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Humoral immunity and protection of mice challenged with homotypic or heterotypic parvovirus.

BACKGROUND AND OBJECTIVES: Two serotypes of autonomously replicating parvoviruses infect laboratory mice. Genome regions coding for the nonstructural proteins of minute virus of mice [MVM] and mouse parvovirus [MPV] are almost identical, whereas capsid-coding sequences are divergent. We addressed these questions: Does humoral immunity confer protection from acute infection after challenge with homotypic or heterotypic parvovirus, and if it confers protection against acute MPV infection, does it also protect against persistent MPV infection? METHODS: Infant mice without maternal antibody or antibody to MVM or MPV and young adult mice given normal mouse serum or antibody to MVM or MPV were challenged with homotypic or heterotypic virus. In situ hybridization with target tissues was the indicator of infection. RESULTS: Humoral immunity failed to confer protection against acute heterotypic parvovirus infection. In passive transfer studies, MPV DNA was observed occasionally in lymph nodes, intestine, or the spleen of MPV-challenged mice given homotypic antibody and kept for 6 or 28 days. Variable proportions of mice given MPV antibody and homotypic challenge had viral DNA in lymphoid tissues 56 days after virus inoculation. CONCLUSION: A mouse or colony that has sustained infection with MVM or MPV is probably fully susceptible to infection with the heterotypic virus.

Animals↗

Hexachlorobenzene-induced stimulation of the humoral immune response in rats.

Rats were fed diets containing 0, 500, 1000, and 2000 mg HCB/kg during a 3-week period. Marked weight increases of spleen, popliteal and mesenteric lymph nodes and of the liver were found. Histologically, the white pulp in the spleen was enlarged because of an increase in size of marginal zones and follicles. In addition, there was an increase of extramedullary hemopoiesis. In the lymph nodes, the number of high endothelial venules was increased at all dose levels. The number of neutrophils, basophils and monocytes in the peripheral blood was significantly increased, whereas peripheral lymphocyte counts were slightly higher. Total serum IgM levels were markedly increased, but IgG concentrations were unaltered. On the basis of this experiment, the 1000 mg HCB/kg diet level was chosen for the different function studies that were carried out after a 3-weeks dietary regimen. Regarding the humoral immunity, IgM antibodies to LPS were unaltered, whereas primary and secondary IgM and IgG antibody titers to tetanus toxoid were increased approximately three-fold. HCB did not significantly alter the cell-mediated immunity, as shown by the following parameters: resistance to Listeria monocytogenes infection, rejection of skin transplants, and delayed-type hypersensitivity to tuberculin. The phagocytizing capacity of macrophages was studied by measuring the blood clearance of carbon particles. HCB did slightly depress the phagocytic index, but the difference with control animals was statistically not significant. The in vitro responsiveness of thymus cells to the mitogens PHA, Con A, and PWM was not changed by in vivo HCB-treatment. On a cell-for-cell basis, the responsiveness of spleen cells was increased when cultured in the presence of LPS. On a whole organ basis, the response to PHA, Con A, PWM, and LPS was markedly enhanced because of an increase in the number of nucleated spleen cells. Regarding peripheral lymphocytes, only the response to the mitogen Con A was higher. On the basis of these studies it is concluded that HCB stimulates the humoral immune response in the rat, enhances the in vitro responsiveness of spleen cells to the different mitogens mainly as a result of an increase in the number of splenic lymphocytes, but does not alter the cell-mediated immunity as shown with in vivo tests. This result contrasts with data in the literature that show that HCB suppresses the humoral and cell-mediated immunity in mice. Finally, HCB pretreatment only marginally increased the susceptibility of rats to endotoxin, whereas mice have been shown to be 20-fold more susceptible to the lethal effects of bacterial endotoxin.

Animals↗

Unusual manifestations of secondary syphilis and abnormal humoral immune response to Treponema pallidum antigens in a homosexual man with asymptomatic human immunodeficiency virus infection.

