PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Immunity, Humoral”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 613 records · Page 34Linked to original sources

Aqueous-based microencapsulation enhances virus-specific humoral immune responses in mice after parenteral inoculation.

Vaccines are commonly administered by the parenteral route. Therefore, adjuvant strategies which include parenteral immunization may improve the efficacy of a number of current vaccines. The capacity of aqueous-based microencapsulation to enhance virus-specific IgG responses in mice inoculated intramuscularly with small quantities of antigen was evaluated. Mice were inoculated with either 10(4), 10(3), or 10(2) p.f.u. of microencapsulated rotavirus (bovine strain WC3), placebo microcapsules plus free virus, or virus alone. Mice were subsequently bled 1, 2, 4, 6, and 9 months after inoculation. Microencapsulation of rotavirus enhanced virus-specific humoral immune responses. In addition, virus-containing microcapsules composed of spermine-chondroitin sulfate induced levels of virus-specific antibodies greater than those found after inoculation with virus-containing microcapsules composed of spermine-alginate. Mechanisms by which microencapsulation may enhance virus-specific humoral immunity are discussed.

Animals↗

Toxicology and humoral immunity assessment of decamethylcyclopentasiloxane (D5) following a 1-month whole body inhalation exposure in Fischer 344 rats.

D5 is a low-molecular-weight cyclic siloxane used for industrial and consumer product applications. The objective of the present study was to assess potential toxic and immunomodulatory consequences of inhalation exposure to D5. Male and female Fischer 344 rats (25/group) were exposed by whole body inhalation to 0, 10, 25, 75, or 160 ppm D5 6 h/day, 7 days/week for 28 days. Clinical signs, body weights, and food consumption were recorded. On the day following the final exposure, 10 rats/group/sex were euthanized and a complete necropsy performed. Following a 14-day nonexposure recovery period, the remaining 5 rats/sex/group were necropsied. Body and organ weights were obtained and a complete set of tissues was taken for histopathology. Samples were also collected for serum chemistry, hematology, and urinalysis. Immunotoxicology-designated rats (10/sex/group) were immunized with sheep erythrocytes (sRBC) 4 days prior to euthanasia and cyclophosphamide (CYP) was administered i.p. to positive controls on days 24 through 28. The anti-sRBC antibody-forming cell (AFC) response was evaluated in a standard plaque assay. Blood was also collected for examination in the anti-sRBC enzyme-linked immunosorbant assay (ELISA). D5 exposure did not modulate humoral immunity, while the internal control, CYP, produced the expected suppression of the AFC response. D5 exposure caused no adverse effects on body weight, food consumption, or urinalysis parameters. Serum alkaline phosphatase (SAP) was significantly decreased in females at terminal (12%, 160 ppm) and recovery sacrifice. A significant increase in the liver-to-body weight ratio was observed in female animals at the end of exposures (13%, 160 ppm), but was not noted in recovery animals from the same exposure group. In males, significant increases in liver-to-body weight (5%) and thymus-to-body weight (14%) ratios were also noted at the high dose at terminal sacrifice and were not present at recovery. At recovery only, a significant increase in spleen-to-body weight ratios (14 and 17%; 25 and 160 ppm, respectively) was noted. At the end of exposure, histopathological analysis indicated an increased incidence and severity of nasal (Level 1) goblet cell proliferation. Focal macrophage accumulation in the lung was also observed to be increased in incidence in both sexes at 160 ppm. At the end of the recovery period, the effects in both of these organs appeared to be reversible. In summary, D5 inhalation exposure did not alter humoral immunity and caused only minor, transient changes in hematological, serum chemistry, and organ weight values. Histopathological changes were confined to the respiratory tract and appeared to be reversible. The no observed effect level for systemic toxicity, based primarily on the liver weight changes, was 75 ppm.

Animals↗

Selective impairment of humoral immunity in feline leukemia virus-induced immunodeficiency.

We used a panel of in vitro assays to investigate the nature of immune dysfunction in cats infected with FeLV-FAIDS, a naturally occurring, molecularly cloned feline leukemia virus (FeLV) isolate which induces a fatal immunodeficiency syndrome in infected cats. During the asymptomatic period preceding immunodeficiency disease, we were unable to detect any deficits in concanavalin A-induced blastogenesis, xenogeneic mixed-lymphocyte reaction assays, stimulation of lymphocytes by soluble protein antigen, and cytotoxic T lymphocyte assays. However, during this period humoral immune responses in the FeLV-FAIDS-infected cats were dramatically impaired. As early as 9 weeks after virus inoculation, the ability to mount either an IgM or IgG response to soluble protein antigens was lost. Neither B cell function, as assessed by lipopolysaccharide-induced blastogenesis or circulating B cell numbers, as assessed by immunofluorescence, differed between infected and control cats. These results suggest that FeLV-FAIDS infection may impair a subpopulation of T helper cells, that provides help for the production of antibody. Consistent with earlier observations of cats naturally infected with FeLV, our results indicate that early impairment of humoral immunity is an important component of the immunodeficiency syndrome induced by FeLV in cats.

