Pathogenesis of type I diabetes
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β-cell destruction via autoimmune response is the key characteristic in type I diabetes. This gives rise to the problematic lack of insulin production, from which all common diabetic symptoms occur. However, type I diabetes’ pathogenesis, i.e. how autoimmunity develops and ultimately destroy β-cells, has not been fully clarified. The islets of Langerhans consisting of β-cells have been observed to be infiltrated by CD4 and CD8 T-cells, as well as macrophages. T-cells are commonly understood to mediate the destruction of invasive, undesirable foreign particles; CD4 and CD8 are the proteins expressed on their surface, hence their names (CD4 T-cells or CD8 T-cells). Many predictions have been given regarding to the mechanism in which T-cells could turn against β-cells specifically in the body through the activation of autoimmune reaction. Islet autoantigens are suggested to be the key activator of T-cell’s autoimmune function. This activation occurs as the autoantigens are presented to T-cells by major histocompatibility complex (MHC) class II molecules on the antigen presenting cell. As autoimmunity occurs specifically to β-cells, the autoantigen is hypothesised to be specific to β-cells as well. Some, not all isoforms of proinsulin have been found to accelerate type I diabetes and thus could be the autoantigen being questioned. Ultimately, the problem lies at the CD4, CD8 T-cells that are somehow proinsulin-specific and destroy β-cells as a result. Therefore, disabling the function of these ‘autoreactive’ T-cells is the logical outcome in approaching type I diabetes.
T.N. Budi A.N. Khuong C. April | Copyright ©2012