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Pattern-Recognition ReceptorsComments

Pattern-Recognition Receptors

Cells of the innate immune system recognize non-self cells by detecting structures unique to microbial pathogens and not present in mammalian cells. This non-adaptive recognition is performed by cell-surface pattern-recognition receptors. Pattern-recognition receptors detect repetitive pathogen-associated molecular patterns (PAMPs). Common PAMPs include nucleic acids, proteins, lipids and carbohydrates, as shown in the table below.

PAMPOverview
Nucleic AcidsNon-mammalian nucleic acids include viral double-stranded RNAs and bacterial unmethylated CpG DNA.
ProteinsCertain protein features are unique to bacteria, such as N-formylmethionine initiation.
Lipids & CarbsNon-mammalian lipids and carbohydrates include Gram-negative bacterial lipopolysaccharide (LPS), Gram-positive bacterial teichoic acids and bacterial glycoprotein mannose-rich oligosaccharides.

Pattern-recognition receptors are: encoded by the genome; expressed by all cells of a particular type (as opposed to clonal expansion); immediately responsive once bound to their ligand; and optimized for a broad range of pathogens. The two tables below chronicle the four steps in which pattern-recognition receptors operate, and the different types of pattern-recognition receptors.

StepOverview
1) RecognitionThe pattern-recognition receptor binds its ligand.
2) InductionInduction of effector molecules which stimulate innate immunity and influence subsequent adaptive response.
3) AttractionAttraction of effector cells (such as neutrophils) to the site of infection via chemotaxis.
4) InflammationRecruitment and activation of leukocytes and plasma proteins to site of infection.
ReceptorOverview
Mannose ReceptorMannose receptor has a lectin which binds terminal mannose and fucose residues of glycoproteins and glycolipids, typically found on microbial cell walls.
Scavenger ReceptorScavenger receptor binds microbes and oxidized or acetylated low-density lipoproteins (LDLs).
Macrophage IntegrinMacrophage integrin is crucial for ahesion and other functions. Mannose receptors, scavenger receptors and macrophage integrins all directly bind microbes.
Opsonin ReceptorsAn opsonin is any molecule which triggers phagocytosis. Opsonin receptors bind to opsonin, triggering phagocytosis and activating the phagocyte.
Toll-Like ReceptorFirst identified in drosophila, binding of a Toll-Like Receptor (TLRs) to its ligand can activate the cell bearing the ligand. This activations leads to production of cytokines and co-stimulatory molecules. TLRs are expressed on many different types of cells, including macrophages, dendritic cells, neutrophils, mucosal epithelial cells and endothelial cells. There are ten known TLRs in mammals, among which are:
TLRLigand
TLR2Certain bacterial lipoproteins; lipoteichoic acid and peptidoglycan on Gram-positive bacteria; zymosan from yeast.
TLR3Double-stranded RNA, which is unique to viruses.
TLR4LPS (component of Gram-negative bacterial membrane); mitochondrial Heat Shock Protein 60 (HSP60); viral proteins.
TLR5Flagellin, a protein component of bacterial flagella.
TLR6Various bacterial lipoproteins and glycolipids.
TLR9Unmethylated CpG dinucleotides (found in bacteria).
α-Helical Receptorsα-Helical Receptors (aka G Protein-Coupled Receptors) stimulate leukocyte migration from blood, through endothelium and to the site of infection. Also, α-helical receptors activate the respiratory burst, which produces biocidal substances. α-helical receptors recognize: peptides with N-formylmethionyl residues; chemokines; C5a; molecules involved inflammation, including platelet-activating factor, prostaglandin E and leukotriene B4.
Cytokine ReceptorsCytokine receptors, including IFNγ-specific Class II Cytokine Receptors, which are the primary activators of macrophages to phagocytose and secrete cytokines.