Chapter 1

History of Immunology

• Immunology is one of three pioneer subjects in life science

• Three pioneer subjects:

Molecular Biology

Neurobiology

Immunology

The position of Immunology in life science

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)

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%

临床试170验

研制中2200

进入市场140

80% 免疫相关

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

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

Mortality of smallpox is 30%

The individual who has suffered from smallpox do not worry about smallpox again

SARS

• 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)

The formation of immunity conception

Chinese medical practitioners : variolation ( 人痘）

• occupational doctor• exposure to cowpox can

prevents smallpox---- vaccination （ 1796 ）

• vaccine

Edawar Jennar

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）

Robert Koch Louis Pasteur(1822-

1895)

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

(I) Discovery of pathogen and Active immunity （ 2 ）

Louis Pasteur

• Anti-cholera :

1878, old attenuated culture of chicken cholera

---- vaccine • Anti-anthrax• rabies vaccine

(attenuated vaccine) Louis Pasteur(1822-1895)

Vaccination and active immunization

(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

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

Active immunity and passive immunity

• 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

3. Recognition about3. Recognition about Structure Structure of antibody and its specificity of antibody and its specificity

binding to antigenbinding to antigen

(II) Discovery of antibody and passive immunity-3

•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

(II) Discovery of antibody and passive immunity-4

Various clones

Clone deletion

Clone selection

birth

Burnet Clonal selection theory

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

 

chimeras

1945, Owen observed phenomena of natural immune tolerance

1953, Medawar confirmed immune tolerance by experiment

dizygotic twins异卵双生

placenta

• 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.

• Polyclonal antibody （多克隆抗体）

• monoclonal antibody （单克隆抗体）

• gene engineering antibody （基因工程抗体）

5. development of technique producing Ab

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）

Mario R. Capecchi ，美国

Martin J. Evans ，英国

Oliver Smithies ，美国

2007年诺贝尔医学奖获得者

• 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 Doherty and Zinkernagel brought forward MHC restriction theory in 1974 and got Noble Prize in 1996restriction 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