Type IV hypersensitivity: delayed T-cell mediated reactions

Type IV hypersensitivity is also called delayed-type hypersensitivity. It is not driven by antibodies. It is mediated by T cells, and the antigen, the molecule that triggers the response, can be environmental or infectious.

The first exposure is called sensitisation. During it, T cells become primed to recognise a particular antigen, and memory T cells are left behind. On later exposure, these memory T cells recognise the antigen. Helper T cells coordinate the response and release cytokines (small signalling proteins) that call in macrophages and other immune cells. Cytotoxic T cells can also damage tissue, because they kill target cells directly.

Gathering and activating cells takes time, so the reaction appears hours to days after exposure. In type I allergy, by contrast, symptoms appear within minutes. In skin reactions such as contact dermatitis, the result of type IV is local inflammation, with redness, swelling and often induration, a firm thickening of the tissue.

Nickel, a metal found in costume jewellery, gives a familiar example. In allergic contact dermatitis to nickel, itch, redness and swelling appear hours to days after contact as a localised rash on the skin that touched the metal. The tuberculin (Mantoux) skin test works in the same way. It injects a little purified protein from the tuberculosis bacterium into the skin. In someone already sensitised to the bacterium, nothing happens immediately, then redness, swelling and induration develop over a day or two.