Pathogen Recognition Receptors

Question 1

What kind of response does innate immune system have to bacteria

Answer 1

Inflammatory

Question 2

What response does innate immune system have to Viruses

Answer 2

Interferon response

Question 3

What fine tunes hose respond to pathogen

Answer 3

The signalling coming from Receptors

Question 4

What are TLR homologous too

Answer 4

Drosophila Toll

Question 5

What Resposne do TLR mainly induce

Answer 5

Pro-inflammatory response in innate immunity

Question 6

What are he functional clusters of PAMPs and what is the basis for the clusters

Answer 6

Lipid
Protein
Nucleic acid

Based on what TLR binds too

Question 7

Where are the TLR localised within cell

Answer 7

TLR1 , 2 , 6 and 4 are in cell membrane. Are lipid cluster

TLR 3, 7, 8, 9 in endosome
Membrane Are nucleic acid cluster

TLR 5,11,12are for flagellin

Question 8

What mediates TLR inflammatory response

Answer 8

NF-Kb and MAPK

Question 9

What is MyD88

Answer 9

A Toll/interleukin-1 receptor TIR
Essential. TIR and DD–containing adaptor protein

Facilitates formation of signalling complexes

Question 10

Which TLR uses multiple adaptor proteins

Answer 10

TLR4 ending in NF-Kb signalling

And or IRF3 signalling

Question 11

What TLR uses MyD88 independent pathway

What does it detect

What TIR adaptor protein does it use

Answer 11

TLR3
Detects dsRNA
Uses TRIF adaptor protein (or TICAM

TRIF platform for NF-Kb activation and IRF3 transcription factors

TLR3 is potent interferon activator

Question 12

Name a gene defect that affects negative regulation

Answer 12

A20 gene defect stops negative regulation of inflammatory

Causes inflammatory diseases

Question 13

What happens to TLR4?

Answer 13

Endocytsosed in endosome from cell membrane

Question 14

Mutations can lead to lack of NF-Kb. What can this cause

Answer 14

Loss of inflammation and therefore reverent Bacterial infections

Question 15

How have pathogens evolved to intervene with signalling?

Answer 15

Evolved to release inhibitory molecules to interfer with signalling and halt innate immune response

No/reduced cytokine/interferon response

Question 16

Why are TLR good drug targets

Answer 16

Direct immune response so can be effective drug targets

TLRs can be effective adjuvants in vaccines to skew immune response in certain direction

Question 17

Give an example of TLRs being used as adjuvant

Answer 17

PolylC in vaccines induce an anti viral response

Question 18

What is IRAK-4 deficiency

What happens to those with it

Answer 18

Means no MyD88 dependent TLR signalling

Suffer disposition to Bacterial infection

High chance of death before 2

Likely to have invasive pneumococcal diseases

Likely to have staphylococcal disease

Question 19

Where were dectin Receptors originally found

Answer 19

Dendritic cells

Question 20

What is dectin 1

Answer 20

TLR independent receptor for fungi

C-lectin related to mannose receptor

Question 21

Where is dectin-1 expressed

Answer 21

Expressed on immune cells (mainly phagocytes) at portals of pathogen entry

Neutrophils, monocytes and macrophages

Question 22

What is dectin-1 main receptor for

Answer 22

Beta-glucans from zymosan(yeast particle)

Carbohydrate polymer found in cell wall of fungi and some bacteria

Question 23

What do mutation in dectin genes cause

Answer 23

Infection and disease

Promoter mutations can affect expression levels of receptor

Leads to vulnerability to particular infection
E.g. Onychomycosis and vaginal candidiasis

Question 24

Role of intracellular receptors ?

Answer 24

Work when bacterium has evaded cell defences and infected a cell

Question 25

Structure of Nod1/nod2

Answer 25

TIR/CC—–NBD—-LRR

Caspase recruitment domain

Nucleotide binding domain

Leuxine rich repeat

Question 26

What does Nod1/Nod2 recognise

Answer 26

Peptidoglycans from bacteria

Only recognised once they enter cell

Leads to NFkB activation and pro inflammatory cytokines

Question 27

People with Nod2 knockout are?

Answer 27

More prone to oral listeria infections and salmonella as they replicate in cytoplasm

Question 28

What do other NLR proteins recognise?

Answer 28

DAMPS
PAMPS

degrdative constituents of peptidoglycan (component of Bacterial cell wall)

Question 29

What are degradation constituents of peptidoglycans

Answer 29

Nod2 ligand: muramyl dipeptide (MDP)

Nod1 ligand iE DAP (mostly gram -be bacteria)

NLR also found in plants and have similar domains

Question 30

How does NOD signalling work

Answer 30

1. Ligand binding induced NOD oligomerisation
2. Conformational changes present CARD domains
3. RIP2 kinase recruited and induces ubiquitylation
4. RIP2 recruits TAB-TAK1 complex which can phosphorylase the IKK and MAP3K complexes
5. Results in activation of NFkB and MAPK pathway
   Triggering inflammation

Question 31

What do defects in NOD genes lead too

Answer 31

Crohn’s disease due to defect in NOD2
Overstimulation of NFkB pathway leading to Overinflammation

Researchers not sure if due to too many bacteria or over detection of bacteria

I think could likely be both as trigger an effect that works together causing

Question 32

Nucleic acid sensing within cells happens where and how?

Answer 32

Occurs in cytsol
Main sensors are RNA helicases
Detect RNA via helicase domain and transmit signals through amino terminal CARD domains

Induce NFkB and IRF signalling pathways

Found in all different types of cells

Signalling proteins tend to cluster around mitochondria