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Effect of hydrazide cysteine on the humoral immune response of mice to sheep erythrocytes.

Hydrazide of cysteine, introduced intraperitoneally or per os in three doses for three consecutive days after immunization of mice with SRBC, caused a stimulation or an inhibition of the humoral immune response, determined on day 4 as a number of cells in the spleen producing antibodies of 19S and 7S class. The stimulation of the humoral immune response was induced by the dose of 100 micrograms per mouse and was more significant in the case of the 7S response. High doses of HD, on the other hand (1 mg per mouse i.p. and 1-5 mg per mouse per os) caused an inhibition of the humoral immune response which was more pronounced in the case of the secondary immune response. The mechanism of action of HD in the course of the immune response and its possible application in therapy is discussed.

Administration, Oral↗

Cell mediated and humoral immune responses in oral submucous fibrosis.

Cell-mediated and humoral immune responses were assessed in 50 patients with oral submucous fibrosis (OSMF) and the results were compared with those of 50 patients with oral-leukoplakia, 50 oral cancer patients, and 50 normal healthy adult controls. The number of high-affinity rosette-forming cells (HARFC) was found to be significantly decreased in OSMF and oral cancer, whereas the number of total rosette-forming cells (TRFC) remained unaltered. Levels of serum IgA, IgD, and IgE were found to be elevated both in OSMF and oral cancer. Immunologic derangements were found to be more pronounced in oral cancer than in OSMF. The enumeration of HARFC along with the estimation of serum levels of IgA, IgD, and IgE indicates that OSMF can be an intermediary stage in the malignant transformation of a normal cell, and that these parameters may serve as markers for the early detection of oral cancer.

Adult↗

Age related differences in humoral immune response to respiratory syncytial virus infection in adults.

The humoral immune response to Respiratory Syncytial Virus (RSV) was investigated in old and young adults. RSV was identified by culture and/or reverse transcription polymerase chain reaction (RT-PCR) in 52 elderly (mean age 74 years) and 15 young adults (mean age 33 years) with respiratory illness. Preinfection serum neutralizing and binding antibody levels were similar in the two age groups, although older persons had significantly greater serum neutralizing responses to group A RSV (log(2) 2.8 increase vs. 1.7, P = 0.001) and group B RSV (log(2) 2.8 vs. 1.3, P = 0.0008). Older persons also had significantly increased responses to the RSV F (log(2) 2.9 vs. 1.1, P < 0.0001), Ga (log(2) 2.1 vs. 1.3, P = 0.0007), and Gb proteins (log(2) 2.7 vs. 1.4, P = 0.0004). The exuberant antibody response seen in older adults may be a reflection of greater viral load and antigenic stimulation and/or a shift from Th1 to Th2 dominant immune response with aging. The relationship of immune response to disease pathogenesis in older persons deserves further study.

Adult↗

Humoral immune response to some benzylpenicillin preparations.

In this study the humoral immune responses to long-term administration of benzylpenicillin preparations with and without adjuvants were compared. In 44.4% of the patients on long-term treatment with a benzylpenicillin preparation containing oil and alum monostearate, an induction of benzylpenicilloyl (BPO)-specific IgG, IgM and IgE was demonstrated during and after the course. Patients treated with a benzylpenicillin preparation containing no oil and alum monostearate showed only a very weak BPO-specific IgM and IgG response during the course. In patients in whom long-term treatment with a benzylpenicillin preparation without adjuvants was initiated by a benzylpenicillin preparation containing oil and alum monostearate, not only BPO-specific IgM and/or IgG but also IgE were demonstrated in 13.0%. The differences in immune response in the various long-term courses were significant (P less than 0.05). The data suggest that the presence of such adjuvants as oil and alum monostearate has an influence on the synthesis of BPO-specific antibodies. However, it can not be excluded that the difference in immunogenicity had some unknown connection with the differences in penicillin/blood levels.

Antibody Specificity↗

Effect of the antitumor antibiotic chromomycin A3 on the humoral immune response in rats.

Chromomycin A3 (250 mug/kg) suppressed the humoral immune response in rats against sheep erythrocytes when administered 48 h or later after antigenic stimulus. The antibiotic at this dose enhanced immunity when given along with or before antigen administration. The natural heterohemagglutinin levels in rabbits and guinea pigs were not affected by the antibiotic (10 mug/kg per day x 7).

