This module focuses on how the immune system can cause pathology by mounting undesired responses to self tissues. It is currently unclear why in about 5% of individuals there is a breakdown in the immunological tolerance mechanisms that normally prevent harmful immunity to our own body constituents. We will explore the genetics and immune mechanisms underlying these responses, as revealed both by mechanistic studies in mouse models of autoimmunity and from the clinical settings, studying diseases in human populations. A number of organ-specific and systemic autoimmune conditions will be covered in detail, as well as a range of relevant animal models of autoimmunity that have led to a better understanding of immune mechanisms. This study of clinical and experimental immunology will illuminate the contribution of the various components of the immune system to the destructive process responsible for disease and understand how modern immune interventions target different stages of disease development.