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MDSC 321 > Lecture 9: Innate Pathogen Recognition > Flashcards

Lecture 9: Innate Pathogen Recognition Flashcards

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1
Q

Does the innate immune system recognize specific cells?

A

No, just self and non-self

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2
Q

What does the innate immune system recognize

A

Molecular patterns on different pathogens but absent from self

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3
Q

What does PAMP stand for?

A

pathogen associated molecular patterns

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4
Q

What are PAMPS recognized by?

A

Various pattern-recognition receptors (PRRs)

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5
Q

Where are PRRs located?

A

On most effector cells

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6
Q

Where does each PRR belong?

A

Cell surface and cytoplasmic receptors

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7
Q

What are the four classes of receptors reviewed?

A
  • TOLL-like receptors
  • Nucleotide binding domain leucine rich repeat receptors
  • Formylated-peptide receptors
  • retinoic acid inducible gene like
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8
Q

What is the abbreviation for TOLL-like receptors?

A

TLRs

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9
Q

What is the abbreviation for Nucleotide-binding domain leucine-rich repeat receptors

A

NLRs, NOD-like receptors

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10
Q

What is the abbreviation for Formylated-peptide receptors

A

FPRs

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11
Q

What is the abbreviation for retinoid-acid inducible gene-like

A

RLRs

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12
Q

Where were TLRs initially discovered?

A

In the fruit fly

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13
Q

What was TOLL initially thought to only do then found to do both in the fruit fly?

A
  • Initially played a role in patterning
  • then the translation and synthesis of antimicrobial peptides
  • defence against gram-positive bacteria and fungal pathogens
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14
Q

How many expressed TLR genes are in humans?

A

10

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15
Q

What is a ligand?

A

A signalling molecule

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16
Q

What are TLRs made of in there extracellular region (outside of the cell)?

A

Around 20 leucine-rich repeat

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17
Q

What are leucine-rich repeat?

A

Proteins that make a half circle (Horse shoe) shape

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18
Q

1A. Explain how bacteria activate TLRs in flies?

A

Recognition of bacteria by pathogen recognition receptors results in a bunch of steps that lead to a proteolytic (breakdown) splitting of a dimer of spatzle

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19
Q

2A. Explain how spatzle induces dimerization?

A

The split spatzle binds 2 TOLL molecules inducing dimerization

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20
Q

3A. What is dimerized TOLL able to do?

A

recruits:

  • 2 dMyD88
  • 2 Pelle
  • 1 TRAF3
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21
Q

4A. What does TRAF3 do?

A

Binds cactus kinase (enzyme) which introduces a phosphate group into cactus

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22
Q

5A. What does phosphorylated cactus do?

A

Releases transcription factor DIF

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23
Q

6A. What does DIF do?

A

Transcription and synthesis of antimicrobial peptides

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24
Q

Does each TLR have a different ligand specificity?

A

yes

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25
What are mammalian TLRs dependent on?
dimerization
26
What do mammalian TLRs bind directly to?
pathogen associated molecular patterns
27
What happens when PAMPs bind to TLRs
It induces dimerization of the TLR
28
What does the dimerization of TLRs (mammals) do?
It brings the cytoplasmic tails of the TLR molecules into close proximity
29
What does the tails of the TLRs in close proximity do?
Induces binding of signalling adapter molecules
30
What is the signalling adapter molecule for all TLRs except TLR-3?
MyD88
31
What is the signalling adapter molecule for TLR-4,3
TRIF
32
1B. What does the binding of MyD88 do?
- binding of MyD88 and MAL to TLR | - allows for binding of IRAK to MyD88
33
2B. What does the binding of IRAK to MyD88 do?
- IRAK binds TRAF-6 & TRICA1 | - these provide foundation for activation of TAK1
34
3B. What does the activation of TAK 1 do?
TAK1 phosphorylates IKK
35
4B. What does IKK do?
IKK phosphorylates IkB
36
5B. What does IkB do?
IkB is degraded releasing NFkB
37
6B. What does NFkB do?
- NFkB translocates to the nucleus | - transcribes target genes
38
1C. What does the binding of TRIF allow for?
- binding of TRIF to TLR3 or 4 | - allows for the binding of the kinases TBK1 and IkKe
39
2C. What do the kinases do?
- kinases become phosphorylated | - resulting in their activation
40
3C. What do the activated kinases do?
-activated kinase phosphorylates IRF3
41
4C. What does IRF3 do?
-IRF3 translocates to the nucleus and transcribes target genes
42
Do we generate different cell responses based on the PAMP?
Yes
43
Since most TLRs use the same signalling adapter molecule MyD88 how do we generate different cellular responses?
This is possible because: - subcellular location of the molecule - signal duration - additional signalling molecules
44
What is subcellular location
The location of TLRs are different not all are transmembrane receptors some are located in the endosome
45
What does the TLRs in the endosome recognize?
PAMPs from within the pathogen, RNA and DNA
46
What is signal duration?
The duration of the TLR signal can vary based on: - magnitude of the signal - number of receptors involved - negative regulators of the TLR
47
What does signal duration modify?
Resulting gene transcription profile
48
What does subcellular location modify?
Which target genes are transcribed
49
What is additional signalling molecules (specificity)
Most use MyD88 some use TRIF or a combination of TRIF and MyD88
50
Is TRIF regulated negatively by Tollip?
No
51
What do the different signalling molecule combinations result in?
Different cellular responses
52
What are NOD-like receptors (NLRs)?
NLRs are cytoplasmic receptors
53
What differs between NLR groups?
They differ depending on their amino-terminal structural motifs (distinct pattern on DNA or protein)
54
What does NOD have
N-terminal CARD motif
55
What does NLRP have?
N-terminal pyrin domain
56
1D. What is the first step in NOD-like receptors?
- binding PAMPs to NOD1 or 2 | - results in dimerization of the NOD
57
2D. What happens in NOD after dimerization?
-dimerization facilitates recruitment of the kinase RIPK2 to the CARD domain of the NOD
58
3D. What happens after RIPK2 is recruited to the CARD domain of NOD?
-RIPK2 phosphorylates TAK1, activating it
59
4D. What happens in NOD-like receptor after TAK1 is activated?
Follows same steps as 3B-6B, binding of MyD88
60
What is the formylated peptide receptor (FPRs)?
- Transmembrane pattern recognition receptor | - G-protein coupled receptor family
61
Where are formylated peptide receptors mainly expressed?
Neutrophils
62
What do formylated peptide receptors recognize?
Bacterial formylated peptides
63
What does activation of formylated peptide receptors give rise to?
Important secondary messengers: - Ca2+ - IP3 - cyclic AMP
64
What do formylated peptide receptors lead to?
-activation -polarization -mobility in neutrophils

MDSC 321 (21 decks)

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