Using a wide spectrum of approaches and disease models, investigators at Penn are focusing their efforts on how immunological tolerance to 'self' develops and how this tolerance is regulated and maintained. The loss of tolerance is associated with destructive inflammatory responses that underlie diseases as diverse as arthritic, multiple sclerosis and lupus. Many laboratories are examining fundamental mechanisms involved in the breakdown of physiological tolerance and are working to develop strategies to block destructive immune responses. Laboratories at Penn are also developing novel approaches for inducing tolerance to organ transplants.
The incidence of asthma and other allergic diseases has reached pandemic proportions in industrialized countries. The type of immune response that promotes the chronic inflammation associated allergic diseases, called type 2 inflammation, is also critically important for protection against some parasites. Penn researchers are employing diverse model of infection and inflammation to elucidate how this type of immune response develops and how it is regulated. In addition, delineating the immunological mechanisms that promote fibrosis and tissue remodeling associated with allergic responses is a major area of interest.
Penn investigators are studying the interface of microbes and innate and adaptive immunity to understand the regulation of appropriate and inappropriate immunity to infection and immunological memory. These studies include understanding the dynamics of host-microbial interactions at epithelial barriers where defense against pathogens is maintained or breached and in the inductive sites of clonal expansion, such as secondary lymphoid tissue. Numerous researchers at Penn are exploring the role and regulation of the traditional and newly discovered helper T cell subsets, as well as their novel cytokine products, during infection with viral, bacterial and parasitic pathogens. There are also many laboratories studying the differentiation and regeneration of effector and memory T cells, both helper and cytotoxic, as well as B cells in the defense against numerous classes of microbes. Integrative techniques include 4-dimensional in vivo imaging of the immune response against pathogens, genomic and systems biology approaches, multiparameter flow cytometry and high-throughput screening of anti-viral immunity.
Inflammation is a rapid and effective early defense system and is characteristic of tissue injury and infection. While inflammation is an essential and important part of the physiological and immunological response to these insults, prolonged or inappropriate inflammation can result in pathological situations including sepsis, respiratory distress, cardiovascular disease, autoimmunity and some types of cancer. Penn immunology researchers investigating how the balance between the healthy and important aspects of inflammation and pathological consequences of dysregulated inflammation is achieved or becomes dysregulated in disease states.
Cancer immunology at Penn encompasses the entire spectrum from basic research of tumor cell recognition and models of tumor-immune system interactions to innovative clinical trials in cancer patients. Penn researchers have, and continue to develop novel tumor models and immunological approaches to study mechanisms of tumor immunity. In addition, a number of investigators have pioneered novel vaccine approaches against malignancy and have developed state-of-the-art techniques for boosting patient immunity. Investigators working on both Immunity to Infections and Cancer Immunology have close ties with the microbiology, infectious diseases, vaccine, gene therapy, HIV, cancer biology and oncology research communities at Penn
Several investigators at Penn are examining fundamental issues in molecular immunology, including signal transduction, transcriptional regulation, antigen receptor recombination and DNA repair in immune cells. Other investigators studies the cell biology of lymphocyte and natural killer cell activation, as well as the developmental biology and homeostasis of immune cells and tissues. These investigators have strong ties with the cell and molecular biology, epigenetics, developmental biology, and signal transduction communities at Penn.
Using a wide spectrum of approaches and disease conditions, numerous investigators at Penn are focusing their efforts on the control of immune reactions. Many laboratories are examining fundamental mechanisms involved in breakdown of physiological tolerance and are working to develop strategies to block destructive immune responses. Several investigators at Penn have pioneered the understanding of how excessive immune response during infection is controlled. Laboratories at Penn are also developing novel approaches for inducing tolerance to organ transplants.