Pattern recognition receptors

Question 1

What is the problem with the adaptive immune system alone/ why do we need innate immunity and PRRs?

Answer 1

development of memory takes weeks and
may not have enough time before the
pathogen results in death, no memory needed
need a rapid response
vaccination may not act quick enough
cross reactivity in the adaptive immune system
need to be able to distinguish good and bad very quickly

Question 2

What do PRRs do?

Answer 2

Self-non-self discrimination by recognition of unchanging patterns of microbes

Question 3

What is pattern recognition?

Answer 3

PRRs do not recognise a single molecule but a broad range of molecules that share the same structural similarities

Question 4

What is pattern recognition contrasted with?

Answer 4

lock and key

Question 5

Describe a lock and key interaction

Answer 5

very specific - one specific molecule binds with one receptor to produce a conformational change leading to signalling

Question 6

Give examples of structures recognised by PRRs

Answer 6

gram +/-
dsDNA
CpG motifs

Question 7

Talk about three main discoveries that led to knowledge about PRRs

Answer 7

PRR knockout in fruit flies (Drosophilia) meant they could not distinguish ventral from dorsal
Fruit flies developed fungal infections when Toll not expressed
A mouse that dies with low doses of bacteria and can’t detect dead bacteria and had a mutation in a Toll gene

Question 8

What are the two types of PRRs?

Answer 8

secreted and circulating

cell associated

Question 9

Name some secreted and circulating PRRs

Answer 9

defensins
cathelicidin
mannose binding lectin
surfactant proteins A and B
CRP

Question 10

Give some examples of cell associated PRRs

Answer 10

TLRs
mannose receptor
NLRs
RLRs

Question 11

Where are cell associated PRRs found?

Answer 11

cell membrane

cytosol

Question 12

What do TLR1 and 2 and 6 detect?

Answer 12

G+ lipopeptides/lipoproteins

G+ bacterial cell walls

Question 13

What does TLR 3 detect?

Answer 13

dsRNA
mRNA
sees virus

Question 14

what does TLR 4 detect?

Answer 14

lipopolysaccharide in G- bacteria

Question 15

what does TLR 5 detect?

Answer 15

flagellin

Question 16

What does TLR 7/8 detect?

Answer 16

single stranded RNA/ viral RNA

Question 17

What does TLR 9 detect?

Answer 17

CpG DNA i.e. bacterial DNA - can tell the difference between bacterial DNAN and our own DNA

Question 18

What do TLRs do?

Answer 18

stimulate pro-inflammatory responses due to cytokine release e.g. TNF and IFN - alpha and beta

Question 19

What do Rig like receptors detect?

Answer 19

They are present intracellularly and can detect intracellular double stranded viral RNA and DNA

Question 20

What do rig like receptors do?

Answer 20

couple to interferon production to produce an antiviral response

Question 21

Explain the role of TLRs in homeostasis

Answer 21

homeostasis of neutrophil numbers (at a set level)

endotoxin tolerance in the newborn gut

Question 22

Explain the role of TLRs in damage recognition

Answer 22

Can detect hydrophobic molecules coming from inside cells that are damaged
can also detect host molecules in unfamiliar situations
means that TLRs couple pathways for wound healing AND response to bacteria to bring in cells to clear debris and stimulate new growth

Question 23

Give examples of extracellular damage molecules

Answer 23

fibrinogen

hyaluronic acid

Question 24

Give examples of intracellular damage molecules

Answer 24

heat shock proteins
mRNA
uric acid

Question 25

How do TLRs link to adaptive immunity?

Answer 25

1. activation of TLRs causes APCs to release cytokines to increase T cell activation
2. TLR4 agonists are used as adjuvants in vaccines

Question 26

What is the role of PRRs and disease?

Answer 26

1. recognising host molecules = autoimmune
2. may not recognise pathogens
3. overativation leads to increased inflammatory response e.g. COPD, asthma, athritis

Question 27

How can we use TLRs to target therapies?

Answer 27

1. enhance TLR signalling to improve immunity and TLR 4 agonists in vaccination
2. can inhibit signalling from TLRs to reduce sepsis, inflammation and arthritis
3. modification of the immune response towards Th and Treg responses
   so enhance, inhibit and modify