Dendritic cells (DC) and their Toll-like receptors (TLR): Vital elements at the core of all individual immune responses. On the Nobel Prize in Physiology or Medicine 2011 awarded to Bruce A. Beutler, Jules A. Hoffmann, and Ralph M. Steinman

Abstract

The protection of the personal integrity, which is exercisedby the immune system against pathogens, has very effectiveand invariant mechanisms; these invariant mechanismsare grouped under the concept of 'innate immunity.' Unlike'adaptive immunity' (developed by lymphocytes and immunoglobulins),innate immunity is not improved with consecutivecontacts (it has not got the immunological memory, as vaccinesinduce) and overall innate immunity remains unchangedthroughout the life of each individual. Unlike the specific recognitionof receptors for antigen (TCR and immunoglobulins) ofadaptatitve immunity, the innate immune response acts in frontof danger of pathogens thanks to the recognition of PathogenAssociated Molecular Patterns (PAMPs), a recognition perhapsless sophisticated but equally or even more effective than adaptativeimmunity. There are several receptors of these molecularpatterns of danger, and among them the Toll-Like Receptors(TLRs)-whose name recalls the concept of "toll that which isstrange"-originally described in cells of Drosophila melanogaster.The description of TLRs is mainly due the work of Drs.Bruce A. Beutler and Jules A. Hoffmann who were recognizedby the Swedish Foundation for their activation studies of innateimmunity by TLRs. Next to them, the third Nobel awarded wasDr. Ralph M. Steinman for his description of Dendritic Cells(DCs), a cell subtype of the innate immune response that determinesthe response (or the tolerance) of adaptative immunity.Unfortunately, Dr. Steinman died of cancer just before the concessionof the prize was made public (the jury had already madeits decision being this the reason for keeping the prize). Thesestudies have revolutionized our understanding of the immunesystem, leading to the description of new diseases (new immunodeficiencies,or intraindividual variations that partly explainsome diseases), the emergence of new therapies (there are approvedtreatments based on the presentation by DCs) and verypromising new fields of research to improve strategies with vaccinesand treatments for infections, cancer and several inflammatorydiseases. The protection of the personal integrity, which is exercised by the immune system against pathogens, has very effective and invariant mechanisms; these invariant mechanisms are grouped under the concept of 'innate immunity.' Unlike 'adaptive immunity' (developed by lymphocytes and immunoglobulins), innate immunity is not improved with consecutive contacts (it has not got the immunological memory, as vaccines induce) and overall innate immunity remains unchanged throughout the life of each individual. Unlike the specific recognition of receptors for antigen (TCR and immunoglobulins) of adaptatitve immunity, the innate immune response acts in front of danger of pathogens thanks to the recognition of Pathogen Associated Molecular Patterns (PAMPs), a recognition perhaps less sophisticated but equally or even more effective than adaptative immunity. There are several receptors of these molecular patterns of danger, and among them the Toll-Like Receptors (TLRs)-whose name recalls the concept of "toll that which is strange"-originally described in cells of Drosophila melanogaster. The description of TLRs is mainly due the work of Drs. Bruce A. Beutler and Jules A. Hoffmann who were recognized by the Swedish Foundation for their activation studies of innate immunity by TLRs. Next to them, the third Nobel awarded was Dr. Ralph M. Steinman for his description of Dendritic Cells (DCs), a cell subtype of the innate immune response that determines the response (or the tolerance) of adaptative immunity.Unfortunately, Dr. Steinman died of cancer just before the concession of the prize was made public (the jury had already made its decision being this the reason for keeping the prize). These studies have revolutionized our understanding of the immune system, leading to the description of new diseases (new immunodeficiencies, or intraindividual variations that partly explain some diseases), the emergence of new therapies (there are approved treatments based on the presentation by DCs) and very promising new fields of research to improve strategies with vaccines and treatments for infections, cancer and several inflammatory diseases.