Autoimmune disease

from Wikipedia, the free encyclopedia

Autoimmune diseases and autoimmune diseases are general terms in medicine for diseases with reactions in the body, which are based on a disturbed tolerance of the immune system to substances in the body and which lead to the formation of antibodies (autoimmunization). In the broader sense of the word, immune reactions against the microbiome , i.e. attacks on microorganisms belonging to the body , are also classified as autoimmune diseases. Autoimmune reactions are often similar to immune reactions against pathogens; in addition, immune complexes or receptors activating or blocking antibodies can lead to symptomatic disease.

In Western countries about five percent of the population is affected by an autoimmune disease, the most common being psoriasis , rheumatoid arthritis and autoimmune thyroid diseases ( Graves' disease and Hashimoto's thyroiditis ). Many autoimmune diseases are more common or more classic in women than in men. Many autoimmune diseases are so far insufficiently understood and cannot be treated causally ; they often persist for life and can be treated with anti-inflammatory or immunosuppressive measures to alleviate the symptoms or to delay or stop the destruction of the affected organs .

Basic considerations

Immune cells have enzymes with which they can attack viruses, cells, parasites and also individual chemical structures and, if necessary, destroy them. To do this, it is necessary to recognize pathogens without attacking the body's own structures, useful microorganisms ( commensal flora) or harmless foreign substances on the skin and mucous membranes. Immune cells check their environment using molecular receptors : Strong binding to a structure (an antigen ) activates the cell and initiates defensive measures, especially if other cells (e.g. T helper cells ) have also recognized a pathogen and use inflammatory mediators to inform them about it. The distinction between the body's own and non-body cells is a problem that should not be underestimated, as pathogens are subject to very rapid evolution , so that more complex living beings are hardly able to develop suitable receptors for recognizing all pathogens through classic coevolution . However, some conserved exist pathogen-associated molecular pattern (PAMP), which by many pathogens expressed and immune cells via pattern recognition receptors are also recognized (PRR); however, more specific receptors are necessary to effectively combat many pathogens.

Therefore, in addition to innate immunity, humans also have an adaptive immunity in the form of B and T cells . Each of these cells expresses exactly one receptor that comes about through random recombination and somatic hypermutation of their DNA. The result is a large variety of immune cells whose antibodies are directed against "everything possible". Cells that are already activated during maturation presumably react to the body's own structures and are therefore sorted out; this is how the central tolerance arises . However, it is by no means the case that receptors can only bind or not, rather it is about the probability and strength of the bond, all levels are possible. If all cells were removed that only weakly bind the body's own structures, some pathogens could no longer be recognized; A compromise has to be found between self-tolerance and defensive strength. The existence of some autoreactive cells and antibodies is normal, some autoreactive T cells (so-called regulatory T cells ) are even reprogrammed in such a way that they suppress immune reactions in their environment when activated.

The central tolerance is supplemented by mechanisms of peripheral tolerance , at this point the tolerance to the commensal flora and to harmless foreign substances is also developed. By division, a single immune cell can produce a large clone of cells of the same receptor, but in addition to binding to an antigen, this requires costimulation via inflammatory mediators (released by cells of innate immunity after recognition of PAMPs), in the case of B cells ( the later antibody-producing plasma cells ) also the direct interaction with activated T cells. B and T cells that recognize harmless structures do not normally receive any costimulation and, because the number of immune cells is limited, are displaced by dividing cell populations. A bond without costimulation can also induce death or at least “paralysis” of the cell or produce regulatory T cells. After all, there are immune-privileged places ( brain , eye , testes ) where there are particularly high hurdles ( blood-brain barrier , blood-testicle barrier ) to initiate inflammation, so that normally no B or T cells can be activated there . Some autoreactive cells are not activated because their target structures are normally not accessible in sufficient concentration, for example because they are located intracellularly; The rapid clearing away of dead cells by scavenger cells ( macrophages ) therefore also contributes to tolerance .

