Manutenção dos padrões de reatividade imunológica durante o processo de senescência

Abstract

The oral tolerance is defined as a sytemic hipo-reactivitiy state against an antigen that was previously orally administrated. Many factors affect the induction of oral tolerance, some of them antigen-related, others are related to the animal. The animal age is one of factors more important that affect the induction of oral tolerance, as the aging process that induces many changes on the immune response. The oral tolerance is maintained during a long period of time. Our study showed that both oral tolerance and immune reactivity is maintained up to a year and a half and that this maintenance can be seen in many aspects of the immune response in older mice that have had previous contact with the antigen when young. It was observed the maintenance of oral tolerance through the humoral response after multiple challenges with OVA (p <0.001) and old animals previously immunized remained susceptible to induction of systemic immunization, because the antibody titers of this these animals presented higher after intraperitoneal immunizations. Moreover, the splenic cells and inguinal lymph nodes of normal animals (challenged only in old age) presents low proliferative potential when compared to the tolerant animals and immune animals that obtained a greater proliferation score, similar to the observed on the anti-OVA antibodies production by the immune animals, tolerant animals and normal old animals treated when young. Regarding to the tolerant group, it presented a lower proliferative ability than immune group, indicating that in senescence both the persistence of oral tolerance and the difference in the immune response pattern presented by normal animals (treated only in old age) and by tolerant animals and immune animals previously treated are observed in vitro. It was also demonstrated that the cellular response of normal mice (challenged only in old age) 24 hours after the challenge, measured through the DTH reaction, was higher than the reaction presented in the mice that were immunized in young age. However, the DTH reaction in old animals tolerized in young age was significantly lower than immune mice (p<0.025), showing once more that the oral tolerance can be maintained for a long period. Our results confirmed again the data of literature that occurs an increase of the general state of immune system activation in senescence. This global increase is reflected on the rising on the seric immunoglobulin titer, the increase of the total numbers of cells producing antibody and also the increase of the proliferative activity of the T cells when compared to 16 the same parameters in the young animals. This immunological hyperactivity probably represents the memory of the interaction with intern and extern antigens cumulated in the animal lifetime. The increase of this interactions makes the immune system of elderly less flexible and, therefore relatively refractory to incorporation of new reactivity to its dynamic operation. The immune system of young, on the other hand, reflects the precarity of its previous experiences, and, at the same time, the great plasticity of this group to changes to news interactions. In the case of normal animals challenged only in old age, the OVA represents news to your immune system, to which it is less susceptible, because its immune system is already activated and involved in other interactions which OVA is not a part. However, the immune animals and the tolerant animals, because they had interacted with Ova in young age, they are able to evoke a reactivity to this antigen. In these animals, the reactivity to OVA does not represent the incorporation of a novelty, but only the reactivation of interactions already present, the recovery of the memory circuits that are now part of the normal activity of the immune system of elderly. This immunological memory refers not only to the quantity of antibodies and proliferative activity, but also to the pattern of response that can be evoked. The pattern of reactivity acquired in youth is apparently maintained by immune memory circuits that can be recovered in old age. Interestingly, even strong stimuli like other adjuvants are unable to modify this pattern indicating that the memory of previous activations is strongly interlaced in probably very stable circuits.