Neuroimmune Interactions

Question 1

What is the resident immune cells of the CNS and what do they do

Answer 1

microglia (resident macrophage 15% of cells in CNS)- regulate inflammation, neuronal function

-likely some t/b cells (but normally in diseased states only as BBB makes it hard for immune cells to get in)

Question 2

Functions of microglia (4)

Answer 2

1. Phagocutosis- damaged cells, tau pros, amyloid beta
2. Synaptic pruning- fine tuning developing neuronal circuits
3. produce inflammatory markers/antimicrobial mediators
4. Coordination of T cell response (MHC)

Question 3

What occurs w microglia in alzheimers disease

Answer 3

may be unable to clear exercise amyloid beta or become inappropriately activated by plaques

Question 4

What immune structures are directly innervated by sympathetic nerves

Answer 4

Central (thymus/BM) and large peripheral organs (spleen/lymph) are directly inn by sympathetic nerves

Question 5

What is the steps of sympathetic activation of immune structures

Answer 5

1. Preganglionic neuronal releases AcH
2. Ach inn post ganglionic neuronal
3. Post gang releases norepinephrine
4. Norepinephrine inn effector tissue

Question 6

What inn the chromaffin cells and what does it release

Answer 6

Adrenal medulla releases E and NE into circulation (fight or flight response)

Question 7

What does E and NE bind to and what is the function of them

Answer 7

Adrenergic receptor

A receptors- typically cause smooth mm contraction

B receptors- Increase HR, cause smooth mm relation

Question 8

What type of adrenergic receptor is on adaptive immune cells and what is its function

Answer 8

Addaptive immune cells (T/B) primarily express B2 adrenergic receptor

-inhibited t cell responses

Question 9

What type of adrenergic receptor is on Macrophages and function

Answer 9

has a and b

• inflammatory impaired by b litigation
• inflammatory increased with a ligation

Question 10

Do lymphocytes have Ach receptors

Answer 10

1. nicotinic alpha 7 receptors

2. Muscarinic m1-5 receptors

Question 11

Nicotinic litigation on lymphocytes lead to what

Answer 11

• Differentiation of Tregs
• Supression of inflammatory cytokines
• release of anti-inflammatory responses

Question 12

Muscarinic litigation on lymphocytes lead to what

Answer 12

• evokes cytotoxicity
• proinflammatory mediators
• cell proliferation (Il2)

Question 13

What occurs in the anti inflammatory cholinergic relfelx (steps)

Answer 13

1. Sense inflammation in periphery by vagal afferents to NTS
2. Vagal efferents synapse on sympathetic ganglia that inn spleen releaseing NE
3. NE binds to b2 adregeneric receptors on t cells and release Ach
4. Ach binds to nicotinic receptors on macrophages limiting TNFA

ANTIinflammatory

Question 14

Steps of activation of HPA Axis (3)

Answer 14

1. Hypothalmus releases corticotropin releasing hormone (due to stress) which is secreted into the portal system
2. Ant pituitary senses CRH and releases adrenocorticotropic hormone (ACTH) into the blood

3, ACTH binds to receptors on adrenal glands which stim the release of glucocorticoids (cortisol) from the cortex

Question 15

What are the biological effects of cortisol

Answer 15

• Increases blood sugar via gluconeogenesis mainly

Question 16

What is the effects of cortisol on the immune system

Answer 16

• pontent immunosuppressive

- -Impaires release of pro inflammatory cytokines (TNFa, Il1, IL12) + cells

Question 17

What does cortisol act on (receptor) and what is the effect

Answer 17

glucocorticoid receptor which results in nuclear translocation and repression of inflammatory genes such as NFkappaB

Question 18

What can sustained stress cause to the body

Answer 18

• create an allostatic load
• Causes modifications of internal regulatory networks (lymphoid tissue atrophy, immune dysfunction and increased risk of infection

Question 19

What is fever and what is it mediated by

Answer 19

mediated by endogenous pyrogens (IL-1, TNFa, IL-6, PGE2)

Question 20

What can pyrogens interact w in the CNS

Answer 20

can interact with the circumventricular organs (CVOs) (which relay to the hypothalamus)

Question 21

When CVOs in the CNS detect pyrogens what occurs (/what is released)

Answer 21

COX1/2 enzymes activate and produce PGE2

PGE2 defuses inside the brain parenchyma activating thermosensitive neurone in the hypothalamus

Question 22

What produces pyrogen stimulated thermogenesis

Answer 22

• increasing metabolism of brown adipose tissue
• peripheral vessel vasoconstriction to prevent passive heat loss
• skeletal mm contraction (shivering)

Question 23

pathogenesis of sickness behaviour

Answer 23

Synthesis of pro inflammatory molecules inside CNS that diffuse into various neural compartments

Question 24

What is the peripheral blood immune signature in those w depression

Answer 24

• increased number of activated peripheral blood leukocytes

- elevated circulating levels of pro inflammatory cytokines and acute phase pros (IL 1, IL 6, TNFa)

Question 25

How do nociceptors detect pain (what is the series of bindings(

Answer 25

PGE2 (created by cox enzymes), binds to PGE2 receptors on nociceptors

-message is transmitted up spinal cord and relayed to the pain centres in the brain

Question 26

Pathogenesis of MS

Answer 26

Focal plaques are located near BBB (associated w its breakdown)
-Damage to the BBB increases the trans endothelial migration of activated t cells and b cells into CNS

*autoreactive t cells/antibodies against myelin antigens