Animals↗

[Role of glucocorticoids in the development of a humoral immune response in the intact organism].

The formation of the humoral immune response in experimental rabbits to typhoid Vi-antigen and to sheep red blood cells was estimated from serum hemagglutinin titres. It was found to vary but insignificantly in the animals were immunized concurrently with the blocking of the hypothalamo-hypophysio-adrenocortical system induced by intraventricular administration of dexamethasone or during stimulation of this system due to a short-term stress. The results obtained show that relatively short-term changes in the plasma 11-HCS concentration cannot lead to significant disorders in the antibody production by the organism.

11-Hydroxycorticosteroids↗

Impaired germinal centre formation and humoral immune response in the absence of CD28 and interleukin-4.

The generation of an optimal humoral immune response requires fully activated T-cells. For complete activation at least two signals are needed. The first one is an antigen dependent one via the T cell receptor, the second one is a costimulatory signal which can be delivered by the CD28 molecule after binding to CD80 (B7.1) or CD86 (B7.2). Fully activated T helper cells are competent to deliver help to B-cells by secreting cytokines (e.g. interleukin (IL)-4) or up-regulating CD40 ligand for proliferation and differentiation of B cells. These interactions mainly take place in germinal centres (GC) that arise after antigen stimulation in B cell-follicles of peripheral lymphatic tissues and are the sites of massive B-cell proliferation, affinity maturation and class switch. The roles of CD28 and IL-4 were investigated in GC formation and antibody production. A markedly diminished humoral immune response was observed in IL-4(-/-) xCD28(-/-) mice whereas in CD28(-/-) and IL-4(-/-) mice the defect was less severe. Especially the formation of germinal centres was significantly reduced in CD28(-/-) or IL-4(-/-) mice and almost undetectable in IL-4(-/-) xCD28(-/-) mice. Taken together these data indicate that CD28 and IL-4 are synergistically involved in GC formation and immunoglobulin production.

Animals↗

Potentiation of the primary humoral immune response in vitro by C5a anaphylatoxin.

The effect of the anaphylatoxin C5a on the primary humoral immune response to SRBC was studied in culture of spleen cells from C3H mice. The addition of human C5a to antigen-stimulated cultures resulted in a significant, dose-dependent augmentation of the primary PFC response to antigen. The specificity of this effect was affirmed by the ability of C5ades Arg, but not of the structurally analogous C3a anaphylatoxin, to act in a parallel fashion. Enhancement could be observed over a range of doses of antigen. Brief preincubation of macrophages, but not of lymphoid cells, with C5a was sufficient to cause subsequent enhancement of the primary humoral immune responses. The duration of preincubation required for this effect closely paralleled that for binding of C5a to peritoneal cells. Immunopotentiation by C5a appears to involve the function of C5a receptor-bearing, Ia- accessory cells as well as Ia+ antigen-presenting cells. Immunopotentiation could be observed when the addition of C5a was delayed for up to 24 hr after initiation of culture. Additionally, augmentation of tritiated thymidine uptake in mixed lymphocyte reactions was enhanced by the addition of C5a in a fashion parallel to that for the primary response to SRBC. These observations support a role for C5a as a modulator of cellular immunity in addition to its role in acute inflammation. Possible cellular mechanisms and implications for immunomodulation of immune responses are discussed.

Adjuvants, Immunologic↗

Evaluation of humoral immune responses in cattle grazing endophyte-infected or endophyte-free fescue.

