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PubMedDate not supplied

[Separate and combined effects of ionizing radiation and cyclophosphamide on thymus-dependent humoral immune response].

The total exposure of gamma-irradiation, (1-2 Gy) or intraperitoneally injection of cyclophosphamide (10-50 mg/kg) resulted in the dose-dependent inhibition of humoral immune response. The immunosuppression was expressed to a greater degree in lymphatic nodules, than in spleen. The combined action of these factors showed the effect of synergism. The injection of cyclophosphamide in mice neutralized the effect of antibody genesis induced by low dose irradiation (0.1 Gy).

Animals↗
PubMed1983

[Cellular and humoral immune phenomena in psoriatic arthritis].

The function of cellular immunity factors (lymphocyte transformation and phagocytosis by polymorphonuclear leucocytes [PMN] and monocytes in connection with the concentration of intracellular ATP) and humoral immunity factors (serum concentration of immunoglobulin and complement factors C'3 and C'4) was investigated in 16 controls, 21 patients with psoriatic arthritis and 19 with psoriasis vulgaris. The results were compared with the clinical and anamnestic data of the patients. PMN phagocytosis of zymosan opsonized with rabbit standard serum was decreased in psoriasis vulgaris in comparison with the controls. Also, monocyte phagocytosis of non-opsonized zymosan was decreased in psoriatic arthritis, as compared with psoriasis vulgaris. Furthermore, in PMNs intracellular ATP was elevated in psoriatic arthritis as compared with the controls, but decreased in comparison with patients with psoriasis vulgaris. The intracellular ATP in monocytes was decreased in psoriasis vulgaris as compared with the controls. Humoral immunological findings: serum IgG concentration was higher in psoriatic arthritis than in controls and in psoriasis vulgaris. Elevated C'3 and decreased C'4 serum concentrations in psoriatic arthritis indicate an activation of the complement system.

Adenosine Triphosphate↗
PubMed1997

Maturation of the cellular and humoral immune responses to persistent infection in horses by equine infectious anemia virus is a complex and lengthy process.

Equine infectious anemia virus (EIAV) provides a natural model system by which immunological control of lentivirus infections may be studied. To date, no detailed study addressing in parallel both the humoral and cellular immune responses induced in horses upon infection by EIAV has been conducted. Therefore, we initiated the first comprehensive characterization of the cellular and humoral immune responses during clinical progression from chronic disease to inapparent stages of EIAV infection. Using new analyses of antibody avidity and antibody epitope conformation dependence that had not been previously employed in this system, we observed that the humoral immune response to EIAV required a 6- to 8-month period in which to fully mature. During this time frame, EIAV-specific antibody evolved gradually from a population characterized by low-avidity, nonneutralizing, and predominantly linear epitope specificity to an antibody population with an avidity of moderate to high levels, neutralizing activity, and predominantly conformational epitope specificity. Analyses of the cell-mediated immune response to EIAV revealed CD4+ and CD8+ major histocompatibility complex-restricted, EIAV-specific cytotoxic T-lymphocyte (CTL) activity apparent within 3 to 4 weeks postinfection, temporally correlating with the resolution of the primary viremia. After resolution of the initial viremia, EIAV-specific CTL activity differed greatly among the experimentally infected ponies, with some animals having readily detectable CTL activity while others had little measurable CTL activity. Thus, in contrast to the initial viremia, it appeared that no single immune parameter correlated with the resolution of further viremic episodes. Instead, immune control of EIAV infection during the clinically inapparent stage of infection appears to rely on a complex combination of immune system mechanisms to suppress viral replication that effectively functions only after the immune system has evolved to a fully mature state 6 to 8 months postinfection. These findings strongly imply the necessity for candidate EIAV and other lentivirus vaccines to achieve this immune system maturation for efficacious immunological control of lentivirus challenge.

Animals↗
PubMed1994

Humoral immune response to Salmonella abortusovis in sheep: in vitro induction of an antibody synthesis from either sensitized or unprimed lymph node cells.

