Hypersensitivity: Type 4

00:01 And then the final type of hypersensitivity, Type IV hypersensitivity - delayed type (T-cell mediated).

00:11 Some examples here of type IV hypersensitivity reactions - the tuberculin reaction, contact dermatitis, Hashimoto’s thyroiditis, multiple sclerosis, type I diabetes, Guillain-Barre syndrome, celiac disease and Crohn’s disease.

00:33 Here we have a cytokine-mediated inflammation causing tissue injury and cell death.

00:40 Antigen presenting cells in the tissues activate CD4+ T-cells.

00:46 This causes them to release cytokines.

00:49 And these cytokines can be involved in the activation of cytotoxic CD8+ T-cells.

00:56 And this can result in inflammation and tissue injury.

01:01 T-cell mediated cytotoxicity by the CD8+ cytotoxic T-lymphocytes can kill our own cells, and again tissue injury is the result.

01:18 The T-cell activation that occurs in type IV hypersensitivity stimulates both macrophages and fibroblasts.

01:27 Dendritic cells can release the cytokine interleukin-12 which is involved in the activation of the Th1 subset of helper T-cells.

01:38 These helper T-cells characteristically produce interleukin-2, which leads to the generation of more Th1 cells. Gamma interferon, another characteristic cytokine of Th1 cells can activate macrophages. In the presence of a persistent stimulus, for example a Mycobacterial infection or an infection with Schistosoma, these macrophages are continually activated and they can end up increasing largely in size. And sometimes they fuse together to form what are called giant cells. And the Th1 cells can also activate fibroblasts leading to angiogenesis and fibrosis.

02:29 One of the characteristic features of type IV hypersensitivity is the generation of structures that are called granuloma. This results from the activation of Th1 cells, and the production of pro-inflammatory cytokines such as tumor necrosis factor and interferon gamma. The result is that monocytes are recruited from the blood circulation into the tissues. And there is a massive activation of macrophages. Some of these fuse as we’ve already heard to form giant cells. This structure becomes surrounded by fibroblasts that are also Th1 lymphocytes within this structure. And this structure can end up damaging the local tissue.