The Info List - Type IV Hypersensitivity

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Type 4 hypersensitivity is often called delayed type hypersensitivity as 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. CD4+ Th1 helper T cells recognize antigen in a complex with the MHC class II major histocompatibility complex 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. Examples[edit]

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Disease Target antigen Effects

Allergic contact dermatitis[1] 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[1] Myosin heavy chain
Myosin heavy chain
protein Cardiomyopathy

Diabetes mellitus type 1[1] Pancreatic beta cell proteins (possibly insulin, glutamate decarboxylase) Insulitis, beta cell destruction

Granulomas[2] Various, depending on underlying disease Walled off lesion containing macrophages and other cells

Some peripheral neuropathies Schwann cell
Schwann cell
antigen Neuritis, paralysis

Hashimoto's thyroiditis[1] Thyroglobulin
antigen Hypothyroidism, hard goiter, follicular thymitis

Inflammatory bowel disease[1] Enteric microbiota and/or self antigens Hyperactivation of T-cells, cytokine release, recruitment of macrophages and other immune cells, inflammation

Multiple sclerosis[1] Myelin
antigens (e.g., myelin basic protein) Myelin
destruction, inflammation

Rheumatoid arthritis[1] Possibly collagen and/or citrullinated self proteins Chronic arthritis, inflammation, destruction of articular cartilage and bone

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

An example of a tuberculosis (TB) infection that comes under control: M. tuberculosis
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
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[edit]

Type I hypersensitivity Type II hypersensitivity Type III hypersensitivity Type V hypersensitivity


^ a b c d e f g Kumar, Vinay; Abbas, Abul K.; Aster, Jon C. (2012-05-01). Robbins Basic Pathology. Elsevier Health Sciences. ISBN 1455737879.  ^ " Hypersensitivity reactions". www.microbiologybook.org. University of South Carolina School of Medicine - Microbiology and Immunology On-line. Retrieved 2016-05-29.  ^ " Hypersensitivity reactions". www.microbiologybook.org. Retrieved 2016-05-29.  ^ 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. Retrieved 18 June 2017.  ^ "eMedicine - Hypersensitivity Reactions, Delayed : Article by Walter Duane Hinshaw". 

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Hypersensitivity and autoimmune diseases (279.5–6)

Type I/allergy/atopy (IgE)


Atopic eczema Allergic urticaria Allergic rhinitis
Allergic rhinitis
(Hay fever) Allergic asthma Anaphylaxis Food allergy

common allergies include: Milk Egg Peanut Tree nut Seafood Soy Wheat

Penicillin allergy


Eosinophilic esophagitis




Hemolytic disease of the newborn



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)


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


Systemic lupus erythematosus Subacute bacterial endocarditis Rheumatoid arthritis

Type IV/cell-mediated (T cells)


Allergic contact dermatitis Mantoux test


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


Transfusion-associated graft versus host disease

Unknown/ multiple


Hypersensitivity pneumonitis

Allergic bronchopulmonary aspergillosis

Transplant rejection Latex allergy
Latex allergy


Sjögren syndrome Autoimmune hepatitis Autoimmune polyendocrine syndrome


Autoimmune adrenalitis Systemic autoim