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[Effect of multiple vaccination against influenza on the specificity of humoral immunity].

The influence of multiple vaccinations against influenza on humoral immunity specificity was studied by titration of sera from the vaccinees and non-vaccinees in radial hemolysis test (RHT). In order to determine the specificity of antihemagglutinins, the sera were adsorbed with the appropriate antigen followed by titration in RHT. The study showed the sera from vaccinees to contain the strain-specific antibody much more frequently, the titres and content being especially high to the vaccine A/Bangkok/1/79 strain used for large-scale vaccination of the human population in the three years preceeding the study. Fewer sera of the vaccinees contained cross-reacting antibodies. Both in vaccinees and non-vaccinees the total number of sera with antibody to the A/Bangkok/1/79 and A/Moscow/30/83 strains was approximately similar, however, antibody mean titre to these epidemiologically important strains was significantly higher in the vaccinees. The results of the study explain the narrow specificity of the protective effect of whole-virion inactivated vaccines used for mass immunization of the human population.

Adult↗

A concept of humoral immunity among ruminants and an approach to its investigation.

My goal has been to piece together bits of information, both old and new, so as to provide you with some concepts of humoral immune function. Specifically I have described concepts of secretory immunity in two different organ systems, the lower respiratory tract and the mammary gland. Should these concepts not even survive this meeting or be proven incorrect by future research, I hope I have at least stimulated your thinking with an alternative view and challenged you to saw off the limb I have put myself on with the concepts I have presented. More than mere conjectural hypotheses, I have presented some data on the ELISA out of my belief that one approach to establishing concepts in humoral immunity depends on the ability to accurately and quantitatively measure the distribution of antibodies among isotypes. I have also shared with you some preliminary data on the transport of SIgA into bile and other secretion which will hopefully encourage others to finally establish the quantitative significance of locally synthesized versus serum-derived IgA in the various exocrine secretions of ruminants. Finally, I have dared to take ruminant immunoglobulin homology "back to sea"; perhaps this last topic will stimulate your palate if not your mind.

Animals↗

Human tumor-associated antigens detected by serological techniques: analysis of autologous humoral immune responses to primary and metastatic human sarcomas by an enzyme-linked immunoabsorbent solid-phase assay (ELISA).

An enzyme-linked immunoabsorbent solid-phase assay was developed for measuring humoral immune responses to human sarcoma-associated antigens, and binding of autologous sera to 1-butanol extracts of fresh sarcomas was determined. Binding of autologous sarcoma patients' sera was reproducible and significantly greater than normal sera. Extensive quantitative competitive binding inhibition tests with normal tissue were unable to completely remove binding to autologous tumor extracts by sera from five of eight patients, thus demonstrating a quantitatively distinct specificity present on tumor tissue. An antibody in autologous sera recognizing a determinant on normal adult tissue was also identified. Autologous humoral immune responses to soluble 1-butanol extracts of paired primary and metastatic human sarcomas from six patients from this group were assessed. Antibody binding was observed to both primary and metastatic tumor extracts; however, binding was significantly greater to the primary extracts in 14 of 16 autologous serum-tumor combinations tested. Absorption and competitive binding inhibition studies demonstrated the presence of common sarcoma-associated antigens in extracts of both the primary tumor and its metastasis from all patients studied. Two individual metastases from the same patient also possessed antigens recognized in that patient's primary tumor extract in two cases. Autologous sarcoma patients' sera recognize sarcoma-associated antigens common to both the primary tumor and its metastasis.

Antibody Formation↗

Humoral immunity and retrobulbar fibroblasts in endocrine ophthalmopathy.

