Neuroimmune Interactions Flashcards
What is the resident immune cells of the CNS and what do they do
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)
Functions of microglia (4)
- Phagocutosis- damaged cells, tau pros, amyloid beta
- Synaptic pruning- fine tuning developing neuronal circuits
- produce inflammatory markers/antimicrobial mediators
- Coordination of T cell response (MHC)
What occurs w microglia in alzheimers disease
may be unable to clear exercise amyloid beta or become inappropriately activated by plaques
What immune structures are directly innervated by sympathetic nerves
Central (thymus/BM) and large peripheral organs (spleen/lymph) are directly inn by sympathetic nerves
What is the steps of sympathetic activation of immune structures
- Preganglionic neuronal releases AcH
- Ach inn post ganglionic neuronal
- Post gang releases norepinephrine
- Norepinephrine inn effector tissue
What inn the chromaffin cells and what does it release
Adrenal medulla releases E and NE into circulation (fight or flight response)
What does E and NE bind to and what is the function of them
Adrenergic receptor
A receptors- typically cause smooth mm contraction
B receptors- Increase HR, cause smooth mm relation
What type of adrenergic receptor is on adaptive immune cells and what is its function
Addaptive immune cells (T/B) primarily express B2 adrenergic receptor
-inhibited t cell responses
What type of adrenergic receptor is on Macrophages and function
has a and b
- inflammatory impaired by b litigation
- inflammatory increased with a ligation
Do lymphocytes have Ach receptors
- nicotinic alpha 7 receptors
2. Muscarinic m1-5 receptors
Nicotinic litigation on lymphocytes lead to what
- Differentiation of Tregs
- Supression of inflammatory cytokines
- release of anti-inflammatory responses
Muscarinic litigation on lymphocytes lead to what
- evokes cytotoxicity
- proinflammatory mediators
- cell proliferation (Il2)
What occurs in the anti inflammatory cholinergic relfelx (steps)
- Sense inflammation in periphery by vagal afferents to NTS
- Vagal efferents synapse on sympathetic ganglia that inn spleen releaseing NE
- NE binds to b2 adregeneric receptors on t cells and release Ach
- Ach binds to nicotinic receptors on macrophages limiting TNFA
ANTIinflammatory
Steps of activation of HPA Axis (3)
- Hypothalmus releases corticotropin releasing hormone (due to stress) which is secreted into the portal system
- 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
What are the biological effects of cortisol
- Increases blood sugar via gluconeogenesis mainly
What is the effects of cortisol on the immune system
- pontent immunosuppressive
- -Impaires release of pro inflammatory cytokines (TNFa, Il1, IL12) + cells
What does cortisol act on (receptor) and what is the effect
glucocorticoid receptor which results in nuclear translocation and repression of inflammatory genes such as NFkappaB
What can sustained stress cause to the body
- create an allostatic load
- Causes modifications of internal regulatory networks (lymphoid tissue atrophy, immune dysfunction and increased risk of infection
What is fever and what is it mediated by
mediated by endogenous pyrogens (IL-1, TNFa, IL-6, PGE2)
What can pyrogens interact w in the CNS
can interact with the circumventricular organs (CVOs) (which relay to the hypothalamus)
When CVOs in the CNS detect pyrogens what occurs (/what is released)
COX1/2 enzymes activate and produce PGE2
PGE2 defuses inside the brain parenchyma activating thermosensitive neurone in the hypothalamus
What produces pyrogen stimulated thermogenesis
- increasing metabolism of brown adipose tissue
- peripheral vessel vasoconstriction to prevent passive heat loss
- skeletal mm contraction (shivering)
pathogenesis of sickness behaviour
Synthesis of pro inflammatory molecules inside CNS that diffuse into various neural compartments
What is the peripheral blood immune signature in those w depression
- increased number of activated peripheral blood leukocytes
- elevated circulating levels of pro inflammatory cytokines and acute phase pros (IL 1, IL 6, TNFa)
How do nociceptors detect pain (what is the series of bindings(
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
Pathogenesis of MS
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
