| 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 |
