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1、Introduction,Advanced Immunology,Molecular Biology Immunology Cell Biology,Troika promoting Modern Life Science:,Brief History of Immunology1. Empirical Immunology2. Scientific Immunology3. Modern Immunology,天花病人局部痂皮磨成粉,鼻吸入,预防儿童天花,中国古代“种人痘”,(1617世纪),1717 England: Lady Mary Montagu,“The small pox, so

2、 fatal, so general amongst us, is entirely harmless here by the invention of ingrafting.I am patriot enough to bring this invention into fashion in England.,Edward Jenner (1749-1823),Jenner种牛痘图,Louis Pasteur,Fowl cholera,1879,Pasteurella multocida,狂犬病疫苗 炭疽病疫苗,vaccine,梅奇尼科夫(Elie, 1845-1916, 俄国动物学家、细菌

3、学家, 曾获1908年诺贝尔生理学-医学奖),贝林(Emilvon, 1854-1917, 德国细菌学家, 曾获1901年诺贝尔生理学-医学奖),科赫 (Robert, 1843-1910, 德国细菌学家, 医学家, 结核菌、霍乱菌发现者, 曾获1905年诺贝尔生理学-医学奖),欧立希(Paul Ehrlich,1854-1915,德国免疫学家,曾获1908年诺贝尔生理学-医学奖),提出体液免疫理论和抗体生成的侧链学说,发现细胞吞噬作用,提出细胞免疫理论,发现结核杆菌;提出病原菌致病的概念,发现抗毒素并治愈一名白喉患者,* Burnet(1957年)Clonal selection theor

4、y,Top Immunologist; 1960 Nobel prize winner,Clonal selection theory,20世纪获得诺贝尔医学生理学奖的免疫学家 年代 学者姓名 国家 获奖成就 1901Behring德国发现抗毒素,开创免疫血清疗法 1905Koch德国发现结核杆菌,发明诊断结核病的结核菌素 1908Ehrlich德国提出抗体生成侧链学说和体液免疫学说 Metchnikoff 俄国发现细胞吞噬作用,提出细胞免疫学说 1912Carrel法国器官移植 1913Richet法国发现过敏现象 1919Bordet比利时发现补体, 建立补体结合试验 1930Landst

5、einer奥地利发现人红细胞血型 1951Theler 南非发明黄热病疫苗 1957Bovet意大利抗组胺药治疗超敏反应 1960Burnet 澳大利亚提出抗体生成的克隆选择学说 Medawar英国发现获得性移植免疫耐受性 1972Edelman美国阐明抗体的化学结构 Porter英国阐明抗体的化学结构 1977Yalow美国创立放射免疫测定法 1980Dausset法国发现人白细胞抗原 Snell 美国发现小鼠H-2系统 Benacerraf 美国发现免疫应答的遗传控制 Jerne丹麦提出天然抗体选择学说和免疫网络学说 Kohler德国杂交瘤技术制备单克隆抗体 Milstein阿根廷 单克隆

6、抗体技术及Ig基因表达的遗传控制 Tonegawa日本抗体多样性的遗传基础 Murray美国第一例肾移植成功 Thomas美国第一例骨髓移植成功 1996Doherty澳大利亚 提出MHC限制性,即T细胞的双识别模式 Zinkernagel瑞士提出MHC限制性,即T细胞的双识别模式,潘建平 邵传森主编医学免疫学浙江大学出版社 2006 何维主编 医学免疫学人民卫生出版社 2005 Abbus A K, et al. Cellular and Molecular Immunology.6th ed. Elsevier Saunders 2007 Janeway C A, et al. Immun

7、obiology. 7th ed. Garland Science Publishing 2007 龚非力主编 医学免疫学第二版 科学出版社 2004 陈蔚峰主编 医学免疫学第五版 人民卫生出版社 2008,References,Contents: Concept of Immunity Immune Response Immune Cells Tissues and Organs of the Immune System Immunopathology,Immunity,1.Immunity: refers to all mechanisms used by the body as prot

8、ection against environmental agents that are foreign to the body. (to recognize and eliminate foreign substances) 2.Agents: microorganisms (viruses, bacteria etc) and their products, foods, chemicals, pollen, tumor cells, etc. 3.Immune system: immune tissues and organs, immune cells, immune molecule

9、s,4.Immune response: collective and coordinated response to the introduction of foreign substances. benefits; damaging effects 5.Immunology: study the structure of immune system and its functions.,Immune Response,Introduction,Innate immune response natural immune response non-specific immune respons

