Chapter 1
History of Immunology
The position of Immunology in life science
• Immunology is one of three pioneer subjects in
life science
• Three pioneer subjects:
Molecular Biology
Neurobiology
Immunology
免疫学的发展带动了生命科学的基础研究
Immunology promotes basic research in life science
自然科学影响因子最高的杂志—2012年 IF=52.761
免疫学的发展推动了临床医学各科的发展
(The immunology promotes the development of
clinical subjects)
免疫与肿瘤(Immunity and tumor)
免疫与感染性疾病( Immunity and infectious diseases )
免疫与移植(immunity and transplantation
免疫与自身免疫性疾病( immunity and autoimmune
diseases)
免疫的发展带动生物制药工业的发展
(The immunology promotes the production of
biomedicine )
免疫相关产品是生物技术产业中的支柱
2004全球生物技术药物
80%免疫相关
临床试
验17 0
进入市
场 140
研制中
2200
2003年全球生物技术药品市
场达到600亿美元，
市场占有率15%以上的5种
产品中免疫相关产品3个:
• EPO:28%
• 干扰素:15%
• 集落刺激因子:15%
Reference textbooks
•
《医学免疫学》十二五规划双语教材，
主编：孙汶生
出版社：高等教育
•
《Immunology》 Chief editor： Roitt
•
Cellular and molecular Immunology
Chief editor: Abbas and Litchman
Medical immunology
Pert I. Introduction of Immunology
Part II. Immune molecules
Part III. Immune cells and immune responses
Part IV. Clinical Immunity and its application
Part I Introduction of immunology
Chapter I. History of Immunology
Chapter II. Modern Immunology and its
development strategies
Chapter III. General Introduction of immune system
Chapter IV. Antigens
Chapter 1
History of Immunology
Immunology was established with process that
human being fought against infectious diseases.
• Period of Experience Immunology
• Period of Experimental Immunology
• Period of Modern Immunology
I. Period of Experience Immunology (16-19‘s)
----Formation of immunity conception
• The term immunity is derived from the Latin word
immunitas, which referred to the protection from
legal prosecution offered to Roma senators
• The immunity was used first time to refer to an
infection that was called” plague” ( 瘟疫）during
the fifth century BC
The individual
who has
suffered from
smallpox do
not worry
about smallpox
again
Mortality of smallpox is 30%
SARS
The formation of immunity conception
• Human smallpox (天花） vaccine ：variolation（人痘）
to prevent smallpox used by Chinese ---first time using
conception of immunity to prevent disease. 17-18's
Ming Dynasty
• Cowpox（牛痘） vaccine (1798 )--- Edward Jenner’s
successful vaccination against smallpox
Edward Jenner: an English physician
Smallpox was first disease that had been eradicated
worldwide by a program of vaccination (1979.12)
Chinese medical practitioners : variolation (人痘）
Edawar Jennar
• occupational doctor
• exposure to cowpox can
prevents smallpox---vaccination（1796）
• vaccine
They should be vaccinated first
Why do they not want to play with my kids?
II. Period of Experimental Immunology
• Late period of 19's ---middle period of 20's
• Establishment and development of immunology
(I) Discovery of pathogen and Active immunization（1）
l . discovery of Pathogen
Louis Paster: anthracoides（炭疽杆菌)
Koch: tubercle bacillus （结核杆菌）
Louis Pasteur(1822-1895)
Robert Koch
(I) Discovery of pathogen and Active immunity（2）
2. Vaccination and Active immunization
Vaccination : (种痘，接种疫苗,预防接种）
Attenuated vaccine ( 减毒疫苗):Louis Pasteur
Anthrax（炭疽） vaccine
chicken cholera ( 鸡霍乱) Vaccine
A rabies ( 狂犬病）vaccine
Vaccination and active immunization
Louis Pasteur
• Anti-cholera :
1878, old attenuated
culture of chicken cholera
---- vaccine
• Anti-anthrax
• rabies vaccine
(attenuated vaccine)
Louis Pasteur(1822-1895)
(II) Discovery of antibody（抗体）and passive immunity（1）
1. Discovery of antibody
1888: Roux and Yersin discovered that exotoxin ( 外毒素）
produced by C. diphtheriae （白喉杆菌） caused
diphtheria
1889. Von Behring and Kitasato discovered bactericidins
( 杀菌素） or antitoxin(抗毒素）in serum of patient
with diphtheria--- first antibody discovered
1890 Von Behring and Kitasato used diphtheriae antitoxin to
treat patient with diphtheria
Antigen: substance that stimulates individual to produce antibody
(II) Discovery of antibody and passive immunity-2
2.passive immunization
• 1888 exotoxin produced by
C.Diphtheriae
• 1891 Diphtheria antitoxin
( Behring and Kitasato)
•
passive immunity
•
Humoral immunity (Ehrlich)
. antiserum , antibody (Ab)
. antigen (Ag)
. serology
Ehrlich
Active immunity and passive immunity
 Immunity is the protection from diseases and
more responsible for infection diseases.