Anecdotal reports suggest cattle with fescue toxicosis may not respond to vaccination and thus, experience increased incidence of Bovine Respiratory Disease Complex (BRDC) when shipped to feedlots. Fescue toxicosis causes hypoprolactemia in cattle. Hypoprolactemia decreases humoral immune responses in mice. Therefore, a study was conducted to compare the magnitude of primary and secondary humoral immune responses against specific antigens in cattle grazing endophyte-infected or endophyte-free fescue. Angus steers were blocked by weight and allocated into four groups. Two groups grazed endophyte-infected (EI) fescue and the other two groups grazed endophyte-free (EF) fescue. All steers were injected IM on d 0 and 21 with lysozyme without adjuvant and concanavalin. A (Con A) with sheep red blood cells (SRBC) in incomplete adjuvant of Freund. Steers were bled on days 0, 21 and 35 post-vaccination. Average daily gains (ADG), alkaline phosphatase (ALP) activity, cholesterol concentrations, rectal temperatures, and serum prolactin concentrations were measured to confirm fescue toxicosis in steers grazing EI fescue. Antibodies to Con A and SRBC were determined by ELISA and hemagglutination assay, respectively. The ADG were decreased for the EI group during the first month. Rectal temperature were elevated and serum prolactin concentrations were decreased in the EI group. Cholesterol and ALP concentrations also were decreased in the EI group. Primary and secondary immune responses against Con A tended to be increased and were increased against SRBC in the EI group. Antibodies against lysozyme were not induced in either group. In conclusion, cattle grazing EI fescue mounted similar humoral immune responses to vaccination, despite hypoprolactemia, as cattle grazing EF fescue. Increases in bovine respiratory disease in cattle maintained on EI fescue probably is not associated with lack of humoral immune response to vaccination protocols as a result of fescue toxicosis.

Acremonium↗

[Induction of specific cytotoxic T lymphocytes and humoral immune response by MUC1 DNA vaccine in mice].

AIM: To observe the specific cytotoxic T lymphocyte and humoral immune response induced by MUC1 DNA inmunization in mice. METHODS: Female BALB/c mice were immunized intramuscularly with 100 microg pcDNA3.1-MUC1 3 times at intervals of 3 weeks. Three weeks after the last immunization, tumor challenge experiments were performed by inoculation of MUC1 positive breast cancer cell line EMT6. Both humoral immune response and CTL-specific cytotoxicity were detected by immunohistochemical staining and (51)Cr release assay, respectively. RESULTS: The cytotoxicity of MUC1-specific CTLs to EMT6 target cells showed that the cytotoxic effect was different at various ratio of effector cells to target cells. At ratios of 100:1, 50:1, 25:1 and 12.5:1, the specific lysis in MUC1cDNA group reached 54.1%, 39.8%, 26.4% and 20.1%, while two control groups 13.2%, 10%, 8.2%, 7.2% and 11.7%, 9.8%, 7.7%, 7.0%, respectively. The former was markedly higher than the two latters(P<0.01). MUC1 expression was exhibited to be positive in breast cancer tissue by immunohistochemical staining with BALB/c mouse sera against MUC1 cDNA. There was only 40% tumorigenic rate in MUC1 cDNA immunized group, while there 100% in pcDNA3.1(+) and NS control groups. There was a significant difference between MUC1 cDNA group and control groups (P<0.05). CONCLUSION: Specific CTLs and antibody prodution are elicited by MUC1 DNA inmunization. MUC1 cDNA inmunization partly inhibit the growth of implanted tumor in mice.

Animals↗

Enhancement of humoral immune responses to HBsAg by heat shock protein gp96 and its N-terminal fragment in mice.

AIM: Most studies on the immune effect of gp96 were focused on its enhancement of CTLs. It is interesting to know whether gp96 could influence the humoral immune response, and whether the recombinant N-terminal fragment of gp96 could substitute native gp96 to stimulate the immune system. METHODS: gp96 isolated from livers of normal mice and its N-terminal fragment (amino acid 22-355) expressed in E coli were used for immunization of BALb/c mice. Eight groups of mice received one of the following regiments subcutaneously in 100 microL phosphate buffered saline (PBS) at an interval of 3 wk. Group 1: PBS only; group 2: gp96 only; group 3: N-terminal fragment only; group 4: HBsAg only; group 5: HBsAg+gp96; group 6: HBsAg+N-terminal fragment; group 7: HBsAg+incomplete Freud's adjuvant; group 8: HBsAg+N-terminal fragment (95 degrees heated for 30 min). Serum anti-HBsAg antibody levels were assayed by ELISA. CTL responses in splenocytes were analyzed by ELISPOT after the last vaccination. RESULTS: The average titer of serum anti-HBsAg antibody in the mice immunized with HBsAg together with gp96 or its N-terminal fragment were much higher than those immunized with HBsAg alone detected by ELISA. The cellular immune response of the mice immunized with HBsAg together with gp96 or its N-terminal fragment was not different with those immunized with HBsAg alone measured by ELISPOT assay. CONCLUSION: gp96 or its N-terminal fragment greatly improved humoral immune response induced by HBsAg, but failed to enhance the CTL response, which demonstrated the potential of using gp96 or its N-terminal fragment as a possible adjuvant to augment humoral immune response against HBV infection.