All mechanisms combined ensure that immune responses are almost always limited to harmful intruders. However, a single autoreactive cell that happens to overcome all these hurdles can set an autoimmune reaction in motion, the inflammatory course of which can bring down hurdles to peripheral tolerance (release of inflammatory mediators, attraction of immune cells, suspension of immune privileges, availability and presentation of intracellular antigens as well through massive cell death, ...). This enables further autoreactive cells to be activated, which attack the same antigen via new substructures (epitope spreading) . It is not known why many autoimmune diseases progress in bursts instead of becoming more and more self-evident, some only appear once for a short time or heal spontaneously after years.


The development of autoimmune diseases can best be described with a risk factor model ( Bad luck and bad genes : 'bad luck and bad genes'): genetic factors on the one hand and environmental and other factors (severe stress, infections, pregnancy, ...) on the other influence the risk of disease without a certain genetic makeup or a certain environment being able to safely cause or prevent an autoimmune disease. This risk model is probably not the only expression of our incomplete knowledge; For the development of an autoimmune disease, chance (“bad luck”) is necessary, as can be seen in the example of an autoreactive B-cell that is activated by an autoreactive T-cell to become an autoantibody-producing plasma cell: First, two cells must escape the central tolerance, which is accidental recognize the same antigen in the body. Both cells must now randomly hit the epitope at the same time and still receive costimulatory signals. After all, both cells must happen to meet in a lymph node in order to be able to interact at all.

Genetic predisposition

Genome-wide association studies have shown that many autoimmune diseases occur more frequently when certain gene variants are present. The genes affected regularly code for receptors of inflammatory mediators and proteins of intracellular signal processing, but particularly often for MHC molecules in alleles characteristic of the disease : T cells, unlike B cells, do not directly recognize structures of potential intruders, but only peptides (short amino acid sequences to them from other cells on specific) membrane proteins , just those MHC molecules presenting be. All body cells constantly break down some of their proteins in order to present fragments from them on MHC class 1 molecules; this ensures that even intracellular pathogens cannot hide from the immune system. Professionally antigen-presenting cells (macrophages, dendritic cells and B-cells) eat ( phagocytize ) suspicious cells and cell debris and present peptides resulting from digestion via MHC class 2 molecules.

MHC molecules occur in great diversity in the population, since the genetically determined shape of the binding pocket only enables the presentation of suitable peptides. The set of MHC molecules that a person has at his disposal determines what the T cells get to see in the first place and thus - in autoimmune diseases and infectious diseases - immune reactions are particularly easily initiated.

Environmental factors

An environmental factor that is easy to understand is infections with pathogens that resemble the body's own structures. Such pathogens are not uncommon, as pathogens are subject to selection pressure to adapt to the host organism in order to be less easily recognized as foreign; this strategy is also known as molecular mimicry . In the immune reaction against the pathogen, autoreactive immune cells are activated, the reproduction of which is acutely useful, but makes autoimmune reactions more likely - even years later, as memory cells are formed. In addition, the antibodies formed in large quantities during the acute infection can be cross-reactive , i.e. bind the body's own cells with sufficient affinity so that they are destroyed by the antibody. One example is rheumatic fever , in which the heart is also attacked by cross-reactive antibodies after an infection with β-hemolytic streptococci .

Some autoimmune diseases show a noticeable increase in industrial nations. One possible explanation is the hygiene hypothesis, which deals with the interactions between bacteria and our immune system. Too little exposure to bacteria in the environment could promote the development of immune diseases. Another facet of this thesis deals with the composition of intestinal bacteria and their effect on the immune system. In principle, women are more often affected by autoimmune diseases, for which the female hormones (estrogens) are usually cited as the reason. However, a study on mice suggests that the different composition of the intestinal bacteria in women and men could be another possible cause.