The case presented here involves a 32-year-old homosexual man with human immunodeficiency virus (HIV) seropositivity and unusual manifestations of secondary syphilis. The patient presented with syphilitic keratoderma and chorioretinitis, and his appearance superficially resembled that of a patient with Reiter's syndrome. Although nontreponemal and treponemal tests for syphilis showed reactivity, the patient's humoral immune response to individual polypeptides of Treponema pallidum, measured by Western blot analysis, was markedly abnormal. The possible relationship between asymptomatic HIV infection and an abnormal humoral immune response to a second pathogen, in this case T. pallidum, is discussed. Our case is one of several recent cases of active syphilis reported in individuals with HIV seropositivity.

Adult↗

Evaluation of IgA-mediated humoral immune response against the mycobacterial antigen P-90 in diagnosis of pulmonary tuberculosis.

BACKGROUND: Serologic methods for diagnosis of tuberculosis have been widely investigated owing to their low cost and rapid technical execution. Sensitivity and specificity of different tests have been reported to be largely variable. STUDY OBJECTIVES: To evaluate the IgA-mediated humoral immune response against the mycobacterial antigen P-90 as a tool for diagnosis of pulmonary tuberculosis. PARTICIPANTS: Eighty-eight patients with microbiologically confirmed diagnosis of pulmonary tuberculosis (32 with positive sputum smears and 56 with negative sputum smears), 28 patients with a definite nontuberculous lung disease, 12 subjects with healed tuberculosis, and 47 healthy volunteers (24 purified protein derivative negative and 23 positive). MEASUREMENTS AND RESULTS: Detection of anti-P-90 IgA was performed by enzyme-immunoassay. At a cutoff of 0.221 optical density, determined by a receiver operating characteristic curve, the overall sensitivity and specificity of the test were 70.4% and 91.9%, respectively. Patients with active tuberculosis showed significantly higher titers of anti-P-90 IgA compared with other groups (p < 0.05). CONCLUSIONS: The evaluation of IgA-mediated humoral immune response against the antigen P-90 might constitute a useful tool for presumptive diagnosis of pulmonary tuberculosis.

Adult↗

2'3'-Dideoxyinosine inhibits the humoral immune response in female B6C3F1 mice by targeting the B lymphocyte.

2',3'-Dideoxyinosine (ddI) is a purine nucleoside analog currently being used for the treatment of HIV-positive individuals and patients with AIDS. Preliminary immunotoxicity studies have shown that a consequence of ddI treatment in female B6C3F1 mice is the inhibition of the humoral immune response. This effect was dose dependent in a range of 100 to 1000 mg/kg with a no observed adverse effect level of less than 100 mg/kg for a 28-day treatment period. These studies were undertaken to investigate the immune cell target of ddI and to determine the mechanism of this toxicity. B6C3F1 mice were treated with 1000 mg/kg/day by oral gavage for 28 days. The B lymphocyte was identified as the cellular target of ddI through separation-reconstitution experiments of the adherent and nonadherent cell populations and of the T and B lymphocyte populations. These studies revealed a deficit in the ability of the nonadherent cells from ddI-treated mice to mount a normal antibody response to sRBC. A further separation of the nonadherent cells into T and B cells revealed a decreased ability of ddI-treated B cells to develop specific humoral immunity. Additional studies were undertaken to determine the mechanism by which ddI is affecting the B cell. Surface marker analysis of splenocytes revealed no difference in the cell populations between vehicle- and ddI-treated mice. B cell proliferation was also unaffected as shown by incubation with either a polyclonal stimulator, lipopolysaccharide, or anti-IgM plus IL-4. These results indicate that the primary cellular target of ddI is the B lymphocyte.

Animals↗

Humoral immune response in patients with hemophilia.

