Pathogen-associated molecular patterns (PAMPs) and receptors (PRRs)

Author: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at LSU (Shreveport) Department of Allergy and Immunology

Pathogen-associated molecular patterns (PAMPs)

Microbial products which stimulate innate immunity are called pathogen-associated molecular patterns (PAMPs). Pathogen-associated molecular patterns (PAMPs) are on bacteria - they bind to receptors called pattern recognition receptors.

Innate immunity reacts to these common bacterial structures - PAMPs, pathogen-associated molecular patterns. PAMPs are produced only by the bacterial invader and not by the host. If it were the other way around, innate immunity would get "confused" and attack the host instantly and immediately as it is typical of its nature.

PAMPs include:

- lipopolysaccharides (LPS) on Gram-negative bacteria
- lipoteichoic acid on Gram-positive bacteria
- peptidoglycans
- mannan
- bacterial RNA and DNA
- glucan

Receptors that bind these PAMPs are called pattern recognition receptors (PRRs). PAMPs are unique to microbes. Mammalian cells do not have PAMPs and this one of the reasons why there is no autoimmune disease caused by innate immunity.

For example, human cells do not have mannose - bacteria do. Receptors recognize mannose on bacteria - and this starts the mannose-lectin complement pathway.

Mannose is one of the PAMPs. TLRs are pattern recognition receptors.

Example of a match: ligand-receptor: mannose (bacteria)-mannose-binding lectin (MBL) (soluble recognition molecule in humans)

Mannose-binding lectin (MBL) starts the third complement pathway. MBL is plasma protein that functions as an opsonin.

APC (macrophages) have PAMPs-recognition receptors, called pattern-recognition receptors in short.

Pathogen Recognition Receptors, TLRs. This video is from: Janeway's Immunobiology, 7th Edition Murphy, Travers, & Walport. Source: Garland Science.

PAMPs Recognition Receptors (PRR)

There are 4 PAMPs receptors remembered by the mnemonic: T-CNS

Toll-like receptors (TLR)
C-type lectin receptors (CLR)
N-formyl Met-Leu-Phe receptors (fMLP)
Scavenger receptors

Caspase activation and recruitment domains (CARD)
Nucleotide-binding oligomerization domains (NODs) (NLR or NACT-LRR)

Pattern-recognition receptors (PRR) (molecules) are divided into 3 groups: SES

S
ecreted
Endocytic
Signaling

C-type lectins

C-type lectins are calcium-dependent carbohydrate-binding molecules expressed on the plasma membranes of macrophages and other cells.

The best known C-type lectin is the mannose receptor. Mannose-binding receptor binds to bacterial carbohydrates. It activates the 3rd complement pathway.

Another C-type lectin is Dectin1.

C
C-type lectins
Calcium-dependent
Carbohydrate-binding molecules

C-type lectins:

- Mannose-binding
- Dectin

Secreted pattern-recognition molecules bind to microbes (opsonization) and make them "tastier" to phagocytes. An example of secreted pattern-recognition molecules is a mannose-binding protein (lecithin). These molecules are associated with serine proteases MASP (mannose-binding lectin-associated serine proteases).

Scavenger receptors

One scavenger receptor, SRB1, is involved in atherogenesis. Scavenger receptors mediate the uptake of oxidized lipoproteins into cells.

NF MLP

N-formyl Met-Leu-Phe (NF MLP) receptors are the most chemoattractive (chemotactic) receptors for PMNs.

N
NF MLP
Neutrophil chemoattractant

All chemokines are proteins.
All chemokines are chemoattractants but not all chemoattractants are chemokines. For example PGD-6 is a chemoattractant but not a chemokine, it is a prostaglandin not a protein.

NLRs

NLRs (NACHT-LRRs) are a family of cytoplasmic molecules.

CARD

Caspase activation and recruitment domain (CARD)-containing proteins. Homozygous mutations in the CARD9 gene are associated with chronic mucocutaneous candidiasis. Dysfunction of CARD9 impairs the innate signaling of dectin-1, an antifungal pattern-recognition receptor (NEJM, 10/2009).

Related reading

Immunodeficiency and Genetic Defects of Pattern-Recognition Receptors. Mihai G. Netea, M.D., Ph.D., and Jos W.M. van der Meer, M.D., Ph.D. N Engl J Med 2011; 364:60-70, January 6, 2011.

Published: 06/28/2010
Updated: 01/08/2011

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