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Biomedical subjects

N M Vaz

Publications and source records attributed to N M Vaz.

At least 19 recordsLinked to original sources
PubMed1997

Immunological induction of flavour aversion in mice. II. Passive/adoptive transfer and pharmacological inhibition.

Mice immunized with ovalbumin develop a strong aversion to ingesting sweetened egg white dilutions or ovalbumin solutions. In immunized animals, gavage or voluntary ingestion of ovalbumin triggers an increase of vascular permeability in the intestine; pretreatment with a mixture of histamine and serotonin antagonists blocked this reaction, but not the aversion; dexamethasone inhibited both the aversion and the increase in permeability. The aversion was transferred to normal recipient mice with high-titre anti-Ova sera obtained with complete Freund's adjuvant, but not with lower-titre serum pools of mice immunized with the help of Al(OH)3 adjuvant. However, the aversion was also (adoptively) transferred with whole spleen cells from immune donors. This later condition is inefficient to transfer the formation of high titres of specific antibodies.

Adoptive Transfer↗
PubMed1997

Indirect effects of oral tolerance cannot be ascribed to bystander suppression.

The addition of tolerated antigens to immunizing doses of unrelated antigens blocks antibody responses to these unrelated antigens. This inhibition, which the authors have called the indirect effects of tolerated antigens, occurs even when the mixture of proteins is injected as soon as 24 h after the oral tolerance induction. The indirect effects also do not require the simultaneous injection of the two proteins: they are still present 72 h after an injection of Ova in Ova tolerant mice, but do not occur if the unrelated protein is injected 24 h before the tolerated protein. In addition, indirect effects do not block secondary responses to unrelated proteins if the primary immunization is made in the absence of the tolerated protein. These results cannot be explained by innocent bystander suppression, which is believed to result from the action of suppressive cytokines released by specific tolerant lymphocytes upon unrelated lymphocytes that would otherwise respond to the second, non-tolerated antigen. Indirect effects may be better understood in terms of network models.

Administration, Oral↗
PubMed1996

Indirect effects are independent of the way of tolerance induction.

Oral tolerance is a T-cell mediated phenomenon defined by a refractoriness to parenteral immunization with a protein that was first contacted by oral route. However, the authors have shown that the injection of a tolerated protein is not neutral for the immune system. In mice made tolerant to KLH by gavage, co-immunization with KLH and DNP-Ova blocks anti-DNP antibody formation. Anti-DNP antibody formation resulting from immunization with DNP-Ova can also be blocked by co-immunization with a dietary protein (zein) or a self component (fibrinogen). The inhibitory effects resulting from immunization with a tolerated protein, designated indirect effects, do not affect the induction of oral tolerance to another protein. These results support the hypothesis that active mechanism are involved in the maintenance of tolerance.

Administration, Oral↗
PubMed1995

Anti-gamma delta T cell antibody blocks the induction and maintenance of oral tolerance to ovalbumin in mice.

The oral administration of antigens is one of the means of inducing tolerance in adult mammals. In this report, the role of gamma delta T cells in the induction and maintenance of orally-induced tolerance to ovalbumin was investigated. The injection of a monoclonal anti-gamma delta T cell monoclonal antibody blocked the induction of oral tolerance, because the secondary immune responses to ovalbumin in these animals were comparable to the corresponding responses in ovalbumin-immunized control mice. Furthermore, depletion of gamma delta T cells either in vivo or in vitro abolished already established oral-tolerance. The fact that the state of tolerance could be adoptively transferred to naive recipients by CD3+ alpha beta- gamma delta + spleen cells from tolerant mice. These results suggest that systemic oral tolerance is induced and actively maintained by mechanisms involving gamma delta T cells.

Administration, Oral↗
PubMed1995

Anti-IL-10 treatment does not block either the induction or the maintenance of orally induced tolerance to OVA.

Herein, the role of IL-10 in the induction and maintenance of oral tolerance was evaluated. The results show that: (1) mice treated with MoAb anti-IL-10 are permissive to the induction of oral tolerance to OVA; (2) anti-IL-10 treatment did not reverse the in vitro blocking of T cell proliferative response found in orally-tolerized mice; and (3) orally-induced tolerance could not be broken by anti-IL-10 treatment. Taken together, these results suggest that IL-10 is not a fundamental cytokine for the establishment and maintenance of oral tolerance.

Administration, Oral↗
PubMed1994

Indirect effects of oral tolerance in mice.

