Immunology
Timeline Outline Index Category
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This list is incomplete; you can help by adding missing items. (December 2020)

The following are notable events in the Timeline of immunology:

• 1550 BCE – The Ebers papyrus recommends placing a poultice on a tumor and then making an incision, which would induce infection and cause regression of the tumor. ^[1]
• 1549 – The earliest account of inoculation of smallpox ( variolation) occurs in Wan Quan's (1499–1582) Douzhen Xinfa (痘疹心法). ^[2]
• 1718 – Smallpox inoculation in Ottoman Empire realized by West, and Henry Kipkosgei , recorded the positive effects of variolation.
• 1761 – A case of breast cancer cured after ulcerating and getting infected is reported by Lambergen ^[3]
• 1796 – First demonstration of smallpox vaccination ( Edward Jenner)
• 1808–1813 – First experimental demonstration of the germ theory of disease by Agostino Bassi though he does not formally propose the theory until 1844
• 1813 – Vautier reports spontaneous remission of cancer after gangrene infection (later to be known as Clostridium perfringens)
• 1829 – Another case of spontaneous remission of breast cancer after a patient refused surgery and the tumor ruptured, became infected and during a febrile illness with purulent discharge, it shrunk and disappeared after a few weeks. ( Guillaume Dupuytren) ^{[4] [5] [6]}
• 1837 – Description of the role of microbes in putrefaction and fermentation ( Theodore Schwann)
• 1838 – Confirmation of the role of yeast in fermentation of sugar to alcohol ( Charles Cagniard-Latour)
• 1850 – Demonstration of the contagious nature of puerperal fever (childbed fever) ( Ignaz Semmelweis)
• 1857–1870 – Confirmation of the role of microbes in fermentation ( Louis Pasteur)
• 1862 – Phagocytosis ( Ernst Haeckel)
• 1867 – Aseptic practice in surgery using carbolic acid ( Joseph Lister)
• 1868 – Busch discovered that a sarcoma patient being surgically intervened to remove the tumor, after being exposed to a patient suffering from erysipelas, got a skin infection and her tumor disappeared. He inoculated some other cancer patients with many successes. ^{[7] [4]}
• 1876 – Demonstration that microbes can cause disease-anthrax ( Robert Koch)
• 1877 – Mast cells ( Paul Ehrlich)
• 1878 – Confirmation and popularization of the germ theory of disease ( Louis Pasteur)
• 1880 – 81 Theory that bacterial virulence could be attenuated by culture in vitro and used as vaccines. Used to make chicken cholera and anthrax "vaccines" ( Louis Pasteur)
• 1882 – Identification of Streptococcus pyogenes as the causative agent of erysipelas ( Friedrich Fehleisen). He repeats Busch experiments inoculating cancer patients with eryisipelas, noting tumor regression in many of them. ^[8]
• 1883–1905 – Cellular theory of immunity via phagocytosis by macrophages and microphages (polymorhonuclear leukocytes) ( Elie Metchnikoff)
• 1885 – Introduction of concept of a "therapeutic vaccination". Report of a live "attenuated" vaccine for rabies ( Louis Pasteur and Pierre Paul Émile Roux).
• 1888 – Identification of bacterial toxins ( diphtheria bacillus) ( Pierre Roux and Alexandre Yersin)
• 1888 – Bactericidal action of blood ( George Nuttall)
• 1890 – Demonstration of antibody activity against diphtheria and tetanus toxins. Beginning of humoral theory of immunity. ( Emil von Behring) and ( Kitasato Shibasaburō)
• 1891 – Demonstration of cutaneous (delayed type) hypersensitivity ( Robert Koch)
• 1893 – Use of live bacteria and bacterial lysates to treat tumors – " Coley's Toxins", based on Busch and Fehleisen experiences ( William B. Coley)
• 1894 – Bacteriolysis ( Richard Pfeiffer)
• 1896 – An antibacterial, heat-labile serum component ( complement) is described ( Jules Bordet)
• 1900 – Antibody formation theory ( Paul Ehrlich)
• 1901 – Blood groups ( Karl Landsteiner)
• 1902 – Immediate hypersensitivity anaphylaxis ( Paul Portier) and ( Charles Richet)
• 1903 – Intermediate hypersensitivity, the "Arthus reaction" ( Maurice Arthus)
• 1903 – Opsonization ^[9]
• 1905 – "Serum sickness" allergy ( Clemens von Pirquet and ( Bela Schick)
• 1909 – Paul Ehrlich proposes "immune surveillance" hypothesis of tumor recognition and eradication
• 1911 – 2nd demonstration of filterable agent that caused tumors ( Peyton Rous)
• 1917 – Hapten ( Karl Landsteiner)
• 1921 – Cutaneous allergic reactions ( Otto Prausnitz and Heinz Küstner)
• 1924 – Reticuloendothelial system
• 1938 – Antigen-Antibody binding hypothesis ( John Marrack)
• 1940 – Identification of the Rh antigens ( Karl Landsteiner and Alexander Weiner)
• 1942 – Anaphylaxis ( Karl Landsteiner and Merill Chase)
• 1942 – Adjuvants ( Jules Freund and Katherine McDermott)
• 1944 – hypothesis of allograft rejection
• 1945 – Coombs test a.k.a. antiglobulin test (AGT)
• 1946 – Identification of mouse MHC (H2) by George Snell and Peter A. Gorer
• 1948 – Antibody production in plasma B cells ( Astrid Fagraeus)
• 1949 – Growth of polio virus in tissue culture, neutralization, and demonstration of attenuation of neurovirulence ( John Enders) and ( Thomas Weller) and ( Frederick Robbins)
