4/26/2019 Type IV hypersensitivity - Wikipedia

Type IV hypersensitivity
Type 4 hypersensitivity is often called delayed type hypersensitivity as
Type IV hypersensitivity
the reaction takes several days to develop. Unlike the other types, it is not
antibody-mediated but rather is a type of cell-mediated response. Specialty Immunology

CD4+ Th1 helper T cells recognize foreign antigen in a complex with the MHC class II on the surface of antigen-presenting
cells. These can be macrophages that secrete IL-12, which stimulates the proliferation of further CD4+ Th1 cells. CD4+ T
cells secrete IL-2 and interferon gamma, inducing the further 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.

Contents
Examples
See also
References
External links

Examples

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Disease Target antigen Effects

Allergic Environmental chemicals, like urushiol (from
epidermal necrosis, inflammation, skin rash, and
contact poison ivy and poison oak), metals (e.g. nickel),
blisters
dermatitis[1] topical medication

autoimmune
Myosin heavy chain protein Cardiomyopathy
myocarditis[1]
Diabetes
Pancreatic beta cell proteins (possibly insulin,
mellitus type Insulitis, beta cell destruction
glutamate decarboxylase)
1[1]
Walled off lesion containing macrophages and
Granulomas[2] Various, depending on underlying disease
other cells
Some
peripheral Schwann cell antigen Neuritis, paralysis
neuropathies
Hashimoto's
Thyroglobulin antigen Hypothyroidism, hard goiter, follicular thymitis
thyroiditis[1]
Inflammatory Hyperactivation of T-cells, cytokine release,
bowel Enteric microbiota and/or self antigens recruitment of macrophages and other immune
disease[1] cells, inflammation

Multiple
Myelin antigens (e.g., myelin basic protein) Myelin destruction, inflammation
sclerosis[1]
Rheumatoid Possibly collagen and/or citrullinated self Chronic arthritis, inflammation, destruction of
arthritis[1] proteins articular cartilage and bone

Tuberculin
reaction Induration and erythema around injection site
Tuberculin
(Mantoux indicates previous exposure
test)[3]

An example of a tuberculosis (TB) infection that comes under control: M. tuberculosis cells are engulfed by macrophages
after being identified as foreign, but due to an immuno-escape mechanism peculiar to mycobacteria,[4] 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. The hyper-activated macrophages secrete TNF-α which recruits
multiple monocytes to the site of infection. These cells differentiate into epithelioid cells which wall off the infected cells,
but results in significant inflammation and local damage.

Some other clinical examples:

Temporal arteritis
Leprosy
Coeliac disease
Graft-versus-host disease[5]
Chronic transplant rejection

See also
Type I hypersensitivity
Type II hypersensitivity

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Type III hypersensitivity

Type V hypersensitivity

References
1. Kumar, Vinay; Abbas, Abul K.; Aster, Jon C. (2012-05-01). Robbins Basic Pathology (https://books.google.com/book
s?id=jheBzf17C7YC). Elsevier Health Sciences. ISBN 1455737879.
2. "Hypersensitivity reactions" (http://www.microbiologybook.org/ghaffar/hyper00.htm). www.microbiologybook.org.
University of South Carolina School of Medicine - Microbiology and Immunology On-line. Retrieved 2016-05-29.
3. "Hypersensitivity reactions" (http://www.microbiologybook.org/ghaffar/hyper00.htm). www.microbiologybook.org.
Retrieved 2016-05-29.
4. McDonough, K.; Kress, Y.; Bloom, B. R. (July 1993). "Pathogenesis of tuberculosis: interaction of Mycobacterium
tuberculosis with macrophages" (http://iai.asm.org/content/61/7/2763.abstract). Infect. Immun. 61 (7): 2763–2773.
eISSN 1098-5522 (https://www.worldcat.org/issn/1098-5522). ISSN 0019-9567 (https://www.worldcat.org/issn/0019-9
567). Retrieved 18 June 2017.
5. "eMedicine - Hypersensitivity Reactions, Delayed : Article by Walter Duane Hinshaw" (http://www.emedicine.com/ME
D/topic1100.htm).

External links
Classification MeSH: D006968 D
(https://www.nlm.ni
h.gov/cgi/mesh/201
5/MB_cgi?field=uid
&term=D006968)

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