Janeway [ 1 ] predicted that activation of the adaptive immune response is controlled by an evolutionary older innate immune system. He also hypothesized the existence of pattern recognition receptors. Twenty years later, i. Also in , the Journal of Innate Immunity was launched with the ambition to publish results of high-quality research in this area. The first editorial was written by Jules Hoffmann and Bruce Beutler [ 3 ] who were awarded the Nobel Prize in Physiology or Medicine in for their discoveries concerning the activation of innate immunity. The prize was shared with the late Ralph Steinman for his discovery of the dendritic cell and its role in adaptive immunity.
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Conveniently, nature offers up plenty of complex questions, just waiting for us to validate, demonstrate, and elucidate our way to the answer. Yet history has taught us that even the most widely respected scientific theories have limited lifespans; they become outmoded as new, more attractive ideas take their place.
For Kuhn, moments of genuine inspiration only occur during the revolutionary phases that can spawn new ways of thinking. Although as a physicist, Thomas Kuhn never got the chance to appreciate a puzzle as extravagant as the design of a colour flow panel.
Yet Kuhn argued that the impetus for change within a paradigm is only triggered when experimental or theoretical anomalies accumulate to a critical mass. But how appropriate is the definition to the more youthful, multidisciplinary field of immunology? Emil von Behring One could consider the early days of immunology as little more than curious diversions from the more established research disciplines.
Variolation and vaccination were medical innovations designed with the primary goal of curbing the rampant scourge of smallpox and other diseases. The discovery of factors that could transfer immune protection, such as complement and antibodies, was the work of biochemists working off on a tangent. Humoral immunity at the turn of the 20th century was as fashionable as the microbiome is today.
Merrill Chase The first challenges to humoral immunity emerged when scientists realized that certain phenomena could not be attributed to the presence of antibodies alone, a chief example being allograft rejection.
The death blow to the hegemony held by the humoral immune paradigm came in the form of the seminal cell transfer experiments by Karl Landsteiner and Merrill Chase. Landsteiner and Chase injected both cells and serum from M. These paradigm-shifting experiments humbled the humoral immunologists and forced them to at least acknowledge the existence of a second arm of the immune system mediated by cells. It was an amazing finding. Frank Burnet Although it was all well and good to know that both cells and antibodies contributed to immunity, researchers of the time remained perplexed with the problem of specificity.
More precisely, how could the immune system account for the near infinite number of different antigens that a host could encounter? The short answer was the clonal selection theory. In , Burnet published his then-hypothesis in a succinct paper of just two pages with no data figures try pulling that off now explaining how the immune system applied a cycle of cell division, mutation, and selection to form a broad diversity of clonal specificities. Much like any revolutionary scientific theory, clonal selection immediately divided opinion and required experimental validation to convince the numerous naysayers.
Nossal and Lederberg immunized rats with two different strains of Salmonella and used the latest in microbiology techniques — single cell microculture on mineral oil — to check the reactivity of the antibodies produced.
Its influential shadow looms as large for immunology research today as it did in the s. Other paradigms have shared the spotlight with clonal selection — some with lasting impact, others less so. In the s and s, Niels Jerne turned immunology inside out by promoting his immune idiotype network theory, which argued that the individual components of the immune system — cells, antibodies, other soluble factors —recognize, bind, and communicate with each other, not just with foreign material, to coordinate complex responses against disease.
Yet this revolution was not to be, as the global immunology community dismissed the network theory when a search for the master regulatory gene during the s came up empty-handed. Jerne actually shared the Nobel Prize in Physiology or Medicine specifically for this theory; unofficially, he won it for his theoretical genius and a lifetime of scientific contributions.
His prediction formed the basis for a new field of innate immunity that was based on recognition of non-clonal patterns found on pathogens. A Time for Change As Kuhn predicted, each and every one of these immunological paradigm shifts brought on a period of incredibly productive science, as researchers could apply the latest in technological approaches within a new set of principles.
Equipped in this day and age with an arsenal of powerful bioinformatics and big data resources, we really do generate more information than we know what to do with. So are we on the verge of figuring out the immune system? Why is it so difficult to generate a protective immune response against some pathogens like HIV? How is the immune system regulated by the brain? Can the existing framework of immunology provide the answer to these questions and more?
If not, is there a Burnet, Jerne, or Janeway of this generation that has the ingenuity and more importantly, the guts, to point us in a new direction? References: Andersson, U. Baxter, A. Eichmann, Klaus. Gitlin, A.
The history of Toll-like receptors — redefining innate immunity
This article has been updated Key Points Caspase 1 and caspase 11 control both the release of inflammatory cytokines and the execution of pyroptosis upon inflammasome activation. Caspase 11, as well as human caspase 4 and caspase 5, bind to LPS with high specificity and affinity, and trigger this pathway. LPS-induced lethality in mice, which has long been ascribed to caspase 1, is rather mediated by caspase New studies show that caspase 8 is integrated into inflammatory signalling pathways downstream of RIG-I, dectin 1 and TLR4, in which caspase 8 either facilitates or attenuates inflammation. Future studies will undoubtedly elucidate the full impact of caspase 8 activity on inflammation. The decision whether cells die by apoptosis or necroptosis is determined by a balance between the activities of caspase 8 and the master orchestrator of necroptosis, RIPK3.
A long-awaited merger of the pathways mediating host defence and programmed cell death
Liu Y, Janeway CA. Extensive cd4 cross-linking inhibits t cell activation by anti-receptor antibody but not by antigen International Immunology. Regulatory responses in contact sensitivity: We are testing a new system for linking publications to authors. Epicutaneous immunization with autoantigenic peptides induces T suppressor cells that prevent experimental allergic encephalomyelitis. A new concept of the role of self-peptide: That meeting also brought together sufficient data on antibody structure to promote the idea that immunoglobulins are encoded in two distinct types of gene segments, variable segments and constant segments, and that a genetic mechanism must exist to direct the August 1, at 8: He enjoys staying active, playing board games, iimmunology supporting his beloved Arsenal FC.
Approaching the Asymptote? Evolution and Revolution in Immunology