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Quantitative aspects of the nonspecific humoral immune response to sheep erythrocytes.

The kinetics and magnitude of the nonspecific humoral immune response was studied at the cellular level in mice immunized with sheep erythrocytes (SRBC). Intravenous injection of the antigen evoked, in addition to a specific anti-SRBC response, a nonspecific response of all immunoglobulin (Ig) classes and subclasses. This nonspecific response peaked on day 4 or 5 after immunization, irrespective of the Ig class. The absolute number of nonspecific Ig-secreting cells induced by immunization varied with the different Ig-classes, and it was not proportional to the background level of Ig-secreting cells of the various classes. The nonspecific IgM-IgG1- and IgG2-response was 3 to 4 times as large as the antigen-specific responses of these classes. The nonspecific IgA-response, however, was many times greater.

Animals↗

The transfer of antigen-specific humoral immunity from marrow donors to marrow recipients.

This study shows that specific humoral immunity could be transferred from marrow donors to marrow recipients. Peripheral blood lymphocytes from long-term human marrow recipients produced IgG anti-tetanus toxoid antibody after in vitro tetanus toxoid stimulation. Antitetanus toxoid antibody biosynthesis was induced using a new tetanus toxoid-specific system employing high lymphocyte numbers, many replicate microcultures, and antigen washout. Anti-tetanus toxoid antibody in 12-day culture supernatants was detected using an enzyme-linked immunosorbent assay. Of 14 marrow recipients, 6 (5 with and 1 without chronic graft-vs-host disease) had lymphocytes that produced anti-tetanus toxoid antibody. Culturing additional numbers of marrow recipient lymphocytes increased in vitro biosynthesis of anti-tetanus toxoid antibody. The presence of circulating serum antibodies to tetanus toxoid and the production of specific anti-tetanus toxoid antibody by peripheral blood lymphocytes from marrow recipients show that engrafted donor lymphocytes can produce in vitro specific antibodies to recall antigens without postgrafting reimmunization.

Adolescent↗

Role of cervical lymph nodes in the systemic humoral immune response to human serum albumin microinfused into rat cerebrospinal fluid.

The humoral immune response to human serum albumin (HSA) microinfused into cerebrospinal fluid (CSF) has been measured in serum, cervical lymph nodes, and spleen of Sprague-Dawley rats. Conditions were designed to promote normal brain barrier function. Serum titers of anti-HSA antibodies, primarily IgG, increased over 10 days and then persisted for at least 10 weeks. A significant role for cervical lymphatics in the systemic response to CSF-administered HSA is suggested, based on results showing that (1) cervical lymph obstruction reduces serum titers of anti-HSA antibodies, and (2) total antibody production by combined superficial and deep cervical nodes, sampled 14 days post-immunization, exceeds that by the spleen.

Animals↗

Bancroftian filariasis in Kwale District of Kenya. II. Humoral immune responses to filarial antigens in selected individuals from an endemic community.

Humoral immune responses to filarial infection were investigated in 162 individuals, covering the full clinical and parasitological spectrum of bancroftian filariasis as seen in an endemic community of Kwale District, Kenya. Sera were tested for specific antifilarial antibodies (total immunoglobulins, IgM, IgGl, IgG4 and IgE) using ELISA. Most individuals showed an immunological response to the filarial antigen (prepared from adult Brugia pahangi). How these responses were related to the clinical manifestations, parasitological status and age was analysed by comparing the mean antibody levels among different categories of endemic individuals, and by comparing these to the levels in control groups from filariasis-free areas. IgM and IgE anti-filarial antibodies were detected with low specificity in unabsorbed sera. A higher specificity, clearly distinguishing the mean antibody levels in the endemic categories from those of control groups, was obtained for total specific immunoglobulins, and for IgE in sera absorbed with protein A. The most specific results were obtained for IgGl and IgG4; clear inter-category differences were observed for these classes. The mean level of specific IgG4 was significantly higher in microfilaraemic groups than in amicrofilaraemic groups, whereas the mean level of specific IgGl was significantly higher in amicrofilaraemic, symptomatic cases than in microfilaraemic, symptomatic cases. In most categories of endemic individuals, and for most antibody isotypes, the mean levels of specific antibodies tended to be higher (although not significantly) in the younger individuals than in the older individuals. Overall, the differences in the filarial antibody responses were more closely related to the presence or absence of microfilariae and to the age of the individuals than to the disease manifestations in this endemic population.

