Type IV hypersensitivity

{PsyPerspective}}

Type 4 hypersensitivity is often called delayed type hypersensitivity as a type of immunologic hypersensitivity. Unlike the other types, it is not antibody mediated but rather is a type of Cell-mediated immunity.

CD4+ helper T cells recognize antigen in a complex with Class 2 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
An example of a TB infection that came under control: M. tuberculosis 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. 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:
 * Temporal arteritis
 * Hashimoto's thyroiditis
 * Symptoms of leprosy
 * Symptoms of tuberculosis
 * Coeliac disease
 * Graft-versus-host disease
 * Chronic transplant rejection