[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Immunology](https://durgical.com/en/immunology/) › [Innate immunity](https://durgical.com/en/immunology/#a-innate) › Pattern recognition: PAMPs, DAMPs, Toll-like receptors

[Immunology](https://durgical.com/en/immunology/) · [Innate immunity](https://durgical.com/en/immunology/#a-innate)

# 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

## Key points

- TLR4 recognizes LPS; TLR5 flagellin; TLR3 dsRNA; TLR7/8 ssRNA; TLR9 CpG DNA.
- Most TLRs signal through MyD88 to NF-κB; the result is TNF, IL-1 and IL-6.
- Nucleic acid sensors sit in endosomes or cytosol, where viruses are found.
- The inflammasome activates caspase-1 to release IL-1β; NLRP3 is activated by crystals such as uric acid.
- NOD2 variants are linked to Crohn disease.

## 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.

## Memory aid

Surface TLRs read the bacterial coat (LPS, lipoproteins, flagellin); inner TLRs read the viral script (RNA and DNA) inside the endosome.

## 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.

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## Related

- [Innate immunity (overview, barriers)](https://durgical.com/en/immunology/innate-immunity/)
- [Acute-phase response and fever (CRP, ESR, procalcitonin)](https://durgical.com/en/immunology/acute-phase-response-and-fever/)
- [Acute inflammation: vascular and cellular events](https://durgical.com/en/immunology/acute-inflammation-vascular-and-cellular-events/)
- [Monocyte and macrophage](https://durgical.com/en/immunology/monocyte-and-macrophage/)
- [Dendritic cell (professional antigen-presenting cell)](https://durgical.com/en/immunology/dendritic-cell/)
- [Fc receptors, BCR and TCR](https://durgical.com/en/immunology/fc-receptors-bcr-and-tcr/)
- [Cytokines: the table to know](https://durgical.com/en/immunology/cytokines-the-table-to-know/)
- [Interleukin-1](https://durgical.com/en/immunology/interleukin-1/)
- [TNF-α](https://durgical.com/en/immunology/tnf/)
- [Type I interferons (α, β)](https://durgical.com/en/immunology/type-i-interferons/)

## Related conditions

- [Sepsis and septic shock](https://durgical.com/en/conditions/sepsis-and-septic-shock/)
- [Crohn disease](https://durgical.com/en/conditions/crohn-disease/)

## Microorganisms

- [Escherichia coli](https://durgical.com/en/microbiology/escherichia-coli/)
- [Neisseria meningitidis](https://durgical.com/en/microbiology/neisseria-meningitidis/)

[← All of immunology](https://durgical.com/en/immunology/)

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](https://openstax.org/books/microbiology/pages/17-4-pathogen-recognition-and-phagocytosis) (OpenStax (Microbiology), 2016); [17.2 Chemical Defenses](https://openstax.org/books/microbiology/pages/17-2-chemical-defenses) (OpenStax (Microbiology), 2016).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/immunology/pattern-recognition-pamps-damps-toll-like-receptors/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/immunology/pattern-recognition-pamps-damps-toll-like-receptors/