模式识别受体PPT演示课件.ppt
《模式识别受体PPT演示课件.ppt》由会员分享,可在线阅读,更多相关《模式识别受体PPT演示课件.ppt(84页珍藏版)》请在三一文库上搜索。
1、1,Innate Immune recognition,2,Threats to the individual,3,Protection from microbial invasion,4,5,Nobel Prize 2011 innate immunity,6,Nobel Prize 2011,Jules A. Hoffmann: In 1996, found “Toll” gene has a role in the flys immunity to fungal infections. Bruce A. Beutler: in 1998, Bruce A. Beutler and col
2、leagues discovered that the Toll-like receptors (TLRs) act as the principal sensors of infection in mammals. Ralph M. Steinman 1973,Ralph Steinman isolate Dentritic Cell)。 DC can activate T cell. DC is the birdge between innate immunity and adaptive immunity.,7,Toll Pathway,Drosophila,8,They all des
3、erve the Nobel Prize,Ruslan Medzhitov,Charles Janeway 19432003,Takashi Fujita, Shizuo Akira,PRR,TLR,RLR,Yale Univ.,Yale Univ.,Kyoto Univ., Osaka Univ.,9,pathogen associated molecular patterns, PAMPs Conserved pattern found only in pathogens, not in host cells。 (Charles Jenaway 1989,at Cold spring ha
4、rbor meeting) Typical PAMPs: 1、Glycans:G- bacteria (lipopolysaccharide, LPS); G+ bacteria (peptidoglycan); Bacterial flagellin 2、Nucleotide: Virus DNA/RNA.,10,PAMPs,GlucanPeptidoglycanLPS Flagellin 。,11,pattern recognition receptors, PRR: Receptors, on the surface or inside the cells, for those path
5、ogen associated molecule patterns. Types of PRRs: Toll-like receptors; TLRs RNA sensor(RIG-I, MDA5) DNA sensor(AIM2,DAI) NOD-like receptors; NLRs C-Lectin receptors Other PRRs,12,PRR-PAMPs engagement activates phagocytes,13,Toll like Receptor (TLR),Nature. 1997 Jul 24;388(6640):394-7. A human homolo
6、gue of the Drosophila Toll protein signals activation of adaptive immunity. Medzhitov R, Preston-Hurlburt P, Janeway CA Jr. Source Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520-8011, USA. Abstract We report here the cloning and characterization of a human
7、 homologue of the Drosophila toll protein (Toll) which has been shown to induce the innate immune response in adult Drosophila. Like Drosophila Toll, human Toll is a type I transmembrane protein with an extracellular domain consisting of a leucine-rich repeat (LRR) domain, and a cytoplasmic domain h
8、omologous to the cytoplasmic domain of the human interleukin (IL)-1 receptor. Both Drosophila Toll and the IL-1 receptor are known to signal through the NF-kappaB pathway. We show that a constitutively active mutant of human Toll transfected into human cell lines can induce the activation of NF-kapp
9、aB and the expression of NF-kappaB-controlled genes for the inflammatory cytokines IL-1, IL-6 and IL-8, as well as the expression of the co-stimulatory molecule B7.1, which is required for the activation of naive T cells.,PUBMED search “Toll like receptor” 24700 papers,14,1-1) Cellular distribution
10、of TLRs,Cell membrane,Endosome membrane,15,PRRs in PMN,16,1-2) TLRs expression in cells,Immune cells and some epithelia cells express TLRs,17,TLRs expressed in immune cells,18,1-3) Structure of TLRs,* Homo-or heterodimers, or together with other molecules,19,1-4) TLRs signaling pathway:,MyD88 depend
11、ent pathway: All TLRs except 3 MyD88 independent pathway: TLR3; part of TLR4,effector genes,20,TLRs signaling pathway:,21,TLRs signaling pathway:,22,1.5) Negative regulation of TLRs signaling,23,1-6) Role of TLRs in immune response,Innate immunity: Activate phagocytosis and killing: regulated expres
12、sion of genes of phagocytosis Promoting secretion of cytokines/ chemokines : IL1, IL6, TNFa, IFNs, CXCLs, CCLs (recruit other immune cells)Promote secretion of anti-peptide: eg: Defensins,24,1-6) Role of TLRs in immune response,Adaptive immunity:TLRs induce DC maturation: cytokine secretion; costimu
13、latory molecules - DC activation - present antigen to activate T cellsTLRs signaling influences Th cell differentiation: to influence the differentiation of T cells: Th1, Th2, Th17TLRs induce Treg activation: regulatory T cells Treg express TLR4/5/7/8, TLR signal directly involved in the biological
14、function of TregB cell activation (eg: CpG DNA TLR9 ligands may be used as adjuvant),25,2-1)RNA sensors(TLRs and RLRs),RIG-I Like Receptors(RLR): RIG-I MDA-5 LGP2 。,Fujita T,Nat Immunol. 2004 J Immunol 2005,26,2-2) structure of RIG-I,RIG-I 结合 5-ppp dsRNA,27,MAVS: adapter for RIG-I,Seth, R.B., Sun, L
15、., Ea, C., and Chen, Z.J., Identification and characterization of MAVS: a mitochondrial antiviral signaling protein that activates NF-B and IRF3. Cell, 122:669-682, 2005,Prion-like protein fight off viruses: MAVS, Cell 2011,University of Texas Southwestern HHMI,28,2-3)RIG-1/MDA-5 signaling pathway,2
16、9,2-4) regulator of RIG-I/MDA-5,30,Ubiquitin (泛素)对PRR信号的调节,泛素由76个氨基酸残基组成,其中包括7个赖氨酸残基(K), 其C末端可与底物的赖氨酸残基形成异肽键,从而引起底物泛素化。泛素的K11、K29、K48和K63均能参与形成泛素与泛素间的异肽键 (Isopeptide bond)。,30,31,Ubiquitination for RIG-I signaling,K63泛素化:激活 K48泛素化:降解,Back,32,3-1) DNA sensor,DNA sensor: TLR9; Pol III; DAI; AIM2,33,4-
17、1) NOD like receptors(NLRs),NLRs: C端:亮氨酸重复序列 (LRR) 中间:NACHT: 寡聚体化,活化 N端:CARD,PYD:相互作用,34,4-2)NLRs activtes inflammasome,PAMP通过NLRs激活炎症反应,35,NLRC4 inflammasome,邵峰 北京生命科学研究所 Shao F. (2011) Nature, 477, 596600.,36,5-1)C-Lectin receptor family,Dectin-1, Mannose Receptors (MRs),37,5-2) The fungal pattern
- 配套讲稿:
如PPT文件的首页显示word图标,表示该PPT已包含配套word讲稿。双击word图标可打开word文档。
- 特殊限制:
部分文档作品中含有的国旗、国徽等图片,仅作为作品整体效果示例展示,禁止商用。设计者仅对作品中独创性部分享有著作权。
- 关 键 词:
- 模式识别 受体 PPT 演示 课件
链接地址:https://www.31doc.com/p-10903726.html