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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
Q

5 general types of genes induced by TLR

A
  1. cytokines
  2. chemokines
  3. chemokine receptors
  4. AMPs
  5. co-stimulatory molecules
26
Q

what are CLRs?

A

superfamily of receptors with 1 or more C-type lectin-like domains with Ca2+-dependent binding to carbohydrates/glycans

27
Q

where are CLRs?

A

secreted OR transmembrane on innate and adaptive cells

28
Q

example of soluble CLR

A

collectins

29
Q

role of collectins (4)

A
  1. phagocytosis
  2. complement
  3. modulate inflammation
  4. inhibit/kill microbes
30
Q

example of transmembrane CLR

A

dectin-1

31
Q

role of dectin-1 (1)

A

trigger intracellular signaling

32
Q

4 results of CLR signaling

A
  1. phagosome to burst microbe
  2. arachidonic acid (prostaglandins)
  3. NETs
  4. cytokines/chemokines
33
Q

what does “RIG” stand for?

A

retinoic acid inducible gene

34
Q

where are RLRs?

A

intracellular (RIG-I, MDA-5, LGP2)

35
Q

role of RLRs

A

recognize viral RNA

36
Q

describe RLR signaling

A
  1. recognize viral RNA
  2. mt involved
  3. IRF induces IFNs, NFkB induces cytokines
  4. leads to antiviral + antibacterial responses
37
Q

what does “NOD” stand for?

A

nucleotide oligomerization domain

38
Q

4 domains of NLRs?

A
  1. CARD (caspase activation + recruitment domain)
  2. PYR
  3. NACHT
  4. LRR
39
Q

what is NACHT?

A

300-400 aa NTPase domain

40
Q

2 examples of NLRs

A

NOD1, NOD2

41
Q

what does NOD1 recognize? (2 examples)

A

PG with meso-DAP –> all gram neg, some gram post

  1. listeria
  2. bacillus
42
Q

what does NOD2 recognize?

A

MDP, PG of all gram pos and neg

43
Q

where are NOD1/2 located?

A

intracellular

44
Q

signaling pathways activated by NOD1/2

A

NFkB and MAPK

without NOD1/2, cannot activate those pathways

45
Q

does NOD1/2 affect innate or adaptive?

A

both

46
Q

healthy vs Crohn’s disease

A

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
Q

What is the inflammasome comprised of?

A

multi-protein complex
- sensor
- adaptor protein
- zymogen

48
Q

2 examples of inflammasome sensor

A
  1. NLR
  2. AIM2
49
Q

example of inflammasome adaptor protein

A

ASC

50
Q

example of zymogen

A

caspase1

51
Q

3 things the inflammasome leads to

A
  1. IL1b
  2. IL18
  3. pyroptosis
52
Q

what stimulates the inflammasome?

A

ion flux, mt dysfunction, ROS, metabolic factors

53
Q

canonical inflammasome?

A

uses caspase 1 –> IL18 and IL1B

54
Q

non-canonical inflammasome?

A

uses caspase 4-8 (human) and 11 (mouse)

55
Q

atypical inflammasome?

A

doesn’t detect PAMPs, but detects HAMPs and acts as signal integrator

56
Q

Example of HAMPs?

A

some bacteria cause Rho GTPase modifications –> pyrin, NLRP6 –> casp1 –> IL18, IL1B, pyroptosis

57
Q

role of IL18 in IEC defense

A

IL18 allows infected cell to be extruded via pyroptosis

58
Q

endometritis in cows

A

indicated by high IL1B postpartum due to caspase 4 inflammasome (NLRP3)

59
Q

4 examples of HAMPs/DAMPs in sterile inflammatory disease

A
  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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