Type IV hypersensitivity
|Type IV hypersensitivity|
|Classification and external resources|
Type 4 hypersensitivity is often called delayed type hypersensitivity as the reaction takes several days to develop. Unlike the other types, it is not antibody-mediated but rather is a type of cell-mediated response.
CD4+ Th1 helper T cells recognize antigen in a complex with the MHC class II major histocompatibility complex 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, 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.
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|Allergic contact dermatitis||Environmental chemicals, like urushiol (from poison ivy and poison oak), metals (e.g. nickel), topical medication||epidermal necrosis, inflammation, skin rash, and blisters|
|autoimmune myocarditis||Myosin heavy chain protein||Cardiomyopathy|
|Diabetes mellitus type 1||Pancreatic beta cell proteins (possibly insulin, glutamate decarboxylase)||Insulitis, beta cell destruction|
|Granulomas||Various, depending on underlying disease||Walled off lesion containing macrophages and other cells|
|Some peripheral neuropathies||Schwann cell antigen||Neuritis, paralysis|
|Hashimoto's thyroiditis||Thyroglobulin antigen||Hypothyroidism, hard goiter, follicular thymitis|
|Inflammatory bowel disease||Enteric microbiota and/or self antigens||Hyperactivation of T-cells, cytokine release, recruitment of macrophages and other immune cells, inflammation|
|Multiple sclerosis||Myelin antigens (e.g., myelin basic protein)||Myelin destruction, inflammation|
|Rheumatoid arthritis||Possibly collagen and/or citrullinated self proteins||Chronic arthritis, inflammation, destruction of articular cartilage and bone|
|Tuberculin reaction (Mantoux test)||Tuberculin||Induration 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, TB bacteria are able to 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, on stimulation with IFN-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:
- Temporal arteritis
- Coeliac disease
- Graft-versus-host disease
- Chronic transplant rejection
- Kumar, Vinay; Abbas, Abul K.; Aster, Jon C. (2012-05-01). Robbins Basic Pathology. Elsevier Health Sciences. ISBN 1455737879.
- "Hypersensitivity reactions". www.microbiologybook.org. University of South Carolina School of Medicine - Microbiology and Immunology On-line. Retrieved 2016-05-29.
- "Hypersensitivity reactions". www.microbiologybook.org. Retrieved 2016-05-29.
- McDonough, K.; Kress, Y.; Bloom, B. R. (July 1993). "Pathogenesis of tuberculosis: interaction of Mycobacterium tuberculosis with macrophages". Infect. Immun. 61 (7): 2763–2773. eISSN 1098-5522. ISSN 0019-9567. Retrieved 18 June 2017.
- "eMedicine - Hypersensitivity Reactions, Delayed : Article by Walter Duane Hinshaw".