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Dysfunction of humoral immunity in anergic surgical patients: absence of anti-tetanus IgG antibody production.

The experiments described have shown that, whereas the injection of tetanus toxoid (tet) into 8 of 12 control individuals resulted in the appearance of specific anti-tet-IgG antibodies in their plasma, immunization of 14 anergic patients did not elicit an antibody response. This observation was extended to an in vitro system, where cells from four control subjects were shown to secrete anti-tet-IgG antibodies in response to polyclonal activators whereas cells from eight anergic patients did not. It is suggested that this failure of humoral immunity could account for the high risk of bacterial infections in anergy.

Adult↗

Trifluoroacetylation potentiates the humoral immune response to halothane in the guinea pig.

Halothane hepatitis appears to result from an inappropriate immune response to the products of halothane metabolism. Attempts to produce an animal model for halothane hepatitis have been largely unsuccessful. Although guinea pigs produce neoantigens following treatment with halothane, the subsequent antibody response is weak, possibly accounting for the failure to produce halothane hepatitis in these animals. In order to increase the antibody response to halothane neoantigens, three methods for trifluoroacetylating proteins were used. Guinea pigs were either treated with S-ethylthiotrifluoroacetate, autologous lymphocytes trifluoroacetylated ex vivo, or immunized with trifluoroacetylated mycobacterial protein, followed by exposure to halothane, and examined for anti-halothane metabolite antibodies (anti-TFA antibodies). Animals treated with S-ethylthiotrifluoroacetate developed anti-TFA antibodies, and following exposure to halothane exhibited an enhanced antibody response. Treatment with trifluoroacetylated lymphocytes also resulted in an enhanced anti-TFA antibody response following halothane exposure. Immunization with trifluoroacetylated mycobacterial proteins resulted in very high anti-TFA antibody titers. However, subsequent exposure to halothane had no observable effect on specific antibody titers. Exposure to halothane, regardless of treatment, resulted in the production of anti-microsomal protein antibodies. Signs of halothane hepatitis were not observed, indicating that enhancement of the humoral immune response does not appear to be sufficient for production of halothane hepatitis.

Alanine Transaminase↗

[The characteristics of the O-specific humoral immune response of mice vaccinated with Salmonella choleraesuis antigens].

The work deals with the results of the comparative enzyme immunoassay (EIA) of serum samples taken from (CBA X C57BL/6) F1 mice immunized with O-specific polysaccharides, O-antigens (O-Ag) obtained by Boivin's method and antigenic preparations isolated with hydroxylamine (HA) from S. choleraesuis and S. typhimurium. O-Ag and lipopolysaccharide (LPS) of the corresponding bacterial species were used as antigens for the sensitization of polystyrene plates. The primary and secondary humoral immune response was studied by means of EIA. As revealed in this investigation, the immunization of mice with HA-isolated antigenic preparations and O-Ag, obtained from S. typhimurium, in a single injection (in doses of 1-100 micrograms) led to the development of weak specific immune response to O-Ag. Response to LPS was absent. After the second immunization of the animals pronounced immune response to O-Ag and LPS was observed. It developed as a response of both IgM and IgG type. The immunization of mice, made in a single injection, with HA-isolated antigenic preparations and O-Ag, obtained from S. choleraesuis, did not lead to the development of O-specific immune response. After the immunization of mice with these antigens in two injections sharply pronounced nonspecific activity of IgM and IgG serum antibodies with respect to O-Ag and LPS of homologous and heterologous bacterial species was noted in EIA. Neither S. typhimurium O-polysaccharide, nor S. choleraesuis O-polysaccharide did not induce O-specific immune response even after the second immunization.

Animals↗

Inhibition of humoral immunity and mitogen responsiveness of lymphoid cells following oral administration of the heterocyclic food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) to B6C3F1 mice.

In these studies, the food promutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was evaluated for its immunotoxicity in B6C3F1 mice following oral 5-day dosing at total doses of 50 and 150 mg/kg. Results indicated that PhIP produced a dose-dependent suppression of the humoral immune response of spleen cells to sheep erythrocytes, with a 50% decrease in the number of PFC detected at the 150 mg/kg dose of PhIP. A 40-90% inhibition of the phytohemagglutinin (PHA) response of spleen cells, mesenteric lymph nodes (MLNs), and Peyer's patch (PP) lymphocytes was seen in the treatment groups. The lipopolysaccharide (LPS) response was somewhat more variable and less affected with 20-30% inhibition observed in the spleen and PPs, whereas PhIP increased the LPS response in the MLNs. There was no effect of PhIP on cell recovery or viability in any of the treatment groups. Flow cytometry analysis revealed a depletion of T cells (Thy 1.2+ cells) and a slight increase in B cells (Ly5+ cells) in the PPs. The percentage of B and T cells present in the spleen and MLNs was unaffected by PhIP. These results demonstrate that the oral administration of PhIP produces immunotoxicity to mice, especially to lymphoid tissues present in the GI tract (i.e., PPs), and demonstrates that T cell mitogen (PHA) responses in PPs are the most sensitive indicator of PhIP-induced immunotoxicity.

