Intracellular sensors: NOD- and RIG-like receptors
These receptors are located directly in the cytoplasm of cells. Their main task is to monitor the intracellular space in case a pathogen manages to breach the outer membrane barriers.
NOD-like receptors (NLRs)
This family of endogenous receptors contains a characteristic NOD domain — a special oligomerization region capable of nucleotide binding. NLRs work as an emergency alert system for bacterial agents entering the cell.
They exhibit clear ligand specificity (to bacterial components):
- NOD1 recognizes muramyl tripeptide.
- NOD2 specializes in muramyl dipeptide.
How it works: When the receptor binds its ligand, the transcription factor NF-κB is activated inside the cell. This triggers a powerful response: the synthesis of pro-inflammatory cytokines and chemokines that recruit other immune cells to the focus.
RIG-like receptors (RLRs)
Unlike NLRs, this group of cytoplasmic sensors targets viruses.
- Specificity: The main target of RLRs is viral genetic material, primarily double-stranded RNA, as well as certain other molecules.
- Effect of activation: Upon detecting a virus, the receptors initiate the production of protective molecules. First, these are interferons $\alpha$ and $\beta$, which provide antiviral defense. Second, they are classic pro-inflammatory cytokines (e.g., IL-6 and TNF-$\alpha$).
Surface catchers: Mannose receptor
To catch microorganisms from the outside, cells use surface structures. A classic example is the mannose receptor, which belongs to the group of lectin receptors.
- Structure and localization: It contains special lectin domains created by nature for tight carbohydrate binding. This receptor is located on the surface of mononuclear phagocytes.
- Target: The ideal "prey" for it is microorganisms whose cell walls have a mannose-rich structure.
- Function: The main task of the mannose receptor comes down to physically binding the microbe. Once contact is established, the cell initiates endocytosis, engulfing the bound pathogen for subsequent digestion.
Body's sanitarians: Scavenger receptors
Innate immunity not only fights external enemies but also maintains internal cleanliness. This is the job of scavenger receptors. They are predominantly present on macrophages and dendritic cells (and to a lesser extent on epithelial cells).
Their main function is "sanitary". They capture and send various modified molecules and dead cells to endocytosis, clearing the body's internal environment.
What scavengers recognize (ligands):
- Cell degradation products (e.g., sialic acid breakdown products).
- Low-density lipoproteins (LDLs) and various oxidized lipids.
- Bacterial cell wall components (such as lipoteichoic acid).
- Apoptotic bodies (fragments of cells that died via programmed cell death).
- The body's own aging cells (a typical example being worn-out erythrocytes).
Briefly: answers to topical questions
What main families of pattern recognition receptors (PRRs) exist besides NLRs, RLRs, lectin, and scavenger receptors?
In addition to the listed families, there are Toll-like, integrin, DAI, and soluble receptors.
- Toll-like receptors (TLRs) are membrane receptors that activate innate immunity cells.
- Integrins are membrane receptors responsible for adhesion and motility.
- DAI are intracellular receptors that recognize DNA.
- Pentraxins are soluble receptors that activate complement and chemotaxis.
- Collectins are soluble receptors that activate complement.
- Complement system components are soluble receptors for opsonization and cytolysis.
- Ficolins are soluble receptors involved in opsonization.
What structural domains are part of NOD-like receptors (NLRs) besides the NOD domain?
In addition to the NOD domain, the structure of NOD-like receptors includes CARD and LRR domains.
- CARD domain (Caspase recruitment domain) is located in the N-terminal part of the molecule and is involved in signal transduction as well as caspase-1 activation.
- LRR domain (leucine-rich repeat) is located in the C-terminal part and is responsible for ligand recognition (peptidoglycans).
What ligands do Toll-like receptors (TLRs) recognize?
Toll-like receptors recognize conservative molecular structures of microorganisms — pathogen-associated molecular patterns (PAMPs).
- Membrane receptors (TLRs 1–11) bind various PAMPs on the surface of pathogens to activate innate immune cells.
- Intracellular receptors (TLRs) specialize in recognizing viral PAMPs after phagocytosis of infected cells.
Which innate immune receptors specialize in recognizing fungal antigens (e.g., beta-glucans)?
Dectin-1, TLR2, and TLR4 receptors specialize in recognizing fungal antigens.
- Dectin-1 is a C-type lectin receptor that binds yeast $\beta$-glucans and plays a key role in antifungal defense.
- Toll-like receptors (TLR2, TLR4) are involved in recognizing components of the multilayer fungal cell wall.
To avoid confusing NLR ligands on the exam, remember this illogical but working rule: NOD1 binds muramyl TRipeptide (1 and 3), whereas for NOD2 the number matches the prefix — muramyl DIpeptide (2 and 2).
Class and exam questions
Where are NOD-like and RIG-like receptors localized and why?
They are localized in the cell cytoplasm. This is necessary to detect intracellular threats: bacterial agents (NLRs) and viral genetic material (RLRs) that have managed to penetrate inside.
What effect does NOD receptor activation lead to?
Binding of the ligand to the NOD receptor activates the transcription factor NF-κB. This triggers the synthesis of pro-inflammatory cytokines and chemokines.
Which molecules are synthesized upon activation of RIG-like receptors?
The cell begins to produce interferons $\alpha$ and $\beta$ for antiviral defense, as well as pro-inflammatory cytokines such as IL-6 and TNF-$\alpha$.
What is the function of macrophage scavenger receptors?
They perform a "sanitary" function: they recognize and capture (via endocytosis) cell degradation products, oxidized lipids, apoptotic bodies, aging erythrocytes, and certain bacterial components.
What else to study on this topic
- Mechanisms of NF-κB transcription factor activation upon NOD receptor stimulation
- The process of microorganism endocytosis mediated by mannose receptors of mononuclear phagocytes
- The role of scavenger receptors in the uptake of oxidized low-density lipoproteins (LDLs)
- Features of type α and β interferon production upon RLR activation by viral double-stranded RNA
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