医学免疫学免疫11a课件.ppt
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1、Antigen-Presenting Cells and Antigen Presentationxiaojian WangInstitute of Immunology Zhejiang University浙江大学医学免疫学免疫11a1 nIntroduction nAntigen-presenting cellsnAntigen processing and presentationContents浙江大学医学免疫学免疫11a2I.Antigen-presenting cell,APCAntigen-presenting cells are required for T cell act
2、ivation浙江大学医学免疫学免疫11a3nA variety of cells specialized in capturing 、processing and present the antigen to the T lymphocytes,causing either tolerance or immunity.nThese cells are name as Anitgen presenting cell,APCn Dendritic cells,monocytes/macrophages and B cells are professional APCs.I.Antigen-pre
3、senting cell,APC浙江大学医学免疫学免疫11a4APC染色彩图Antigen-presenting cellsDendritic cellsMacrophagesB cells浙江大学医学免疫学免疫11a5 Non-professional APCnEndothelial cell(EC)nFibroblastic cellnActivated T cellUnder some circumstances,they can express MHC II and present Ags浙江大学医学免疫学免疫11a6II.Antigen presentation The proces
4、s by which APC express peptide-MHC on their cell surface in a form recognizable by lymphocytes.浙江大学医学免疫学免疫11a7Antigen-presenting cells浙江大学医学免疫学免疫11a8I.Dendritic cellsnhighly branched morphologyncan active naive T cellsnmarkers浙江大学医学免疫学免疫11a9The Nobel Prize in Physiology or Medicine 2011拉尔夫拉尔夫斯坦曼(斯坦曼
5、(Ralph M.Steinman)【已故已故】1943年出生于加拿大蒙特利尔,在麦吉年出生于加拿大蒙特利尔,在麦吉尔大学学习生物学和化学。之后在美国哈佛医学院学习医学,尔大学学习生物学和化学。之后在美国哈佛医学院学习医学,1968年获得医学博士学位(年获得医学博士学位(MD)。于)。于1970年被纽约洛克菲勒大学接纳,从年被纽约洛克菲勒大学接纳,从1988年起成为免疫学教授。担任该校免疫年起成为免疫学教授。担任该校免疫学与免疫性疾病中心主任。学与免疫性疾病中心主任。发现树突状细胞发现树突状细胞Dendritic cells,DC是启动适应性免疫应答是启动适应性免疫应答的关键细胞的关键细胞R.
6、M.Steinman and Z.A.Cohn.J.Exp.Med.137,11421162;1973 浙江大学医学免疫学免疫11a101.Surface markersnMHC class I/II moleculesnCD1a,CD11c,CD83(human)n33D1,NLDC145(mouse)nCo-stimulatory molecules:B7.1(CD80)/B7.2(CD86),CD40,CD44,CD54浙江大学医学免疫学免疫11a112.Sources of DC单 核 细 胞巨 噬 细 胞中 性 粒 细 胞B 细 胞T 细 胞N K 细 胞髓 系 D CBTN K髓
7、系 D C淋 巴 系 D C淋 巴 系 前 体 细 胞髓 系 前 体 细 胞多 能 造 血 干 细 胞GM-CSFTNF-aIL-4HSCMyeloid progenitorLymphoid progenitorMyeloid DC MomacrophageMyeloid DCPMNLymphoid DC浙江大学医学免疫学免疫11a123.Distribution and Classification of DCDCs are found in many organs throughout the body nDC in lymphoid tissue-Lymphoid tissue DCnI
8、nterdigitating cell,IDCnFollicular DC,FDCnthymic dendritic cell,TDCnDC not in lymphoid tissue-Non-lymphoid tissue DCnLangerhans cells nInterstitial DCnDC in body fluid-Circulating DCnVeiled cellsnPeripheral blood DC浙江大学医学免疫学免疫11a13nLocated in lymph follicles which are rich in B cells;nDerived from i
9、nterstitial DC;nHighly express FcR,CR1 and CR2;nInvolved in the generation and maintenance of memory B cells.1)Follicular DC(FDC)浙江大学医学免疫学免疫11a14Follicular DC,FDCB cellsFDCFDC express high levels of membrane receptors for antibody and complement.By these,FDC actives the B cells in lymph nodes.浙江大学医学
10、免疫学免疫11a152)Interdigitating DC(IDC)nMain APC to induce primary immune response;nDerived from Langerhans cells;nFcR-and C3bR-,MHC I and IIhigh;nDistributed mainly in the T cell area of secondary lymphoid tissue,present Ags to T cells.浙江大学医学免疫学免疫11a163)Langerhans cells(LC)nFound in the epidermis(skin)