Hemophiliacs require frequent infusions of allogeneic proteins to control bleeding. Previous reports have demonstrated that thymus-derived lymphocytes (T cells) from hemophiliacs are antigenically primed to the lyophilized antihemophilic factor and that natural killer cells from hemophiliacs demonstrate impaired response to interferon-beta and -gamma Some aspects of the humoral immune response were investigated in eight patients who require large amounts of Factor VIII. Polyclonal hypergammaglobulinemia was detected in six patients and seven had elevated titers of autoantibodies of various specificities. There was no evidence of impaired concanavalin A-inducible T-suppressor cell activity. Polyclonal immunoglobulin secretion secondary to pokeweed mitogen in vitro was elevated in three of eight patients and depressed in five. Spontaneous production of both B-cell growth and differentiation factors (BCGF and BCDF) was elevated but mitogen-induced production was impaired. These data demonstrate that the humoral immune response of hemophiliacs may be chronically stimulated, thus impairing their ability to respond to new antigens such as viruses.

AIDS-Related Complex↗

Diminished cellular and humoral immunity in workers occupationally exposed to low levels of ionizing radiation.

BACKGROUND: It has been reported that subgroups of T-lymphocytes are affected at different levels and different cell groups of immune system give different responses in individuals exposed to long-term ionizing radiation. The aim of this study was to investigate the effect of occupational exposure to low levels of ionizing radiation in selected indices of cellular and humoral immunity in radiology workers. METHODS: Level of subgroups of peripheral blood lymphocytes, complements (C(3), C(4)), and total immunoglobulins (IgG, IgA, IgM) were analyzed in 50 radiology workers occupationally exposed to low levels of ionizing radiation and 35 age-matched healthy controls. RESULTS: CD4(+) T lymphocyte (T-helper) levels were determined as significantly low in radiology workers exposed to ionizing radiation compared with controls (p <0.05). There were no statistically significant differences in groups in terms of other subgroups of lymphocytes (p >0.05). In addition, levels of serum total IgG, IgA, IgM, C(3,) and C(4) were determined as significantly lower in workers exposed to ionizing radiation compared with controls (p <0.001). Total IgA and IgM levels in radiology workers who were smokers were determined as significantly lower compared with non-smoking radiology workers (p >0.05). CONCLUSIONS: Levels of CD4(+) T lymphocytes and humoral immune response (total immunoglobulins and complements) were determined as weaker in workers exposed to low levels of ionizing radiation compared with controls, indicating the importance of taking appropriate measures to protect radiology workers from exposure to ionizing radiation and for these workers to avoid smoking. Further studies are needed for determining the appropriateness of periodic check-ups of immune functions and the most efficient and cost-effective ways of monitoring immune functions in radiology workers for detecting early changes in the immune system.

Adult↗

Cell-mediated and humoral immune responses in chickens infected with Salmonella typhimurium.

The cellular immune responses of leghorn and New Hampshire chickens following oral challenge at 4 weeks of age with Salmonella typhimurium were measured using assays for lymphocyte proliferative responses to mitogens and cytotoxic activity of natural killer (NK) cells. In addition, the humoral immune response to Newcastle disease virus (NDV) vaccine was assessed in S. typhimurium-infected chickens. At 8 and 20 days after infection with S. typhimurium, lymphocyte proliferative responses to various mitogens were significantly higher in S. typhimurium-infected chickens than in uninfected birds of the same breeds. Cytotoxic activity of NK cells was also significantly increased in infected birds on these days. Thirteen days after S. typhimurium infection, infected NDV-vaccinated chickens had higher antibody titers in response to NDV vaccination than uninfected vaccinated birds. NDV titers did not differ among groups at any other time of testing. These results show that both cellular and humoral immune functions are activated in the first 3 weeks following infection of 4-week-old chickens with S. typhimurium.

Animals↗

Evaluation of humoral immunity on leprosy patients in Taiwan: a preliminary report.

