Ever since Edward Jenner injected a young English boy with cowpox virus in the 1790s to prevent smallpox, scientists have tried to conquer infectious diseases by understanding and strengthening the human body’s immune response. Yet as recently as three decades ago, the most basic principles of modern immunology eluded researchers.All that would change, however, when the medical school decided to continue the work of the late Richard Gershon, M.D., who had established an immunology group within the pathology department. In 1988, a visionary scientist was recruited to create one of the first free-standing immunobiology sections in the world.Almost 20 years later, Richard A. Flavell, Ph.D., Sterling Professor of Immunobiology, remains chair, but in January the section became a full-fledged department in the School of Medicine. The group that started out as a handful of scientists has grown to include 13 world-renowned researchers, whose publications appear regularly in top-ranked scientific journals. “We strategized about it and planned very carefully what we wanted to build, and that’s what we built,” said Flavell.Representative of the group’s far-reaching influence is the discovery of the workings of the innate immune system in the 1990s. While most researchers focused on the adaptive immune system, which creates B and T cells that target specific bacterial or viral invaders, the late Charles A. Janeway Jr., M.D., wondered how these immune responders are able to act so effectively and precisely every time the body is invaded by an infectious microbe. In a scientific tour de force, he and Ruslan M. Medzhitov, Ph.D., professor of immunobiology, showed that components of the innate system known as toll-like receptors provide the adaptive system with the necessary advance intelligence to do its job.“It was like saying there are only four planets in the solar system and then one day somebody comes along and says no, there are eight,” said David G. Schatz, Ph.D., professor of immunobiology.Uncovering the role of toll-like receptors in the innate immune system is just one of the advances made by the department. Flavell’s lab has identified molecules that are involved in activating and differentiating T cells and that could have implications for HIV and cancer.Other areas of research are the similarities between allergens and microbes that jump-start the immune system; how proteins get broken down and then “presented” by antigen-presenting cells that allow T cells to recognize them; proteins that are involved in antibody production; and a protein that allows toll-like receptors to send signals and is involved in every inflammatory process.The explosive growth of knowledge coming from the department over the last two decades has increased the awareness that the clinical relevance of immunobiology goes far beyond protection against disease. Immune mechanisms may lie at the root of numerous chronic diseases, including cancer, congestive heart failure and Alzheimer’s disease.