In vitro culture conditions were determined to induce an anti-Salmonella abortusovis antibody synthesis from lymph node leucocytes of three immunized sheep and two unprimed lambs maintained in culture in the presence of heat-inactivated bacteria for 2 weeks. Humoral immune responses were assessed by enumerating specific antibody-secreting cells using ELISASPOT and by titrating immunoglobulins secreted into culture supernatants using ELISA techniques. Optimal secondary antibody response was observed from cultures performed with fetal calf serum (compared with horse serum) and with an antigen concentration of one to ten bacteria per cell. This kind of antigenic stimulation allowed induction of numerous antibody-secreting cells without adsorption of the secreted antibodies. Maximal numbers of antibody-secreting cells could reach a rate of 1% of the sheep leucocytes initially put into culture. Kinetic profiles of antibody production from boosted lymph node cells were characterized by an ascending phase from the sixth to the twelfth day of culture and then showed a plateau phase until Day 14. Most of the responses were composed of IgM and IgG1 antibodies, traces of IgG2 being detected at the end of experiments. From the twelfth day of antigenic stimulation, the IgM isotype was preferentially expressed with high antigen concentration (100 bacteria per cell), whereas the highest amounts of IgG1 were detected at lower concentration (one to ten bacteria per cell). While anti-Salmonella IgM appeared to be mainly specific for the lipopolysaccharide (LPS) cell wall fraction, some IgG1 recognized other bacterial antigens. Kinetic profiles and magnitudes of primary antibody responses induced in vitro from lamb lymph node cells did not differ from those defined in cultures of sheep boosted leucocytes. But these immune reactions were mainly made up of anti-LPS IgM. Few anti-Salmonella IgG1 were detected from the tenth day of culture. So these in vitro assays allowed induction of antibody synthesis from either in vivo sensitized or unprimed sheep lymph node leucocytes. This methodology would permit achievement of more detailed studies on interactions between Salmonella and lymph node leucocytes, leading to a better understanding of the mechanisms controlling bacterial dissemination through the lymphoid tissue.

Animals↗
PubMed1996

The humoral immune response of turbot, Scophthalmus maximus L., to spore-surface antigens of microsporidian parasites.

Experiments based on enzyme-linked immunosorbent assay (ELISA) revealed considerable antigenic homology in turbot between two species of microsporidian, Tetramicra brevifilum (a parasite of the turbot, Scophthalmus maximus) and Glugea caulleryi (a parasite of the lesser sand-eel, Ammodytes tobianus). We next investigated whether G. caulleryi is able to suppress the turbot immune response. Intraperitoneal inoculation of turbot with G. caulleryi spores (whether heat-killed or viable) did not suppress the humoral immune response to injection of G. caulleryi spores plus adjuvant 15 days later; in fact, specific serum antibody levels (as revealed by ELISA) reached maximum levels by about Day 30 post re-exposure. Similar results were obtained with cellular enzyme-linked immunosorbent assay: 15 days after injection with G. caulleryi spores plus adjuvant, specific antibody secretion rate was higher in turbot which had been pre-exposed to G. caulleryi spores than in turbot which had not been pre-exposed.

Animals↗
PubMed2004

The regulatory effect of polychromatic (visible and infrared) light on human humoral immunity.

