RESUMEN
A classical paradigm in immunology establishes that for the isotype switch to take place in antibodies, it is a sine qua non condition that the antigen is presented by an antigen presenting cell to a helper T cell. In the present study an animal model of the immune response against two typical antigens was designed in BALB/c mice. Dextran was chosen as a T independent antigen (TIAg), and bovine seroalbumin (BSA) as a T dependant antigen (TDAg), and the response was studied, analyzing the isotypes of the specific antibodies produced. The results show that the response against dextran, in the presence of BSA, takes place with isotype switch, essentially from IgM to IgG1. These experiments suggest that BSA generates a switch inductor biochemical environment in its own processing pathway as well as in the dextran's. These results indicate that the exclusive association of TDAgs with isotype switch responses is inaccurate. Considering the proposed model, it seems unlikely the finding of a spontaneous in vivo case in which TIAgs enter the organism isolated; instead, it is much more probable that they would enter together with TDAgs, and in consequence the isotype switch would take place.
Asunto(s)
Antígenos T-Independientes/inmunología , Dextranos/inmunología , Cambio de Clase de Inmunoglobulina/inmunología , Albúmina Sérica Bovina/inmunología , Animales , Bovinos , Dextranos/farmacología , Femenino , Cambio de Clase de Inmunoglobulina/efectos de los fármacos , Inmunoglobulina G/efectos de los fármacos , Inmunoglobulina G/inmunología , Inmunoglobulina M/efectos de los fármacos , Inmunoglobulina M/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , Modelos Animales , Albúmina Sérica Bovina/farmacologíaRESUMEN
Un paradigma clásico de la inmulogía plantea que para que ocurra cambio de isotipo en los anticuerpos es condición sine qua non la presentación del antígeno a un linfócito T colaborador por parte de una célula presentadora de antígenos. En el presente trabajo se diseñó un modelo animal, ratones BALB/c, de respuesta inmune frente a dos antígenos típicos. Se utilizo dextrán como antígeno T independiente (AgTI) y seroalbúmina bovina (SAB) como antígeno T dependiente (AgTD), y se estúdio la respuesta, analizando los isotipos de los anticuerpos específicos producidos. Los resultados obtenidos muestran que la respuesta a dextrán en presencia de SAB ocurre con cambio de isotipo (swith), essencialmente de IgM a IgG. Estos experimentos sugieren que la SAB genera un entorno bioquímico inductor de cambio de isotipo tanto en supropia via de procesamiento como en del dextrán. Los resultados señalan que la asociación exclusiva de los AgTDs con las respuestas em las que ocurre cambio de isotipo es incorrecta. Considerando el modelo propuesto resulta poco probable encontrar in vivo y en forma espontÔnea casos en los que los AgTIs ingreses al organismo aislados; en cambio, es mucho más probable que el ingreso ocurra conjuntamente con AgTDs, y en consecuencia ocurra cambio de isotipo. (AU)
Asunto(s)
Bovinos , Ratones , Animales , Masculino , Femenino , Cambio de Clase de Inmunoglobulina/inmunología , Antígenos T-Independientes/inmunología , Dextranos/inmunología , Albúmina Sérica Bovina/inmunología , Cambio de Clase de Inmunoglobulina/efectos de los fármacos , Dextranos/farmacología , Albúmina Sérica Bovina/farmacología , Inmunoglobulina M/inmunología , Inmunoglobulina M/efectos de los fármacos , Inmunoglobulina G/inmunología , Inmunoglobulina G/efectos de los fármacos , Ratones Endogámicos BALB C , Modelos AnimalesRESUMEN
Un paradigma clásico de la inmulogía plantea que para que ocurra cambio de isotipo en los anticuerpos es condición sine qua non la presentación del antígeno a un linfócito T colaborador por parte de una célula presentadora de antígenos. En el presente trabajo se diseñó un modelo animal, ratones BALB/c, de respuesta inmune frente a dos antígenos típicos. Se utilizo dextrán como antígeno T independiente (AgTI) y seroalbúmina bovina (SAB) como antígeno T dependiente (AgTD), y se estúdio la respuesta, analizando los isotipos de los anticuerpos específicos producidos. Los resultados obtenidos muestran que la respuesta a dextrán en presencia de SAB ocurre con cambio de isotipo (swith), essencialmente de IgM a IgG. Estos experimentos sugieren que la SAB genera un entorno bioquímico inductor de cambio de isotipo tanto en supropia via de procesamiento como en del dextrán. Los resultados señalan que la asociación exclusiva de los AgTDs con las respuestas em las que ocurre cambio de isotipo es incorrecta. Considerando el modelo propuesto resulta poco probable encontrar in vivo y en forma espontânea casos en los que los AgTIs ingreses al organismo aislados; en cambio, es mucho más probable que el ingreso ocurra conjuntamente con AgTDs, y en consecuencia ocurra cambio de isotipo.