Acute Disease↗

Inhibitory and stimulatory effects of dianhydrogalactitol, an alkylating cytostatic agent on the humoral immune response.

The effect of an alkylating agent, dianhydrogalactitol (DAG), on the humoral immune response of C57B1 mice immunized with sheep erythrocytes was studied. Different inhibitory or stimulatory effects could be achieved by varying the time and the dose of drug administration. DAG in a dose of 1.5 mg/kg given either before or after immunization induced enhanced immune responses. Higher doses (greater than 5 mg/kg) administered in the inductive phase had a marked suppressive effect while treatments at this dosage preceding immunization resulted in a stimulation. The functionally distinct cell populations acting in the immune response to sheep red blood cells are postulated to have different sensitivity to the drug.

Animals↗

[Determination of cellular and humoral immunity in mice of autoimmune ovarian failure].

OBJECTIVE: To determine cellular and humoral immunity in mice of autoimmune ovarian failure. METHODS: A mice model of autoimmune ovarian failure was established. The percentages of help T cell (CD4+) and suppressor T cell (CD8+), the ratio of CD4/CD8 and anti-ovarian antibody (AOA) were determined. RESULTS: No significant changes were found in CD4+ fraction, but the percentage of CD8+ was reduced and the ratio of CD4/CD8 increased. AOA was positive which was probably the cause of damage of the ovarian tissues, reduction of sex hormone secretion and impaired fertility. CONCLUSION: Autoimmune ovarian failure is correlated with the abnormal change of CD4/CD8 and the increase of B-lymphocytes function.

Animals↗

[Comparison of various methods for the measurement of the humoral immune response in mice vaccinated with aphthous fever virus].

Kinetics of the humoral immune primary response and seven-day secondary response of adult CF1 mice to FMDV O1 Campos adjuvanted in aluminium hydroxide-saponin (AHS) or in oil emulsion (OE) were evaluated by means of ELISA and passive hemagglutination (PH). Analysis of the response to AHS vaccine showed that ELISA measured maximal titres of primary response at 23 days post-vaccination (dpv), and at day 17 of secondary response, while PH detected maximal titres for primary as well as secondary response around day 60 pv. Mice immunized with OE vaccine studied by ELISA presented a plateau of primary response around 40 dpv, while secondary response was maximal around 80 dpv. The same sera tested by PH showed the highest titres for primary response on day 50 pv and secondary response was maximal on day 40 pv. A criterion for the evaluation of vaccination efficiency in the murine model is proposed based on the methods employed in the determination of antibody level.

Animals↗

Cell-mediated and humoral immune responses in patients with localized juvenile periodontitis.

Cell-mediated and humoral immune responses were assessed in 21 patients with localized juvenile periodontitis (LJP), and in an equal number of control subjects. The cell-mediated immunity, assessed by enumeration of total rosette forming cells [TRFC] and high affinity rosette forming cells [HARFC], was found to be depressed in LJP patients compared to controls. Estimation of serum immunoglobulins G,A,M,D and E levels were done using single radial immunodiffusion. All the immunoglobulins except IgD were found to be elevated significantly in LJP patients. The defective immune response found in LJP patients may be the cause or effect of the disease process. Further investigations are necessary to determine whether these defects are genetically controlled.

Adolescent↗

[The effect of synthetic protein fragments on humoral immune response].

Effect of some protein and immunopeptide synthetic fragments on the humoral immune response has been studied. Some investigated peptides are shown to influence the antibody genesis at the secondary immune response to T-dependent antigen (bovine serum albumin) in mice. The serum antibody level specific for the bovine serum albumin is measured by enzyme-linked immunosorbent assays (ELISA). Possible mechanisms of the influence of such peptide fragments on the immune system is discussed.

