Chapter 2 Study Guide 1 PDF

Chapter 2 • 2 What is the difference between RIG-like receptors and the NLRP3 inflammasome? RLRs primarily detect viral RNA and induce an antiviral response, while the NLRP3 inflammasome responds to various forms of cellular stress or damage, activating inflammatory processes. • The RIG-like rec...

Chapter 2 • 2 What is the difference between RIG-like receptors and the NLRP3 inflammasome? RLRs primarily detect viral RNA and induce an antiviral response, while the NLRP3 inflammasome responds to various forms of cellular stress or damage, activating inflammatory processes. • The RIG-like receptors (RLRs) are cytosolic proteins that sense viral RNA and induce the production of the antiviral type I IFNs. RIG-like receptors (RLRs): Cytosolic receptors of the innate immune system that recognize viral RNA and induce production of type I interferons. The two best-characterized RLRs are RIG-I (retinoic acid–inducible gene I) and MDA5 (melanoma differentiation-associated gene 5). One of the best-characterized inflammasomes uses NLRP3 (NOD-like receptor family, pyrin domaincontaining 3) as a sensor. The NLRP3 inflammasome is expressed in innate immune cells, including macrophages and neutrophils, as well as keratinocytes in the skin and other cells. How NLRP3 recognizes such diverse types of cellular stress or damage is not clearly understood. Inflammasome activation is tightly controlled by post-translational modifications such as ubiquitination and phosphorylation, which block inflammasome assembly or activation, and some micro-RNAs, which inhibit NLRP3 messenger RNA. NLRP3 (a NOD-like pattern recognition receptor). • What is the difference between RIG-like receptors and the STING pathway? RLRs primarily recognize viral RNA, whereas the STING pathway is activated in response to cytosolic DNA. RLRs signal through interactions with MAVS on the mitochondrial membrane, while the STING pathway involves cGAMP binding to STING on the endoplasmic reticulum. RLR activation leads to the production of type I interferons, contributing to an antiviral response. In contrast, the STING pathway also leads to type I interferon production but is more broadly involved in detecting cytosolic DNA from various pathogens. T The RIG-like receptors (RLRs) are cytosolic proteins that sense viral RNA and induce the production of the antiviral type I IFNs. RIG-like receptors (RLRs): Cytosolic receptors of the innate immune system that recognize viral RNA and induce production of type I interferons. The two best-characterized RLRs are RIG-I (retinoic acid–inducible gene I) and MDA5 (melanoma differentiation-associated gene 5). Most innate cytosolic DNA sensors engage the Stimulator of IFN genes (STING) pathway to induce type 1 IFN production. In this pathway, cytosolic dsDNA binds to the enzyme cyclic GMP-AMP synthase (cGAS), which activates the production of a cyclic dinucleotide signaling molecule called cyclic GMP-AMP (cGAMP). This cGAMP molecule binds to an endoplasmic reticulum membrane adaptor protein called stimulator of interferon gene (STING). In addition, bacteria themselves produce other cyclic dinucleotides that also bind to STING. Upon binding these cyclic dinucleotides, STING initiates signaling events that lead to transcriptional activation and expression of type I IFN genes. STING also stimulates autophagy, a mechanism by which cells degrade their own organelles in lysosomes. Autophagy is used in innate immunity to deliver cytosolic microbes to the lysosome, where they are killed by proteolytic enzymes. Other cytosolic DNA sensors besides cGAS can also activate STING (Stimulator of IFN Genes), an adaptor protein located in the endoplasmic reticulum membrane, which is utilized by several cytoplasmic DNA sensor molecules to transduce signals that activate the IRF3 transcription factor, leading to type 1 IFN gene expression.