Type IV hypersensitivity

Type IV hypersensitivity
Classification and external resources
MeSH	D006968

Type 4 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.

CD4+ helper T cells recognize antigen in a complex with Class II major histocompatibility complex. The antigen-presenting cells in this case are macrophages that secrete IL-12, which stimulates the proliferation of further CD4+ T_h1 cells. CD4+ T cells secrete IL-2 and interferon gamma, further inducing the release of other T_h1 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.

Examples

Disease	Target antigen	Effects
Diabetes mellitus type 1	Pancreatic beta cell proteins (possibly insulin, Glutamate decarboxylase)	Insulitis Beta cell destruction
Multiple sclerosis	Oligodendrocyte proteins (myelin basic protein, proteolipid protein)	Demyelinating disease Perivascular inflammation Paralysis Ocular lesions
Some peripheral neuropathies	Schwann cell antigen	Neuritis Paralysis
Hashimoto's Thyroiditis	Thyroglobulin antigen	Hypothyroidism Hard goiter Follicular thymitis
Crohn's disease	Unknown	Chronic inflammation of ileum and colon
Allergic contact dermatitis	Environmental chemicals, e.g. poison ivy, nickel	Dermatitis with usually short-lived itching
Mantoux test* (diagnostic)	Tuberculin	Skin induration indicates TB exposure
Unless else specified in boxes, then ref is:^[1] * - Mantoux test not taken from ^[1]

An example of a TB infection that came under control: M. tuberculosis are engulfed by macrophages 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 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. However 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:

References

1 2 Table 5-5 in: Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson. Robbins Basic Pathology. Philadelphia: Saunders. ISBN 1-4160-2973-7. 8th edition.
↑ "eMedicine - Hypersensitivity Reactions, Delayed : Article by Walter Duane Hinshaw".

Hypersensitivity and autoimmune diseases (279.5–6)

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's 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's syndrome Autoimmune hepatitis Autoimmune polyendocrine syndrome APS1 APS2 Autoimmune adrenalitis Systemic autoimmune disease

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Type IV hypersensitivity

Examples

See also

References