2C. Pattern Recognition Receptors (PRRs)
Protein sensors in and on cells (some soluble) that detect evidence of infection or tissue damage.
They launch a “signalling cascade” designed to deal with the threat.
Intro
- Engagement of a PRR triggers intracellular signalling cascades that activate transcription factors such as NF-kB and IRFs leading to rapid production
Signals
PAMPs
Pathogen-Associated Molecular Patterns
DAMPs
Damage-Associated Molecular Patterns
PAMPs
PAMPs are molecules, sequences, or patterns only found in pathogens.
Examples:
- Components of bacterial cell walls
- Nucleic acids found in viral genomes
Can Include
- bacterial lipopolysaccharide
- Unmethylated CpG DNA
- Viral Double Stranded RNA
PAMPs are highly conserved:
- Many different pathogens share them
- They are molecules pathogens need to survive
- This prevents pathogens from easily evolving away from innate immune recognition.
DAMPs
DAMPs are host molecules in the wrong place at the wrong time.
Example:
- ATP is rarely found outside cells
- Extracellular ATP suggests cell damage
Can include:
- Extracellular ATP
- Heat shock proteins
- HMGB1
Location of PRRs
PRRs can be:
- Extracellular (on the cell surface)
- Cytosolic
- Endosomal (on endosomes formed during endocytosis)
Distribution of membrane-bound PRRs can be polarised.
Example:
- Intestinal epithelial cells have most PRRs on the basolateral side to avoid constant inflammation from GI microbiota.
Basolateral = facing adjacent cells
Major PRR Families
Four major families of PRR are commonly taught
- Toll-like receptors (TLRs)
- C-Type lectin receptors (CLRs)
- NOD-like receptors (NLRs)
- RIG-I-Like receptors (RLRs)
TLRs (Toll-Like Receptors)
- Homologs of the Toll fruit fly protein
- Found in mammals, invertebrates, and plants
- Ancient family of receptors
Structure
- Single-pass transmembrane proteins
- Part of the protein passes through the membrane once
Note: TLR diagram later
CLRs (C-Type Lectin Receptors)
Surface receptors that bind to carbohydrate structures on fungi and bacteria
NLRs (NOD-Like Receptors)
Cytoplasmic sensors for bacterial peptidoglycan fragments & other intracellular danger signals
RLRs (RIG-I-Like Receptors)
cytoplasmic receptors that detect viral RNA
Source
Professor Dave, Anara, See book for sources and add later