Type IV hypersensitivity
Encyclopedia
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 cell
s 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 enzyme
s and, on presentation with certain intracellular pathogens, transform into multinucleated giant cell
s.
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:
Hypersensitivity
Hypersensitivity refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. These reactions may be damaging, uncomfortable, or occasionally fatal. Hypersensitivity reactions require a pre-sensitized state of the host. The four-group classification...
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 cell
Cytotoxic T cell
A cytotoxic T cell belongs to a sub-group of T lymphocytes that are capable of inducing the death of infected somatic or tumor cells; they kill cells that are infected with viruses , or are otherwise damaged or...
s and CD4+ helper T cells recognize antigen in a complex with either type 1 or 2 major histocompatibility complex
Major histocompatibility complex
Major histocompatibility complex is a cell surface molecule encoded by a large gene family in all vertebrates. MHC molecules mediate interactions of leukocytes, also called white blood cells , which are immune cells, with other leukocytes or body cells...
. The antigen-presenting cells in this case are macrophages that secrete IL-12
Interleukin 12
Interleukin 12 is an interleukin that is naturally produced by dendritic cells, macrophages and human B-lymphoblastoid cells in response to antigenic stimulation.-Gene and structure:...
, which stimulates the proliferation of further CD4+ T cells. CD4+ T cells secrete IL-2
Interleukin 2
Interleukin-2 is an interleukin, a type of cytokine immune system signaling molecule, which is a leukocytotrophic hormone that is instrumental in the body's natural response to microbial infection and in discriminating between foreign and self...
and interferon
Interferon
Interferons are proteins made and released by host cells in response to the presence of pathogens—such as viruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.IFNs belong to...
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 enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s and, on presentation with certain intracellular pathogens, transform into multinucleated giant cell
Giant cell
A giant cell is a mass formed by the union of several distinct cells . It can arise in response to an infection or foreign body.Types include:* foreign-body giant cell* Langhans giant cell* Touton giant cells...
s.
Examples
| Disease | Target antigen | Effects |
|---|---|---|
| Diabetes mellitus type 1 Diabetes mellitus type 1 Diabetes mellitus type 1 is a form of diabetes mellitus that results from autoimmune destruction of insulin-producing beta cells of the pancreas. The subsequent lack of insulin leads to increased blood and urine glucose... |
Pancreatic beta cell Beta cell Beta cells are a type of cell in the pancreas located in the so-called islets of Langerhans. They make up 65-80% of the cells in the islets.-Function:... proteins (possibly insulin Insulin Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle.... , Glutamate decarboxylase Glutamate decarboxylase Glutamate decarboxylase or glutamic acid decarboxylase is an enzyme that catalyzes the decarboxylation of glutamate to GABA and CO2. GAD uses PLP as a cofactor. The reaction proceeds as follows:... ) |
|
| Multiple sclerosis Multiple sclerosis Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms... |
Oligodendrocyte Oligodendrocyte Oligodendrocytes , or oligodendroglia , are a type of brain cell. They are a variety of neuroglia. Their main function is the insulation of axons in the central nervous system of some vertebrates... proteins (myelin basic protein Myelin basic protein Myelin basic protein is a protein believed to be important in the process of myelination of nerves in the central nervous system .MBP was initially sequenced in 1971 after isolation from myelin membranes... , proteolipid protein) |
Demyelinating disease A demyelinating disease is any disease of the nervous system in which the myelin sheath of neurons is damaged. This impairs the conduction of signals in the affected nerves, causing impairment in sensation, movement, cognition, or other functions depending on which nerves are involved.The term... |
| Rheumatoid arthritis Rheumatoid arthritis Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development... |
Antigen in synovial membrane (possibly type II collagen) |
|
| Some peripheral neuropathies | Schwann cell Schwann cell Schwann cells or neurolemmocytes are the principal glia of the peripheral nervous system . Glial cells function to support neurons and in the PNS, also include satellite cells, olfactory ensheathing cells, enteric glia and glia that reside at sensory nerve endings, such as the Pacinian corpuscle... antigen |
|
| Crohn's disease Crohn's disease Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms... |
Unknown |
Ileum The ileum is the final section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms posterior intestine or distal intestine may be used instead of ileum.The ileum follows the duodenum... and colon Colon (anatomy) The colon is the last part of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body, and is the site in which flora-aided fermentation of unabsorbed material occurs. Unlike the small intestine, the colon does not play a... |
| Contact dermatitis Contact dermatitis Contact dermatitis is a term for a skin reaction resulting from exposure to allergens or irritants . Phototoxic dermatitis occurs when the allergen or irritant is activated by sunlight.... |
Environmental chemicals, e.g. poison ivy, nickel Nickel Nickel is a chemical element with the chemical symbol Ni and atomic number 28. It is a silvery-white lustrous metal with a slight golden tinge. Nickel belongs to the transition metals and is hard and ductile... |
Dermatitis -Etymology:Dermatitis derives from Greek derma "skin" + -itis "inflammation" and genetic disorder.-Terminology:There are several different types of dermatitis. The different kinds usually have in common an allergic reaction to specific allergens. The term may describe eczema, which is also called... with usually short-lived itching |
| Mantoux test Mantoux test The Mantoux test is a diagnostic tool for tuberculosis. It is one of the two major tuberculin skin tests used in the world, largely replacing multiple-puncture tests such as the Tine test... |
Tuberculin Tuberculin Tuberculin is the name given to extracts of Mycobacterium tuberculosis, M. bovis, or M. avium that is used in skin testing in animals and humans to identify a tuberculosis infection. Several types of tuberculin have been used for this, of which purified protein derivative is the most important.... |
Tuberculosis Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body... exposure |
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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
Lysosome
thumb|350px|Schematic of typical animal cell, showing subcellular components. [[Organelle]]s: [[nucleoli]] [[cell nucleus|nucleus]] [[ribosomes]] [[vesicle |vesicle]] rough [[endoplasmic reticulum]]...
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:
- Temporal arteritisTemporal arteritisGiant-cell arteritis or Horton disease is an inflammatory disease of blood vessels most commonly involving large and medium arteries of the head...
- Hashimoto's thyroiditisHashimoto's thyroiditisHashimoto's thyroiditis or chronic lymphocytic thyroiditis is an autoimmune disease in which the thyroid gland is gradually destroyed by a variety of cell- and antibody-mediated immune processes. It was the first disease to be recognized as an autoimmune disease...
- Symptoms of leprosyLeprosyLeprosy or Hansen's disease is a chronic disease caused by the bacteria Mycobacterium leprae and Mycobacterium lepromatosis. Named after physician Gerhard Armauer Hansen, leprosy is primarily a granulomatous disease of the peripheral nerves and mucosa of the upper respiratory tract; skin lesions...
- Symptoms of tuberculosisTuberculosisTuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...
- Coeliac diseaseCoeliac diseaseCoeliac disease , is an autoimmune disorder of the small intestine that occurs in genetically predisposed people of all ages from middle infancy onward...
- Graft-versus-host diseaseGraft-versus-host diseaseGraft-versus-host disease is a common complication after a stem cell transplant or bone marrow transplant from another person . Immune cells in the donated marrow or stem cells recognize the recipient as "foreign". The transplanted immune cells then attack the host's body cells...
- Chronic transplant rejection