Twenty-four tuberculoid (T)-type and 31 lepromatous (L)-type leprosy patients from Taiwan Provincial Lo-Sheng Leprosarium were enrolled in this study. Twenty-six age- and sex- matched normal subjects were also studied as a control group. The evaluation of their general and specific humoral immunity included B-cell subpopulations, 3 major classes of immunoglobulin (G, A and M) and antibodies in the IgG class against lepromin suspension and Bacillus Calmette-Guerin (BCG) sonicate. T-type patients showed a larger B-cell percentage than L-type patients (p less than 0.01). In general, patients with leprosy, both T and L types, had higher serum immunoglobulin levels than the control group. T-type patients showed greater antibody levels than the control group (p less than 0.05 for anti-lepromin and p less than 0.0001 for anti-BCG). L-type patients demonstrated a higher anti-BCG IgG level than the control group (p less than 0.0001). The level of anti-BCG IgG was more frequently above the cutoff level than that of anti-lepromin IgG in leprosy patients (p less than 0.01 for T, p less than 0.005 for L). In conclusion, humoral immunity is not impaired in leprosy patients. Discrepancies for T- and L-type patients among B-cell subpopulation, serum immunoglobulin levels and specific antibody levels reflect different aspects of cell-mediated immunity impairment. Though leprosy patients had elevated anti-BCG IgG levels, it is impossible to differentiate L- and T-type patients; specific antigens are needed for serodiagnosis of leprosy patients in Taiwan.

Adult↗

Maternal humoral immune response to incompatibility at multiple minor histocompatibility loci in mice.

Mice of the H-2b haplotype were mated with males of the same MHC haplotype, but differing at multiple minor histocompatibility loci. Mice were bled during each pregnancy and at 2-day intervals post-partum. The sera were assayed by indirect immunofluorescence for evidence of a humoral immune response to paternal minor histocompatibility antigens. Alloantibody was first detected in the post-partum period following the third pregnancy, and was also detected during the fourth pregnancy. Thereafter, alloantibody levels dropped and by the post-partum period following the fifth pregnancy, fell to control values. Assays on a panel of cells from mice of different inbred strains revealed specificity of the alloantibody to H-3.1, H-4.1 and H-7.1 antigens. A conventional dye exclusion cytotoxicity test revealed the pregnancy-induced alloantibody did not exhibit complement-dependent cytotoxicity. These findings are discussed in relation to the regulation and functional significance of the humoral immune response in allogeneic pregnancy.

Animals↗

The CD9 tetraspanin is not required for the development of peripheral B cells or for humoral immunity.

The CD9 tetraspanin is known to be expressed at high levels on marginal zone (MZ) B cells, B-1 B cells, and plasma cells, and its expression is believed to be dependent on signals derived via Btk. In CD9 null mice, however, the development and survival of MZ B cells, B-1 B cells, and plasma cells all appear to be unaffected, and humoral immune responses to T-dependent and T-independent Ags are similar to those seen in wild-type littermate controls. In wild-type mice, CD9 levels may serve to distinguish between the presumed MZ precursor B cell population in the spleen and other IgD-expressing transitional B cells that express lower levels of CD21 and CD1d. These results suggest that CD9 is dispensable for B cell development and humoral immunity, but that this protein may serve as an additional marker for the presumed MZ precursor population of splenic B cells.

Animals↗

Cell-mediated and humoral immune response to tetanus vaccinations in onchocerciasis patients.

In order to assess the possible suppression of immune responses to non-specific antigens in patients with generalized onchocerciasis, a vaccination study was conducted among the population of eight Liberian villages. Hundred and eighty-four persons infected with Onchocerca volvulus and 142 non-infected individuals were tested for delayed cutaneous hypersensitivity to tetanus antigen using the Multitest Mérieux. Prevalence of malaria and infections with intestinal nematodes with larval migration to the lung were much the same in all the villages examined. Other parasitic diseases had no significant influence. Persons aged 2-29 years with onchocerciasis had a significantly lower prevalence of positive tetanus reactions (p less than 0.05). Hundred and eighty persons showing a negative skin test were vaccinated twice with 75 i.u. tetanus toxoid and cell-mediated as well as humoral immune responses were recorded three months later. Analysis of sera collected before vaccinations indicated that 56% of the vaccinees had tetanus antibody levels of 0.01 i.u./ml or more and had, therefore, received a booster vaccination. Rates of seroconversion or booster were the same in persons with or without onchocerciasis (81% and 82% respectively). The conversion rate in the delayed cutaneous hypersensitivity test, however, was significantly lower in those infected with O. volvulus (67%) as compared to the controls (92%, p less than 0.001). These results demonstrate a diminished cell-mediated immune response to tetanus toxoid vaccinations in patients with generalized onchocerciasis. Considering the unimpaired humoral immune response, no changes in vaccination schedules are recommended.

