What do infectious diseases, cancer, allergies, and autoimmunity have in common? They all result from imperfect functioning of the immune system. When the immune system reacts too weakly, infectious pathogens and mutated tumor cells can escape elimination and lead to life-threatening diseases. On the other hand, when the immune system reacts too strongly, responses to a benign substance such as pollen can cause allergies, and responses to body tissues can cause autoimmune diseases. The immune system also limits the success of organ transplantation, since the foreign organ is rejected by an especially vigorous immune response. Research directed at studying the immune system can therefore have critical importance for many aspects of medical science. In addition, the immune system is a highly inter-dependent, developmentally regulated organ system that can be studied as an important model system in genetics, physiology, and cellular biochemistry. Cancer Immunology Some members study the underlying genetic or biochemical defects that lead to cell transformation and tumorigenesis, with an emphasis on intracellular signal transduction, programmed cell death, and oncogene function. Other members study the immune response to tumor cells, with an emphasis on the induction and regulation of both Natural Killer cells and T lymphocytes directed at tumor antigens. These studies employ and extend the most current knowledge in areas such as antigen presentation, lymphocyte specificity and activation, cytokine action, and in vivo vaccination strategies to develop safe and effective treatments of cancer by strengthening the immune response to tumor cells. Infectious Disease Immunology The study of infectious diseases and pathogenic microorganisms necessarily involves study of the immune system. It is not possible to truly understand microbial pathogenesis without addressing the interaction of the microbe with the host immune system. Infectious diseases occur when an organism evades the immune responses meant to contain it. The Program members study viruses, bacteria, and parasites. Program members involved in the study of the immunology of infectious diseases focus on evasion of immune responses by the pathogen, and the mechanisms by which immunity to the organism can be enhanced, such as immunotherapy or vaccines. In addition, the program members use the interaction of pathogens with the host to conduct basic studies of immune processes necessary to control infections, such as cytokine production by T cells, complement activation and macrophage activation. Transplantation Immunology Some members direct their research at weakening the immune response to foreign organ and tissue transplants. Program members focus both on the basic biology of immune cell non-reactivity (tolerance) to foreign organs and tissues, and on the use of new immunomodulatory drugs to promote transplant acceptance without endangering patients' abilities to resist infections. Insights gained from members' studies of transplant immunology also directly contribute to the research of other Program members who focus on the immunology of autoimmunity. Autoimmunity Diseases such as rheumatoid arthritis, lupus, and diabetes, (immune responses analogous in many ways to transplant rejection responses) are directed at self-tissues and underlie the autoimmune syndrome. Program members are therefore investigating how these deleterious immune responses can be down-regulated, using many of the same strategies and experimental techniques as the transplant immunologists. Of course, this is a two-way street and the transplant immunologists also learn from the autoimmunity researchers. In fact, each area of research in the Program strenghtens every other area, since learning how the immune response is normally organized and can be therapeutically regulated is the goal of all Program labs. Immunology of Lung Diseases The lung is the main portal of entry for a variety of airborne pathogens, allergens and other environmental pollutants. The lung has the unique ability to maintain homeostasis in the face of constant external provocation. Once this property is jeopardized, different types of lung diseases ensue. Although the underlying mechanisms of some of these diseases are not known, it is now becoming clear that immune imbalances contribute to many of these disorders. The cell types that orchestrate immunologic responses to allergens and other pathogens are dendritic cells (DCs), the key antigen presenting cell in the lungs, and T cells. Program members are involved in studying both basic mechanisms of dendritic cell maturation and their influence on T cell differentiation and the relevance of these interactions in disease and tolerance. Immunological Mechanisms Many members also study aspects of immunology that are not directly related to a disease process. The focus of basic immunology research in the program is on understanding the fundamental processes that underlie, for example, the development of the immune system, antigen processing and presentation, immunoglobulin gene expression, and mathematical modeling of T cell interactions. Basic immunology research is critically important since it provides many of the key findings that are subsequently applied to research focused on immunologic diseases.

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