The exact role of retrobulbar fibroblasts in the immunopathogenesis of endocrine ophthalmopathy still remains to be elucidated. To evaluate the in vitro influence of humoral immunity on retrobulbar fibroblasts, the effects of immunoglobulin G as well as of the sera of 50 euthyroid patients with endocrine ophthalmopathy and 30 controls on both porcine and human (patients' and controls') retrobulbar fibroblasts were measured by means of several assays: a colorimetric test involving a heterocyclic chemical, a tetrazolium bromide, was applied to quantify the activity of mitochondrial dehydrogenases; the incorporation of 3H-thymidine was determined as a sensitive parameter for cell proliferation, and an enzyme-linked immunosorbent assay was to reveal specific binding of antibodies to the cells. There was consistently no significant difference between patients' (untreated or treated) and controls' IgG to bind to, to activate or to stimulate the proliferation of porcine and human (patients and controls) retrobulbar fibroblasts. The effects of patients' heat-inactivated and non-inactivated sera were indistinguishable from those of the controls. Incubation of autologous sera, however, led to an activation of retrobulbar fibroblasts which was both higher than the median caused by the patients' group and that engendered by incubation of autologous IgG. Yet, a significant role that humoral immunity might play directly on retrobulbar fibroblasts could not be detected in the experiments conducted in this study.

Adult↗

Cellular and humoral immune responses to heat shock protein 65 are both involved in promoting fatty-streak formation in LDL-receptor deficient mice.

OBJECTIVES: This study was designed to determine the role of cellular and humoral immune responses to heat shock protein 65 (HSP65) in murine atherosclerosis. BACKGROUND: Inflammatory processes appear to influence the progression of atherosclerosis. Immunization with HSP65 was previously shown to induce arteriosclerosis in rabbits and to enhance fatty-streak formation in mice. However, it has not been demonstrated directly whether HSP65-reactive antibodies and lymphocytes are separately capable of influencing lesion formation. METHODS: Low density lipoprotein-receptor deficient (LDL-RD) mice were immunized with HSP65 or control bovine serum albumin (BSA). Lymph-node cells, splenocytes and immunoglobulin G (IgG) were obtained from the immunized mice and transferred separately to six groups of syngenic LDL-RD mice. RESULTS: Adoptive transfer of HSP65-reactive lymph node cells increased fatty-streak formation in comparison with mice treated with BSA-primed cells. Similarly, transfer of splenocytes reactive with HSP65 led to enhanced fatty-streak generation compared with mice injected with BSA-sensitized splenocytes. Repeated intraperitoneal administration of IgG from serum of HSP65-immunized mice (every 10 days) enhanced fatty-streak formation in mice in comparison with their anti-BSA-IgG injected littermates. CONCLUSIONS: Antibodies and lymphocytes reactive to HSP65 promote fatty-streak formation in mice, providing direct evidence for the proatherogenic properties of cellular and humoral immunity to HSP65.

Animals↗

[Specific humoral immune response against B-cell lymphoma elicited by mixed immunoglobulin fragments].

OBJECTIVE: To explore the feasibility of construction of the universal nucleic acid vaccine against B-cell lymphoma. METHODS: RT-PCR was employed to obtain the immuncy losulin heavy chain variable region (IgHV1) gene fragments of the Namalwa cell, normal fetal umbilical cord blood and adult peripheral blood. Then these RT-PCR products were cloned into the eukaryotic expression vector pcDNA3.0 and sequenced. Six plasmids that had high identities with the germ line genes were mixed to serve as vaccines. Eighteen Balb/c mice were divided randomly into three groups and were immunized respectively with the six mixed plasmids, the specific IgHV1 fragment of the Namalwa cell and the blank plasmid pcDNA3.0. 100 microg plasmid and 5 microg hIL-6 per mouse were injected into the muscle, 3 times in 4 weeks. Western blotting and indirect immunofluorescence staining were used to assess the humoral immune responses against the Namalwa cell. RESULTS: The specific humoral immune responses against the Namalwa lymphoma cell could be induced in both the IgHV1-mix group and the Na-IgHV1 group, and the antibodies could recognize the nature antigenic determinants in the surface of the Namalwa cell. The antibodies could be detected since the fourth week after the first immunization, and reached the climax at the sixth week. There was no significant difference of the titers of the antibodies between the two groups. The antibody couldn't be found in the negative control group. CONCLUSION: The mixed IgHV plasmids can be used as the universal nucleic acid vaccine against the B-cell lymphoma which expresses the same IgHV1 family genes.

