Classification and external resources
Autoimmunity is the failure of an organism to recognize its own constituent parts (down to the sub-molecular levels) as self, which results in an immune response against its own cells and tissues. The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. The Mendelian Inheritance in Man project is a Database that catalogues all the known Diseases with a genetic component, and—when possible—links them The Diseases Database is a free Website that provides information about the relationships between medical conditions Symptoms, and Medications. Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books Any disease that results from such an aberrant immune response is termed an autoimmune disease. Prominent examples include Coeliac disease, diabetes mellitus type 1 (IDDM), systemic lupus erythematosus (SLE), Sjögren's syndrome, Churg-Strauss Syndrome, multiple sclerosis (MS), Hashimoto's thyroiditis, Graves' disease, idiopathic thrombocytopenic purpura, and rheumatoid arthritis (RA). Coeliac Insulin-dependent diabetes mellitus (IDDM is a medical term that describes diabetes mellitus that requires Insulin therapy to avoid ketoacidosis. Systemic lupus erythematosus ( SLE or lupus,) is a chronic autoimmune disease that can be fatal though with recent medical advances fatalities are becoming Sjögren's syndrome is an autoimmune disorder in which Immune cells attack and destroy the Exocrine glands ref name="pmid18289371"> that Churg-Strauss syndrome (also known as allergic Granulomatosis) is a medium and small vessel autoimmune Vasculitis, leading to Necrosis Multiple sclerosis (abbreviated MS also known as disseminated sclerosis or encephalomyelitis disseminata) is an autoimmune condition in which the Hashimoto's thyroiditis or chronic lymphocytic thyroiditis is an Autoimmune disease where the body's own T-cells attack the cells of the Thyroid Graves' disease is a Thyroid disorder characterized by goiter, Exophthalmos, "orange-peel" skin and Hyperthyroidism. Idiopathic thrombocytopenic purpura (ITP is the condition of having a low Platelet count ( Thrombocytopenia) of no known cause ( Idiopathic) Rheumatoid arthritis ( RA) is a chronic systemic autoimmune disorder that causes the Immune system to attack the Joints, where See List of autoimmune diseases. Autoimmune diseases arise from an overactive Immune response of the body against substances and tissues normally present in the body
The misconception that an individual's immune system is totally incapable of recognizing self antigens is not new. Paul Ehrlich, at the beginning of the twentieth century, proposed the concept of horror autotoxicus, wherein a 'normal' body does not mount an immune response against its own tissues. Paul Ehrlich ( March 14, 1854 &ndash August 20, 1915) was a German Scientist who won the 1908 Nobel Thus, any autoimmune response was perceived to be abnormal and postulated to be connected with human disease. Now, it is accepted that autoimmune responses are vital to the development and functioning of vertebrate immune systems, and central to the development of immunological tolerance to self-antigens. Immune or immunological tolerance is the process by which the Immune system does not attack an Antigen. The latter concept has been termed natural autoimmunity. Autoimmunity should not be confused with alloimmunity. Alloimmunity is a condition in which the body gains immunity, from another individual of the same species against its own cells.
While a high level of autoimmunity is unhealthy, a low level of autoimmunity may actually be beneficial. First, low-level autoimmunity might aid in the recognition of neoplastic cells by CD8+ T cells, and thus reduce the incidence of cancer.
