Pattern recognition: PAMPs, DAMPs, Toll-like receptors !
- Process
Innate cells carry receptors that spot molecules shared by many microbes or released by damaged tissue, and sound the alarm.
Updated 2026-11-01
What it is
Pattern recognition receptors (PRRs) detect pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide, flagellin or viral RNA, and damage-associated patterns (DAMPs) released by stressed or dying cells. Toll-like receptors (TLRs) on the cell surface and in endosomes, and cytosolic sensors such as NOD-like receptors and RIG-I, turn this recognition into cytokines, interferons and inflammation. This is how the body knows that something is dangerous before any antibody exists.
Key facts
- DAMPs include HMGB1, extracellular ATP, uric acid crystals and heat-shock proteins.
- Uric acid and cholesterol crystals activate the NLRP3 inflammasome, which helps explain gouty inflammation.
- Excessive TLR4 signaling by LPS drives the cytokine surge of gram-negative sepsis.
Step by step
- A PAMP (for example LPS of a gram-negative bacterium) or a DAMP binds its receptor on a macrophage or dendritic cell.
- Most TLRs signal through the adaptor MyD88; TLR3 uses TRIF, and TLR4 can use both.
- Signaling activates transcription factors such as NF-κB and IRFs.
- The cell secretes TNF, IL-1, IL-6, chemokines and, after viral sensing, type I interferons.
- Inflammasomes (for example NLRP3) activate caspase-1, which cuts pro-IL-1β into active IL-1β.
- Activated dendritic cells raise B7 (CD80/CD86) and migrate to lymph nodes to start the adaptive response.
Main receptors and what they detect
| Receptor | Location | Detects |
|---|---|---|
| TLR4 | Cell surface | Lipopolysaccharide (gram-negative bacteria) |
| TLR2 (with TLR1 or TLR6) | Cell surface | Lipoproteins, lipoteichoic acid, peptidoglycan components |
| TLR5 | Cell surface | Bacterial flagellin |
| TLR3 | Endosome | Double-stranded RNA (viruses) |
| TLR7 and TLR8 | Endosome | Single-stranded RNA (viruses) |
| TLR9 | Endosome | Unmethylated CpG DNA (bacteria, viruses) |
| NOD2 | Cytosol | Muramyl dipeptide from peptidoglycan |
| RIG-I and MDA5 | Cytosol | Viral RNA, leading to type I interferons |
Clinical notes
- Sepsis: massive PAMP recognition releases TNF, IL-1 and IL-6, causing vasodilation, fever and shock.
- NOD2 variants are associated with Crohn disease.
- Vaccine adjuvants work in part by stimulating pattern recognition receptors.
Test yourself
Think of the answer, then tap the question to see it.
Which Toll-like receptor recognizes the lipopolysaccharide of gram-negative bacteria?
TLR4 (with the co-receptors CD14 and MD-2).
Why are TLR3, TLR7, TLR8 and TLR9 located in endosomes?
They detect nucleic acids; inside endosomes they meet ingested microbial DNA or RNA and are less exposed to the body's own nucleic acids.
What does the NLRP3 inflammasome do?
It activates caspase-1, which cleaves pro-IL-1β and pro-IL-18 into their active forms; crystals such as uric acid can trigger it.
What is a DAMP, and what is one example?
A danger-associated molecular pattern released by stressed or dying host cells, such as HMGB1, extracellular ATP or uric acid crystals.
Related
- Innate immunity (overview, barriers)
- Acute-phase response and fever (CRP, ESR, procalcitonin)
- Acute inflammation: vascular and cellular events
- Monocyte and macrophage
- Dendritic cell (professional antigen-presenting cell)
- Fc receptors, BCR and TCR
- Cytokines: the table to know
- Interleukin-1
- TNF-α
- Type I interferons (α, β)
Related conditions
Microorganisms
Educational content on the immune system; not a treatment or individual vaccination guide and no substitute for a health professional's advice. No doses are given.
Sources: 17.4 Pathogen Recognition and Phagocytosis (OpenStax (Microbiology), 2016); 17.2 Chemical Defenses (OpenStax (Microbiology), 2016).
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Representative model, for educational purposes only.