RESUMEN
If human antibody responses undergo molecular shifts similar to those identified in mice, the appropriate immunization strategy for the elderly would be a passive administration of the protective antibody from young donors rather than an attempt to boost the individual's own response with a more potent vaccine, because the shifted immune system can no longer make the right kind of antibody.
Asunto(s)
Envejecimiento/inmunología , Formación de Anticuerpos , Animales , HumanosRESUMEN
RIIIS/J mice lack an autosomal dominant gene(s) that influences the magnitude of the antibody response to several polysaccharide antigens of bacterial origin. Low responsiveness is demonstrable whether polysaccharide is administered as a T-helper-cell-independent or -dependent antigen conjugated to an immunogenic carrier; however, RIIIS/J mice make good anti-hapten antibody responses to haptenated polysaccharides. The low antibody responses of RIIIS/J mice to type III pneumococcal polysaccharide do not appear to be the results of an imbalance in the activity of regulatory T lymphocytes. Compared with other strains of mice, RIIIS/J mice elicit low antibody responses to lipopolysaccharide (LPS). They do not develop a cyclic primary or secondary antibody response to Escherichia coli O113 LPS; the latter is not due to a lack of mitogenic response to E. coli O113 LPS. They also produce auto-anti-idiotypic antibody after being immunized with trinitrophenyl-Ficoll.
Asunto(s)
Síndromes de Inmunodeficiencia/inmunología , Ratones Mutantes/inmunología , Polisacáridos/inmunología , Animales , Formación de Anticuerpos , Antígenos de Diferenciación/análisis , Antígenos Ly/análisis , Antígenos CD5 , Concanavalina A/farmacología , Haptenos , Memoria Inmunológica , Lipopolisacáridos/inmunología , Activación de Linfocitos , Ratones , Ratones Mutantes/genética , Polisacáridos Bacterianos/inmunología , Bazo/inmunologíaRESUMEN
Serum IgD levels were studied in mice. Strain-related variability of serum IgD levels was noted, and advanced age was associated with markedly increased IgD levels in a large percentage of mice from all strains. Strains prone to spontaneously arising autoimmune disease had elevated IgD levels; in NZB mice this was already present very early after birth (one week), whereas in MRL mice the elevated serum IgD levels were first seen somewhat later (3 months). In contrast, mice with collagen type II (CII)-induced autoimmune arthritis had no increase in serum IgD. Injection of the immunomodulating agents LPS and complete Freund's adjuvant (CFA) did not have a significant effect on serum IgD levels, but IL-1 induced a significant decrease in IgD.
Asunto(s)
Envejecimiento/inmunología , Enfermedades Autoinmunes/inmunología , Inmunoglobulina D/metabolismo , Adyuvantes Inmunológicos/farmacología , Animales , Ratones , Ratones Endogámicos , Especificidad de la EspecieRESUMEN
RIIIS/J mice produce low antibody responses to several polysaccharide Ag of bacterial origin. They have low levels of serum IgM and IgG3 and high levels of serum IgG2a and IgG2b. Low serum IgM and IgG3 have been attributed to a low frequency of CD5 (Ly-1) B cells, which play an important role in the production of natural antibodies. Indeed, RIIIS/J mice have a low frequency of CD5 (Ly-1)+, IgM bright+, Ly-5 (B220)dull+ (i.e., CD5 (Ly-1) B) cells in their peritoneum. RIIIS/J mice treated with LPS produce a low anti-bromelain-treated mouse RBC splenic plaque-forming cell response and a normal anti-mouse transferrin splenic PFC response. Those data are compatible with the fact that CD5 (Ly-1) B cells contain the precursors of B lymphocytes secreting anti-bromelain-treated mouse RBC antibody. However, they have a higher frequency of IgM bright+, Mac-1+ cells in their peritoneum. These cells represent the CD5 (Ly-1) "sister population" of CD5 (Ly-1) B cells described by others. This suggests that characteristics usually associated with the CD5 (Ly-1) lineage are applicable only to the CD5 (Ly-1)+ Mac-1+ IgM+ population, but not the related CD5 (Ly-1)- Mac-1+ IgM+ population. RIIIS/J mice should thus prove a valuable model to study the CD5 (Ly-1) B cell lineage.
