Pattern Recognition Receptors (PRRs)
The human body has the receptors that can identify the invading microbial pathogens, these receptors are called Pattern Recognition Receptors (PRRs). PRRs are the major part of the innate immune system, recognizing the pathogens. PRRs can perform their function by recognizing conserved patterns present in microbial molecules, these molecular patterns are usually called as Pathogen-Associated Molecular Patterns (PAMPs). However, these PAMPs are not particular for pathogens, these can also found in non-pathogenic microorganisms.
Figure: Inhibitors of the signaling pathways initiated by pattern recognition receptors (PRRs). These inhibitory molecules intervene in the different steps of PRR activation and signaling cascade, including ligand binding and interaction with adapters. Image Source: InvivoGen
Major Types Of PRRs
The following are the major types of PRRs.
1. Transmembrane PRRs
They are usually present at the surface of macrophages and neutrophils and recognize extracellular pathogens. These PRRs can engulf the pathogens in the phagosome and fuse with the lysosome. Lysosomal enzymes then destroy these extracellular pathogens.
2. Intracellular PRRs
These PRRs are found intracellularly and are specific for the recognition of intracellular pathogens like viruses.
3. Secreted PRRs
These PRRs are secreted and bind to extracellular pathogens. The pathogens are then eliminated phagocytes or by the complement system.
Classes of PRRs
1. Toll-like receptors (TLRs)
These receptors have a leucine-rich domain. Mammals usually have 10 different types of TLRs, each recognizing their specific ligands. For example, TLR4 recognizes lipopolysaccharide (LPS) of Gram-negative bacteria.
2. NOD-like receptors (NLRs)
NLRs also have leucine-rich motifs and are cytoplasmic. NLRs are capable to detect specific bacterial molecules.
3. RIG‑like receptors (RLRs)
RLRs are also cytoplasmic and recognize unique viral molecules.
4. C‑type lectin receptors (CLRs)
CLRs are transmembrane proteins on the cell surface and recognize specific carbohydrate moieties on different microbes.
Activated PRRs Trigger an Inflammatory Response
Usually, PRRs trigger a local inflammatory response at site of infection by stimulating the secretion of cytokines and other extracellular signals by the cells. The inflammatory response includes dilation of local blood vessels, so blood vessels become permeable to blood proteins that having a defensive role in the body’s immune system. The characterization of Inflammation is done by redness, heat, swelling, and local pain. The blood vessels dilate and become permeable to fluid and proteins, leading to local swelling and an accumulation of blood proteins that aid in defense. The white blood cells are recruited to the site of infection, including neutrophils, lymphocytes, and monocytes.
PRRS Detect Pathogenic Microorganisms But Not Commensals (Normal Flora)
The following may be the possible reasons:
- Accessibility to immune cells
- Compartmentalization of PRRs
- Sensing virulence factors
1. Accessibility to immune cells
Pathogens usually have virulence factors so they can adhere to Intestinal epithelial cells and eventually gain access to the underlying Peyer’s patches. While commensals lack such virulence factors.
2. Compartmentalization of PRRs
TLR4, a major type of PRRs, is restricted to mononuclear cells of the lamina propria and crypt epithelial cells and induces pro-inflammatory response to those pathogens that can cross these barriers. Thus, compartmentalization of TLR4 can prevent immune activation by normal flora.
3. Sensing virulence factors
The activities of pathogens having virulence factors activate innate immunity. So, the normal flora cannot provoke the innate immune system as lacking virulence factors.
- Molecular Biology of the Cell (Sixth Edition) by Bruce Alberts.
- Srinivasan, N. (2010). Telling apart friend from foe: discriminating between commensals and pathogens at mucosal sites. Innate immunity, 16(6), 391-404.
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