neuroinflammation

Question 1

innate immunity
first line of defence

Answer 1

Skin & hair: physical barrier to microbes
Mucous membranes: mucus secreted to trap and kill
Bodily functions that expel microbes (mechanical)
Gastric secretions, tears, perspiration, lysozyme (chemical)

Question 2

innate immunity
second line of defence

Answer 2

interferons (interfere with viral replication)
complement (inflammation)
iron binding proteins (reducing iron available for bacterial growth)
antimicrobial proteins (peptides with antimicrobial activity)

Question 3

innate immunity
if second line of defence fails

Answer 3

NK cells (attack any unusual cell by perforin that causes catalysis)
Macrophages (phagocytosis, antigen presenting cells)

Question 4

adaptive immunity

Answer 4

specificity & memory
against specific invaders
t cells, b cells & antibodies

Question 5

microglia

Answer 5

resident immune cells of the brain (80% of brain immune cells)

Question 6

what makes central capillaries so different?

Answer 6

Structural Differences:
- Central has NO fenestrations (gaps between)
- More extensive tight junctions
Functional Differences:
- Impermeable to most substances
- Sparse pinocytic vesciular transport
- Increase expression of transport and carrier proteins: receptor mediated endocytosis
- Limited paracellular and transcellular transport

Question 7

3 complement pathways

Answer 7

lectin, alternate, classic

Question 8

alternative pathway?

Answer 8

inflammation via destruction of microbes by leukocytes (via C3a)

Question 9

classical pathway

Answer 9

phagocytosis via bounding of C3b to C3b receptor

Question 10

lectin pathway

Answer 10

cell lysis via MAC

Question 11

cytokines in degenerative disease (e.g. alzheimers)

Answer 11

resident CNS cells are predominant producers of pro-inflammatory cytokines

Question 12

cytokines in neuroinflammatory disease (e.g. MS)

Answer 12

pro-inflammatory cytokines are the majoy factor delivered by tissue-invasing leukocytes

Question 13

is neuroinflammation beneficial?

Answer 13

initial response is beneficial, long-term chronic overproduction of cytokines is detrimental
fuels degeneration

Question 14

cytokines

Answer 14

allow cells to communicate with one another, orchestrating complex processes
(a chemokine is also a cytokine)

Question 15

where are cytokines synthesised?

cns vs pns

Answer 15

cns: glial cells
pns: immune cells

Question 16

cytokines role

Answer 16

Host response to infection
Immune cell signalling
Inflammation

Question 17

TNF-a

Answer 17

microglia and astrocyte activation, regulation of BBB, febrile responses, glutamatergic transmission, synaptic plasticity

Question 18

TGF-B

Answer 18

Ability to transform cell lines, and induce cells to not need intracellular matrix (anchorage-independent)
Signals through receptors I, II, or III
Regulation of neuroinflammation and apoptosis in traumatic brain injury

Question 19

chemokines

Answer 19

stimulate chemotaxis of macrophages, neutrophils, regulate infiltration across BBB during inflammation and disease

Question 20

pro-inflammatory

Answer 20

IL-1a
IL-1B
TNF-a
IFN-y
IL-6
IL-17

Question 21

anti-inflammatory

Answer 21

IL-4
IL-10
TGF-B

Question 22

microglia during disease, injury, illness

Answer 22

Large scale cytokine production
Recruitment of peripheral immune cells
Pathogen destruction
Debris clearance
Tissue repair

Question 23

astrocyte activation

Answer 23

upregulation of GFAP
interact with endothelial cells -> increase BBB permeability and facilitate leukocyte infiltration

Question 24

NF-KB

Answer 24

pro-inflammatory responses
activated via cytokines from microglia
inactivated by AHR

Question 25

ischemia stroke

Answer 25

permanent of transient occlusion of a major brain artery or one of its branches

Question 26

common feature: alzheimer’s & parkinsons disease & frontotemporal dementia

Answer 26

microglia activation

Question 27

CVO

Answer 27

vascularised structures located around 3rd and 4th ventricles
lack BBB
Role in sodium & water balance, cardiovascular regulation, energy metabolism, immunomodulation
fenestrations present to allow sensory substances to enter

Question 28

SFO & bp

Answer 28

SFO drives blood pressure in LPK. rats linked to PVN
block PVN = less fall in bp
Therefore, SFO via PVN of hypothalamus

Question 29

RVLM

Answer 29

Stim increases bp and sna

Question 30

hypertensive rats

Answer 30

increased mRNA levels of pro-inflammatory cytokines in BM derived mononuclear cells (compared to normal)
elevated CCL2 in BM, serum, CSF

Question 31

normal bone marrow into hypertensive animal

Answer 31

levels go down
decreased activated microglia in hypothalamus