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The mucosal humoral immune response of the horse to infective challenge and vaccination with equine herpesvirus-1 antigens.

Equine herpesvirus-1 (EHV-1) remains a frequent cause of upper respiratory tract infection and abortion in horses worldwide. However, little is known about the local antibody response elicited in the upper airways of horses following exposure to EHV-1. This study analysed the mucosal humoral immune response of weanling foals following experimental infection with virulent EHV-1, or vaccination with either of 2 commercial vaccines. Twenty weanlings were assigned to 5 groups and were inoculated with, or vaccinated against, EHV-1 following different regimens. Finally, all weanlings were simultaneously challenged intranasally with virulent EHV-1 Army 183 (A183). Nasal wash and serum samples were collected at regular intervals until 13 weeks after final challenge. Nasal washes were assayed for EHV-1-specific equine IgGa, IgGb, IgG(T), IgA, IgM and total virus-specific antibody using an indirect, quantitative ELISA. Total serum antibody responses were also monitored, and clinical signs of EHV-disease were recorded for each individual. Virus-specific IgA dominated the mucosal antibody response elicited in weanlings inoculated with A183, being detectable at up to 3.1 microg/mg total IgA 13 weeks after challenge. Neither inactivated EHV-1 administered i.m., nor attenuated EHV-1 administered intranasally induced detectable mucosal antibodies. EHV-1-specific mucosal antibodies impeded EHV-1 plaque formation in vitro. Such virus-neutralising antibody probably contributes to a reduction of shedding of EHV-1 from the respiratory tract of virus-infected horses.

Administration, Intranasal↗

[The role of chorionic gonadotropin in regulating the humoral immune response].

A study was made of the effect of chorionic gonadotropin (CG) on the formation of a primary immune response and generation of antigen-specific T-suppressors in normal and ovariectomized female mice. CG at doses of 40 or 200 U. strongly suppressed the generation of suppressor cells in noncastrated animals, and significantly raised the level of a humoral immune response at a small dose (40 U.). In ovariectomized mice CG at various doses made a selective stimulating effect on T-suppressor generation which depended on the synthesis of endogenous prostaglandins. A CG effect resulted in a significant decrease in the level of a primary immune response in castrated animals. Choriogonin was assumed to cause an immunostimulating effect in normal female mice as a result of raised secretion of sex steroids by the ovaries. The hormone proper produced an immunosuppressive effect which was implemented at the level of suppressor cells.

Animals↗

[Changes of local resistance of oral cavity and humoral immunity among workers of metallurgical and chemical production during parodontitis].

On the basis of the data of immunological investigations of 142 workers of metallurgical (melting shops of Zestaphoni's Farroalloy Plant) and chemical (electrolytic shops of manganese and dioxide manganese of Farroalloy Plant and "Azoti") production it was found that during parodontitis among studied contingent local resistance of mouth cavity and humoral immunity are changed, the compound of lysozyme and amylase in saliva is lowered, in the layers of saliva and blood is revealed the misbalance of immunoglobulin's system. First of all was established, that during parodontitis among the studied workers autoimmune processes are developed directed against the I-st type collagen and the tissue of gum. Changes of local and common homeostasis as well as the changes of intensity of autoimmune process are in direct correlation with the severity of parodontitis and the pollution of production environment with the spray of manganese dioxide.

Chemical Industry↗

[Effect of preventive use of dexamethasone on various indicators of humoral immunity in mothers and newborn infants].

In order to explore the immunosuppressive effect of glucocorticoids as accelerators of fetal lung maturity, 98 women with imminent premature labor were examined in respect to the effect of dexamethasone on IgG, IgA and IgM levels in mothers and infants. No convincing immunosuppressive effect was found on the production of the above mentioned markers of humoral immunity in the treated groups of pregnant women and their newborns.

Dexamethasone↗

Sex differences in photoperiod control of antigen-specific primary and secondary humoral immunity in Siberian Hamsters.

