers to hepatitis B vaccines*)

32. Cytokines:
Cells Must Communicate And They Do It With Cytokines
• Since the immune system is made up of lots of different kinds of cells
spread out all over, and, since they depend on each other, they
communicate through cytokines.
• They tell immune cells to grow in number, they tell them where the action
is, and they tell them when the enemy has been destroyed among other
things.
• Cytokines determine whether Th1 or Th2 helper T cells are dominate in any
given area based on information given by NK cells .What if the NK cells
aren’t working right.
Long term stress:
• Persistent inflammatory activity (e.g., increased pro-inflammatory cytokine
production)
• Increased cortisol knocks out cytokine pathways leads to damage in
communication pathways.

33. B cells –(Humoral) Specific Targets: Secrete protein
molecules that coat and neutralize infected cells.
• Helps other cells.
• identify and kill infected cells
• Facilitates NK and T-cell killing.
– What happen to b cells during stress??

34. Research Evidences
• Evidence suggests that stress can reduce the body's resistance to illness by
suppressing the immune system (Riley 1981; Schliefer et al 1983).
• Relationships exist between stress and ulcers (Brady 1958), hypertension
(Cobb and Rose, 1973), and coronary heart disease (Friedman and
Rosenman 1959)
• New research Evidences? A growing body of research has found that
negative psychological states such as stressful experiences and depression
may influence health and disease by altering immune system (Glaser et al.
1987; Kiecolt-Glaser & Glaser 1994). Evidences indicate that stress
suppresses immune functions and consequently impairs resistance to
infectious diseases (Glaser & Kiecolt-Glaser, 2005) and lends support to
the idea that stress related immune changes mediates the relationship
between stressors and various diseases

35. Conclusion
• Majority of the research on stress and immunity
revealed a negative impact of stress on immune
responses.
• Research indicates that both objective as well as
perceived stress may negatively influence immune
functions.
• The nature of stressor (acute or chronic) may have
significant impact on the immune functioning.
• Brief acute stressors appear to enhance some
parameters of immunity whereas chronic stress
consistently showed detrimental effect on almost all
parameters of immune functions.

36. • Thankyou

37. References
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