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Humoral immune responses in healthy heterosexual, homosexual and vasectomized men and in homosexual men with the acquired immune deficiency syndrome.

In homosexual men, the acquired immune deficiency syndrome (AIDS) is associated with sexual promiscuity and the appearance of circulating immune complexes (CICs) and antibodies to spermatozoa which crossreact with lymphoid cells. A comparative study was initiated to determine whether similar humoral responses existed in 38 heterosexual men lacking sperm antibodies, 13 heterosexuals with sperm antibodies, 42 heterosexual vasectomized men, 22 healthy homosexual men, 26 homosexuals with lymphadenopathy and 16 with AIDS or Kaposi's sarcoma (KS). Sperm antibodies were detected in 12% of the vasectomized heterosexual men, 23% of the healthy homosexuals, 35% of the lymphadenopathy patients and 44% of the men with KS-AIDS. IgG reactive with peripheral blood T lymphocytes was present in only 3% of heterosexuals lacking sperm antibody and 5% of vasectomized men. In contrast, 23% of heterosexuals with sperm antibody, 36% of healthy homosexuals, 31% of men with lymphadenopathy and 62% of KS-AIDS patients were positive in this assay. Antibodies to the neutral glycolipid asialo GM1 were found in none of the vasectomized men, 3% of the heterosexuals without and 8% with sperm antibodies, 17% of healthy homosexuals and 38% and 31% in patients with lymphadenopathy or KS-AIDS, respectively. Lastly, the incidence of CICs, determined by the Raji cell assay, was 0% in vasectomized men, 3% in heterosexuals lacking sperm antibody, 31% in heterosexuals with sperm antibody, 69% in healthy homosexuals, 81% in lymphadenopathy patients and 87% in KS-AIDS. In the homosexuals with lymphadenopathy and KS-AIDS, levels of CICs, T cell-reactive IgG and asialo GM1 antibody were positively correlated (p less than 0.01). Sperm antibody levels were negatively correlated (p less than 0.01) with CICs levels and T cell reactive IgG in heterosexuals and lymphadenopathy and KS-AIDS patients. The results demonstrate that vasectomized men do not manifest at all, and that non-vasectomized heterosexuals with sperm antibodies manifest to a much lesser extent the range of humoral immune responses exhibited by the three homosexual groups. Thus, the route of sperm immunization and/or exposure to autologous vs. heterologous spermatozoa may be of critical importance for eliciting specific immune responses.

Acquired Immunodeficiency Syndrome↗

Mycoplasma suis antigens recognized during humoral immune response in experimentally infected pigs.

Today, serodiagnostic tests for Mycoplasma suis infections in pigs have low accuracies. The development of novel serodiagnostic strategies requires a detailed analysis of the humoral immune response elicited by M. suis and, in particular, the identification of antigenic proteins of the agent. For this study, indirect enzyme-linked immunosorbent assay (ELISA) and immunoblot analyses were performed using pre- and sequential postinoculation sera from M. suis-infected and mock-infected control pigs. M. suis purified from porcine blood served as the antigen. Eight M. suis-specific antigens (p33, p40, p45, p57, p61, p70, p73, and p83) were identified as targets of the immunoglobulin G (IgG) antibody response during experimental infection, with p40, p45, and p70 being the preferentially recognized M. suis antigens. Besides the M. suis-specific antigens, porcine immunoglobulins were identified in blood-derived M. suis preparations. By immunoglobulin depletion, the specificity of the M. suis antigen for use in indirect ELISA was significantly improved. M. suis-specific Western blot and ELISA reactions were observed in all infected pigs by 14 days postinfection at the latest and until week 14, the end of the experiments. During acute clinical attacks of eperythrozoonosis, a derailment of the antibody response, determined by decreases in both the M. suis net ELISA values and the numbers of M. suis-specific immunoblot bands, was accompanied by peaking levels of autoreactive IgG antibodies. In conclusion, the M. suis-specific antigens found to stimulate specific IgG antibodies are potentially useful for the development of novel serodiagnostic tests.

