This year´s Nobel Laureates have revolutionized our understanding of the immune system by discovering key principles for its activation.
Scientists have long been searching for the gatekeepers of the immune response by which man and other animals defend themselves against attack by bacteria and other microorganisms. Bruce Beutler and Jules Hoffmann discovered receptor proteins that can recognize such microorganisms and activate innate immunity, the first step in the body´s immune response. Ralph Steinman discovered the dendritic cells of the immune system and their unique capacity to activate and regulate adaptive immunity, the later stage of the immune response during which microorganisms are cleared from the body.
The discoveries of the three Nobel Laureates have revealed how the innate and adaptive phases of the immune response are activated and thereby provided novel insights into disease mechanisms. Their work has opened up new avenues for the development of prevention and therapy against infections, cancer, and inflammatory diseases.
Two lines of defense in the immune system
We live in a dangerous world. Pathogenic microorganisms (bacteria, virus, fungi, and parasites) threaten us continuously but we are equipped with powerful defense mechanisms. The first line of defense, innate immunity, can destroy invading microorganisms and trigger inflammation that contributes to blocking their assault. If microorganisms break through this defense line, adaptive immunity is called into action. With its T and B cells, it produces antibodies and killer cells that destroy infected cells. After successfully combating the infectious assault, our adaptive immune system maintains an immunologic memory that allows a more rapid and powerful mobilization of defense forces next time the same microorganism attacks. These two defense lines of the immune system provide good protection against infections but they also pose a risk. If the activation threshold is too low, or if endogenous molecules can activate the system, inflammatory disease may follow.
The components of the immune system have been identified step by step during the 20th century. Thanks to a series of discoveries awarded the Nobel Prize, we know, for instance, how antibodies are constructed and how T cells recognize foreign substances. However, until the work of Beutler, Hoffmann and Steinman, the mechanisms triggering the activation of innate immunity and mediating the communication between innate and adaptive immunity remained enigmatic.
More information is available on the Karolinska Institutet website.