The Mechanisms That Contribute to the Development of Autoimmunity - Essay Example

To understand the mechanism behind autoimmunity, it is imperative to understand the mechanism behind self-tolerance. Immunological tolerance can be central or peripheral (Mitchell et al 2006). In central tolerance, immature T cells which recognize self-tissues are destroyed in the thymus and similar B cells are destroyed in the bone marrow. Peripherally, mature lymphocytes which are autoreactive and escape developmental deletion in thymus and bone marrow, are either destroyed or inactivated by various methods such as energy, clonal deletion by apoptosis, and suppression by regulatory T cells (Mitchell et al 2006).

Extensive research has been conducted in this field to understand the mechanisms that allow tolerance to be bypassed, allowing autoreactive lymphocytes to escape and thereby, contribute to the pathogenesis of autoimmunity. It has been demonstrated that a combination of genetic and environmental factors is responsible. The following mechanisms have been proposed: 1) Genetic factors – The role played by genetic factors in the development of autoimmunity can be easily explained by single-gene disorders in which there is a direct correlation between the genetic variant and the disease, for example, the gene for insulin in type 1 diabetes and AIRE (autoimmune regulator) in APS 1(autoimmune polyendocrine syndrome).

In both these disorders, there is a lack of thymic expression and autoreactive T cells escape tolerance. One more example is of foxp3 gene whose mutations lead to the development of autoimmune disease by T regulator cell dysfunction. Also, Fas mutation causes the autoimmune lymphoproliferative syndrome, as autoreactive T and B cells fail to undergo apoptosis. Thus, different mechanisms of energy, T cell regulation, and apoptosis of autoreactive lymphocytes appear to be involved here (Rioux & Abbas 2005).

However, these single gene autoimmune disorders are infrequent and most commonly, autoimmune disorders are multi-genetic diseases. Sequence variations and single nucleotide polymorphism in genomic mapping have been found for diseases such as type 1 diabetes (genetic locus is in the major histocompatibility complex), Crohn’s disease, rheumatoid arthritis, and SLE.