Second, autoimmunity is likely to have a role in allowing a rapid immune response in the early stages of an infection when the availability of foreign antigens limits the response (i. An antigen (from antibody-generating) or immunogen is a substance that prompts the generation of Antibodies and can cause an immune response e. , when there are few pathogens present). A pathogen (from Greek πάθος pathos "suffering passion" and γἰγνομαι (γεν- gignomai (gen- "I give birth to" infectious In their study, Stefanova et al. (2002) injected an anti-MHC Class II antibody into mice expressing a single type of MHC Class II molecule (H-2b) to temporarily prevent CD4+ T cell-MHC interaction. MHC ( Major histocompatibility complex) Class II molecules are found only on a few specialized cell types including Macrophages Dendritic cells and Antibodies (also known as immunoglobulins, abbreviated Ig) are Gamma globulin Proteins that are found in Blood or other Bodily Naive CD4+ T cells (those that have not encountered any antigens before) recovered from these mice 36 hours post-anti-MHC administration showed decreased responsiveness to the antigen pigeon cytochrome C peptide, as determined by Zap-70 phosphorylation, proliferation, and Interleukin-2 production. An antigen (from antibody-generating) or immunogen is a substance that prompts the generation of Antibodies and can cause an immune response Cytochrome c, or cyt c (horse heart PDB 1HRC is a small Heme Protein found loosely associated with the inner membrane ZAP-70 is an abbreviation for Zeta-chain-associated protein kinase 70 (70 is the molecular weight in KDa) Phosphorylation is the addition of a Phosphate (PO4 group to a Protein molecule or a small molecule Interleukin-2 ( IL-2) is an Interleukin, a type of Cytokine Immune system signaling molecule that is instrumental in the body's natural response Thus Stefanova et al. (2002) demonstrated that self-MHC recognition (which, if too strong may contribute to autoimmune disease) maintains the responsiveness of CD4+ T cells when foreign antigens are absent.  This idea of autoimmunity is conceptually similar to play-fighting. The play-fighting of young cubs (TCR and self-MHC) may result in a few scratches or scars (low-level-autoimmunity), but is beneficial in the long-term as it primes the young cub for proper fights in the future.
Pioneering work by Noel Rose and Witebsky in New York, and Roitt and Doniach at University College London provided clear evidence that autoimmune diseases are a result of loss of tolerance. Ernst Witebsky, also Ernest Witebsky (* 3 September 1901 in Frankfurt am Main; † 7 December 1969) was a German-American Professor Ivan Maurice Roitt (born 30 September 1927) was educated at King Edward's School Birmingham and Balliol College, Oxford University Professor Deborah Doniach MD FRCP (born April 6, 1912 Geneva, Switzerland - died January 1, 2004 University College London ( UCL) is a multi-faculty university institution based in the United Kingdom and a constituent college of the University of London An essential prerequisite for the pathogenesis of autoimmune diseases is indeed the breakage of immunological tolerance, which is the ability of an individual to differentiate 'self' from 'non-self'. Immune or immunological tolerance is the process by which the Immune system does not attack an Antigen. This breakage leads to the immune system's mounting an effective and specific immune response against self determinants. The exact genesis of immunological tolerance is still elusive, but several theories have been proposed since the mid-twentieth century to explain its origin.
Three hypotheses have gained widespread attention among immunologists:
In addition, two other theories are under intense investigation:
Tolerance can also be differentiated into 'Central' and 'Peripheral' tolerance, on whether or not the above-stated checking mechanisms operate in the central lymphoid organs (Thymus and Bone Marrow) or the peripheral lymphoid organs (lymph node, spleen, etc. , where self-reactive B-cells may be destroyed). It must be emphasised that these theories are not mutually exclusive, and evidence has been mounting suggesting that all of these mechanisms may actively contribute to vertebrate immunological tolerance.
Certain individuals are genetically susceptible to developing autoimmune diseases. This susceptibility is associated with multiple genes plus other risk factors. Genetically-predisposed individuals do not always develop autoimmune diseases.
Three main sets of genes are suspected in many autoimmune diseases. These genes are related to:
The first two, which are involved in the recognition of antigens, are inherently variable and susceptible to recombination. These variations enable the immune system to respond to a very wide variety of invaders, but may also give rise to lymphocytes, which are capable of self-reactivity. A lymphocyte is a type of White blood cell in the Vertebrate Immune system.
