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Humoral immune response of dogs vaccinated with leptospiral pentavalent outer envelope and whole culture vaccines.

The humoral immune response of dogs vaccinated with leptospiral pentavalent outer envelope and whole culture vaccines was monitored with the microscopic agglutination (MA) test and leptospiricidal activity (LA) test for a 2-year period. The leptospiral serovars in the vaccines was canicola, icterohaemorrhagiae, grippotyphosa, pomona, and hardjo. The LA test was markedly more sensitive than the MA test for detecting anti-Leptospira antibodies and was least noticeable with anti-pomona antibodies. Both Igm and IgG were produced in similar amounts in the vaccinated dogs, and both classes of immunoglobulins were reactive in the MA and LA tests. The IgM class of antibodies was slightly more reactive in the MA test, whereas IgG antibodies were somewhat more reactive in the LA test. A direct correlation between protective antibodies, as determined by the hamster passive-protection test, and antibodies reactive in the MA and LA tests was observed.

Agglutination Tests↗

[Humoral immune response after splenic experimental autotransplantation in the dog (author's transl)].

Primary and secondary humoral immune responses were studied in a group of 40 dogs after splenectomy and two types of splenic autotransplantation. The results enable the authors to conclude that splenectomy alone induces a depletion of immunoglobulins which is statistically significant. On the other hand, both types of autotransplantation made possible the maintenance of normal levels of anti-BSA antibodies. When autotransplantation was performed in the abdominal rectus muscle there was an enhancement of the primary immune response. The authors advise this procedure in all splenectomies for trauma in the first five years of life.

Animals↗

Correlations between humoral immunity and successful chemotherapy-immunotherapy.

Experiments were designed to evaluate the characteristics of the humoral immune response induced by active immunotherapy, both specific (neuraminidase-treated tumore cells) and nonspecific (Bacillus Calmette-Guérin organisms), in the L1210-C57BL/6 X DBA/2F tumor-host system. Tumor burden was minimized with chemotherapy (1,3-bis-(2-chloroethyl)-1-nitrosourea) prior to immunotherapy. A marked increase in the concentration of serum immunoglobulins (immunoglobulin M, immunoglobulin G, and immunoglobulin G) was observed following successful therapy. The highest concentration of these immunoglobulins was found in mice given both Vibrio cholerae neuraminidase-treated cells and B. Calmette-Guérin after chemotheraphy. Tumor-specific immunoglobulin M and immunoglobulin G, as measured by indirect immunofluorescnece, were detected in the sera during the course of successful therapy. Positive immunofluorescence was not observed with progressive sera. Complement-dependent cytotoxic activity against L1210 cells was first detected 5 days after immunotherapy, and increased for several weeks. A high level of cytotoxic activity correlated with successful therapy, whereas low levels were foun in treated mice with recurring tumors. Serum cytotoxicity was not detected in untreated mice with progressively growing tumor.

Animals↗

Giardia duodenalis: analysis of humoral immune response in experimentally infected gerbils (Meriones unguiculatus).

In this work, we have analyzed the humoral immune response in Mongolian gerbils infected with Giardia duodenalis trophozoites of strains P-1 and WB. The course of infection in the animals was assessed by monitoring cyst shedding in feces, and serum samples were collected at weekly intervals to measure antibody levels by ELISA. Parallel studies were carried out to determine the patterns of total and surface antigens of the parasite recognized by antibodies using Western blot and radioimmunoprecipitation (RIP) assays with the use of homospecific enzyme conjugates. Typical patterns of cyst shedding were observed in the infected animals and cyst numbers per gram of feces were consistently higher in gerbils infected with WB strain. Antibody levels to G. duodenalis antigens were observed by week 2 post-infection and were still detectable 4 months after infection. G. duodenalis antigens showed a complex but quantitatively and qualitatively different recognition pattern by infection-induced antibodies in Western blot assays which related to infecting strain. However, RIP assays showed a more restricted and common pattern of recognition of surface antigens from either strain. Taken together, the data obtained in this study provides further information regarding direct comparisons among infecting strain, patterns of infectivity, and host immune response toward G. duodenalis antigens in the gerbil model.

