3 - Pattern Recognition Receptors - Angyal Flashcards

1
Q

What are PAMPs? and give 2 examples

A

Pathogen Associated Molecular Patterns

  • differ from self cells
  • critical to the survival/function of the pathogen therefore cannot differ too much and will most always be recognised by innate cels
    • shared by many microbes
  • eg lipoteichoic acid - G+ve, LPS G-ve
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2
Q

What are DAMPs?

A

Damage Associated Molecular Patterns

- host-derived molecules indicative of infection, stress, transformation, cellular damage

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3
Q

What are the 4 receptors of the innate immune system and describe v briefly what they do?

A

cytoplasmic signalling receptors, membrane-bound phagocytic, membrane-bound signalling, soluble receptor
- job is to recognise conserved/relatively invariant patterns frequently found on pathogenic surfaces

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4
Q

Give examples of PAMPs for bacteria, viruses, fungi and protozoa

A

Bacteria; G+ve lipoteichoic acid, G-ve LPS, flagellin (normally monomeric broken down version), unmethylated CpG DNA, N-formylated proteins (fMLP)
Viruses; dsRNA
Protozoa; mannose rich glycans, GPI-linked proteins
Fungi; B-glycan, chitin

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5
Q

Give some examples of DAMPs

A
  • mitochondrial components (should be in mitochondria)
  • DNA (should be in nucleus)
  • phosphatidylserine. normally kept on intracellular side of membrane by flippases. when cell undergoes apoptosis flippases stop working, PS can then be released -> extracellular side
  • HMGB1 (high mobility group box 1 proteins), histones that should be bound to DNA but found in cytoplasm
  • uric acid - indicative of kidney damage, oxidative stress
  • heat shock proteins - eg Hsp70 responds under stress
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6
Q

Are PRRs expressed exclusively by cells of innate immune system?

A

NO PRRs expressed by both immune and non immune cells (encoded for by germline)

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7
Q

Give the 4 types of PRR and give examples of each

A
  • soluble receptors (complement, ficolins, MBL)
  • membrane bound phagocytic (complement, mannose receptors, scavenger)
  • membrane bound signalling (scavenger, TLR4)
  • cytoplasmic signalling (NOD-like, TLR7/8)
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8
Q

What do soluble receptors recognise?

A

DAMPs - altered self/non self molecular patterns

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9
Q

What is efferocytosis and why is it important that it is done?

A

soluble receptors are important opsonins that aid the clearance of apoptic cells. prevents inflammation being induced in tissue when not needed

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10
Q

What are NETs and name 2 soluble receptors that recognise these?

A

NETs - released genomial, mitochondrial DNA

recognised by collectins , ficolins

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11
Q

What is the long name for collectins?

A

collagenous lectin-binding proteins

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12
Q

What is the structure of a collectin?

A

collagen domain and a Ca2+ binding domain

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13
Q

Describe the 2 types of collectin proteins from the lecture

A

SP-A. expressed by lung alveolar macrophages that can bind to and aid clearance of pathogens
SP-D binds to genomic DNA/phospholipids and Abs and can also aid in the clearance of pathogens

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14
Q

Describe the 3 types of membrane - bound phagocytic receptors and

A
  • scavenger receptors. recognise anionic polymers, acetylated LDL eg CD14 recognises LPS, CD36 -> LDL
  • complement receptors
  • C-type lectins eg macrophage mannose receptors
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15
Q

What type of receptor (of the 4 described) are chemotactic receptors on phagocytes?

A

membrane-bound signalling

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16
Q

How do chemotactic receptors on phagocytes allow phagocytes to stop infection? Give an example

A

chemotactic receptors bind CHEMOATTRACTANTS and allow them to move to the site of infection, they also increase efficency of intracellular killing. eg neutrophils have fMLP receptors which bind to Nformylated proteins (common on bacteria) and therefore migrate to the site of infection because higher conc of fMLP here

17
Q

Describe TLRs ie how many in humans? where they’re located? how it differs from drosophila toll? names of different Toll.

A

Toll-Like receptors. membrane-bound signalling. 10 in humans/12 in mice that each recognise distinct PAMPs. located on cell surface and on intracellular membranes eg endoscopes. differ to drosophila toll because bind directly to microbial ligands (drosophila interact w/ pathogen products vi other proteins). TLR1/2/4/5 on SURFACE and TLR3/7/8/9 ON ENDOSOMAL membrane

18
Q

Draw the 2 structures of a TLR (one of the individual structures and a 2nd of how they all join up)

A

311 - 3

19
Q

Name 2 TLRs, what are their ligands and what cells are they found in?

A

TLR3 - dsRNA (viruses) found in macrophages, dendritic cells, intestinal epithelium
TLR4 (and MD-2/CD14) - LPS (G-ve), Lipoteichoic acid (G+ve).
Found on macrophages, dendritic cells, mast cells, eosinophils

20
Q

Describe the complex that recognises LPS

A

TLR4 monomer with MD-2 adaptor protein required to reach cell surface membrane. CD14 (membrane bound or free) concentrates (extracellular) LPS and allows it to bind to TLR4. promotes dimerisation. (shown in 311-3 word)

21
Q

Draw a diagram and explain the TLR mediated signalling pathway.

A

see 311 - 3 word doc

22
Q

Name the 2 types of cytoplasmic receptors.

A

NOD-like receptors (NLRs) and RIG-1 like receptors

both PRRs

23
Q

What does NOD stand for?

A

nucleotide binding oligomerisation domain

24
Q

What are NLRs and what is the result of their activation?

A

cytoplasmic sensor receptors that recognise bacterial components eg peptidoglycan, flagellin. signal expression of pro-inflammatory cytokines and (for eg NLRs in neutrophils) signal expression of enzymes to produce NO.
can also trigger assembly of inflammasomes.

25
Q

What are the functions of NOD1/2?

A

have caspase recruitment domain (CARD)

recruit components of cascade cascade -> apoptosis

26
Q

What are inflammasomes?

A

cleave and activate procytokines to cytokines so they can become active and released from cell

27
Q

What does RIG-1 like receptor stand for?

A

retinoic acid inducible gene

28
Q

What do RIG-1 like receptors recognise and what do they result in following activation?

A

Recognise viral ssRNA uncapped that is produced w/in the cell. signal expression of interferons (because these are v helpful in viral responses)