Delayed-type hypersensitivity (DTH) - Type IV hypersensitivity, Mechanism, Significance, Etiology

Introduction to Delayed-type hypersensitivity (DTH)

Delayed-type hypersensitivity (DTH), also known as type IV hypersensitivity, is a type of hypersensitivity reaction that takes one or more days to develop. This is an exaggerated cell-mediated response that is induced by certain antigens (allergens) resulting in contact dermatitis. It involves the interaction of T-cells, monocytes, and macrophages.

Delayed-type hypersensitivity (DTH) occurs more than 12 hours after exposure to certain allergens – with maximal reaction time between 48 and 72 hours.

Delayed-type hypersensitivity (DTH) is not a response of the humoral immune system (not antibody mediated). According to Gell and Coombs's classification of allergic reactions, the first three types of hypersensitivity reactions are immediate hypersensitivity reactions as they occur within 24 hours.

Mechanism of Delayed-type hypersensitivity (DTH)

Delayed-type hypersensitivity (DTH) is caused when CD4+ Th1 cells (a type of T-cell), recognize exogenous or endogenous antigens in a complex with the MHC class II on the surface of antigen-presenting cells (APC). APC such as macrophages stimulates the proliferation of further CD4+ Th1 cells and can secrete Interleukin-12 (IL-12).

Further on, CD4+ T cells secrete interferon-gamma (IFNγ) and IL-2 which further secretes the release of other Th1 cytokines. Thus, the host immune response is mediated.

The activated CD8+ T cells destroy target cells on contact. Activated macrophages, on the other hand, produce hydrolytic enzymes which when presented with certain intracellular pathogens, result in the formation of multinucleated giant cells.

Hence, the overproduction of cytokines and overreaction of the helper T cells results in inflammation and cell death. The resulting conditions of Delayed-type hypersensitivity (DTH) include contact dermatitis and drug hypersensitivity

In certain cases, monocytes, eosinophils, and neutrophils can be involved in Delayed-type hypersensitivity (DTH). Depending upon the type of T cell (CD4 T-helper type 1 and type 2 cells) involved and the cytokines/chemokines produced, Delayed-type hypersensitivity (DTH) is subdivided into type IVa, IVb, IVc, and Ivd.

Significance of Delayed-type hypersensitivity (DTH)

Delayed-type hypersensitivity (DTH) plays a crucial role in the body’s immune system. It fights against intracellular pathogens such as fungi, and mycobacteria and has a principle role in tumor immunity and transplant rejection.

In patients with acquired immunodeficiency syndrome (AIDS), due to a progressive decline in the number of CD4 cells, a defective type IV hypersensitivity occurs.

Etiology of Delayed-type hypersensitivity (DTH)

A dysfunctional Delayed-type hypersensitivity (DTH) can result in multiple opportunistic infections.

Poison ivy as an allergen can result in contact dermatitis.

Drugs such as antibiotics and anticonvulsants can lead to drug hypersensitivity.

Certain viral infections when exposed to certain drugs can cause Delayed-type hypersensitivity (DTH). Eg: Epstein Barr virus with amoxicillin, cytomegalovirus with antibiotics, herpesvirus 6 with anticonvulsants. 

Drugs such as lamotrigine and allopurinol and materials such as latex have caused Delayed-type hypersensitivity (DTH).