Asunto(s)
Bovinos , Ratones , Animales , Masculino , Femenino , Antígenos T-Independientes/inmunología , Dextranos/inmunología , Cambio de Clase de Inmunoglobulina/inmunología , Albúmina Sérica Bovina/inmunología , Dextranos/farmacología , Cambio de Clase de Inmunoglobulina/efectos de los fármacos , Inmunoglobulina G/efectos de los fármacos , Inmunoglobulina G/inmunología , Inmunoglobulina M/efectos de los fármacos , Inmunoglobulina M/inmunología , Ratones Endogámicos BALB C , Modelos Animales , Albúmina Sérica Bovina/farmacologíaRESUMEN
Purified GM1 and GM2 gangliosides incorporated into liposomes were injected subcutaneously in BALB/c mice every 3-4 days after pretreatment of the animals with low-dose cyclophosphamide. Serum samples were collected at different intervals and tests by ELISA for the presence of anti-ganglioside antibodies. Four doses (50 micrograms each) were sufficient to raise a measurable primary type of response to GM1, while nine doses were required to obtain measurable IgM antibody titers to GM2. Three monoclonal antibodies (MAbs) wer generated by fusing splenocytes with mouse myeloma cells. The specificity of MAbs was determined by ELISA and HPTLC-immunostaining using a panel of purified glycolipids. The MAb designated E1 showed a high degree of specificity because it reacted only with N-acetyl GM2. Monoclonal antibody A3 reacted predominantly with GM2 and GM1, but also reacted moderately with the GM3 ganglioside. The epitope recognized by this MAb is suggested to be the trisaccharide sequence GalNAc beta 1-4(NeuAc alpha 2-3)Gal. The third MAb (F6) reacted strongly with GM1 but a weak reactivity was also observed with GD1b as well as with asialo-GM1, indicating that the terminal tetrasaccharide Gal beta 1-3GalNAc beta 1-4(NeuAc alpha 2-3)Gal- structure is probably involved in antigenic recognition. Formalin-fixed and paraffin-embedded tissue sections were stained with the E1 and A3 MAbs, using the avidin-biotin complex (ABC) technique. Strong immunoreactivity for E1 appeared in the tumor cells of five primary lung carcinomas and in five malignant melanomas. No immunoreactivity was demonstrated in the parenchyma of a lung without malignancy, or in a metastasis from a colon carcinoma.
Asunto(s)
Anticuerpos Monoclonales/biosíntesis , Antígenos T-Independientes/inmunología , Autoantígenos/inmunología , Linfocitos B/metabolismo , Gangliósido G(M1)/inmunología , Gangliósido G(M2)/inmunología , Animales , Sitios de Unión de Anticuerpos , Secuencia de Carbohidratos , Femenino , Ratones , Ratones Endogámicos BALB C , Datos de Secuencia MolecularRESUMEN
The titers of serum antibodies to natural infection with enteric and respiratory pathogens, to a food antigen and to tetanus and diphtheria toxoid were evaluated by enzyme-linked immunosorbent assay in 1,554 Ecuadorian children younger than 5 years of age. The nutritional status of the children was assessed by anthropometry and measurement of biochemical status indicators. The children were enrolled in a representative national nutrition and health survey. Antibody titers were analyzed as a function of the nutritional status of the children. For 12 of 14 antibody concentrations tested, underweight children showed lower antibody titers than did control children. The difference was statistically significant for antibody to both T-cell-dependent antigens (tetanus toxoid, rotavirus, respiratory syncytial virus) and T-cell-independent antigens (lipopolysaccharide, polyribosyl-ribitol phosphate, capsular polysaccharide). When children with a recent episode of diarrhea were excluded, many of the differences remained significant. When these children were further classified by age, only difference in titers of antibodies to respiratory syncytial virus and tetanus toxoid remained significant. No statistically significant difference was detected between underweight and control children with respect to protective antibody levels to four bacterial antigens. Anemic children showed significantly lower antibody levels to both T-cell-dependent and T-cell-independent antigens than did control children, and a higher proportion of anemic children had diphtheria antitoxin below a conservatively defined protective antibody level. No major differences in antibody titers were seen between children with different retinol and zinc concentrations in serum.
Asunto(s)
Anticuerpos Antibacterianos/sangre , Anticuerpos Antivirales/sangre , Trastornos Nutricionales/inmunología , Factores de Edad , Anemia/sangre , Anemia/epidemiología , Anemia/inmunología , Antropometría , Antígenos T-Independientes/inmunología , Peso Corporal , Preescolar , Comorbilidad , Corynebacterium diphtheriae/inmunología , Diarrea/sangre , Diarrea/epidemiología , Diarrea/inmunología , Ecuador/epidemiología , Humanos , Lipopolisacáridos/inmunología , Trastornos Nutricionales/sangre , Trastornos Nutricionales/epidemiología , Encuestas Nutricionales , Polisacáridos/inmunología , Polisacáridos Bacterianos/inmunología , Virus Sincitiales Respiratorios/inmunología , Rotavirus/inmunología , Streptococcus pneumoniae/inmunología , Toxoide Tetánico/inmunología , Deficiencia de Vitamina A/sangre , Deficiencia de Vitamina A/inmunología , Zinc/sangreRESUMEN
T lymphocyte responses in vitro are not all-or-none choices to environmental stimulation, but follow at least three distinct patterns: full activation and expansion, anergy induction, and receptor-mediated suicide by apoptosis. In vitro model systems were devised to investigate the differential control of T cell responses by surface CD activation molecules, CD4+ T cells from T. cruzi-infected mice are severely impaired in their proliferative response to TCR stimulation. TCR stimulation leads to CD4+ T cell suicide by apoptosis, but CD3 stimulation is less efficient in this effect. Triggering of normal CD4 T cells through CD4 coincident with TCR activation, does not affect proliferative responses, but induces marked morphological changes in the T cells, which become adherent, form extended cytoplasmic projections, and acquire motile behavior. This response requires IL4 production, and can be markedly upregulated by exogenous IL4. Autoreactive CD4 T cell functioning can help syngeneic B cells to produce a TH2 pattern of immunoglobulin isotypes following stimulation by a thymus independent antigen. These results indicate that distinct patterns of functional behavior in vitro can be induced, depending both on the past experience of the T cell and on the exact array of stimulatory CD antigens engaged in the process of activation. The relevance of these constraints in generating variable behavior for immunoregulation is discussed.