Asunto(s)
Antígenos Ly/inmunología , Linfocitos B/inmunología , Síndromes de Inmunodeficiencia/inmunología , Animales , Autoanticuerpos/biosíntesis , Autoantígenos/inmunología , Linfocitos B/clasificación , Femenino , Citometría de Flujo , Técnica de Placa Hemolítica , Isotipos de Inmunoglobulinas/metabolismo , Síndromes de Inmunodeficiencia/sangre , Síndromes de Inmunodeficiencia/genética , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos NZB , Fenotipo , BazoRESUMEN
Three lines of evidence are presented which suggest that autoimmune-prone mice are deficient in the production of auto-anti-idiotype antibody during their immune response to trinitrophenylated Ficoll (TNP-F). NZB, MRL lpr/lpr and older BXSB male mice have no hapten-augmentable plaque-forming cells (PFC). Hapten-augmentable PFC have been previously shown to be cells whose secretion of antibody has been inhibited by the binding of auto-anti-idiotype antibody to cell surface idiotype. Sera from TNP-F immunized NZB mice lack PFC inhibiting activity (anti-idiotype antibody). Spleen cells from TNP-F immune NZB mice fail to transfer anti-idiotype antibody-mediated suppression to naive mice as do spleen cells from immune non-autoimmune-prone mice. Taken together these data suggest that autoimmune-prone mice are deficient in auto-anti-idiotype antibody-mediated downward regulation of their immune responses. It was further shown that the immune response of NZB mice to TNP-F shows a slower decline in splenic PFC and a greater heterogeneity of PFC affinity than do the responses of non-autoimmune-prone strains. Since athymic (nude) mice, which were previously shown to be defective in the production of auto-anti-idiotype antibody, also show a slower decline in splenic PFC and an increased heterogeneity of PFC affinity, it is suggested that these peculiarities of the immune responses of autoimmune-prone and athymic mice are also the consequences of the lack of auto-anti-idiotype antibody-mediated down-regulation.
Asunto(s)
Anticuerpos Antiidiotipos/inmunología , Autoanticuerpos/inmunología , Enfermedades Autoinmunes/inmunología , Ratones Endogámicos NZB/inmunología , Ratones Desnudos/inmunología , Animales , Afinidad de Anticuerpos , Inmunización Pasiva , Idiotipos de Inmunoglobulinas/inmunología , Síndromes de Inmunodeficiencia/inmunología , Masculino , Ratones , Ratones Endogámicos AKR/inmunología , Ratones Endogámicos BALB C , Bazo/inmunologíaRESUMEN
Antibody responses to T-dependent and T-"independent" antigens were studied in disease-susceptible (BALB/c and C57BL/10) and disease-resistant (A/J) mice infected with Leishmania donovani chagasi. Disease-susceptible mice but not disease-resistant mice showed a transient decrease in PFC responses to TNP on a T-dependent carrier (BGG) during the period of 4-8 weeks after infection. Infected disease-susceptible animals also showed increased responses to TNP on a type II T-independent carrier (Ficoll), which persisted until at least 14 weeks after infection. The increased responses were associated with a significant increase in anti-TNP antibody of the IgG2b subclass. When T-enriched spleen cells from infected mice and B-enriched spleen cells from uninfected mice were transferred to irradiated recipients immunized with TNP-Ficoll, increased anti-TNP PFC were observed over numbers seen in irradiated recipients which received both B and T cells from uninfected mice. Increased responses to TNP-Ficoll were also induced by prior administration of soluble leishmania extract in CFA. Infected mice immunized with TNP-LPS, a T-independent type I antigen, also had increased anti-TNP antibody responses, but had normal anti-LPS antibody responses. The elevated antibody production which occurred in response to the T-"independent" antigens could not be attributed to the relatively low polyclonal response which occurred in both disease-resistant and disease-susceptible mice infected with L. donovani chagasi. The observations are consistent with leishmania induced, transient alterations in some T-cell functions including response to haptens on T-dependent carriers, and a lack of down regulation of T-"independent" responses. Subtle lesions in immunoregulation may be important correlates of successful protozoal infection and may be responsible for some of the immunologic manifestations of the disease.
