ABSTRACT
In the present review we address oral tolerance as an important biological phenomenon and discuss how it is affected by aging. Other factors such as frequency of feeding and previous digestion of the antigen also seem to influence the establishment of oral tolerance. We also analyze immunoglobulin isotypes of specific antibodies formed by tolerant and immunized animals of different ages submitted to different conditions of oral antigen administration. Isotypic patterns were studied as a parameter for assessing the pathways of B and T cell interactions leading to antibody production.
Subject(s)
Aging/immunology , Immune Tolerance/immunology , Immunoglobulin Isotypes/analysis , Aging/physiology , Animals , Immune Tolerance/physiology , Mice , Mucous MembraneABSTRACT
In the present review we address oral tolerance as an important biological phenomenon and discuss how it is affected by aging. Other factors such as frequency of feeding and previous digestion of the antigen also seem to influence the establishment of oral tolerance. We also analyze immunoglobulin isotypes of specific antibodies formed by tolerant and immunized animals of different ages submitted to different conditions of oral antigen administration. Isotypic patterns were studied as a parameter for assessing the pathways of B and T cell interactions leading to antibody production.
Subject(s)
Mice , Animals , Aging/immunology , Diet , Immune Tolerance/immunology , Immunoglobulin Isotypes/analysis , Aging/physiology , Enzyme-Linked Immunosorbent Assay , Immune Tolerance/physiology , Mucous MembraneABSTRACT
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.
Subject(s)
Aging/immunology , Immunization/methods , Ovalbumin/administration & dosage , Administration, Oral , Animals , Antibody Formation , Enzyme-Linked Immunosorbent Assay , Immune Tolerance , Immunization Schedule , Mice , Mice, Inbred Strains , Ovalbumin/immunologyABSTRACT
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.
Subject(s)
Aging/immunology , Immune Tolerance/immunology , Immunotherapy, Adoptive , Mouth/immunology , Spleen/immunology , Animals , Antibodies/blood , Antibody Specificity/immunology , Enzyme-Linked Immunosorbent Assay , Female , Immunization/methods , Male , Mice , Mice, Inbred Strains , Ovalbumin/immunology , Spleen/cytologyABSTRACT
A cholera toxoid was prepared by iodinating purified cholera toxin having an activity of 25 Limit of blueing (Lb) doses/1 microgram with 0.8 mumol of iodine monochloride per mg toxin, and the residual lesion capacity was tested in mice. The blueing dose (BD) test was strongly positive for the native toxin, and completely abolished in the iodinated toxoid when tested at up to 25 times on Lb dose. The dermal microscopic lesions with intradermal doses of 1 microgram virulent toxin presented intense leucocyte infiltration, proteinaceous edema and active hyperemia, whereas none of these effects was observed with the same amount of toxoid. To determine antigenicity, two groups of mice received toxin or toxoid, 8.5 micrograms adsorbed to aluminum hydroxide, followed by a booster of 17 micrograms in saline 21 days later. Measurement of antibodies by ELISA at day 28 indicated that the toxoid was 2.5 times more antigenic than the toxin. These data show that iodination converts cholera toxin to an effective toxoid.
Subject(s)
Cholera Toxin/immunology , Toxoids/isolation & purification , Animals , Antibodies, Bacterial/blood , Cholera Toxin/administration & dosage , Dose-Response Relationship, Immunologic , Enzyme-Linked Immunosorbent Assay , Evans Blue/administration & dosage , Female , Iodine , Male , Mice , Time Factors , Toxoids/administration & dosage , Toxoids/immunology , Vibrio cholerae/immunologyABSTRACT
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. Immune responsiveness (secondary antibody formation) to intraperitoneal immunization to Ova was the same in 7-week or 70-week old B6D2F1 mice. 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. In BALB/c mice, which are refractory to oral tolerance to Ova, the adoptive transfer of spleen cellsfrom neonate or young donors into old recipients failed to modify the lack of susceptibility to the induction of oral tolerance
Subject(s)
Mice , Age Factors , Immune Tolerance , Immunotherapy, Adoptive , Ovalbumin , Spleen/cytologyABSTRACT
A cholera toxoid was prepared by iodinating purified cholera toxin having an activity of 25 Limit of blueing (Lb) doses/l ug with 0.8 umol of iodine monochloride per mg toxin, and the residual lesion capacity was tested in mice. The Blueing Dose (BD) test was strongly positive for the native toxin, and co0mpletely abolished in the iodinated toxoid when tested at up to 25 times one Lb dose. The dermal microscopic lesions with intradermal doses of 1 ug virulent toxin presented intense leucocyte infiltration, proteinaceous edema and active hypertemia, whereas none of these effects was observed with the same amount of toxoid. To determine antigenicity, two groups of micereceived toxin or toxoid, 8.5 ug adsorbed to aluminum hydroxide, followed by a booster of 17 ug in saline 21 days later. Measurement of antibodies by ELISA at day 28 indicated that the toxoid was 2.5 times more antigenic than the toxin. These data show iodination converts cholera toxin to an effective toxoid