Animals↗

[Tests of specific cellular and humoral immunity in herpetic infections of the eyes].

The ratio of the values of lymphocyte blast transformation and leukocyte migration inhibition to the level of humoral antibodies, detection of HSV antigen in the eye and activity of the clinical process in the time course of disease was studied in 213 patients with ophthalmoherpes. The immunological markers characterizing the features of pathogenesis and prognosis of herpetic eye disease were determined. In the favourable course of ophthalmoherpes blast transformation of 5-10% and stable migration inhibition throughout the disease were observed. A decrease in the functional activity of lymphocytes determined in the blast transformation test with phytohemagglutinin, the lack of specific blast transformation and migration inhibition, as well as marked increase of blast formation (above 10-15%) are the factors aggravating the course of the disease. The infectious and infectious-allergic period in the course of ophthalmoherpes were identified. The infectious stage was characterized by changes in the values of both cellular and humoral immunity. In the infectious-allergic stage cellular immunity reactions prevail in the presence of stable humoral antibody levels.

Adolescent↗

Cell-mediated and humoral immune responses to chlamydial antigens in guinea pigs infected ocularly with the agent of guinea pig inclusion conjunctivitis.

Cell-mediated immune response and humoral response to chlamydial antigens were investigated in guinea pigs infected with the agent of guinea pig inclusion conjunctivitis (GPIC). Pronounced cell-mediated immune response to the homologous antigen, as well as to two other chlamydial antigens, 6BC (Chlamydia psittaci) and LB-1 (C. trachomatis), occurred in all infected animals. Cell-mediated immune response to GPIC, and to a lesser extent to 6BC and LB-1 as well, was enhanced with time after infection even without the re-inoculation of the infectious agent. Extensive cross-reactions among the three chlamydial antigens during the cell-mediated immune response appeared to be due to shared species-specific and group-reactive antigens. Serum antibody response was pronounced and uniform to GPIC; it was less marked to 6BC and LB-1, with fewer cross-reactions than seen in tests for cell-mediated immunity.

Animals↗

[Immune response to heart in rabbits: study of cellular and humoral immunity (author's transl)].

Four groups of rabbits injected with cardiac tissue and complete Freund's adjuvant or aluminum hydroxide gel adjuvant and two groups only injected with aluminum hydroxide gel adjuvant or complete Freud's adjuvant were studied. The humoral and cellular immunity in immunized animals was studied using heart soluble and insoluble extracts. The tests results from hemagglutination, immunoelectrophoresis and immunofluorescence have presented cross-reactions among sera and hearts of the several species. Similar cross-reactions were not revealed by immunodiffusion. The immunoelectrophoresis and hemagglutination reactions were related to heart soluble extract and the immunofluorescence reactions were related to insoluble extract located in sarcolemal, subsarcolemal and intermyofibrilar sites. By hemagglutination, it was verified the presence of antibodies to heart and skeletal muscle in the antisera. Is was not possible to negative completely the reactivity of these antibodies to heart by absorptions with skeletal muscle. Inhibition tests to leucocytes migration revealed that leucocytes from immunized animals present migration inhibition when faced to antigens sedimented at.....56.500 g.

Animals↗

Expression of human immunodeficiency virus type 1 gp120 from herpes simplex virus type 1-derived amplicons results in potent, specific, and durable cellular and humoral immune responses.

