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 known to the body as foreign as they are expressed as pathogen-associated molecular patterns (PAMPs) which are recognised by pattern recognition receptors (PRRs) expressed on mammalian cells. These receptors are expressed on many different cell types, not just on phagocytes, though 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

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The engagement of PRRs by PAMPs triggers:

• Phagocytosis
• The expression of cytokines, which brings about inflammation and other immune responses

Pattern Recognition Receptors

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
fMLP	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