Animals↗

Suppression of the humoral immune response by mycophenolate mofetil.

BACKGROUND: No conventional immunosuppressive agent preferentially inhibits antibody production. Studies in experimental animals and in human cells in vitro suggested mycophenolate mofetil (MMF) might have such an effect. If this was the case in vivo it could have significant implications in terms of both MMF toxicity and the rational design of immunotherapeutic regimens. METHODS: Subjects were renal transplant recipients (25 patients treated with prednisolone, cyclosporine and azathioprine, and 13 treated with prednisolone, cyclosporine and MMF) and 20 normal controls. The three groups received influenza vaccination, and the antibody response to it was measured 4-6 weeks later using a standard haemagglutination assay. RESULTS: MMF profoundly suppressed the humoral immune response to influenza vaccination when added to prednisolone and cyclosporine. This effect could be seen when comparing the rise in the mean titre of antibody after vaccination. It was also reflected in the number of patients mounting responses deemed to be clinically protective by either demonstrating a 4-fold rise in titre or an increase in titre to > or = 40. CONCLUSIONS: Suppression of the humoral immune response by MMF has implications for the design of immunization protocols to protect the immunosuppressed, and raises the possibility that MMF use may be accompanied by more or different infections than complicate more conventional immunosuppression. More importantly, consideration should be given to harnessing the relatively specific effect of MMF on antibody production to treat antibody-mediated diseases.

Adolescent↗

Humoral immune responses against Wilms tumor gene WT1 product in patients with hematopoietic malignancies.

Wilms tumor gene WT1 is expressed at high levels in hematopoietic malignancies, such as leukemias and myelodysplastic syndromes (MDS), and in various kinds of solid tumors, including lung cancer, and it exerts an oncogenic function in these malignancies. IgM and IgG WT1 antibodies were measured by means of dot blot assay in 73 patients with hematopoietic malignancies (16 acute myeloid leukemia [AML], 11 acute lymphoid leukemia [ALL], 13 chronic myeloid leukemia [CML], and 33 MDS) and 43 healthy volunteers. Immunoglobulin IgM, IgG, and IgM+IgG WT1 antibodies were detected in 40 (54.8%), 40 (54.8%), and 24 (32.8%), respectively, of the 73 patients with hematopoietic malignancies, whereas 7 (16.2%), 2 (4.7%), and none of the 43 healthy volunteers had IgM, IgG, or IgM+IgG WT1 antibodies, respectively. Furthermore, immunoglobulin isotype class switching of WT1 antibodies from IgM to IgG occurred in conjunction with disease progression from refractory anemia (RA) to RA with excess of blasts (RAEB), and further to RAEB in transformation (RAEB-t) in MDS patients. These results showed that humoral immune responses against the WT1 protein could be elicited in patients with WT1-expressing hematopoietic malignancies, and they suggested that the helper T-cell responses needed to induce humoral immune responses and immunoglobulin isotype class switching from IgM to IgG were also generated in these patients. Our findings may provide new insight into the rationale for elicitation of cytotoxic T-cell responses against the WT1 protein in cancer immunotherapy using the WT1 vaccine.

Adolescent↗

Co-immunization of rhesus macaques with plasmid vectors expressing IFN-gamma, GM-CSF, and SIV antigens enhances anti-viral humoral immunity but does not affect viremia after challenge with highly pathogenic virus.

To investigate the adjuvant capacity of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon (IFN-gamma), we cloned these rhesus cytokines into a mammalian expression vector. Two groups of six rhesus macaques (Macaca mulatta) received intradermal immunizations of plasmid DNA coding for SIV Eng and Gag, and influenza virus nucleoprotein (Flu-NP), with or without the co-administration of plasmid DNA coding for these cytokines. Humoral immune responses to antigens of both of these viruses and SIV specific T cell proliferative responses were significantly enhanced by co-immunization with the cytokines. These twelve monkeys, and a group of six naive controls, were challenged by the oral mucosal route with the uncloned and highly pathogenic SIVmac251. All monkeys became infected. The early CD4 decline was reduced in the group co-immunized with cytokine and viral plasmids. Unexpectedly, plasma viremia set points were not different in this co-immunized group and the non-immunized control group. On the other hand, monkeys vaccinated with equivalent amounts of empty vector plasmid (i.e. no cytokine inserts) along with plasmids expressing viral antigens demonstrated a slight but significant decrease in acute viremia compared to non-immunized controls (P<0.02). However, viral loads at set points were not significantly different between both the immunized and the non-immunized control group. Thus, although the cytokine vectors demonstrated detectable enhancement of the immune response to different viral antigens, such enhanced response did not translate into better anti-viral control in our experiment. These results underscore the need for further testing of cytokines as vaccine adjuvants in relevant animal models.

