Publisher Summary Atherosclerosis is a histopathological condition that entails accumulation of lipid laden lesions in the vessel walls at sites of shear stress. Recent data implies that the immune system plays a dominant role in atherogenesis, as manifested by the observation of T cells and immunoglobulin within lesions. Further evidence stems from creation of knockout mouse models simulating human atherogenesis that have manipulated immunologically to result in various effects on atherogenesis. Further exciting realms within this field holds that autoimmune processes contribute significantly to the evolution of the mature plaque. Classical autoimmune diseases are recognized by autoreactivity against distinct antigens expressed in the host. Identification of the specific autoantigen, aids in establishing the diagnosis of the disorder, and subsequently furnishes tools by which to manipulate the immune system in the intention of treatment. Common denominators by which to establish the diagnosis of autoimmune diseases have been formulated by the Rose and Witebsky criteria. The principal experimental support relies on the isolation of a target autoantigen, specific for a given disease. Subsequently, when used for immunization, the autoantigen leads to production of antibodies and signs of the respective autoimmune disease.