Pathogen Recognition Receptors amp Innate immune Response Tolllike Receptors

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#immunology #tolllikereceptor #virus • In the early phases of an immune response, the innate immune system detects pathogens and acts as the first line of defence. • Dendritic cells, which circulate throughout tissues, can detect the presence of pathogen-associated molecular patterns, or PAMPs. • PAMPS are pathogen traits that are conserved, such as lipopolysaccharides (LPS), which are components of the cell membranes of all gram-negative bacteria. • Dendritic cells can recognise PAMPs by expressing a family of Toll-like receptors, also known as TLRs. • In the case of LPS, it is identified by TLR-4, a member of the TLR family expressed on the surface of dendritic cells. • LPS is carried to the dendritic cell surface by the soluble LPS-binding protein, LBP, and deposited on the cell surface protein CD14. • TLR-4 detects the presence of LPS by interacting with and recognising LPS bound to CD14. • The signal produced by the TLR stimulates dendritic cell maturation. • At this point, the dendritic cell can move to regional lymph nodes and activate the acquired immune response. • Immune system cells, such as macrophages and dendritic cells, serve as the first line of defence in identifying pathogens of various types. • These cells have evolved a variety of receptors for identifying various pathogen-associated molecular patterns (PAMPs). • These proteins are divided into groups that identify various types of PAMPs. • Toll-like receptors, or TLRs, are made up of numerous leucine-rich repeats that help TLRs recognise different PAMPs. • TLRs are membrane-associated proteins. • Some are on the cell's surface, while others are on endocytic vesicles, where they check the degraded contents of pathogens picked up by endocytosis. • Different types of PAMPs are recognised by each member of the TLR family. • TLR-5, for example, identifies flagellin, a highly conserved component of the bacterial flagellum. • Bacterial genomes include methylated CpG oligonucleotide patterns that TLR-9 recognises after the genome is destroyed in the lysosome. • TLR-6 and TLR-2 form a dimer that detects diacyl lipopeptides; TLR-1 and TLR-2 form a dimer that recognises triacyl lipopeptides; and TLR-4 recognises lipopolysaccharide, or LPS, a gram-negative bacterium component. • TLR-3 and TLR-7, like TLR-9, are found on endocytic vesicles and identify double-stranded and single-stranded RNA, respectively. • When any TLR is triggered, transcription factors are activated, which sends a signal to the nucleus. • However, not all infections live in the extracellular space or are phagocytosed. • Viruses and other pathogens live and proliferate in the cytosol. • There are at least two types of receptors that can detect infections in the cytosol and alert the immune system to their presence. • Members of the Nucleotide Oligomerization Domain family, or NOD proteins, are one type of such receptor. • The cytosolic NOD2 protein, for example, may detect bacterial proteoglycans of intracellular bacteria. • When the NOD2 protein identifies its ligand, muramyl dipeptide, it sends a signal to the nucleus, causing transcription to begin. • Finally, an RNA helicase domain and two caspase recruitment domains, or CARD domains, are found in a class of intracellular receptor proteins. • RIG-I, a member of this family, identifies double-stranded RNAs, which are involved in the life cycle of many RNA viruses. • This protein class, like TLRs and NODs, delivers a signal to the nucleus, but unlike TLRs and NODs, it triggers the synthesis of Type-1 interpherons. • Toll-like receptors, NOD proteins, and the RNA helicase CARD domain family all enable the innate immune system to recognise external and intracellular pathogens and mount an immune response against them.

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