| 1549 |
|
The earliest account of inoculation of smallpox (variolation) occurs in Wan Quan's (1499–1582) Douzhen Xinfa (痘疹心法).[1] |
| 1718 |
West. Lady Mary Wortley Montagu, the wife of the British ambassador to Constantinople |
Smallpox inoculation in Ottoman Empire realized by West. Lady Mary Wortley Montagu, the wife of the British ambassador to Constantinople, observed the positive effects of variolation on the native population and had the technique performed on her own children. |
| 1796 |
Edward Jenner |
First demonstration of smallpox vaccination (Edward Jenner) |
| 1837 |
Theodore Schwann |
Description of the role of microbes in putrefaction and fermentation (Theodore Schwann) |
| 1838 |
Charles Cagniard-Latour |
Confirmation of the role of yeast in fermentation of sugar to alcohol (Charles Cagniard-Latour) |
| 1840 |
Jakob Henle |
Proposal of the germ theory of disease (Jakob Henle) |
| 1850 |
childbed fever |
Demonstration of the contagious nature of puerperal fever (childbed fever) (Ignaz Semmelweis) |
| 1857–1870 |
Louis Pasteur |
Confirmation of the role of microbes in fermentation (Louis Pasteur) |
| 1862 |
Ernst Haeckel |
Phagocytosis (Ernst Haeckel) |
| 1867 |
Joseph Lister |
Aseptic practice in surgery using carbolic acid (Joseph Lister) |
| 1876 |
Robert Koch |
Demonstration that microbes can cause disease-anthrax (Robert Koch) |
| 1877 |
Paul Ehrlich |
Mast cells (Paul Ehrlich) |
| 1878 |
Louis Pasteur |
Confirmation and popularization of the germ theory of disease (Louis Pasteur) |
| 1880 – 1881 |
Louis Pasteur |
Theory that bacterial virulence could be attenuated by culture in vitro and used as vaccines. Proposed that live attenuated microbes produced immunity by depleting host of vital trace nutrients. Used to make chicken cholera and anthrax "vaccines" (Louis Pasteur) |
| 1883 – 1905 |
Elie Metchnikoff |
Cellular theory of immunity via phagocytosis by macrophages and microphages (polymorhonuclear leukocytes) (Elie Metchnikoff) |
| 1885 |
Louis Pasteur and Pierre Paul Émile Roux |
Introduction of concept of a "therapeutic vaccination". Report of a live "attenuated" vaccine for rabies (Louis Pasteur and Pierre Paul Émile Roux). |
| 1888 |
Pierre Roux and Alexandre Yersin |
Identification of bacterial toxins (diphtheria bacillus) (Pierre Roux and Alexandre Yersin) |
| 1888 |
George Nuttall |
Bactericidal action of blood (George Nuttall) |
| 1890 |
Emil von Behring |
Demonstration of antibody activity against diphtheria and tetanus toxins. Beginning of humoral theory of immunity. (Emil von Behring) and (Kitasato Shibasaburō) |
| 1891 |
Robert Koch |
Demonstration of cutaneous (delayed type) hypersensitivity (Robert Koch) |
| 1893 |
William B. Coley |
Use of live bacteria and bacterial lysates to treat tumors-"Coley's Toxins" (William B. Coley) |
| 1894 |
Richard Pfeiffer |
Bacteriolysis (Richard Pfeiffer) |
| 1896 |
Jules Bordet |
An antibacterial, heat-labile serum component (complement) is described (Jules Bordet) |
| 1900 |
Paul Ehrlich |
Antibody formation theory (Paul Ehrlich) |
| 1901 |
Karl Landsteiner |
Blood groups (Karl Landsteiner) |
| 1902 |
Paul Portier |
Immediate hypersensitivity anaphylaxis (Paul Portier) and (Charles Richet) |
| 1903 |
Maurice Arthus |
Intermediate hypersensitivity, the "Arthus reaction" (Maurice Arthus) |
| 1903 |
|
Opsonization[2] |
| 1905 |
Clemens von Pirquet and (Bela Schick |
"Serum sickness" allergy (Clemens von Pirquet and (Bela Schick) |
| 1909 |
Paul Ehrlich |
Paul Ehrlich proposes "immune surveillance" hypothesis of tumor recognition and eradication |
| 1911 |
Peyton Rous |
2nd demonstration of filterable agent that caused tumors (Peyton Rous) |
| 1917 |
Karl Landsteiner |
Hapten (Karl Landsteiner) |
| 1921 |
Otto Prausnitz and Heinz Küstner |
Cutaneous allergic reactions (Otto Prausnitz and Heinz Küstner) |
| 1924 |