11、and mucous membranes;nMHC I and IIhigh,highly express FcR and C3bR,Birbeck particle(due to langerin expression);nPowerful ability to capture and process Ags and migration to lymph node after activation.Langerhans IDC浙江大学医学免疫学免疫11a174.Development of myeloid DCnFour phasesnPre-DCnMonocyte,MonImmature
12、DC nUptake antigennMigrationnMature DCnExpress high levels of MHC I and II,CD80,CD86,CD40,CD54,HSP,etc.浙江大学医学免疫学免疫11a18nImmature DC Phenotype:high expression of receptors related to phagocytosis(FcR,CR,mannose receptor,DC-sign);low expression of CD54,CD40,CD80;CD86 and MHC II,CD14-Function:1)strong
13、capacity to ingest and process Ags,but weak ability to present Ags 2)induction of immune tolerance 3)sensing of infectious agents by TLR(pattern recognition receptors)浙江大学医学免疫学免疫11a19nMature DC Phenotype:low expression of receptors related to phagocytosis(FcR,CR,mannose receptor);high expression of
14、CD54,CD40,CD80,CD86 and MHC II;CD83+and CD25+Function:weak ability to capture and process Ags,powerful ability to present Ags.浙江大学医学免疫学免疫11a20 Dendritic Cell Maturation MHC II浙江大学医学免疫学免疫11a21浙江大学医学免疫学免疫11a225.DC in immune activation and immune tolerance1)DC in immune activation Present antigen and a
15、ctivate T cells The first signal MHC II-Ag:CD4+T cells MHC I-Ag:CD8+T cells The second signal co-stimulating molecules cytokines IL-12 浙江大学医学免疫学免疫11a23n Peripheral tolerance:immature DC capture autoantigen when they migrate from non-lymphoid tissue to T cell area of secondary lymphoid tissue,and ind
16、uce peripheral tolerance.nCentral tolerance:induced in negative selection of T cells in the thymus.n 2)DC induce immune tolerance浙江大学医学免疫学免疫11a24 Bone marrow Blood TissueHSCMyeloid progenitorPre-monocyteMonocyte Monocyte Macrophage II Mononuclear phagocyte system(MPS)1.Differentiation and distributi
17、on浙江大学医学免疫学免疫11a25Different names in different tissuesnMonocyte(blood)nKupffer cells(liver)nMesangial cells(kidney glomerulus)nMicroglia(brain)nAlveolar macrophages(lung)nHistiocyte(connective tissue)浙江大学医学免疫学免疫11a26nMHC-I and II molecules;nCAM:LFA-1,ICAM-1,B7,CD40;nFcR;nCR:CR1,CR3,CR4;nPattern-reco
18、gnition receptor(PRR):mannose receptor,scavenger receptor(CD91),Toll-like receptors 2.Surface markers浙江大学医学免疫学免疫11a273.Biological functions of M Antigen processing and presentation phagocytosis pinocytosis receptor-mediated endocytosis浙江大学医学免疫学免疫11a28 Antimicrobial and cytotoxic activity:a number of
19、 antimicrobial and cytotoxic substances produced by activated M can destroy phagocytosed microorganisms.Reactive oxygen intermediates,nitric oxide.浙江大学医学免疫学免疫11a29n Secretion of soluble factors:enzymes:lysozyme,myeloperoxidase,etc.cytokines:IL-1,IL-6,TNF,IL-12,IL-18,plement:C1C9,Bf coagulation facto
20、rs,PG,LTs,ACTH,etc.浙江大学医学免疫学免疫11a30phagocytosis浙江大学医学免疫学免疫11a31macrophage浙江大学医学免疫学免疫11a32浙江大学医学免疫学免疫11a33浙江大学医学免疫学免疫11a34Ag presentationM a c r o p h a g e s T a k e U p A n t ig e n M a c r o p h a g e s T a k e U p A n t ig e n I n t o V e s ic le s a n d P r e s e n t P e p t id e I n t o V e s i
21、c le s a n d P r e s e n t P e p t id e F r a g m e n t s F r o m P r o t e in sF r a g m e n t s F r o m P r o t e in sin M H Cin M H C-I II I浙江大学医学免疫学免疫11a35III.B cellsbone marrow-dependent lymphocyteAbout 5-15%of the circulating lymphoid pool are B cells defined by the presence of surface immunog
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