Herpes simplex virus type 1 (HSV-1) infects a wide range of cells, including dendritic cells. Consequently, HSV-1 vectors may be capable of eliciting strong immune responses to vectored antigens. To test this hypothesis, an HSV-1 amplicon plasmid encoding human immunodeficiency virus type 1 gp120 was constructed, and murine immune responses to helper virus-free amplicon preparations derived from this construct were evaluated. Initial studies revealed that a single intramuscular (i.m.) injection of 10(6) infectious units (i.u.) of HSV:gp120 amplicon particles (HSV:gp120) elicited Env-specific cellular and humoral immune responses. A potent, CD8(+)-T-cell-mediated response to an H-2D(d)-restricted peptide from gp120 (RGPGRAFVTI) was measured by a gamma interferon ELISPOT and was confirmed by standard cytotoxic-T-lymphocyte assays. Immunoglobulin G enzyme-linked immunosorbent assay analysis showed the induction of a strong, Env-specific antibody response. An i.m. or an intradermal administration of HSV:gp120 at the tail base elicited a more potent cellular immune response than did an intraperitoneal (i.p.) inoculation, although an i.p. introduction generated a stronger humoral response. The immune response to HSV:gp120 was durable, with robust cellular and humoral responses persisting at 171 days after a single 10(6)-i.u. inoculation. The immune response to HSV:gp120 was also found to be dose dependent: as few as 10(4) i.u. elicited a strong T-cell response. Finally, HSV:gp120 elicited significant Env-specific cellular immune responses even in animals that had been previously infected with wild-type HSV-1. Taken together, these data strongly support the use of helper-free HSV-1 amplicon particles as vaccine delivery vectors.

Animals↗

A prospective study of the association between the human humoral immune response to Plasmodium falciparum blood stage antigen gp190 and control of malarial infections.

The human humoral immune response to the Plasmodium falciparum merozoite surface antigen gp190 was analyzed to determine the rate of reinfection by the parasite and the ability to control parasite density. The prospective study was carried out in a West African village where malaria is hyperendemic. No correlation between the antibody titers and protection against infection was observed within the group of children. Positive and negative associations of antibody specificities with protection against and/or control of parasitemia were, however, found for adolescents and adults, respectively. Thus, in adolescents, the presence of antibodies to gp190 fragment M6 correlates with a 50% reduced risk of P. falciparum infection and an increased ability to control parasitemia, whereas in adults, the humoral response to some of the polymorphic regions of gp190 associates with an increased risk of infection.

Adult↗

Cellular and humoral immune responses to a tetanus toxoid booster in perinatally HIV-1-infected children and adolescents receiving highly active antiretroviral therapy (HAART).

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) infected children treated with highly active antiretroviral therapy (HAART) may develop a significant reduction of plasma viremia associated with an increase in CD4+ T-cell counts. Functional capacity of this reconstituted immune system in response to recall antigens is important to maintain protective immunity to vaccine-preventable diseases. We therefore determined cellular and humoral immune responses to tetanus toxoid (TT) booster in perinatally HIV-1-infected children and adolescents receiving HAART. METHODS: Immune responses were prospectively evaluated pre- and post-tetanus booster using lymphocyte proliferation assay (LPA) stimulation index (SI > or = 3.0) and tetanus antibody (TAb > or = 0.15) in 15 patients. The median interval from primary tetanus immunization series was 6 years (range 2-12 years). We compared patients by their virological response to HAART (complete responders, CR, n=7; incomplete responders, ICR, n=8). RESULTS: There were no significant differences in median age 12.6 years (CR: 12.9; ICR: 10.6) or median CD4 T-cell pre-booster (CR: 35%/819; ICR: 26%/429) between groups. Tetanus LPA responses were observed in one patient prior to booster and in seven patients post-booster. In contrast, 38% of patients had protective TAb pre-booster, but 92% developed protective TAb post-booster. All of the CR and 5/6 ICR patients developed protective TAb. CONCLUSIONS: HIV-1-infected children and adolescents had modest LPA responses to tetanus following booster, similar to HIV-1-infected adults. However, the majority of patients developed protective TAb levels after booster and maintained the response. Shorter intervals may need to be considered for TT immunization boosters in HIV-1-infected pediatric patients, as only 38% had protective TAb at baseline.