Scientists such as H. McDevitt, G. Nepom, J. Bell and J. Todd have also provided strong evidence to suggest that certain MHC class II allotypes are strongly correlated with specific autoimmune diseases:
Fewer correlations exist with MHC class I molecules. The most notable and consistent is the association between HLA B27 and ankylosing spondylitis. Ankylosing spondylitis ( AS; previously known as Bechterew's disease, Bechterew syndrome, Marie Strümpell disease and a form of Spondyloarthritis Correlations may exist between polymorphisms within class II MHC promoters and autoimmune disease. Polymorphism in biology occurs when two or more clearly different Phenotypes exist in the same population of a species — in other words the occurrence of more than one
The contributions of genes outside the MHC complex remain the subject of research, in animal models of disease (Linda Wicker's extensive genetic studies of diabetes in the NOD mouse), and in patients (Brian Kotzin's linkage analysis of susceptibility to SLE). Systemic lupus erythematosus ( SLE or lupus,) is a chronic autoimmune disease that can be fatal though with recent medical advances fatalities are becoming
Sex also seems to have a major role in the development of autoimmunity; most of the known autoimmune diseases tend to show a female preponderance, the most important exceptions being ankylosing spondylitis, which has a male preponderance, and Crohn's disease, which has a roughly equal prevalence in males and females. Ankylosing spondylitis ( AS; previously known as Bechterew's disease, Bechterew syndrome, Marie Strümpell disease and a form of Spondyloarthritis Crohn's disease is a Disease of the Digestive system which may affect any part of the Gastrointestinal tract from Mouth to Anus The reasons for this are unclear. Apart from inherent genetic susceptibility, several animal models suggest a role for sex steroids. Sex steroids, also known as gonadal steroids, are Steroid hormones that interact with Vertebrate Androgen or Estrogen receptors
It has also been suggested that the slight exchange of cells between mothers and their children during pregnancy may induce autoimmunity.  This would tip the gender balance in the direction of the female.
Another theory suggests the female high tendency to get autoimmunity is due to an imbalanced X chromosome inactivation. X-inactivation (also called lyonization) is a process by which one of the two copies of the X chromosome present in Female Mammals is inactivated 
An interesting inverse relationship exists between infectious diseases and autoimmune diseases. In areas where multiple infectious diseases are endemic, autoimmune diseases are quite rarely seen. The reverse, to some extent, seems to hold true. The hygiene hypothesis attributes these correlations to the immune manipulating strategies of pathogens. In Medicine, the hygiene Hypothesis states that a lack of early childhood exposure to infectious agents Symbiotic microorganisms (e Whilst such an observation has been variously termed as spurious and ineffective, according to some studies, parasite infection is associated with reduced activity of autoimmune disease. 
The putative mechanism is that the parasite attenuates the host immune response in order to protect itself. This may provide a serendipitous benefit to a host that also suffers from autoimmune disease. The details of parasite immune modulation are not yet known, but may include secretion of anti-inflammatory agents or interference with the host immune signaling.
A paradoxical observation has been the strong association of certain microbial organisms with autoimmune diseases. For example, Klebsiella pneumoniae and coxsackievirus B have been strongly correlated with ankylosing spondylitis and DM Type 1, respectively. Klebsiella pneumoniae is a Gram-negative, non- Motile, Encapsulated, Lactose fermenting, Facultative anaerobic Coxsackie B is the name of a group of six serotypes of Pathogenic Enteroviruses that trigger illness ranging from mild gastrointestinal distress to full-fledged Ankylosing spondylitis ( AS; previously known as Bechterew's disease, Bechterew syndrome, Marie Strümpell disease and a form of Spondyloarthritis This has been explained by the tendency of the infecting organism to produce super-antigens that are capable of polyclonal activation of B-lymphocytes, and production of large amounts of antibodies of varying specificities, some of which may be self-reactive (see below). Superantigens (SAgs are secreted proteins ( Exotoxins) that exhibit highly potent lymphocyte-transforming ( Mitogenic activity directed towards T Lymphocytes Polyclonal antibodies (or antisera are antibodies that are derived from different B cell lines B cells are Lymphocytes that play a large role in the humoral immune response (as opposed to the cell-mediated immune response, which is governed by
Certain chemical agents and drugs can also be associated with the genesis of autoimmune conditions, or conditions that simulate autoimmune diseases. The most striking of these is the drug-induced lupus erythematosus. Drug-induced lupus erythematosus (DIL or DILE is an Autoimmune disorder similar to Systemic lupus erythematosus (SLE which is induced by chronic use of certain Usually, withdrawal of the offending drug cures the symptoms in a patient.
