cmi2014chapter3iducedinnateimmunity1ppt课件.ppt

思考题 固有免疫系统如何通过不同的PRR识别不同亚细胞部位的病原体感染？ 诱导性固有免疫反应的主要效应机制有哪些？ 简述炎症小体的激活通路。 The end of chapter 3 NALP3 (NLRP3) and Gout (痛风) The disease gout has been known for many years to be caused by monosodium urate (尿酸钠) crystals deposited in the cartilaginous tissues of joints, causing inflammation. Urate crystals (尿酸钠晶体) activate the NALP3 inflammasome, and that this induces the inflammatory cytokines that cause the symptoms of gout. Pattern recognition by cells of the innate immune system. 3-9 The RIG-I-Iike helicases (解旋酶) detect cytoplasmic viral RNAs and stimulate interferon production. (RIG-I监测胞浆病毒RNA，刺激I型干扰素产生) TLR-3, TLR-7, and TLR-9 can detect viral RNAs and DNAs, but they interact primarily with extracellular material entering the endocytic pathway rather than with nucleic acids present in the cytoplasm of a virus-infected cell as a result of viral replication. Cytoplasmic viral RNAs are sensed by proteins called the RIG-I-like helicases (RLHs), which have an RNA helicase-like domain that binds to viral RNAs, and two amino-terminal CARD domains that interact with adaptor proteins and activate signaling when viral RNAs are bound. RIG-I: retinoic acid-inducible gene I (视黄酸诱导性基因I) RIG-I is widely expressed across tissues and cell types and serves as an intracellular sensor for several kinds of infections. RIG-I senses the unmodified 5-triphosphate end of ssRNA. (RIG-I识别ssRNA 5未修饰的三磷酸末端) MDA-5 (melanoma differentiation-associated 5) is similar in structure to RIG-I, but it senses dsRNA. (MDA-5识别dsRNA 5未修饰的三磷酸末端) Sensing of viral RNAs by RIG-I and MDA-5 induces the production of type I interferons. (RIG-I和MDA-5感知病毒RNA后诱导I型干扰素的产生) RIG-I and MDA-5 are cytoplasmic sensors of viral RNA Pattern recognition by cells of the innate immune system. 3-10 Activation of TLRs and NLRs triggers changes in gene expression in macrophages and dendritic cells that have far-reaching effects on the immune response. C