This type of hypersensitive (allegic) reaction occurs when an antigen interacts with antigen-specific lymphocytes that release inflammatory and toxic substances, which attract other white blood cells and results in tissue injury.

In type IV hypersensitivity, CD8 cytotoxic T-cells and CD4 helper T-cells recognize either intracellular or extracellular synthesized antigen when it is complexed with class I or class II MHC molecules, respectively. Macrophages function as antigen-presenting cells and release interleukin-1 , which promotes the proliferation of helper T-cells. Helper T-cells release interferon -gamma and interleukin-2 , which together regulate delayed hypersensitivity reactions centered around macrophage activation and T-cell mediated immunity.

Three examples of Type IV reaction :

• Contact Hypersensitivity is characterized by a reaction at the site of contact with the allergen (cf. contact dermatitis ). It is an epidermal response most often elicited by small molecules called haptens. The cell involved in antigen presentation at this site is the Langerhans cell . The pathway from initial exposure involves sensitization (with Langerhans cells presenting Ag to CD4+ helper T-cells) and exposure , followed by aggregation of mononuclear cells around blood vessels and glands in the epidermis and edema . A variety of cytokines are involved in this process, including IL-2, IL-3, IFN and GM-CSF. The reaction decreases 48-72 hours following exposure.

• Tuberculin Hypersensitivity . This response was first observed when soluble antigens from organisms such as mycobacteria were administered subcutaneously. In these individuals fever, general unwellness, plus an area of red, hard swelling was observed. The skin test for Tuberculosis is of this nature. This reaction is induced by a series of cellular migrations and activations :
  1. T-cell migration from capillaries.
  2. Disruption of collagen in dermis.
  3. Macrophage infiltration.
  4. Lymphocytes and macrophages express HLA-DR.
  5. Granulomatous appearance, no edema, self-limiting.

• Granulomatous Hypersensitivity . This type of reaction is characterized by persistance of the antigen within macrophages as well as of the lesion. Such antigens are particulate matter such as talc and silica but also mycobacteria. The characteristic cells found in the lesion are epitheloid cells (probably macrophages) and giant-cells (multi-nucleated macrophages). The granuloma consists of a hard core of cells sometimes with a necrotic core. This is surrounded by lymphocytes with a deposition of collagen fibres.