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Nobel Prizes, Transplantation and the Immune System

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Javier Carbone, MD, PhD
Complutense University
Madrid, Spain

Immune response during transplantation is quite complex. Several components participate in distinct phases before and after transplantation and there's a huge amount of variability. Here, we briefly review more than a century of accomplishments in studying some of these components by Nobel Prizes in Physiology or Medicine. Each of these discoveries have provided us with a better understanding of how this system works.

Emil von Behring (Nobel Prize in 1901) identified serum specific factors that neutralize the toxic products from tetanus and diphtheria bacteria. Specific hyper immune immunoglobulins can now be used for a better control of severe infectious complications after transplantation.

Ilya Ilyich Mechnikov (1908) identified phagocyte cells and phagocytosis. However, the role of this important, innate immune function in heart and lung transplantation remains poorly explored.

Paul Ehrlich's side-chain theory (1908) proposed how antibodies released in blood can control infection.

Charles Richet (1913) discovered anaphylaxis, a life-threatening allergic reaction, as one of the first evidences that the immune system can damage its host.

Jules Bordet (1919) described serum factors that work with antibodies to destroy bacteria: The complement system. Complement factors are now extensively investigated as biomarkers of rejection and infection risk in heart and lung transplantation. Recent work indicates that complement activation regulates key metabolic pathways, and thus, can impact cellular processes, such as survival, proliferation, and autophagy.

Karl Landsteiner (1930) discovered human blood groups. His system for typing blood allowed blood transfusions to be performed without the risk of adverse reactions.

Sir Frank MacFarlane Burnet and Peter Medawar were awarded the Nobel Prize in 1960 for their contribution to the understanding of the concept of acquired immunological tolerance.

Two scientists independently deciphered the chemical structure of antibodies: Gerald Edelman and Rodney Porter in 1972.

Baruj Benacerraf, Jean Dausset and George Snell were awarded the Nobel Prize in 1980. Investigations from these researchers helped to understand the genetic basis of the immunological reactions, how a specific set of proteins found on the surface of cells (The MHC complex) can regulate this system.

In 1984, Nils Jerne, Georges Kohler, and C├ęsar Milstein were awarded the Nobel Prize. Jerne's theories provided a clearer image of how the immune system engages antibodies to fight microorganisms. Köhler and Milstein's techniques for producing specific antibodies helped to create better diagnostic tests and new treatments (monoclonal antibodies).

Susumu Tonegawa was awarded the Nobel Prize in 1987 for his discoveries of the diversity of antibodies and the genetic mechanism for their construction.

Joseph E Murray and E Donnall Thomas were awarded the Nobel Prize in 1990 for their discoveries concerning organ (kidney) and cell (BMT) transplantation in the treatment of human disease.

Peter Doherty and Rolf Zinkernagel (1996) proposed how the immune system specifically recognizes virus-infected cells: The immune system can distinguish foreign agents from its own cells and tissues.

Bruce A Beutler, Jules A Hoffman, and Ralph M Steinman were awarded the Nobel Prize in 2011 for their discoveries concerning the activation of innate immunity and discovery of the dendritic cells and its role in adaptive immunity.

Last year's Nobel Prize in medicine (2016) went to Yoshinori Ohsumi for his work in cell recycling and discoveries of mechanisms for autophagy. To date, little is known about the role of autophagy in heart and lung transplantation. ■

Disclosure Statement: The author has no conflicts of interest to disclose.

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