Amino Acid Sequence↗

Immunological study of typhoid fever in man: humoral immune response.

Widal and indirect haemagglutination test were used to study the humoral immune response of 45 patients with typhoid fever. The Widal and IHA tests were positive in 41 (91.1%) and 42 (93.3%) of patients with typhoid fever after the second week of illness. Comparison between the Widal and IHA test showed that the latter was more sensitive as assessed by Wilcoxon matched-pairs signed-ranks test (p less than 0.01). The anti-LPS antibody belongs to all three classes of immunoglobulins namely IgG, IgM and IgA with the confinement mostly to IgG and IgM. It was found that the level of haemagglutinating enhancement activity was strongest in IgG class. The low level of anti LPS-antibody was found in healthy persons with the pattern of immunoglobulin class of antibody similar to that in patients with typhoid fever.

Adolescent↗

Humoral immune responses to the human immunodeficiency virus type-1 (HIV-1) in the genital tract compared to other mucosal sites.

Infection with the human immunodeficiency virus-1 (HIV-1) must be considered as a primarily mucosal disease. On a worldwide basis, the absolute majority of HIV infections occur through mucosal surfaces of the genital and intestinal tracts, and the earliest and most dramatic immunologic alterations are induced by the virus in mucosal tissues. However, individual compartments of mucosal components of the immune system display remarkable differences with respect to dominant antibody isotypes, virus phenotypes, densities and origins of cells involved in innate and specific immunity, presence or absence of inductive sites, and routes of immunizations that induce humoral and cellular responses. In this regard, the mucosal immune system of the female and male genital tracts exhibit several features which are distinct from other mucosal tissues, including dominance of the IgG isotype, local as well as pronounced systemic origin of antibodies, the absence of organized lymphoepithelial inductive sites and limited humoral responses stimulated by local antigen administration. Furthermore, it is evident that, irrespective of the route of infection, HIV-1 induces easily detectable IgG but not IgA specific antibody responses. These differences must be considered in the design of protective vaccines against infection with HIV and other agents of sexually transmitted diseases.

AIDS Vaccines↗

Comparison of humoral immune responses and tumor immunity in mice immunized with recombinant SV40 large tumor antigen and a monoclonal anti-idiotype.

We compared the humoral immune responses induced in BALB/c mice by immunization with recombinant SV40 large tumor antigen (T-ag) with those induced by a monoclonal anti-idiotype (anti-Id), designated 58D, that is specific for SV40 T-ag-induced Id network components. We also challenged immunized mice with a lethal dose of SV40-transformed cells to assess in vivo tumor immunity. Two biweekly immunization with either SV40 T-ag or anti-Id 58D induced humoral responses that recognized both SV40 T-ag and anti-Id 58D. Four biweekly immunizations with SV40 T-ag increased the antigen-specific antibody titers and decreased the response to anti-Id 58D, while four biweekly immunizations of anti-Id 58D increased antibody titers to both itself and SV40 T-ag. Comparison of specific T-ag epitope and idiotope specificities indicated that SV40 T-ag and anti-Id 58D immunization generated responses that recognized a similar epitope on SV40 T-ag and expressed a shared idiotope recognized by anti-Id 58D. SV40 T-ag immunized mice challenged with a lethal dose of SV40-transformed cells were completely protected and no tumors were observed. This is despite the fact that little or no SV40 T-ag-specific cytotoxic T-lymphocyte activity was detectable. In contrast, only 3 of 10 mice immunized with anti-Id 58D were protected from a lethal challenge. These results indicate that, although monoclonal anti-Id immunization can induce responses that recognize similar SV40 T-ag epitopes and express shared idiotopes associated with antibodies to SV40 T-ag, the recombinant antigen itself induces superior in vivo tumor immunity.

Animals↗

Local immunity in the pig respiratory tract. I. -- Cellular and humoral immune responses following swine influenza infection.

By serial lung washings on living pigs, kinetics of humoral and cellular local immune responses have been studied following intranasal inoculation of swine influenza virus. Local and serum antibodies appeared 8 days post-infection (p.i.) and reached a maximal titer 2 weeks p.i. Antibody titer decreased faster in lung secretions than in serum. Local and systemic cell-mediated immune responses were detected, by in vitro transformation tests, during the second week p.i.

