醫(yī)學(xué)免疫學(xué)課件：NK細胞與免疫記憶

1、我們畢業(yè)啦其實是答辯的標(biāo)題地方Natural killer cell Immunological MemoryCONTANTSBACKGROUNDNK cellReceptorImmunological MemoryMECHANISMHapten-inducedMCMV-inducedCytokine-inducedHUMANDiscovery and futureSummeryNatural Killer CellInnate lymphocytesdevelop in bone marrowdifferentiate by microenvironment10-15% in PB, 30%

2、 in liverno gene rearranged receptornull cell BACKGROUND/natural_killer_cells.htmlBACKGROUNDSubsetsCD56bright10%immunoregulatory cytokinesCD56dim90%high cytotoxic potentialHigh CD16ADCCFarag S S, Caligiuri M A. Farag SS, Caligiuri MA. Human natural killer cell development and biology. Blood Rev 20:

3、123-137J. Blood Reviews, 2006, 20(3):123-37.BACKGROUNDReceptorInhibiting receptor： KIR，KLRActivating receptor： KAR、NCR，NKG2DOther receptors： CD16、Ly49、Ly49H、TLR/course/yxmyx/chapter6/NK.htmBACKGROUNDActivation vs InhibitionMorvan M G, Lanier L L. NK cells and cancer: you can teach innate cells new t

4、ricks.J. Nature Reviews Cancer, 2015, 16(1):7-19.1964 - Bone marrow transplantF1 murine rejection2006 - Hapten induction testVon AdrianRag2/, SCID micecontact hypersensitivity (CHS) responseBACKGROUNDImmunological MemoryWild Type + DNFBCHS responseWeeks later +DNFBNo T/B cell + DNFBMemory immune res

5、ponseNo T/B/NK cell + DNFBNo CHS responseDNFB infected NK cellMemory immune responseCONTANTSBACKGROUNDNK cellReceptorImmunological MemoryMECHANISMHapten-InducedMCMV-InducedCytokine-InducedHUMANDiscovery and futureSummeryHapten-InducedMECHANISMLiverCXCR6 (CXC-chemokine receptor6) CXCL16: in liversinu

6、soidalendothelialcellIFN- IFN- IL-12Cerwenka, A. and L.L. Lanier, Natural killer cell memory in infection, inflammation and cancer. Nat Rev Immunol, 2016. 16(2): p. 112-23.MCMV-InducedCMV DNA virusHCMV (human cytomegalovirus); MCMV(murine cytomegalovirus)Ly49H: on NK cellM157: on MCMVAdoptive transf

7、er Ly49H+1000 times proliferationIFN- enhancedMECHANISMO Sullivan, T.E., J.C. Sun and L.L. Lanier, Natural Killer Cell Memory. Immunity, 2015. 43(4): p. 634-645.MECHANISMCytokinesFunctionIL-12，STAT4NK cell activation，IFN- generationIFN-gNK cell proliferation and differentiationIL-33，IL-18，MyD88Speci

8、fic NK cell proliferationIL-12，IL-18，type I IFNsProliferation and protectionCostimulatoryMoleculesDNAM-1Recognize CD155、CD112DNAM-1-PKC pathwayDNAM-1-Fyn pathwayInflammatoryCytokinesIL-12 IL-18 IL-33MECHANISMSignalingLy49HM157DNAM-1CD155Cytokines: IL-12 IL-18 IL-33MCMV-InducedCerwenka, A. and L.L. L

9、anier, Natural killer cell memory in infection, inflammation and cancer. Nat Rev Immunol, 2016. 16(2): p. 112-23.MCMV-InducedApoptosisBcl-2 promoting signalBim inhibiting signalIL-15Mcl-1 Bim Erk1、2 Bim PI(3)K、Akt Foxo3a BimMitochondria Bim ApoptosismTOR and AMPKMECHANISMCytokine-InducedIL-12、IL-15、

10、IL-18Adoptive transferIn vitro experimentFluorescent labeling immune responseIFN- CytotoxicityMECHANISMCerwenka, A. and L.L. Lanier, Natural killer cell memory in infection, inflammation and cancer. Nat Rev Immunol, 2016. 16(2): p. 112-23.Cytokine-InducedIfng expression enhancedAgainst tumorlymphoma

11、 melanomaCD4+T cell IL-2 activate NK cell side effectMECHANISMCONTANTSBACKGROUNDNK cellReceptorImmunological MemoryMECHANISMHapten-inducedMCMV-inducedCytokine-inducedHUMANDiscovery and futureSummaryNK cell against virusHCMV、EB virus、 HHV 、 VZV 、HPVHCMV infectedNKG2C+NK cellProliferation and last for

12、 250d80% in PBHUMANGeneral immune responseInfluenza vaccineIFN- enhanced after vaccinationHUMAN.au/blog/could-alzheimer%E2%80%99s-disease-vaccine-be-reality.summaryDevelopment and ChallengeMechanism and RegulationApplication and FutureFarag S S, Caligiuri M A. Farag SS, Caligiuri MA. Human natural k

13、iller cell development and biology. Blood Rev 20: 123-137J. Blood Reviews, 2006, 20(3):123-37.OLeary, J.G., et al., T cell- and B cell-independent adaptive immunity mediated by natural killer cells. Nat Immunol, 2006. 7(5): p. 507-16.Cooper MA, Elliott JM, Keyel PA, et al. Cytok ine-induced memory-l

14、ike natural killer cells J. Proc Natl Acad Sci USA, 2009, 106(6):1915-1916.Paust S, Gill HS, Wang BZ, et al. Critical role for the chemokine receptor CXCR6 in NK cell mediated antigen-specific memory of haptens and viruses J. Nat. Immunol, 2010, 11:11271135.Cytomegalovirus generates long-lived antig

15、en-specific NK cells with diminished bystander activation to heterologous infection J. J. Exp. Med., 2014, 211:26692680.Karo JM, Schatz DG, Sun JC. The RAG recombinase dictates functional heterogeneity and cellular fitness in natural killer cells J. Cell, 2014, 159:94107.O Sullivan, T.E., J.C. Sun a

16、nd L.L. Lanier, Natural Killer Cell Memory. Immunity, 2015. 43(4): p. 634-645.REFERENCEMartinet, L. and M.J. Smyth, Balancing natural killer cell activation through paired receptors. Nat Rev Immunol, 2015. 15(4): p. 243-54.Artis D, Spits H. The biology of innate lymphoid cells. Nature. 2015; 517:293

17、301. Morvan M G, Lanier L L. NK cells and cancer: you can teach innate cells new tricks.J. Nature Reviews Cancer, 2015, 16(1):7-19.Kamimura Y, Lanier LL. Homeostatic control of memory cell progenitors in the natural killer cell lineage. Cell reports. 2015; 10:280291.Hari P, Raj RV, Olteanu H. Targeting CD38 in Refractory Extranodal Natural Killer Cell-T-Cell Lymphoma. N Engl J Med. 2016. 375(15):1501-1502.Cerwenka, A. and L.L. Lanier, Natural killer cell m