The History of Immunology

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The History of Immunology Vaccinology

• Jian-Tai Qiu MD,PhD
• ???
• e-mail jtqiu_at_mail.cgu.edu.tw
• Office 3494

He who ignores history is doomed to repeat it.
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Stages of Immunology

• Descriptive early period
• Early attempts at vaccination Smallpox
• Early experiments Bacteria cause disease
• Humoral v. cellular immunity
• Selective v. instructive theories of I.R.
• The molecular revolution ? present

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Descriptive Early Period

• Plagues pandemics, esp. bubonic plague
  (Pasteurella pestis) smallpox.
• Causes of disease unknown until 19th C. Thought
  to be caused by poisons virus (latin).
• Thucydides (5thC. B.C.) people who recovered
  immune
• http//en.wikipedia.org/wiki/Thucydides

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Early Attempts at Immunisation

• Mithradates VI (Anatolian King) took increasing
  daily doses of poisons.
• Immunisation against Smallpox
• Chinese dried matter from pustules inserted in
  nostrils.
• Turks used variolation, hence Variola Virus.

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A Smallpox Victim
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Immunisation against Smallpox (1) Variolation

• Early 18th C. Lady Mary Wortley Montagu (wife of
  British Ambassador, Constantinople) inoculated
  own children.
• The Royal Experiment
• George I pardoned 7 criminals inoculated 1
  lay with smallpox victim every night to end. All
  recovered. Repeated with 6 more criminals 5
  orphans.
• Then 2 daughters of Prince Princess of Wales
  inoculated, hence became popular.

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In contrast to Asians and Africans who inoculated
by blowing dried smallpox scabs up the nose,
Europeans and their American cousins tended to
innoculate through a puncture in the skin.
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Immunisation against Smallpox (2) Vaccination

• End of 18th C. Edward Jenner
• Inoculated 7 subjects with cowpox. 2 challenged
  with smallpox. All O.K.  
• Cowpox Vaccinia virus, hence vaccination ?
  general term.

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Edward Jenner inoculating James Phipps with cowpox
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Immunisation against Smallpox (3) WHO Programme

• 1978 WHO Programme completed.

Smallpox completely eradicated worldwide.
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19th C. Bacteria cause disease

• Robert Koch Louis Pasteur established bacteria
  as cause of diseases.
• Pasteur Injected animals with live attenuated
  micoorganisms ? immunity v. chicken cholera,
  anthrax, rabies.

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Wars of The Cells and Antibodies

• Cellular Theory Elie Metchnikoff Phagocytes in
  starfish larvae surround a splinter phagocytosis
  digestion of bacteria by M?s polymorphs ?
  Phagocytic Theory (innate immunity).
• G.B. Shaw, The Doctors Dilemma .stimulate
  the phagocytes.
• Humoral Theory Koch, Ehrlich et al. (Berlin)
• Showed serum from immunised animals kills
  bacteria.

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Ilya Metchnikoff
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Humoral Immunity

• Bordet discovered complement.
• Behring Kitasato immunity to diphtheria
  tetanus due to Abs. v. toxins. Passive tf. of
  immune serum ? protection 1st immunotherapy. 

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Wars of The Cells and Antibodies Truce

• Sir Almoth Wright Douglas - Opsonisation of
  bacteria by Abs. Attempted fusion of Cellular
  and Humoral Theories Sir Almost Right.
• Little progress in cellular immunology for 50
  years (unfashionable).

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20th C How are Abs. made? Selective v.
Instructive Theories

• Are Abs pre-made (selective) or moulded by ag
  (instructive)?
• Ehrlichs Side Chain Theory (selective)
• Pauling - Instructive Theory 
• Sir MacFarlane Burnet Clonal Selection Theory.

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Chemical approach to Abs. Ags.

• Landsteiner Specificity diversity blood group
  ags.
• Abs as proteins
• Porter Edelman 1st Description of structure
  of IgG

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R. R. Porter
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Return to Cellular Theories

• (In parallel with studies of Abs.)
• Humoral immunity cannot explain graft rejection,
  tolerance, immunity to viruses. 
• Medawar tolerance to skin allografts
• Role of T-cells Th cells (T-B cell cooperation),
  Tc cells (kill virus infected cells).
• Zinkernagel Doherty Tc recognise ag. bound to
  MHC

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1975 present The Molecular Revolution (1)

• Köhler Milstein Monoclonal Abs

Nobel Prize 1984
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1975 present The Molecular Revolution (2)

• Tonegawa genetic basis of Ab variability
• PCR gene cloning techniques Mabs. ?
  identification, structure function of Ig TCR
  genes, cell surface ags. cytokines. 

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1975 present The Molecular Revolution (3)

• Genetic manipulation Gene K.O. and transgenic
  mice enable study of effects of molecular
  components of I.S., signalling pathways etc.
• Applications to Disease MAbs for diagnosis
  immunotherapy recombinant DNA vaccines gene
  therapy