• 1951 – A vaccine against yellow fever
• 1953 – Graft-versus-host disease
• 1953 – Validation of immunological tolerance hypothesis
• 1957 – Clonal selection theory ( Frank Macfarlane Burnet)
• 1957 – Discovery of interferon by Alick Isaacs and Jean Lindenmann ^[10]
• 1958–1962 – Discovery of human leukocyte antigens ( Jean Dausset and others)
• 1959–1962 – Discovery of antibody structure (independently elucidated by Gerald Edelman and Rodney Porter)
• 1959 – Discovery of lymphocyte circulation ( James Gowans)
• 1960 – Discovery of lymphocyte "blastogenic transformation" and proliferation in response to mitogenic lectins-phytohemagglutinin (PHA) ( Peter Nowell)
• 1961–1962 Discovery of thymus involvement in cellular immunity ( Jacques Miller)
• 1960 – Radioimmunoassay – ( Rosalyn Sussman Yalow)
• 1961 – Demonstration that glucocorticoids inhibit PHA-induced lymphocyte proliferation ( Peter Nowell)
• 1963 – 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 – Discovery of lymphocyte mitogenic activity, "blastogenic factor" ( Shinpei Kamakura) and ( Louis Lowenstein) ( J. Gordon) and ( L.D. MacLean)
• 1965 – Discovery of "immune interferon" ( gamma interferon) ( E.F. Wheelock)
• 1965 – Secretory immunoglobulins
• 1967 – Identification of IgE as the reaginic antibody ( Kimishige Ishizaka)
• 1968 – Passenger leukocytes identified as significant immunogens in allograft rejection ( William L. Elkins and Ronald D. Guttmann)
• 1969 – The lymphocyte cytolysis Cr51 release assay ( Theodore Brunner) and ( Jean-Charles Cerottini)
• 1971 – Peter Perlmann and Eva Engvall at Stockholm University invented ELISA
• 1972 – Structure of the antibody molecule
• 1972 – Discovery of invertebrate immunity by Hans G. Boman ^[11]
• 1973 – Dendritic Cells first described by Ralph M. Steinman
• 1974 – Immune Network Hypothesis ( Niels Jerne)
• 1974 – T-cell restriction to MHC ( Rolf Zinkernagel and ( Peter C. Doherty)
• 1975 – Generation of monoclonal antibodies ( Georges Köhler) and ( César Milstein) ^[12]
• 1975 – Discovery of Natural Killer cells ( Rolf Kiessling, Eva Klein, Hans Wigzell)
• 1976 – Identification of somatic recombination of immunoglobulin genes ( Susumu Tonegawa)
• 1980–1983 – Discovery and characterization of interleukins, 1 and 2 IL-1 IL-2 ( Robert Gallo, Kendall A. Smith, Tadatsugu Taniguchi)
• 1981 – First description of an animal antimicrobial peptide in Cecropia silk moths ^[13]
• 1983 – Discovery of the T cell antigen receptor TCR ( Ellis Reinherz) ( Philippa Marrack) and ( John Kappler) ^[14] ( James Allison)
• 1983 – Discovery of HIV ( Luc Montagnier) ( Françoise Barré-Sinoussi) ( Robert Gallo)
• 1985–1987 – Identification of genes for the T cell receptor
• 1986 – Hepatitis B vaccine produced by genetic engineering
• 1986 – Th1 vs Th2 model of T helper cell function ( Timothy Mosmann)
• 1988 – Discovery of biochemical initiators of T-cell activation: CD4- and CD8-p56lck complexes ( Christopher E. Rudd)
• 1990 – Gene therapy for SCID
• 1991 – Role of peptide for MHC Class II structure (Scheherazade Sadegh-Nasseri & Ronald N. Germain) ^[15]
• 1992 – Discovery of transitional B cells (David Allman & Michael Cancro) ^{[16] [17]}
• 1994 – Danger model of immunological tolerance is described by Polly Matzinger at the NIH
• 1995 – James P. Allison is the first to describe the function of the critical immune checkpoint CTLA-4
• 1995 – Regulatory T cells ( Shimon Sakaguchi)
• 1995 – First Dendritic cell vaccine trial reported by Mukherji et al.
• 1995 – Discovery of the insect Imd NF-κB pathway ^[18]
• 1996–1998 – Identification of Toll-like receptors as immune-regulating molecules ^[19]
• 1997 – Discovery of the autoimmune regulator and the AIRE gene.
• 2000 – Characterization of M1 and M2 macrophage subsets by Charles Mills ^[20]
• 2001 – Discovery of FOXP3 – the gene directing regulatory T cell development
• 2005 – Development of human papillomavirus vaccine ( Ian Frazer)
• 2006 – Antigen-specific NK cell memory first reported by Ulrich von Andrian's group after discovery by Mahmoud Goodarzi
• 2010 – The first autologous cell-based cancer vaccine, Provenge, is approved by the FDA for the treatment of metastatic, asymptomatic stage IV prostate cancer.
• 2010 – First immune checkpoint inhibitor, ipilimumab (anti-CTLA-4), is approved by the FDA for treatment of stage IV melanoma
• 2011 – 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. Pembrolizumab and nivolumab are approved within months of each other.
• 2016 – The role of dendritic cell expressed CTLA-4 in Th immune polarization is first described
• 2016 – A third class of immune checkpoint inhibitor, anti-PD-L1 ( atezolizumab), is approved for the treatment of bladder cancer
• 2017 – First autologous CAR T-cell therapy tisagenlecleucel approved for the treatment of pediatric B-ALL; second autologous CAR T-cell therapy axicabtagene ciloleucel (Yescarta) is approved.
• 2020 – The first mRNA vaccines ( BNT162b2, mRNA-1273), are developed for SARS-CoV-2 infection; this new technology completed design, testing, and emergency approval in under one year.

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