| Type IV hypersensitivity | |
|---|---|
| Other names | delayed-type hypersensitivity; DTH; cell-mediated hypersensitivity |
| Specialty | Immunology  |
Type IV hypersensitivity, in theGell and Coombs classification of allergic reactions, often calleddelayed-type hypersensitivity, is a type ofhypersensitivity reaction that can take a day or more to develop.[1] Unlike the other types, it is nothumoral (notantibody-mediated) but rather is a type ofcell-mediated response. This response involves the interaction ofT cells,monocytes, andmacrophages.
This reaction is caused whenCD4+ Th1 cells recognize foreign antigen in a complex with theMHC class II on the surface ofantigen-presenting cells. These can bemacrophages that secreteIL-12, which stimulates the proliferation of further CD4+ Th1 cells. CD4+ T cells secreteIL-2 andinterferon gamma (IFNγ), inducing the further release of other Th1cytokines, thus mediating the immune response. ActivatedCD8+ T cells destroy target cells on contact, whereas activated macrophages producehydrolytic enzymes and, on presentation with certain intracellularpathogens, transform intomultinucleated 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.[1]
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| Disease | Target antigen | Effects |
|---|---|---|
| Allergic contact dermatitis[2] | Environmental chemicals, likeurushiol (frompoison ivy andpoison oak), metals (e.g.nickel), topical medication | epidermal necrosis,inflammation,skin rash, andblisters |
| Autoimmune myocarditis[2] | Myosin heavy chain protein | Cardiomyopathy |
| Diabetes mellitus type 1[2] | Pancreaticbeta cell proteins (possiblyinsulin,glutamate decarboxylase) | Insulitis,beta cell destruction |
| Granulomas[3] | Various, depending on underlying disease | Walled-off lesion containingmacrophages and other cells |
| Someperipheral neuropathies | Schwann cell antigen | Neuritis,paralysis |
| Hashimoto's thyroiditis[2] | Thyroglobulin antigen | Hypothyroidism,hard goiter, follicular thymitis |
| Inflammatory bowel disease[2] | Enteric microbiota and/or self antigens | Hyperactivation of T-cells, cytokine release, recruitment of macrophages and other immune cells, inflammation |
| Multiple sclerosis[2] | Myelin antigens (e.g., myelin basic protein) | Myelin destruction, inflammation |
| Rheumatoid arthritis[2] | Possiblycollagen and/orcitrullinated self proteins | Chronic arthritis, inflammation, destruction ofarticular cartilage and bone |
| Tuberculin reaction (Mantoux test)[3] | Tuberculin | Induration anderythema around injection site indicates previous exposure |
An example of atuberculosis (TB) infection that comes under control:M. tuberculosis cells are engulfed bymacrophages after being identified as foreign but, due to an immuno-escape mechanism peculiar to mycobacteria,[4] TB bacteria block the fusion of their enclosingphagosome withlysosomes 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 withinterferon gamma, the macrophages become capable of killingM. tuberculosis by forming phagolysosomes andnitric oxideradicals. The hyper-activated macrophages secreteTNF-α which recruits multiplemonocytes to the site of infection. These cells differentiate intoepithelioid cells which wall off the infected cells, but results in significantinflammation and local damage.
Some other clinical examples: