These studies, however, largely neglected the contribution of innate immunity during the early Ganetespib phases of infection, perhaps because, until recently, the necessary conceptual views and technologies were missing. Of upmost importance to the development of the field has been the infusion of molecular biology into immunology and the utilization of the central dogma of genetics, which holds that cellular information flows from DNA to RNA to protein. As a result, today’s understanding of immunology merges humoral and cellular aspects,

and knowledge on adaptive immune responses has advanced by quantum leaps during past decades. The Clonal Selection Theory [[8]] states that each lymphocyte is equipped with many identical copies of an antigen-specific receptor, and when this receptor binds its ligand with high

avidity, T and B cells undergo clonal expansion and differentiation. selleck chemicals llc However, for naive T cells to become activated and for adaptive immunity to be initiated, antigen must be presented by a specialized cell type called the dendritic cell (DC), as was first brought to our attention in 1973 by the Nobel Laureate Ralph Steinman, together with Zanvil Cohn [[12]]. Ralph Steinmann’s contribution in transforming the “novel cell type of 1973” into one of the brightest stars of the immunology firmament has often been highlighted, for example [[13]] and is therefore not a focus of this article. The upregulation of costimulatory signals on DCs, induced by postulated pathogen-associated molecular patterns (PAMPs), was speculated by the late Charles Janeway [[14]] in 1989 to play an essential role in alerting adaptive immunity [[15]]. In addition, although microbes

had long been recognized as the cause of infectious diseases, and Metchnikoff’s nonspecific phagocyte model as the first line of immune defense had been with us since the end of the 19th century, the fundamental question as to how the immune system perceives infection remained largely unknown. A clue came from the observation that the inbred mouse strains mafosfamide C3H/HeJ and C57BL/10ScCr resisted doses of lipopolysaccharide (LPS; endotoxin) that were lethal in other mice strains [[16]]. Was it possible that these inbred mice harbored a nonfunctional (mutated) receptor sensing LPS? The critical tools provided by Christiane Nüsslein-Vollhard, Edward Lewis, and Eric Wieschaus (Nobel Prize Laureates in 1995) assisted in the revelation of how the mammalian host recognizes infection. These researchers isolated a set of master genes in Drosophila. Of note, Nüsslein Vollhard’s group showed that the Toll gene controls the establishment of the dorsoventral axis in fruitfly embryos [[17]].