Adolescent↗

Cell-mediated and humoral immune responses to BCG and rubella vaccinations and to recall antigens in onchocerciasis patients.

In seven Liberian villages of different endemicity for onchocerciasis 629 persons were tested for tuberculin reactions using 5 i.u. purified protein derivative or old tuberculin. No correlation between infection with Onchocerca volvulus and reactivity to tuberculin was detected on a community level, but a direct comparison of results of infected and non-infected individuals in two neighboring villages revealed a lower responsiveness in persons with onchocerciasis. The conversion rate three months after BCG vaccination was significantly lower in children with onchocerciasis (48%) than in controls (85%). The possible impact of this finding on the efficacy of BCG vaccinations is discussed. Girls aged 2-16 years were screened for rubella antibodies using a latex agglutination test. Sera from 74 girls, who showed no antibodies, were examined before and four months after rubella vaccination by haemagglutination-inhibition-test and haemolysis-in-gel-test. No difference in the humoral immune response of girls with or without onchocerciasis was found. Seroconversion rates were 98% and 100%. Delayed cutaneous hypersensitivity (DCH) to seven ubiquitous recall antigens was tested in 147 persons infected with O. volvulus and compared to the results of 142 non-infected controls. A reduced responsiveness was seen in persons with onchocerciasis, the difference being greatest in young children 2-7 years of age. In connection with the results of tetanus vaccinations reported earlier, these findings verify the existence of a reduced in vivo responsiveness of cell-mediated immunity to non-specific antigens in onchocerciasis in the rain forest of West Africa. Humoral immune responses however appeared to be unaffected.

Adolescent↗

Protection against pulmonary blastomycosis: correlation with cellular and humoral immunity in mice after subcutaneous nonlethal infection.

A model of pulmonary blastomycosis in the mouse, in which the portal of entry is the same as natural human infection, was used to study resistance to challenge after subcutaneous infection. One week after subcutaneous infection, mice were partially resistant to pulmonary challenge, and mice challenged two weeks after infection were resistant. Measurement of cellular and humoral immune responses to Blastomyces dermatitidis antigens after subcutaneous infection showed the following. (i) Delayed-type hypersensitivity appeared 1 week after infection, and responses increased for 3 weeks thereafter. (ii) Proliferative responses in vitro appeared in spleen cells at 1 week and in contralateral lymph node cells at 3 weeks, (iii) Serum antibody, detected by an enzyme-linked immunosorbent assay, appeared 1 week after infection and then increased in titer. (iv) Peritoneal macrophages were activated to inhibit replication of B. dermatitidis in vitro by the first week after infection. Prior subcutaneous infection also resulted in rapid clearing of a second subcutaneous challenge, as well as resistance to a lethal intraperitoneal challenge. This resistance was associated with the development of cell-mediated and humoral immune responses. These data provide a chronological framework for selective transfer experiments.

Animals↗

Humoral immune response in infectious mononucleosis. Late emergence of anti-EA(R) and the effects of corticosteroid therapy.

The antibody response to Epstein-Barr virus (EBV) antigens in patients with infectious mononucleosis (IM) was studied to assess antibody appearance to the restricted (R) component of the early antigen (EA) complex and to determine the effect of corticosteroids on all aspects of the humoral immune response. Sixty college students with heterophil-positive clinical IM, confirmed by EBV-specific serology, were followed for a period of 4-26 weeks, Half received prednisone for six days, and the remainder received no corticosteroid therapy. Regardless of therapy, 48% of the patients developed anti-EA(R) antibodies. The response to other antigens was similar in both groups with the exception that antibodies to the EB-associated nuclear antigen (EBNA) developed later during convalescence and at lower titers in the corticosteroid-treated group. We conclude that 1) anti-EA(R) antibodies develop with considerable frequency following IM and are not a marker, as previously proposed, of unusually severe disease, and 2) corticosteroid therapy may retard the formation of anti-EBNA antibodies but it does not otherwise influence the humoral immune response to EBV.

Adrenal Cortex Hormones↗

Experimentally increased social competition compromises humoral immune responses in house finches.

Although social behavior can substantially influence an individual's physiology, few studies have examined whether intraspecific competition compromises individual immunocompetence. We experimentally manipulated the intensity of social competition in captive non-breeding house finches (Carpodacus mexicanus) by supplying few (high competition) or many (low competition) feeding sites. We tested whether elevated levels of social competition caused individual changes in aggression rates, humoral immunity, body mass, and baseline and stress-induced corticosterone concentrations. We also examined whether physiological responses to social competition were related to an individual's social status. We found that house finches under high social competition had significantly higher aggression rates, lower antibody responses, and lost more body mass. Within flocks, dominant individuals mounted stronger immune responses in both competition treatments. Our statistical power to detect differences in circulating corticosterone concentrations was low, but we did not find any support for the hypothesis that corticosterone concentrations mediate immunosuppression among or within flocks: baseline and stress-induced corticosterone concentrations did not differ under high and low social competition, were unrelated to individual social status, and did not predict the extent of immunosuppression among individuals. Overall, we documented that two universal components of social behavior, intraspecific competition and social status, modulated the strength of a humoral immune response in house finches.

Adaptation, Physiological↗

Humoral immunity alterations after environmental asbestos exposure.

The inhabitants of Metsovo in northwestern Greece have been environmentally exposed to asbestos from childhood because they had been using a tremolite-containing material for whitewash, without knowing its consistency. As a result, they have a very high incidence of calcified pleural plaques and malignant pleural mesothelioma but no pulmonary fibrosis. In the present study we examined certain aspects of the humoral immunity in the serum of 109 individuals: levels of immunoglobulins, C-reactive protein and complement components, as well as the presence of antinuclear antibodies, rheumatoid factor, antibodies to extractable nuclear antigens, to ds-DNA and to cardiolipin. Our results show that, compared to controls, those exposed to asbestos have increased IgG and C3 levels. Those with pleural plaques have, in addition, increased IgA levels and an increased incidence of antinuclear antibodies. The results of the study suggest that nonoccupational asbestos exposure affects humoral immunity. The presence of pleural plaques accentuates this effect.

Adult↗

Humoral immune response to a sevoflurane degradation product in the guinea pig following inhalation exposure.

Compound A (2-fluoromethoxy-1,1,3,3,3-pentafluoro-1-propene) is produced by reaction of the inhalation anesthetic, sevoflurane, with CO2 absorbents. Compound A has been reported to directly react with protein. Since adduction of proteins can transform them into antigenic material, Compound A was assessed for its ability to produce a humoral immune response. Male outbred Hartley guinea pigs (500-600 g, N = 7) were exposed via inhalation for 4 h to a subtoxic level (100 ppm) of Compound A, 3 times, at 42 day intervals. Blood samples obtained at 2, 14, 28 and 40 days after each exposure were measured for ALT, creatinine, and urea nitrogen and for the presence of antibodies to trifluoroacetylated guinea pig albumin (TFA-GSA). All indicators of liver and kidney injury remained within normal range throughout the course of the study. A humoral immune response to TFA-GSA was observed following each exposure to Compound A with a titer appearing by day 14 after exposure, peaking near day 28, and resolving to normal levels by day 40. The titer levels were approximately equivalent after each exposure and about one-third that previously seen in guinea pigs after multiple exposures to halothane. Compound A would appear to have the ability to form antigenic adducts during inhalation exposure. These findings are similar to those observed for halogenated inhalation anesthetics that have been linked to cases of immune-medicated idiosyncratic hepatitis and indicate that Compound A exposure may pose the same hazard.

Alanine Transaminase↗