Overexposure to pesticides and toxins may also induce autoimmunity.
Several mechanisms are thought to be operative in the pathogenesis of autoimmune diseases, against a backdrop of genetic predisposition and environmental modulation. It is beyond the scope of this article to discuss each of these mechanisms exhaustively, but a summary of some of the important mechanisms have been described:
The roles of specialized immunoregulatory cell types, such as regulatory T cells, NKT cells, γδ T-cells in the pathogenesis of autoimmune disease are under investigation. Regulatory T cells (sometimes known as suppressor T cells) are a specialized subpopulation of T cells that act to suppress activation of the Immune system Natural killer T (NKT cells are a heterogeneous group of T cells that share properties of both T cells and natural killer (NK cells.
Autoimmune diseases can be broadly divided into systemic and organ-specific or localised autoimmune disorders, depending on the principal clinico-pathologic features of each disease.
Diagnosis of autoimmune disorders largely rests on accurate history and physical examination of the patient, and high index of suspicion against a backdrop of certain abnormalities in routine laboratory tests (example, elevated C-reactive protein). C-reactive protein ( CRP) is a Plasma protein, an Acute phase protein produced by the Liver and by Adipocytes. In several systemic disorders, serological assays which can detect specific autoantibodies can be employed. An autoantibody is an Antibody (a type of Protein) manufactured by the Immune system that is directed against one or more of the individual's own proteins Localised disorders are best diagnosed by immunofluorescence of biopsy specimens. Immunofluorescence is the labeling of antibodies or Antigens with fluorescent Dyes This technique is often used to visualize the subcellular
Current treatments for autoimmune disease are usually immunosuppressive, anti-inflammatory, or palliative. Immunosuppression involves an act that reduces the activation or Efficacy of the Immune system. Anti-inflammatory refers to the property of a substance or treatment that reduces Inflammation. Palliative care (from Latin palliare to cloak is any form of medical care or treatment that concentrates on reducing the severity of Disease Symptoms  Non-immune therapies, such as hormone replacement in Hashimoto's thyroiditis or DM Type 1 treat outcomes of the autoaggressive response. Dietary manipulation limits the severity of celiac disease. Steroidal or NSAID treatment limits inflammatory symptoms of many diseases. IVIG is used for CIDP and GBS. More specific immunomodulatory therapies, such as the TNFα antagonists etanercept, have been shown to be useful in treating RA. An immunomodulator is a drug used for its effect on the Immune system. Etanercept (Enbrel is a Recombinant -DNA drug made by combining two proteins (a fusion protein These immunotherapies may be associated with increased risk of adverse effects, such as susceptibility to infection. Autoantibodies are used to diagnose many autoimmune diseases. The levels of autoantibodies are measured to determine the progress of the disease.
Helminthic therapy has developed based on these observations and involves inoculation of the patient with specific parasitic intestinal nematodes (helminths). Helminthic therapy is the treatment of Autoimmune diseases and Immune disorders by means of deliberate infestation with a Helminth or with the ova of a helminth The nematodes or roundworms ( Phylum Nematoda from Greek (nema "thread" + -ode "like" are one of the most common There are currently two closely-related treatments available, inoculation with either Necator americanus, commonly known as hookworms, or Trichuris Suis Ova, commonly known as Pig Whipworm Eggs. The hookworm is a parasitic Nematode worm that lives in the Small intestine of its host which may be a Mammal such as a Dog, Research is available that demonstrates this approach is highly effective in treating a variety of autoimmune disorders, including Crohn's, Ulcerative Colitis, Asthma, allergies, Multiple Sclerosis, and chronic inflammatory disorders.