Administration, Oral↗

Dendritic cells genetically modified to express CD40 ligand and pulsed with antigen can initiate antigen-specific humoral immunity independent of CD4+ T cells.

We have investigated whether dendritic cells genetically modified to express CD40 ligand and pulsed with antigen can trigger B cells to produce antigen-specific antibodies without CD4+ T-cell help. Dendritic cells modified with a recombinant adenovirus vector to express CD40 ligand and pulsed with heat-killed Pseudomonas induced naive B cells to produce antibodies against Pseudomonas in the absence of CD4+ T cells in vitro, initiated Pseudomonas-specific humoral immune responses in vivo in wild-type and CD4-/- mice, and protected immunized wild-type and CD4-/-, but not B-cell -/- mice, from lethal intrapulmonary challenge with Pseudomonas. Thus, genetic modification of dendritic cells with CD40 ligand enables them to present a complex mixture of microbial antigens and establish CD4+ T cell-independent, B cell-mediated protective immunity against a specific microbe.

Animals↗

[Some indices of cellular and humoral immunity in infants with acute purulent otitis media].

The examination of 32 infants with acute otitis media purulenta identified shifts in immunological indices: T-cell immunity appeared 1.5-times weaker (up to 31.5 +/- 2.6%) than in healthy controls, synthesis of serum immunoglobulins intensified (IgA, IgM and IgG levels rose to 161 +/- 18 mg%, 124 +/- 11 mg% and 963 +/- 47 mg%, respectively). Thus, infants with acute otitis media purulenta need not only conventional therapeutic measures but also correction of disturbed cellular and humoral immunity.

Child, Preschool↗

Humoral immunity in aging.

The interactions between B and T lymphocytes, leading to the development of humoral responses, are reviewed with references to the changes occurring in aged people. Aging is perceived as a process of impairment of immune functions; it is known that T cells from aged subjects have a reduced ability to produce IL-2. However, other functions seem to be upregulated in elderly subjects; indeed, IL-1, IL-3, IL-4, IL-6 and TNF alpha production are increased both in aged mice and humans. These cytokines are known to control B cell differentiation, through isotype switch and Ig production. A significant increase in IgG subclasses and IgA is observed in sera of aged subjects. This contrasts with the significant decrease in circulating B lymphocytes. The impairment of primary responses to immunization, and other aspects of humoral immunity, including mucosal responses, autoantibody production and correlations with phenotypic markers of T and B cell subsets, are discussed.

Adult↗

Humoral immunity in steroid-dependent children with asthma and hypogammaglobulinemia.

OBJECTIVE: To determine primary and secondary antibody responses in children with hypogammaglobulinemia attributed to corticosteroid use. RESULTS: In seven patients with steroid-dependent asthma and significant hypogammaglobulinemia (IgG concentration, 275 to 443 mg/dl), antibody responses to protein and polysaccharide antigens were shown to be normal, as were primary and secondary responses to a neoantigen, bacteriophage phi X174. CONCLUSIONS: Patients with asthma, and with hypogammaglobulinemia resulting from steroid therapy, have normal humoral immunity, and immunoglobulin replacement therapy is not indicated.

Adolescent↗

Cellular and humoral immunity to varicella zoster virus glycoproteins in immune and susceptible human subjects.

To further delineate the immune responses that protect against serious primary varicella zoster virus (VZV) infection and inhibit viral reactivation, antibody responses and T lymphocyte reactivity to three major VZV glycoproteins, gpI, gpII, and gpIII, were studied. Individual viral glycoproteins were purified using murine monoclonal antibodies. Cellular immunity was measured by lymphocyte proliferation. Antibody responses were tested in enzyme-linked immunosorbent assays. Individual glycoproteins induced VZV-specific proliferation by mononuclear cells from 15 of 20 immune subjects. Serologic responses to the VZV glycoproteins occurred in 16 of 20 immune subjects. Of note, gpII served as a potent T and B cell antigen during both acute infection and convalescence. Cell-mediated responses to the glycoprotein antigens represented proliferation by T lymphocytes and required antigen presentation by adherent mononuclear cells. These findings indicate that virally encoded glycoproteins contain epitopes that stimulate VZV-specific cellular and humoral immune responses.

