Erakina

Pattern Recognition Molecules (PRM/PRR)

Published Date : June 15, 2022

Pattern recognition molecules (PRM) are protein molecules that can recognize different molecules to initiate relative responses. 

Colourful spheres with branches

Chemical structure of molecules

Pattern recognition molecules (PRM) are also known as pattern recognition receptors (PRR), which recognize molecules from various sources to initiate interaction with these molecules. Molecules found in pathogens are called pathogen-associated molecular patterns (PAMPs). In contrast, molecules produced by damaged cells are known as damage-associated molecular patterns (DAMPs). The primary function of PRR is to interact with these molecules to produce signals to induce immune responses. Therefore, these molecules are considered a part of the innate immune system. The influence of PAMPs and DAMPs initiates the signal produced by PRR. PRRs are present either on the extracellular surface of pathogens or in the cytoplasm and endosomes of cells that are often invaded by viruses. PRRs can recognize different pathogens such as; bacteria, fungi, parasites, protozoa, and viruses. In addition to identifying the pathogens and damaged cells, the PRRs can initiate the mechanism of cell death leading to the production of DAMPs. 

Table of Contents

Brief Overview of PRM

Role of PRM

Mechanism of PRR

Brief Overview of PRM

The innate immune system responds to the first line of defense against any foreign pathogens by recognizing the molecular patterns of the pathogen. Pattern recognizing molecules are the receptors (PRR) that can recognize the PAMPs that are unique to each pathogen and DAMPs that are associated with molecules released during their cell damage. PRRs are a part of the innate immune system as they have a broad spectrum of receptor-mediated recognizing molecule patterns like PAMPs and DAMPs. 

Small flower-like structures on a purple surface

 Illustration of receptors on the cell surface

PRRs are classified based on their location and functionality. Firstly, Membrane-bound PRRs contain two types of receptors: Toll-like receptors (TLR) and C-type lectin receptors (CLR). These receptors are present on the surface of the membrane. Secondly, cytoplasmic PRRs contain Nucleotide oligomerization-like receptors (NLRs) and retinoic acid-inducible gene I-like receptors (RLR) present in the cell’s cytoplasm. Finally, secreted PRRs from the cells bound to microorganisms. 

Role of PRM

PRRs consist of different types of receptors classified based on their location: membrane-bound PRRs, cytoplasmic PRRs, and secreted PRRs. 

  • TLR, a membrane-bound receptor, consists of 10 variants, such as TLR1, TLR2, to TLR10. The primary functions of TLR include the recognition of bacterial lipids, viral RNA, bacterial DNA, and proteins associated with bacteria and parasites. Once the pathogen is detected in the intracellular zone of the receptors, a signal is produced to activate the NF-kappa B pathway responsible for generating cytokines and other co-simulatory molecules that aid in inflammation and anti-microbial defense. 
  • Another membrane-bound receptor, CLRs, is classified into group I belonging to the family of mannose receptors and group II belonging to the family of the asialoglycoprotein receptors. CLRs recognize; mannose (a sugar monomer) present on the surface of viruses, fungi, and mycobacteria; fucose found in bacteria and parasites; glucans present on the fungi and mycobacteria. 
  • Cytoplasmic PRRs present intracellular consist of two types: Nucleotide oligomerization like receptors (NLRs) and retinoic acid-inducible gene I like receptors (RLR). Nucleotide oligomers (NOD) contain NOD1 and NOD2, responsible for recognizing peptidoglycan patterns in bacteria. Hence the NLRs aid in modulating the inflammation and apoptosis. 
  • Other cytoplasmic PRRs, are retinoic acid-inducible gene I (RIG-I), DDX3, and melanoma differentiation-associated with gene 5 (MDA5) aid in recognizing the viral RNA, which activates helicases to produce antiviral signals. 
  • PRRs are secreted by cells that bind to the microorganisms that invade the cells directly, such as ficolins, collectins, peptidoglycan recognition proteins (PGRs), lipid transferases, etc. 

Mechanism of PRR

When a pathogen enters a body, the innate immune system initiates the immune response to this foreign microbe. The innate response molecules are immediate and non-specific as they attack the foreign body. The PRRs are the sensor machines that detect typical molecules for pathogens. The innate immune system is triggered when the PRRs recognize molecular patterns of the foreign microbes or the damaged cell. Typically the cells are incapable of detecting foreign particles, instead they have sensors capable of differentiating between self and non-self. These sensors are the PRRs. 

Cylindrical shaped different colored structures on a green surface

Illustration of multiple receptors on the surface of the cell membrane, 

Hence, the PRRs detect molecules associated with the pathogens (PAMPs) and the damaged cells (DAMPs). Non-functional cells are considered a threat since they are harmful to the body. Hence the immune system will detect these DAMPs and eradicate these DAMPs from the body. Membrane-bound PRRs contain receptors like TLR and CLR, cytoplasmic PRRs contain NOD and RIG-I like receptors, and inflammasomes are multiprotein complexes that aid in detecting PAMPs and DAMPs. The PRRs are expressed by the innate immune cells such as monocytes, neutrophils, dendritic cells, macrophages, and epithelial cells. 

PAMPs consist of bacterial carbohydrates such as mannose and lipopolysaccharides, nucleic material like DNA, and bacterial peptides like flagellin or microtubules. NOD2 is associated with loss or gain of function leading to Crohn’s disease. When NOD2 is mutated due to environmental factors, it leads to chronic inflammation in the intestine. PRRs can be exploited in human medicine associated with intestinal tumor malignancies caused by Helicobacter pylori. Furthermore, plant defense systems can be controlled by enhancing the capacity of PRRs to detect pathogens. The defense system is genetically enhanced by engineering the PRRs to recognize a broad spectrum of pathogens, thereby inducing a rapid immune response against the pathogens. The genetically engineered PRRs will have increased resistance against more pathogens, hence increasing the ability of plants to produce yield with high quality and quantity. 

Asha Rachel Thomas

26/05/2022

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