institute for immunobiology
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INSTITUTE FOR IMMUNOBIOLOGY. 抗体研究给我们带来的启示 Apocalypse from the Study on Antibody Institute for Immunobiology Department of Immunology Center for Gene Immunization and Vaccine Research Fudan University 熊思东： 021-54237749 or 55664923 [email protected] or [email protected]. Shanghai, China. - PowerPoint PPT PresentationTRANSCRIPT
INSTITUTE FOR IMMUNOBIOLOGY
抗体研究给我们带来的启示抗体研究给我们带来的启示Apocalypse from the Study on AntibodyApocalypse from the Study on Antibody
Institute for ImmunobiologyDepartment of Immunology
Center for Gene Immunization and Vaccine ResearchFudan University
熊思东： 021-54237749 or [email protected] or [email protected]
Shanghai, China
《圣经》启示录中代表瘟疫的第四骑士《圣经》启示录中代表瘟疫的第四骑士
杜勒，画于 1498 年。画中我们可以看到启示录中的四骑士，他们分别代表了预示世界末日的四种力量，战争、饥荒、死亡以及最为可怕的一个——瘟疫。
Pandora and her boxPandora and her box
唐开元间（ 618 ～）江南赵氏：鼻苗种痘法（清《牛痘新书》》董玉山 (1884) ）：“考上世无种痘，诸经自唐开元间，江南赵氏，始传势苗种痘之法”。
Edward Jenner, Sarah Nelmes, Joseph Meister and his motherEdward Jenner, Sarah Nelmes, Joseph Meister and his mother
"Getting the jab." Jenner inoculated an 8 year old boy James Phipps w"Getting the jab." Jenner inoculated an 8 year old boy James Phipps with cowpox on May 14 1796. The boy died of TB at 21. ith cowpox on May 14 1796. The boy died of TB at 21.
我们，全球扑灭天花证实委员会委员，
我们，全球扑灭天花证实委员会委员，
证实扑灭天花已经在全世界实现。
证实扑灭天花已经在全世界实现。
Louis Pasteur (1822-1895)
1880 Vaccine
1881 Vaccine to Anthrax
1885 Vaccine to Rabies
Robert Koch (1843-1910)
M. TuberculosisKoch Phenomenon
1905 "for his investigations and discoveries in relation to tuberculosis"
How does vaccine work ???
Paul Ehrlich (1854-1915)Paul Ehrlich (1854-1915) Elie Metchnikoff (1845-1916)Elie Metchnikoff (1845-1916)
1908 "in recognition of their work on immunity"
1888 Roux/Yersin Diphtheria toxin
1890 Behring/Kitasato Serum therapy
Emil Adolf von Behring
Marburg University Marburg, Germany
1854 - 1917
"for his work on serum
therapy, especially its
application against
diphtheria, by which he has
opened a new road in the
domain of medical science
and thereby placed in the
hands of the physician a
victorious weapon against
illness and deaths"
The Nobel Prize in Physiology or Medicine 1901The Nobel Prize in Physiology or Medicine 1901
1897 Ehrlich Humoral immunity
Rodney R. Porter
1917 Liverpool U.
1946 Cambridge U.
1972 Nobel Prize
1985
110KD: 分子量太大
Antibody: Fab
Fc
Single chain
Gerald M. Edelman
1929 生于纽约
1950 学士
1954 宾大博士
1957 洛克菲勒大学
Antibody: H
L
H Ab
L Ab
Anti-H Anti-L
Fab + +
Fc + -
抗体的 基本结构
1 ）四肽链通过链间二硫键组成 H2L2
重链： 450aa, Mr.5X104, 五类 ( 、、、、 )
轻链： 214aa, Mr.2.5X104 , 两型 ( 、
2 ）分三个功能区：
可变区 (Variable region, VH/VL, Fv) ：结合抗原
恒定区 (Constant region, CH/CL) ：次级反应、抗原性
绞链区 (Hinge region)CH1-CH2 间 , 30aa,2-5 链间二硫键
3 ）蛋白酶可酶解
木瓜蛋白酶 (papain) ： Fab 、 Fc
胃蛋白酶 (pepsin) ： F(ab’)2 →2XFab’ 、 pFc’
The Nobel Prize in Physiology or Medicine 1972The Nobel Prize in Physiology or Medicine 1972
for their discoveries concerning the for their discoveries concerning the chemical structure of antibodieschemical structure of antibodies
Gerald M. EdelmanRodney R. Porter
César Milstein César Milstein
Argentina and United Kingdom
MRC Laboratory of Molecular Biology Cambridge, United Kingdom
b. 1927(in Bahia Blanca, Argentina)d. 2002
Federal Republic of Germany
Basel Institute for Immunology Basel, Switzerland
b. 1946d. 1995 Georges J.F. KöhlerGeorges J.F. Köhler
for the discovery of the principle for production of monoclonal antibodies
César Milstein César Milstein Georges J.F. KöhlerGeorges J.F. Köhler
the Nobel Prize in Physiology or Medicine for 1984the Nobel Prize in Physiology or Medicine for 1984
P. EhrlichP. Ehrlich
Side-chain theorySide-chain theory
Clonal selectionClonal selection
Sir FM Burnet
(1899-1985)
The Self-Nonself ModelThe Self-Nonself Model
Burnet’s original model
each lymphocyte expresss mutiple copies of a single surface receptor specific for a foreign entity.
signaling through this surface antibody initiates the immune response.
the self-reactive lymphocytes are deleted early in life
"for his discovery of the genetic principle for generation of antibody diversity"
Susumu TonegawaSusumu Tonegawa (1939-) , MIT(1939-) , MIT
The Nobel Prize in Physiology or Medicine 1987The Nobel Prize in Physiology or Medicine 1987
The Nobel Prize in Physiology or Medicine 1984The Nobel Prize in Physiology or Medicine 1984
for theories concerning the specificity in for theories concerning the specificity in
development development
Niels K. Jerne
杀伤性 T细胞对靶细胞的杀伤作用
1
2 3
Classic experiment of Zinkernagel and Doherty demonstrating that Ag recognition by T cells exhibits MHC restriction
Clonal selectionClonal selection
Altered-self modelDual receptor model
Identifying and cloning Identifying and cloning
the TCR genesthe TCR genes
The T-cell receptor resembles The T-cell receptor resembles a membrane-bound Fab fraga membrane-bound Fab frag
mentment
for their discoveries concerning "the specificity of the cell mediated immune defense
Peter C. DohertyPeter C. Doherty Rolf M. ZinkernagelRolf M. Zinkernagel
the Nobel Prize in Physiology or Medicine for 1984the Nobel Prize in Physiology or Medicine for 1984
谢 谢谢 谢