Animals↗

[Decreased humoral immunity to the tick-borne encephalitis virus in the population of the western Urals].

A serological survey of the human population in the western Urals in 1966-1968 and repeated survey in 1988-1989, the decrease in humoral immunity to tick-borne encephalitis virus in all age groups of people was established in most of landscape subzones of the region. The most expressive decrease of humoral immunity was noted in middle-aged people living in the subzone of broad-leaved and coniferous forests and forest steppe.

Age Factors↗

Adjuvant formulation for use in vaccines to elicit both cell-mediated and humoral immunity.

Adjuvant formulations which elicit both humoral and cell-mediated immunity will be required for vaccines based on peptides, viral and bacterial subunits and genetically engineered antigens. This report describes an adjuvant formulation which increases both cell-mediated and humoral immunity and is free of significant side effects encountered with other adjuvants or vehicles. The components include the threonyl analogue of muramyl dipeptide, Tween 80, Pluronic L121 and squalane. This formulation was found to be effective with several antigens, in several species, including rodents, cats and monkeys. These results suggest that the formulation will be useful for both human and veterinary vaccines.

Acetylmuramyl-Alanyl-Isoglutamine↗

Mother-to-baby transfer of humoral immunity against retrovirus-induced neurologic disorders and immunodeficiency.

Neonatal FVB/N mice inoculated with ts1, a temperature-sensitive mutant of Moloney murine leukemia virus TB, developed fatal immunodeficiencies and neurologic disorders. In this study, we tested the role of transfer of maternal humoral immunity in preventing ts1-induced disease syndrome in the neonatal mice. We compared the levels of protection provided through maternal antibodies both pre- and postnatally by separating infected neonatal mice into four different groups. The first group was born of and nursed by nonimmune mothers, the second was born of immune mothers but nursed by nonimmune mothers, the third was born of nonimmune mothers but nursed by immune mothers, and the fourth was born of and nursed by immune mothers. Our major findings are: (1) adult mice generate a strong antiviral antibody response; (2) maternal antibody is protective for the newborns and primarily transferred by breast milk; (3) virus titers were cleared in the periphery and the CNS of neonates nursing on immune mothers; and (4) the majority of antiviral antibody generated was specific for the gp70. These results indicate that humoral immunity can be passed efficiently from mother to baby through breast milk and can provide strong protection against neurotropic retrovirus.

Animals↗

The use of 125I-labelled protein A for the detection of humoral immunity to gross murine leukaemia virus.

A solid-phase radioimmunoassay utilising bind of 125I-labelled protein A to antibodies bound to virus adsorbed onto microtitre plates was shown to be suitable for detection of humoral immunity to Gross murine leukaemia virus (MuLV). The specificity of the reaction was shown by the fact that only homologous or closely related viruses effectively inhibited binding of antibodies to adsorbed virus. With this method a low level of spontaneous humoral immunity was demonstrated in sera from AKR/Crc mice, a strain with high concentrations of endogenous virus, whereas little or no anti-viral activity was found inCBA/H-T6Crc, a subline that does not appear to express MuLV.

AKR murine leukemia virus↗

Human leukocyte antigen polymorphisms: variable humoral immune responses to viral vaccines.

Antibody formation in response to antigen stimulation remains the basis for measuring an individual's response and protection for most viral vaccines. A significant proportion of the variation in individual humoral immune response to vaccination appears to be genetic. The collection of genes found on chromosome 6 forming the human leukocyte antigen system provides one of the greatest sources of genetic variation in individuals with respect to their immunological responses. Recent research has demonstrated significant associations between vaccine response and human leukocyte antigen alleles. These associations not only explain why vaccine-induced humoral immune responses vary among individuals and between populations, but these variations may also hold the key to the development of future generations of vaccines.

Animals↗

In vivo treatment with anti-interleukin-13 antibodies significantly reduces the humoral immune response against an oral immunogen in mice.

