Brief history of immunology

1. Brief History of Immunology
Discovery of Vaccines & Understanding the
Mechanisms of Immunity
Dr. Dhanya KC
Assistant Professor, Department of Microbiology
St. Mary’s College, Thrissur-20, Kerala

2. Immunology
The Latin term immunis - mean “exempt”
State of protection from infectious disease
Immune system
Diversity, specificity, memory, and self/nonself recognition
Effector response - eliminate or neutralize invader
Memory response - rapid & enhanced during subsequent encounter
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3. In 430 BC
Thucydides, the great historian of the Peloponnesian War
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• Described a plague in Athens
• Who recovered from plague could nurse the sick because they would
not contract the disease a second time

4. In fifteenth century - Chinese and Turks
• Dried crusts from smallpox pustules - inhaled through nostrils or
inserted into small cuts in skin - to prevent deadly and fatal
Smallpox - Variolation
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5. In 1718 Lady Mary Wortley Montagu
• Performed variolation on her own children
In 1798 Edward Jenner
• Improved variolation
• Observation on milkmaids – developed
cowpox disease - immune to smallpox
• Fluid from a cowpox pustule - protect from
smallpox
• Inoculated a boy with cowpox pustule fluid
- Later infected the child with smallpox -
did not develop smallpox
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6. Technique to protect against smallpox - Spread quickly in Europe
Edward Jenner - Honored as father of immunology
But, not applied to other diseases for nearly 100 years - lack of
knowledge and disease targets
Serendipity & astute observation - next advance in immunology

7. Louis Pasteur
• Grew bacterium - for fowl cholera
• Chickens injected - developed cholera
• Cultures left in incubation for long period -
attenuated bacteria
• Chickens became ill –recovered - injection of fresh
culture - did not develop disease
Pasteur hypothesized & proved
• Aging weakened virulence of pathogen
• Administering attenuated strain - protection against disease
Named as vaccine - from the Latin word ‘vacca’ means “cow”
In honor of Jenner’s technique of cowpox inoculation

8. Pasteur -attenuated other disease pathogens
Bacillus anthracis - causative agent of anthrax
• Attenuation techniques to prepare anthrax vaccine
• By treating cultures with potassium bichromate
• By incubating the bacteria at 42 to 43°C
• In 1881, vaccinated sheep against Anthrax
Rabies vaccine
• Attenuated by growing in abnormal host, rabbit
• In 1885, vaccinated a young boy, Joseph Meister
• Injected 13 times over 10 days with attenuated virus
• He survived

9. Works by Pasteur - Marked beginnings of immunology
Contributions from all over world, Pasteur Institute constructed
Initial task of the Institute - vaccine production

10. Robert Koch - Bacillus anthracis and anthrax in 1876
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Koch’s postulates

11. In 1890
Emil von Behring and Shibasaburo Kitasato
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• Tetanus antitoxin
• Insights into the mechanism of immunity

12. Next decade
Active component from the serum of immune animals
• Neutralize toxins -antitoxin
• Precipitate toxins -precipitin
• Agglutinate bacteria -agglutinin
Elvin Kabat
Gamma-globulin present in serum
The immunoglobulin fraction – antibodies
Present in body fluids or humors - humoral immunity

13. In 1883 - Elie Metchnikoff : Father of natural immunity
• White blood cells – phagocytes
• Phagocytosis
• The concept - cell-mediated immunity
Further studies
• Humoral immunity - Using blood and biochemical techniques
• Immune cells – lagged behind –modern tissue culture techniques

14. In 1940s, Merrill Chase
• Transferred immunity against - WBC from immune guinea pigs
In 1950s - lymphocyte - cellular and humoral immunity

15. Bruce Glick
• Using chickens - two types of lymphocytes
• T lymphocytes - thymus - cellular immunity
• B lymphocytes - bursa of Fabricius - humoral immunity
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Jules Bordet
• Immune reactivity to nonpathogenic substances, such
as RBC from different species

16. Karl Landsteiner
• Injecting an animal with any organic chemical
• Induce antibody - bind specifically to the chemical
• Human ABO blood group system
• Identified A, B, AB, and O groups
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• Other blood factors - M, N, P and Rhesus system
• Helped blood transfusions carried out safely

17. Karl Landsteiner
• Causative agent - poliomyelitis
• Worked for polio vaccine
• Worked to identify pathogen for syphilis
• Studied haptens - Small variations in structure - changes in
antibody production
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18. • Antibodies - unlimited range of reactivity
• Even to compounds never before existed in nature
• High Specificity - structurally almost similar molecules -recognized
as different
Early theories to explain specificity of Antigen-Antibody interaction
Selective theory
Instructional theory

19. Selective theory - by Paul Ehrlich in 1900
• Cells in blood expressed receptors - “side-chain receptors”
• React and bind with infectious agents – like a lock and key
• Induce cell to produce and release more similar receptors
• Specificity of Receptor – Predetermined
• Antigen select the appropriate Receptor

20. 1930s and 1940s, instructional theories
By Friedrich Breinl and Felix Haurowitz
• A particular antigen - template
• Antibody would fold around template - assume complementary
configuration
• Disproved in 1960s

21. Selective theories - resurface In 1950s
Refined by Niels Jerne, David Talmadge, F. Macfarlane Burnet
The clonal selection theory
• Lymphocyte - membrane receptors - specific for antigen - even
before antigen exposure
• Binding of antigen to specific receptor - activates cell
• Cell proliferate - clone of cells - same immunologic specificity

22. The clonal selection theory -
underlying paradigm of modern
immunology
1. HSC
2. Immature lymphocytes with Ag receptors
3. Those that bind to self Ag - destroyed
4. Rest mature to inactive lymphocytes
5. Encounter foreign antigen- activated
6. Produce many clones of themselves

23. Brief History of
Immunology