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HISTORY OF IMMUNOLOGY 4.

EDWARD JENNER
 Discovered the cowpox vaccine as a safe vaccine
1. THUCYDIDES for smallpox
 Plague of Athens of 430 BC  Observed that those milkmaids with cowpox were
 “Those who have plague were not able to contract the not infected with smallpox
disease for the second time”  1st to use the method: Benjamin Jesty, a farmer,
 Resistance to plague inoculated his wife with vaccinia virus
 recorded that individuals who had previously  Inoculated James Phipps (8-year old boy) with
contracted the disease recovered and recognized their cowpox
“immune” status  Failed to provide a plausible explanation
 Why is cowpox a vaccine for smallpox?
2. VARIOLATION BY CHINESE &  Due to cross immunity
 Protection one gets on exposure to one antigen
ARABS may be applicable to another antigen provided
 Variola or smallpox that these antigens are related to each other
 involved exposing healthy people to material from the  Both share same antigen (antigenic
lesions caused by the disease, either by putting it relationship)
under the skin, or, more often, inserting powdered  Same antibody site for antigen yet smallpox is
scabs from smallpox pustules into the nose. not a perfect fit as that of the cowpox
 Family Pox viridae (family of DNA viruses)  Antibody may vary
 Most complicated structure  Both belong to Family Poxviridae (family of
 With complex symmetry DNA virus)
 “Naked” viruses  Memory cells can be antibodies
 Lesions cover the entire body  Even if minimal infection, it can still have an
 Cause pustules (elevation with pus cells) effect
 Cause macules (reddish, hot le)
 Unfortunately, because there was no standardization of
the inoculum, the variolation occasionally resulted in
5. LOUIS PASTEUR
death or disfigurement from smallpox, thus limiting its  “Father of Immunology”
acceptance.  Development of better and safer vaccine
 PRACTICES:  Cultured chicken cholera (Pasteurella multocida)
1. Chinese pulverized the scabs then blew it and rabies during summertime
into the nose  Therapeutic vaccination
2. Indians use of pustular fluid then cut skin  left a flask of the bacillus on the bench over the
running the thread with fluid onto the wound summer and inoculated 8 chickens with this “old but
3. Cut skin then put the scabs viable” stock of chicken cholera bacillus.
4. Arabs store scabs in books for a year then  He found that not only did the chickens not die, but
scratch the skin to produce an opening for the they did not even appear ill
scabs  Also discovered anthrax vaccine
 “CONCEPT OF ATTENUATION”
 Pasteur said that the virulent chicken cholera
3. LADY MARY WORTLEY bacillus had become attenuated by sitting on
the bench over the summer months.
MONTAGUE  Weaken antigenicity / immunogenicity /
 Brought variolation in England virulence / pathogenicity
 Wife of Lord Edward Wortley Montague, British  Do not reduce the stimulation of the immune
Ambassador of Constantinople (Istanbul) system so there is still antibody production
 Practiced on her 4-year old son and 5-year old  Not enough to cause disease
daughter  The longer the culture, the weaker the
 Worked together with Charles Maitland (surgeon) who antigenicity
made the Royal Experiment to prisoners who survived  Can also be caused by varying the temperature

6. FRANCIS HOME
 Always carried a pocket book with cotton pledgets
that covered measles & stored them for a year
 Protected individuals by rubbing cotton pledgets
on infected skin
 With Solomon Berson: how thyroid glands and
7. EMILE ADOLPH VON BEHRING & kidneys remove iodine from blood
SHIBASABURO KITASATO  Used to screen blood for Hepatitis virus
 Diphtheria and Tetanus (Clostridium tetani) vaccine  Used to determine effective dosage levels of drugs
 Pathogenicity from toxins  Detect foreign substances in blood
 Small doses are enough just to stimulate immune  Treat dwarfed children with growth hormones
response  Test and correct hormones of infertile couples
 Diphtheria anti-toxin & Anti-tetanus (antibodies)
 Roux: Diphtheria toxin with yersin 15. BARUJ BENACERRAF
 “Passive Serum Therapy” or “Serotherapy”  Discovery of immune response gene or Major
 Also called “Passive Aggressive Therapy” Histocompatibility gene
 Passive: body does not produce immune factors  Development of MHC restriction
but antibodies are supplied from external source  Governing rule on how T-cells recognized
 Active: supplied by the body; lifelong protection antigens
 Antitoxins = antibodies  Worked with George Snell & Jean Dausset