Interleukin-13 (IL-13) is a cytokine which significantly enhances the proliferation and differentiation of B lymphocytes. We therefore evaluated its role in the formation of a humoral immune response in vivo. Upon oral immunization with the B subunit of Escherichia coli heat-labile enterotoxin (LT-B), rapid up-regulation of IL-13 mRNA expression in the mesenteric lymph nodes of LT-B intubated mice occurred. This result suggested that IL-13 might be involved in the formation of a mucosal antibody response against LT-B if this cytokine was in fact secreted. To test this possibility, the coding region for murine IL-13 was cloned into the pFLAG-1 expression vector. Recombinant murine IL-13 was purified from bacterial lysates and used as an immunogen to produce polyclonal anti-IL-13 antibodies. Groups of BALB/c mice treated in vivo with anti-IL-13 antibody 2 days before and on the day of oral immunization with LT-B had significantly reduced intestinal IgA and serum IgG and IgA anti-LT-B antibody responses when compared to mice treated with control antibody. Furthermore, groups of mice primed with LT-B and then treated with anti-IL-13 antibody prior to oral immunization with a second dose of LT-B also had significantly reduced intestinal IgA and serum IgG and IgA anti-LT-B antibody titres compared to controls. In vitro LT-B restimulation experiments using splenic mononuclear leucocytes isolated from LT-B primed mice treated with anti-IL-13 antibody demonstrated decreased expression of IL-4 and IL-13 mRNA and decreased IL-4 secretion when compared to controls. Together these results demonstrate an important role for IL-13 in the formation of a humoral immune response at mucosal surfaces.

Administration, Oral↗

Humoral immune response to mesothelin in mesothelioma and ovarian cancer patients.

PURPOSE: Mesothelin is a glycosyl-phosphatidylinositol-anchored glycoprotein present on the cell surface. Mesothelin is a differentiation antigen that is highly expressed on mesothelioma, ovarian cancer, and pancreatic cancer. The existence of a spontaneous humoral immune response to mesothelin in humans has not been fully studied. Here we addressed the issue of whether mesothelin elicits a humoral immune response in patients with mesothelioma and ovarian cancer. EXPERIMENTAL DESIGN: Using an ELISA, we analyzed immunoglobulin G antibodies specific for mesothelin in sera from patients with mesothelioma and epithelial ovarian cancer. Tumor specimens were examined by immunohistochemistry for mesothelin protein expression. RESULTS: Elevated levels of mesothelin-specific antibodies were detected in the sera of 39.1% of patients with mesothelioma (27 of 69 patients) and 41.7% with epithelial ovarian cancer (10 of 24 patients) when compared with a normal control population (44 blood donors; P < 0.01 for both mesothelioma and ovarian cancer). We also found that 53% to 56% of patients with mesothelin immunostaining-positive mesothelioma and ovarian cancer had antibodies specific for mesothelin, whereas only 0% to 8% of patients with negative mesothelin immunostaining had detectable mesothelin-specific antibodies (chi(2) test: P < 0.01 for mesothelioma and P = 0.025 for ovarian cancer). CONCLUSIONS: Our findings indicate that mesothelin is a new tumor antigen in patients with mesothelioma and ovarian cancer and the immunogenicity of mesothelin is associated with its high expression on the tumor cells. Mesothelin represents an excellent target for immune-based therapies.

Adult↗

Immune mechanisms in organ allograft rejection. III. Cellular and humoral immunity in rejection of organ allografts transplanted across MHC subregion disparity RT1.B (RT1.D).

