Pattern recognition receptors Flashcards
What is the problem with the adaptive immune system alone/ why do we need innate immunity and PRRs?
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
What do PRRs do?
Self-non-self discrimination by recognition of unchanging patterns of microbes
What is pattern recognition?
PRRs do not recognise a single molecule but a broad range of molecules that share the same structural similarities
What is pattern recognition contrasted with?
lock and key
Describe a lock and key interaction
very specific - one specific molecule binds with one receptor to produce a conformational change leading to signalling
Give examples of structures recognised by PRRs
gram +/-
dsDNA
CpG motifs
Talk about three main discoveries that led to knowledge about PRRs
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
What are the two types of PRRs?
secreted and circulating
cell associated
Name some secreted and circulating PRRs
defensins cathelicidin mannose binding lectin surfactant proteins A and B CRP
Give some examples of cell associated PRRs
TLRs
mannose receptor
NLRs
RLRs
Where are cell associated PRRs found?
cell membrane
cytosol
What do TLR1 and 2 and 6 detect?
G+ lipopeptides/lipoproteins
G+ bacterial cell walls
What does TLR 3 detect?
dsRNA
mRNA
sees virus
what does TLR 4 detect?
lipopolysaccharide in G- bacteria
what does TLR 5 detect?
flagellin
What does TLR 7/8 detect?
single stranded RNA/ viral RNA
What does TLR 9 detect?
CpG DNA i.e. bacterial DNA - can tell the difference between bacterial DNAN and our own DNA
What do TLRs do?
stimulate pro-inflammatory responses due to cytokine release e.g. TNF and IFN - alpha and beta
What do Rig like receptors detect?
They are present intracellularly and can detect intracellular double stranded viral RNA and DNA
What do rig like receptors do?
couple to interferon production to produce an antiviral response
Explain the role of TLRs in homeostasis
homeostasis of neutrophil numbers (at a set level)
endotoxin tolerance in the newborn gut
Explain the role of TLRs in damage recognition
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
Give examples of extracellular damage molecules
fibrinogen
hyaluronic acid
Give examples of intracellular damage molecules
heat shock proteins
mRNA
uric acid