8. MAX THEILER 16. GEORGE SNELL


 Virologist  Discovered Major Histocompatibility complex in
 Born in Africa where yellow fever is endemic congenic mice (having same genectic except for 1
 “Yellow fever vaccine” allele)
 Yellow fever: spread by the bite of a female mosquito  Introduced concept of H-antigen
(Aedes aegypti); RNA virus of the genus flavivirus
17. JEAN DAUSSET
9. WALTER REED  French Hematologist and Immunologist
 “Yellow fever vaccine in US army”  Found Major Histocompatibility complex in
humans
 Described HLA-A2: 1st leukocyte antigen
10. IAN HECTOR FRAZER  Described the 1st tissue group: Human leukocyte
 Developed “Human Papillomavirus vaccine” or antigen (HLA)
“Gardasil”
 There is a connection between HPV and cervical 18. ERNST WITEBSKY
cancer
 German-American Immunologist and Bacteriologist
 Conducted a research on Hepatitis B
 A and B antigens
 Discovered HTLV-III cause immune problems: HIV
 Neutralization of certain antibodies
 With Noel Rose: experimental autoimmune
11. JONAS SALK & ALBERT BRUCE thyroiditis
SABIN
 Jonas Salk: injectable polio vaccine
19. ROLF M. ZINKERNAGEL
 Albert Bruce Sabin: oral polio vaccine  With Peter Doherty: How immune T-cells
recognize virus-infected host cells and tumor cells
 Viral antigen & MHC
12. LUC MONTAGNIER  Studied the co-evolution of viruses
 Discovery of HIV as lymphadenopathy-associated  Breakthrough in understanding concept of
virus (old name) Cell-Mediated Immunity
 Development of SARS vaccine: Severe acute
respiratory syndrome 20. JOHN MICHAEL BISHOP
 1st Human oncogene c-src (“Proto-oncogene”)
13. ROBERT GALLO  Regulates activities of normal cells
 Pioneered on retrovirus  Breeded congenic mice (identical genetic make-up)
 Named HIV as retrovirus causing AIDS
 Renamed Lymphadenopathy-associated virus to HIV 21. TAH WAH MAK
 Discovery of T-cell receptor
14. ROSALYN YALLOW  Became interested in apoptosis: programmed cell
 Development of Radioimmunoassays death
 Previously used for detection of hormones  With Lewis Cantley & Craig Thompson: “Agios”
 Now used for detection of antibodies  CFI-400945: “Sharpshooter drug”
 With Roel Nusse: Wnt-1 proto-oncogene
22. ERNST HAECKEL  With Donald Ganem: replication cycle of Hepa B
 Recognized phagocytosis virus
 “Ontology recapitulates phylogeny”  WithTyler Jacks: Ribosomal frameshifting
 1st to divide multicellular from unicellular  With John Young & Paul Bates: cellular receptor
for avian retroviruses
23. ALBERT COONS  With William Pao: mutations on epidermal growth
 Fluorescent dyes factor receptor gene in human lung cancers
 Immunofluorescence to identify antibodies
27. GERALD EDELMAN
24. PAUL EHRLICH  Whole complement structure
 1st to know complete structure of Antibody
 “Father of Humoral Immunity”
 Use of denaturing agents such as disulfide bonds
 Explained the appearance of antibodies in the
 Discovered Light and Heavy chains of antibodies
circulation
 IgG with myeloma protein
 Discovered “Side Chain Receptor Theory”
 Antibody synthesis
 Antibody Formation Theory 28. ROBERT KOCH
 Large population of cells that produce side chain  “Father of Modern Microbiology”
radicals called Haptophores  Discovered causative agents of tuberculosis,
 Stereochemical configuration of haptophores are anthrax, and cholera
complementary to an analogous structure in the  Demonstration of Delayed-type cutaneous
antigen complement molecule hypersensitivity (Type IV hypersensitivity)
 When haptophores combine with analogous  Cell-mediated response
structures on antigens, the reaction brings about a  “Germ cell theory”
specific interaction  Anthrax: Germ theory disease; led to rejection of
 Forms the basis of chemical and specific spontaneous generation
interaction between Ag and Ab (specificity)  “Koch’s Postulates”
 B-lymphocytes – produce one type of Ab
(haptophores) which when exposed to Ag transforms 29. WILLIAM BOYD
into plasma cells; produces antibodies  Blood groups are inherited and cannot be altered
 Paratopes – formerly known as haptophores;  13 geographically distinct races with different allels
combining site of Ab; where Ag combines to Ab; and blood group gene profiles
receptor site of Ag  Discovery of Lectins: Antibody-like proteins in
 Epitopes – analogous structure in Ag molecule plants; Carbohydate-rich protein which react with
 Proposed chemotherapy particular blood type of antibody specificity
 “Salvarsan”: 1st drug of syphilis  “Legere/Lego” Latin: among other things, to select

