In this article we will discuss about:- 1. Meaning of Autoimmune Disease 2. Causes of Autoimmune Disease 3. Treatment.
Meaning of Autoimmune Disease:
Autoimmunity is a condition characterized by the presence of serum autoantibodies and self-reactive lymphocytes (T-cells).
It manifests sometimes when the body loses immune tolerance (body’s condition to distinguish its own self-antigens from foreign non-self-antigens and not mounting on immunogenic attack against the former) and mounts an abnormal immune attack, either with antibodies or T-cells, against a person’s own self-antigens.
In other words, the immune system of the body, like any complex multi-component system, is subject to failure of some or all of its parts. When the system loses its sense of “self” and begins to attack cells and tissues of the body, the result is autoimmunity. Autoimmune reactions can cause serious damage to cells/tissues and organs and may result in diseases called autoimmune diseases.
Human beings suffer from several autoimmune diseases, some of which are listed in Table 43.2. Some of these diseases are caused by autoantibodies, while others are due to T- cells that cause tissue destruction. Autoimmune diseases arc cither organ-specific or systemic.
In case of organ-specific diseases, the immune response is directed to a target antigen unique to a single gland or organ. As a result, the manifestations are largely limited to that organ; the manifestation may be tissue damage or blockage/overstimulation of the normal function of the organ.
Direct cellular damage occurs when lymphocytes or antibodies bind to cell-membrane antigens causing cellular lysis and/or an inflammatory response in the affected organ. Gradually, the damaged cellular structure is replaced by connective tissue leading to a decrease in function of that organ.
Examples of such diseases are autoimmune anaemias insulin- dependent diabetes mellitus, etc. In some diseases, e.g., Grave’s disease, the antibodies bind to hormone receptors and activate them, while in some others, e.g., myasthenia gravis, antibody binding blocks the activation of the receptors.
In case of systemic autoimmune diseases, the immune response is directed towards a broad range of target antigens and, as a result, involves a number of organs and tissues.
These diseases reflect a general defect in immune regulation that results in hyperactive T-cells and B-cells. Tissue damage is widespread, is caused by both T-cells, e.g.. multiple sclerosis and autoantibodies, e.g., systemic lupus erythematous, or by accumulation of immune complexes, e.g., rheumatoid arthritis.
Causes of Autoimmune Disease:
Autoimmune diseases could arise in many possible ways, some of which are as follows:
(1) A tissue antigen that is sequestered from circulation will not be employed in the thymus for clonal deletion of T cells reactive to this antigen. When such an antigen is released into circulation due to trauma to tissues caused by an accident or a viral or bacterial infection, it may induce autoantibody formation.
(2) A number of bacteria and viruses have antigenic determinants that are identical or similar to, normal host cell components. Infection by such pathogens may initiate autoimmunity.
(3) A number of viruses and bacteria can induce nonspecific polyclonal B cells that produce IgM in the absence of TH cells. Such infections could activate B cells reactive to self-antigens and, thereby, cause autoimmunity.
(4) Expression of MHC II in cells that normally do not express them could lead to autoimmunity. Such an inappropriate expression of MHC II is induced by certain agents like IFN-γ.
Treatment of Autoimmune Diseases:
The current therapies provide relief by nonspecific suppression of the immune system. Some agents like cyclosporin A are somewhat selective in that they inhibit only antigen-activated T cells.
More directed approaches are still at experimental level; some of these are briefly summarise below:
(i) T cells specific for the concerned antigen are injected into individuals to immunize them against these T cells (T cell vaccination).
(ii) A synthetic peptide differing by only one (or few) amino acid from the auto-antigenic peptide may be used as therapy. The synthetic peptide competes with the auto-antigenic peptide for MHC molecules (peptide blockade of MHC molecules).
(iii) Monoclonal antibodies may be directed against the following:
(a) CD4 (depletes all TH cells),
(b) The α subunit of IL-2 receptor, which is expressed only by antigen-activated TH cells (blocks antigen- activated TH cells),
(c) Specific T cell receptor, and
(d) The specific allelic variant of the MHC molecule that is associated with the autoimmune disease.
(iv) Oral administration of the concerned auto-antigen way induce tolerance to the antigen.