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Type IV hypersensitivity
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<h2 id="forms">Forms</h2> <table><tbody><tr><th>Disease</th><th>Target antigen</th><th>Effects</th></tr><tr><td><a href="/facts/Allergic_contact_dermatitis/cNyAKVe7">Allergic contact dermatitis</a><a class="footnote-ref" id="fnref:3" href="#fn:3"><sup>3</sup></a></td><td>Environmental chemicals, like <a href="/facts/Urushiol/K0D4Njqr">urushiol</a> (from <a href="/facts/Poison_ivy_(plant)/GnLEC4Ur">poison ivy</a> and <a href="/facts/Poison_oak/ae0vY7NC">poison oak</a>), metals (e.g. <a href="/facts/Nickel_allergy_(nickel_allergic_contact_dermatitis)/2Yrh1HwQ">nickel</a>), topical medication</td><td><a href="/facts/Necrosis/zCPsTeWx">epidermal necrosis</a>, <a href="/facts/Inflammation/Ura86MIy">inflammation</a>, <a href="/facts/Skin_rash/W97qGpq6">skin rash</a>, and <a href="/facts/Blister/qGhqaeQV">blisters</a></td></tr><tr><td><a href="/facts/Myocarditis/ypoBJ4Pp">Autoimmune myocarditis</a><a class="footnote-ref" id="fnref:4" href="#fn:4"><sup>4</sup></a></td><td><a href="/facts/Myosin_heavy_chain/7zGeRkpS">Myosin heavy chain</a> protein</td><td><a href="/facts/Cardiomyopathy/rhXF3Vcj">Cardiomyopathy</a></td></tr><tr><td><a href="/facts/Diabetes_mellitus_type_1/IkuQadGx">Diabetes mellitus type 1</a><a class="footnote-ref" id="fnref:5" href="#fn:5"><sup>5</sup></a></td><td>Pancreatic <a href="/facts/Beta_cell/MXcTmlDL">beta cell</a> proteins (possibly <a href="/facts/Insulin/oXG0myt1">insulin</a>, <a href="/facts/Glutamate_decarboxylase/YqIQsrgs">glutamate decarboxylase</a>)</td><td><a href="/facts/Insulitis/pBQUonHy">Insulitis</a>, <a href="/facts/Beta_cell/MXcTmlDL">beta cell</a> destruction</td></tr><tr><td><a href="/facts/Granuloma/mqEhHfjS">Granulomas</a><a class="footnote-ref" id="fnref:6" href="#fn:6"><sup>6</sup></a></td><td>Various, depending on underlying disease</td><td>Walled-off lesion containing <a href="/facts/Macrophage/z7hkQu3o">macrophages</a> and other cells</td></tr><tr><td>Some <a href="/facts/Peripheral_neuropathies/2KjA7nyD">peripheral neuropathies</a></td><td><a href="/facts/Schwann_cell/fcdM1444">Schwann cell</a> antigen</td><td><a href="/facts/Neuritis/9WAVapCY">Neuritis</a>, <a href="/facts/Paralysis/Sh1Rqr8R">paralysis</a></td></tr><tr><td><a href="/facts/Hashimoto%27s_thyroiditis/myBntJv5">Hashimoto's thyroiditis</a><a class="footnote-ref" id="fnref:7" href="#fn:7"><sup>7</sup></a></td><td><a href="/facts/Thyroglobulin/whhQ9Dyb">Thyroglobulin</a> antigen</td><td><a href="/facts/Hypothyroidism/oqtQDu2F">Hypothyroidism</a>, <a href="/facts/Goiter/0kNGMcb6">hard goiter</a>, follicular thymitis</td></tr><tr><td><a href="/facts/Inflammatory_bowel_disease/RuxcPW5A">Inflammatory bowel disease</a><a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a></td><td><a href="/facts/Human_microbiota/KerK9YGP">Enteric microbiota</a> and/or self antigens</td><td>Hyperactivation of T-cells, cytokine release, recruitment of macrophages and other immune cells, inflammation</td></tr><tr><td><a href="/facts/Multiple_sclerosis/vghXl0IQ">Multiple sclerosis</a><a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a></td><td><a href="/facts/Myelin/DKgJB8s8">Myelin</a> antigens (e.g., myelin basic protein)</td><td>Myelin destruction, inflammation</td></tr><tr><td><a href="/facts/Rheumatoid_arthritis/qFK4Xwv7">Rheumatoid arthritis</a><a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a></td><td>Possibly <a href="/facts/Collagen/KsyAb72K">collagen</a> and/or <a href="/facts/Citrullinated/gsMUqv0n">citrullinated</a> self proteins</td><td>Chronic arthritis, inflammation, destruction of <a href="/facts/Hyaline_cartilage/aH44t8b7">articular cartilage</a> and bone</td></tr><tr><td><a href="/facts/Tuberculin/Pcy2d05s">Tuberculin</a> reaction (<a href="/facts/Mantoux_test/bkmsTRYs">Mantoux test</a>)<a class="footnote-ref" id="fnref:11" href="#fn:11"><sup>11</sup></a></td><td>Tuberculin</td><td><a href="/facts/Induration/Vkr5XpeG">Induration</a> and <a href="/facts/Erythema/VUsgXRlB">erythema</a> around injection site indicates previous exposure</td></tr></tbody></table> <p>An example of a <a href="/facts/Tuberculosis/ggPyovAl">tuberculosis</a> (TB) infection that comes under control: <i><a href="/facts/M._tuberculosis/cbRjnhIQ">M. tuberculosis</a></i> cells are engulfed by <a href="/facts/Macrophage/z7hkQu3o">macrophages</a> after being identified as foreign but, due to an immuno-escape mechanism peculiar to mycobacteria,<a class="footnote-ref" id="fnref:12" href="#fn:12"><sup>12</sup></a> TB bacteria block the fusion of their enclosing <a href="/facts/Phagosome/tEHvpGy9">phagosome</a> with <a href="/facts/Lysosome/0mcrzJU9">lysosomes</a> 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 <a href="/facts/Interferon_gamma/r51CXVph">interferon gamma</a>, the macrophages become capable of killing <i>M. tuberculosis</i> by forming phagolysosomes and <a href="/facts/Nitric_oxide/UvhdvDzp">nitric oxide</a> <a href="/facts/Radical_(chemistry)/qFymuVoT">radicals</a>. The hyper-activated macrophages secrete <a href="/facts/TNF-%CE%B1/7NWNIaCb">TNF-α</a> which recruits multiple <a href="/facts/Monocyte/FW4NNMKM">monocytes</a> to the site of infection. These cells differentiate into <a href="/facts/Epithelioid_cell/R6SBUFfV">epithelioid cells</a> which wall off the infected cells, but results in significant <a href="/facts/Inflammation/Ura86MIy">inflammation</a> and local damage. </p><p>Some other clinical examples: </p> <ul><li><a href="/facts/Urushiol-induced_contact_dermatitis/M8lw810J">Urushiol-induced contact dermatitis</a><a class="footnote-ref" id="fnref:13" href="#fn:13"><sup>13</sup></a></li> <li><a href="/facts/Chronic_transplant_rejection/d9jSqs2x">Chronic transplant rejection</a></li> <li><a href="/facts/Coeliac_disease/AKd5PkTc">Coeliac disease</a></li> <li><a href="/facts/Giant_cell_arteritis/3X1GdNRR">Giant cell arteritis</a></li> <li><a href="/facts/Graft-versus-host_disease/UjspvMVa">Graft-versus-host disease</a><a class="footnote-ref" id="fnref:14" href="#fn:14"><sup>14</sup></a></li> <li><a href="/facts/Leprosy/FSjTpMEB">Leprosy</a></li></ul> <h2 id="see-also">See also</h2> <ul><li><a href="/facts/Hypersensitivity/j2AWmqCD">Hypersensitivity</a></li> <li><a href="/facts/Type_I_hypersensitivity/fSqwUhBH">Type I hypersensitivity</a></li> <li><a href="/facts/Type_II_hypersensitivity/zaDMNcly">Type II hypersensitivity</a></li> <li><a href="/facts/Type_III_hypersensitivity/DJmeS5HU">Type III hypersensitivity</a></li></ul> <h2 id="external-links">External links</h2> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>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. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3245432" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3245432</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>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. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3245432" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3245432</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>Kumar, Vinay; Abbas, Abul K.; Aster, Jon C. (1 May 2012). Robbins Basic Pathology. Elsevier Health Sciences. ISBN 978-1455737871. <a href="978-1455737871" target="_blank">978-1455737871</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>Kumar, Vinay; Abbas, Abul K.; Aster, Jon C. (1 May 2012). Robbins Basic Pathology. Elsevier Health Sciences. ISBN 978-1455737871. <a href="978-1455737871" target="_blank">978-1455737871</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>Kumar, Vinay; Abbas, Abul K.; Aster, Jon C. (1 May 2012). Robbins Basic Pathology. Elsevier Health Sciences. ISBN 978-1455737871. <a href="978-1455737871" target="_blank">978-1455737871</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>"Hypersensitivity reactions". microbiologybook.org. University of South Carolina School of Medicine - Microbiology and Immunology On-line. Retrieved 29 May 2016. <a href="https://www.microbiologybook.org/ghaffar/hyper00.htm" target="_blank">https://www.microbiologybook.org/ghaffar/hyper00.htm</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>Kumar, Vinay; Abbas, Abul K.; Aster, Jon C. (1 May 2012). Robbins Basic Pathology. Elsevier Health Sciences. ISBN 978-1455737871. <a href="978-1455737871" target="_blank">978-1455737871</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></p></li> <li id="fn:8"><p>Kumar, Vinay; Abbas, Abul K.; Aster, Jon C. (1 May 2012). Robbins Basic Pathology. Elsevier Health Sciences. ISBN 978-1455737871. <a href="978-1455737871" target="_blank">978-1455737871</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></p></li> <li id="fn:9"><p>Kumar, Vinay; Abbas, Abul K.; Aster, Jon C. (1 May 2012). Robbins Basic Pathology. Elsevier Health Sciences. ISBN 978-1455737871. <a href="978-1455737871" target="_blank">978-1455737871</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></p></li> <li id="fn:10"><p>Kumar, Vinay; Abbas, Abul K.; Aster, Jon C. (1 May 2012). Robbins Basic Pathology. Elsevier Health Sciences. ISBN 978-1455737871. <a href="978-1455737871" target="_blank">978-1455737871</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></p></li> <li id="fn:11"><p>"Hypersensitivity reactions". microbiologybook.org. University of South Carolina School of Medicine - Microbiology and Immunology On-line. Retrieved 29 May 2016. <a href="https://www.microbiologybook.org/ghaffar/hyper00.htm" target="_blank">https://www.microbiologybook.org/ghaffar/hyper00.htm</a> <a href="#fnref:11" class="footnote-back-ref">↩</a></p></li> <li id="fn:12"><p>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. <a href="http://iai.asm.org/content/61/7/2763.abstract" target="_blank">http://iai.asm.org/content/61/7/2763.abstract</a> <a href="#fnref:12" class="footnote-back-ref">↩</a></p></li> <li id="fn:13"><p>Marwa, K; Kondamudi, NP (1 January 2021). "Type IV Hypersensitivity Reaction". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID 32965899. Retrieved 28 November 2021. <a href="https://www.ncbi.nlm.nih.gov/books/NBK562228/#_NBK562228_pubdet_" target="_blank">https://www.ncbi.nlm.nih.gov/books/NBK562228/#_NBK562228_pubdet_</a> <a href="#fnref:13" class="footnote-back-ref">↩</a></p></li> <li id="fn:14"><p>Walter Duane Hinshaw (26 June 2021). "eMedicine - Hypersensitivity Reactions, Delayed". <a href="http://www.emedicine.com/MED/topic1100.htm" target="_blank">http://www.emedicine.com/MED/topic1100.htm</a> <a href="#fnref:14" class="footnote-back-ref">↩</a></p></li> </ol>