Asunto(s)
Antígenos T-Independientes/inmunología , Haptenos/inmunología , Leishmaniasis Visceral/inmunología , Linfocitos T/inmunología , Animales , Formación de Anticuerpos , Femenino , Ficoll/análogos & derivados , Ficoll/inmunología , Técnica de Placa Hemolítica , Inmunidad Innata , Leishmaniasis Visceral/parasitología , Lipopolisacáridos/inmunología , Ratones , Ratones Endogámicos A , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Trinitrobencenos/inmunología , gammaglobulinas/inmunologíaRESUMEN
An eluate prepared by brief incubation of spleen cells from 2,4,6-trinitrophenyl (TNP) lysyl-Ficoll immunized mice with TNP-epsilon-amino-n-caproic acid causes a specific inhibition of the induction of contact sensitivity by 2,4,6-trinitrochlorobenzene skin painting. The active factor in the eluate binds to an anti-mouse immunoglobulin (Ig) immunoadsorbent column but not to a TNP immunoadsorbent column and is therefore Ig but not anti-TNP antibody. The active factor does bind to an immunoadsorbent prepared from anti-TNP antibody, suggesting that the factor has anti-idiotype specificity. Evidence based upon hapten-reversible inhibition of plaque formation and an enzyme-linked immunosorbent assay (ELISA) indicates that the eluates contain auto-anti-idiotype antibody specific for anti-TNP antibody. It is suggested that auto-anti-idiotype antibody spontaneously produced during the immune response to a T-independent antigen can specifically downregulate contact sensitization to the same epitope.
Asunto(s)
Anticuerpos Antiidiotipos/inmunología , Formación de Anticuerpos , Autoanticuerpos/inmunología , Dermatitis por Contacto/inmunología , Idiotipos de Inmunoglobulinas/inmunología , Animales , Sueros Inmunes/inmunología , Técnicas de Inmunoadsorción , Masculino , Ratones , Ratones Endogámicos AKR , Ratones Endogámicos BALB C , Oxazolona/inmunología , Receptores de Antígenos de Linfocitos T/inmunología , Bazo/citología , Trinitrobencenos/inmunologíaRESUMEN
Tolerance was induced in young and old mice by the i.v. injection of TNP-modified syngeneic spleen cells. The tolerant state was associated with the development of hapten-specific suppressor T cells. The specificity of suppressor T cells was studied by transferring T cells from tolerant donors to normal, nonirradiated, syngeneic recipients, which were then immunized with TNP-Ficoll or TNP-bovine gamma-globulin. Suppressor T cells induced in young mice depressed the plaque-forming cell response of young but not old mice to both antigens. Similarly, suppressor T cells induced in old mice depressed the response in old but not young mice. These findings suggest that aging is associated with changes in idiotype repertoire which influence the specificity of the suppressor T cells present in tolerant mice.
Asunto(s)
Envejecimiento , Tolerancia Inmunológica , Idiotipos de Inmunoglobulinas/inmunología , Activación de Linfocitos , Linfocitos T Reguladores/fisiología , Animales , Ficoll/análogos & derivados , Ficoll/inmunología , Técnica de Placa Hemolítica , Inmunización Pasiva , Idiotipos de Inmunoglobulinas/genética , Idiotipos de Inmunoglobulinas/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Albúmina Sérica Bovina/inmunología , Bazo/citología , Linfocitos T Reguladores/inmunología , Trinitrobencenos/inmunologíaRESUMEN
An enzyme-linked immunosorbent assay (ELISA) to detect anti-idiotype (Id) antibody is described. Using this assay auto-anti-Id was detected in the serum of aged mice immunized with 2,4,6-trinitrophenylated-Ficoll (TNP-F). Hapten eluates from anti-TNP-F immune spleen cells also contained readily detectable auto-anti-Id.
