Ubiquitous germline encoded receptor involved in innate immunity that detects non-self structures
Pattern Recognition Receptors (PRR)
Molecular structures common to many microbes that are identified by PRRs - and give examples
Pathogen Associated Molecular Patterns (PAMP) eg. bacterial LPS, glycoproteins have mannose residues in bacteria, dsRNA, unmethylated CpG DNA
Major PRR family
Toll-like receptors (TLRs)
Cell surface TLRs #
Endosomal TLRs #
Cell surface: TLR1, TLR2, TLR4, TLR5, TLR6
Endosomal: TLR3, TLR7, TLR8, TLR9
Components of Toll-like receptor and function
Exterior domain (ligand recognition) and intracellular Toll/IL-1 receptor domain (TIR) for downstream signalling after ligand binding
What do the exterior domains of TLRs detect in cell surface vs endosomal TLRs?
Cell surface TLRs: exterior domain contains leucine-rich repeats that detects microbial membrane components
Endosomal TLRs: exterior domain is in endosome and detects nucleic acids
PRR function
Activates phagocytosis or stimulate the activation of immune cells (cyto/chemokines)
TLR vs PRR location
TLR: cell surface and endosome
PRR: cell surface, endosome, and cytoplasm
MyD88 binding to TIR domain of TLRs recruits/induces
IRAK (IRAK-4?)
Activation of NF-kB vs. Interferon Response Factors
NF-kB - requires degradation of IkB which inhibits it
IRF - requires phosphorylation
What are NF-kB and IRF and what do they do
Transcription factors that enter the nucleus, induce immune response and anti-viral genes
Cytoplasmic PRRs that sense viruses and two examples
Rig-like receptors (RLRs) - RIG-I & MDA5
Similar signalling pathway to TLRs
PRR signalling results
Production of interferons (anti-viral eg. IFN-I), pro-inflammatory cytokines, and immune response genes
Advantages of PRRs (speed, economy, amplification)
Speed - innate (only takes minutes) vs adaptive (days)
Economy - small number of TLRs detect many different pathogens
Amplification - large systemic responses from a localized detection
Cross talk between different PRR pathways allows for
Modulated immune responses (more control)
