Pillars Article: Approaching the Asymptote? Evolution and Revolution in Immunology. Cold Spring Harb Symp Quant Biol. 1– Author: Janeway CA Jr, Journal: Cold Spring Harbor symposia on quantitative biology. Author: Janeway CA Jr, Journal: Journal of immunology (Baltimore, Md.: )[ /11] Evolution and revolution in immunology. Cold spring harb symp.
|Published (Last):||8 April 2009|
|PDF File Size:||3.25 Mb|
|ePub File Size:||5.93 Mb|
|Price:||Free* [*Free Regsitration Required]|
As scientists, we love to answer questions. 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?
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. 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. 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.
Approaching the asymptote? Evolution and revolution in immunology. – Abstract – Europe PMC
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.
Now attributed to Frank Immujology Burnet, this theoretical masterwork required the input of three men: Burnet himself, David Talmage and Niels Jerne. InBurnet 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 iin 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 evoluhion 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.
As Kuhn predicted, each and every one of these immunological asympgote 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?
Excellent historical and present day synopsis of the scientific pursuit and of the field of immunology.
Approaching the Asymptote? Evolution and Revolution in Immunology
It continues to surprise me that something that I should know, without question, can still surprise me when expressed in a slightly different way the early perception of a serum-antibody-centric immune universe.
Inflammation and thus innate immunity were regarded as separate entities. When we asymptoet of inflammation, many will envisage the angry, swollen redness of a boil, or an infected wound, or a gout affected joint that the sufferer is loathe to touch. But inflammation ranges from the mildest of mild to these angry states.
Intact apoptotic bodies, reflect a controlled cell shutdown that provokes virtually no inflammation even though these bodies are packed with debris. However, this debris is, necessarily, first processed by cells into peptide fragments.
Revolutions in Immunology
We have two basic forms of i,munology processing: The major change in this classification of debris is that we now need a spectrum of effector responses that run from tolerance inflammation-suppressing debris to aggression inflammation promoting debris.
Now ghe have a system that is driven by the context in which debris is first presented paproaching it becomes an inflammo-centric immune system. BUT, the story gets deeper now, because it is clear that the inflammo-immune system can destroy self tissues and it is equally clear that the inflammatory response resolves with a phase appgoaching tissue repair and regeneration. Now the whole system starts to look like a tissue homeostatic mechanism.
The persisting illusion that lymphocytes attack pathogens is groundless. Antibodies have a bit more leeway but, in vivo, not as much as you may anticipate. Lymphocytes respond to Mhc-peptide debris. Lymphocytes are being used to recognise early the fresh presentation of this peptide junk and then to ramp up apoptosis of tagged cells or ramp up the contextual inflammatory response that went with it on the first encounter into either strong tolerance or strong aggression.
I reckon that this change from a lympho-centric to an inflammo-centric system is pretty much comparable to a Copernican shift. The trick is whether or not the people know how to use the data effectively. Your email address will not be published.
Approaching the asymptote? Evolution and revolution in immunology.
Want the scoop on immunology and graduate education? Subscribe to IMMpress Magazine for all the latest updates. Check out their websites for more great reading on science, research and graduate life.
The following two tabs change content below. Michael Le Managing Editor. Michael is a 4th year PhD student in the Department of Immunology at the University of Toronto studying how B cells diversify their antibodies to fight infections. He enjoys staying active, playing board games, and supporting his beloved Arsenal FC. Latest posts by Michael Le see all. June 15, at 1: August 1, at 8: November 16, at 5: Leave a Reply Cancel reply Your email address will not be published.