Photoperiod was hypothesized to mediate T cell-dependent B cell production of IgM and IgG. Antigens induced production of specific immunoglobulins; serum IgM but not IgG, was higher in males in long vs. short days (16 vs. 8 h light/day) and similarly among all groups of females. A second immunization with KLH robustly enhanced serum IgM, as well as IgG; increases were blunted in short- vs. long-day males but not in females. Thus, in male but not female hamsters, winter-like short days restrain aspects of primary and secondary humoral immune responses to xenoantigens. Actions on lymphocyte activities or clonal expansion are in considerations.

Animals↗

In vivo administration of lymphocyte-specific monoclonal antibodies in nonhuman primates. V. Evidence that humoral immune response to monoclonal antibodies and immunotoxin conjugates abrogates their cytotoxic activity.

Monoclonal antibodies, either alone or conjugated to toxins, hold promise as important therapeutic agents. However, the immune response to these foreign protein agents may markedly limit their therapeutic utility in vivo. We have administered both an interleukin-2 receptor-specific monoclonal antibody (anti-IL-2R) and a CD2-specific monoclonal antibody linked to the ribosome-inactivating protein gelonin to macaque monkeys. The monkeys developed high-titer antibody responses to mouse Ig and, when immunotoxin was administered, to the toxin gelonin. Their antimouse Ig antibody responses were broadly reactive with mouse Ig of differing idiotypes and isotypes. Furthermore, sera from these monkeys blocked the in vitro cytotoxic effect of anti-IL-2R or immunotoxin. This blocking was mediated by both the antimouse Ig and the antigelonin antibodies. Serum from a monkey infused with one CD2-specific monoclonal antibody blocked the in vitro cytotoxicity of two other isotypically different CD2-specific monoclonal antibody conjugates. In addition, this serum blocked the in vitro cytotoxicity of a gelonin-monoclonal antibody conjugate of an unrelated specificity. These data indicate that the immune response to some monoclonal antibodies and toxins might preclude the later use of this class of substances in an individual. Therefore, strategies for the parental therapeutic use of monoclonal antibodies and immunotoxins must take into consideration the possible limiting effects of the humoral immune response to these agents.

Animals↗

In vivo cocaine administration influences lymphokine production and humoral immune response.

The effect of in vivo cocaine administration on in vitro mitogen-induced lymphokine production was examined. Splenocyte cultures from BALB/c mice treated with an acute (1 mg/kg) or daily cocaine administration (1 mg/kg/day for 7 consecutive days) were less responsive to induction of IFN-gamma, IL-2 and IL-4 production by mitogen stimuli. We also evaluated the humoral immune response to both a T-dependent (HEL) and a T-independent antigen (rHBcAg). It was found that cocaine inhibits T-dependent antibody production only. This inhibition was greatest when cocaine was given during immunization. The results suggest that T-cell-mediated responses may be more affected by cocaine use/abuse.

Animals↗

Depletion of natural killer cells in mice by monoclonal antibody to NK-1.1. Reduction in host defense against malignancy without loss of cellular or humoral immunity.

Weekly injections of a monoclonal antibody (MAb) to the antigen NK-1.1 were used to sustain depletion of NK cells from the spleens of adult C57BL/6 mice for up to 8 wk. Mice depleted of NK cells in this manner had no lasting alteration in the distribution of other lymphocyte subsets in the spleen and did not demonstrate reduced cellular or humoral immunity. Depletion of NK cells, however, markedly increased the localization and growth of B16 melanoma cells or CT 38 colon carcinoma cells in the lung after i.v. administration of tumor cells. Moreover, mice given B16 tumors and treated with anti-NK-1.1 had reduced survival. NK cells were important in host resistance to sublines of B16 that had been passaged either in vivo or in vitro, which express, respectively, high and low levels of class I major histocompatibility antigens. These findings support a role for NK cells in host defense against malignancy. The ability to selectively remove NK cells in vivo by MAb will permit a better understanding of their physiologic role.

Adenocarcinoma↗

Humoral immunity to Candida albicans (anti-candida antibody titers) in premature infants.

