2009CB522407). The authors have no financial conflict of interest. “
“The 2011 Nobel Prize in Physiology/Medicine to Ralph Steinmann, Jules Hoffmann, and Bruce Beutler recognized a paradigm shift in our understanding of innate immunity, and its impact on adaptive immunity. The Prize highlighted
the initial discoveries of Toll’s role in immunity in flies, Toll-like receptors in mammals, and the establishment of dendritic cells as the initiators of adaptive immunity. This historical Commentary focuses on the developments in our understanding of innate immunity. In 1908, the Nobel Prize in Physiology/Medicine went jointly to Ilya Ilyrich Metchnikoff, the original champion of cellular immunity, and Paul Ehrlich, then ambassador of humoral defenses, “in recognition of their work in immunity.” Metchnikoff advocated the idea that phagocytic cells, far from being harmful to the organism, as was the Alisertib concentration current paradigm, in fact constituted a first
line of defense by nonspecifically ingesting and digesting invading pathogens and other foreign material []. His cellular theory of immunity, however, was challenged when Emil von Behring and Shibasaburo Kitasato discovered that immunity to tetanus and diphtheria was explained MK-2206 mouse by antibodies (Abs) specific for their respective exotoxins []. Subsequently, Ehrlich proposed the “side-chain theory” to explain how Abs functioned []. However, the discovery by Almoth Wright and Stewart Douglas that “the body fluids modify bacteria in a manner which renders them ready prey to phagocytes” (where body fluids can now be interpreted as Abs in immunized animals) was the first report that
both branches (cellular and humoral) of the immune system may work together []. Wright named this observation the “opsonic phenomenon,” and the factors were called opsonins (from the Greek opsono (I prepare victuals for)). Even Ehrlich, an enthusiastic Methocarbamol believer in humoral immunity, acknowledged in his landmark review of 1908 [] that infections are cleared by cellular and humoral immunity. Nevertheless, most immunologists at that time became followers of the humoral theory to explain how immune defenses worked, mainly because Abs could be easily studied in a test tube. Therefore—and perhaps mirroring the work of the more chemically oriented Ehrlich—immunology began to shift from cellular immunology toward chemistry, led by scientists such as Karl Landsteiner, Felix Haurowitz, Michael Heidelberger, John Marrack, and Linus Pauling. In the early 1960s, the tide changed again and immunology transformed from a chemical to a more biological discipline mainly through the work of N. Avrion Mitchison [] and Peter Medawar [] who showed that cellular rather than humoral mechanisms were sufficient to account for allograft rejection, immunological tolerance, and resistance and memory against tumors.