The immunological effects of visible and infrared light from laser and non-laser sources have remained insufficiently studied, which has restricted the use of light in the treatment of diseases associated with immune system disorders. The present randomised, placebo-controlled double-blind trial was designed to study changes in the humoral immunity of a large group of volunteers after exposure of a small body area to polychromatic visible and infrared polarized (VIP) and non-polarized (VInP) light (400-3400 nm, 95% polarization, 40 mW cm(-2), 12 J cm(-2) and 400-3400 nm, no polarization, 38 mW cm(-2), 11.2 J cm(-2), respectively). Serum immunoglobulins (Ig) M, A, and G were determined turbidimetrically, and the immune complexes (ICs) by precipitation with 5% polyethylene glycol and subsequent spectrophotometric analysis. A single VIP irradiation induced an average rise in serum IgM levels of 13% (p < 0.05). By the end of the 10 day course, it has exceeded the baseline level by 26%, with an increase in IgA levels of 17 and 12% (p < 0.04) one week after the last session. In subjects with a high IC content, it decreased rapidly to the normal level. A single exposure of volunteers to VInP light rapidly produced changes similar to those observed on VIP irradiation, but with an increase in IgM 2.3 to 3 times lower, independent of the initial levels. On the other hand, VInP light exposure decreased the IC content more than VIP light.

Adult↗
PubMed1997

Induction of an epitope-specific humoral immune response by lipopeptide-hapten conjugates: enhancement of the anti-melittin response by a synthetic T helper (Th)-cell epitope.

Lipopeptides of bacterial origin constitute potent immunoadjuvants when combined with antigens. After the immunization with lipopeptides covalently coupled to non-immunogenic low-molecular-mass antigens or haptens, a hapten-specific humoral immune response can often be obtained. The response against synthetically prepared melittin fragments was further enhanced by the additional introduction of a T helper (Th)-cell epitope into the lipopeptide-hapten conjugate. The Th-cell epitope applied, which is presented by the MHC class II molecule of the BALB/c (H-2d) haplotype, consisted of a synthetic 16-amino-acid oligopeptide derived from sperm whale myoglobin. The immune-enhancing effect was most pronounced for the melittin-derived peptide fragments [Mel(1-16)] and [Mel(17-26)-CONH2]. Antibodies obtained after 3 immunizations with the conjugates recognized the synthetic as well as the native melittin molecule. Our results show that it is possible to markedly enhance a weak hapten-specific immune response by coupling the haptens to a lipopeptide conjugated to a haplotype-specific T helper-cell epitope. The novel conjugates are well suited for the optimization of immunization procedures, and for the development of novel synthetic vaccines.

Adjuvants, Immunologic↗
PubMed2000

Suppression of the humoral immune response of Atlantic salmon, Salmo salar L. by the 64 kDa serine protease of Aeromonas salmonicida.

Bacteria-free supernatants of broth cultures of Aeromonas salmonicida inhibited the humoral immune response, but not the cell-mediated immune response, of Atlantic salmon to bacteriophage MS2. The immunosuppressive factor was the 64 kDa serine protease secreted by A. salmonicida. The suppressive activity was not due to degradation of epitopes of MS2, and although serine protease degraded the heavy chain of salmon IgM in vitro there was no evidence for significant degradation in vivo. The principal lethal toxin of A. salmonicida, the glycerophospholipid: cholesterol acyltransferase did not inhibit the immune response of salmon.

Aeromonas↗
PubMed1983

Syngeneic humoral immune responses to tumor-associated antigens expressed by K-1735 UV-induced melanoma and its metastases.

An enzyme-linked immunoassay (ELISA) was developed to study syngeneic humoral immune response to a primary tumor and its metastases in the K-1735 ultraviolet light (UV)-induced C3H murine melanoma system. Binding of sera from syngeneic animals previously immunized with primary tumor or metastatic tumor tissue (M-3, M-4) to corresponding 3 M KCl extracts of tumor was significantly greater than binding of control C3H mouse serum. Antibody binding was not significantly reduced by competitive binding with syngeneic murine muscle or liver extracts, indicating the presence of tumor antigen(s) not shared by normal murine tissue. Antibodies to the tumor-associated antigens were selectively removed by competitive binding with syngeneic K-1735 tumor extracts but not by the unrelated 102 murine sarcoma from C57BL/6. However, EL-4 extracts (C57BL/6) did inhibit antibody binding to the primary and both metastases. Further competitive binding studies demonstrated the presence of a common antigen(s) present on the primary tumor and both metastases. We conclude that the K-1735 UV-induced melanoma primary tumor and its metastases express serologically detectable shared antigenic determinate.

