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Antigens of subcellular fractions of Trypanosoma cruzi. III. Humoral immune response and histopathology of immunized mice.

The relation of humoral antibody response to protection was evaluated in mice immunized with whole homogenates of Trypanosoma cruzi or with its flagellar fraction by direct agglutination and indirect fluorescent antibody test as well as by lytic and neutralizing activity against blood trypomastigotes. The results indicated that lytic antibodies were not implicated directly in protection against these trypanosomes. It was evident from histopathologic examination that the higher the degree of protection achieved, the lower the tissue damage observed in the challenged mice. Serum-neutralizing activity was highest in the groups protected most effectively.

Animals↗

CD4+ T cells from mice primed for humoral immunity to sheep erythrocytes (SRBC) specifically inhibit cell-mediated immunity and vice versa.

The aim of this study was to demonstrate whether development of the humoral or cellular immunity to sheep erythrocytes (SRBC) can be inhibited by a transfer of antigen-specific CD4+ T cells isolated from mice exhibiting cellular or humoral response. For generation of the humoral immune response and suppressor T cells for the cellular immunity, mice were immunized with a high dose of SRBC intraperitoneally (i.p.). On the other hand, for development of the cellular response and generation of T cells with inhibitory activity in relation to the humoral response, mice were immunized subcutaneously (s.c.) with SRBC emulsified with complete Freund's adjuvant or intravenously (i.v.) with low dose of SRBC (10(5)). We showed that depletion of CD4+ but not CD8+ T cells in the populations of transferred T cells abolished their inhibitory activity. The phenomenon of this suppression was dependent on a dose of T cells transferred and was antigen-specific, since T cells specific for chicken erythrocytes did not inhibit anti SRBC-response. The data indicate the importance of antigen specific CD4+ T cells in the mutual regulation of the two major type of the immune response.

Animals↗

Vaccinia virus pathogenicity in atopic dermatitis is caused by allergen-induced immune response that prevents the antiviral cellular and humoral immunity.

Atopic dermatitis (AD) serves as a contraindication for the immunization of AD patients with a live vaccinia virus (VV) vaccine. The antiallergen IgE interacts with the Fc receptors (FcepsilonRI) on dendritic cell (DC) membranes and with allergen molecules. The immunological events that lead to AD disease, the activation of the T-helper 2 (Th2) immune response, the synthesis of the cytokines IL-4, IL-5, IL-13, and the inhibition of the T-helper 1 (Th1) damage the capacity of the host to develop anti-VV cytotoxic cells (CTLs). In the presence of Th2-derived cytokine IL-4 in the AD skin and the synthesis of VV proteins that interfere recruitment of DCs by host cytokines, the VV can cause a generalized infection. Conceptually, new VV recombinants may be needed for human immunization. Such VV recombinants should lack the genes that interfere with the host immune system and express a mutated human IL-4 cytokine gene that will prevent negative regulatory mechanisms. Such improved VV recombinants may be used to express genes from pathogenic viruses.

Allergens↗

Principle of the bark of Phellodendron amurense to suppress the cellular immune response: effect of phellodendrine on cellular and humoral immune responses.

Previously we have isolated the quaternary base alkaloids, magnoflorine and phellodendrine, from Phellodendri Cortex (cortex of Phellodendron amurense Rupr., Rutaceae) as the biologically active principles to suppress local graft-versus-host (GvH) reactions in mice. In this paper, we focus on phellodendrine. Phellodendrine suppressed local semisyngeneic GvH reactions and systemic allogeneic GvH reactions in X-ray irradiated recipient mice. Phellodendrine also suppressed the induction phase of sheep red blood cell (SRBC)-induced delayed type hypersensitivity in mice and tuberculin-induced delayed type hypersensitivity in guinea pigs, but did not suppress the effector phase of these reactions. Surprisingly, phellodendrine, unlike prednisolone and cyclophosphamide, did not affect antibody production in mice to SRBC. Phellodendrine was expected to be a valuable new type of immunosuppressor against the cellular immune response.

