Type IV Hypersensitivity reaction and it’s mechanism

Type IV hypersensitivity reaction result from inappropriate T-cell activation. It takes at least 3 days to develop its action for this reason it is also called delayed type hypersensitivity (DTH). It is the only hypersensitivity category, that is purely cell mediated rather than antibody mediated.

Mentioned disorders: Contact dermatitis, Chronic transplant rejection, Multiple sclerosis, Granuloma annulare etc.

Mediators: This delayed type of hypersensitivity reaction is mediated by T-helper cells. T-helper1 cell plays the kay role and also helped by some other cells like T-helper17, T-helper2 and cytotoxic T-cell.

Mechanism of reaction: Type IV or delayed type hypersensitivity reaction has two phases of action. These are – A. Sensitization phase, B. Effector phase.

  • Sensitization phase: A DTH response begins with the initial sensitization by the antigens (peptide derived from the intracellular pathogen) followed period at least 1 to 2 weeks. The antigen MHC-II complex is expressed on the surface of antigen presenting cells (APC) including Langerhans cells (dendritic cell), macrophages etc, which further activated the specific T-cell. In this sensitization phase, after the initial contact with the antigen, the helper-T cells start to proliferate and differentiates into T-helper1 cell. After activation the T-helper1 cell secretes some cytokines.
  • Effector phase: This phase of classical delayed type hypersensitivity reaction is induced by the second exposure to the specific sensitizing antigen. After the second exposure the memory T-cells start to secrete a variety of cytokines and chemokines such as interferons. They recruit and activate the macrophages, neutrophils and other inflammatory cells and enhance the activity of T-helper1 cells, amplifying the response. It causes the inflammatory response and ultimately can lead to tissue damage.

As a result of the phagocytic activity the lytic enzymes, from the macrophages in the area of the infection lead to a non-specific destruction to the cells and thus of any intracellular pathogen, such as Mycobacteria. Usually the presented pathogen is cleared rapidly with little tissue damage. But in some cases, and especially, if the antigen is not easily cleared then a prolonged DTH response can develop, which become destructive to the host and causing a visible granulomatous-reaction.

The presence of type IV or delayed type hypersensitivity reaction can be measured by skin test.

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