Animals↗

An antagonistic IL-4 mutant prevents type I allergy in the mouse: inhibition of the IL-4/IL-13 receptor system completely abrogates humoral immune response to allergen and development of allergic symptoms in vivo.

We have analyzed in vivo effects of the murine IL-4 mutant Q116D/Y119D (QY), which forms unproductive complexes with IL-4Ralpha and is an antagonist for IL-4 and IL-13 in vitro. Treatment of BALB/c mice with QY during immunization with OVA completely inhibited synthesis of OVA-specific IgE and IgG1. BALB/c-derived knockout mice lacking either IL-4 or IL-4Ralpha also did not develop specific IgE or IgG1, but mounted a much stronger IgG2a and IgG2b response than wild-type mice. In contrast, QY treatment of normal BALB/c mice suppressed specific IgG2a, IgG2b, and IgG3 synthesis, which may indicate the development of tolerance toward the allergen. Associated with the lack of IgE synthesis in QY-treated wild-type mice and in IL-4(-/-) mice used as a control was the failure to develop immediate cutaneous hypersensitivity or anaphylactic shock upon rechallenge. Interestingly, QY treatment also inhibited humoral immune responses and allergic reactivity in SJL/J mice, a strain that did not produce IgE, but displayed IgE-independent mast cell degranulation mediated by specific IgG1. We conclude that QY inhibits Ag-specific humoral immune responses and allergic symptoms mediated either by IgE or IgG1. It needs to be clarified how QY abrogates synthesis of IgG2a, IgG2b, and IgG3, but the induction of tolerance toward nonhazardous protein Ags should be advantageous for therapy of atopic disorders and other Th2-dominated diseases.

Allergens↗

Enhanced suppression of humoral immunity in DBA/2 mice following subchronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

Previous studies have indicated that mice which differ in their acute susceptibility to responses mediated by the Ah receptor have a pattern of suppression of the antibody response which is consistent with a role by the putative dioxin receptor. The objective of the present investigation was to compare the TCDD-induced suppression of the antibody response following acute and subchronic exposures in B6C3F1 mice, an Ah-high-responder strain, and DBA/2 mice, an Ah-low-responder strain. Results of our initial studies demonstrate that suppression of humoral immunity can be enhanced in DBA/2 mice approximately 10-fold following subchronic versus acute exposures to the same cumulative doses of TCDD. This change in suppression of the antibody response in DBA/2 mice was not accompanied by significant changes in liver weight (hepatomegaly), as was observed in the B6C3F1 strain when exposed under comparable conditions. In contrast, effects on thymus weight (involution) were enhanced in the DBA/2 mice following subchronic exposure and demonstrated a higher degree of atrophy than was seen in the B6C3F1 strain (68 versus 56% decrease in thymic weight at the 42 micrograms/kg cumulative dose). These findings suggest that multiple mechanisms may be operating to suppress humoral immunity in vivo and that the conditions of exposure can alter the toxic effects of TCDD in the DBA/2, Ah-low responsive, mouse strain.

Animals↗

Evidence against humoral immune attack as the cause of sheep-goat interspecies and hybrid pregnancy failure in the doe.

The failure of interspecies and hybrid pregnancies between the domestic sheep (Ovis aries) and goat (Capra hircus) is not completely understood. The sheep-goat hematopoietic chimera is a unique model for studying the role of the maternal immune response in failure of interspecies and hybrid pregnancies between these species. Hematopoietic chimeras were created by in utero transplantation of sheep fetal liver cells into goat fetuses. The resulting chimeric females were recipients of sheep demi-embryos genetically identical to their sheep cells and/or were bred to a ram to create a hybrid pregnancy. Pregnancy sera were analyzed for the presence of anti-species antibodies (Ab) using a lymphocyte microcytotoxicity assay. None of the concepti survived to term. Gross and histological evaluations of two interspecies sheep concepti revealed abnormal placentome formation. The humoral immune response of several hematopoietic chimeras to the challenging concepti differed from control animals. We observed delayed onset of Ab production, low and absent titers, and persistent Ab titers with delayed fetal death. Ultrasonography typically revealed normal fetal development associated with high volumes of placental fluids and retarded placentome development. We conclude that fetal death was associated with abnormal placental development that was not the result of maternal humoral immune attack.