Animals↗

Induction of humoral immunity toward 2-acetylaminofluorene in mice: modulation of DNA binding after 4 weeks dietary exposure to the carcinogen.

In order to investigate the modulatory effect of the immune response induced by recurrent carcinogen exposure, anti-2-acetylaminofluorene (anti-2-AAF) IgG were elicited in Swiss mice before subsequent carcinogen administration. The immunization schedule consisted of three weekly i.p. injections of 2-acetylaminofluorene (2-AAF)-gelatin conjugate, followed by a final immunogen injection 14 days later. At the end of treatment, the presence of specific anti-2-AAF antibodies in blood serum of all immunized animals was demonstrated. The immunization procedure did not affect liver metabolic activities, as evaluated using liver homogenates for the exogenous activation of 2-AAF to mutagen. After immunization, mice were fed 2-AAF pelleted in the diet at 50 and 150 p.p.m. for 4 weeks and killed at the end of treatment. The determination of DNA adducts by ELISA in liver and spleen of treated animals revealed significantly (P < 0.01-0.001) lower 2-AAF adduct levels in both tissues of immunized mice with respect to non-immunized animals (both naive and pretreated with the adjuvant alone). This result suggests that the specific humoral immunity elicited by repeated carcinogen exposure may be able to modulate the genotoxic effect induced by subsequent carcinogen administration.

2-Acetylaminofluorene↗

Cellular and humoral immune parameters in women with pathological hyperprolactinemia before and during treatment with bromocriptine.

PROBLEM: Experimental and clinical evidence has suggested an immunostimulatory effect of prolactin and that bromocriptine, an inhibitor of prolactin release, counteracts the actions of prolactin on the immune system. The aim of this study was to determine the impact of elevated serum prolactin levels on the immune system in patients with pathological hyperprolactinemia. METHOD: For this purpose, parameters of the cellular and humoral immune system were studied in six women with prolactinomas and one with idiopathic hyperprolactinemia. Studies were performed when serum prolactin concentrations were high as well as during different phases of the menstrual cycle when prolactin levels had been normalized through treatment with bromocriptine. RESULTS: Hyperprolactinemic subjects, when compared with six age-matched normal women, had significantly higher percentages of total lymphocytes and CD2+ cells. Elevation of CD4+ cells was also observed although to a lesser extent. Bromocriptine-treated patients, when compared with normal women were characterized by increased numbers of total lymphocytes and CD4+ cells, decreased percentage of CD8+ cells, and increased concentrations of serum IgM. These last two findings were also significantly different when compared to those observed in hyperprolactinemia. CONCLUSION: In this study we have described the changes on cellular and immune parameters in patients with hyperprolactinemia before and during bromocriptine therapy, which support the links of communications between the immune and endocrine systems in humans.

Adolescent↗

Humoral immune responses to recombinant tree pollen allergens (Bet v I and Bet v II) in mice: construction of a live oral allergy vaccine.

Recombinant tree pollen allergens (recombinant Bet v I and recombinant birch profilin, Bet v II) were purified and used to immunize BALB/c and B6D2F1 mice with Al(OH)3 to elicit a specific IgE response. Serum from immunized mice was then used to detect immunoblotted natural tree pollen allergens. The onset of the humoral immune response was monitored using antimouse IgE, IgG1, IgG2a/b, IgG3 and IgA. In both strains, a specific and long-lasting IgE response could be elicited with both recombinant allergens. Mice immunized continuously with recombinant Bet v I + Al(OH)3 showed a significant decrease of specific IgE antibodies indicating that continuous application of allergens can reduce specific IgE responses. The possibility of inducing a different type of immune responses is indicated by the fact that mice fed with Bet v I expressed in apathogenic Salmonella strains showed a Th1 immune response to Bet v I accompanied by specific IgG2a/b without detectable IgG1 or IgE. Recombinant allergens can hence be used to decrease or even modulate specific IgE responses in vivo.

