In this episode, Dr. Shaun Jackson uses a compelling patient case to illuminate the complex mechanisms of immune tolerance and autoimmunity. He explains how B cells learn to avoid targeting the body's own tissues through central and peripheral tolerance—and how these safeguards can fail. The discussion covers the roles of germinal centers, T cells, and rare genetic disorders in shaping immune regulation, with Alport's syndrome and post-transplant Goodpasture's disease serving as striking examples. Dr. Jackson also reflects on emerging directions in autoimmune research and shares his journey from medical training in South Africa to leading a research program in Seattle, offering valuable insights for future physician-scientists.