Oral Tolerance

The therapy by oral tolerance uses the natural mechanism that the immunologic system uses to permit the process of the nourishment without provoking rejections or reactions of hypersensibility. In this mechanism are involved intestinal lymphoid tissue, some of them are: the Peyer patches, epithelial cells of the villi, lympocyte intraepithelial, and lymphocytes disseminated through its own plate. The Peyer patches are rich nodules in lymphocytes B and T (Th1 and Th2), macrophags, dentritic cells, a germinal center that contain lymphocytes B and M cells, this last commissioned with permitting the entrance and the transfer of the antigen.

The proteins that enter the digestive duct can stay intact, partially hydrolysated or degraded to amino acids. These molecules enter through the M cells (in the Peyer patches) or of specialized cells that are found in the villi. Small peptides that formed part of the hydrolysated protein, are presented on the surface of the antigenic cells and stimulate the lymphocytes T and B to react as compared to the peptide. Some of the stimulated lymphocytes T are induced to act as regulating cells, Th2. These cells, when they are stimulated by the same peptide releases suppressive substances of the immune reaction as IL-4, IL-10 and TGF-beta. These substances reduce the inflammatory reaction produced in the autoimmune diseases.

There exist three mechanisms known that induce the oral tolerance effect, depending on the dose of autoantigenic: active suppression, clonal anergy and clonal deletion. These three mechanisms can act individually or in a combined way. The active suppression mechanism is favored by the low dose of autoantigenic while the high dose favors the clonal anergy and the clonal deletion.

In the active suppression, the low dose of autoantigenic presented by the antigenic cells in the intestine stimulate the regulating cells (Th2), that then move to the general circulation. There they are found with antigens similar to the ingested (that provoke the disease) and begin to secrete inhibiting cytokines, suppressing the autoimmune reaction and attenuating the disease.

On the other hand, the clonal anergy is produced when the high dose of autoantigenic induces a lack of response of the lymphocytes Th1, primary origin for the autoimmunity. The anergy can originate in the high concentration of cytokines capable of generating a secondary response, that ends by inhibiting the own inflammatory reaction of the disease.

The third mechanism known is the clonal deletion that consists of the elimination of the clone responsible for the autoimmune reaction, to be in contact with high dose of autoantigen. This mechanism is similar to what occurs in the thymus during the autoantigenic development, but in this case the process takes place in the Peyer patches.

For any of the methods which induce the oral tolerance effect, it is a natural immunologic process that can be employed with success in the treatment of the autoimmune pathologies. Furthermore, the disease is not always provoked by the same antigen and sometimes is produced by the presence of multiple autoantigens, those which do not need to be intact to produce the desired effect.

The Instituto Sucesores Alfredo Villar designed specific products for the specific treatment of pathologies, hydrolysated partial protein, that contain specific antigens capable of stimulating the lymphocytes responsible for unfettering the oral tolerance effect, such has been demonstrated projects carried out by our Institute and the Medical Center Regina Mater, of the city of Buenos Aires, in vivo as well as in vitro.