Recognition of Microorganisms

Pattern Recognition Receptors - B. Catchpole, RVC 2008

• The innate immune system recognises components of pathogens which are intrinsically foreign (i.e. not present on normal mammalian cells), such as:
  • Lipopolysaccharides of gram-negative bacteria
  • Peptidoglycans of gram-positive bacteria
  • Mannose sugars
  • D-isoform amino acids
• These are given away as foreign by expressing pathogen-associated molecular patterns (PAMPs)
• PAMPs are recognised by pattern recognition receptors (PRRs) expressed on mammalian cells
  • Pattern recognition receptors are expressed on many different cell types, not just on phagocytes
  • Not all are expressed by all cells: different cell types express a different range of PRRs
  • PRRs are either intracellular, membrane-associated or soluble:
    • Recognition of pathogens via the cellular PRRs results in phagocytosis and inflammation
    • Recognition of pathogens via the humoral PRRs results in various killing mechanisms
• Engagement of PRRs by PAMPs triggers:
  • Phagocytosis
  • The expression of cytokines, which brings about inflammation and other immune responses

Examples of Pattern Recognition Receptors

Receptor	Location	Ligands
TLR2 (Toll-like receptor)	Cell Membrane	Peptidoglycan of gram +ve bacteria
TLR3	Cell Membrane	dsRNA of RNA viruses (e.g. avian influenza)
TLR4	Cell Membrane	Lipoplysaccharide from gram-negative bacteria (e.g. E. coli, Salmonella)
TLR5	Cell Membrane	Bacterial flagellin
TLR9	Cell Membrane	Bacterial DNA (CpG DNA)
C-type lectins	Soluble	Carbohydrates, all bacteria, dead cells
fmlf	Soluble	Formyl peptides (i.e. all bacteria)
Complement receptors	Soluble	Fixed complement components (e.g. iC3b)
NOD2	Cytoplasm	Peptidoglycan of gram +ve bacteria
dsRNA-dependent Protein Kinase Receptor	Cytoplasm	ds RNA of RNA viruses

Originally funded by the RVC Jim Bee Award 2007