Type IV hypersensitivity

Type IV hypersensitivity
Classification and external resources
MeSH D006968

Type 4 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.

CD4+ helper T cells recognize antigen in a complex with Class II major histocompatibility complex. The antigen-presenting cells in this case are macrophages that secrete IL-12, which stimulates the proliferation of further CD4+ Th1 cells. CD4+ T cells secrete IL-2 and interferon gamma, further inducing the 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.

Examples

Disease Target antigen Effects
Diabetes mellitus type 1 Pancreatic beta cell proteins
(possibly insulin, Glutamate decarboxylase)
Multiple sclerosis Oligodendrocyte proteins
(myelin basic protein, proteolipid protein)
Rheumatoid arthritis Antigen in synovial membrane
(possibly type II collagen)
  • Chronic arthritis
  • Destruction of articular cartilage and bone, a Type III hypersensitivity (Antibodies made against IgG)
Some peripheral neuropathies Schwann cell antigen
  • Neuritis
  • Paralysis
Hashimoto's Thyroiditis Thyroglobulin antigen
Crohn's disease Unknown
  • Chronic inflammation of ileum and colon
Allergic contact dermatitis Environmental chemicals, e.g. poison ivy, nickel
Mantoux test* (diagnostic) Tuberculin
  • Skin induration indicates TB exposure
Unless else specified in boxes, then ref is:[1]

* - Mantoux test not taken from [1]

An example of a TB infection that came under control: M. tuberculosis 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. 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:

See also

References

  1. ↑ 1.0 1.1 Table 5-5 in: Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson. Robbins Basic Pathology. Philadelphia: Saunders. ISBN 1-4160-2973-7. 8th edition.
  2. ↑ "eMedicine - Hypersensitivity Reactions, Delayed : Article by Walter Duane Hinshaw".