Type IV hypersensitivity, in the Gell and Coombs classification of allergic reactions, often called delayed-type hypersensitivity, is a type of

hypersensitivity Hypersensitivity (also called hypersensitivity reaction or intolerance) is an abnormal physiological condition in which there is an undesirable and adverse immune response to an antigen. It is an abnormality in the immune system that causes Imm ...

reaction that can take a day or more to develop. Unlike the other types, it is not humoral (not

antibody An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as pathogenic bacteria, bacteria and viruses, includin ...

-mediated) but rather is a type of cell-mediated response. This response involves the interaction of T cells,

monocyte Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and monocyte-derived dendritic cells. As a part of the vertebrate innate immune system monocytes also ...

s, and

macrophage Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...

s. This reaction is caused when CD4⁺ T_h1 cells recognize foreign antigen in a complex with the

MHC class II MHC Class II molecules are a class of major histocompatibility complex (MHC) molecules normally found only on professional antigen-presenting cells such as dendritic cells, macrophages, some endothelial cells, thymic epithelial cells, and B cell ...

on the surface of antigen-presenting cells. These can be

s that secrete IL-12, which stimulates the proliferation of further CD4⁺ T_h1 cells. CD4⁺ T cells secrete

IL-2 The Ilyushin Il-2 (Russian language, Russian: Илью́шин Ил-2) is a Ground attack aircraft, ground-attack plane that was produced by the Soviet Union in large numbers during the World War II, Second World War. The word ''shturmovík'' (C ...

and interferon gamma (IFNγ), inducing the further release of other T_h1

cytokine Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...

s, 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

pathogen In biology, a pathogen (, "suffering", "passion" and , "producer of"), in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a Germ theory of d ...

s, transform into multinucleated 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.

Forms

An example of a

tuberculosis Tuberculosis (TB), also known colloquially as the "white death", or historically as consumption, is a contagious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can al ...

(TB) infection that comes under control: '' M. tuberculosis'' cells are engulfed by

s after being identified as foreign but, due to an immuno-escape mechanism peculiar to mycobacteria, TB bacteria block the fusion of their enclosing

phagosome In cell biology, a phagosome is a vesicle formed around a particle engulfed by a phagocyte via phagocytosis. Professional phagocytes include macrophages, neutrophils, and dendritic cells (DCs). A phagosome is formed by the fusion of the cel ...

with

lysosome A lysosome () is a membrane-bound organelle that is found in all mammalian cells, with the exception of red blood cells (erythrocytes). There are normally hundreds of lysosomes in the cytosol, where they function as the cell’s degradation cent ...

s which would destroy the bacteria. Thereby TB can continue to replicate within macrophages. After several weeks, the immune system somehow echanism as yet unexplainedramps up and, upon stimulation with interferon gamma, the macrophages become capable of killing ''M. tuberculosis'' by forming phagolysosomes and

nitric oxide Nitric oxide (nitrogen oxide, nitrogen monooxide, or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes den ...

radicals. The hyper-activated macrophages secrete TNF-α which recruits multiple

s to the site of infection. These cells differentiate into epithelioid cells which wall off the infected cells, but results in significant

inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...

and local damage. Some other clinical examples: *

Urushiol-induced contact dermatitis Urushiol-induced contact dermatitis (also called Toxicodendron dermatitis or Rhus dermatitis) is a type of allergic contact dermatitis caused by the oil urushiol found in various plants, most notably sumac family species of the genus ''Toxicodendr ...

* Chronic transplant rejection *

Coeliac disease Coeliac disease (British English) or celiac disease (American English) is a long-term autoimmune disorder, primarily affecting the small intestine. Patients develop intolerance to gluten, which is present in foods such as wheat, rye, spelt ...

* Giant cell arteritis *

Graft-versus-host disease Graft-versus-host disease (GvHD) is a syndrome, characterized by inflammation in different organs. GvHD is commonly associated with bone marrow transplants and stem cell transplants. White blood cells of the donor's immune system which rema ...

Leprosy Leprosy, also known as Hansen's disease (HD), is a Chronic condition, long-term infection by the bacteria ''Mycobacterium leprae'' or ''Mycobacterium lepromatosis''. Infection can lead to damage of the Peripheral nervous system, nerves, respir ...

References

External links

{{Hypersensitivity disease by cause Hypersensitivity

Forms

See also

References

External links