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Type IV hypersensitivity

Type of allergic reaction


Type of allergic reaction

FieldValue
nameType IV hypersensitivity
synonymsdelayed-type hypersensitivity; DTH; cell-mediated hypersensitivity

| Type IV hypersensitivity, in the Gell and Coombs classification of allergic reactions, often called delayed-type hypersensitivity, is a type of hypersensitivity reaction that can take a day or more to develop. Unlike the other types, it is not humoral (not antibody-mediated) but rather is a type of cell-mediated response. This response involves the interaction of T cells, monocytes, and macrophages.

This reaction is caused when CD4+ Th1 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 (IFNγ), 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.

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

DiseaseTarget antigenEffects
Allergic contact dermatitisEnvironmental chemicals, like urushiol (from poison ivy and poison oak), metals (e.g. nickel), topical medicationepidermal necrosis, inflammation, skin rash, and blisters
Autoimmune myocarditisMyosin heavy chain proteinCardiomyopathy
Diabetes mellitus type 1Pancreatic beta cell proteins (possibly insulin, glutamate decarboxylase)Insulitis, beta cell destruction
title=Hypersensitivity reactionswebsite=microbiologybook.orgpublisher=University of South Carolina School of Medicine - Microbiology and Immunology On-lineurl=https://www.microbiologybook.org/ghaffar/hyper00.htmaccess-date=2016-05-29}}Various, depending on underlying diseaseWalled-off lesion containing macrophages and other cells
Some peripheral neuropathiesSchwann cell antigenNeuritis, paralysis
Hashimoto's thyroiditisThyroglobulin antigenHypothyroidism, hard goiter, follicular thymitis
title=Robbins Basic Pathologylast1=Kumarfirst1=Vinaylast2=Abbasfirst2=Abul K.last3=Asterfirst3=Jon C.date=2012-05-01publisher=Elsevier Health Sciencesisbn=978-1455737871url=https://books.google.com/books?id=jheBzf17C7YC}}Enteric microbiota and/or self antigensHyperactivation of T-cells, cytokine release, recruitment of macrophages and other immune cells, inflammation
Multiple sclerosisMyelin antigens (e.g., myelin basic protein)Myelin destruction, inflammation
Rheumatoid arthritisPossibly collagen and/or citrullinated self proteinsChronic arthritis, inflammation, destruction of articular cartilage and bone
Tuberculin reaction (Mantoux test)TuberculinInduration and erythema around injection site indicates previous exposure

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, TB bacteria 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, upon stimulation with interferon 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:

  • Urushiol-induced contact dermatitis
  • Chronic transplant rejection
  • Coeliac disease
  • Giant cell arteritis
  • Graft-versus-host disease
  • Leprosy

References

References

  1. (2011-11-10). "An introduction to immunology and immunopathology". Allergy, Asthma & Clinical Immunology.
  2. "Hypersensitivity reactions". University of South Carolina School of Medicine - Microbiology and Immunology On-line.
  3. (2012-05-01). "Robbins Basic Pathology". Elsevier Health Sciences.
  4. (July 1993). "Pathogenesis of tuberculosis: interaction of Mycobacterium tuberculosis with macrophages". Infect. Immun..
  5. Marwa, K. (2021-01-01). "StatPearls". StatPearls Publishing.
  6. Walter Duane Hinshaw. (26 June 2021). "eMedicine - Hypersensitivity Reactions, Delayed".
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