Asunto(s)
Anticuerpos Antiidiotipos/biosíntesis , Formación de Anticuerpos , Autoanticuerpos/biosíntesis , Idiotipos de Inmunoglobulinas/inmunología , Envejecimiento , Animales , Anticuerpos Monoclonales/inmunología , Ensayo de Inmunoadsorción Enzimática , Hibridomas , Masculino , Ratones , Trinitrobencenos/inmunologíaRESUMEN
After immunization with trinitrophenyl (TNP)-Ficoll, mice produced both anti-TNP antibodies and auto-anti-idiotype (auto-anti-Id) antibodies specific for the anti-TNP antibody. Older animals produced more auto-anti-Id than did young animals. When mice were exposed to a normally lethal dose of irradiation while their bone marrow (BM) was partially shielded, they survived and slowly (6 wk) regained immune function, as indicated by the number of nucleated cells in their spleen and the in vitro primary plaque-forming cell (PFC) response of their spleen cells to TNP-treated aminoethylated polyacrylamide beads. Recovery is presumably the result of repopulation of the peripheral lymphoid system by cells originating in the BM. By enzyme-linked immunosorbent assay (ELISA), and by hapten-augmentable PFC assay, we show that, after recovery from irradiation with their BM shielded, old animals produce low auto-anti-Id responses, like those of young animals. The transfer of splenic T cells into mice irradiated with their BM shielded provided evidence that the magnitude of the auto-anti-Id response is controlled by the peripheral T cells. Thus, mice that received splenic T cells from aged donors produced high levels of auto-anti-Id while those that received splenic T cells from young donors produce low levels of auto-anti-Id.
Asunto(s)
Envejecimiento , Autoanticuerpos/biosíntesis , Médula Ósea/fisiología , Idiotipos de Inmunoglobulinas/inmunología , Linfocitos T/fisiología , Resinas Acrílicas/inmunología , Animales , Células Productoras de Anticuerpos/metabolismo , Células Productoras de Anticuerpos/efectos de la radiación , Médula Ósea/inmunología , Médula Ósea/efectos de la radiación , Técnica de Placa Hemolítica , Tejido Linfoide/efectos de la radiación , Masculino , Ratones , Ratones Endogámicos C57BL , Linfocitos T/inmunología , Linfocitos T/efectos de la radiaciónRESUMEN
The ontogeny of antibody responses to trinitrophenylated (TNP) thymus-independent (TI) antigens was compared in two partially inbred strains of chicken: the SC strain (B2/B2 genotype) and the FP strain (B15/B22 genotype). In the SC chicken, maturation of both the splenic anti-TNP plaque-forming cell (PFC) response and the 19S hemagglutinating antibody response to TI type 2 (TI-2) antigens, TNP-Ficoll and TNP-dextran, were delayed to a significantly later time in ontogeny (20 wk of age) than in the FP chickens (9 wk of age). Four- to 6-wk-old SC chickens were virtually immunologically unresponsive to stimulation with TI-2 antigens. The TI-1 antigen TNP-Brucella abortus was equally immunogenic in both FP and SC chickens of different age groups tested. Kinetic studies of the primary PFC response to TNP-Ficoll in immunologically mature chickens of the SC and FP strains demonstrated a peak PFC response 4 days after antigen injection, followed by a rapid decline in numbers of splenic PFC/spleen on day 6. The results of these studies are discussed in relation to earlier observations that suggested there may be a delay or a defect in the ontogeny of the thymus in the SC chicken.
Asunto(s)
Envejecimiento , Células Productoras de Anticuerpos/fisiología , Antígenos T-Independientes/inmunología , Pollos/inmunología , Animales , Células Productoras de Anticuerpos/metabolismo , Antígenos T-Independientes/administración & dosificación , Pollos/crecimiento & desarrollo , Dextranos/administración & dosificación , Dextranos/inmunología , Ficoll/administración & dosificación , Ficoll/análogos & derivados , Ficoll/inmunología , Técnica de Placa Hemolítica , Cinética , Bazo/citología , Trinitrobencenos/administración & dosificación , Trinitrobencenos/inmunologíaRESUMEN
The responses to 2,4,6-trinitrophenyl conjugates of different Ficoll preparations differ with respect to the magnitude of the accompanying auto-anti-idiotype (Id) response in both mice and chickens. Evidence is presented that reduced auto-anti-Id production in the chicken is due to the activation of suppressor activity by some preparations of Ficoll.