The role of T and B lymphocytes in rejection of cardiac allografts bearing isolated major histocompatibility complex (MHC) subregion RT1.B/D encoded class II "Ia" disparities was investigated using natural and congenic recombinant inbred rats (RP, PVG RT1r1). RT1.B/D-disparate heart grafts were shown in 3 strain combinations (RP leads to WF, WF leads to [RP x PVG RT1l] F1, and PVG RT1r1 leads to PVG RT1 alpha) to induce a brisk humoral response (complement-dependent cytotoxicity [CDC] titers greater than 2(6] with specificity for class II determinants as evidenced by strain and tissue distribution of susceptible targets. Cytotoxic T cells (Tc) generated in parallel effected equivalent lysis (in the 4-hr 51Cr-release LMC assay) of con A and lipopolysaccharide (LPS) blasts of the same strains. Specificity of Tc for class II determinants was demonstrable by specific inhibition of killing (congruent to 50%) by anti-Ia antibody preparations (monoclonal 0X4 and antiserum ATH anti-ATL) with specificity for class II products of MHC subregions RT1.B and RT1.D, respectively. Adoptive transfer studies revealed that antibody and cytotoxic effectors (W3/25+, OX8+) with specificity for class II "Ia" determinants, though potentially injurious, are not required for rejection of cardiac allografts transplanted across isolated RT1.B/D disparities (RP leads to WF) because transfer even of small numbers (0.5 X 10(6] of helper T cells (W3/25+, OX8-) previously shown to be responsible for adoptive transfer of delayed type hypersensitivity to alloantigen, effected rejection in the absence of detectable antibody or Tc. In the immune response to alloantigen both cytotoxic T cell generation and a humoral immune response develop in parallel with that other form of cellular immunity, akin to classic delayed or tuberculinlike hypersensitivity, itself potentially a potent effector mechanism in organ allograft rejection.

Animals↗

Effects of mushroom and herb polysaccharides on cellular and humoral immune responses of Eimeria tenella-infected chickens.

We investigated the effects of polysaccharide extracts from 2 mushrooms, Lentinus edodes (LenE) and Tremella fuciformis (TreE), and an herb, Astragalus membranaceus (AstE), on cellular and humoral immune responses of Eimeria tenella-infected chickens. A total of 150 broiler chicks were assigned to 5 treatment groups: 3 groups were infected with E. tenella and fed with extracts (LenE, TreE, and AstE), and 2 control groups were infected with or without E. tenella. The 3 extracts were given at the level of 1 g/kg of the diet from 8 to 14 d of age. Specific systemic and cecum mucosal antibody production, proliferation of splenocytes, and peripheral T and B lymphocytes were measured during the 3 wk following Eimeria infection. A significantly higher production of specific IgA, IgM (at d 14 and 21 postinfection), and IgG (at d 21 postinfection) were detected in the Eimeria-infected groups fed with the extracts than in the infected group not fed with the extracts. Of the 3 extracts, TreE stimulated a slightly higher production of specific IgM (P = 0.052), and a significantly higher IgG production at 21 d postinfection. The cecal antibody production showed a similar trend to that of serum antibodies. The overall mean levels of cecal-specific IgA and IgG of the groups fed with extracts were significantly higher at 14 and 21 d postinfection compared with the group not fed with extracts. Of the 3 extracts, the AstE-fed group showed the highest IgG production at d 7 postinfection. Both TreE- and LenE-fed groups had significantly higher IgM and IgG levels compared with the AstE group at d 21 postinfection. The extract-fed groups also showed a significantly higher antigen-specific proliferation of splenocytes at 14 and 21 d postinfection compared with the group not fed with the extracts. The overall mean of erythrocyte rosette-forming cells (ERFC %) (at d 14 and 21) and erythrocyte-antibody-complement cells (EAC %) (at d 14) of the groups fed with the extracts was significantly higher compared with the group not fed the extracts. It is concluded from this study that supplementation with mushroom and herb extracts resulted in enhancement of both cellular and humoral immune responses in E. tenella-infected chickens.

Animals↗

[Local and systemic humoral immune response to protein I of Neisseria gonorrhoeae].