Animals↗

[Effect of unilateral nephrectomy in mice on the level of the humoral immune response to T-independent antigen].

The influence of unilateral nephrectomy on the degree of humoral immune response to T-independent (polyvinylpyrrolidone, PVP) and T-dependent (sheep red blood cells, SRBC) antigens was studied. The increase in the number in antibody-forming cells (AFC) and nonspecific immunoglobulin-forming cells (nIFC) was investigated by means of the adaptive transfer model. The lethally irradiated recipients were injected with the antigen and also the spleen cells of operated and intact donors. PVP did not induce significant alterations of antibody genesis in mice receiving spleen cells of unilaterally nephrectomized animals comparing with recipients of intact spleen cells. At the same time, the kidney operation induced the increase in the number of AFC and nIFC when the SRBC were used. Hence the activation of humoral immune response induced by kidney operation was related not to the direct activation of B-lymphocytes but to T-cells. The possible causes of this activation were analyzed. Spleen cells of operated animals enhance both specific and antigen-dependent nonspecific immune response.

Animals↗

Humoral immune response to intralymphatic immunotherapy for disseminated melanoma: correlation with clinical response.

Since September 1979, 44 stage III melanoma patients treated with intralymphatic immunotherapy (ILI) with an oncofetal antigen (OFA-I)--enriched tumor cell vaccine (TCV) had evaluable humoral immune responses and clinical follow-up. Fourteen patients (32%) had stabilization or regression of tumors or remained free of resected disease. The median survival was 17 months, compared with 6 months for controls (P less than 0.001). Humoral immune responses were monitored by immune adherence using an OFA-positive human melanoma cell line, M14, as target. Alloantibodies were removed by absorption with L14 lymphoblasts autologous to M14. Twenty-two patients (50%) developed elevated antibody titers within 4 months, and 12 of the 22 (55%) had no disease progression. In contrast, 20 of 22 patients (91%) who failed to develop elevated titers had disease progression (P less than 0.01). The median titer was significantly higher during the first 4 months in the group whose disease did not progress (P less than 0.04). This study demonstrated that ILI with allogeneic OFA-I-enriched TCV can induce objective tumor regression and prolonged survival in patients with disseminated melanoma. Furthermore, because the specific humoral immune response correlates with clinical results, immunization efficacy can be monitored within a short period of time, which should aid future efforts to achieve optimal immunotherapy.

Adult↗

Comparison of the murine humoral immune response to recombinant simian virus 40 large tumor antigen: epitope specificity and idiotype expression.

Baculovirus-derived recombinant simian virus 40 (SV40) large tumor antigen (SV40 T-Ag) was used to immunize inbred strains of mice to compare the humoral immune responses. Specifically we examined the epitope specificities and idiotype (Id) expression on anti-(SV40 T-Ag) responses induced in BALB/c and C57BL/6 inbred strains of mice. The predominant SV40 T-Ag epitopes recognized by the anti-(SV40 T-Ag) responses appeared to differ between these two inbred strains, this being based on the ability of sera to inhibit the binding of several murine monoclonal antibodies specific for SV40 T-Ag. In addition, anti-(SV40 T-Ag) responses produced in C57BL/6 mice failed to express a previously described cross-reactive Id expressed in the anti-(SV40 T-Ag) response in BALB/c mice. This cross-reactive Id is detected by a mouse monoclonal anti-Id, designated 58D, which has been shown to represent a potential focal point for manipulating the humoral immune response to SV40-induced tumors in BALB/c mice. Together, these data indicate that the functional duality of the humoral immune response, as assessed by epitope recognition and Id expression, differs between these two inbred strains of mice when immunized with a recombinant SV40 T-Ag.

Animals↗

Dynamics of the humoral immune response of calves infected and re-infected with Cooperia punctata.