Asunto(s)
Autoanticuerpos/biosíntesis , Ficoll/inmunología , Idiotipos de Inmunoglobulinas/inmunología , Nitrobencenos/inmunología , Polisacáridos/inmunología , Trinitrobencenos/inmunología , Animales , Células Productoras de Anticuerpos/metabolismo , Pollos , Ficoll/administración & dosificación , Ficoll/análogos & derivados , Ficoll/farmacología , Haptenos/inmunología , Técnica de Placa Hemolítica , Inmunosupresores/farmacología , Cinética , Activación de Linfocitos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos BALB C , Bazo/citología , Linfocitos T Reguladores/inmunología , Trinitrobencenos/administración & dosificación , Trinitrobencenos/farmacologíaRESUMEN
Using hapten-reversible inhibition of plaque formation as an assay for auto-anti-idiotype antibody (anti-Id) and as a means for following idiotype (Id) expression, we have obtained evidence that following immunization with trinitrophenyl (TNP) conjugates (a) there are differences in Id expression in the anti-TNP antibody response to different TNP conjugates although there is some overlap; (b) different strains, although showing some differences in Id expression, tend to produce cross-reactive Ids, thus no obvious allotype linked inheritance of Id expression is observed in this heterogeneous immune response; (c) the auto-anti-Id produced following immunization with TNP-Brucella abortus or TNP-Ficoll tends to be of the IgG2a and IgG2b isotypes.
Asunto(s)
Formación de Anticuerpos , Autoanticuerpos/inmunología , Idiotipos de Inmunoglobulinas/inmunología , Animales , Bovinos/inmunología , Haptenos , Técnica de Placa Hemolítica , Ratones , Ratones Endogámicos C57BL , Trinitrobencenos/inmunología , gammaglobulinasRESUMEN
Splenic plaque-forming cell (PFC) responses to TNP-BGG (thymus-dependent) and TNP-Ficoll (thymus-independent) were measured during acute and chronic T. cruzi infections produced in C57BL/10 mice. The number of anti-TNP PFC to both antigens was suppressed as has been shown. Approximately 40% of untreated mice survived acute disease to enter chronic T. cruzi infection characterized by a decrease in parasitemia, a reduction in spleen size, a return to normal of the IgM responses to TNP-BGG and TNP-Ficoll, persistant polyclonal activation, and continued suppression of the IgG responses to TNP-BGG. Mice that were drug-treated during the acute disease had high survival rates and similar immune response patterns, ie., suppressed IgG PFC responses to TNP-BGG and normal IgM PFC responses to TNP-BGG and TNP-Ficoll. The selective suppression of the IgG response was transferred to nonirradiated syngeneic recipients by Thy-1.2-positive cells present in the spleens of chronically infected mice. These observations may be interpreted to suggest the persistence of nonspecific suppressor T cells during chronic T. cruzi infections.
Asunto(s)
Antígenos/administración & dosificación , Enfermedad de Chagas/inmunología , Inmunoglobulina G/biosíntesis , Linfocitos T Reguladores/inmunología , Animales , Células Productoras de Anticuerpos/inmunología , Antígenos/inmunología , Suero Antilinfocítico/administración & dosificación , Enfermedad de Chagas/parasitología , Enfermedad Crónica , Técnica de Placa Hemolítica , Activación de Linfocitos , Ratones , Ratones Endogámicos C57BL , Bazo/citología , Ácido Trinitrobencenosulfónico/administración & dosificación , Ácido Trinitrobencenosulfónico/inmunologíaRESUMEN
Mice of the NZB and NZW strains and their F1 hybrid produce antihapten plaque-forming cell (PFC) responses to T-dependent antigens (trinitrophenylated bovine gamma globulin and dansylated keyhole limpet hemocyanin) which are of unusually restricted heterogeneity of affinity, are relatively lacking in low-affinity PFC, and are of relatively high average affinity. Since some low-affinity PFC are present in NZB mice early after immunization, the results suggest a particularly marked down-regulation of low-affinity antibody production by these strains. The non-autoimmune-prone F1 hybrid (NZB X CBA) produces a typical heterogeneous response containing a high proportion of low-affinity PFC. Thus, the tendency to down-regulate low-affinity PFC is not inherited as a simple Mendelian dominant trait. The response of NZB mice to T-independent antigens does not show the same restricted heterogeneity of affinity. In fact, late after injections of trinitrophenylated Ficoll, NZB mice tend to have more heterogeneous responses than nonautoimmune-prone BALB/c mice in which a marked down-regulation of high-affinity antibody-producing PFC is seen. The possible relationship between these unusual features of the immune response of NZB and some related strains and their tendency to develop autoimmune disease is discussed.
