Pattern Recognition Receptors Flashcards
What are PRRs?
Pattern recognition receptors- receptors used by innate immune system to detect the presence of infection
What do PRRS recognise?
PAMPs- pathogen-associated molecular patterns
DAMPs- damage-associated molecular patterns
What are PAMPs?
Conserved structural motifs in pathogens
What are DAMPs?
Molecules released by stressed, damaged, or dying host cells
What is the role of PRRs?
Trigger rapid innate anti-microbial/immune responses.
What are C-type lectin receptors (CLRs)?
Family of PRRs characterised by the presence of one or more carbohydrate recognition domains (CRDs), which require calcium for binding
What do CLRs bind to?
Carbohydrates from various pathogens (bacteria, fungi and viruses)
What is a good example of a c-type lectin receptor?
Dectin-1
What does dectin-1 recognise?
Fungal carbohydrate B-glucan, which is found in fungal cell walls.
Evidence of role of Dectin-1
Dectin-1 KO mice are more susceptible to Candida albicans
What are toll like receptors?
Toll like receptors (TLRs) are a type of PRR that recognise PAMPs (and sometimes DAMPs).
They are transmembrane proteins found on the cell surface and within endosomes
How many TLRs are there in humans?
There are 10 distinct TLRs in humans, each specialised in recognising different PAMPs
Give 2 examples of PAMPs that specific TLRs recognise
Lipopolysaccharide (found in g-ve bacteria outer cell membrane) is recognised by TLR4
WHEREAS
Fungal DNA is recognised by TLR9
What is the structure of TLRs?
They have a characteristic horseshoe shape.
They are often found as dimers, and can be homo (same TLR) or hetero (different TLRs) dimers
What are the TIR domains of TLRs?
The cytoplasmic end of the TLRs (the bit that sticks out into the cytoplasm).
For ones on cell surface that’s obvious yunno, and for endosome ones its the same but like sticking into the endosome that is floating in the cytoplasm ygm?
What is the important of TIR domain?
They are essential for initiating downstream signalling
How do TIR domains initiate downstream signalling?
Once a PAMP is recognised, TLRs will dimerise, bringing their TIR domains together.
The close proximity of the TIR domains recruits adaptor proteins, initiation downstream signalling pathways
How and why must TLR activation be regulated?
One important way in which TLR activation is regulated is by compartmentalisation.
It ensures that TLRs are only exposed to invasive microbes (microbes that aren’t where commensal microbes are)
Regulatory proteins ensure trafficking and maturation of TLRs only within specific compartments.
This is crucial to avoid them being activated by commensal microbes, to prevent constant inflammation
Example of why regulation of TLRs is important
Over 1000 different commensal bacteria in the large intestine
Give an example of a microbe that can modulate TLR activation
Candida albicans can induce IL-10 through TLR2. IL-10 is an immunosuppressant, which allows the pathogen to prevent immune activation
What are NLRs?
NOD (nucleotide-binding oligomerisation domain)-like receptors are another family of PRRs. They are cytoplasmic (intracellular) sensors of infection/danger
What does NOD1 recognise?
iE-DAP, which is primarily from Gram - bacteria
What does NOD2 recognise?
MDP, which is found in all types of peptidoglycan (so both Gram + and -)
What are inflammasomes?
Intracellular protein complexes that act as sensors of danger signals, triggering the activation of caspase-1, which in turn leads to the release of pro-inflammatory cytokines
