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高度暴露医护人员体内抗结核保护性免疫反应研究

摘要第3-4页
Abstract第4页
Abbreviations第9-10页
Chapter 1 Introduction第10-38页
    1.1 Tuberculosis-a global problem第10-11页
    1.2 History of tuberculosis第11-12页
    1.3 Mycobacterium tuberculosis第12-15页
        1.3.1 General characteristics第13页
        1.3.2 Cell wall structure第13-15页
    1.4 TB vaccine development第15-17页
    1.5 The role of macrophages in tuberculosis第17-19页
    1.6 The role of humoral immunity in tuberculosis第19-28页
        1.6.1 B cells contributions towards tuberculosis control第20-21页
        1.6.2 Antibodies contributions towards tuberculosis control第21-24页
        1.6.3 Characteristics of protective antibodies to Mtb第24-25页
        1.6.4 Fc receptors roles in Mtb infection第25-28页
    1.7 The role of T cells response in tuberculosis第28-31页
        1.7.1 T cells第28-29页
        1.7.2 T cells receptor第29-31页
    1.8 Animal models for tuberculosis第31-34页
        1.8.1 Murine models第32-33页
        1.8.2 Guinea pig model第33页
        1.8.3 Non-human primate model第33-34页
    1.9 TCR deep sequencing第34-36页
    1.10 The purpose of this project第36-38页
Chapter 2 Materials and Methods第38-52页
    2.1 Materials第38-41页
        2.1.1 Cell lines第38页
        2.1.2 Mycobacterial strains and culture第38页
        2.1.3 Culture medium第38-39页
        2.1.4 Mycobacterial culture第39-40页
        2.1.5 Buffers第40页
        2.1.6 Reagents第40-41页
        2.1.7 Mice第41页
    2.2 Methods第41-52页
        2.2.1 Ethics statement第41页
        2.2.2 Study design and participants第41-42页
        2.2.3 T-SPOT.TB Test第42页
        2.2.4 Human peripheral blood mononuclear cell (PBMCs) Isolation第42-43页
        2.2.5 T cells isolation第43页
        2.2.6 Analysis of purity of T cells by Flow Cytometry第43页
        2.2.7 T cell genome DNA extraction第43-44页
        2.2.8 Isolation and identification of Beijing genotype strains第44页
        2.2.9 DNA gel electrophoresis analysis第44-45页
        2.2.10 Immunoglobulin purification, concentration and dialysis第45页
        2.2.11 SDS-PAGE analysis第45页
        2.2.12 M.tuberculosis lysates preparation第45-46页
        2.2.13 Antibodies titer determination by ELISA第46页
        2.2.14 Mouse protection assay第46-47页
        2.2.15 Whole blood killing assay第47-48页
        2.2.16 Mtb proteome binding array第48页
        2.2.17 Antibodies depletion assay第48页
        2.2.18 Mtb capsule immune assay第48-49页
        2.2.19 THP-1 cells differentiation第49页
        2.2.20 Phagocytosis by flow cytometry第49-50页
        2.2.21 Fc receptors blocking assay第50页
        2.2.22 T cell depletion assay第50页
        2.2.23 Human antibodies isotyping assay第50-51页
        2.2.24 Antibodies persistence calculation第51页
        2.2.25 TCR deep sequencing第51页
        2.2.26 Statistical analysis第51-52页
Chapter 3 Results and Discussion第52-90页
    3.1 Results第52-85页
        3.1.1 Clinical data and Information第52-55页
        3.1.2 The purity of the isolated T cells第55页
        3.1.3 T cells DNA genome第55-56页
        3.1.4 Beijing genotype clinical strains isolation第56-57页
        3.1.5 Human immunoglobulin purification第57-58页
        3.1.6 Healthcare workers exposed to TB make detectable antibody responses第58-59页
        3.1.7 Individual HCWs make protective antibody responses against tuberculosis in a mouse infection model第59-61页
        3.1.8 Protective antibodies have no protective effect against Mtb in nude mice .第61-62页
        3.1.9 Protective antibodies inhibit Mtb growth in Vitro第62-63页
        3.1.10 Protective antibodies have the protection in Vitro in a dose dependent manner第63-64页
        3.1.11 The whole blood assay in vitro is in good correlation with the murine protection assay第64-65页
        3.1.12 The antigen hits identified by Mtb proteome assay第65-68页
        3.1.13 Protective antibodies are directed at the M. tuberculosis surface第68-71页
        3.1.14 Protective antibodies have no effect on Mycobacteria phagocytosis by macrophage第71-73页
        3.1.15 Blocking both of CD16 and CD32 abrogates the efficacy of protective antibodies第73-74页
        3.1.16 Protective antibodies require CD4+ T cells for efficacy against Mtb infection第74-75页
        3.1.17 Antibodies isotypes and persistence in vivo are not responsible for protection第75-79页
        3.1.18 The summary features of TCRB and TCRAD statistics第79-80页
        3.1.19 Distribution characteristics of CDR3 length of the 6 subjects第80-82页
        3.1.20 Distribution of TCRBV, TCRADV, TCRBJ and TCRADJ genes among the 3 groups第82-85页
    3.2 Discussion第85-90页
Chapter 4 Conclusions and Future Perspectives第90-96页
    4.1 Conclusions第90-92页
    4.2 Future perspectives第92-96页
References第96-119页
Acknowledgements第119-121页
个人简历、在学期间发表的学术论文与研究成果第121-122页

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