Damage Mechanisms

Autoimmune reactions include the interaction of different cell types (T cells, B cells; phagocytes, granulocytes ) and soluble factors ( antibodies ; complement system ) of both the acquired and the innate immunity; in their complexity they do not differ from immune reactions against pathogens. The damage mechanisms are also often the same, for example antibody-dependent cytotoxicity (through activation of complement or natural killer cells ) or T-cell cytotoxicity. As with allergies , autoimmune diseases can be roughly divided into three groups according to their pathogenesis :

A special feature are antibodies that intervene in intercellular communication by binding to receptors and activating or blocking them. For example, in Graves' disease there is excessive hormone production in the thyroid because autoantibodies against the TSH receptor activate it through their binding. Antibodies against the nicotinic acetylcholine receptor , on the other hand, lead to muscle weakness in myasthenia gravis by blocking communication between nerve and muscle. As rheumatoid factor antibodies are referred against the constant portion of IgG antibodies. Anti-neutrophil cytoplasmic antibodies (ANCA) are antibodies against neutrophil granulocytes, which can also activate these immune cells.

Some autoimmune diseases are strikingly often associated with one another, which is attempted to be explained by similar pathomechanisms . Antibodies seem to be of particular importance for some autoimmune diseases and of particular importance for other subgroups of T cells; such findings offer approaches for more specific therapies. Autoantibodies are much easier to detect than autoreactive cells; If an autoantibody has been shown to be suitable for diagnosing a certain autoimmune disease, this does not yet mean that this antibody triggers the disease, contributes to its course or represents an essential mechanism of damage.

Antibody diagnostics


The decisive factor is the level of the existing serological autoantibody titre as a criterion for the diagnosis of an autoimmune disease, because autoantibodies are mostly physiological (for example ANA , dsDNA antibodies and anti- phospholipid antibodies). Exceeding a given titer is then considered pathological. Some autoantibodies are not physiological and should be considered pathological from the outset (for example ANCA and endomysial antibodies). Furthermore, increased or existing autoantibody titers are not absolutely necessary for the diagnosis of an autoimmune disease, since an autoimmune disease is established on the basis of serological and clinical criteria. Increased or existing pathological autoantibody titers alone are not sufficient for a diagnosis, since this is made on the basis of a score (reaching a certain number of points).


Depending on the organ affected, autoimmune diseases are treated by the respective specialist doctors, such as internists , rheumatologists , dermatologists , neurologists , endocrinologists or nuclear medicine specialists . The treatment is symptomatic or includes pharmacotherapy with anti-inflammatory , specifically immunosuppressive drugs that generally inhibit immune reactions (including those against pathogens). Among the immunosuppressants, cortisone is the body's own hormone, which is best tolerated in acute cases, but in the long term it is burdened by the risk of Cushing's syndrome . More modern drugs that specifically intervene in the communication between immune cells and are thus better adapted to the specific disease are clinically referred to as biologicals . These are genetically engineered proteins (often antibodies or derived from them) that intercept inflammatory mediators or block receptors on immune cells.

So far, healing has only been possible through radical destruction of the immune system (with subsequent stem cell transplantation ); however, this procedure is so dangerous that it is only used in exceptional cases. An end to the autoimmune reaction (if autoimmunity persists) can be achieved by completely surgically removing the antigen, which is only possible in organs whose function is unnecessary or can be replaced. In type 1 diabetes , the autoimmune reaction itself succeeds in completely eliminating the antigen (insulin-producing β cells), only the loss of function is treated (through administration of insulin).

Research history

The first researcher to recognize the difference between “self” and “foreign” was the German microbiologist Paul Ehrlich . Originally around 1900 he wanted to find out what happens to blood that remains after internal bleeding. So he started an experiment by injecting goats with sheep's blood. The amazing thing was that the immune system immediately destroyed the foreign blood cells (erythrocytes).

When Ehrlich later carried out the experiment with animals of the same species, the same thing happened. The immune system fought against the foreign blood cells.

