| Type IV hypersensitivity | |
|---|---|
| Classification and external resources | |
| MeSH | D006968 |
Type IV hypersensitivity is often called delayed type hypersensitivity as the reaction takes two to three days to develop. Unlike the other types, it is not antibody mediated but rather is a type of cell-mediated response.
CD8+ cytotoxic T cells and CD4+ helper T cells recognize antigen in a complex with either type 1 or 2 major histocompatibility complex. The antigen-presenting cells in this case are macrophages that secrete IL-12, which stimulates the proliferation of further CD4+ T cells. CD4+ T cells secrete IL-2 and interferon gamma, further inducing the release of other Type 1 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.
| Disease | Target antigen | Effects |
|---|---|---|
| Diabetes mellitus type 1 | Pancreatic beta cell proteins (possibly insulin, Glutamate decarboxylase) |
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| Multiple sclerosis | Oligodendrocyte proteins (myelin basic protein, proteolipid protein) |
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| Rheumatoid arthritis | Antigen in synovial membrane (possibly type II collagen) |
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| Some peripheral neuropathies | Schwann cell antigen |
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| Crohn's disease | Unknown | |
| Contact dermatitis | Environmental chemicals, e.g. poison ivy, nickel |
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| Mantoux test* (diagnostic) | Tuberculin |
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| Unless else specified in boxes, then ref is: [1]
* - Mantoux test not taken from [1] |
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The pathophysiology of the Tuberculin reaction is explained thus: M. tuberculi are engulfed by macrophages after being identified as foreign, but due to a self- preserving mechanism peculiar to TB it is able to block the fusion of the phagosome within which it is existing with the lysosome which would destroy it. So it can continue existing and replicating within the immune cell designed to destroy it. 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. tuberculi by forming phagolysosomes and nitric oxide radicals. However unfortunately the hyper-activated macrophages secrete TNF which recruits multiple monocytes into the battle. These cells differentiate into epithelioid histiocytes which wall off the infected cells, but at the cost of significant inflammation and local damage.
Some other clinical examples:
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