Adjuvants, Immunologic↗

Humoral immune response to the anti-malaria vaccine SPf66 in the Colombian Atrato River region.

The immunogenicity of anti-malaria synthetic vaccine SPf66 was tested in a region of the Colombian middle Atrato river. The specific serum antibodies against SPf66 were quantified in vaccinees and placebo injected controls for a two-years period post-immunization. The frequency of individuals showing seroconversion of anti-SPf66 antibodies three months after completion of the immunization schedule was higher in vaccinees than in controls (52.7% and 25.5%, respectively, p < 0.01). However, an over than four-fold increase of the specific anti-SPf66 antibody titers was observed only in 1.4% of vaccinees and 0.2% of the controls (p < 0.01). The anti-SPf66 antibody titers augmented in vaccinees from first dose application to three months after the third dose, continuously decreasing thereafter to reach below baseline values two years after completion of the immunization schedule. The results show that SPf66 has very low immunogenicity and induces a short term humoral immune response (six months).

Adolescent↗

Immunization of salmonids against Yersinia ruckeri: significance of humoral immunity and cross protection between serotypes.

Brook trout (Salvelinus fontinalis) were immunized with bacterins containing either Serotype 1 or 2 isolates of Yersinia ruckeri to determine the relative degree of cross-protection afforded when the fish were challenged with the homologous or heterologous serotype. While fish immunized with pH-lysed bacterins produced highly specific agglutinins that did not cross-react with antigens derived from a heterologous serotype of Y. ruckeri all fish were protected against experimental challenge, regardless of which serotype was used for bacterin production and experimental challenge. Other experiments indicated that brook trout injected intraperitoneally with highly specific antibodies could not be passively immunized against experimental challenge.

Animals↗

[Animal experimental studies on the increase in the humoral immune response caused by whole body irradiation].

The production of antibodies against heterologous erythrocytes (sheep erythrocytes) can be significantly increased in mice and rats by total body irradiation. This effect depends upon the radiation dose applied and can be demonstrated only in animals immunized first and then irradiated at intervals of six hours. In vitro assays show indirectly that the radiogenic immune stimulation is caused by the varying radiosensitivity of the individual cell populations involved in the humoral immune reaction, leading to a relatively selective inactivation of T-suppressor cells.

Animals↗

Antibody-mediated immunity in CFW mice infected with Mycobacterium lepraemurium. Humoral immune response in murine leprosy.

A depression in antibody-mediated immunity (AMI) measured both in terms of circulating antibody and plaque-forming cells in the spleen was observed in CFW mice infected with M. lepraemurium when sheep red blood cells (SRBC) and human gammaglobulin (HGG) were used as antigens. The impairment in AMI was evident only after 75 days of infection thereafter the antibody response to SRBC antigen progressively decreased until the last day of experimentation (135 days). Within the first 60 days of infection no alteration in AMI was observed with the HGG antigen while the response to the SRBC antigen was significantly higher in the infected animals than in uninfected controls.

Animals↗

Impact of differential housing on humoral immunity following exposure to an acute stressor in rats.

The purpose of this study was to examine the effect of differential housing on humoral immunity following exposure to an acute stressor. Forty male Sprague-Dawley adult rats were randomly assigned to either a singly housed or group-housed (five rats/cage) condition. Approximately 2 weeks after the start of the study, all animals were immunized with 1 ml of a 10% suspension of sheep red blood cells (SRBC) in saline. After the injections, half of the animals from each housing condition were subjected to an acute stressor (forced swim, 60 min/day for 3-5 days). Animals exposed to the acute stressor displayed adrenal gland hypertrophy and reduced thymus and spleen weights compared to the unstressed (control) animals. Both behavioral stimuli (housing and forced swim) demonstrated no effect on antibody production to SRBC. However, singly housed animals showed an increase in lymphocyte percentage, and corticosterone and glucose levels regardless of subsequent exposure to acute stress. Within a treatment condition, there were no significant correlations between the immune and endocrine measures. It was concluded that reduced social contact (i.e., individual housing) with subsequent exposure to an acute stressor does not appear to inhibit immunological responsiveness to an antigen.

