Hapten
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A hapten is a small molecule that can elicit an immune response only when attached to a large carrier such as a protein; the carrier may be one that also does not elicit an immune response by itself. (In general, only large molecules, infectious agents, or insoluble foreign matter can elicit an immune response in the body.) Once the body has generated antibodies to a hapten-carrier adduct, the small-molecule hapten may also be able to bind to the antibody, but it will usually not initiate an immune response; usually only the hapten-carrier adduct can do this. Sometimes the small-molecule hapten can even block immune response to the hapten-carrier adduct by preventing the adduct from binding to the antibody, a process called hapten inhibition.
The mechanisms of absence of immune response may vary and involve complex immunological mechanisms, but can include absent or insufficient co-stimulatory signals from antigen-presenting cells.
The concept of haptens emerged from the work of Karl Landsteiner[1] [2] who also pioneered the use of synthetic haptens to study immunochemical phenomena.[3]
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Examples of haptens [edit]
The first haptens used were aniline and its carboxyl derivatives (o-, m-, and p-aminobenzoic acid).[4]
A well-known example of a hapten is urushiol, which is the toxin found in poison ivy. When absorbed through the skin from a poison ivy plant, urushiol undergoes oxidation in the skin cells to generate the actual hapten, a reactive molecule called a quinone, which then reacts with skin proteins to form hapten adducts. Usually, the first exposure causes only sensitization, in which there is a proliferation of effector T-cells. After a subsequent, second exposure, the proliferated T-cells can become activated, generating an immune reaction that produces typical blisters of a poison ivy exposure.
Some haptens can induce autoimmune disease. An example is hydralazine, a blood pressure-lowering drug that occasionally can produce drug-induced lupus erythematosus in certain individuals. This also appears to be the mechanism by which the anaesthetic gas halothane can cause a life-threatening hepatitis, as well as the mechanism by which penicillin-class drugs cause autoimmune hemolytic anemia.
Other haptens that are commonly used in molecular biology applications include fluorescein, biotin, digoxigenin, and dinitrophenol. This concept of hapten is very original and innovative. Time and experimentation only prove the truth of this concept. Probably 'all' drug reactions are mediated through this type drug protein complex. Sulfa drugs, Fluroquinolones and almost all drugs and chemicals act through mechanism probably. It may takes years with reapeated exposures. Only in case of injection penicillin induced anaphylactic reaction may be due to presence traces of proteins from fungi. As stomach and intestine will digest the proteins, reactions occuring after oral drugs are mediated through hapten only. Or the ascending myelitis caused by antirabies injection may be due to traces of proteins present in the vaccine. In case of hapten reactins you do not have E.S.R. raised. As small molecules are not expected to induce immunological response, hapten is the only alternative remains to explain the immune response. Dr Karl Landsteiner got the Nobel prize which he obviously deserves.
Hapten inhibition [edit]
Hapten inhibition is the inhibition of a type III hypersensitivity response towards a molecule by introducing a fraction of it that works as a hapten. The rest of the molecule may be regarded as the carrier, and the entire molecule as the adduct. The hapten binds up antibodies toward that molecule without causing the immune response, leaving less antibodies left to bind to the molecule itself. An example of a hapten inhibitor is dextran 1, which is a small fraction (1 kilodalton) of the entire dextran complex, which is enough to bind anti-dextran antibodies, but insufficient to result in the formation of immune complexes and resultant immune responses.[5]
References [edit]
- ^ Landsteiner, Karl (1945). The Specificity of Serological Reactions. Cambridge: Harvard Univ. Press.
- ^ Landsteiner, Karl (1990). The Specificity of Serological Reactions, 2nd Edition, revised. Courier Dover Publications. ISBN 0-486-66203-9.
- ^ Shreder, Kevin (March 2000). "Synthetic Haptens as Probes of Antibody Response and Immunorecognition". Methods (Academic Press) 20 (3): 372–379. doi:10.1006/meth.1999.0929. PMID 10694458.
- ^ Based on K. Landsteiner, 1962, The Specificity of Serologic Reactions, Dover Press
- ^ Promiten, drug information from the Swedish official drug catalog Last updated: 2005-02-17
See also [edit]
External links [edit]
- Haptens at the US National Library of Medicine Medical Subject Headings (MeSH)
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