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Fundamental Immunology MCQ #1 > LECTURE 4 > Flashcards

LECTURE 4 Flashcards

1
Q

4 immune components of host microbiota

A
  1. mucous
  2. epithelial barrier
  3. AMP
  4. TLRs, NODs
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2
Q

describe mucous in host microbiota

A

inner layer = firmly adherent
outer layer = loosely adherent

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3
Q

3 cells in epithelial cells in host microbiota

A
  1. enterocytes
  2. goblet cells
  3. paneth cells
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4
Q

3 AMPs in host microbiota

A
  1. defensins
  2. C-type lectins
  3. galectins
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5
Q

describe PAMPs

A

conserved, specific to microorganism, and essential for viability

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6
Q

examples of PAMPs for bacteria, virus, parasite, and yeast

A

bacteria: LTA, PG, lipoprotein, DNA, flagellin, LPS

virus: coat protein, nucleic acid

parasite: GPI anchor

yeast: zymosan, B-glucan

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7
Q

what type of receptors are TLRs?

A

type 1 transmembrane receptors

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8
Q

2 types of TLRs and their domains

A
  1. IL-1R: Ig-like domain and TIR domain
  2. TLR: LRR domain and TIR domain
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9
Q

3 roles of TIR

A
  1. recruit signaling molecules
  2. activate gene transcription
  3. inflammation, anti-microbial
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10
Q

TLRs are homologs of:

A

drosophila Toll receptor for immunity and development (toll-mutant fly = fungal infection)

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11
Q

how many TLRs in mammals?

A

12
- 1-10 = human
- 1-9, 11-13 = mouse

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12
Q

mTLR11 and hTLR8

A

mTLR11 = profilin

hTLR8 = ssRNA

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13
Q

describe TLR8 in mice?

A

missing 8 aa –> humanized mouse with hTLR8 gene, found involved in autoimmunity and more TLR8 copies = wasting disease

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14
Q

TLR1,2,4,6

A

bacterial lipids
2/6 = gram pos
4 = LPS

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15
Q

TLR3,7,8,9

A

nucleic acid (detected on organelle membrane)
3/7/8 = viral RNA
9 = bacterial DNA

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16
Q

TLR5/10

A

bacterial or parasitic proteins

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17
Q

2 classes of effector proteins for TLRs

A
  1. sorting adaptors
  2. signaling adaptors
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18
Q

describe sorting adaptors and 2 examples

A

survey PM and endosomal membrane for dimerized TLRs –> thru myristoylation and interacting w active phosphoinositides

  1. TIRAP –> TIR domain-containing adaptor prot
  2. TRAM –> TRIF-related adaptor molecule
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19
Q

2 examples of signaling adaptors

A
  1. MYD88
  2. TRIF
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20
Q

TIRAP pathway

A

most common!!

TIRAP recruits myddosome –> MYD88 and IRAK S/T kinases

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21
Q

3 pathways activated by TLRs

A
  1. MAPK
  2. NFkB –> cytokines/chemokines
  3. IRF –> IFN
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22
Q

pro-inflammatory cytokines?

A

IL6, TNFa, IL12

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23
Q

anti-inflammatory cytokines?

A

IL10

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24
Q

role of type I IFN?

A

anti-viral

25
5 general types of genes induced by TLR
1. cytokines 2. chemokines 3. chemokine receptors 4. AMPs 5. co-stimulatory molecules
26
what are CLRs?
superfamily of receptors with 1 or more C-type lectin-like domains with Ca2+-dependent binding to carbohydrates/glycans
27
where are CLRs?
secreted OR transmembrane on innate and adaptive cells
28
example of soluble CLR
collectins
29
role of collectins (4)
1. phagocytosis 2. complement 3. modulate inflammation 4. inhibit/kill microbes
30
example of transmembrane CLR
dectin-1
31
role of dectin-1 (1)
trigger intracellular signaling
32
4 results of CLR signaling
1. phagosome to burst microbe 2. arachidonic acid (prostaglandins) 3. NETs 4. cytokines/chemokines
33
what does "RIG" stand for?
retinoic acid inducible gene
34
where are RLRs?
intracellular (RIG-I, MDA-5, LGP2)
35
role of RLRs
recognize viral RNA
36
describe RLR signaling
1. recognize viral RNA 2. mt involved 3. IRF induces IFNs, NFkB induces cytokines 4. leads to antiviral + antibacterial responses
37
what does "NOD" stand for?
nucleotide oligomerization domain
38
4 domains of NLRs?
1. CARD (caspase activation + recruitment domain) 2. PYR 3. NACHT 4. LRR
39
what is NACHT?
300-400 aa NTPase domain
40
2 examples of NLRs
NOD1, NOD2
41
what does NOD1 recognize? (2 examples)
PG with meso-DAP --> all gram neg, some gram post 1. listeria 2. bacillus
42
what does NOD2 recognize?
MDP, PG of all gram pos and neg
43
where are NOD1/2 located?
intracellular
44
signaling pathways activated by NOD1/2
NFkB and MAPK without NOD1/2, cannot activate those pathways
45
does NOD1/2 affect innate or adaptive?
both
46
healthy vs Crohn's disease
healthy: - NOD2 maintains barrier surveillance and control inflammation - recognize PG and induce inflammation, increase IL22 to make AMP Crohn's - mutant NOD2 causes lots of inflammation, reduced barrier function - more immune cells - DYSBIOSIS
47
What is the inflammasome comprised of?
multi-protein complex - sensor - adaptor protein - zymogen
48
2 examples of inflammasome sensor
1. NLR 2. AIM2
49
example of inflammasome adaptor protein
ASC
50
example of zymogen
caspase1
51
3 things the inflammasome leads to
1. IL1b 2. IL18 3. pyroptosis
52
what stimulates the inflammasome?
ion flux, mt dysfunction, ROS, metabolic factors
53
canonical inflammasome?
uses caspase 1 --> IL18 and IL1B
54
non-canonical inflammasome?
uses caspase 4-8 (human) and 11 (mouse)
55
atypical inflammasome?
doesn't detect PAMPs, but detects HAMPs and acts as signal integrator
56
Example of HAMPs?
some bacteria cause Rho GTPase modifications --> pyrin, NLRP6 --> casp1 --> IL18, IL1B, pyroptosis
57
role of IL18 in IEC defense
IL18 allows infected cell to be extruded via pyroptosis
58
endometritis in cows
indicated by high IL1B postpartum due to caspase 4 inflammasome (NLRP3)
59
4 examples of HAMPs/DAMPs in sterile inflammatory disease
1. steatohepatitis --> ER-stress in hepatocytes --> NLRP3 2. aging --> metabolic, cardio, neurodegenerative diseases --> homeostatic defects 3. AD --> amyloid-B taken up by autophagy, mt oxidative stress --> NLRP3 4. COVID --> K+ efflux --> NLRP3, increase LDH

Fundamental Immunology MCQ #1 (6 decks)

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