Anti-DNP antibody formation resulting from intraperitoneal (i.p.) immunization with DNP-KLH may be blocked by simultaneous (i.p.) injection of DNP-Ova or native Ova in mice orally tolerant to Ova, but not in normal mice. In Ova-tolerant mice the inhibition of anti-DNP antibody formation also occurred when DNP-Ova and DNP-KLH were given by separate routes of immunization: subcutaneous (s.c.) and i.p. A second exposure to Ova by gastric intubation (gavage) or intravenous administration simultaneously with i.p. immunization with DNP-KLH failed to inhibit anti-DNP antibody formation. There was inhibition of responses to DNP-KLH i.p. by DNP-Ova given 24 h before, but not 24 h after, and in the Ova-tolerant mice, addition of DNP-Ova only to the primary immunization with DNP-KLH inhibited secondary and tertiary responses to DNP-KLH in the absence of further exposures to DNP-Ova. These results suggest that the indirect effects of parenteral exposure of tolerant mice to the tolerated immunogen may inhibit unrelated immune responses. This inhibition is not due to 'innocent bystanding' suppression, i.e., to inhibitory cytokines provided locally by specific suppressor lymphocytes; it may derive from more durable perturbations of immune system.

Administration, Oral↗
PubMed1994

Immunological induction of flavor aversion in mice.

1. Young adult BALB/c and B6D2F1 mice of both sexes (20 +/- 2 g) immunized ip with 2 doses of 10 micrograms ovalbumin (Ova), but not with 2 doses of 10 micrograms bovine gammaglobulins (BGG), show aversion to the ingestion of sweetened egg white or crystallized Ova solutions which are avidly ingested by normal mice. In 24 h, normal mice or mice immunized with BGG ingested, respectively, 340 +/- 80 and 265 +/- 56 mg of sweetened egg white per gram of body weight (mg/gbw); in the same period, Ova-immunized mice ingested less than one tenth these amounts (18 +/- 5 mg/gbw). ELISA-titers of anti-Ova and anti-BGG antibodies in immune mice were of similar magnitude. 2. Aversion arises coincidentally with the emergence of anti-ovalbumin antibodies in serum in the primary response, 14 days after primary immunization. 3. Previous induction of oral tolerance to ovalbumin by a single gavage with 20 mg Ova 7 days before primary ip immunization, which blocks the increase of specific antibodies in serum, also blocks the development of the aversive phenomenon. 4. Aversion was induced to 1 mg/ml but not 0.1 mg/ml sweetened crystallized ovalbumin solutions and was already noticeable 2 h after exposure of immunized mice to sweetened egg white solutions. 5. We conclude that, at least in experimental situations, immunological factors may be of decisive importance in diet selection.

Administration, Oral↗
PubMed1993

Systemic immunization of mature mice by the oral route.

1. Mice of several strains which are susceptible to the induction of oral tolerance by a single gavage with 20 mg of ovalbumin (Ova) when young adults (7-8 weeks old) become less susceptible or refractory to tolerance induction when mature (20-40 weeks old). The antibody-forming capacity of these mature animals remains invariant compared to young adults (8-10 weeks old). 2. Mature mice of several strains display significant serum antibody responses to 3 gavages (days 0, 7 and 28) with Ova; as assessed by ELISA titers, these responses are similar in magnitude to those elicited by standard ip immunization with small doses of Ova. 3. In mature H-III mice, gavages on days 0, 7 and 28 induced significant antibody formation. On the contrary, the ingestion of the same amounts of Ova on days 0, 7 and 28 induced oral tolerance. Concomitant gavage with saline on the days of Ova ingestion failed to inhibit tolerance induction. 4. In H-III mice displaying circulating antibodies induced by repeated gavage with Ova, additional ip injections of Ova failed to increase the antibody titers.

Administration, Oral↗
PubMed1993

Hydroxyurea before oral antigen blocks the induction of oral tolerance.

1. Treatment with hydroxyurea (HU, 1 mg/g ip, 2 doses applied 7 h apart) eliminates the majority of cells undergoing mitosis (cycling cells) without affecting non-cycling cells. Oral tolerance, induced by a single gavage with 20 mg of ovalbumin, results in a drastic inhibition of anti-Ova antibody responses in young adult mice. Oral tolerance is actively maintained by the presence of specific suppressor T cells which may adoptively transfer the tolerance to naive syngeneic recipients. Under the clonal selection hypothesis, the induction of oral tolerance should be blocked by HU treatment applied soon after oral exposure to the antigen by the elimination of specific clones of lymphocytes activated by tolerogenic presentation of the antigen. 2. However, treatment with HU initiated 3, 6 or 24 h after oral exposure to ovalbumin had no effect on the induction of oral tolerance in B6D2F1 mice. However, treatment with HU 24 h before antigen exposure, totally blocked the induction of tolerance. Treatment with HU 72 h before ovalbumin had no effect. 3. In animals treated with HU 24 h before, the adoptive transfer of normal thymus, bone marrow or spleen cells partially restored the susceptibility to the induction of oral tolerance. 4. The results suggest that cycling cells, which may be totally regenerated within 72 h after treatment with HU, and are present in normal thymus, bone marrow and spleen, are crucially important for the induction of oral tolerance.

Administration, Oral↗
PubMed1993

Decrease in susceptibility to oral tolerance induction and occurrence of oral immunization to ovalbumin in 20-38-week-old mice. The effect of interval between oral exposures and rate of antigen intake in the oral immunization.