10、e Adaptive immune response acquired immune response specific immune response,Innate immune response,Physiological barriers skin mucous membranes Phagocytosis polymorphonuclear leukocytes (PMN) monocytes/macrophages Natural killer (NK) cell Complement and acute phase proteins,Introduction,Innate immu

11、ne response,Introduction,Adaptive immune response,The T cells and B cells in the body recognize the antigen and, in turn, become activated. The activated lymphocytes then proliferate and carry out their specific effector functions.,Adaptive immune response,Introduction,1. The activation of lymphocyt

12、es antigen interacts with specific receptors: B cell- BCR (B cell receptor): membrane Ig T cell- TCR (T cell receptor) 2. Proliferation and differentiation of lymphocytes B cell-cytokines (IL-4,etc.) T cell-Antigen-TCR; co-stimulatory signal; cytokines(IL-2,IL-7,IL-15) 3. Effector cells and their fu

13、nctions B cell-Antibody; T cell-CTL, Th 4. Memory cells,The innate and adaptive immune response,Introduction,Downloaded from: StudentConsult (on 31 May 2006 05:26 PM), 2005 Elsevier,Links between innate and adaptive immunity,Immune Cells,Introduction,hematopoietic stem cell (HSC),Myeloid progenitor,

14、Lymphoid progenitor,Granulocytes (eosinophils, neutrophils, basophils) Monocytes, macrophages Dendritic cell Erythrocyte Megakaryocyte,T lymphocyte B lymphocyte NK cell Dendritic cell,Introduction,Immune Cells,1.Lymphocytes (except NK cells) are wholly responsible for the specific immune recognition

15、 of pathogens, so they initiate adaptive immune responses. 2.Lymphocytes are derived from bone-marrow stem cells. 3.B lymphocytes develop in the bone marrow. T lymphocytes develop in the thymus.,Introduction,Lymphocytes,B Lymphocytes, BCR: a surface receptor (mIg) specific for a particular antigen B

16、 cells plasma cells antibody (the same specificity as the BCR) humoral immunity,Introduction,Ag,secrete,TCR: T-cell antigen receptor TCR+ 95% TCR+ 15% 1. Cytotoxic T cells (CTL) 2. helper T cells: Th0, Th1, Th2, Th3, Th17 3. Regulatory T cells (Treg) and suppressor T cells (Ts),Introduction,T Lympho

17、cytes,Introduction,T Lymphocytes,Human T-lymphocyte Attacking Fibroblast Tumor Cells,Antigen presenting cells (APC),Dendritic cells (DC): powerful in antigen processing and presentation. Macrophage: powerful in antigen processing and destruction, but low in antigen presentation.,Introduction,Antigen

18、 presenting cells,Introduction,Natural killer cells (NK),1. 5-10% of blood lymphocytes, LGL 2. express neither T-cell nor B-cell antigen receptors,Introduction,Phagocytic cells,Monocytes (blood)/Macrophages (tissues) functions: 1. remove particulate antigens 2. take up, process and present antigenic

19、 peptides to T cells distribution: Kupffer cells in the liver microglial cells in the brain,Introduction,Phagocytic cells,Introduction,monocyte,neutrophil,Phagocytic cells,Polymorphonuclear granulocytes 1.neutrophils; basophils; eosinophils 2.neutrophils are short-lived phagocytic cells multilobed n

20、ucleus; 10-20 m 3.neutrophils have a large arsenal of antibiotic proteins granules: lysosomes; lactoferrin,Introduction,Phagocytic cells,Introduction,eosinophil,neutrophil,Tissues and organs of the immune system,Primary (or central) lymphoid organs bone marrow thymus Secondary (or peripheral) lympho

21、id organs spleen lymph nodes Mucosal-associated lymphoid tissue (MALT),Introduction,The place in which proliferation of HSC takes place The place in which development and maturation of B cells occur. The lymphoid progenitor cells are transported by circulating blood to the thymus and differentiate i

22、nto functional T lymphocytes.,Introduction,Bone marrow,The thymus,1. Cells: thymic stromal cells (TSC) epithelial cells, monocytes (macrophage), TDC thymocytes T cell (+) 2. Structure: cortex-immature thymocytes medulla-mature thymocytes M, TDC 3. Function: the site of T cell maturation/selection; It determines the specificity of the TCR expressed on the T cells released to periphery.,Introduction,The lymph node,Human:2-10mm in diameter Round and kidney shaped Consists of : cortex (B-cell area) paracortex (T-cell area) central medulla (B-cell area),Introduction,The l

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