Aging affects oral tolerance induction but not its maintenance in mice

Faria, Ana Maria Caetano; Ficker, Sabine Madsen; Speziali, Elaine; Menezes, José Elmo de; Stransky, Beatriz; Rodrigues, Vanessa Gregório; Vaz, Nelson M.

doi:10.1016/s0047-6374(98)00024-4

Cited by 46 publications

(53 citation statements)

References 33 publications

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“…These results indicate that the immune system of young and old animals displays the same functioning pattern, although at different levels of antibody response, with old mice (72 weeks of age) being less responsive to the antigen after both primary and secondary immunization. These results may reflect a more limited repertoire in the older individuals rather than a reduced response capacity (14,35,36). Alternatively, the lower antibody levels observed in the older mice may reflect alterations in T cell function, as suggested by several investigators (for reviews, see Refs.…”

Section: Discussionmentioning

confidence: 89%

Aging reduces the primary humoral response and the in vitro cytokine production in mice

Simioni

Costa

Tamashiro

2007

Braz J Med Biol Res

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Aging is accompanied by a decrease in several physiological functions that make older individuals less responsive to environmental challenges. In the present study, we analyzed the immune response of female BALB/c mice (N = 6) of different ages (from 2 to 96 weeks) and identified significant age-related alterations. Immunization with hapten-protein (trinitrophenyl-bovine serum albumin) conjugates resulted in lower antibody levels in the primary and secondary responses of old mice (72 weeks old). Moreover, young mice (2, 16, and 32 weeks old) maintained specific antibodies in their sera for longer periods after primary immunization than did old mice. However, a secondary challenge efficiently induced memory in old mice, as shown by the increased antibody levels in their sera. The number of CD4 + and CD8 + T cells in the spleen increased until 8 weeks of age but there was no change in the CD4 + /CD8 + ratio with aging. Splenic T cells from old mice that had or had not been immunized were less responsive to concanavalin-A and showed reduced cytokine production compared to young mice (IL-2: 57-127 vs 367-1104 pg/mL, IFN-γ: 2344-12,836 vs 752-23,106 pg/mL and IL-10: 393-2172 vs 105-2869 pg/mL in old and young mice, respectively). These data suggest that there are significant changes in the organization of the immune system throughout life. However, the relevance of these alterations for the functioning of the immune system is unknown.

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Section: Discussionmentioning

confidence: 89%

Aging reduces the primary humoral response and the in vitro cytokine production in mice

Simioni

Costa

Tamashiro

2007

Braz J Med Biol Res

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“…However, the differences in the antibody levels of immunized and tolerized mice decreased with advancing age. Literature data show that the capacity of becoming tolerant to an orally administered antigen is better preserved in younger animals, but that some degree of tolerance can be induced in very old animals (11,15,16,19). Cultures were stimulated with 500 μg/ mL OVA for 96 h, and cytokine levels in the supernatants were determined by ELISA.…”

Section: Discussionmentioning

confidence: 99%

“…Besides aging, genetic background can also influence the susceptibility to induction or maintenance of oral tolerance (11,(15)(16)(17)(18)(19). Several murine models have been developed to study the phenomenon of central tolerance, and deletion of autoreactive clones of lymphocytes is the main mechanism involved (20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

Effect of aging and oral tolerance on dendritic cell function

Simioni¹,

Fernandes²,

Gabriel³

et al. 2010

Braz J Med Biol Res

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“…Among many experiments reported by this group, Zorzenon dos Santos and Bernardes chose the one showing a refractory (saturation) behavior related to the immunization protocol [14] that could not be explained by clonal selection theory. However, the aging experiment chosen [15,16] is one among others obtained by the group showing the same result: a reduction on the intensity of the response as the system ages.…”

Section: Results Obtained From Previous Studiesmentioning

confidence: 82%

“…These results suggested that this model would be a good candidate to model a real immune system behavior. Zorzenon dos Santos and Bernardes then applied it [8] to reproduce immunization and aging experiments performed with mice under multiple antigen presentations [14,15,16] obtained by the group of Nelson Vaz.…”

Section: Results Obtained From Previous Studiesmentioning

confidence: 99%

Long term and short term effects of perturbations in an immune network model

Santos¹,

Copelli²

2003

Braz. J. Phys.

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In this paper we review the trajectory of a model proposed by Stauffer and Weisbuch in 1992 to describe the evolution of the immune repertoire and present new results about its dynamical behavior. Ten years later this model, which is based on the ideas of the immune network as proposed by Jerne, has been able to describe a multi-connected network and could be used to reproduce immunization and aging experiments performed with mice. The immunization protocol is simulated by introducing small and large perturbations (damages), and in this work we discuss the role of both. Besides its biological implications, the physical aspects of the complex dynamics of this network is very interesting per se. In a very recent paper we studied the aging effects by using auto-correlation functions, and the results obtained apparently indicated that the small perturbations would be more important than the large ones, since their cumulative effects may change the attractor of the dynamics. However our new results indicate that both types of perturbations are important. It is the cooperative effects between both that lead to the complex behavior which allows to reproduce experimental results. I IntroductionThe main task of the immune system is to protect the organism against dangerous elements: antigens (virus, bacteria, poison, cell residues, etc). Depending on the antigen the immune system may elicit different kinds of responses: the cell-mediated immune response or the humoral response. The models discussed in this paper are related to the humoral responses generated by B cells (one of the main classes of lymphocytes), which are the cells that produce the antibodies. The antibodies produced by a given population of B cells are replicas of its molecular receptor. Each molecular receptor exhibited by a given B cell population recognize different recognition sites (epitopes) of the antigen by lockkey interactions.The clonal selection theory [1] is the most accepted theory about the B cells and was proposed by Burnet in 1959. It states that the antigen chooses by pattern recognition the clones of B cells (population of B cell and antibodies) that will proliferate. In order to recognize any foreign (or dangerous) element the immune repertoire must be complete. According to estimates the human immune system is able to express at least the order of 10 11 different receptors [1]. Due to the completeness of the repertoire, the immune system would be able to recognize and be recognized (recognizing epitopes of its own antibodies), therefore the same mechanism of recognition should work for both antibodyantigen and antibody-antibody reactions. In 1974 Jerne [2], taking into account these different mechanisms, suggested that when the antigen is presented to the organism it will activate a set of clones of B cells, leading to the production of specific antibodies; those antibodies will in turn be recognized by a second set of clones activating them, and so on. Due to the interplay of the mechanisms of activation and suppression, this chain of...

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Aging affects oral tolerance induction but not its maintenance in mice

Cited by 46 publications

References 33 publications

Aging reduces the primary humoral response and the in vitro cytokine production in mice

Aging reduces the primary humoral response and the in vitro cytokine production in mice

Effect of aging and oral tolerance on dendritic cell function

Long term and short term effects of perturbations in an immune network model

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