The key distinction of Type IV Hypersensitivity Reactions is their mediation by T cells, rather than antibodies which mediate the first three types of hypersensitivities. These reactions consist of two phases: the sensitization phase and the elicitation phase. During sensitization, an antigen presenting cell, such as a macrophage, presents a newly encountered antigen to CD4+ and CD8+ T cells. These T cells become familiar or sensitized to this antigen.
Upon repeated exposure, the elicitation phase ensues. Here, CD4+ T cells release inflammatory mediators like interferon gamma in response to the recognized antigen, while CD8+ T cells directly target and kill the offending cells. Type IV Hypersensitivity is also called a delayed reaction because T cells need repeated contact with the antigen before instigating their immune response. Moreover, different forms of pathologies associated with Type IV Hypersensitivity include contact dermatitis (e.g., poison ivy exposure), tuberculin type hypersensitivity, granulomatous type hypersensitivity (e.g., sarcoidosis), and acute transplant rejection. This reaction type uniquely involves pathogens like the Th17 cell, which secretes IL-17 and recruits neutrophils, causing further inflammation. The differentiation in the timing of hypersensitivity reactions is crucial as tests can often cause confusion between, for instance, acute transplant rejection (Type IV) which occurs weeks to months after transplant, and hyperacute transplant rejection (Type II), developing within hours.
Type IV Hypersensitivity Reaction, also known as cell-mediated or delayed hypersensitivity, is a response mediated by T cells and primarily occurs through the sensitization and elicitation phases. Unlike the other hypersensitivity reactions which are immediate and antibody-mediated, Type IV Hypersensitivity Reaction generally takes 48-72 hours to develop and is orchestrated by specific T cells rather than antibodies.
CD4+ T cells, also known as T helper cells, mobilize the immune response. When they encounter an antigen presented by an antigen-presenting cell (APC), they release cytokines, such as interferon gamma, to stimulate macrophages or B cells. CD8+ T cells, also known as cytotoxic T cells, can directly kill host cells that are infected with pathogens. In the context of a Type IV hypersensitivity reaction, these T cells respond to the antigens and mediate the inflammatory response.
The sensitization phase in a Type IV hypersensitivity reaction is the initial phase where T cells are primed to react to a specific antigen. During this phase, the antigen is captured by antigen presenting cells, processed and presented to CD4+ T cells. The subsequent proliferation and differentiation of these T cells into memory T cells set the stage for the elicitation phase, should the body encounter the antigen again.
In contact dermatitis, allergens penetrate the skin and are picked up by antigen presenting cells, which activate T cells and trigger a Type IV hypersensitivity reaction. This results in an inflammatory reaction in the skin. In acute transplant rejection, the donated organ is seen as foreign by the recipient's immune system. The organ's cells are then targeted by T cells, leading to tissue damage and possibly rejection of the transplant, characterizing a Type IV hypersensitivity reaction.
The tuberculin skin test, used to diagnose tuberculosis, is a classic example of a Type IV hypersensitivity reaction. The test involves injecting a purified protein derivative of the TB bacteria into the skin. If a person has been exposed to TB, their immune system will recognize the antigen, leading to a delayed, but a strong immune response involving T cells and resulting in a visible swelling at the site of injection. This immunological response is characteristic of a Type IV hypersensitivity reaction.