Pathology of Type 1 Diabetes

Discuss the current knowledge of the contribution of cellular and molecular components of the immune system to the pathology of type 1 diabetes.

Abstract

Type 1 diabetes (T1D) occurs when insulin-producing cells are attacked and killed by various immune mechanisms in the body. The pathology of type 1 diabetes is thought to be heavily T-cell mediated however in this essay the role of cytokines, B lymphocytes, macrophages and dendritic cells in the pathogenesis of type 1 diabetes will be discussed. There are many mechanisms that contribute to T1D, the main ones include T cells and their recognition of beta cell antigens to cause insulitis and therefore destroy insulin-producing pancreatic beta cells.

Introduction

Type 1 diabetes is a very prevalent autoimmune disease that is characterised by beta cells, within the islets of Langerhans, being attacked and destroyed by various cellular and molecular components in the pancreas. The main function of beta cells is to produce insulin therefore the destruction of these cells prevents the body from being able to produce sufficient insulin to efficiently stabilise glucose levels in the blood. This causes accumulation of high levels of glucose in the body which can only be treated by artificial insulin injections (Bortell et al, 2008). A fault in the body’s immune response is what causes the pathogenesis of type 1 diabetes, in which the immune system is mislead to target and kill beta cells. As more and more insulin producing cells in the pancreas, usually 90% of the patients beta cell mass, are lost the body becomes insufficient in maintaining the blood glucose levels causing the patient to exhibit early symptomatic signs of type 1 diabetes (Bortell et al, 2008).

Type 1 Diabetes is an insulin-dependent metabolic disorder that can cause many complications such as ketoacidosis, renal and cardiac problems, stroke, and blindness. T1D is commonly known as early-onset diabetes because it normally develops in those under 30 years, however research shows that it can arise at any age (Budde, 2009). T1D is a well-known autoimmune disease that comes about when β-cell antigens are targeted by a specific immune response. T1D can also be characterised by the inflammation of the islets in the pancreas, commonly known as insulitis. Insulitis is what eventually leads to the destruction of β-cells and thus triggering diabetes. The infiltration of innate immune cells, which produce pro-inflammatory cytokines that trigger β-cell death and promote activation of T cells to attack and destroy β-cells, is associated with causing insulitis (Atkinson and Gianani, 2009).

Discussion

The pathology of type 1 diabetes is primarily lead by the contribution of cellular and molecular componenets of the immune system. The mechanisms involved in the β-cell destruction are still to be investigated however it is generally believed that T lymphocytes, macrophages, β-cell cytokines and chemokines, dendritic cells and B lymphocytes significantly contribute to the β-cell-specific immune response. The Innate immune system uses pattern recognition receptors (PRR's), that are found the blood and tissues, to identify the receptors of foreign cells (Medzhitov and Janeway, 1997).

The innate immune system cells initiate an immune response by using PRR's, specifically toll-like receptors. When these receptors are activated they stimulate the up-regulated production of cytokines responsible for inflammatory pathways. These pathways insure the protection of the body against more damage from foreign pathogens (Luppi and Trucco, 1999) . Although that being said, extreme inflammatory signalling is thought to have negative consequences on the body instead of protecting it and therefore can increase the chance of T1D pathogenesis (Eizirik, Colli and Ortis, 2009). Recent research illustrates that inflammatory cytokines have a significant role in the pathogenesis of T1D (Feldman, Pike and Adams, 2011). Cytokines have been found to contribute to the pathogenesis of TID by activating transcription factors NF┢┚ and STAT-1, which surpresses the expression of PDX1 and GLUT1, as a result of which insufficient insulin is produced and secreted (Eisenbarth, 2004). Activation of the transcription factors is also found to trigger apoptosis and release of beta-cell cytokines, which further amplifies the destructive attack (Eisenbarth, 2004).

The main cellular contribution to the pathogenesis