Immune-mediated diseases affect multiple organ systems and do not adhere to the traditional medical paradigm that organizes physician-scientists and clinicians into organ-based specialties to investigate and treat these diseases. Investigators interested in immune-mediated diseases have lacked a formal mechanism for integrating their individual efforts in a manner that efficiently fosters scientific discovery and translation thereof. Moreover, clinicians that care for patients with a broad spectrum of immune-mediated disorders have operated in a system that neither facilitates the delivery of optimal and integrated health care nor the translation of breaking scientific discoveries. In the current environment, development of an over-arching strategic vision and pursuit of collaborative efforts are hindered by an archaic separation into departmental and subspecialty spheres of influence. Recognizing this “disconnect”, scientists and clinicians at Penn have embraced a new, exciting paradigm that emphasizes the immunocentric basis of autoimmune, immunodeficiency, allergic, infectious, transplantation, and malignant disorders. Drawn together by common interests in the pathogenesis, diagnosis, and treatment of immune-mediated diseases, Penn clinicians and scientists across a broad spectrum of clinical and basic science departments including Medicine, Pediatrics, Surgery, Dermatology, Neurology, Pathology, and Microbiology have joined ranks under the auspices of the Penn Center For Clinical Immunology (PCCI).