Animals↗
PubMed1994

The influence of Maloprim chemoprophylaxis on cellular and humoral immune responses to Plasmodium falciparum asexual blood stage antigens in schoolchildren living in a malaria endemic area of Mozambique.

We examined the impact of chemoprophylaxis on the cellular and humoral immune responses to polypeptides of the asexual Plasmodium falciparum blood stage antigens, the glutamate rich protein GLURP and Pf155/RESA, both of which in previous field studies have been identified as potentially protective antigens. The study was carried out in the Escola Primária de Lingamo, a primary school in a suburban area of Maputo, Mozambique. A cohort of 392 schoolchildren (aged 7-12 years) was randomly allocated to two equal groups, one receiving chemoprophylaxis with dapsone/pyrimethamine (Maloprim), the other receiving placebo every week from December 1989 to November 1990. The groups were then followed until November 1991 without chemoprophylaxis. Cellular responses to immunodominant epitopes from Pf155/RESA and GLURP, and to non malaria antigens C. albicans and PPD, were assessed by lymphocyte proliferation assays in vitro. Anti-GLURP and anti-Pf155/RESA antibodies were detected by enzyme-linked immunosorbent assay (ELISA) and erythrocyte membrane immunofluorescence (EMIF), and total anti-P. falciparum antibodies were measured by indirect fluorescent antibody test (IFAT). Immunological reactivities were evaluated every six months, at the end of the rainy season and at the end of the dry season, both during the period of chemoprophylaxis and during the follow-up. The antibody response rate to the GLURP was lower in the Maloprim group than in the placebo group during the intervention phase. The lymphoproliferative response rate to the malaria antigens was significantly lower at the end of the rainy season than at the end of the dry season, but the difference between the experimental group and the control group of schoolchildren was not statistically significant. These results suggest that the antibody responses to the GLURP molecule and partly to the Pf155/RESA antigen in this study population were shortlived and dependent on frequent boostering, but whether these antigens play a role in the development of natural clinical immunity remains open. In the experimental group of schoolchildren weekly chemoprophylaxis successfully reduced the parasite rate during the rainy season from 43% to 4%, and during the dry season from 18% to 0%. Chemoprophylaxis may therefore have a useful role in combination with another partially effective malaria control measure such as insecticide-impregnated bed nets or a malaria vaccine.

Animals↗
PubMed1996

Modulation of humoral immune response by central administration of leucine-enkephalin: effects of mu, delta and kappa opioid receptor antagonists.

The effect of leucine-enkephalin (Leu-Enk) on primary humoral immune response was investigated following intracerebroventricular (i.c.v.) administration of the peptide in the rat. Leu-Enk stimulated plaque-forming cell (PFC) response in rats i.c.v. injected with 0.1 and 1 micrograms/kg, whereas does of 20 and 50 micrograms/kg exerted immunosuppressive effects. I.c.v. treatment of rats with delta opioid receptor antagonist ICI 174,864 and kappa opioid receptor antagonist nor-binaltorphimine (nor-BNI) blocked stimulation and suppression of PFC response induced by Leu-Enk, respectively. The mu opioid receptor antagonist beta-funaltrexamine (beta-FNA) reversed both immunomodulatory effects produced by Leu-Enk. Since beta-FNA alone had no effect on PFC response (unlike ICI 174,864 and nor-BNI), these data showed that central effects of Leu-Enk on PFC response were mediated by brain mu opioid receptors, and suggested a possible involvement of delta and kappa opioid receptors.

Adjuvants, Immunologic↗
PubMed1994

Immunoblot analysis of humoral immune responses to Mycobacterium bovis in experimentally infected cattle: early recognition of a 26-kilodalton antigen.

