Type IV hypersensitivity

Other names: Delayed type hypersensitivity
Video explanation

Type IV hypersensitivity is often called delayed type hypersensitivity as the reaction takes several days to develop.[1] Unlike the other types, it is 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 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.

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.[1]

## Contents

* 1 Forms
* 2 See also
* 3 References
* 4 External links

## Forms[edit | edit source]

Disease | Target antigen | Effects

|
|

Allergic contact dermatitis[2] | Environmental chemicals, like urushiol (from poison ivy and poison oak), metals (e.g. nickel), topical medication  | epidermal necrosis, inflammation, skin rash, and blisters
Autoimmune myocarditis[2] | Myosin heavy chain protein  | Cardiomyopathy
Diabetes mellitus type 1[2] | Pancreatic beta cell proteins (possibly insulin, glutamate decarboxylase)  | Insulitis, beta cell destruction
Granulomas[3] | Various, depending on underlying disease  | Walled off lesion containing macrophages and other cells
Some peripheral neuropathies | Schwann cell antigen  | Neuritis, paralysis
Hashimoto's thyroiditis[2] | Thyroglobulin antigen  | Hypothyroidism, hard goiter, follicular thymitis
Inflammatory bowel disease[2] | Enteric microbiota and/or self antigens  | Hyperactivation of T-cells, cytokine release, recruitment of macrophages and other immune cells, inflammation
Multiple sclerosis[2] | Myelin antigens (e.g., myelin basic protein)  | Myelin destruction, inflammation
Rheumatoid arthritis[2] | Possibly collagen and/or citrullinated self proteins  | Chronic arthritis, inflammation, destruction of articular cartilage and bone
Tuberculin reaction (Mantoux test)[4] | Tuberculin  | Induration 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,[5] 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[6]
* Chronic transplant rejection

## See also[edit | edit source]

* Hypersensitivity
* Type I hypersensitivity
* Type II hypersensitivity
* Type III hypersensitivity
* Type V hypersensitivity

## References[edit | edit source]

1. ↑ 1.0 1.1 Warrington, Richard; Watson, Wade; Kim, Harold L.; Antonetti, Francesca Romana (10 November 2011). "An introduction to immunology and immunopathology". Allergy, Asthma & Clinical Immunology. 7 (1): S1. doi:10.1186/1710-1492-7-S1-S1. ISSN 1710-1492. PMC 3245432. PMID 22165815.
2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 Kumar, Vinay; Abbas, Abul K.; Aster, Jon C. (1 May 2012). Robbins Basic Pathology. Elsevier Health Sciences. ISBN 978-1455737871.
3. ↑ "Hypersensitivity reactions". www.microbiologybook.org. University of South Carolina School of Medicine - Microbiology and Immunology On-line. Archived from the original on 26 May 2016. Retrieved 29 May 2016.
4. ↑ "Hypersensitivity reactions". www.microbiologybook.org. Archived from the original on 26 May 2016. Retrieved 29 May 2016.
5. ↑ McDonough, K.; Kress, Y.; Bloom, B. R. (July 1993). "Pathogenesis of tuberculosis: interaction of Mycobacterium tuberculosis with macrophages". Infect. Immun. 61 (7): 2763–2773. eISSN 1098-5522. ISSN 0019-9567. Archived from the original on 29 August 2021. Retrieved 18 June 2017.
6. ↑ "eMedicine - Hypersensitivity Reactions, Delayed : Article by Walter Duane Hinshaw". Archived from the original on 15 September 2008.

## External links[edit | edit source]

Classification|

* MeSH: D006968

|

* v
* t
* e

Hypersensitivity and autoimmune diseases

Type I/allergy/atopy
(IgE)|

| Foreign|

* Atopic eczema
* Allergic urticaria
* Allergic rhinitis (Hay fever)
* Allergic asthma
* Anaphylaxis
* Food allergy
* common allergies include: Milk
* Egg
* Peanut
* Tree nut
* Seafood
* Soy
* Wheat
* Penicillin allergy

|

Autoimmune|

* Eosinophilic esophagitis

Type II/ADCC

*     * IgM
* IgG

| Foreign|

* Hemolytic disease of the newborn

|

Autoimmune|

| Cytotoxic|

* Autoimmune hemolytic anemia
* Immune thrombocytopenic purpura
* Bullous pemphigoid
* Pemphigus vulgaris
* Rheumatic fever
* Goodpasture syndrome
* Guillain–Barré syndrome

|

"Type V"/receptor|

* Graves' disease
* Myasthenia gravis
* Pernicious anemia

Type III
(Immune complex)|

| Foreign|

* Henoch–Schönlein purpura
* Hypersensitivity vasculitis
* Reactive arthritis
* Farmer's lung
* Post-streptococcal glomerulonephritis
* Serum sickness
* Arthus reaction

|

Autoimmune|

* Systemic lupus erythematosus
* Subacute bacterial endocarditis
* Rheumatoid arthritis

Type IV/cell-mediated
(T cells)|

| Foreign|

* Allergic contact dermatitis
* Mantoux test

|

Autoimmune|

* Diabetes mellitus type 1
* Hashimoto's thyroiditis
* Multiple sclerosis
* Coeliac disease
* Giant-cell arteritis
* Postorgasmic illness syndrome
* Reactive arthritis

GVHD|

* Transfusion-associated graft versus host disease

Unknown/
multiple|

| Foreign|

* Hypersensitivity pneumonitis
* Allergic bronchopulmonary aspergillosis
* Transplant rejection
* Latex allergy (I+IV)

|

Autoimmune|

* Sjögren syndrome
* Autoimmune hepatitis
* Autoimmune polyendocrine syndrome
* APS1
* APS2
* Autoimmune adrenalitis
* Systemic autoimmune disease

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