Animals↗

Humoral immune reactions in uremic pericarditis.

Clinical data from 41 patients with pericarditis or pericardial effusion in acute and chronic renal failure were analyzed in respect to the diagnostic relevance of humoral immune reactions. In patients with pericardial effusion in acute renal failure due to surgery or trauma (n = 10), antimyocardial antibodies were rarely detected. In contrast, in the sera of all patients with pericarditis or pericardial effusion following renal failure in chronic or acute glomerulonephritis (n = 6), complement-fixing antisarcolemmal antibodies of the IgM and IgG classes were observed. In patients in whom pericarditis or pericardial effusion evolved during chronic hemodialysis (n = 25), the incidence of complement-fixing antimyolemmal antibodies was 64%. Only sera with complement-fixing antimyolemmal antibodies induced cytolysis of vital adult cardiocytes in vitro suggesting that the antimyolemmal antibodies may not only play a diagnostic but also a pathogenetic role in 'uremic' pericarditis in vivo.

Acute Kidney Injury↗

[The inhibiting effect of a low-dose ionizing radiation on the primary humoral immunity in the early period of an postnatal ontogeny].

The single exposition of 3- and 4-week mice in a dose 0.1 Gy resulted in depressing primary T-dependent humoral immune response. Unlike juvenile ones at adult 16-week animals the stimulation antibody-formation took place. As a result of the administration of immunomodulating drugs, thymogene and nucleinate of a sodium in irradiation mice of 3-week age was an augmentation of the number of antibody-producing cells relatively in 2 and 4 times. At the same time at irradiated in dose 0.1 Gy of adult mice thymogene abrogated the stimulating effect of radiation. It is suggested that the probable cause of the immunosuppressing effect of a small dose of radiation can be an inactivation of a radiosensitive subpopulation of helper cells or selective stimulation of the functional activity of neonatal suppressor cells.

Aging↗

Cellular and humoral immunity in psoriatic patients.

The degree of cellular immunity was found to be reduced in about 23% of 56 psoriatics, especially so in those with flexural and arthropathic lesions. Humoral immunity was only slightly reduced. Lysozyme activity levels in serum were normal, while those of healthy skin were depressed in 6 patients.

Adolescent↗

[More precise characterization of humoral immune reactivity to cartilage tissue in patients with resorption of cartilage transplants in the area of the head and neck].

The problems with repeated failure of cartilage grafting in reconstructive surgery are not yet resolved. Humoral immunoreactivity against chondrocytes as well as typical cartilage collagens type II, IX and XI was investigated in patients who showed resorptions and/or rejections of transplanted cartilage grafts. The presence of antibodies against isolated human chondrocytes was determined using an indirect immunofluorescence method, an enzyme-linked immunosorbent assay (ELISA) for chondrocytes and immunoblotting with chondrocyte cell membranes. Furthermore, an ELISA for collagens type II, IX and XI as well as immunoblotting with purified collagens type II and XI were used. The control groups consisted of patients with successful cartilage transplantation, patients suffering from rheumatoid arthritis and healthy persons. Patients with unsuccessful cartilage transplantation showed significantly elevated titres of antibodies against chondrocytes (p < 0.001) and collagens type IX and XI (p < 0.001) compared to the control groups. In one patient with unsuccessful cartilage graft, we could also find a humoral reactivity against collagen type XI by immunoblotting. In contrast, no humoral immune reactivity was demonstrable against chondrocyte cell membranes by immunoblotting. In all examined patients fifty percent of patients with repeated resorptions or rejections of transplanted grafts showed antinuclear antibodies (ANA), demonstrating a possible but not yet declared autoimmune disease. These data confirm a humoral immunoreactivity against chondrocytes as well as against collagen which could be responsible for resorptions and/or rejections observed after cartilage graft.

Adult↗

Humoral immune responses to gag and env proteins from human immunodeficiency virus type 1 in hemophiliac patients.