immunity possesses specificity
• Active immunity: The form of immunity that is induced by
exposure to a foreign antigen, in which the immunized
individual plays an active role in responding to the antigen
• Passive immunity :The form of immunity that is established
in one individual by transfer of antibodies or lymphocytes
from another individual who is immune to that antigen
(II) Discovery of antibody and passive immunity-3
3. Recognition about Structure
of antibody and its specificity
binding to antigen
• Antibody：a type of glycoprotein molecule, also
called immunoglobulin (Ig) , produced by B cells
that bind antigens .often with a high degree of
specificity
The basic structural unit of antibody is composed
of two identical heavy chains and two identical light
chains
(II) Discovery of antibody and passive immunity-4
•4.Hypothesis for the formation of antibodies
Templates postulate (lock and key)
模板假说
Natural selection postulate(1955,Jerne)
自然选择假说
Clonal selection theory : 1957, Burnet
克隆选择学说: (cells as center)
Jerne got it in 1984
Burnett Got Nobel prize in1960，
In physiology and medicine
Burnet Clonal selection theory
Various clones
Clone deletion
birth
Clone selection
Clone expansion
Clonal selection theory
（1）Each lymphocyte bears a single type of receptor with
a unique specificity
（2）lymphocyte bearing receptors specific for ubiquitous self
molecules are deleted in early stage of lymphoid cell
development and are therefore absent from the repertoire
of mature
（3）Interaction between a foreign molecule and specific
receptor with high affinity leads to lymphocyte activation
（4）The differentiated effective cells derived from an activated
lymphocyte will bear receptor of identical specificity
(III) Mechanism of immunity
Humoral immunity-----Paul Erlich
antibody in blood binds to antigen
Cellular immunity----- Elie Metchnikoff
Chicken phagocytes in blood
phagocytized anthracoides
Got Nobel prize in1908
In physiology and medicine
(IV) Immune tolerance
placenta
chimeras
dizygotic twins
异卵双生
1945, Owen observed phenomena of natural immune tolerance
1953, Medawar confirmed immune tolerance by experiment
• Immunologic tolerance is defined as
unresponsiveness to an antigen that is
induced by prior exposure to that antigen.
V. Immunopathology
 Anaphylaxis（过敏反应）or
hypersensitivity：超敏反应
 graft rejection（移植排斥）
 autoimmune disease（自身免疫性疾病）
 Immunodeficiency（免疫缺陷）
New conception of Immunity
In a broader sense , immunity is refers to the ability to
respond to foreign substances (antigen), including
microbes , as well as to macromolecules such as proteins
and polysaccharides, regardless of the physiologic or
pathologic consequence of such a reaction to foreign
substance
Chapter 1
History of Immunology
Immunology was established with process that
human being fought against infectious diseases.
• Period of Experience Immunology
• Period of Experimental Immunology
• Period of Modern Immunology
1. Diversity (多样性）of antigen receptor
2. Pathway of signal transduction（信号传导 ）
3. Pathway of programmed cell death
4. Cytokine and adhesion molecules
（细胞因子） （黏附分子）
Cytokine and adhesive molecules
• Cytokines: a group of low molecule weight proteins
with high activity and multiple functions that are
secreted by many different kinds of cells and that
mediate immune response and inflammatory reaction
• Adhesive molecules:
The cell surface molecules whose function is to promote
adhesive interactions with other cells or the extracellular
matrix and play crucial roles in cell interaction, recognition ,
activation and migration Leukocytes express various types
of adhesion molecules, such as selectins, integrins, and
members of the Ig superfamily, cadherin.
5. development of technique producing Ab
• Polyclonal antibody （多克隆抗体）
• monoclonal antibody （单克隆抗体）
• gene engineering antibody（基因工程抗体）
 Polyclonal antibody: a mixture of Abs with
different specificities and affinities
• Monoclonal antibody Abs produced by single B
cell clone (or one hybridoma clone ) possess
same structure and specificity.
• gene engineering antibody:Abs prepared by the
method of gene recombination
Established monoclonal Ab product methods
in 19745 and got Nobel Prize in 1984
César Milstein
Georges J.F. Köhler
Gene engineering Ab：Abs prepared by the
method of gene recombination
6. transgenic animal（转基因动物）and
gene knockout animal（基因敲除动物）
2007年诺贝尔医学奖获得者
Martin J. Evans ，英国
Mario R. Capecchi ，美国
Oliver Smithies ，
美国
• This year's Nobel Laureates have made a series of ground-breaking discoveries
concerning embryonic stem cells and DNA recombination in mammals.
• Their discoveries led to the creation of an immensely powerful technology referred
to as gene targeting in mice.
• It is now being applied to virtually all areas of biomedicine – from basic research to
the development of new therapies
• Gene targeting is often used to inactivate single genes. Such gene "knockout"
experiments have elucidated the roles of numerous genes in embryonic development,
adult physiology, aging and disease.
•
To date, more than ten thousand mouse genes (approximately half of the genes in
the mammalian genome) have been knocked out.
•
Ongoing international efforts will make "knockout mice" for all genes available
within the near future.
7.MHC ( major histocompatibility complex, 组织相容性复
合体） and finding of MHC restriction (MHC 限制性)
Doherty and Zinkernagel brought forward MHC
restriction theory in 1974 and got Noble Prize in 1996
The Nobel Prize in Physiology or Medicine 1996
for their discoveries concerning the specificity of the cell
mediated immune defense"
"
Peter C. Doherty (1940)
1/2 of the prize
Australia St. Jude Children's Research
Hospital
Memphis, TN, USA
Rolf M. Zinkernagel (1944)
1/2 of the prize
Switzerland , University of Zurich,
Institute of Experimental Immunology
Zurich, Switzerland