It was only when he treated a goat with its own blood that Ehrlich realized that the body is able to differentiate between external and endogenous. The goat did not destroy the injected blood cells in this experiment (although Ehrlich retained the blood for a period of time). As a result of these experiments Ehrlich established the biological principle of horror autotoxicus (fear of self-destruction), according to which immune reactions against the body do not occur because they are incompatible with life. The existence of autoimmune diseases was not scientifically recognized until decades later, also on the basis of this theorem.


Hundreds of autoimmune diseases are known, of which around 400 diseases are attributed to the “ rheumatic type ”. The spectrum of the diseased organs is large. It must be assumed that virtually any organ or tissue can be the target of an autoimmune disease.

These diseases can be divided into three groups:

  1. Organ- specific diseases: These include diseases in which specific organs (tissue structures) are attacked by the immune system.
  2. Systemic diseases or non-organ-specific diseases: Systemic inflammatory rheumatic diseases such as collagenoses , which make up five to ten percent of diseases of the rheumatic type, belong to this group. Typical autoantibodies here are the antinuclear antibodies (ANA), which are directed against the structures of the cell nucleus , but also partly against the cytoplasm .
  3. Intermediate diseases: They are mixed forms or transitional forms. A broad immune response is triggered in this type of disease.
illness Affected tissue
Alopecia areata hair
Autoimmune enteropathy Enterocytes of the large and small intestines
Autoimmune hepatitis liver
APECED Pancreas , adrenal cortex , thymus
Bullous pemphigoid Hemidesmosomes of basal keratinocytes of the skin , often also oral mucosa
Chronic type A gastritis : Deficiency in vitamin B12 leads to pernicious anemia stomach
eosinophilic granulomatosis with polyangiitis Vessels
CIDP Myelin layer of the nerves of the peripheral nervous system
Ulcerative colitis Large intestine or rectum
Dermatomyositis Muscles and skin
Type 1 diabetes mellitus Beta cells of the pancreas
Dermatitis herpetiformis Duhring Skin , small intestine
Endocrine orbitopathy eyes
Epidermolysis bullosa acquisita skin
Glomerulonephritis Kidneys
Gluten ataxia Purkinje cells in the cerebellum
Goodpasture Syndrome Basement membranes of the kidneys and lungs
Granulomatosis with polyangiitis u. a. Kidneys , lungs , ENT area
Guillain-Barré Syndrome Myelin layer of the nerves of the peripheral nervous system
Hashimoto's thyroiditis thyroid
Idiopathic thrombocytopenic purpura Platelets
Lichen sclerosus skin
Lichen mucosae Mucous membrane
Linear IgA dermatosis skin
Lupus erythematosus Internal organs and skin
Microscopic polyangiitis Skin, kidney, lungs
Graves disease TSH receptors of the thyroid gland
Behçet's disease Blood vessels
Crohn's disease Digestive tract
ankylosing spondylitis Spine , iris
multiple sclerosis Myelin sheaths in the central nervous system
Myasthenia gravis Acetylcholine receptors on the motor endplate
Narcolepsy Orexin ( hypocretin ) producing nerve cells in the brain
PANDAS Basal ganglia of the brain
Pemphigus foliaceus skin
Pemphigus seborrhoicus skin
Pemphigus vulgaris Keratinocytes of the oral mucosa, v. a. but skin
Polychondritis Articular cartilage as well as ear and nasal cartilage
Polymyalgia rheumatica Shoulder and pelvic muscles
Polymyositis Muscles
psoriasis skin
Pyoderma gangrenosum (ulcerative dermatitis) skin
Rheumatic fever Connective tissue of the joints , heart tissue, basal ganglia of the brain , skin
Rheumatoid arthritis Connective tissue of the joints , tendons
Giant cell arteritis Vessels
SAPHO syndrome Skeleton ( joint inflammation , hyperostosis , bone inflammation ), skin ( acne )
Sarcoid (Boeck's disease) Lymph nodes , lungs , connective tissue
Sjogren's syndrome Salivary glands , lacrimal glands
Scleroderma Connective tissue under the skin
Stiff Man Syndrome Nerve cells of the central nervous system
Sympathetic ophthalmia eyes
Systemic lupus erythematosus Skin , joints , kidneys , CNS , vessels
Henoch-Schönlein purpura Skin, kidney, gastrointestinal tract, joints
Vitiligo Melanocytes
Celiac disease Small intestine