Although the role of humoral and cell mediated immunity in neonatal defense against candida infections is not precisely defined, one of the contributing immunologic factors may be a lack of decreased specific passive humoral immunity. Thus, serum samples from the umbilical veins of 98 term gestation and 105 premature neonates (majority less than 33 wk gestation) and their mothers (n = 100) were tested for the presence of hemagglutinating antibodies to commercially available candida antigen. The titers of candida antibodies (mean log2 +/- SEM) were significantly higher in 11 term neonates (4.73 +/- 0.69) of mothers with high antibody titers (5.18 +/- 0.40, less than 0.001) as contrasted with 87 normal term (2.38 +/- 0.15) and 105 premature (2.87 +/- 0.15) infants with normal mothers (1.96 +/- 0.13 and 3.31 +/- 0.26, respectively). Contrary to our belief 81% of term infants and all of the preterm infants (majority less than 33 wk gestation) had passive specific anti-candida antibody titers less than 1:16.

Antibodies, Fungal↗

Protective effect of Cassia occidentalis L. on cyclophosphamide-induced suppression of humoral immunity in mice.

Cassia occidentalis L. (Kasaundi) is a widely used medicinal plant. Earlier, we have shown that it possesses antimutagenic activity against benzo[a]pyrene (BaP) and cyclophosphamide (CP)-induced mutagenicity in mice. In this study, we investigated if this plant could also provide protection against CP-induced immunosuppression in animal models. Swiss albino male mice were treated per os with the aqueous extract of C. occidentalis (100 mg/kg, body weight (b.w.)) for 14 days. Cyclophosphamide was given intraperitoneally in a single dose of 50 mg/kg b.w. Body weight, relative organ weight, lymphoid organ cellularity, hemagglutination titre (HT), plaque forming cell (PFC) assay and quantitative hemolysis of SRBC (QHS) were studied in these animals. CP, as expected, showed suppressive effects on lymphoid organ weight and cellularity and other parameters of humoral immunity. Plant extract treatment itself produced no toxicity. The administration of plant extract to CP-exposed animals resulted in improved humoral responses. C. occidentalis treatment significantly (P<0.01) enhanced PFC response in CP-treated animals. In QHS assay, also C. occidentalis showed protection in CP-treated animals. Bone marrow cell counts, which were reduced in CP-treated animals, were reversed significantly (p<0.01) to normal levels in CP+ plant extract group animals. In our earlier study, we found that C. occidentalis modulated hepatic drug metabolizing enzymes. It is suggested that by a similar mechanism, it may be influencing the hematotoxic and immunotoxic responses of cyclophosphamide.

Animals↗

Humoral immune response elicited by highly attenuated variants of vaccinia virus and by an attenuated recombinant expressing HIV-1 envelope protein.

Attenuated variants of vaccinia virus have excellent potential for the construction of safe recombinant live vaccines. In this investigation, highly attenuated variants of vaccinia virus with several genetic markers and a variant recombinant were tested in Balb/c mice for their ability to induce humoral immune response. Mice primed with variants that had an 8-MDa deletion at the left end of the viral genome induced similar levels of circulating anti-vaccinia antibodies as the wild-type virus. However, mice primed with variants that had several genetic lesions (deletions and point mutations) induced lower levels of circulating anti-vaccinia antibodies. Mice primed and boosted with a recombinant variant with several genetic lesions, and containing the complete envelope gene of the human immunodeficiency virus (HIV) and the bacterial beta-galactosidase (beta-gal) gene, induced significant antibody response to gp 160 and beta-gal. The antibody response to gp 160 was markedly increased by successive inoculations with the recombinant variant. Our findings provide evidence that the extent of activation of the immune system by vaccinia variants can be modulated by the nature of the virus genetic lesion. In addition, when these variants are used as recombinant vaccines, it is possible to induce low levels of circulating anti-vaccinia antibodies after priming and yet achieve significant antibody response to virus-expressed foreign antigens, even after repeated boosters. Such variants could be useful in the design of live recombinant viruses as safe vaccines.