Solid-phase enzyme immunoassays using recombinant gag and env proteins were developed to study humoral immune responses to HIV infection in a cohort of 105 hemophiliac patients. Thirteen patients with ARC or AIDS and 92 asymptomatic patients were studied. A cross-sectional study showed a wide range of antibody responses to gag and env proteins; however, the differences between the ARC/AIDS and asymptomatic patients were statistically significant for both antigens (P less than .0004). In a longitudinal study, antibody levels in sera from 11 asymptomatic patients with gag antibody log units less than or equal to 1.5 were compared to levels in sera from 10 ARC/AIDS patients and 8 asymptomatic patients with gag antibody greater than 1.5. These patient groups were followed for comparable periods of time (67.1-71.7 mo). The asymptomatic patients with low gag antibody and the ARC/AIDS patients showed a similar pattern of antibody response to gag protein overtime. In hemophiliac patients with HIV-1 infection a low titer of antibody to gag protein is not invariably associated with clinical deterioration and is not a useful serologic marker of impending progression to AIDS.

AIDS-Related Complex↗

Suppression of humoral immunity in chickens with carrageenans.

Carrageenans (CGN), sulphated polygalactans, have been reported to be cytotoxic for macrophages in vitro. On this basis, the effect of the 3 major CGN types on humoral immune responses in chickens was investigated. Carrageenan had no effect on body and lymphoid organ weights. Histologically, CGN produced a significant proliferation of reticuloendothelial cells in liver and spleen, but no changes were observed in lymphocyte populations of the bursa of Fabricius, thymus, or spleen. Intracoelomic pretreatment with high doses of CGN induced a marked suppression of primary responses to sheep red blood cells (SRBC) given by the same route. However, if SRBC were injected intravenously into chickens already treated intracoelomically with CGN, no evidence of suppression was demonstrated. Antibody responses to Brucella abortus (BA), a T-independent antigen, were not affected by intracoelomic treatment with CGN. Intravenous pretreatment with CGN did not alter antibody responses to SRBC and BA given by the same route.

Animals↗

Potentiating effect of adjuvants on humoral immunity to porcine parvovirus vaccines in guinea pigs.

Fourteen different adjuvants, given either in single or combined form with another compound were compared in guinea pigs for their ability to potentiate humoral immunity to porcine parvovirus (PPV) antigen after 2 vaccinations. Two injections were given, the second 3 weeks following the initial vaccination. Antibody concentrations to PPV in sera from injected animals were measured over a 5-week period by the hemagglutination inhibition test. At the conclusion of the experiment, guinea pigs injected with the following adjuvants and PPV antigen: CP-20 961 (Avridin), 50% aluminum hydroxide gel, ethylene maleic anhydride (EMA), oil and water emulsion (O/W) and dimethyl-dioctadecyl-ammonium bromide (DDA) immunologically responded with high geometric mean HI titers (380, 224 and 427, 602, 512, 1202 respectively), whereas guinea pigs receiving Emulsan, sodium dodecyl sulfate (SDS), L-121, combinations of Emulsan/aluminum hydroxide, SDS/aluminum hydroxide and B. pertussis/aluminum hydroxide responded with low mean titers (54, 64, 18, 27, 11, 64, 14, 20 respectively). Guinea pigs injected with antigen without adjuvant responded weakly with geometric mean titers of 3.3 and 16 for the 2 groups tested. Prior to booster injection, guinea pigs immunized with 13 of the preparations had low (less than 4) or undetectable antibody titers. Antibody titers from guinea pigs receiving DDA adjuvant continued to rise throughout the duration of the experiment and at the conclusion had the highest mean titers of the groups tested (1202). The 2 groups immunized with 50% aluminum hydroxide gel had high mean titers (224, 427), but in both instances there was a wide range of titers within a group evidenced by high standard deviations. In contrast, guinea pigs receiving either DDA, CP-20 961, O/W or EMA had antibody titers within a narrow range and small standard deviation. The significance of aluminum hydroxide gel concentration on immunogenicity is discussed.