Antibody Formation↗

Mechanisms of humoral immunity during Ehrlichia chaffeensis infection.

Our laboratory has been investigating the mechanisms of host defense during Ehrlichia chaffeensis infection in the mouse. Although major roles are clearly played by T cells, we found that antibodies could also control infection in both normal and immunocompromised SCID mice, and could protect the latter from lethal infection. Antibodies are not generally effective during such intracellular infections, so we would like to understand exactly how antibodies can mediate immunity in this model. We have found that much of the humoral immune response is directed at the bacterial outer membrane proteins (OMPs), and that highly effective OMP antibodies (mostly IgG2a) exhibited picomolar affinities and very long binding half-lives. These antibodies, which could mediate bacterial clearance from tissues as early as 24 hours after administration, require host Fc receptors for their function(s). In contrast, we have failed to find any role for complement or reactive nitrogen intermediates, or for neutrophils, or for NK cells. One possible mechanism is that antibodies or immune complexes trigger microbiocidal activities in infected macrophages that lead to the elimination of bacteria residing inside host macrophages. Alternatively, it is proposed that antibodies opsonize bacteria exposed during intercellular transfer. This notion is supported by studies that have demonstrated the presence of bacteria in the extracellular milieu during infection, and suggests that our understanding of the behavior of the bacterium in the host may be key to our understanding of its susceptibility to antibody-mediated host defenses.

Animals↗

Engagement of OX40 enhances antigen-specific CD4(+) T cell mobilization/memory development and humoral immunity: comparison of alphaOX-40 with alphaCTLA-4.

Increasing the long-term survival of memory T cells after immunization is key to a successful vaccine. In the past, the generation of large numbers of memory T cells in vivo has been difficult because Ag-stimulated T cells are susceptible to activation-induced cell death. Previously, we reported that OX40 engagement resulted in a 60-fold increase in the number of Ag-specific CD4(+) memory T cells that persisted 60 days postimmunization. In this report, we used the D011.10 adoptive transfer model to examine the kinetics of Ag-specific T cell entry into the peripheral blood, the optimal route of administration of Ag and alphaOX40, and the Ag-specific Ab response after immunization with soluble OVA and alphaOX40. Finally, we compared the adjuvant properties of alphaOX40 to those of alphaCTLA-4. Engagement of OX-40 in vivo was most effective when the Ag was administered s.c. Time course studies revealed that it was crucial for alphaOX40 to be delivered within 24-48 h after Ag exposure. Examination of anti-OVA Ab titers revealed a 10-fold increase in mice that received alphaOX40 compared with mice that received OVA alone. Both alphaOX40 and alphaCTLA-4 increased the percentage of OVA-specific CD4(+) T cells early after immunization (day 4), but alphaOX40-treated mice had much higher percentages of OVA-specific memory CD4(+) T cells from days 11 to 29. These studies demonstrate that OX40 engagement early after immunization with soluble Ag enhances long-term T cell and humoral immunity in a manner distinct from that provided by blocking CTLA-4.

Abatacept↗

Simultaneous cellular and humoral immune response against mutated p53 in a patient with lung cancer.

We recently identified several Ags recognized by tumor-infiltrating B lymphocyte-derived Ab using SCID mice and a xenografted non-small cell lung cancer system. One of these identified Ags was mutated p53 with a point mutation resulting in the alteration of codon 158 from Arg to Leu. The aim of this study was to ascertain whether cellular immunity against mutated p53 exists in the same patient together with humoral immunity. Two different nona peptides (mutated p53(150) and p53(155) peptides), including a mutated amino acid derived from p53, were synthesized according to the binding motif of HLA class I of the established cancer cell line A904L from the patient. Mediastinal lymph node lymphocytes of the patient were stimulated weekly with the peptides. The mutated p53(155) peptide-stimulated lymphocytes showed specific cytotoxicity against both autologous EBV-transformed B cells pulsed with mutated p53(155) peptide and A904L. The mutated p53(155) peptide-specific CTL clone in an HLA-Cw*0702 restriction was established and analyzed for its TCR usage. Clonotypic PCR using CDR3-specific primers was applied to the tumor tissue containing the tumor-infiltrating lymphocytes. The specific amplification of PCR was found in the tumor tissue. These results demonstrated that not only B lymphocytes producing specific Ab against the p53 protein, but also CTL against mutated p53, expressed in autologous lung cancer cells exist in the tumor tissue. This approach may allow us to better understand the mechanisms of T and B cell immunity against the same tumor Ag in cancer patients.

