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.

PAMP	Overview
Nucleic Acids	Non-mammalian nucleic acids include viral double-stranded RNAs and bacterial unmethylated CpG DNA.
Proteins	Certain protein features are unique to bacteria, such as N-formylmethionine initiation.
Lipids & Carbs	Non-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.

Step	Overview
1) Recognition	The pattern-recognition receptor binds its ligand.
2) Induction	Induction of effector molecules which stimulate innate immunity and influence subsequent adaptive response.
3) Attraction	Attraction of effector cells (such as neutrophils) to the site of infection via chemotaxis.
4) Inflammation	Recruitment and activation of leukocytes and plasma proteins to site of infection.

Receptor

Overview

Mannose Receptor

Mannose receptor has a lectin which binds terminal mannose and fucose residues of glycoproteins and glycolipids, typically found on microbial cell walls.

Scavenger Receptor

Scavenger receptor binds microbes and oxidized or acetylated low-density lipoproteins (LDLs).

Macrophage Integrin

Macrophage integrin is crucial for ahesion and other functions. Mannose receptors, scavenger receptors and macrophage integrins all directly bind microbes.

Opsonin Receptors

An opsonin is any molecule which triggers phagocytosis. Opsonin receptors bind to opsonin, triggering phagocytosis and activating the phagocyte.

Toll-Like Receptor

First 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:

TLR	Ligand
TLR2	Certain bacterial lipoproteins; lipoteichoic acid and peptidoglycan on Gram-positive bacteria; zymosan from yeast.
TLR3	Double-stranded RNA, which is unique to viruses.
TLR4	LPS (component of Gram-negative bacterial membrane); mitochondrial Heat Shock Protein 60 (HSP60); viral proteins.
TLR5	Flagellin, a protein component of bacterial flagella.
TLR6	Various bacterial lipoproteins and glycolipids.
TLR9	Unmethylated CpG dinucleotides (found in bacteria).

α-Helical Receptors

α-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 Receptors

Cytokine receptors, including IFNγ-specific Class II Cytokine Receptors, which are the primary activators of macrophages to phagocytose and secrete cytokines.