Basic Overview of Autoimmune Disease: What is an Autoimmune Disease?
There are certain pathogenetic mechanisms that are common to all autoimmune diseases; this includes the presence of self-reactive CD4-positive T lymphocytes. Before continuing, it is important to talk about T-Cell function and its role in the adaptive immune system. Each cell in the body presents an antigen, a structural component that is recognizable. Antigens are used to identify normal cells from foreign invaders. T Cells produce antibodies that recognize antigens. If a T-Cell accidentally identifies a self-antigen, there are mechanisms in place to prevent the T Cell from harming the host cell. Antibodies are attached to the surface of T Cells and are freely released into the body. Autoimmunity describes the event in which antibodies recognize self-antigens as foreign. This can occur through the release of free autoantibodies or T-cell mediated immunity.
Graves’ Disease as an Example for Deleterious Effects of Autoantibody Mechanism
For instance, antigens on the surface of circulating cells such as red blood cells are readily available to circulating antibodies and may be readily damaged or eliminated by autoantibodies acting with complement, killer T cells, or phagocytes. The receptors on cell surfaces such as the TSH receptor on the thyroid cell or on the acetylcholine receptor at neuromuscular junctions may also be directly attacked by autoantibody. This interaction may result in stimulating the receptor in Graves’ disease or in blocking the neuromuscular transmission as observed in myasthenia gravis. In other diseases, autoantibodies are designed to isolate a specific enzyme. For example, antibodies specific for the P450 enzymes is found in autoimmune hepatitis and primary biliary cirrhosis. These enzymes are widely distributed in the body, and the question arises of why the diseases are organ-specific. Evidence suggests that the enzymes are accessible to antibodies or T cells primarily in reactivated locations.
T-Cell Mediated Autoimmune Disease Mechanism
Many other autoimmune diseases are not due to the direct effects of autoantibody, but are associated with T-cell-mediated immune responses. Sometimes, cytotoxic T cells may be generated that can damage their respective target cell. In other cases, cytokines are produced that are harmful to surrounding tissue cells. Finally, T cells may activate macrophages, which can produce a great deal of tissue injury through their soluble products, including cytokines and reactive oxygen intermediates.
The exact reason why T-cells begin attacking our own cells remains elusive. Several studies have pointed to different mechanisms, such as a diminished capacity of CD4+ regulatory T Cells (Tregs) to regulate autoimmune response. Specifically, Tregs operate mainly through the release of soluble suppressive cytokines interleukin-10 and transforming growth factor-beta.
Treatments for T-Cell Mediated and Autoantibody Autoimmune Diseases
In human disease, it is frequently impossible to clearly separate the injury that is due to antibody-mediated from cell-mediated reactions. In general, however, the cell-mediated responses are associated with the Th1 subset of CD4+ T cells. Antibody-mediated mechanisms in general associate with Th2 responses. A therapy capable of regulating both Th1- and Th2-mediated inflammatory pathways could affect a wide-array of autoimmune disorders. Immune modulation is an emerging therapy; in fact, recent studies showed the introduction of interferon-gamma (IFN-g), a prototypic Th1 cytokine, helps downregulate some autoimmune diseases. Immune modulation may be key in properly treating autoimmune diseases.