Asunto(s)
Afinidad de Anticuerpos , Enfermedades Autoinmunes/inmunología , Haptenos/inmunología , Ratones Endogámicos NZB/inmunología , Animales , Células Productoras de Anticuerpos/inmunología , Antígenos/inmunología , Susceptibilidad a Enfermedades , Inmunogenética , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos , Linfocitos T/inmunología , Trinitrobencenos/inmunologíaRESUMEN
We have previously shown that old mice produce more hapten-augmentable plaque-forming cells (PFC) than do young animals, suggesting a greater auto-antiidiotype antibody (auto anti-Id) component in their immune response. In the present studies this is confirmed serologically. The marked auto-anti-Id response of aged mice can be transferred to lethally irradiated young recipients with spleen but not bone marrow cells from old donors, suggesting that it is an intrinsic property of their peripheral B cell population and that the distribution of Id arising from the bone marrow of old and young mice is similar. In contrast with young mice the auto-anti-Id response of old animals is relatively T cell-independent and old donors do not show an increase in their ability to transfer an auto-anti-Id response after priming with TNP-F. These observations suggest that old mice behave as if already primed for auto-anti-Id production. Irradiated mice reconstituted with bone marrow cells from either young or old donors together with splenic T cells from old donors generate a relatively large auto-anti-Id response, whereas mice reconstituted with bone marrow from either young or old donors together with splenic T cells from young donors produce few hapten-augmentable PFC. It is suggested that differences in Id expression and auto-anti-Id production are the consequences of the interaction of Id (and anti-Id) arising from the marrow with anti-Id (and Id) present in the peripheral T cell population which serves as a repository of information about shifts in Id distribution, resulting from lifelong interactions with environmental and self-antigens.
Asunto(s)
Envejecimiento , Células Productoras de Anticuerpos/inmunología , Autoanticuerpos/biosíntesis , Idiotipos de Inmunoglobulinas/inmunología , Animales , Antígenos T-Independientes/inmunología , Sitios de Unión de Anticuerpos , Médula Ósea/inmunología , Células de la Médula Ósea , Femenino , Ficoll/análogos & derivados , Ficoll/inmunología , Técnica de Placa Hemolítica , Inmunización Pasiva , Masculino , Ratones , Ratones Endogámicos AKR , Ratones Endogámicos C57BL , Bazo/citología , Bazo/inmunología , Linfocitos T/inmunología , Trinitrobencenos/inmunologíaRESUMEN
(1) Evidence has been presented that the detection of hapten-augmentable plaques indicates cells whose secretion of antibody had been blocked by the binding of auto-anti-id to cell surface idiotypes. Because of the dependence of the assay on the affinities of the various species for one another, the number of hapten-augmentable plaques detected should be regarded as a minimal estimate of the number of cells whose secretion of antibody is inhibited by auto-anti-id. For confirmation that hapten-augmentable PFC are due to auto-anti-id 2 principal controls are important: (a) incubation of the spleen cell population with hapten prior to plaquing should remove the hapten-augmentable PFC; (b) the dialyzed supernate from hapten incubated cells should inhibit plaque formation in a hapten-reversible manner. (2) Evidence has been presented that hapten-reversible inhibition of plaque formation can serve as an assay for anti-id. Apparent false positive assays can result from the presence of anti-hapten antibody or antigen-antibody complexes; however, these apparent false positives are rarely reversed by hapten. Removal of anti-hapten antibody, by passage over an antigen immunoadsorbent, will eliminate this source of false positives and the procedure is recommended. False negative results can arise from mismatching of the anti-ids in the sample to be assayed and the idiotypes of the target cells used in the assay. This can result from shifts in idiotype expression related to age and time after antigen injection. False negatives can also result from the presence of idiotype-anti-id complexes in the sample to be assayed. This source of false negatives can sometimes be eliminated by passage of the sample through an antigen immunoadsorbent.