This book provides a history of the foundational concepts of immunology and recognizes the central role of paradoxes, and their resolution, in advancing the canon. It identifies many paradoxes in the context of the contemporary, dominant frameworks employed by researchers in the last few decades to analyse how immune responses are regulated. The foundational ideas proposed resolve these paradoxes. The resulting framework emerges as a powerful platform for elucidating common immune mechanisms and proposing strategies to prevent and treat autoimmunity, cancer and certain problematical infectious diseases, such as AIDS and tuberculosis. This holistic approach underscores the significance of fundamental immunological principles, showcasing the potential of the framework to revolutionize immunotherapy and disease management. The focus on paradoxes and their resolution results in a short, jargon-free text, accessible to the engaged general reader, and provides a platform for researchers to debate central issues of the field. This book illustrates how the recognition and resolution of paradoxes can transcend the challenges posed by the information overload.