Adjuvants, Immunologic↗

The humoral immune response to recombinant nucleocapsid antigen of canine distemper virus in dogs vaccinated with attenuated distemper virus or DNA encoding the nucleocapsid of wild-type virus.

This study compared the humoral immune response against the nucleocapsid-(N) protein of canine distemper virus (CDV) of dogs vaccinated with a multivalent vaccine against parvo-, adeno-, and parainfluenza virus and leptospira combined with either the attenuated CDV Onderstepoort strain (n = 15) or an expression plasmid containing the N-gene of CDV (n = 30). The vaccinations were applied intramuscularly three times at 2-week intervals beginning at the age of 6 weeks. None of the pre-immune sera recognized the recombinant N-protein, confirming the lack of maternal antibodies at this age. Immunization with DNA vaccine for CDV resulted in positive serum N-specific IgG response. However, their IgG (and IgA) titres were lower than those of CDV-vaccinated dogs. Likewise, DNA-vaccinated dogs did not show an IgM peak. There was no increase in N-specific serum IgE titres in either group. Serum titres to the other multivalent vaccine components were similar in both groups.

Animals↗

[Effect of modified low density lipoproteins on humoral immune response and functional activity of macrophages in mice].

Intravenous injection of acetylated low density lipoproteins (acLDL) in mice in a dose of 0.5 mg per mouse decreased the intensity of humoral immune response to sheep red blood cells (SRBC) by 35%. The addition of acLDL to mouse peritoneal macrophages in vitro resulted in inhibition of Fc-dependent phagocytosis of SRBC and fourfold increased secretion of prostaglandins E2 by macrophages. Fc-dependent phagocytosis of SRBC was also found to be inhibited by oxysterols (25-hydroxycholesterol and 7-ketocholesterol), added to the incubation medium of macrophages in vitro in doses of 0.5-5 mg/ml. The conclusion was made that oxidative metabolism of cholesterol and arachidonic acid, contained in LDL, may mediate the immunomodulating effects of modified LDL.

Adjuvants, Immunologic↗

Detection and partial characterization of an anti-steroidogenic peptide from the humoral immune system of the chicken.

Phenomenological association of alterations of immune system function at the time of puberty (e.g. involution of the chicken bursa of Fabricius) has led to postulation that the humoral immune system may negatively affect the hypothalamo-adenohypophyseal-gonadal axis of the neonate. Presently, we examined the effect of an acidic aqueous bursa of Fabricius extract, derived from prepubescent chickens, on in vitro basal and LH-stimulated progesterone biosynthesis by isolated ovarian granulosa cells of the largest preovulatory chicken follicles (F1 and F2). Crude extracts of < 5kDa and > 3kDa inhibited LH-stimulated progesterone secretion (P < 0.05). The bioactive component was observed to be heat labile and is sensitive to the endopeptidases chymotrypsin, trypsin and papain. The peptide is not sensitive to the exopeptidase, aminopeptidase M. Partial purification by reversed phase HPLC resulted in a fraction capable of inhibiting in vitro steroidogenesis. This fraction suppressed LH-stimulated progesterone biosynthesis to approximately basal levels (79% suppression). Following removal of the peptide, granulosa cells were capable of LH-stimulated progesterone biosynthesis similar to control cells. Bursal extract significantly inhibited cAMP analog-stimulated progesterone biosynthesis. These data indicate that the anti-steroidogenic peptide derived from the chicken bursa of Fabricius is a single heat labile, amino terminally blocked peptide with bioactivity independent of the gonadotropin receptor of the granulosa cell.

Analysis of Variance↗

Short-term toxicity studies of O-chlorobenzylidene malononitrile on humoral immunity in mice.

