Type IV Hypersensitivity

2.1.9 – Type IV Hypersensitivity

Watch the video Type IV Hypersensitivity

Type IV hypersensitivity is the only one of the four hypersensitivity reactions that is carried by the cell mediated immune system (aka cytotoxic T-cells). The other three hypersensitivities are mediated by humoral immunity and involve antibodies. Cell mediated immunity is the principal mechanism used by the body to fight several microorganisms including viruses, tuberculosis bacteria, fungi, protozoa, and parasites. It can also lead to tissue injury as it responds to some chemicals and even self-antigens (autoimmunity).

Type 4 hypersensitivity reactions can be divided into two basic responses:

1. Direct Cell-Mediated Cytotoxicity

In this response, cytotoxic T lymphocytes (CTLs) bind to antigens expressed by cells on their MHC I glycoproteins. This binding results in the release of granzymes and perforins via degranulation of the CTL. The target cell becomes punctured by the perforins. The granzymes can then enter the target cell. Granzymes are proteases that damage intracellular proteins in the target cell and activate apoptotic pathways to induce a programmed cell death. Activated CTLs also express what is known as a Fas ligand that is similar to TNF-alpha. This Fas ligand binds to Fas receptors located on the target cells to activate apoptotic pathways. An example of this direct cell-mediated cytotoxicity is type 1 diabetes where cytotoxic T-cells target insulin secreting beta cells of the pancreas. Another example is graft rejections where cytotoxic T-cells target foreign grafted tissues.

2. Delayed Hypersensitivity

Delayed hypersensitivity is a delayed immune reaction that involves immune cells but not antibodies. It is referred to as delayed because it takes 24-72 hours to have a peak in the response. This is due to the fact that the effector cells of the reaction have to be recruited and accumulate near the area that antigen is discovered and then make cytokines involved in immune signaling. This long setup is why we refer to this response as delayed type hypersensitivity or DTH. Here are some examples of this type of hypersensitivity:

***Please note that “Farmer’s Lung” or hypersensitivity pneumonitis is also frequently referred to as a type III hypersensitivity. It appears that individuals can form antibodies against the moldy hay allergens that are inhaled and these antibodies can sometimes precipitate and create complexes that can trigger the complement cascade and create inflammation in various tissues.

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