The dynamics of the humoral immune response of calves were analysed after primary infection and re-infection with the intestinal nematode Cooperia punctata. 12 male 5 month-old Holstein-Friesian calves were randomly divided into two groups A and B. At the beginning of the experiment Group A animals were each infected experimentally with a single oral dose of 130,000 infective third stage larvae (L3) of C. punctata. The animals of Group B were kept as non-infected controls. The two calves from Group A with the highest infections died of cooperiosis at 32 and 44 days after infection (DAI), respectively. On DAI 100 the calves were treated with the recommended dose of oxfendazole. On DAI 180 the remaining four calves of Group A and three animals of Group B (B1) were infected with 260,000 L3 of C. punctata, while the other three calves of Group B (B2) served as non-infected controls. Monitoring of the humoral immune response predominantly demonstrated an IgG1 response against both adult and L3 antigen of C. punctata. Moreover, re-infections increased the levels of these immunoglobulins. IgA levels were less increased than IgG1 and no significant increase was observed in IgG2 and IgM levels. Immunoblotting analysis showed that total IgG present in the serum of the primary infected animals mainly reacted against adult proteins of 12-14 and 17-20 kDa and against L3 proteins of 33 and 43 kDa. After re-infection total IgG reacted with the same adult proteins but also with an adult 29 kDa protein.

Animals↗

Cell-mediated and humoral immune responses in guinea pigs sensitized with the thermostable antigen of human granulocytes (TSGA).

Cell-mediated and humoral immune responses are induced shortly after a single injection of the human thermostable granulocyte antigen TSGA to guinea pigs. This was proved by means of the lymphocyte transformation assay and the estimation of MIF and LIF activity in supernatants of antigen-stimulated lymph node cells as well as by immunodiffusion, immunoelectrophoresis and immunohistology. The maximum of the cellular response was observed 10 days after immunization. The antibody production appeared after a lag time and increased continuously thereafter. The antisera of guinea pig yields a strong specific fluorescence in neutrophils and a weak fluorescence in monocytes of man. The humoral immune responses of guinea pig antisera correspond to the results obtained with antisera from rabbits.

Animals↗

Protective effect of melatonin against propoxur-induced oxidative stress and suppression of humoral immune response in rats.

Effect of melatonin in attenuation of propoxur induced oxidative stress and suppression of humoral immune response was studied in rats. Oral administration of propoxur (10 mg/kg) increased lipid peroxidation in serum after 28 days treatment. Superoxide dismutase, catalase and glutathione were also altered following propoxur exposure. In addition propoxur exposure markedly suppressed humoral immune response as assessed by antibody titre and plaque forming cell assay. Simultaneous treatment with melatonin (5 mg/kg, ip) markedly attenuated the effect of propoxur on (a) lipid peroxidation, (b) oxidative stress parameters and (c) immunotoxicity. Results have been discussed in the light of possible immunopotentiating and antioxidant effects of melatonin to understand the influence of oxidative stress on propoxur induced immunomodulation.

Animals↗

CpG immuno-stimulatory motifs enhance humoral immune responses against hepatitis C virus core protein after DNA-based immunization.

Chronic HCV infection is associated with a high morbidity and mortality rate, and currently a prophylactic or therapeutic vaccine is not available. DNA-based immunization is a powerful method to generate cellular and humoral immune responses. However, DNA immunization against HCV core results only in a weak humoral immune response demonstrated in several studies. Therefore, co-immunization with a novel adjuvant may enhance such potentially important immune responses. We examined whether unmethylated CpG motifs in the form of oligodeoxynucleotides (ODN) or E. coli DNA can act as adjuvants for a DNA vaccination approach, since CpG motifs have been shown to stimulate the innate immune system as well as B and T cell immune reactivity. The present study demonstrates that CpG motifs enhance in vivo antibody levels after DNA immunization against HCV core. However, despite some in vitro activity of CpG motifs, no enhancement of T cell responses in vivo was observed after immunization with HCV plasmid DNA and CpG motifs in mice. Our results suggest that co-immunization with CpG-ODN may strengthen humoral immune responses but show no potential effect as an adjuvant to induce cellular immunity against HCV core.

Adjuvants, Immunologic↗