Gluten Immunochemistry - Innate Immunity

Innate Immunity

Underlying conditions
The normal intestine
Wheat proteins interact with the immune system by means of DQ2-mediated programmed cell death (apoptosis) of the gut in sensitive individuals. New research is finding that the coeliac gut may be predisposed to sensitivity in the absence of HLA genetic factors.

How diet proteins reach the blood
In the normal gut, proteins are digested to peptides by pepsin (stomach), trypsin and chymotrypsin (derived from the pancreas and activated in the gut). Peptides are further digested when they approach the villi, where brush border peptidases break proteins into amino acids. Over much of the small intestine only small solutes, like water, can cross the tight junctions, however some regions of the intestine peptides as large as 500 daltons (4 amino-acids residues in length can cross).

The gluten sensitive gut

There is a growing body of evidence that the gluten-sensitive intestine differs from the normal gut, several gluten peptides can enter behind the brush border membrane cells. For example, a "33mer" of α-2 gliadin is a magnitude larger than the size exclusion of the tight junction, ω-5 gliadin peptides have been found in the blood stream of people with exercise-induced anaphylaxis, aided by salicylates. And the innate 25 is capable of reaching mononuclear cells in coeliac gut, but in normal gut is broken down by brush border peptidases. It may be this lower peptidase activity that explains the presence of these peptides behind the brush border membrane. Recently, it was found that an α-9 gliadin peptide was capable of binding the "CXCR3" receptor, increasing zonulin production and weakening tight junctions, this may explain how, generally, larger peptides can enter the gluten-sensitive gut.

Innate immunity to gluten refers to an immune response that works independently of T-cell receptor or antibody recognition of the 'innate' peptide. This peptide acts directly on cells, such as monocytes, stimulating their growth and differentiation. Innate immunity to gluten is complicated by an apparent role gluten has in bypassing normal host defense and peptide exclusion mechanisms in the gut. While not truly innate, these activities allow gliadin to enter into areas where many lymphocytes patron. In bypassing these filters gliadin alters the normal behavior of both digestive cells, called enterocytes or epithelial cells, and lymphocytes. This increases the potential of causing sensitivity (see Underlying Conditions). One potential explanation of why certain people become sensitive is that these individuals may not produce adequate peptidases in some areas of the gut, allowing these peptides to survive. Other explanation for some may be that food chemicals or drugs are weakening the defenses. This can be the case with ω5-gliadin allergy with salicylate sensitivity. There is no clear reasoning, either from genetics or from long term studies of susceptible individuals why these gut peptide restrictions would change.

Once inside, α-9 gliadin 31-55 shows the ability to activate undifferentiated immune cells that then proliferate and also produce inflammatory hormones notably Interleukin 15. This produces a number of downstream responses that are pro-inflammatory. The other peptide that may have innate behavior is the "CXCR3" receptor binding peptides, the receptor exists on enterocytes, the brush border membrane cells. The peptide displaces an immune factor and signals the disruption of the membrane seal, the tight junctions, between cells.

Read more about this topic:  Gluten Immunochemistry

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