Amino Acid Sequence↗

Humoral immune response to mutans streptococci associated with dental caries.

BACKGROUND: Mutans streptococci are important aetiological agents in dental caries and their prolonged contact with oral tissues evokes a variety of immune responses through local secretory and systemic antibodies. Patterns of such humoral responses in Indian children have not been reported and we undertook the present study to examine these. METHODS: One hundred and twenty-six children with dental caries and 55 matched controls were studied and saliva and sera collected from them. The tests on these specimens included total salivary and systemic immunoglobulins of different classes using radial immunodiffusion and Streptococcus mutans specific IgA, IgG and IgM using specifically standardized enzyme immunoassays. RESULTS: Children with caries had higher levels of IgG (1350 +/- 9.9 mg/dl; controls 1110 +/- 6.7 mg/dl) and IgA (260 +/- 1.8 mg/dl; controls 190 +/- 1 mg/dl) in the serum but their saliva had lower levels of total IgG (160 +/- 0.7 mg/dl; controls 340 +/- 2.9 mg/dl) and IgA (130 +/- 0.5 mg/dl; controls 410 +/- 3 mg/dl). IgM levels in caries children and controls were not significantly different. Higher levels of Streptococcus mutans specific IgA were detected in the saliva of 95 out of 126 (75%) children with caries compared to 13 out of 55 (22%) controls. Specific serum IgG and IgA levels were also increased in 105 and 114 children with caries, although the levels were not as high as those in saliva. Total and specific salivary and serum IgM antibodies were similar in children with caries and control subjects. CONCLUSION: The nature of the humoral immune response in Indian children with dental caries suggests that Streptococcus mutans specific salivary and serum antibodies may play a major role in pathogenesis. Our findings may have importance when devising methods for follow up and prognosis as well as for vaccination strategies.

Adolescent↗

[Cellular and humoral immunity in patients with acute disorder of coronary circulation].

The condition was studied of cell-bound and humoral immunity in patients with ischemic heart disease. The data secured permit reaching the conclusion that the unstable clinical course of angina pectoris is accompanied by unspecific alterations in the cellular link of immunity such as increase in the absolute number of T-lymphocytes and T-suppressors. In patients with myocardial infarction, in the acute period of the illness there develop inflammatory reactions involving participation of cell-bound (neutrophilic leucocytosis, a drop in the absolute number of acidophilic granulocytes, absolute number of lymphocytes, T-lymphocytes, T-suppressors, increase in T-helpers--T-suppressors ratio; decline in T-lymphocytes activity) and humoral (a drop in the level of Ig A, increase in blood serum concentration of circulating immune complexes) links of immunity.

Acute Disease↗

Comparison of ELISA and plaque-forming cell assays for measuring the humoral immune response to SRBC in rats and mice treated with benzo[a]pyrene or cyclophosphamide.