Knowledge of the immune response to natural infection with Neisseria gonorrhoeae is presupposition for the development of a gonococcal vaccine. Pili and protein I have gained importance for a subunite vaccine. A pilus vaccine proved to be ineffective in a field trial due to extensive pilus variability. According to an alternative strategy protein I may represent an important vaccine candidate for a gonococcal vaccine. To study the local and systemic, humoral immune response to N. gonorrhoeae cervical secretion, vaginal fluid and serum from prostitutes and family planning patients were compared by the use of a protein I ELISA. In local secretions and in serum patients in the study group showed significantly higher anti-protein-I-IgA-levels than patients in the control group. In cervical secretion immune response to an acute gonococcal infection consisted of a short lived, significant increase of anti-protein-I-IgA, while anti-protein-I-IgG showed a lower, but longer lasting significant increase. The course of the immune response in vaginal fluid reflected the immune response of cervical secretion at a lower level. In serum antigenic stimulus of a local gonococcal infection resulted in a significant but short lived protein I specific IgG immune response. In local infection with N. gonorrhoeae protein I represents a target antigen of the local and systemic immune response. Clear differences exist between local and systemic humoral immune response in the protein I reactive immunoglobulin class and in the course of reactivity. In the future it may be possible to define epitopes on protein I which induce protective immunity.

Adult↗

Humoral immunity to immunodominant epitopes of Hepatitis C virus in individuals infected with genotypes 1a or 1b.

Cellular immunity against multiple Hepatitis C virus (HCV) proteins is observed in patients acutely infected with HCV most of whom later resolve infection. We wished to assess humoral immunity in patients infected with HCV 1a or 1b genotypes in relation to viral load using plasma samples from HCV-infected individuals and a panel of peptides representing immunodominant epitopes of HCV structural and nonstructural proteins. Plasma from HCV 1a- and 1b-infected patients, respectively, were divided into two groups: patients with low viral load (<==100,000 RNA copies/ml) and patients with high viral load (>/=10,000,000 RNA copies/ml). The antigens were peptides representing epitopes from immunodominant regions of HCV core, E2, NS3, and NS4 proteins, as well as the hypervariable (HVR) epitopes in E2 from genotypes 1a and 1b. Individuals infected with HCV 1a evoked a stronger immune response to many immunodominant epitopes of HCV relative to individuals infected with HCV 1b. Moreover, among individuals infected with HCV 1a, those with low viral loads mounted significantly greater responses against these epitopes than did individuals with high viral loads. Our observations demonstrate that quantitatively different antibody responses are elicited against HCV depending on the genotype of infecting virus, and suggest that humoral immunity directed against multiple immunodominant epitopes in HCV 1a-infected individuals may help lower viral load in vivo.

Antibody Formation↗

Stimulatory effects of B7-related protein-1 on cellular and humoral immune responses in mice.

Inducible costimulator (ICOS) and B7-related protein-1 (B7RP-1) constitute a receptor-ligand pair involved in T cell costimulation. In this study, the stimulatory effects of B7RP-1 on cellular and humoral immune responses were investigated giving mice a construct with the extracellular domain of murine B7RP-1 fused with human IgG1 Fc (B7RP-1-Fc). B7RP-1-Fc stimulated contact hypersensitivity (CH) given near either the time of sensitization or challenge with oxazolone. When given near challenge time, B7RP-1-Fc stimulated CH more than a construct containing the extracellular domain of murine B7.2 and Fc (B7.2-Fc). B7RP-1-Fc increased the number of cells in lymph nodes draining the skin sensitized with oxazolone, especially activated T cells. B7RP-1-Fc also increased the ability of the cells in these lymph nodes to induce CH when transfused into naive mice. B7RP-1-Fc stimulated the production of anti-keyhole limpet hemocyanin (KLH) Ab, increasing anti-KLH IgG, IgG2a, and IgE, whereas B7.2-Fc did not affect this production. B7RP-1-Fc also increased the number of cells in lymph nodes draining the skin immunized with KLH and their production of IFN-gamma, IL-4, and IL-10 in response to KLH. Finally, B7RP-1-Fc increased the presence of eosinophils in the bronchoalveolar lavage and lungs of mice sensitized and challenged with OVA so to mount an asthmatic reaction. B7RP-1-Fc stimulates both cellular and humoral immune responses in vivo by increasing number and function of T and B cells reacting to Ag exposure.

Abatacept↗