Animals↗

[The status of general and local humoral immunity in patients with peptic ulcer and chronic gastroduodenitis].

The content of secretory immunoglobulins A and serum immunoglobulins A, M, G, D in the blood serum and biological. fluids (saliva, gastric juice and duodenal contents) was examined in 108 patients with gastric and duodenal ulcer and in 68 patients with chronic gastroduodenitis. The obtained data evidence tense states of the general and local humoral immunity in all patients with gastric and duodenal ulcer and chronic gastroduodenitis. Monotypical changes in patients with diseases of the gastroduodenal zone, apparently, reflect the participation of the immunological component of the ulcerogenic situation already at the stage of preulcer condition.

Adolescent↗

Cellular and humoral immune responses of cattle to purified Mycobacterium bovis antigens.

Cellular responses to several purified antigens of Mycobacterium bovis were examined in experimentally infected cattle over a period of 36 months, using in vitro cellular proliferation and interferon-gamma assays. These antigens (12, 19, 22a, b, 24, 25, 30, 32, 39, 65 and 70 kDa) included the majority of M. bovis protein antigens described to date and are highly homologous to those purified from M. tuberculosis. Cellular responses were examined at 3-month time intervals during the 36-month course of infection. All purified antigens induced cellular immune responses in the infected animals. The onset and magnitude of response to individual antigens varied among the animals. At any specific time during the period of infection one or more antigens appeared to be immunodominant but the immunodominance profile changed as the infection progressed. Humoral immune responses were low or absent in the first half of the infection period, but increased substantially for some of the antigens during the second half. Variation was observed among the different animals as to which antigens they recognized.

Animals↗

Vaccination with a feline immunodeficiency virus multiepitopic peptide induces cell-mediated and humoral immune responses in cats, but does not confer protection.

Cats were immunized with a 46-residue multiepitopic synthetic peptide of feline immunodeficiency virus (FIV) comprising immunodominant epitopes present in the third variable domain of the envelope glycoprotein, transmembrane glycoprotein (TM), and p24 Gag core protein, using Quil A as an adjuvant. All vaccinated cats developed a humoral response which recognized the synthetic peptide immunogen and the intact viral core and envelope proteins. A FIV Gag- and Env-specific effector cytotoxic T-lymphocyte response was also detected in the peripheral blood of vaccinated cats, which peaked at week 30. This response appeared to be major histocompatibility complex restricted. Epitope mapping studies revealed that both the cellular and humoral immune responses were directed principally to a peptide within the TM glycoprotein, CNQNQFFCK. However, vaccination did not confer protection when cats were challenged with the Petaluma isolate of FIV at week 35.

Adjuvants, Immunologic↗

Use of protein microarrays to define the humoral immune response in leprosy patients and identification of disease-state-specific antigenic profiles.

Although the global prevalence of leprosy has decreased over the last few decades due to an effective multidrug regimen, large numbers of new cases are still being reported, raising questions as to the ability to identify patients likely to spread disease and the effects of chemotherapy on the overall incidence of leprosy. This can partially be attributed to the lack of diagnostic markers for different clinical states of the disease and the consequent implementation of differential, optimal drug therapeutic strategies. Accordingly, comparative bioinformatics and Mycobacterium leprae protein microarrays were applied to investigate whether leprosy patients with different clinical forms of the disease can be categorized based on differential humoral immune response patterns. Evaluation of sera from 20 clinically diagnosed leprosy patients using native protein and recombinant protein microarrays revealed unique disease-specific, humoral reactivity patterns. Statistical analysis of the serological patterns yielded distinct groups that correlated with phenolic glycolipid I reactivity and clinical diagnosis, thus demonstrating that leprosy patients, including those diagnosed with the paucibacillary, tuberculoid form of disease, can be classified based on humoral reactivity to a subset of M. leprae protein antigens produced in recombinant form.

Antibodies, Bacterial↗

Quantitative and qualitative analysis of anti-tetanus toxoid antibody response in the elderly. Humoral immune response enhancement by thymostimulin.

