Immunologists are delighted that the field of innate immunity has been recognized by this year's Nobel Prize in Physiology or Medicine. However, we believe that the Nobel Committee should also have acknowledged the seminal contributions of immunologists Charles A. Janeway Jr (1943–2003) and Ruslan Medzhitov.

Janeway laid out the major theory that unifies the principles of innate and adaptive immunity (C. A. Janeway Cold Spring Harb. Symp. Quant. Biol. 54, 1–13; 1989), later experimentally verified with Medzhitov and then by many others. He recognized that antigen alone is insufficient to elicit an adaptive immune response, and postulated that both primitive and higher animals have specialized 'pattern-recognition receptors' that induce the innate immune response when activated by a particular class of conserved microbial products ('pathogen-associated molecular patterns').

The most important tenet of his theory was the connection between innate immune signalling and initiation of the adaptive immune response through enhancement of antigen processing and presentation, induction of co-stimulatory signals and cytokine release.

Medzhitov and Janeway subsequently cloned a human 'Toll-like' receptor and showed that it activated signalling pathways that induce adaptive immunity (R. Medzhitov et al. Nature 388, 394; 1997). This remarkable demonstration also provided a framework for interpreting the significance of Toll-like receptors and their ligands for the immune response.

The innate–adaptive connection is now a fundamental principle in immunology. We believe that the work of Janeway and Medzhitov was a Nobel-standard breakthrough for immunology.