Adrenal Glands↗

Humoral immunity in the central nervous system of Lewis rats infected with Borna disease virus.

The aim of this study was to investigate the humoral immune response to Borna disease (BD) virus in the brain of experimentally infected Lewis rats. Abundant IgG was detected in BD-rat brain with isotype variation throughout infection. IgG was locally produced as indicated by an intact blood-brain barrier, Ig kappa light chain mRNA-containing cells in brain and accumulation of virus-specific antibodies in cerebrospinal fluid. Treatment with BD-rat serum altered viral gene expression in persistently infected cultured rat glioblastoma cells. These data suggest that antibodies, produced in the brain, may influence viral gene expression.

Animals↗

Changes in CD4+CD8-/CD4-CD8+ ratio and humoral immune functions in vitamin B12-deficient rats.

To clarify the role of vitamin B12 in the function of cell-mediated and humoral immune functions, the splenocytes expression of CD4, CD8 and serum C3, IgM, IgG concentrations were examined in vitamin B12-deficient rats, and the effect of the administration of methylcobalamin was also studied. The CD4+CD8-/CD4-CD8+ ratio in splenocytes was significantly higher in vitamin B12-deficient rats than in control rats (p < 0.05). The value in the 48 hours after methylcobalamin administration group, was within the normal range (p < 0.05). From these results, the elevation of the CD4+CD8-/CD4-CD8+ ratio by vitamin B12-deficiency was confirmed in rats. The serum C3, IgM and IgG concentrations were lower in the vitamin B12-deficient group than in the control group. These findings suggest that vitamin B12 plays a role in maintaining the immune function in rats.

Animals↗

The antigenic specificity of the humoral immune response to primary and repeated ocular infections of the guinea pig with the GPIC agent (Chlamydia psittaci).

The antigenic specificity of the humoral immune response in guinea pigs to primary and repeated ocular infections with the guinea pig inclusion conjunctivitis (GPIC) chlamydial agent was analysed using microbiological, serological and Western blotting techniques. The results indicate that although there was a response to many minor polypeptide antigens, there was a marked lack of reactivity to the major outer membrane protein (MOMP), particularly following reinfection of guinea pigs. It is suggested that, lack of a good antibody response to the MOMP, may be one of the reasons why guinea pigs are susceptible to repeated ocular infections with this chlamydial agent.

Animals↗

Systematic method for determining intravenous drug treatment strategies aiding the humoral immune response.

This paper delineates a systematic method for determining "optimal" intravenous drug delivery strategies for patients having illnesses that primarily evoke a humoral immune response and are treatable by antibiotics. The method derives from a nonlinear, distributed predator-prey model that captures the dominant antigen and antibody interaction. This model is developed from relevant physiology, past predator-prey-type modeling work, available data, and pertinent parameter identification. Embedding this predator-prey model into a larger class of uncertain systems, by a finite dimensional approximation and a transformation to a linear fractional representation, enables the application of robust control based on linear matrix inequality optimization techniques. The optimization problem is solved by minimizing an upper bound on a measure of the total drug delivered subject to patient recovery (stability to healthy equilibrium state). Specifically, the paper addresses the treatment of Haemophilus influenzae through modeling, controller development, and simulations of infected adult patients subjected to typical and proposed intravenous antibiotic treatments. Through simulations the proposed intravenous drug strategy shortens patient recovery time, lowers peak drug concentrations and decreases the total drug administered when compared to standard antibiotic strategies.

AIDS-Related Opportunistic Infections↗