Let’s now look at celiac disease, yet another example
where autoimmune reactions result in pathology.
In celiac disease, there is T-cell reactivity to the
gliadin component of wheat gluten in the small intestine.
Gluten that is absorbed from the
gut is taken up by dendritic cells.
It is processed and presented to
T-cells in the mesenteric lymph nodes.
The cytokine interleukin-15 stimulates
dendritic cells to go on and activate
proinflammatory T-helper cells which
secrete IL-21 and gamma interferon.
There is an induction of gluten
specific helper T-cells and B-cells.
The lymphocytes home to
the gut lamina propria.
IL-15 also induces expression of the cytotoxicity-activating
receptor NKG2D on CD8+ intraepithelial lymphocytes.
The NKG2D recognizes stress-induced
self ligands such as MICA and MICB.
The NKG2D+ CD8+ intraepithelial lymphocytes destroy
gut epithelial cells, resulting in celiac disease.
In addition, autoantibodies against
transglutaminase 2 (TG2) are present.
Gluten binds to TG2.
Therefore, IgA+ B-cells specific for TG2 may process and
present the gliadin component of gluten to the T-helper cells.
Again, contributing to pathology.