The effect of O-chlorobenzylidene malononitrile (CS) on the immune system was studied in mice given 8 and 16 mg/kg body weight i.p. of the compound, daily for 10 days. The humoral immune response to SRBC was suppressed at both doses, as determined by the antibody producing cells in the spleen. To find out whether the immunosuppression observed was due to the indirect effect of CS on the nutritional status and endocrine balance, serum proteins and corticosterone levels were measured. While the serum proteins did not alter, corticosterone levels rose significantly only in mice receiving higher dose of CS.

Adrenal Cortex Hormones↗

FTY720 suppresses humoral immunity by inhibiting germinal center reaction.

FTY720 is a novel immunosuppressant that is highly effective in inhibiting rejection of allografts and autoimmunity in various animal models. It has been shown that the sphingosine 1 phosphate (S1P) receptors are the direct molecular targets of FTY720. However, the mechanisms responsible for inhibiting specific immune responses by FTY720 are not well resolved. In particular, there is no available information on whether or how this compound affects humoral immunity. We have investigated the effect of FTY720 treatment on B-cell response during the immune response to a well-defined T-dependent antigen. Our data demonstrated that germinal center reaction was significantly reduced in peripheral lymphoid tissues of mice treated with FTY720. In addition, FTY720 treatment inhibited the production of high-affinity, class-switched antibodies, but not the production of low-affinity, immunoglobulin M (IgM) antibody. Consistently, FTY720 did not have a significant effect on antibody response to a T-independent antigen. Our results may have important implications in application of FTY720 in immune regulation.

Animals↗

Interleukin-6 fused to an anti-idiotype antibody in a vaccine increases the specific humoral immune response against CA125+ (MUC-16) ovarian cancer.

Anti-idiotypic (Id) monoclonal antibodies can serve as surrogate for tumor-associated antigens in vaccination strategies. The murine anti-Id monoclonal antibody ACA125 that mimics the CA125 carbohydrate antigen expressed on ovarian cancer cells induces an anti-anti-Id antibody (Ab3) response that is associated with prolonged survival of ovarian cancer patients. To increase the Ab3 antibody response, we evaluated two strategies in a mouse model: (a) coinjection of human interleukin (IL)-6 together with the fusion protein chACA125, which consists of the anti-Id ACA125 single-chain Fv antibody joined to the human IgG1 CH2/CH3 domain; and (b) injection of the fusion protein chACA125-IL-6, which consists of the ACA125 single-chain Fv fused to human IL-6 via the IgG1 CH2/CH3 domain. Vaccination of mice with the chACA125-IL-6 fusion protein resulted in higher titers of anti-CA125 (Ab3) antibodies compared with application of the chACA125 antibody with or without systemic coadministration of IL-6. Application of the chACA125-IL-6 fusion protein did not elicit detectable antihuman IL-6 antibody titers, whereas coinjection of human IL-6 did. Taken together, these data suggest that the chACA125-IL-6 fusion protein directly stimulates ACA125-specific B cells via the IL-6 domain, whereas coinjection of IL-6 leads to an overall immune stimulation. Antigen-IL-6 fusion proteins will improve vaccination regimens and anticancer immunotherapeutic strategies by increasing the antigen-specific humoral immune response.

Animals↗

Immunity in Graves' disease at diagnosis: correlation between activated T cells and humoral immune factors.

Activated T cells, T-cell subsets, thyrotropin receptor antibodies and immune complexes were evaluated in 31 patients with newly diagnosed Graves' disease. Activated T cells were assayed by monoclonal antibodies against early (4F2) and late activation surface lymphocyte antigens (different epitopes of class II antigens). In comparison with the normal population, Graves' patients showed a significant decrease in the suppressor cytotoxic T-cell subset. Significant increases of 4F2-positive cells (70% of patients studied), class II antigen-positive cells (65%), thyrotropin receptor antibodies (93%), Clq-immune complexeses (44%) and conglutinin-immune complexes (37%) were observed. A significant inverse correlation between the increase in 4F2-positive cells and thyrotropin receptor antibody values was also observed. Lymphocytes from Graves' patients were cultured in the presence of thyrotropin receptor antibody-positive or -negative sera, with or without mitogen stimulation. Thyrotropin receptor antibodies were shown not to interfere with the expression of activation antigens in cultured cells. The different patterns of humoral and cellular immune phenomena may indicate the existence of either different stages of Graves' disease or a heterogeneity of the immunopathogenesis in different patients.

