Lecture 27: Intracellular Receptors Flashcards
What alerts the innate immune system to strangers and danger ?
PAMPs and DAMPS
When are DAMPS released ?
In dangerous situations like stress, injury, cell death
What can detect PAMPS and DAMPS ?
- CLR
- TLR
- NLR
- RLR
What are CLRs ?
Transmembrane proteins localised at the plasma membrane
What do CLR recognise?
Glycans from the wall of fungi and some bacteri
What do CLR activate ?
Kinase syk and CARD9/MALT1/Bcl-10 adapter complex
What are TLRs
Transmembrane proteins localised either at the plasma membrane or in endosomes
What do TLR activate ?
MAP kinase, NFkappaB and IRF
What are NLR ?
Cytoplasmic sensors
What do NLPRs recognise ?
Bacterial, viral, parasitic and fungal PAMPS
What does AIM2 detect ?
Viral and bacterial DNA
What does AIM2 do ?
- Forms inflammasomes
- Activates caspase-1-mediated processing and activation of pro-interleukins IL-1B and IL18
What do NOD1 and NOD2 recognise ?
Bacterial peptidoglycan
What are RLRs ?
Cytoplasmic sensors of viral RNA
What do RLRs signal via ?
MAVS
What do RLRs trigger ?
Antiviral responses including the production of type 1 interferons
How many NLRS in human genome ?
22
What do all NLRs contain ?
- N-terminal effector domain
- Nucleotide binding domain
- Leucine rich repeats
When is apoptosome triggered ?
Following detection of cytosolic cyt. c by Apaf-1
When are inflammasomes triggered ?
Following detection of PAMP or DAMP by NLR
What do apoptosomes and inflammasome form ?
Large, multiprotein complexes to facilitate caspase activation
What to apoptosomes activate ?
Caspase 9
What do inflammasomes activate ?
Caspase 1
What is apoptosis ?
Programmed cell death, immunologically silent
What is pyropoptosis ?
Inflammatory cell death, IL-1B release inflammation
What can inflammasomes in cells be visualised as ?
Distinct specks r puncta
How is caspase 1 activated ?
NLRP3 inflammasome
What are the PYTHIN proteins ?
Pyrin and HIN-200 domain containing
What detects dsDNA in the cytosol ?
AIM2
What does caspase 11 sense ?
Intracellular LPS
What does caspase 11 activate ?
Non-canonical inflammasome
What was caspase 11 identified as ?
3rd regulatory signal for non-canonical inflammasome
What can active caspase 11 cleave ?
GSDMD
What does the cleavage of GSDMD lead to ?
Pyroptosis
What can caspase 11 not do ?
IL-1B or IL18 into their mature active forms
What do RIG-I receptors recognise ?
dsRNA containing 5’PPP or 5’PP
What do MDA5 form ?
Filaments along dsRNA backbone