Type IV hypersensitivity (cell-mediated) – causes, symptoms, treatment & pathology

What is type IV hypersensitivity? Type IV hypersensitivity is a T-cell-mediated hypersensitivity, meaning the inflammation and potential tissue damage is caused by either T helper cells (CD4+) or cytotoxic T cells (CD8+).

This video covers the pathophysiology, symptoms, and several examples, including contact dermatitis as with poison ivy, as well as several other systemic diseases.

Hypersensitivity occurs when an immune reaction harms the body instead of healing or protecting it. The fourth type of hypersensitivity is caused by T cells, so it is sometimes referred to as T cell mediated hypersensitivity.

T cells are named for the thymus, where they are created. There are two types of T cells: CD4 positive helper cells and CD8 killer cells. Killer T cells are cytotoxic toward specific targets. Helper T cells release cytokines, which are capable of stimulating or inhibiting other cells. Helper T cells coordinate the other immune cells around them.

Until the T cell receptor binds with a target antigen, both types of T cells are referred to as naïve cells. Let’s follow the process of a type four hypersensitive reaction, using poison ivy as the triggering antigen.

Urushiol, the chemical present in poison ivy, makes contact with the skin and quickly makes its way through the epidermis and dermis. It combines with proteins and is then picked up by a dendritic cell, which then takes it to a lymph node. The dendric cell presents the urushiol on its surface for T cells to examine. A T cell recognizes the antigen and binds to it. At this point, the dendric cell releases interleukins that turn the naïve T cell into a helper T cell. The newly activated helper T cell then releases interleukin two and interferon gamma, which activates phagocytes and creates more helper T cells. The activated phagocytes release pro-inflammatory cytokines, which causes leaking in cell barriers and allows more immune cells to enter the area. The process leads to localized swelling, redness, and warmth, as well as a fever.

The activated macrophages release lysosomal enzymes, complement components, and reactivated oxygen species to the area, which cause damage to the tissue. In the example of poison ivy, the resulting condition is called dermatitis.

Another example of a type four hypersensitivity reaction may occur during a tuberculin skin test, during which bacteria involved in tuberculosis is injected into the skin. If the person has previously been exposed to tuberculosis, TB specific helper T cells will respond to the injection site and create an inflammatory response. The skin thickens, signaling a positive test result. This process may take 48 to 72 hours, and is referred to as delayed hypersensitivity.

Type four hypersensitivity is also involved in systemic diseases like rheumatoid arthritis, in which helper T cells cause inflammation to the joints, and multiple sclerosis, in which helper T cells damage the myelin surrounding nerve fibers. In a patient with inflammatory bowel disease, the helper T cells cause inflammation in the lining of the intestine.

The type of helper T cells created in a type four reaction depend on the cytokines secreted by the dendritic cells.

During a type four reaction, damage may also be caused by killer T cells. Killer T cells target antigens that are presented on MHC molecules. These molecules are present on all nucleated cells of the body. MHC molecules present antigens from inside the cell. If the cell is infected or mutated, such as in the case of infection or cancer, the killer T cell binds to the molecule and releases perforin. The perforin forms pores in the target cell, allowing granzymes to enter and induce apoptosis.

Other examples of this type of reaction include type one diabetes, in which killer T cells attack pancreas islet cells, and Hashimoto’s diseases, in which the killer T cells attack epithelial cells in the thyroid.