MicrobiologyBytes: Infection & Immunity: Clinical immunology Updated: October 21, 2004 Search

Clinical Immunology

Auto-immunity is the situation in which the host's immune system can be demonstrated to exhibit reactivity to self antigens. It is not always accompanied by any disease. Auto-immune disease is the situation in which a disease is associated with demonstrable auto-immunity. It includes conditions where self-reactivity, though present in the disease, does not explain the features or consequences of the disease i.e. auto-immunity is simply acting as tissue damaging responses may occur as a consequence of involvement of the immune system, especially when these responses are exaggerated. This is known as hypersensitivity. In some, but not all instances, the immune response is targeted against self. Hypersensitivity responses have been classified by Gell and Coombs into 4 types. It is important to realise that more than one type may be ongoing simultaneously, and that it is an over-simplification of the true state of affairs.

Immunological tolerance is established during T cell development within the thymus. This assumes that all self antigens will be tested, but this may not always be the case e.g. certain antigens are not presented during T cell development within the thymus. These include lens and uveal proteins, plus sperm antigens. In order to prevent auto-immune disease, these antigens have to be sequestrated away from immune surveillance. This theory has several weaknesses. Can you think of any?

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It is more useful to think of the immune system as potentially self-reactive, but possessing a control system to prevent this from occurring. We know this, because even in health, self reactive T and B cells can be demonstrated. We thus require a system of immune regulation to prevent this happening. Immune regulation is brought about in several ways.

Auto-immunity may be antibody or cell mediated. In the case of antibodies, B lymphocytes, although possessing receptors for self antigens (e.g. thyroglobulin, DNA, IgG), do not normally produce significant quantities of antibodies unless they receive T cell help. This will not, in health, be given, because T cells with high affinity for self determinants will have undergone apoptosis in the thymus. However, if the antigen is presented in a slightly altered form, or way, e.g. chemically altered or with upregulated MHC class II, then helper T cells may be activated. Consequently, auto-antibodies may be made. MHC class II upregulation may occur following gamma interferon release from virally infected T cells (CD4+ TH1 cells). Alternatively, B cells can be polyclonally activated by EB virus, (the causative agent of glandular fever), resulting in the appearance of auto-antibodies. These autoantibodies can be harmful, e.g. smooth muscle antibody arising during glandular fever.

Auto-immune diseases can be divided into organ-specific and non-organ specific. Organ specific means the auto-immunity is directed against a component of one particular type of organ e.g. the cells of the adrenal glands, causing Addison's disease q.v. In non-organ specific auto-immune disease, the auto-immunity is directed against an antigen that is present at many different sites and can include involvement of several organs e.g. antibody against DNA, resulting in the disease systemic lupus erythematosus (SLE). In Sjögren's syndrome, patients experience dry eyes and mouth, caused by the production of autoantiboies against salivary ducts, as shown in this biopsy specimen, and rheumatoid arthritis. Auto-immunity may be the result of attack by antibodies, cells or both.

T cells may attack antigens found within the thyroid gland in auto-immune thyroiditis (Hashimoto's disease), which is an example of an organ-specific auto-immune disease, and was the first auto-immune disease to be described. In this disease, there are also antibodies to thyroid antigens, which may interfere with uptake of iodine. Thus, both antibodies and immune cells contribute to this disorder. Some of the antibodies are probably harmless, since not all patients with thyroid antibodies have any evidence of functional impairment. In this situation, antibodies serve as markers of auto-immunity. Likewise, T cells may attack the beta cells within the islets of Langerhans in the pancreas, resulting in insulin-dependent diabetes mellitus. In SLE, there are circulating immune complexes of DNA-anti DNA, which may settle at various sites e.g. glomerular basement membrane, or dermo-epidermal junction of skin. There, complement activation may occur, resulting in local tissue damage. In the disease myasthenia gravis, there are acetyl choline receptor antibodies, which block neuro-muscular transmission, i.e. in this situation the auto-antibody is a receptor blocker. By contrast, in Graves' disease (hyperthyroidism), there is an auto-antibody which binds to the thyrotropin stimulating hormone receptor (TSH receptor), but instead of blocking, it mimics the TSH signal and stimulates instead.

© AJC 2007.