Lecture 3: Stress and immune function

Question 1

What is psychoneuroimmunology?

Answer 1

The broad interdisciplinary research field that addresses the interactions of the CNS, endocrine system and the immune system

Question 2

What is the role of a stressor?

Answer 2

A stressor is a stimulus that activates the HPA axis and SNS to help an organism to adapt physiologically to deal with a threat. They can categorize stressors by duration and course.

Question 3

How do stressors influence the immune response?

Answer 3

• brief stressors can enhance some aspects of immune function like trafficking cells from lymphoid organs to peripheral blood and skin
• can increase susceptibility to infectious agents and severity of infectious disease, diminish immune response strength to vaccines
• can increase production of pro-inflammatory cytokines

Question 4

How does the HPA axis connect to immune-system dysregulation?

Answer 4

• Stressors can activate the sympathetic-adrenal-medullary axis, HPA axis and release of pituitary and adrenal hormones like ACTH, growth hormone and prolactin which are influenced by negative emotions and negative events. Hormones can bind to receptors directly or indirectly by inducing dysregulation of cytokines

Question 4

How is stress assessed?

Answer 4

By asking about number and type of recent significant stressful life changes and rate their perceptions of stress. Or also by studying the psychological and immunological responses of those experiencing a distress-generating event or following natural disasters

Question 5

How is communication between the CNS and immune system bidirectional?

Answer 5

Cytokines influences production of CRH by the hypothalamus which affects the HPA axis and releasing hormones which dysregulates immune function

Question 6

What is the relationship between negative emotions and vaccines?

Answer 6

• modulates antibody and T cell responses to antiviral vaccines
• antibody responses to antibacterial vaccines was influenced by stress (delayed, weaker and short-lived immune responses)
• adults who shower poorer responses to vaccines have higher rates of clinical illness

Question 7

What have mice studies found about restraint stress?

Answer 7

Mice were placed in tubes and the immune response to the influenza virus was alerted due to the suppression of pro-inflammatory and anti-inflammatory cytokine responses. Cell trafficking was significantly reduced in the stressed animals. In humans, stress led to clear deficits in cellular and humoral immune responses. Antiviral vaccines also performed less well in inducing stress responses

Question 8

How has research investigated susceptibility to infection with distress?

Answer 8

• healthy volunteers were given 5 strains of the respiratory virus and were given a stress index
• no difference in risk between the strains
• those who experienced more interpersonal difficulties with family or friends were more likely to develop a cold

Question 9

What has research found about HIV infection?

Answer 9

• when animals were in the stable social condition, they had lower concentrations of SIV RNA in plasma and survived longer than those in the unstable conditions
• faster progression of HIV in men with more stressful life events and less social/interpersonal support

Question 10

How is HSV (herpes) affected by stress?

Answer 10

Stress increases the development and severity of HSV in the peripheral nervous system and CNS and suppresses components of primary and memory T lymphocyte responses. HPA and SAM play a central role in mediating stress-induced modulation of immunity. When exposed to stressors there was more reactivation of the latent virus as well.

Question 11

What has been found on EBV and stress?

Answer 11

• EBV also can be modulated by psychological stressors and can reactivate latent EBV
• can downregulate specific T-cell response to the virus
• glucocorticoid hormones can reactivate the virus
• different types of stress could impact this reactivation

Question 11

What can influence the incidence of Herpes zoster?

Answer 11

• caused by the reactivation of VZV which increases with age and psychological stress which leads to a decline in cell-mediated immunity

Question 12

What is the process of wound healing?

Answer 12

1. Vasoconstriction and blood coagulation is followed by platelet activation and platelet-derived growth factors
2. Chemoattractant factors are released by injured parenchymal cells
3. These promote migration of phagocytes and other cells to the wound
4. The proliferation phase includes recruitment and replication of cells for tissue regeneration and capillary regrowth
5. Wound remodelling

Question 13

What is the role of cytokines in wound healing?

Answer 13

They protect against infection and prepare injured tissue for repair by enhancing the recruitment and activation of phagocytes. Stress can disrupt this production of cytokines (wounds heal more quickly in holidays than the exam periods). Glucocorticoids can slow this healing process by altering cytokine function

Question 14

Suction-blister model

Answer 14

Measuring immune responses after raising several blisters and removing their roofs and covering with plastic templates with wells will allow cells to migrate sites and collect there.

Question 15

How does stress influence inflammation?

Answer 15

Stressors can increase pro-inflammatory cytokines and depression as well as stressors can increase responsiveness to following stressful events and to antigen challenge. This increase in cytokines has been linked to age-related diseases and conditions and cancers.

Question 16

What has research found about the pre-mature aging of immune cells?