Antibodies, Viral↗

CD28-B7 T cell costimulatory blockade by CTLA4Ig in the rat renal allograft model: inhibition of cell-mediated and humoral immune responses in vivo.

Blocking CD28-B7 T-cell costimulation by CTLA4Ig induces tolerance to rat renal allografts and inhibits Th1, but spares Th2, cytokines. We now report on the mechanisms of CD28-B7 blockade in this model. Lymphocytes from CTLA4Ig-treated animals showed significant reduction of mixed lymphocyte response, as well as antidonor cytotoxic T-cell effector function, as compared with rejecting controls. Flow cytometry studies on sera of renal allograft recipients showed complete inhibition of antidonor humoral responses by CTLA4Ig. Analysis by reverse transcriptase-polymerase chain reaction and immunohistology showed that intragraft macrophage products, monocyte chemoattractant protein-1 and inducible nitric oxide synthase, were reduced by CTLA4Ig therapy. Immunohistologic studies also showed reduced intragraft macrophage infiltration and decreased staining for the fibrogenic and mitogenic growth factor, transforming growth factor-beta. These results indicate that CD28-B7 blockade inhibits cell-mediated and humoral immune responses, and suggest that strategies targeting T-cell costimulation may provide a novel approach to prevent chronic allograft rejection.

Abatacept↗

Humoral immune response to hypervariable region 1 of the putative envelope glycoprotein (gp70) of hepatitis C virus.

We recently found that alterations of amino acids in hypervariable region 1 (HVR1) of the putative envelope glycoprotein (gp70) of hepatitis C virus (HCV) occurred sequentially in the chronic phase of hepatitis at intervals of several months. This finding suggests that mutations in HVR1 are involved in the mechanism of persistent chronic HCV infection involving escape from the immunosurveillance system. To explore this possibility, we examined the humoral immune response to HVR1 with our assay system, in which immunoprecipitation was carried out with sera from patients by using an HVR1 (27-amino-acid) dihydrofolate reductase fusion protein synthesized by in vitro transcription and translation. Results showed that HVR1 contains a sequence-specific immunological epitope that induces the production of antibodies restricted to the specific viral isolate. Furthermore, analysis of the kinetics of the appearance of antibodies in two patients with chronic hepatitis, with whom successive alterations of amino acids of HVR1 have been observed, showed that the titers of anti-HVR1 antibodies usually reached maximal levels several months after the isolation of HCV having the specific sequence of HVR1. This observation suggests that anti-HVR1 antibodies are involved in the genetic drift of HVR1 (minor antigenic variation) by immunoselection. However, the coexistence of HVR1 as an antigen and its specific antibody was sometimes observed. The possibility that HVR1 acts as a neutralizing epitope is discussed.

Adult↗

Humoral immunity in stage I mycosis fungoides: an increased incidence of lymphocytotoxic antibodies.

Thirteen patients with stage I mycosis fungoides (MF) were studied for the presence of circulating autoantibodies including cold-reactive lymphocytotoxic antibodies (LCA), antinuclear antibodies and rheumatoid factor antibodies to common food antigens, bovine gamma globulin and casein; and immune complexes as measured by cryoglobulins and I125 Clq binding. A significantly increased incidence (11/13) of LCA was found in the MF patients, and this may be related to the alterations in subpopulations of T cells seen in these patients. No significant increase in any other test was noted. there was no evidence of a diffuse hyperactivity of the humoral immune system as seen in systemic lupus erythematosus, which has a similar imbalance of T cell subpopulations.

Adult↗

[Genetic and phenotypic aspects of the interrelationship between cellular and humoral immune response to sheep erythrocytes in mice].

The presence of the two types of immune reactivity has been shown earlier: 1st--with prevalence of delayed type hypersensitivity reaction over antibody response (in mice of C57Bl/6 strain), 2nd--with prevalence of antibody responses (in mice of CBA strain). These differences first of all have been displayed in case of using by suboptimal doses of antigen. In the present study the character of local and common immune response in mice of BALB/c, DBA/2, CC57BR, C3H strains and (CBA x C57Bl/6)F1 hybrid on different sheep erythrocyte doses has been investigated. It has been revealed, that DBA/2, BALB/c and CC57BR mice react according to the first type and mice of C3H strain--according to the second. It has been concluded, that the relationship between cellular and humoral immune response depends on the structure of H-2 complex and in F1 hybrid mice any of parents' haplotypes can predominate, depending on phenotypical factors.

