**2.2 Immunological factors**

The most accepted model for explaining CD immunopathogenesis is the twosignal model mediated by a first innate immune response (direct toxic effect of gluten on the epithelium) followed by a secondary antigen-specific adaptive response (through CD4+ T lymphocytes of the lamina propria) [20, 21]. Some peptides, such as, the 19-mer gliadin peptide, trigger an innate immune response mainly characterized by the production of IL-15 by epithelial cells. Result is the disruption of the epithelial barrier, by increasing the permeability and inducing enterocyte apoptosis [20]. These peptides enter the lamina propria of the small intestine via transcellular or paracellular routes [20] where, in affected individuals, an adaptive immune reaction occurs that is facilitated by increased intestinal permeability that allows the passage of immunogenic peptides, such as 33-mer, to the lamina propria. At the same time, some glutamine residues of these peptides are catalytically

### *Celiac Disease, Management, and Follow-Up DOI: http://dx.doi.org/10.5772/intechopen.104652*

deaminated by tissue transglutaminase (tTG). This deamination, in turn, increases the immunogenicity of peptides due to high-affinity interactions between modified residues and ligand binding sites of HLA-DQ2 and HLA-DQ8 molecules [22] expressed by dendritic cells. Gliadin peptides are then presented to gliadin-reactive CD4+ T cells. During this process, antibodies against tTG, gliadin, and actin are made through unclear mechanisms. These antibodies might contribute to extra-intestinal manifestations of CD, such as dermatitis herpetiformis and gluten ataxia. Moreover, the immune response initiates a cascade of reactions that degenerate into crypt hyperplasia and flattening of the intestinal villi.