Development of a serodiagnostic test for bovine tuberculosis necessitates an understanding of the humoral immune responses of animals following infection with Mycobacterium bovis. The antibody responses in groups of calves challenged intranasally with different doses of M. bovis (approximately 10(2), 10(4), and 10(6) CFU) or placed in contact with the infected animals were analyzed by immunoelectrophoretic blotting in which a whole-cell sonicate of M. bovis was utilized as an antigen. Antibody responses were evident early in infections in which calves were exposed to high doses of M. bovis, while in groups exposed to lower doses, the time until antibody was detected increased as the challenge dose decreased. In cattle exposed to M. bovis, immunoblot analysis showed antibody responses to three main antigens of 26, 22, and 16 kDa. It was further demonstrated that antibody responses to the 26-kDa antigen appeared earliest in the course of infection. Preliminary investigations in this study have identified a 26-kDa antigen for potential use in improved serodiagnosis by enzyme-linked immunosorbent assays.

Animals↗
PubMed1997

Molecular characterization of murine humoral immune response to botulinum neurotoxin type A binding domain as assessed by using phage antibody libraries.

To produce antibodies capable of neutralizing botulinum neurotoxin type A (BoNT/A), the murine humoral immune response to BoNT/A binding domain (H(C)) was characterized at the molecular level by using phage antibody libraries. Mice were immunized with BoNT/A H(C), the spleens were harvested, and single-chain Fv (scFv) phage antibody libraries were constructed from the immunoglobulin heavy and light chain variable region genes. Phage expressing BoNT/A binding scFv were isolated by selection on immobilized BoNT/A and BoNT/A H(C). Twenty-eight unique BoNT/A H(C) binding scFv were identified by enzyme-linked immunosorbent assay and DNA sequencing. Epitope mapping using surface plasmon resonance in a BIAcore revealed that the 28 scFv bound to only 4 nonoverlapping epitopes with equilibrium constants (Kd) ranging from 7.3 x 10(-8) to 1.1 x 10(-9) M. In a mouse hemidiaphragm assay, scFv binding epitopes 1 and 2 significantly prolonged the time to neuroparalysis, 1.5- and 2.7-fold, respectively, compared to toxin control. scFv binding to epitopes 3 and 4 showed no protection against neuroparalysis. A combination of scFv binding epitopes 1 and 2 had an additive effect on time to neuroparalysis, which increased to 3.9-fold compared to the control. The results suggest that there are two "productive" receptor binding sites on H(C) which lead to toxin internalization and toxicity. Blockade of these two epitopes with monoclonal antibodies may provide effective immunoprophylaxis or therapy against BoNT/A intoxication.

Amino Acid Sequence↗
PubMed1988

The development of humoral immunity to tissue-specific tubular basement membrane alloantigens after renal transplantation across the major histocompatibility barrier in rats immunomodulated with blood transfusions and cyclosporin.

The development of a humoral immune response to the tubular basement membrane (TBM) alloantigen of Brown-Norway (BN) rat kidneys was studied after transplantation of BN rat kidneys into bilaterally nephrectomized Lewis (LEW) rats. The LEW rat recipients consisted of four groups receiving no form of immunosuppression, pretransplantation cyclosporin alone, or pretransplantation donor-specific or donor-nonspecific transfusions combined with cyclosporin. The latter two regimens induce indefinite allograft survival in the majority of recipients. Circulating antibody to collagenase-solubilized BN rat renal basement membrane (CS-BN-RBM) was present in all four groups of transplant recipients within 1 week after transplantation, and no significant differences in antibody levels were noted between rats receiving no immunosuppression (survival of 1-2 weeks) and the groups of rats who received various immunosuppressive regimens and survived longer. Circulating antibody to BN-CS-RBM continued to increase in quantity in the cyclosporin-treated group until the time of death (2-10 weeks post-transplantation). In the much longer lived combined transfusion and cyclosporin-treated groups, circulating antibody to BN-CS-RBM generally attained a maximum at approximately 2 to 4 months post-transplantation and then plateaued or decreased somewhat before the time of death (3-16 months post-transplantation). No correlation was found between quantity of circulating anti-BN-CS-RBM antibody and post-transplantation survival. Comparative study of the quantity of circulating antibody to BN-CS-RBM (the presumed nephritogenic antigen of experimental tubulointerstitial nephritis in the BN rat) in serum from transplant recipients as compared to serum from BN rats with severe experimental tubulointerstitial nephritis (TIN) (as induced by immunization with heterologous TBM antigens) demonstrated a greater quantity of potentially nephritogenic antibody circulating in transplant recipients than in BN rats with experimental TIN. Histologically, the transplanted kidneys in immunomodulated recipients demonstrated focal chronic interstitial inflammatory infiltrates with tubular atrophy and relative sparing of the glomeruli. The development of immune responses to tissue-specific alloantigens may become of clinical significance as graft-survival times are increased.

