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
• 1549 – The earliest account of inoculation of smallpox occurs in Wan Quan's Douzhen Xinfa
• 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
• 1796 – First demonstration of smallpox vaccination
• 1808–1813 – First experimental demonstration of the germ theory of disease
• 1813 – Vautier reports spontaneous remission of cancer after gangrene infection
• 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.
• 1837 – Description of the role of microbes in putrefaction and fermentation
• 1838 – Confirmation of the role of yeast in fermentation of sugar to alcohol
• 1850 – Demonstration of the contagious nature of puerperal fever
• 1857–1870 – Confirmation of the role of microbes in fermentation
• 1862 – Phagocytosis
• 1863 – Mast cells
• 1867 – Aseptic practice in surgery using carbolic acid
• 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
• 1876 – Demonstration that microbes can cause disease-anthrax
• 1878 – Confirmation and popularization of the germ theory of disease
• 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"
• 1882 – Identification of Streptococcus pyogenes as the causative agent of erysipelas. He repeats Busch experiments inoculating cancer patients with eryisipelas, noting tumor regression in many of them
• 1883–1905 – Cellular theory of immunity via phagocytosis by macrophages and microphages
• 1885 – Introduction of concept of a "therapeutic vaccination". Report of a live "attenuated" vaccine for rabies
• 1888 – Identification of bacterial toxins
• 1888 – Bactericidal action of blood
• 1890 – Demonstration of antibody activity against diphtheria and tetanus toxins. Beginning of humoral theory of immunity. and
• 1891 – Demonstration of cutaneous hypersensitivity
• 1893 – Use of live bacteria and bacterial lysates to treat tumors – "Coley's Toxins", based on Busch and Fehleisen experiences
• 1894 – Bacteriolysis
• 1896 – An antibacterial, heat-labile serum component is described
• 1900 – Antibody formation theory
• 1901 – 1907 - Blood groups
• 1902 – Immediate hypersensitivity anaphylaxis and
• 1903 – Intermediate hypersensitivity, the "Arthus reaction"
• 1903 – Opsonization
• 1905 – "Serum sickness" allergy
• 1909 – Paul Ehrlich proposes "immune surveillance" hypothesis of tumor recognition and eradication
• 1911 – 2nd demonstration of filterable agent that caused tumors
• 1917 – Hapten
• 1921 – Cutaneous allergic reactions
• 1924 – Reticuloendothelial system
• 1925 – Adjuvants
• 1938 – Antigen-Antibody binding hypothesis
• 1940 – Identification of the Rh antigens
• 1942 – Anaphylaxis
• 1944 – hypothesis of allograft rejection
• 1945 – Coombs test antiglobulin test
• 1946 – Identification of mouse MHC
• 1948 – Antibody production in plasma B cells
• 1949 – Growth of polio virus in tissue culture, neutralization, and demonstration of attenuation of neurovirulence, and
• 1951 – A vaccine against yellow fever
• 1953 – Graft-versus-host disease
• 1953 – Validation of immunological tolerance hypothesis
• 1957 – Clonal selection theory
• 1957 – Discovery of interferon
• 1958–1962 – Discovery of human leukocyte antigens
• 1959–1962 – Discovery of antibody structure
• 1959 – Discovery of lymphocyte circulation
• 1960 – Discovery of lymphocyte "blastogenic transformation" and proliferation in response to mitogenic lectins-phytohemagglutinin
• 1961–1962 Discovery of thymus involvement in cellular immunity
• 1960 – Radioimmunoassay –
• 1961 – Demonstration that glucocorticoids inhibit PHA-induced lymphocyte proliferation
• 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" and, and
• 1965 – Discovery of "immune interferon"
• 1965 – Secretory immunoglobulins
• 1967 – Identification of IgE as the reaginic antibody
• 1968 – Passenger leukocytes identified as significant immunogens in allograft rejection
• 1969 – The lymphocyte cytolysis Cr51 release assay
• 1971 – ELISA is invented at Stockholm University
• 1972 – Structure of the antibody molecule
• 1972 – Discovery of invertebrate immunity
• 1973 – Dendritic Cells first described
• 1974 – Immune Network Hypothesis
• 1974 – T-cell restriction to MHC
• 1975 – Generation of monoclonal antibodies
• 1975 – Discovery of Natural Killer cells
• 1976 – Identification of somatic recombination of immunoglobulin genes
• 1980–1983 – Discovery and characterization of interleukins, 1 and 2 IL-1 IL-2
• 1981 – First description of an animal antimicrobial peptide in Cecropia silk moths
• 1983 – Discovery of the T cell antigen receptor TCR,
• 1983 – Discovery of HIV
• 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
• 1988 – Discovery of biochemical initiators of T-cell activation: CD4- and CD8-p56lck complexes
• 1990 – Gene therapy for SCID
• 1991 – Role of peptide for MHC Class II structure
• 1992 – Discovery of transitional B cells
• 1994 – Danger model of immunological tolerance is described by Polly Matzinger at the NIH
• 1995 – First description of the function of the critical immune checkpoint CTLA-4
• 1995 – Regulatory T cells
• 1995 – First Dendritic cell vaccine trial reported
• 1995 – Discovery of the insect Imd NF-κB pathway
• 1996–1998 – Identification of Toll-like receptors as immune-regulating molecules
• 1997 – Discovery of the autoimmune regulator and the AIRE gene
• 2000 – Characterization of M1 and M2 macrophage subsets
• 2001 – Discovery of FOXP3 – the gene directing regulatory T cell development
• 2005 – Development of human papillomavirus vaccine
• 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, 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 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, 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 is approved
• 2020 – The first mRNA vaccines, are developed for SARS-CoV-2 infection; this new technology completed design, testing, and emergency approval in under one year
• 2025 – After completing phase I clinical trials in 2024 dubodencel, an autologous personalized dendritic cell vaccine platform, enters randomized trials for the treatment of newly-diagnosed glioblastoma