Animals↗

[Local humoral immunity in women with combined forms of infertility].

An evaluation was done of the immunity status in 100 women presenting with infertility of associated genesis. An immunologic investigation into blood serum, follicular fluid (FF) and peritoneal fluid (PF) was carried out at day 14-16 and 18-23 of the menstrual cycle. The functional status of spermatozoa was characterized with the aid of the index of their survival in FF and PF. Local humoral immunity of FF and PF differs from the indices in blood serum, which fact was manifested by a striking reduction of Igs G, A, M. Sperm-immobilizing antibodies (SIAB) have been identified in blood serum, FF, and PF in 14, 4%, 22.4%, and 25% of women. SIAB production is associated with inadequacy of local immunity, such as low levels of SIgA, IgA, and lysozyme. Occurrence of SIAB in PF and FF worsens general motility of spermatozoa by agglutination of the latter, which fact undoubtedly affects conception.

Adult↗

The effect of early treatment with methyl-CCNU on the lymphoid organs and the humoral immune response in chickens.

Presented are data upon the effect of a single or muliple administration of methyl-CCNU (a nitrosourea derivative an alkylating agent, and anticancer drug) to newly-hatched chicks. Lethal and sublethal doses of methyl-CCNU caused temporary damage to the lymphoid organs, of which the bursa was apparently the most sensitive. The decreased weight and the morphological changes observed in the bursa of treated chicks were accompanied by a parallel decrease in serum gamma-globulins level. The humoral immune response of animals treated with me-CCNU to sheep red blood cells and to killed Brucella abortus organisms was impaired in about 30% of the treated animals examined 8-10 weeks following 2 injections of 3 mg me-CCNU (given at the day of hatching and the next day). The thymus recovered rather rapidly from treatment. The time schedule of mortality and the early and late toxic manifestations of the drug as observed in chickens, in this study, are similar to previous reports obtained in mammals. Prolonged effects, however, were noted to some extent on body and spleen weight, and most dramatically, on testicular weight, morphology, and function.

Animals↗

Studies on Pasteurella multocida. VII. Dynamics and temporal development of local humoral immunity induced by a live avirulent fowl cholera vaccine.

Vaccination of turkeys by administering the CU strain of Pasteurella multocida in drinking water induced local antibodies in the tracheal secretions. Their appearance and persistence were demonstrated by the indirect immunofluorescence technique. Local antibodies were induced by the 10th day and persisted up to the 42nd day postvaccination, whereas none were induced by an oil-adjuvanted bacterin throughout the observation period (56 days). Thus, the CU strain of P. multocida appeared to generate a local humoral immunity in the respiratory system whereas the bacterin did not.

Administration, Oral↗

Suppressed humoral immunity in chicks fed diets deficient in sodium, chloride, or both sodium and chloride.

Four experiments were conducted to determine the effect of Na and Cl on the antibody response to sheep red blood cells (SRBC). In the first two experiments, Na and Cl were supplemented in the diet together as NaCl at levels from 0 to .75%. In two additional experiments, Na and Cl were supplemented independently; levels varied from .04 to .24% total dietary Na and from .07 to .36% total dietary Cl. Results of the first two experiments indicated that dietary Na and Cl levels above that found in a corn-soybean diet improved the antibody response to SRBC. Additional studies showed that the humoral immunity was significantly suppressed when chicks consumed diets with less than .14% Na and .17% Cl. Increasing dietary Cl from .17 to .27% when dietary Na was .04% suppressed the antibody response. Also, increasing dietary Cl from .21 to .36% when dietary Na was .14 or .24% suppressed the antibody response. The immunosuppression of the humoral response of chicks was determined to be not related to the decreased feed intake resulting from inadequate Na and Cl in the diet.

Animals↗

Immunopharmacology of auranofin and gold sodium thiomalate: effects on humoral immunity.

The effect of auranofin and gold sodium thiomalate (GST) on antibody production was evaluted using antibody-dependent cellular cytotoxicity and complement-dependent antibody responses to sheep red blood cells (SRBC) and L929 fibroblasts. The results indicated that auranofin was capable of depressing antibody production to L929 cells, but inconsistently depressed the response to SRBC in the mouse. GST, however, stimulated both responses. In vitro, both compounds inhibit secretion of antibody. These results demonstrate that auranofin, in contrast to GST, is capable of suppressing humoral immunity which may explain its more rapid effect on immunological parameters in RA.

Animals↗