|
Reticuloendothelial system |
| 1938 |
John Marrack |
Antigen-Antibody binding hypothesis (John Marrack) |
| 1940 |
Karl Landsteiner and Alexander Weiner |
Identification of the Rh antigens (Karl Landsteiner and Alexander Weiner) |
| 1942 |
Karl Landsteiner and Merill Chase |
Anaphylaxis (Karl Landsteiner and Merill Chase) |
| 1942 |
Jules Freund and Katherine McDermott |
Adjuvants (Jules Freund and Katherine McDermott) |
| 1944 |
|
hypothesis of allograft rejection |
| 1945 |
|
Coombs Test a.k.a. antiglobulin test (AGT) |
| 1946 |
George Snell and Peter A. Gorer |
Identification of mouse MHC (H2) by George Snell and Peter A. Gorer |
| 1948 |
|
Antibody production in plasma B cells |
| 1949 |
(John Enders) and (Thomas Weller) and (Frederick Robbins) |
Growth of polio virus in tissue culture, neutralization with immune sera, and demonstration of attenuation of neurovirulence with repetitive passage (John Enders) and (Thomas Weller) and (Frederick Robbins) |
| 1951 |
|
vaccine against yellow fever |
| 1953 |
|
Graft-versus-host disease |
| 1953 |
|
Validation of immunological tolerance hypothesis |
| 1957 |
Frank Macfarlane Burnet |
Clonal selection theory (Frank Macfarlane Burnet) |
| 1957 |
Alick Isaacs and Jean Lindenmann |
Discovery of interferon by Alick Isaacs and Jean Lindenmann[3] |
| 1958–1962 |
Jean Dausset and others |
Discovery of human leukocyte antigens (Jean Dausset and others) |
| 1959–1962 |
independently elucidated by Gerald Edelman and Rodney Porter |
Discovery of antibody structure (independently elucidated by Gerald Edelman and Rodney Porter) |
| 1959 |
James Gowans |
Discovery of lymphocyte circulation (James Gowans) |
| 1960 |
Peter Nowell |
Discovery of lymphocyte "blastogenic transformation" and proliferation in response to mitogenic lectins-phytohemagglutinin (PHA) (Peter Nowell) |
| 1961 |
Jacques Miller |
Discovery of thymus involvement in cellular immunity (Jacques Miller) |
| 1960 |
Rosalind Yallow |
Radio immuno assay – (Rosalind Yallow) |
| 1961 |
Peter Nowell |
Demonstration that glucocorticoids inhibit PHA-induced lymphocyte proliferation (Peter Nowell) |
| 1963 |
Niels Jerne and Albert Nordin |
Development of the plaque assay for the enumeration of antibody-forming cells in vitro by Niels Jerne and Albert Nordin |
| 1963 |
|
Gell and Coombs classification of hypersensitivity |
| 1964–1968 |
|
T and B cell cooperation in immune response |
| 1965 |
(Shinpei Kamakura) and (Louis Lowenstein) (J. Gordon) and (L.D. MacLean) |
Discovery of lymphocyte mitogenic activity, "blastogenic factor" (Shinpei Kamakura) and (Louis Lowenstein) (J. Gordon) and (L.D. MacLean) |
| 1965 |
E.F. Wheelock |
Discovery of "immune interferon" (gamma interferon) (E.F. Wheelock) |
| 1965 |
|
Secretory immunoglobulins |
| 1967 |
Kimishige Ishizaka |
Identification of IgE as the reaginic antibody (Kimishige Ishizaka) |
| 1968 |
William L. Elkins and Ronald D. Guttmann |
Passenger leukocytes identified as significant immunogens in allograft rejection (William L. Elkins and Ronald D. Guttmann) |
| 1969 |
(Theodore Brunner) and (Jean-Charles Cerottini) |
The lymphocyte cytolysis Cr51 release assay (Theodore Brunner) and (Jean-Charles Cerottini) |
| 1971 |
Peter Perlmann and Eva Engvall |
Peter Perlmann and Eva Engvall at Stockholm University invented ELISA |
| 1972 |
|
Structure of the antibody molecule |
| 1973 |
Ralph M. Steinman |
Dendritic Cells first described by Ralph M. Steinman |
| 1974 |
Niels Jerne |
Immune Network Hypothesis (Niels Jerne) |
| 1974 |
Rolf Zinkernagel and Peter C. Doherty |
T-cell restriction to MHC (Rolf Zinkernagel and Peter C. Doherty) |
| 1975 |
Georges Köhler and César Milstein |
Generation of monoclonal antibodies (Georges Köhler) and (César Milstein)[4] |
| 1975 |
Rolf Kiessling, Eva Klein, Hans Wigzell |
