Pattern Recognition Receptor
PRRs (Pattern Recognition Receptors) are non-specific receptors: a PRR recognises molecular patterns associated with microorganisms (MAMP Microbe Associated Molecular Patterns) or associated with cellular damage (DAMP Damage Associated Molecular Patterns).
A PRR can recognise different molecular patterns, and a molecular pattern can be recognised by different PRRs.
Molecular description
Comparison between innate and adaptive immunity receptors
| PRR | TCR/BCR | |
|---|---|---|
| Immunity | Innate | Adaptive |
| Specificity | Non-specific | Ultra-specific: 1 antigen ⬄ 1 receptor |
| Recombination somatic | No | Yes |
| Diversity | Mild | Theoretically infinite |
| Response | Inflammation | Fine and highly regulated immunity |
| Phylogenia | Highly conserved also in invertebrates | In all vertebrates |
There are several PRR families, including:
- TLRs (Toll-Like Receptors)
- NLRs (Nod-Like Receptors)
- CLRs (C-type Lectin Receptors)
PRRs can be membrane, cytosolic, or extracellular.
Membrane PRRs
Membrane PRRs expressed at the plasma membrane will recognise patterns from intact microorganisms (bacterial lipopolysaccharides, fungal sugars, etc.), while the PRRs expressed on the membrane of endosomes will recognise patterns resulting from the degradation of microorganisms (e.g., nucleic acids).
Cytosolic PRRs
Cytosolic PRRs will be able to detect viral nucleic acids (MAMP) or potassium efflux when a cell is damaged (DAMP).
Extracellular PRRs
Soluble extracellular PRRs such as CRP (C-Reactive Protein) or MBP (Mannose-Binding Protein) will be capable of detecting microorganisms, while others will be able to recognise nucleic acids, heat shock proteins, ATP, fragments of hyaluronic acid, etc., released into the extracellular environment during cell death or during cellular stress (DAMP).
PRR ligands
PRR ligands are DAMPs or MAMPs:
- DAMPs (Damage Associated Molecular Pattern) are normally intracellular molecules that are released into the extracellular environment during cell death or stress.
- MAMPs (Microbe Associated Molecular Patterns) are redundant molecular patterns in pathogens that can be recognized as potentially harmful by PRRs. The typical example of MAMPs are lipopolysaccharides (LPS) on the surface of gram-negative bacilli, which contain a highly conserved structure recognised by TLR4.
Certain bacteria are capable of masking their LPS so as not to be recognised by PRRs and thus escape the immune system.
PRR downstream pathways
When they recognise their ligand, PRRs activate downstream molecular pathways leading to:
- a modification of the actin cytoskeleton to internalise the recognised target.
- the synthesis of pro-inflammatory and chemoattractant cytokines, which will both recruit and activate innate immunity cells. The result of this activation is the initiation of the innate immune response, in other words the inflammatory response.
What needs to be remembered
PRRs are danger sensors that recognise molecular patterns associated either with the presence of microbes (MAMP) or with non-physiological situations (DAMP). The downstream pathways of PRR are pro-inflammatory, including the synthesis of pro-inflammatory and chemoattractant cytokines, which will recruit the players of innate immunity in order to set up the inflammatory response.
PRRs are non-specific receptors, i.e. a PRR can recognise several danger signals, and a danger signal can be recognised by different PRRs.