Animals↗

Qualitative assessment of the humoral immune status against FMDV in post-vaccination cattle.

Analyses on diluted sera would not measure the complete activity of the natural in-vivo serum environment used by humoral immune responses. Since these humoral defences must react rapidly, serum reactions occurring during 10 and 60 s were analysed. Primo- and multiple-vaccinated, efficiently responsive, and protected animals were differentiated. A variation in the responses, particularly the quality of response, of individual animals was also now discernible. The critical importance of antibody-antigen contact time was demonstrated, wherein natural immunoglobulins and non-immunoglobulin opsonins would influence specific antibody reactivity, through an increased avidity of reaction with antigen. Although not measured directly, the influence of the non-specific serum components would be manifest through increased specific antibody binding. By considering serum as an entity, analysis of all constituent components permits increased qualitative assessment of post-vaccination sera.

Age Factors↗

Cellular and humoral immune responses of hydatidosis patients to Echinococcus granulosus purified antigens.

The cellular and humoral immune responses of 41 hydatidosis patients, 12 healthy uninfected individuals, and seven patients with other parasitic diseases were determined using serologic and lymphoproliferative assays (LPAs), respectively. Echinococcal antigens were obtained by gel filtration of crude hydatid cyst fluid (HCF) on a Sephadex G-200 column. The fractions contained either a mixture of antigens A plus B or antigen B alone that was further enriched by boiling. All the hydatidosis patients responded positively by LPA to either crude or purified echinococcal antigens: 95% of them responded to either crude HCF, or a mixture of antigens A plus B and 83% to antigen B alone. The degree of the response to crude HCF (mean stimulation index [SI] = 75.3) was higher than that of purified antigens (SI = 39.1 for a mixture of antigens A plus B and SI = 36.9 for antigen B alone). No positive LPA response was obtained with the control groups. Serologic examinations showed that 78% of cases were positive by immunoblot, 73% by indirect hemagglutination, and 46% by immunoelectrophoresis. No correlation between the degree of cellular and humoral responsiveness to both crude and purified echinococcal antigens was observed. Nine of the 41 patients examined who were serologically negative also developed a high lymphoproliferative (LP) response to either crude or purified echinococcal antigens. The LP response remained positive over a long period after successful treatment. No relationship was observed between the results of treatment and the LP response. The present study indicates that the LPA could be used as an additional tool for the diagnosis of hydatid disease, particularly in seronegative cases, although it is unsuitable for effective monitoring treatment/surgery.

Adolescent↗

Immunization of human HIV-seronegative volunteers with recombinant p17/p24:Ty virus-like particles elicits HIV-1 p24-specific cellular and humoral immune responses.

OBJECTIVE: To evaluate the immune response to HIV-1 p24 generated in vivo by p17/p24:Ty virus-like particles (p17/p24:Ty-VLP) by examining the lymphoproliferative and antibody (Ab) responses to HIV-1 p24, as well as Gag-specific cytotoxic T lymphocytes (CTL), in HIV-seronegative volunteers immunized with hybrid p17/p24:Ty-VLP. DESIGN AND METHODS: Sixteen HIV-seronegative volunteers were immunized with p17/p24:Ty-VLP at two dose levels (100 or 500 micrograms) and monitored for the following 48 weeks for production of anti-p24 and anti-p17 Ab, in vitro lymphoproliferative responses to HIV-1 p24 and p17, and in vitro CTL responses to HIV-1 Gag. RESULTS: Twelve out of the 16 volunteers had significant p24-specific proliferative responses, with volunteers on the higher dose schedule exhibiting earlier proliferative responses than those on the lower dose schedule. Proliferative responses in both volunteer groups were similar in overall magnitude but appeared at different times during the immunization schedule. Anti-p24 Ab were detected in six out of the nine individuals in the lower dose group and in five out of the seven in the higher dose group. There was a good correlation between the presence of p24-specific Ab and the detection of lymphoproliferative responses to the p24 protein in peripheral blood mononuclear cells isolated from the same individuals. Anti-p17 Ab were detected in five volunteers. No Gag-specific CTL responses were detected. CONCLUSION: We conclude that hybrid HIV-1 p17/p24:Ty-VLP are capable of inducing both cellular and humoral immunity to HIV-1 Gag p17 and p24 components and are worthy of further study as a potential HIV immunotherapeutic.