The humoral immune response against sheep red blood cells (SRBC) is one of the most sensitive and frequently used end-points in evaluating the immunotoxicity of drugs and chemicals in experimental animals. Currently, most immunotoxicology studies measure the SRBC IgM antibody response by quantitating the number of SRBC-specific IgM antibody-forming cells using the hemolytic plaque assay. On the other hand, measurement of serum SRBC-specific IgM could be an easier, more cost effective endpoint in evaluating the SRBC antibody response in rodents. A validated method to measure SRBC-specific IgM, however, has not been developed. Thus, the objectives of the studies presented were to develop and validate an enzyme-linked immunosorbent assay (ELISA) for SRBC-specific IgM. Hemoglobin-free, detergent-solubilized membrane preparations were chosen as antigen for the ELISA. Various sources of SRBC were found to be equally useful, and as little as 0.1 micrograms of protein per well was optimal. Kinetic studies of the IgM response showed the peak day to be on Day 5 (mice) and Day 6 (rats). To validate the usefulness of the method for immunotoxicologic studies, serum SRBC-specific IgM levels and number of SRBC-specific plaque-forming cells were compared in rats and mice treated with two well-characterized immunosuppressive agents: benzo[a]pyrene and cyclophosphamide. Administration of these chemicals was found to produce very similar dose-dependent decreases in serum SRBC IgM and IgM-specific plaque-forming cells. These two endpoints were equally sensitive to the effects of the immunosuppressive drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on humoral immunity and lymphocyte subpopulations: differences between mice and rats.

While the effect that TCDD has on humoral immunity has been well documented for the mouse, it has not been for the rat. In this study, the effect that TCDD has on the antibody plaque-forming cell (PFC) response to sheep red blood cells (SRBC) in adult female B6C3F1 mice and F344 rats was compared. The effect that TCDD has on the PFC response of male F344 and female Long-Evans rats was also determined. Mice or rats were given a single intraperitoneal injection of TCDD at doses ranging from 0.1 to 30 micrograms/kg, 7 days prior to intravenous immunization with SRBC. Four days later the PFC response to SRBC was determined. Mice showed a dose-related suppression of the PFC response, with an ED50 of 0.7 micrograms/kg TCDD. In contrast, TCDD failed to suppress and in fact enhanced the PFC response to SRBC in rats at doses as high as 30 micrograms/kg. The inability of TCDD to suppress the PFC response in rats was unrelated to hepatic CYP1A1 and CYP1A2 induction which was detectable at doses of 1 and 0.3 microgram/kg TCDD, respectively. There was no shift in the time to peak PFC response in rats dosed with TCDD, nor was the failure of TCDD to suppress the PFC response in rats related to gender or strain. Phenotypic analysis of thymocytes and splenic lymphocytes from TCDD-dosed (i.e., 3, 10, or 30 micrograms/kg) and SRBC-immunized mice and rats revealed that CD4-CD8+ splenocytes were reduced in a dose-related manner in rats only and that this reduction in CD4-CD8+ was accompanied by a dose-related increase in IgM+ splenocytes. These results demonstrate species differences in the effect of TCDD on the PFC response to SRBC which were unrelated to hepatic CYP1A1 or CYP1A2 induction, time to peak response, gender, and strain. The failure of TCDD to suppress and in fact to enhance the PFC response to SRBC in rats appears to be related to alterations in splenic CD4-CD8+ lymphocytes.

Animals↗

Effect of corticosterone infusion on plasma corticosterone concentration, antibody production, circulating leukocytes and growth in chicken lines selected for humoral immune responsiveness.

The effect of corticosterone on antibody production was studied in chicken lines selected for humoral immune response. 2. Twelve cockerels (33 days old) from lines selected for high or low antibody responses after immunisation with sheep red blood cells (SRBC) were implanted with mini-infusion pumps delivering corticosterone or vehicle continuously for 14 d. 3. Three days after implantation, the chickens were immunised intramuscularly with 0.25 ml packed SRBC. Blood samples were taken before implantation, before immunisation and 3, 5, 7 and 11 d after immunization. 4. Corticosterone infusion induced higher plasma corticosterone concentrations and heterophil/lymphocyte ratios than infusion of vehicle only. Growth was considerably depressed and relative weights of the thymus, bursa of Fabricius and spleen were less in the corticosterone-infused chickens. 5. An effect of corticosterone on antibody production could not be demonstrated, and differences between selection lines were unaffected.

Animals↗