RESUMEN
Initial contacts with a T-dependent antigen by mucosal routes may result in oral tolerance, defined as the inhibition of specific antibody formation after subsequent parenteral immunizations with the same antigen. We describe here an additional and permanent consequence of these initial contacts, namely, the blockade of secondary-type responsiveness to subsequent parenteral contacts with the antigen. When repeatedly boosted ip with small doses (3 microg) of ovalbumin (OVA) (or lysozyme), primed B6D2F1 mice showed progressively higher antibody responses. In contrast, mice primed after a single oral exposure to the antigen, although repeatedly boosted, maintained their secondary antibody titers on a level which was inversely proportional to the dose of antigen in the oral pretreatment. This phenomenon also occurred in situations in which oral tolerance was not induced. For example, senile 70-week-old B6D2F1 mice pretreated with a single gavage of 20 mg OVA did not become tolerant, i.e., they formed the same secondary levels of anti-OVA antibodies as non-pretreated mice. However, after 4 weekly challenges with 3 microg OVA ip, orally pretreated mice maintained the same anti-OVA serum levels, whereas the levels of control mice increased sequentially. This "stabilizing" effect of mucosal exposure was dose dependent, occurred with different proteins and was triggered by single or multiple oral or nasal exposures to the antigen.
Asunto(s)
Formación de Anticuerpos/inmunología , Tolerancia Inmunológica/inmunología , Inmunidad Mucosa/inmunología , Administración Intranasal , Administración Oral , Análisis de Varianza , Animales , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Inmunización Secundaria , Infusiones Parenterales , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Ovalbúmina/administración & dosificación , Ovalbúmina/inmunologíaRESUMEN
Initial contacts with a T-dependent antigen by mucosal routes may result in oral tolerance, defined as the inhibition of specific antibody formation after subsequent parenteral immunizations with the same antigen. We describe here an additional and permanent consequence of these initial contacts, namely, the blockade of secondary-type responsiveness to subsequent parenteral contacts with the antigen. When repeatedly boosted ip with small doses (3 æg) of ovalbumin (OVA) (or lysozyme), primed B6D2F1 mice showed progressively higher antibody responses. In contrast, mice primed after a single oral exposure to the antigen, although repeatedly boosted, maintained their secondary antibody titers on a level which was inversely proportional to the dose of antigen in the oral pretreatment. This phenomenon also occurred in situations in which oral tolerance was not induced. For example, senile 70-week-old B6D2F1 mice pretreated with a single gavage of 20 mg OVA did not become tolerant, i.e., they formed the same secondary levels of anti-OVA antibodies as non-pretreated mice. However, after 4 weekly challenges with 3 æg OVA ip, orally pretreated mice maintained the same anti-OVA serum levels, whereas the levels of control mice increased sequentially. This "stabilizing" effect of mucosal exposure was dose dependent, occurred with different proteins and was triggered by single or multiple oral or nasal exposures to the antigen
Asunto(s)
Animales , Ratones , Formación de Anticuerpos/inmunología , Tolerancia Inmunológica/inmunología , Inmunidad Mucosa/inmunología , Ovalbúmina/administración & dosificación , Administración Intranasal , Análisis de Varianza , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Inmunización Secundaria , Infusiones Parenterales , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Ovalbúmina/inmunologíaRESUMEN
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.
Asunto(s)
Envejecimiento/inmunología , Tolerancia Inmunológica/inmunología , Isotipos de Inmunoglobulinas/análisis , Envejecimiento/fisiología , Animales , Tolerancia Inmunológica/fisiología , Ratones , Membrana MucosaRESUMEN
B6D2F1 mice, which are very susceptible to tolerance induction by a single gavage with 20 mg of ovalbumin (Ova) at age 8 weeks, become less susceptible at age 25 weeks and totally refractory at age 70 weeks. However, 70-week-old mice may be rendered tolerant by repeated ingestion of Ova. Mice orally exposed to Ova at age 8 weeks remain tolerant at age 70 weeks. The isotypic pattern of anti-Ova antibodies formed by orally-tolerant and normal mice after immunization is similar and all isotypes are equally suppressed by oral tolerance. In old mice, oral exposures to Ova alone triggered an early transient antibody response; some of these responding animals were, nevertheless, tolerant to subsequent parenteral injection of Ova in adjuvant.
Asunto(s)
Envejecimiento/inmunología , Formación de Anticuerpos/fisiología , Tolerancia Inmunológica/fisiología , Ovalbúmina/inmunología , Inhibidores de Serina Proteinasa/inmunología , Administración Oral , Envejecimiento/fisiología , Hidróxido de Aluminio/administración & dosificación , Hidróxido de Aluminio/inmunología , Animales , Anticuerpos Antiidiotipos/sangre , Anticuerpos Antiidiotipos/efectos de los fármacos , Formación de Anticuerpos/efectos de los fármacos , Antígenos/administración & dosificación , Femenino , Tolerancia Inmunológica/efectos de los fármacos , Inmunización/métodos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Ovalbúmina/administración & dosificación , Inhibidores de Serina Proteinasa/administración & dosificaciónRESUMEN
Airway inflammation plays a major role in human asthma. Increasing evidence points to a close correlation between eosinophil infiltration and allergic lung disease. A new murine model of eosinophilic lung inflammation has recently been developed; it consists of immunizing mice with small fragments of solidified hen egg white implanted (EWI) into the subcutaneous tissue. In this model, which is further characterized here, mice challenged with ovalbumin (OVA) present an intense and persistent lung eosinophilia, as well as histopathological findings that resemble human asthma. In the present work, the effect of oral tolerance on the development of allergic lung inflammation in B6 mice immunized with antigen plus adjuvant or with EWI is investigated. It was found that in mice rendered orally tolerant by previous exposure to antigen in the drinking water, the T-helper type 2 cell (Th2)-associated allergic responses in both protocols of immunization were almost completely abolished. The allergic responses were assessed by pulmonary and bone marrow eosinophilia, lung histopathology and antigen-specific IgE and IgG1 production. These findings provide the first indication that Th2-associated lung pathology can be prevented by oral tolerance.
Asunto(s)
Tolerancia Inmunológica/inmunología , Inmunoterapia , Eosinofilia Pulmonar/prevención & control , Administración Oral , Adsorción , Hidróxido de Aluminio/administración & dosificación , Hidróxido de Aluminio/inmunología , Animales , Clara de Huevo , Peroxidasa del Eosinófilo , Eosinófilos/enzimología , Femenino , Hipersensibilidad/inmunología , Hipersensibilidad/prevención & control , Inmunización , Isotipos de Inmunoglobulinas/análisis , Ratones , Ratones Endogámicos C57BL , Ovalbúmina/administración & dosificación , Ovalbúmina/inmunología , Peroxidasas/inmunología , Peroxidasas/metabolismo , Eosinofilia Pulmonar/inmunología , Células Th2/inmunologíaRESUMEN
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.