Discovery of Natural Killer cells (Rolf Kiessling, Eva Klein, Hans Wigzell) |
| 1976 |
Susumu Tonegawa |
Identification of somatic recombination of immunoglobulin genes (Susumu Tonegawa) |
| 1980–1983 |
Robert Gallo, Kendall A. Smith, Tadatsugu Taniguchi |
Discovery and characterization of interleukins, 1 and 2 IL-1 IL-2 (Robert Gallo, Kendall A. Smith, Tadatsugu Taniguchi) |
| 1983 |
(Ellis Reinherz) (Philippa Marrack) and (John Kappler)[5] (James Allison) |
Discovery of the T cell antigen receptor TCR (Ellis Reinherz) (Philippa Marrack) and (John Kappler)[5] (James Allison) |
| 1983 |
(Luc Montagnier) (Françoise Barré-Sinoussi) |
Discovery of HIV (Luc Montagnier) (Françoise Barré-Sinoussi) |
| 1985–1987 |
|
Identification of genes for the T cell receptor |
| 1986 |
|
Hepatitis B vaccine produced by genetic engineering |
| 1986 |
Timothy Mosmann |
Th1 vs Th2 model of T helper cell function (Timothy Mosmann) |
| 1988 |
Christopher E. Rudd |
Discovery of biochemical initiators of T-cell activation: CD4- and CD8-p56lck complexes (Christopher E. Rudd) |
| 1990 |
|
Gene therapy for SCID |
| 1991 |
Scheherazade Sadegh-Nasseri & Ronald N. Germain |
Role of peptide for MHC Class II structure (Scheherazade Sadegh-Nasseri & Ronald N. Germain) |
| 1992 |
David Allman & Michael Cancro |
Discovery of transitional B cells (David Allman & Michael Cancro)[6][7] |
| 1994 |
Polly Matzinger |
'Danger' model of immunological tolerance (Polly Matzinger) |
| 1995 |
James P. Allison |
James P. Allison describes the function of CTLA-4 |
| 1995 |
Shimon Sakaguchi |
Regulatory T cells (Shimon Sakaguchi) |
| 1995 |
Mukherji et al. |
First Dendritic cell vaccine trial reported by Mukherji et al. |
| 1996 – 1998 |
|
Identification of Toll-like receptors |
| 2000 |
Charles Mills |
Characterization of M1 and M2 macrophage subsets by Charles Mills[8] |
| 2001 |
|
Discovery of FOXP3 – the gene directing regulatory T cell development |
| 2005 |
Ian Frazer |
Development of human papillomavirus vaccine (Ian Frazer) |
| 2006 |
reported by Ulrich von Andrian's group after discovery by Mahmoud Goodarzi |
Antigen-specific NK cell memory first reported by Ulrich von Andrian's group after discovery by Mahmoud Goodarzi |
| 2010 |
The manufacturer, Dendreon Inc, declares bankruptcy in 2014. |
The first autologous cell-based cancer vaccine, PROVENGE, is approved by the FDA for the treatment of metastatic, asymptomatic stage IV prostate cancer. The treatment is marketed at a cost of $93,000 and imparts, on average, only an extra four months of life expectancy. The manufacturer, Dendreon Inc, declares bankruptcy in 2014. |
| 2010 |
|
First immune checkpoint inhibitor, ipilimumab (anti-CTLA-4), is approved by the FDA for treatment of stage IV melanoma |
| 2011 |
Carl H. June |
Carl H. June reports first successful use of CAR T-cells expressing the 4-1BB costimulatory signaling domain for the treatment of CD19+ malignancies |
| 2014 |
|
A second class of immune checkpoint inhibitor (anti-PD-1) is approved by the FDA for the treatment of melanoma. Two different drugs, pembrolizumab and nivolumab are approved within months of each other. |
| 2016 |
Halpert and Konduri |
Halpert and Konduri first characterize the role of dendritic cell CTLA-4 in Th-1 immunity |
| 2016 |
|
A third class of immune checkpoint inhibitor, anti-PD-L1 (atezolizumab), is approved for the treatment of bladder cancer |
| 2017 |
|
The first autologous CAR T-cell therapy tisagenlecleucel also known as Kymriah is approved for the treatment of pediatric B-ALL. Marketed at a cost of $475,000, the treatment provides an 83% rate of durable remission among poor prognosis patients for whom a bad outcome would otherwise be expected. |
| 2017 |
|
The Indian government approves Apceden, the first potentially curative dendritic cell vaccine for the treatment of prostate, ovarian, colon, and lung cancers. |