Let's discuss the mechanisms of a type 4 hypersensitivity reaction. In watching the previous videos discussing types 1, 2, and 3 hypersensitivity, you may have noticed that all three of these types involved antibodies. For this reason, they are classified as humoral-mediated responses. In contrast, a type 4 hypersensitivity reaction does not involve antibodies and is therefore not a humoral-mediated response.
It is a T-cell-mediated response. This is because a type 4 hypersensitivity reaction involves T helper cells and or cytotoxic T cells. To visualize the case of the T helper cells, let's assume for a moment you're out camping.
It's nighttime and the campfire's out and you're sleeping in your tent. When you hear a strange rustling noise outside, you're brave. So you grab a flashlight and go out to investigate.
It's dark. You follow the noise out away from your tent. and land the light on a squirrel, it dashes off as you grumble quietly to yourself.
You start making your way back to your tent, but realize you've walked right into a patch of poison ivy. Everyone knows poison ivy causes a rash or reaction in the skin. Please realize this is a type 4 hypersensitivity reaction. Poison ivy contains a compound known as urushayl, which binds with proteins in the skin and alters the proteins. The immune system now recognizes these changed proteins as foreign.
These immunogens are recognized and processed by an antigen-presenting cell, or APC, and presented to a naive T helper cell. The APC will present a portion of the protein using an MHC class II receptor, which T helper cells are able to recognize and bind to. After binding of the APC to the T helper cell, the APC will release cytokines.
that cause the naive T helper cell to differentiate. If the APC releases certain cytokines, including IL-12, then the naive T helper cell will differentiate into a type 1 T helper cell, known as a Th1 cell. The Th1 cell will then release several cytokines, including IFN-gamma, which activates macrophages.
The activated macrophages will release IL-1 and TNF-alpha, which cause expression of receptors on endothelial cells to recruit more leukocytes to the area. Activated macrophages perform phagocytosis and release reactive oxygen species and toxic lysosomal enzymes that cause the tissue damage that manifests itself after exposure to poison ivy. The APC may also release IL-6 and other cytokines that cause naive T helper cells to differentiate into a subtype of T helper cells known as TH17. A TH17 cell will then release IL17 that activates neutrophils that then cause similar inflammatory actions as were caused by the macrophages. Let's remember that a type 4 hypersensitive reaction is cell-mediated and thus takes more time to develop than other hypersensitivity types.
This is because the T cells must be activated and recruited to cause the response. As is known to occur after coming in contact with poison ivy, one can develop a rash known as vesicular dermatitis within 24 to 72 hours. For these reasons, a type 4 hypersensitive reaction may also be referred to as delayed type hypersensitivity, or DTH.
Another clinical example of DTH is type 4 reaction that can result from tuberculosis. or a TB skin test. TB skin tests are administered to determine whether or not a patient has been infected with mycobacterium tuberculosis. Protein components of the bacteria are injected into the skin, and if the patient has been previously infected by the tuberculosis bacterium, the immune system will attack the injected protein components by way of the type 4 mechanism just described.
A positive test So it shows a significantly raised lesion at the site of injection that forms within hours and sometimes days. Other important type 4 hypersensitive reactions include contact dermatitis resulting from metal allergies, like wearing nickel jewelry, as well as contact dermatitis in susceptible individuals after exposure to latex. Type 4 hypersensory reactions can also involve cytotoxic T cells, which attack target cells directly. Examples include type 1 diabetes, where cytotoxic T cells target insulin-secreting beta cells of the pancreas. Rheumatoid arthritis, also, where the cytotoxic T cells target joint tissue.
Hashimoto's disease, where cytotoxic T cells attack thyroid hormone-producing follicular cells. And also in graft rejection, where cytotoxic T cells target foreign grafted cells. In these cases, target cells are recognized by cytotoxic T cells, which then release a vesicle.
containing a perforin-granzime complex that the target cell takes in through endocytosis. The perforins then allow granzimes to be released from the complex. Remember that the granzimes are proteases that induce apoptosis, or programmed cell death, of the target cell. A cytotoxic T cell may also bind to a FAST receptor, expressed on a target cell utilizing a FAST ligand.
This mechanism also activates apoptotic cell death of the target cell. Now for some questions for review. Pause the video now to consider your answers. If you answered the following, you are correct.
Thanks for watching.