25. RODNEY R. PORTER 30. BARRY MARSHALL


 Initiated/pioneered on chemical structure of  With Robin Warren: Discovery of Helicobacter
antibody pylori (gastritis and peptic ulcers)
 Cleaved the molecule with papain (sequencing) then
broken down into 3 parts (a large component that had no 31. SIR WALDEMAR MORDECAI
antigen-binding capability (the base of the Y) and two smaller fragments
with active sites that bound to the antigen (the Y's arms). WOLFF HAFFKINE
 Sample: rabbit serum isolated IgG
 Discovery of Anti-cholera & Anti-bubonic plague
 Rgt: Enzymatically digested/protein-degrading
vaccine
enzymes (Cyanobromide proteases)
 Created a stigma: Mulkowal accident or Little
 Large: fragment crystallizable
Dreyfus affair
 Small fragments: Fab (fragment antigen-binding)
32. EVA ENGVALL
26. HAROLD E. VARMUS  ELISA: Enzyme-linked immunosorbent assay
 Retroviral DNA synthesis/replication causing cancer in
animals 33. DEBORAH DONIACH
 Cellular gene (c-src) gave rise to v-src oncogene of
 Autoimmune diseases
Rous Sarcoma virus
 With Ivan Roitt (author) & Peter Campbell:
 Chromosome integration
Antibodies are not directed against external
 Normal cells can be converted to tumor cells
microbes but at the thyroid
 1st demonstrated phagocytosis
34. MICHAEL HEIDELBERGER  With Emile Roux: Calomel
 “Father of Modern Immunology”  Ointment to prevent contraction of syphilis
 Investigated chemotherapeutic drugs
 “Immunochemistry”
 Developed polysaccharide-based vaccine against a 41. KARL LANDSTEINER
several common types of pneumonia  ABO Human Blood groups

35. FRANK MACFARLANE BURNET 42. BRUCE ALAN BEUTLER


 “Clonal Selection Theory”  Activation of innate immunity
 Acquired immunological tolerance and how the body  With Jules Hoffman & Steinman: Toll-like
recognizes self from nonself receptors
 Strain of Influenza A  Toll-like receptors: used by cells, phagocytes, and
 With W.I.B. Beveridge: technique for cultivating neutrophils in recognizing pathogens
viruses on the chorioallantoic membrane of chicken  B-cell: Antibody
embryos  T-cell: T-cell receptor
 With Stone: receptor-destroying enzyme present in  Phagocytes: Toll-like receptors
Vibrio cholerae  Pathogen-associated molecular pattern
(PAMP)
 Activator of onset immunity
36. SIR GUSTAV NOSSAL  First to isolate TNF-alpha and demonstrate
 “One-cell-one-antibody specificity” inflammatory potential of cytokines
 Isotype switching from IgM to IgG
 In T-cell-B-cell collaboration, only B-cells produce
antibodies 43. JOHN FRANKLIN ENDERS
 “Father of Modern Vaccines”
 Cultivated poliomyelitis virus
37. NEILS KAJ JERNE  With Frederick Robbins & Thomas Weller:
 “Natural Selection theory of Immunology” proposed mumps and chicken pox
by Ehrlich 50 years ago  Measles virus from David Edmonton (11-year old
 Body has specific antibodies to fight antigens boy)
 Self from nonself  MMR vaccine: Mumps, Measles, Rubella
 Network Theory: antigens stimulate production of 
antibodies
 Hemolysis Plaque assay
 Theory on Antibody formation 44. POLLY MATZINGER
 Danger Model:How the body mounts a response to
cells in distress
38. RALPH STEINMAN
 Dendritic cells
 With cytoplasmic functions 45. CESAR MILSTEIN
 T-cell activator  Hybridoma technology: for detection of antigen
 Professional antigen presentors and for production of monoclonal antibodies
 Present antigen to T-cells  With George Kohler: development of methods in
producing antibodies
39. SUSUMU TONEGAWA
 Generation of Antibody diversity and T-cell receptor 46. WILLIAM BRADLEY COLEY
due to distribution of genes  Tried to explain body’s response against tumor
 Somatic recombination of genes: factor in  Immunotherapy for cancer
generation of Antibody and T-cell receptor
47. JACQUES MILLER
40. ELIE METCHNIKOFF  With Graham Mitchell: T-cells and B-cells
 “Father of Natural Immunity”  Discovery of Thymus for immunity
 “Father of Cellular Immunity”
 Cell-mediated immunity via phagocytosis
 Coined the term “Gerontology”: study of aging and
48. CHARLES ROBERT RICHET
longetivity  Anaphylaxis: severe form of hypersensitivity
 Aging: caused by toxic bacteria in gut  With Paul Portier
 Longetivity: due to lactic acid
49. JULES BORDET 58. LUDWIG ASCHOFF
 Discovery of complement  Aschoff’s bodies – in muscles with rheumatic
 Complement fixation tests viruses
 Identification of bacterium that causes Whooping  Reticuloendothelial system
cough (Bordetella pertussis)
 Thermolabile components in serum sample Complete
the immune response
59. ELVIN KABAT
 Destroys the Ag  Quantitative immunochemistry
 Specificity of immune response by chemically
altering antigens
50. STANLEY BENJAMIN  Template Theory
 Development of antibodies
PRUSINER  Immunoglobulin structure
 Discovery of Prion: proteinaceous infectious particle  IgG

