Timeline of immunology

• 1549 – The earliest account of inoculation of smallpox occurs in Wan Quan's Douzhen Xinfa.
• 1718 – 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 – First demonstration of smallpox vaccination
• 1837 – Description of the role of microbes in putrefaction and fermentation
• 1838 – Confirmation of the role of yeast in fermentation of sugar to alcohol
• 1840 – Proposal of the germ theory of disease
• 1850 – Demonstration of the contagious nature of puerperal fever
• 1857–1870 – Confirmation of the role of microbes in fermentation
• 1862 – Phagocytosis
• 1867 – Aseptic practice in surgery using carbolic acid
• 1876 – Demonstration that microbes can cause disease-anthrax
• 1877 – Mast cells
• 1878 – Confirmation and popularization of the germ theory of disease
• 1880 – 1881 -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"
• 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"
• 1894 – Bacteriolysis
• 1896 – An antibacterial, heat-labile serum component is described
• 1900 – Antibody formation theory
• 1901 – 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
• 1938 – Antigen-Antibody binding hypothesis
• 1940 – Identification of the Rh antigens
• 1942 – Anaphylaxis
• 1942 – Adjuvants
• 1944 – hypothesis of allograft rejection
• 1945 – Coombs test antiglobulin test
• 1946 – Identification of mouse MHC by George Snell and Peter A. Gorer
• 1948 – Antibody production in plasma B cells
• 1949 – Growth of polio virus in tissue culture, neutralization with immune sera, and demonstration of attenuation of neurovirulence with repetitive passage and and
• 1951 – vaccine against yellow fever
• 1953 – Graft-versus-host disease
• 1953 – Validation of immunological tolerance hypothesis
• 1957 – Clonal selection theory
• 1957 – Discovery of interferon by Alick Isaacs and Jean Lindenmann
• 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 and
• 1971 – Peter Perlmann and Eva Engvall at Stockholm University invented ELISA
• 1972 – Structure of the antibody molecule
• 1973 – Dendritic Cells first described by Ralph M. Steinman
• 1974 – Immune Network Hypothesis
• 1974 – T-cell restriction to MHC
• 1975 – Generation of monoclonal antibodies and
• 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
• 1983 – Discovery of the T cell antigen receptor TCR and
• 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
• 1995 – James P. Allison describes the function of CTLA-4
• 1995 – Regulatory T cells
• 1995 – First Dendritic cell vaccine trial reported by Mukherji et al.
• 1996 – 1998 – Identification of Toll-like receptors
• 1997 – Discovery of the autoimmune regulator and the AIRE gene.
• 2000 – Characterization of M1 and M2 macrophage subsets by Charles Mills
• 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
• 2008 - Françoise Barré-Sinoussi and Luc Montagnier win the Nobel Prize in Physiology or Medicine for their discovery of human immunodeficiency virus
• 2010 – 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, 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. Two different drugs, pembrolizumab and nivolumab are approved within months of each other.
• 2016 – 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, 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. It is developed by an Indian Biotechnology company, APAC Biotech.
• 2018 - James_P._Allison and Tasuku_Honjo won the Nobel Prize in Physiology or Medicine for their discovery of cancer therapy by inhibition of negative immune regulation