AIDS Vaccines↗

Gene conjugation of molecular adjuvant C3d3 to hCGbeta increased the anti-hCGbeta Th2 and humoral immune response in DNA immunization.

Human chorionic gonadotropin (hCG) has been used as an anti-fertility vaccine and as a target for cancer immunotherapy. We have explored the use of three copies of C3d in DNA vaccine as molecular adjuvant to improve the immunogenicity of this hormone in previous work and found that the immune response induced by pcDNA3-hCGbeta-C3d3 has been enhanced 243-fold compared with pcDNA3-hCGbeta following DNA immunization in BALB/c mice. In the present study, a new functionally active DNA vaccine of hCGbeta-C3d3 chimera based on pCMV4 vector has been described. We compared the expression efficiency of pCMV4 and pcDNA3 eukaryotic vectors for hCGbeta and hCGbeta-C3d3 fusion protein and the immune response of mice immunized with pcDNA3-hCGbeta, pCMV4-hCGbeta, pcDNA3-hCGbeta-C3d3 and pCMV4-hCGbeta-C3d3, respectively, at 25, 50 and 100 pmol dose, and further analyzed the levels of Th1 and Th2 cytokines produced by spleen lymphocytes of the immunized mice upon hCG restimulation in vitro. It was found that pCMV4 vector achieved 1.3-1.5-fold higher protein expression and raised 1.1-1.2 (primary) and 1.2-1.3 (booster) logs higher titer of anti-hCGbeta IgG than pcDNA3. Mice vaccinated with 50 pmol of hCGbeta-C3d3-DNAs elicited the highest titer of hCGbeta-specific antibody among the serial doses and the immune response induced by pCMV4-hCGbeta-C3d3 were, respectively, 1.3, 1.3 and 1.2 logs higher than that of pcDNA3-hCGbeta-C3d3 and 2.2, 2.9 and 2.4 logs higher than that of pCMV4-hCGbeta at week 2 following the booster immunization. Moreover, we observed that the production of IL-4 and IL-10 increased in mice vaccinated with hCGbeta-C3d3-DNAs and the ratio of IL-4/IFN-(gamma) showed a Th2 bias of immune response in the mice immunized with hCGbeta-C3d3-DNAs. These findings indicated that gene fusion of C3d3 to hCGbeta, as a means of harnessing the adjuvant potential of the innate immune system, may improve the antigen-specific Th2 humoral immune response of the hCGbeta DNA vaccine and the pCMV4 vector is a more ideal eukaryotic vector for DNA vaccine than pcDNA3.

Animals↗

T cell mediated and humoral immunity in a mouse Chlamydia psittaci systemic infection.

Immunity against Chlamydia psittaci, an obligate intracellular parasite, was studied in a mouse model of systemic infection. Sera (0.1 ml) and splenic cells (2 X 10(8)) from immunised mice were given intravenously to susceptible mice 16 hours before intravenous challenge with 1 X 10(5) plaque forming units (pfu) of virulent strain AB7. Transfer of immune cells primed with virulent strain AB7 or vaccinal strain 1B, lowered splenic and hepatic colonisation by approximately 5.5 log pfu. Treatment of immune cells with antithymocyte serum plus complement, before transfer, abrogated the protection. Transfer of sera raised against the virulent strain AB7, or the attenuated vaccinal strain 1B, lowered hepatic colonisation by approximately 1.5 log pfu. Sera containing antigenus antibodies, raised against heat-killed chlamydiae from strain AB7 or the non-virulent intestinal strain iB1, were not protective. Cellular immunity is mainly responsible for the observed protection, although humoral immunity may play some role.

Animals↗