51. PETER BRIAN MEDAWAR 60. JAMES GOWANS


 Skin grafts  Lymphocyte traffic/recirculation
 Immunologic tolerance
 “Father of Transplantation”
 Hypothesis of allograft rejection 61. ALICK ISAACS & JEAN
LINDENMANN
52. PERNESSA SEELE  Interferons
 Information material on HIV
62. ROBERT GOOD
53. MERRILL WALLACE CHASE  1st successful bone marrow transplant
 Demonstrated the phenomenon of cell-mediated  David the bubble boy
immunity and precipitated a surge of interest in cellular
immunology
 Adaptive Response
63. KENDALL SMITH
 According to Phylogeny:  Generation of 1st monoclonal T-cells
 Cell-mediated immunity  IL-1, IL-2
 Humoral-mediated immunity  IL-2 receptor
 With Doreen Cantrell: 1st single cell analysis of
lymphocyte proliferation
54. NICOLAS MAURICE ARTHUS
 “Arthus reaction”/response of intermediate
hypersensitivity
64. JEAN BOREL
 Localizing allergic reaction  Cyclosporines – immunosuppressive drugs
 From Tolypocladiuminflatum

55. ALMOTH WRIGHT & STEWART 65. KIMISHIGE “KIMI” ISHIZAKA


DOUGLAR  IgE as reaginic antibodies
 Autogenous vaccine – organisms harboured by an
individual 66. JULES HOFFMANN & BRUNO
 Opsonization: Ab coats bacteria for phagocytosis
LEMAITRE
56. CLEMENS VON PIRQUET  Discovered the function of the fruit fly toll gene in
innate immunity
 With Bela Schick: Serum sickness – form of
hypersensitivity
 Immune responses can be deleterious 67. JOHN MARRACK
 Coined the term “Allergy”  Hypothesis of antigen-antibody binding

57. ALEXANDER WIENER 68. TIMOTHY MOSMANN


 With Karl Landsteiner: Rh factor/antigens  Th1 versus Th2 model of T helper cell function
69. MORTON SIMONSEN &
WILLIAM JAMES DEMPSTER
 Graft-versus -Host disease

70. BARUCH SAMUEL BLUMBERG


& IRVING MILLMAN
 Hepatitis B vaccine

71. PHILIPPA MARRACK, ELLIS


REINHERZ, JOHN KAPPLER,
JAMES ALLISON
 T-cell antigen receptor

72. THOMAS TOMASI


 Secretory immunoglobulin

73. SHIMON SAKAGUCHI


 Regulatory T-cells

74. JAMES RILEY & GEOFFREY


WEST
 Discovery of histamine in mast cells

75. ASTRID FAGRAEUS


 Antibody production in Plasma B cells

76. PEYTON ROUS


 Viral immunology theory

77. SVANTE ARRHENIUS


 Coined “immunochemistry”

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