Celiac Disease

00:01 Let’s now look at celiac disease, yet another example where autoimmune reactions result in pathology.

00:09 In celiac disease, there is T-cell reactivity to the gliadin component of wheat gluten in the small intestine.

00:17 Gluten that is absorbed from the gut is taken up by dendritic cells.

00:23 It is processed and presented to T-cells in the mesenteric lymph nodes.

00:30 The cytokine interleukin-15 stimulates dendritic cells to go on and activate proinflammatory T-helper cells which secrete IL-21 and gamma interferon.

00:44 There is an induction of gluten specific helper T-cells and B-cells.

00:50 The lymphocytes home to the gut lamina propria.

00:53 IL-15 also induces expression of the cytotoxicity-activating receptor NKG2D on CD8+ intraepithelial lymphocytes.

01:06 The NKG2D recognizes stress-induced self ligands such as MICA and MICB.

01:15 The NKG2D+ CD8+ intraepithelial lymphocytes destroy gut epithelial cells, resulting in celiac disease.

01:29 In addition, autoantibodies against transglutaminase 2 (TG2) are present.

01:36 Gluten binds to TG2.

01:41 Therefore, IgA+ B-cells specific for TG2 may process and present the gliadin component of gluten to the T-helper cells.

01:54 Again, contributing to pathology.