Adolescent↗

HSP60, HSP70 and HSP90 from Trichinella spiralis as targets of humoral immune response in rats.

This study identifies three heat shock proteins (HSPs) using purified preparations from Trichinella spiralis larvae. The proteins: HSP60, HSP70 and HSP90 were found to be targets of the humoral immune response in rats. Three approaches were adopted to obtain T. spiralis HSP-enriched material and/or to purify HSPs to homogeneity. The former product was prepared using affinity chromatography on gelatin sepharose and elution with ATP. Pure 90 kDa-protein was isolated from parasite extract by sequential DEAE (A50) column chromatograpy and preparative electrophoresis. Immunoblot analysis using monoclonal antibodies to HSP60, HSP70 and HSP90 detected the HSP60 and HSP70 in the affinity-purified product and HSP90 in the product obtained by sequential anionic chromatography and preparative electrophoresis. Finally, the reactivy of preimmune, T. spiralis immune and irrelevant immune rat sera on immunoblots were also examined. Only sera taken from infected rats at time-points after day 7 following the first infection exhibited activity against 60, 70 and 90 kDa proteins on blots. The fact that the serum antibodies were anti-HSP was established by immunoadsorption of HSPs to microtiter plates coated with anti-HSP60, anti-HSP70, or anti-HSP90 and using rat sera, positive on blots, to also give positive scores by continued enzyme-linked immunosorbent assay.

Animals↗

The quantitative humoral immune response to the hepatitis C virus is correlated with disease activity and response to interferon-alpha.

BACKGROUND/AIM: Virus-host interactions may have pathogenetic significance in chronic hepatitis. Thus the humoral immune response was evaluated during the clinical course of HCV-infected patients. METHODS: Eighteen selected chronic HCV patients received three doses of 3 or 6 MU interferon-alpha 2a weekly for 6 to 12 months and were followed up for 6 to 60 months. Anti-HCV antibody levels were serially measured either in end-point diluted sera with the Matrix-Assay or with quantitative anti-HC34-IgG and -IgM ELISA. Circulating immune complexes were assessed by flow cytometry and the results were correlated with histology, quantitative HCV-RNA levels and genotypes. RESULTS: Nine complete responders (CR; genotypes 1a n = 4; 1b n = 1; 2a n = 1; 3a n = 3) showing sustained virus elimination and ALT normalisation had low HCV-RNA pretreatment levels (mean 14 x 10(3) copies/ml) compared to six nonresponders and three partial responders (NR/PR; genotypes 1a n = 2; 1b n = 7) who had significantly higher HCV-RNA pretreatment levels (mean 254 x 10(3) copies/ml; p < 0.01). In untreated NR/PR the HC34 core-antigen was most immunogenic, in CR the NS3-derived HC29-antigen. Pre-treatment levels of anti-HC 34-IgG and -IgM antibody levels in NR/PR were higher than in CR (IgM/IgG p = 0.05, n.s.) and these differences became significant during or after therapy (3 months therapy: IgM p < 0.02/IgG p < 0.07; end of therapy: IgM 0.006/IgG p < 0.04; 6 months post-therapy: IgM p < 0.002/IgG p < 0.004). The PR patients showed recurrent anti-HC34 antibody levels that preceded disease reactivation and detectable HCV-RNA in serum. Immune complex formation increased in some patients during treatment but did not correlate with disease activity, quantitative viraemia, antibody levels or therapy outcome. CONCLUSION: Anti-HC34 antibodies, i.e. of the IgM-subtype, correlated quantitatively with viraemia and disease activity. Monitoring the antibody levels may predict the long-term therapy outcome during interferon-alpha treatment.

Adult↗