Animals↗
PubMedDate not supplied

[Functional activity of cells suppressing the humoral immune response in internal irradiation].

In the adoptive transfer system of (CBA X C57BL/6)F1 mice, the estimation was made of the function of splenic cells, suppressors of the humoral immune response to sheep erythrocytes 1 and 6 months following the injection of 125I and 131I. Low absorbed doses of the radioactive isotopes were shown to stimulate the activity of the suppressors generated in mouse spleen.

Animals↗
PubMed2001

The human IgG3 hinge mediates the formation of antigen dimers that enhance humoral immune responses to DNA immunisation.

A series of plasmid DNA constructs containing the 45W antigen gene from Taenia ovis were used to investigate the impact of antigen dimerisation on the humoral immune response to genetic immunisation. Genes encoding dimeric 45W were generated via fusion to the hinge region of human IgG3 (hIg). This region was selected because it is compact and contains 11 inter-chain disulphide-bridges. The DNA encoding the IgG3 hinge contains four exons, with the last three exons being repeats and possibly superfluous. Plasmids containing the 45W gene linked to exons 1-2, 1-3 or 1-4 of the hIgG3 hinge, were compared to a control plasmid containing a form of the 45W gene which encodes secreted, monomeric 45W protein. Western blot analysis was used to investigate the formation of the fusion-proteins in transfected Cos-7 cells. The full-length fusion construct expressed predominantly dimeric forms of the fusion-protein, while truncation of the hinge region decreased the abundance of dimeric fusion-protein and increased the proportion monomeric fusion antigen. In immunised BALB/c mice, 45W-specific antibody titres were increased 3 to 4-fold via fusion to the full-length hinge region, whereas the truncated constructs were similar to the control. IgG subclass analysis indicated that all mice generated predominantly IgG1, IgG2a and IgG2b antibodies. Therefore, these results suggest that the efficient formation of dimeric antigen, via fusion to the full-length hinge of human IgG3, can increase the immunogenicity of expressed antigens without altering the form of the immune response elicited by DNA immunisation.

Animals↗
PubMed2003

Identifying the MAGUK protein Carma-1 as a central regulator of humoral immune responses and atopy by genome-wide mouse mutagenesis.

In a genome-wide ENU mouse mutagenesis screen a recessive mouse mutation, unmodulated, was isolated with profound defects in humoral immune responses, selective deficits in B cell activation by antigen receptors and T cell costimulation by CD28, and gradual development of atopic dermatitis with hyper-IgE. Mutant B cells are specifically defective in forming connections between antigen receptors and two key signaling pathways for immunogenic responses, NF-kappaB and JNK, but signal normally to calcium, NFAT, and ERK. The mutation alters a conserved leucine in the coiled-coil domain of CARMA-1/CARD11, a member of the MAGUK protein family implicated in organizing multimolecular signaling complexes. These results define Carma-1 as a key regulator of the plasticity in antigen receptor signaling that underpins opposing mechanisms of immunity and tolerance.

Aging↗