  • Andrea Kamphuis: The Autoimmune Book , Volume 1: Biology of the Immune System , Cologne 2018, ISBN 978-3752830682
  • Kenneth Murphy, Casey Weaver: Janeway's Immunobiology . 9th edition. Garland Science, 2017, ISBN 978-0-8153-4551-0 , Chapter 15 Autoimmunity and Transplantation .
  • Vinay Kumar, Abul K. Abbas, Nelson Fausto, Jon Aster (Eds.): Robbins and Cotran Pathologic Basis of Disease. 8th edition. Saunders / Elsevier, Philadelphia PA 2010, ISBN 978-1-4160-3121-5 .
  • Ronald Asherson (Ed.): Handbook of Systemic Autoimmune Diseases . 10 volumes. Elsevier, Amsterdam a. a .:
    • Ronald Asherson, Andrea Doria, Paolo Pauletto: The Heart in Systemic Autoimmune Diseases. Volume 1, 2004, ISBN 0-444-51398-1 ;
    • Ronald Asherson, Andrea Doria, Paolo Pauletto: Pulmonary Involvement in Systemic Autoimmune Diseases. Volume 2, 2005, ISBN 0-444-51652-2 ;
    • Ronald Asherson, Doruk Erkan, Steven Levine: The Neurologic Involvement in Systemic Autoimmune Diseases. Volume 3, 2005, ISBN 0-444-51651-4 ;
    • Michael Lockshin, Ware Branch (Ed.): Reproductive and Hormonal Aspects of Systemic Autoimmune Diseases. Volume 4, 2006, ISBN 0-444-51801-0 ;
    • Piercarlo Sarzi-Puttini, Ronald Asherson, Andrea Doria, Annegret Kuhn, Giampietro Girolomoni (eds.): The Skin in Systemic Autoimmune Diseases. Volume 5, 2006, ISBN 0-444-52158-5 ;
    • Rolando Cimaz, Ronald Asherson, Thomas Lehman (Eds.): Pediatrics in Systemic Autoimmune Diseases. Volume 6, 2008, ISBN 978-0-444-52971-8 ;
    • Justin Mason, Ronald Asherson, Charles Pusey (Eds.): The Kidney in Systemic Autoimmune Diseases. Volume 7, 2008, ISBN 978-0-444-52972-5 ;
    • Ronald Asherson, Manel Ramos-Casals, Joan Rodes, Josep Font: Digestive Involvement in Systemic Autoimmune Diseases. Volume 8, 2008, ISBN 978-0-444-53168-1 ;
    • Ronald Asherson, Sara Walker, Luis Jara: Endocrine Manifestations of Systemic Autoimmune Diseases. Volume 9, 2008, ISBN 978-0-444-53172-8 ;
    • Richard Cervera, Ronald Asherson, Munther Khamashta, Joan Carles Reverter (Eds.): Antiphospholipid Syndrome in Systemic Autoimmune Diseases. Volume 10, 2009, ISBN 978-0-444-53169-8 .

Web links

Wiktionary: autoimmune disease  - explanations of meanings, word origins, synonyms, translations

Individual evidence

  1. JGM Markle, DN Frank, S. Mortin-Toth, CE Robertson, LM Feazel, U. Rolle-Kampczyk, M. von Bergen, KD McCoy, AJ Macpherson, JS Danska: Sex Differences in the Gut Microbiome Drive Hormone-Dependent Regulation of autoimmunity. In: Science , March 2013, Vol. 339, Issue 6123, pp. 1084-1088, doi: 10.1126 / science.1233521 .