- Resource
- BR1DGE
- Pathophysiology
- Video
Type 1 Diabetes: Mechanism of Beta Cell Loss Caused by Autoimmune T Cells
This animated video provides an overview of the key immunological processes that underlie the development of autoimmunity in T1D. Autoreactive T cells drive pancreatic beta-cell destruction, resulting in insulin deficiency and, ultimately, hyperglycemia and symptoms of T1D.
Learning Objectives
- Educate on the pathophysiological mechanisms underlying T1D
- Visually depict the sequence of events that leads to the development of T1D
- Explain how autoimmune processes drive beta-cell destruction in T1D
Summary
The immune system depends on complex interactions between cells, signaling molecules and receptors. Among these, T cells surveil the body for potential invaders using cell-surface molecules called the T cell receptor complex, TCR, which includes the CD3 subunit. The TCR works with cells called antigen-presenting cells, APCs.
The job of APCs is to hold peptides from infections on their surface to present to T cells. APCs display the offending peptides on molecules called HLA to the TCR complex, to activate the T cells, and also display self-peptides to T cells.
Depending on a person's genetics, T cells may be more or less predisposed to react to self-peptides. Usually, T cells ignore self-peptides. This is known as tolerance. But sometimes, T cells mistakenly recognize self-peptides and attack the body's own cells. These T cells are known as autoreactive. The peptides involved are called autoantigens, and the disease is an autoimmune disease. It is hypothesized that certain infections provide peptides similar to self-peptides, and T cells developed against these infections are autoreactive. Type 1 diabetes is one such autoimmune disease. Both genetics and environment contribute to T1D development. Pancreatic beta cells in the islets of Langerhans produce insulin to allow uptake of glucose into muscle and other cells. In T1D, the autoantigens to which T cells respond are derived from beta cells.
Other immune cells develop autoantibodies to the autoantigens and they can be identified by blood test before dysglycemia is seen. The autoimmune process may be rapid or may last several years as autoreactive T cells destroy beta cells directly, and also by releasing cytokines and recruiting other immune cells. Over time, more beta cells are destroyed. Eventually, there are too few beta cells to make sufficient insulin to support the body's metabolic needs, resulting in hyperglycemia and symptoms of T1D.
MAT-GLB-2405104-1.0 - 08/2024
