Ever since Edward Jenner first prevented smallpox infection by injecting an English boy with cowpox virus in the 1790s, scientists have worked to conquer infectious diseases by understanding and strengthening the immune response. Yet as recently as three decades ago, the most basic principles of modern immunology eluded researchers, who were scattered across university departments, working largely in isolation.

At the School of Medicine all that began to change in 1988. The administration decided to continue the work of the late Richard Gershon, M.D., who had established an immunology division within the pathology department, by recruiting Richard A. Flavell, Ph.D., to create the Section of Immunobiology, one of the first freestanding groups in the country devoted to teaching and research in immunology.

Almost 20 years later, Flavell, now Sterling Professor of Immunobiology, continues to lead the School of Medicine’s immunologists, but in January his Section of Immunobiology became a full-fledged academic department. What started out in 1988 as a handful of scientists has grown to include 13 world-renowned researchers, including four investigators of the highly competitive Howard Hughes Medical Institute and two members of two of the world’s most prestigious scientific societies: the National Academy of Sciences (NAS) and the United Kingdom’s Royal Society. “We strategized about it and planned very carefully what we wanted to build, and that’s what we built,” says Flavell.

Yale’s newly christened Department of Immunobiology was named the best in its field in the United States in a Chronicle of Higher Education survey published in January. In 2006, department members had over $18,000,000 in combined federal and non-federal research funding; between 1999 and 2006 the faculty collectively published more than 70 scientific articles in the top science journals Science, Nature and Cell.

A prime example of the department’s far-reaching influence is the discovery of the so-called toll-like receptors of the innate immune system in the 1990s. At that time, most immunology researchers were focused on the adaptive immune system, which quickly creates custom-made B and T cells that target specific bacterial or viral invaders. But the late Charles A. Janeway Jr., M.D. wondered how the adaptive immune system is able to act so precisely every time the body is invaded by an infectious microbe.

In a scientific tour de force published in 1997 in the journal Nature, Janeway and Ruslan M. Medzhitov, Ph.D., professor of immunobiology, showed that toll-like receptors, a component of the innate system, 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,” says David G. Schatz, Ph.D., professor of immunobiology.

According to the National Library of Medicine, nearly 6,000 scientific articles on toll-like receptors have been published in the wake of Janeway and Medzhitov’s seminal article, but this is just one of many important contributions that have emanated from the department.

Flavell has focused on genetics by examining how different genes contribute to the decision-making process that gives rise to two important immune cells known as Th1 and Th2 cells, which regulate the type of immune response generated by the body. Flavell’s lab has identified molecules involved in activating and differentiating T cells that could have implications for treating HIV and cancer.

T cells are also an area of interest for Kim Bottomly, Ph.D., Yale’s deputy provost for science, technology and faculty development and professor of immunobiology, dermatology and molecular, cellular and developmental biology. Bottomly’s lab has shown that the immune response to allergens, such as those that provoke asthma, stems from their similarities to microbes that jump-start the immune system.

Understanding the immune response is also crucial to untangling how it goes awry in autoimmune diseases. Peter Cresswell, Ph.D., professor of immunobiology, dermatology and cell biology studies how proteins get broken down and then “displayed” by antigen-presenting cells that allow T cells to recognize them.

Schatz is focusing on two proteins he discovered that are involved in antibody production and without which there would be no adaptive immune response.

Sankar Ghosh, Ph.D., professor of immunobiology, molecular biophysics and biochemistry and molecular, cellular and developmental biology, has concentrated on a protein called NF-κB that allows toll-like receptors to send signals. NF-κB is involved in every kind of inflammatory process, from the redness that results when a splinter penetrates the skin to cancer.

The explosive growth of knowledge from the Department of Immunobiology’s basic research over the last two decades has led to an increasing 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, coronary artery disease and Alzheimer’s disease. The department remains in the scientific vanguard with the recently launched Human and Translational Immunology program, which will work on applying lessons learned in the lab to human beings.