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Type IV hypersensitivity
Medical condition

Type IV hypersensitivity, in the Gell and Coombs classification of allergic reactions, often called delayed-type hypersensitivity, is a type of hypersensitivity reaction that can take a day or more to develop. Unlike the other types, it is not humoral (not antibody-mediated) but rather is a type of cell-mediated response. This response involves the interaction of T cells, monocytes, and macrophages.

This reaction is caused when CD4+ Th1 cells recognize foreign antigen in a complex with the MHC class II on the surface of antigen-presenting cells. These can be macrophages that secrete IL-12, which stimulates the proliferation of further CD4+ Th1 cells. CD4+ T cells secrete IL-2 and interferon gamma (IFNγ), inducing the further release of other Th1 cytokines, thus mediating the immune response. Activated CD8+ T cells destroy target cells on contact, whereas activated macrophages produce hydrolytic enzymes and, on presentation with certain intracellular pathogens, transform into multinucleated giant cells.

The overreaction of the helper T cells and overproduction of cytokines damage tissues, cause inflammation, and cell death. Type IV hypersensitivity can usually be resolved with topical corticosteroids and trigger avoidance.

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Forms

DiseaseTarget antigenEffects
Allergic contact dermatitis3Environmental chemicals, like urushiol (from poison ivy and poison oak), metals (e.g. nickel), topical medicationepidermal necrosis, inflammation, skin rash, and blisters
Autoimmune myocarditis4Myosin heavy chain proteinCardiomyopathy
Diabetes mellitus type 15Pancreatic beta cell proteins (possibly insulin, glutamate decarboxylase)Insulitis, beta cell destruction
Granulomas6Various, depending on underlying diseaseWalled-off lesion containing macrophages and other cells
Some peripheral neuropathiesSchwann cell antigenNeuritis, paralysis
Hashimoto's thyroiditis7Thyroglobulin antigenHypothyroidism, hard goiter, follicular thymitis
Inflammatory bowel disease8Enteric microbiota and/or self antigensHyperactivation of T-cells, cytokine release, recruitment of macrophages and other immune cells, inflammation
Multiple sclerosis9Myelin antigens (e.g., myelin basic protein)Myelin destruction, inflammation
Rheumatoid arthritis10Possibly collagen and/or citrullinated self proteinsChronic arthritis, inflammation, destruction of articular cartilage and bone
Tuberculin reaction (Mantoux test)11TuberculinInduration and erythema around injection site indicates previous exposure

An example of a tuberculosis (TB) infection that comes under control: M. tuberculosis cells are engulfed by macrophages after being identified as foreign but, due to an immuno-escape mechanism peculiar to mycobacteria,12 TB bacteria block the fusion of their enclosing phagosome with lysosomes which would destroy the bacteria. Thereby TB can continue to replicate within macrophages. After several weeks, the immune system somehow [mechanism as yet unexplained] ramps up and, upon stimulation with interferon gamma, the macrophages become capable of killing M. tuberculosis by forming phagolysosomes and nitric oxide radicals. The hyper-activated macrophages secrete TNF-α which recruits multiple monocytes to the site of infection. These cells differentiate into epithelioid cells which wall off the infected cells, but results in significant inflammation and local damage.

Some other clinical examples:

See also

References

  1. Warrington, Richard; Watson, Wade; Kim, Harold L.; Antonetti, Francesca Romana (10 November 2011). "An introduction to immunology and immunopathology". Allergy, Asthma & Clinical Immunology. 7 (1): S1. doi:10.1186/1710-1492-7-S1-S1. ISSN 1710-1492. PMC 3245432. PMID 22165815. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3245432 ↩

  2. Warrington, Richard; Watson, Wade; Kim, Harold L.; Antonetti, Francesca Romana (10 November 2011). "An introduction to immunology and immunopathology". Allergy, Asthma & Clinical Immunology. 7 (1): S1. doi:10.1186/1710-1492-7-S1-S1. ISSN 1710-1492. PMC 3245432. PMID 22165815. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3245432 ↩

  3. Kumar, Vinay; Abbas, Abul K.; Aster, Jon C. (1 May 2012). Robbins Basic Pathology. Elsevier Health Sciences. ISBN 978-1455737871. 978-1455737871 ↩

  4. Kumar, Vinay; Abbas, Abul K.; Aster, Jon C. (1 May 2012). Robbins Basic Pathology. Elsevier Health Sciences. ISBN 978-1455737871. 978-1455737871 ↩

  5. Kumar, Vinay; Abbas, Abul K.; Aster, Jon C. (1 May 2012). Robbins Basic Pathology. Elsevier Health Sciences. ISBN 978-1455737871. 978-1455737871 ↩

  6. "Hypersensitivity reactions". microbiologybook.org. University of South Carolina School of Medicine - Microbiology and Immunology On-line. Retrieved 29 May 2016. https://www.microbiologybook.org/ghaffar/hyper00.htm ↩

  7. Kumar, Vinay; Abbas, Abul K.; Aster, Jon C. (1 May 2012). Robbins Basic Pathology. Elsevier Health Sciences. ISBN 978-1455737871. 978-1455737871 ↩

  8. Kumar, Vinay; Abbas, Abul K.; Aster, Jon C. (1 May 2012). Robbins Basic Pathology. Elsevier Health Sciences. ISBN 978-1455737871. 978-1455737871 ↩

  9. Kumar, Vinay; Abbas, Abul K.; Aster, Jon C. (1 May 2012). Robbins Basic Pathology. Elsevier Health Sciences. ISBN 978-1455737871. 978-1455737871 ↩

  10. Kumar, Vinay; Abbas, Abul K.; Aster, Jon C. (1 May 2012). Robbins Basic Pathology. Elsevier Health Sciences. ISBN 978-1455737871. 978-1455737871 ↩

  11. "Hypersensitivity reactions". microbiologybook.org. University of South Carolina School of Medicine - Microbiology and Immunology On-line. Retrieved 29 May 2016. https://www.microbiologybook.org/ghaffar/hyper00.htm ↩

  12. McDonough, K.; Kress, Y.; Bloom, B. R. (July 1993). "Pathogenesis of tuberculosis: interaction of Mycobacterium tuberculosis with macrophages". Infect. Immun. 61 (7): 2763–2773. doi:10.1128/iai.61.7.2763-2773.1993. eISSN 1098-5522. ISSN 0019-9567. PMC 280919. PMID 8514378. S2CID 19523447. Retrieved 18 June 2017. http://iai.asm.org/content/61/7/2763.abstract ↩

  13. Marwa, K; Kondamudi, NP (1 January 2021). "Type IV Hypersensitivity Reaction". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID 32965899. Retrieved 28 November 2021. https://www.ncbi.nlm.nih.gov/books/NBK562228/#_NBK562228_pubdet_ ↩

  14. Walter Duane Hinshaw (26 June 2021). "eMedicine - Hypersensitivity Reactions, Delayed". http://www.emedicine.com/MED/topic1100.htm ↩