Stress and Immunity

Question 1

Why is the term stress problematic?

Answer 1

Used liberally with regard to its scientific definition, and often circular defintion - “a state of stress occurs when an animal encounters an adverse physical or emotional condition which causes a disturbance of its normal physiological and mental equilibrium.”
= a stressor is a factor that causes stress

Question 2

Give 4 effects of glucocorticoids

Answer 2

Apoptoisis of T cells and eosinophils
Precents T cell and eosinophil proliferation
Gluconeogensis
Inhibits/prevents formation of collaginase/gelatinase

Question 3

What is PNI?

Answer 3

Pyschoneuroimmunology

Question 4

What did early PNI studies use a a stressor?

Answer 4

Electric shock

Question 5

What did early studies of PNI look for in vitro effects on?

Answer 5

T-cell proliferation (in response to mitogens plant derived lectins that bind carbohydrates and cross link T cell receptors)
Cytotoxic activity of NK cells (large granular lymphocytes that kill cells with v MHC expression)
Humoral immunity - primary and seconday antibody responses eg. to tetanus vaccine
Cell mediated immunity - resistance to syngenic tumour cell engraftment or tuberculin (Mantoux test)

Question 6

What type of energy do T cells rely on?

Answer 6

Glycoloysis not oxidative - therefore work well in anaerobic conditions
Will use oxidative when “resting”

Question 7

What was the flaw in early experiments?

Answer 7

Little attention paid to environment or behaviour response

• v effect if animal had control over stressor
• young rats exposed to dominant older male -> v antibody responses. Effect greatest in submissive rats cf. those that fought ie. immunosupression not associated with injury

Question 8

How may the type of stressor impact the results of studies?

Answer 8

> Electric shock - suppresses mitogen response and NK cells
Naloxone - opiate blocker abrogates effect on NK cells but not mitogen responses (therefore not a simple stresor event)
swim stress - suppresses mitigoen and NK
Naloxone no effect on either response

Question 9

What are stress and depression associated with in human studies?

Answer 9

reduced NK function

^ stress -> v Ab responses (primary nd secondary)

Question 10

Where are mast cells found?

Answer 10

Every tissue except the CNS they are like RBCs

Question 11

How does stimulation of a nerve with bradykinin affect mast cells?

Answer 11

Causes Ca influx (depolarisation)

Question 12

What does Ca influx in mast cells do to neurones?

Answer 12

Ca spike following antigen presentation -> spikes in neurone potentials

Question 13

How are monocyte-macrophages and NK cells described?

Answer 13

Sentinels of the immune system
Major source of pro-inflammatory cytokines (IL1, IL6, TNF and IFN)
Responses stimulated by PRRs

Question 14

How does septic shock occur?

Answer 14

LPS (lipopolysacharide) binds to TLRs on macrophages -> massive cytosine release
eg. colicking horse, ischeamia

Question 15

Give examples of actue virus infections

Answer 15

Heamorrhagic fever - high virulence influence -> inflammation of the lungs and asphyxia from drowning or death due to shock from cytokine storm

Question 16

How is inflammation associated with ischeamia?

Answer 16

DAMPs released due to sterile inflammation

Question 17

Give an example of am autoimmune inflammatory disease

Answer 17

rheumatoid arthritis

Question 18

What does vagal stimulation protect against in mice?

Answer 18

Septic shock and exogenous TNF adminstration

• cholinergic nerves innervate T helper lymphocytes
• v their inflammatory cytokine secretion
• stimulate T cell synthesis of Ach, suppressing excess cytokine production by monocytes

Question 19

What doe NA cause?

Answer 19

Paradoxically -> Ach production by memory T cells -> down regulation of monocytes
(explains why acute stress has same effect)

Question 20

How may immune responses affect the nervous system?

Answer 20

Lymphoid cells produce classical hormones eg. ACTH, GH

Stimulation of CNS by IL1 stimulates the HPA and causes release of GCs

Question 21

Give 4 specific ways the immune response may affect the nervous system

Answer 21

1. affernet nn stimulated by peripheral cytokines (vagus n, innervation of lymphoid organs including mast cells)
2. monocytes and endothelium in corroid plexus and cercumventricular organs respond to LPS by releasing iL1 - crosses the BBB
3. Uptake of IL1 from the circulation by specific receptors on blood vessel endothelium
4. IL1 receptors on endothelium, macrophage like cells in the brain vasculature release PGs etc. (microglial cells push dendrites thoruggh endothelium into blood vessel)

Question 22

Define sickness behaviour and fever

Answer 22

Motivational state responsible for reorganising perceptions and actions to enable ill individuals to better cope with an infection

Question 23

What are the different elements of sickness behaviour?

Answer 23

1. v motor activity
2. social withdrawal and reduced responsiveness
3. v food and water intake
4. ^ slow wave sleep
5. altered cognition -> ^ pain senstivity

Question 24

What is sickness behaviour mediated by?

Answer 24

Pro-inflammatory cytokines (IL-1, IL-6, TNF, interferons) released in response to PAMPs

Question 25

What can sickness behaviour be induced by?

Answer 25

> LPS endotoxin
- stimulates TLRs - pro-inflam cytokines (IL-1, IL-6, TNF) from monocytes/macrophages (v amount needed if injected straight into CNS)
Cytokines - IL1 and TNF have direct effect on CNS
- IL6 has indirect effec tby activating and priming monocytes

Question 26

hat is the purpose of the BBB?

Answer 26

Stop un-detoxified foods getting into brain or stop inflame cytokines

Question 27

Does chronic inflammation affect mood?

Answer 27

Chronix inflame disease associated with fatigue and depression (eg. cancer, allergic rhinitis)
BUT whether chronic fatigue syndromes/affective disorders can be caused by non-resolving inflammatory processes remains CONTROVESIAL
Complicatino with interplay between oxidative stress sinflam and energy metabolism

Question 28

How may diabetes lead to stiff joints?

Answer 28

Chronic ^ blood sugar -> glycosylated proteins seen most common in connective tissue due to slow turnover

Question 29

What is the turnover rate of glycated Hb?

Answer 29

120days

Question 30

What effect have IL1 antagonists or regulatory cytokines eg. IL10 been shown to have on sickness behaviour and depression?

Answer 30

Impressive study results - less clear in vivo
Measures of cytokines in plasma not shown positive results but may not reflect CNs accurately
Evidence for oxidative stress in ME/CFS patients
-> so are CFS inflammatory, immunological, infectious, metabolic or psychological in origin?

Question 31

What are the effects of sickness behaviour?

Answer 31

Can enhance survival
But long term effects -> catabolic tissue loss
- immunosupression may be adaptive by limiting inflammatory tissue damage

Question 32

What may immune hypersensitivity and depression be examples of ?

Answer 32

Maladaptive immune responses caused by unnatural combination of stimuli

Question 33

How do the effects of acute and chronic stress differ?

Answer 33

ACUTE
- ^ immune response by ^ monocyte function and release of pro-inflam cytokines
- indices sickness behaviour - allows resources to be concentrated on responding to damage/infection
CHRONIC
- overall impaired immune response
- corticostroids -> lymphocyte apoptoisis
- may cause behavioural abnormalities and may cause/exaccerabate depression