Maturation into adulthood, from 8 to 24 weeks of age, significantly influences the induction of oral tolerance in different strains of mice. Animals from strains which are susceptible to the induction of oral tolerance to ovalbumin (OVA) at 8 weeks of age become refractory at 24 weeks of age. Furthermore, in several strains, intermittent exposure to OVA exclusively by gavage resulted in high titres of circulating anti-OVA antibodies. However, the voluntary intake of similar doses of OVA at the same intervals failed to immunize mice of one of the most responsive strains, H-III.

Administration, Oral↗
PubMed1992

Influence of age on the induction of oral tolerance in mice and its adoptive transfer by spleen cells.

1. Seven-week-old B6D2F1 mice were highly susceptible to the induction of oral tolerance to ovalbumin (Ova), whereas 70-week-old mice were totally refractory. 2. Immune responsiveness (secondary antibody formation) to intraperitoneal immunization to Ova was the same in 7-week- or 70-week-old B6D2F1 mice. 3. In B6D2F1 mice, the adoptive transfer of spleen cells from old donors into young recipients hindered, and, reciprocally, transfer of spleen cells from young donors into old recipients facilitated the induction of oral tolerance. 4. In BALB/c mice, which are refractory to oral tolerance to Ova, the adoptive transfer of spleen cells from neonate or young donors into old recipients failed to modify the lack of susceptibility to the induction of oral tolerance.

Aging↗
PubMed1990

Specific responses to two unrelated antigens in mice made orally tolerant to one of them.

BDF1 and B10 mice, either normal or exclusively fed egg white diluted in water, were immunized with ovalbumin (OVA), sheep erythrocytes (SRBC) or OVA + SRBC. BDF1, but not B10, mice became tolerant to OVA and presented a 100% increase in the total number of immunoglobulin-secreting cells in the spleen. Immunization with OVA + SRBC markedly increased the response to OVA, except in tolerant BDF1 mice, and had no effect on the anti-SRBC PFC response, except in normal (non-tolerant) BDF1 mice.

Animals↗
PubMed1990

Local anaphylactic reactions to the penetration of cercariae of Schistosoma mansoni.

1. In order to study local tissue anaphylactic responses to infection with Schistosoma mansoni cercariae, mice of three different strains (C57BL/10J, Balb/cJ and CBA/J) were infected by subcutaneous injection of 15 to 20 cercariae. Eleven to 16 weeks later the animals were reinfected through one ear with 250 to 350 cercariae. 2. Throughout the infection period, the histamine content of the ears increased up to 150% of control values. Upon reinfection, the penetration of cercariae through the ear reduced its histamine content to near normal values. 3. Reinfection causes inflammation as judged by a 1.5 to 2.3-fold increase in the amounts of plasma leaking through the ear vessels as measured by leakage of Evans blue dye. 4. These results suggest that the local inflammatory reaction mediated by mast cells is important in the resistance of mice to reinfection with S. mansoni.

Anaphylaxis↗
PubMed1990

Evidence for the participation of mast cells in the innate resistance of mice to Schistosoma mansoni: effects on in vivo treatment with the ionophore 48-80.

1. Evidence is presented for the participation of mast cells in the resistance of mice to infection by Schistosoma mansoni. 2. Intravenous injection of 1 micrograms/g body weight of the ionophore 48-80, a potent mast cell degranulator, significantly reduced (42-62%) the histamine content of the ear tissue of normal mice and either increased or decreased resistance to parasite penetration and infection depending on whether the injection of the ionophore was 5 min or 2 days before cercarial penetration. 3. When 48-80 was injected 5 min before the beginning of cercarial penetration, the number of parasites recovered from ear tissue 2 days later or from the portal system 30 days later was significantly reduced (39-71% and 27-40%, respectively) in relation to untreated controls. This resistance caused by 48-80 was blocked when mice were simultaneously treated with cyproheptadine, an antagonist of vasoactive amines. 4. In contrast, when 48-80 was administered 2 days before the beginning of cercarial penetration, the number of parasites retrieved from ear tissue 2 days later or from the portal system 30 days later was 32-64% and 28-30% larger, respectively, in relation to untreated controls. 5. These findings indicate that the local inflammatory reaction mediated by mast cells is important in the resistance of mice to infection with S. mansoni.

Animals↗
PubMed1988

Tolerance induction and immunological priming initiated by mucosal contacts with protein antigens in inbred strains of mice.

1. We show that mouse strains differ widely in susceptibility to tolerance induction and/or immunization (priming) following contact of protein antigens (ovalbumin, human or bovine gamma globulins) with different mucosal surfaces. 2. When compared to a control group pretreated with saline, mice pretreated by the oral (intragastric) route with antigen became significantly less responsive to subsequent parenteral immunization (i.e., tolerant). This was observed in most, but not all, antigen/strain combinations. 3. Similar, although less prominent changes were induced by pretreatments with antigen by the ocular (conjunctival) route. 4. No significant effects were observed following pretreatments by the nasal, vaginal or rectal routes. 5. Genes present in strains selected for multispecific "high" or "low" responsiveness are included among those involved in tolerance induction following mucosal contacts with protein antigens.

Animals↗