Answer 16

Higher levels of perceived stress was linked to lower telomerase activity and shorter telomere length which has been linked to aging

Question 17

Functions of the immune system

Answer 17

• to protect against infectious disease
• destruction of malignant transformations
• promotion of tissue repair

Question 18

Effects of the immune system

Answer 18

• Discomfort and sickness
• Tissue damage
• Often disease is not caused by the pathogen, but by the
  immune system responses to the pathogen

Question 19

Different types of immune cells

Answer 19

Also known as white blood cells and leukocytes which are produced by stem cells in bone marrow.
Lymphoid lineage: lymphocytes
Myeloid lineage: granulocytes, monocyte, mast cell and dendritic cell

Question 20

General immune response

Answer 20

1. Infection
2. Microbes intercepted by sentinel cells
3. Microbes presented to lymphocytes
4. Lymphocytes become effector cells

Question 21

Front line defenses

Answer 21

1. Physical barriers-> body temp
2. Chemical barriers-> antimicrobial proteins (lysozymine, lactoferrin, antibodies)
3. Phagocytic cell responses like neutrophils, monocytes, dendritic cells

Question 22

Phagocytic cells

Answer 22

• use pattern recognition receptors to detect pathogens
• 3 functions: to eat and destroy the infectious agent, initiate the inflammatory response, transport antigen to lymphoid organs

Question 23

Activation

Answer 23

Cellular or molecular changes that initiate or facilitate an immune response

Question 24

Antigen

Answer 24

Formal meaning:
Molecule that initiates the production of antibodies
(antibody generator)
Usual meaning:
Any molecule that activates the immune system

Question 25

Where do antigen-presenting cells migrate to?

Answer 25

2nd lymphoid tissues through draining lympathics to concentrate antigen and lymphocytes to maximize the change that a unique antigen will encounter its unique receptor

Question 26

Different types of immune cells

Answer 26

• naive lymphocytes which can become antigen-eliminating effector cells
• cytotoxic T cells which destruct and kill virally infected cells
• helper T cells which regulate the immune system and release cytokines
• B lymphocytes produce antibodies which are secreted from antigen receptors

Question 27

2 types of immune response and their characteristics

Answer 27

Innate immunity: lymphocytes, broad specificity of pattern recognition, fast response and does not learn
Adaptive immunity: narrow specificity of unique molecules, slow response at first and fast response on subsequent encounter, learns and develops memory

Question 28

Phases in lymphocyte development

Answer 28

1. Naive cells
2. Effector cells like helper T cells, cytotoxic T cells, B cells
3. Memory cells which leads to life long protection
4. With re-infection the immune response is faster and more vigorous

Question 29

What is the relationship between depression and the immune system?

Answer 29

• depressive symptoms predict slower wound healing
• not depression specifically but psychopathology more likely to predict rheumatoid arthritis and pain
• elevated inflammation and cytokines were found in depressed patients-> inflammation seen as a mediator of depression
• inflammation can cause sickness behaviour which involves negative mood, irritability, fatigue and reduced motivation, psychomotor retardation, hyperalgesia, social withdrawal
• anti-inflammatory drugs have anti-depressant effects

Question 30

The immune enhancement model (from ChatGPT do not need to learn)

Answer 30

Explains how acute stress can enhance immune function rather than suppress it.
Acute Stress as a Positive Stimulus:
Short-term or acute stress (e.g., the body’s response to an immediate challenge like a competitive event or injury) can enhance immune function. This is in contrast to long-term or chronic stress, which is harmful.
During acute stress, the body enters a state of heightened alertness, preparing it to deal with possible threats like infections or injuries. This boosts the immune system temporarily.
Fight-or-Flight Response:
In stressful situations, the body releases hormones like adrenaline and cortisol. These hormones, in moderate amounts, help direct immune cells (like leukocytes) to areas of the body that are likely to face an infection or injury (e.g., the skin).
This enhanced immune response helps the body deal with potential harm by making sure immune cells are in place to respond to infections quickly.
Window of Enhancement:

The immune-enhancing effect is time-limited and occurs during a specific window of stress. Once the stressful event passes, the body returns to baseline, and the immune system returns to its normal functioning.
Effects on Wound Healing and Vaccination:

This model explains why acute stress might lead to faster wound healing or more effective responses to vaccinations, as it temporarily boosts immune surveillance and preparedness.
Context of Stress:

The model emphasizes that context matters. Stress during an event that requires immune readiness (e.g., surgery or fighting an infection) can be beneficial, while stress in situations where it’s chronic or ongoing can be damaging

Question 31

What is required for experimental research?

Answer 31

1. Participants are healthy
2. Intervention does not cause complaints
3. Allowed by ethics review board
   Minimal health risk or discomfort

Question 32

What did an experiment looking into vaccination and theory of mind find?

Answer 32

When being given a salmonella vaccination and reported no physical symptoms/mood effects led to worse accuracy into reading the mind the eyes test (impaired theory of mind- ability to infer other’s mental states), reduced motor speed and reduced adaptive behaviour (less accuracy in change and overlearning compared to placebo) and increased brain fog (lower ability to direct and maintain attention) and more negativity bias

Question 33

How does inflammation impair dopamine-related functions?

Answer 33

Reduces:
* D-receptor expression
* D-receptor function
* Transmitter availability
All of which play a role in anhedonia and psychomotor retardation