In order to explore the humoral primary and secondary response to tetanus toxoid (TT), and to define the possible immunopotentiating effect of the thymic hormone thymostimulin, we studied 13 elderly people, selected according to the Senieur Eurage protocol, vaccinated against TT, an antigen never encountered before. Six of them were treated with thymostimulin before and during the immunization protocol. Specific anti-TT antibody level measurement and spectrotypic analysis were performed on the sera collected from the subjects at different times over the immunization protocol. In addition, spontaneous in vitro production of anti-TT antibodies as well as cutaneous delayed hypersensitivity reactions were also studied. Only one patient showed a detectable humoral immune response after the first immunization. After the booster, four of six thymostimulin-treated individuals, compared with only two of seven controls, showed in vivo anti-TT humoral response; at the same time, spontaneous anti-TT production was detected in peripheral blood mononuclear cells from five of six thymostimulin-treated individuals but only three of seven untreated controls. These differences were highly significant (p < 0.0001). In addition, only in thymostimulin-treated subjects were the levels of serum anti-TT antibodies 14, 21 and 28 days after the booster significantly (p < 0.05) higher than the baseline values. The spectrotypic analysis of anti-TT antibodies performed by isoelectric focusing and reverse blotting showed total agreement with the results from enzyme-linked immunosorbent assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗

Mechanisms of 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (HpCDD)-induced humoral immune suppression: evidence of primary defect in T-cell regulation.

The antibody response of C57B1/6 mice to sheep erythrocytes (SRBCs), a macrophage and T-cell-dependent antigen, is highly sensitive to suppression by 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (HpCDD), a major immunotoxic contaminant of pentachlorophenol. The present studies have used several in vivo approaches to characterize the humoral immune suppression produced by an acute oral exposure to HpCDD and to assess the potential cellular defects responsible for the suppression. Administration of HpCDD at various times prior to or following antigen challenge indicated that HpCDD induced rapid yet prolonged suppression of the antibody response. Timing studies also suggested that initial processing of antigen by the macrophage and antibody production by the mature plasma cell were resistant to HpCDD. The demonstration that antibody responses could not be improved by either increasing or decreasing the antigen dose indicated that the effects of HpCDD were not related to the level of antigenic stimulation per se. In addition, there was no evidence for a shift in the kinetics of the antibody response of HpCDD-treated mice at any antigen dose that might have reflected a delay in the development of the response. The dose-response effects of HpCDD on antibody responses to T-helper-cell-dependent (SRBC) and T-helper-cell-independent type 1 (TNP-LPS) and type 2 (DNP-Ficoll) antigens indicated that sensitivity to HpCDD-induced suppression directly correlated with the sensitivity of the response to T-cell regulation. Nonspecific activation of T-amplifier cells with concanavalin A was capable of reconstituting the depressed antibody response of mice treated with 100 micrograms/kg HpCDD but not of mice treated with 500 micrograms/kg HpCDD, further suggesting that regulatory T cells are most sensitive to HpCDD. Definitive evidence for the role of regulatory T cells in mediating HpCDD-induced suppression of the antibody response was obtained in studies using congenitally T-cell-deficient nude (nu/nu) mice. The antibody response to DNP-Ficoll was was assayed since the anti-DNP response proceeds in the absence of T-helper cells in nu/nu mice yet the response can be modulated by changes in the activity of T-amplifier and T-suppressor cells present in nu/+ mice. Results of these studies showed that nu/nu mice were significantly more resistant to the immunosuppressive effects of HpCDD as compared with their nu/+ littermates.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

[Changes of various factors of nonspecific humoral immunity in acute dysentery].

The level of total Enterobacterial Enterotoxins of the blood serum, of beta-lysins, lysozyme activity, complement and normal antibodies were studied in 191 patients with acute Flexner dysentery and in 285 patients with acute Sonne dysentery, depending on the period of the disease, its severity, the treatment applied, and the species of the causative agent. The level of the nonspecific humoral immunity factors increased before the treatment and its normalization depended on the treatment applied.

Acute Disease↗