Professor Robert Braidwood Sim-"Bob"-A Career in Complement Research Spanning 1973-2021.

Bob joined the MRC Immunochemistry Unit, within the Department of Biochemistry at Oxford University, as a D [...].

A Personal Tribute to Robert B. Sim with Reflections on Our Work Together on Factor H.

Robert (Bob) Sim had a profound effect on almost every aspect of my approach to scientific research, acting as a mentor and moral compass through the many different stages of my career [...].

Towards a paradigm shift in innate immunity-seminal work by Hans G. Boman and co-workers.

Four decades ago, immunological research was dominated by the field of lymphoid biology. It was commonly accepted that multicellular eukaryotes defend themselves through phagocytosis. The lack of lymphoid cells in insects and other simpler animals, however, led to the common notion that they might simply lack the capacity defend themselves with humoral factors. This view was challenged by microbiologist Hans G. Boman and co-workers in a series of publications that led to the advent of antimicrobial peptides as a universal arm of the immune system. Besides ingenious research, Boman ignited his work by posing the right questions. He started off by asking himself a simple question: 'Antibodies take weeks to produce while many microbes divide hourly; so how come we stay healthy?'. This led to two key findings in the field: the discovery of an inducible and highly potent antimicrobial immune response in Drosophila in 1972, followed by the characterization of cecropin in 1981. Despite broadly being considered an insect-specific response at first, the work of Boman and co-workers eventually created a bandwagon effect that unravelled various aspects of innate immunity.This article is part of the themed issue 'Evolutionary ecology of arthropod antimicrobial peptides'.

['Specificity' in microbiology and immunochemistry between 1880 and 1930]. / Il problema della specificità nella microbiologia e nell'immunochimica tra il 1880 e il 1930.

During the second half of the XIX Century, microbiological sciences acquired a set of conceptual, methodological and technological tools that radically transformed theoretical and empirical knowledge of the microorganisms, with particular regard to their biochemical properties and their etiopathological role in infectious diseases. During that period, theoretical and experimental researches in general microbiology and immunochemistry addressed the nature and empirical appearances of microbes, both pathogens and not, and the origins of chemical properties of immune sera. In other words, microbiologists tried operatively explaining the origins of the morphological, physiological, and pathogenetic differences between the microbial species. At the same time physiologists and biochemists investigated the chemical basis of the selective or specific interactions between microorganisms or their chemical components and humoral factors contained into the sera produced by the body in response to the contact with microbes. During the half a century, between 1880 and 1930, qualitative and quantitative experimental studies demonstrated that the specificity of microbiological phenomena depended on the biology of microbes and that the specificity of immune reactions hinged upon the biochemical properties of special molecules synthesized by some physiological system which can recognize and react against any foreign substance.

The early history of plasma cell tumors in mice, 1954-1976.

Plasma cell tumors (PCTs) in mice became available at an exciting period in immunology when many scientists and laboratories were occupied with how to explain the genetic basis of antibody diversity as well as antibody structure itself. An unlimited source of PCTs in an inbred strain of mice became a useful adjunct in these efforts. A PCT was a greatly expanded monoclone and a source of a single molecular species of immunoglobulin (Ig) molecule. The PCTs provided not only the components of the Ig-producing cell but also potentially functional secreted products. Many of the monoclonal Igs produced by PCTs in the mouse and others found in humans were found to have specific antigen-binding activities. These became the prototypes of monoclonal antibodies. This chapter describes the origins of PCTs in mice and attempts to recapture some of the ambience of the day albeit from personal recollection. The great discovery of the hybridoma technology by Cesar Milstein and Georges Kohler in 1975 began a new direction in immunology.

Michael Heidelberger and the demystification of antibodies.

Having defined the protein nature of antibodies under the tutelage of Oswald Avery, Michael Heidelberger was the first to apply mathematics to the reaction of antibodies and their antigens (the "precipitin reaction"). Heidelberger's calculations launched decades of research that helped reveal the specificity, function, and origin of antibodies.

How Heidelberger and Avery sweetened immunology.

In 1923, a young chemist-turned-microbiologist and his mentor made the startling discovery that bacterial sugars could be targeted by the immune system--a groundbreaking finding that helped launch the field of immunochemistry.

Monoclonal antibodies in the prehybridoma era: a brief historical perspective and personal reminiscence.

Emil von Behring, an immunologist, received the first Nobel Prize in Physiology or Medicine in 1901 for his studies on serum therapy of diphtheria. Seventeen Nobel Prizes have been awarded to scientists for their work in immunology and related disciplines. E. Metchnikoff and P. Ehrlich were pioneers who became associated with cellular and humoral theories of immunity, respectively. Almroth Wright described opsonins and was a vigorous advocate of vaccine therapy for bacterial diseases. He was an influential scientist and mentor who served as the model for Bernard Shaw's play, The Doctor's Dilemma. Immunochemistry developed through the work of K. Landsteiner, M. Heidelberger, E. Kabat, and many others. At mid-20th century, cell-selection theories of antibody formation championed by N. Jerne and F.M. Burnet shifted the field from a chemical to a biological orientation. Myeloma immunoglobulins, Bence Jones proteins, and monoclonal macroglobulins from patients and mice played a central role in elucidation of normal immunoglobulin structure, genetics, synthesis, and metabolism. By the late 1960s, antibody activity in some human myeloma and Waldenström macroglobulin paraproteins had been documented. Subsequently, other human paraproteins were shown to have antigen-binding properties, principally to auto- or bacterial antigens. The development of hybridoma technology by G. Köhler and C. Milstein revolutionized immunology after 1975. These investigators demonstrated that antibody-producing cells of virtually any desired specificity could be fused with a myeloma cell line, the result being unlimited amounts of homogeneous (monoclonal) antibodies carrying that specificity. Monoclonal antibodies have been shown to have efficacy in cancer therapy, particularly in patients with lymphoma and breast cancer. It is likely that this approach, alone and in combination with other modalities, will prove useful for patients with additional types of malignancies.

Historia de la inmunología / Immunology history

Los 200 años de historia de la inmunología se pueden separar en 2 períodos: 1796-1958 y 1959 a la fecha. Este último período se ha caracterizado por avances científicos a nivel molecular. Veinticuatro investigadores han obtenido 15 premios Nobel por sus aportes en el campo de la inmunología: Boehring, Koch, Erlich, Metchnikoff, Carrel, Richet, Bordet, Lansteiner, Theiler, Bovet, Burnet, Medawar, Edelman, Porter, Yalow, Benacerraf, Dausset, Snell, Jerne, Koller, Milstein, Tonegawa, Zinkernagel y Doherty. En este capítulo se mencionan los avances más importantes en inmunidad, serología, inmunoquímica e inmunobiología, realizados por alrededorde 70 científicos durante los dos siglos de historia de esta ciencia