Type IV hypersensitivity, often called delayed-type hypersensitivity, is a type of

hypersensitivity Hypersensitivity (also called hypersensitivity reaction or intolerance) refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. They are usually referred to as an over-reaction of the immune s ...

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

humoral Humoral immunity is the aspect of immunity that is mediated by macromolecules - including secreted antibodies, complement proteins, and certain antimicrobial peptides - located in extracellular fluids. Humoral immunity is named so because it invo ...

(not

antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

-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 conventional dendritic cells. As a part of the vertebrate innate immune system monocytes also inf ...

s, and

macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...

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, mononuclear phagocytes, some endothelial cells, thymic epithelial ce ...

on the surface of

antigen-presenting cells An antigen-presenting cell (APC) or accessory cell is a cell that displays antigen bound by major histocompatibility complex (MHC) proteins on its surface; this process is known as antigen presentation. T cells may recognize these complexes using ...

. These can be

macrophages Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...

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: Илью́шин Ил-2) is a ground-attack plane that was produced by the Soviet Union in large numbers during the Second World War. The word ''shturmovík'' ( Cyrillic: штурмовик), the generic Russian term ...

and

interferon gamma Interferon gamma (IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons. The existence of this interferon, which early in its history was known as immune interferon, was described by E. F. Wheelock ...

(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 peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...

s, thus mediating the immune response. Activated CD8⁺ T cells destroy target cells on contact, whereas activated macrophages produce

hydrolytic enzymes Hydrolase is a class of enzyme that commonly perform as biochemical catalysts that use water to break a chemical bond, which typically results in dividing a larger molecule into smaller molecules. Some common examples of hydrolase enzymes are este ...

and, on presentation with certain intracellular

pathogen In biology, a pathogen ( el, πάθος, "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 ...

s, transform into

multinucleated giant cells A giant cell (also known as multinucleated giant cell, or multinucleate giant cell) is a mass formed by the union of several distinct cells (usually histiocytes), often forming a granuloma. Although there is typically a focus on the pathological ...

. 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) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in ...

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

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 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 cell mem ...

with

lysosome A lysosome () is a membrane-bound organelle found in many animal cells. They are spherical vesicles that contain hydrolytic enzymes that can break down many kinds of biomolecules. A lysosome has a specific composition, of both its membrane prot ...

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, on stimulation with

IFN-gamma Interferon gamma (IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons. The existence of this interferon, which early in its history was known as immune interferon, was described by E. F. Wheelock ...

, the macrophages become capable of killing ''M. tuberculosis'' by forming phagolysosomes and

nitric oxide Nitric oxide (nitrogen oxide 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 denoted by a dot in its che ...

radicals. The hyper-activated macrophages secrete

TNF-α Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homolog ...

which recruits multiple

monocytes 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 conventional dendritic cells. As a part of the vertebrate innate immune system monocytes also infl ...

to the site of infection. These cells differentiate into

epithelioid cells According to a common point of view epithelioid cells (also called epithelioid histiocytes) are derivatives of activated macrophages resembling epithelial cells. Structure and function Structurally, epithelioid cells (when examined by light mi ...

which wall off the infected cells, but results in significant

inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...

and local damage. Some other clinical examples: *

Urushiol Urushiol is an oily mixture of organic compounds with allergenic properties found in plants of the family Anacardiaceae, especially ''Toxicodendron'' ''spp.'' (e.g., poison oak, Chinese lacquer tree, poison ivy, poison sumac), ''Comocladia sp ...

-induced

contact dermatitis Contact dermatitis is a type of acute or chronic inflammation of the skin caused by exposure to chemical or physical agents. Symptoms of contact dermatitis can include itchy or dry skin, a red rash, bumps, blisters, or swelling. These rashes are ...

Temporal arteritis Temporal may refer to: Entertainment * Temporal (band), an Australian metal band * ''Temporal'' (Radio Tarifa album), 1997 * ''Temporal'' (Love Spirals Downwards album), 2000 * ''Temporal'' (Isis album), 2012 * ''Temporal'' (video game), a 200 ...

Leprosy Leprosy, also known as Hansen's disease (HD), is a long-term infection by the bacteria ''Mycobacterium leprae'' or ''Mycobacterium lepromatosis''. Infection can lead to damage of the nerves, respiratory tract, skin, and eyes. This nerve damag ...

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

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 remain wit ...

* Chronic transplant rejection

References

External links

{{Use dmy dates, date=May 2019 Hypersensitivity

Forms

See also

References

External links