Animals↗

Interleukin-21 triggers both cellular and humoral immune responses leading to therapeutic antitumor effects against head and neck squamous cell carcinoma.

BACKGROUND: Interleukin-21 (IL-21) plays important roles in the regulation of T, B, and natural killer (NK) cells. We hypothesized that the cytokine may provide a novel immunotherapy strategy for cancer by stimulating both Th1 and Th2 immune responses. In this context, antitumor immunity induced by IL-21 was examined in mice bearing subcutaneous head and neck squamous cell carcinomas (HNSCC). METHODS: A plasmid vector encoding murine IL-21 was injected intravenously into mice with pre-established HNSCC tumors, either alone or in combination with a vector construct expressing IL-15. Cytotoxic T lymphocyte (CTL) and NK killing activities were evaluated by chrome release assays, while HNSCC-specific antibody was examined by flow cytometry and ELISA. RESULTS: Significant antitumor effects were obtained by repeated transfection with either the IL-21 or the IL-15 gene. Co-administration of both cytokine genes resulted in increased suppression of tumor growth, significantly prolonging the survival periods of the animals. Thirty percent of the tumor-bearing mice that received the combination therapy survived for more than 300 days, completely rejecting rechallenge with the tumor at a distant site. IL-21 induced significant elevation of HNSCC-specific CTL activity, while IL-21 and IL-15 augmented NK activity in an additive manner. IL-21 gene transfer also promoted the production of tumor-specific IgG. CONCLUSIONS: In vivo transduction of the IL-21 gene elicits powerful antitumor immunity, including both humoral and cellular arms of the immune response, and results in significant suppression of pre-established HNSCC. Co-transfer of the IL-15 gene further improved the therapeutic outcome, mainly by augmenting NK tumoricidal activity. The biological effects of IL-21 may be in sharp contrast to those of conventional Th1 and Th2 cytokines, suggesting intriguing implications of this cytokine for the classical concept of Th1 vs. Th2 paradigm.

Animals↗

Protective and destructive immunity in the periodontium: Part 1--innate and humoral immunity and the periodontium.

Based on the results of recent research in the field, the present paper will discuss the protective and destructive aspects of the innate vs. adaptive (humoral and cell-mediated) immunity associated with the bacterial virulent factors or antigenic determinants during periodontal pathogenesis. Attention will be focused on: (i) the Toll-like receptors (TLR), the innate immune repertoire for recognizing the unique molecular patterns of microbial components that trigger innate and adaptive immunity for effective host defenses, in some general non-oral vs. periodontal microbial infections; (ii) T-cell-mediated immunity, Th-cytokines, and osteoclastogenesis in periodontal disease progression; and (iii) some molecular techniques developed and used to identify critical microbial virulence factors or antigens associated with host immunity (using Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis as the model species). Therefore, further understanding of the molecular interactions and mechanisms associated with the host's innate and adaptive immune responses will facilitate the development of new and innovative therapeutics for future periodontal treatments.

Adaptor Proteins, Signal Transducing↗

FTY720 inhibits TH1-mediated allogeneic humoral immune response.

Phosphorylated FTY720 is an analog of Sphingosine 1 Phosphate (S1P) with immunosuppressive activity that negatively regulates the expression of S1P-Receptor 1. It also inhibits the migration of CD4 and CD8 single-positive T cells from the thymus to the periphery, sequesters peripheral blood lymphocytes in lymph nodes and Peyer's patches, and delays the exit of effector T cells toward the graft. The aim of our work was to study the effect of FTY720 on the kinetics of skin allograft rejection in a fully mismatched model; euthymic (Euthy) versus thymectomized (ATX) C57BL/6 mice (haplotype H-2(b)) recipients of BALB/c mice (haplotype H-2(d)) donor cells. The animals were injected daily with FTY720 (1 mg/kg) intraperitoneally for 2 weeks. To monitor the humoral immune response, serum samples collected at day 0 (pre-immune) and at day 23 after skin graft rejection were examined using BALB/c thymocytes as antigens in flow cytometry. To confirm the effect of FTY720 on peripheral lymphocytes, peripheral blood was analyzed by flow cytometry. Euthy and ATX FTY720-treated mice showed prolongation of skin allograft survival when compared with nontreated Euthy and ATX controls (P < .005). Unexpectedly, FTY720-treated Euthy mice showed significantly delayed graft rejection when compared to similarly treated ATX mice (P < .005). The delayed graft rejection in FTY720-treated Euthy mice correlated with a reduced content of Th1-mediated IgG(2a) and IgG(2b) antibodies when compared with FTY720-treated ATX mice (P < .05). In conclusion, FTY720 delays the kinetics of allograft rejection in a fully mismatched model by inhibiting Th1-mediated humoral immune responses. The presence of the host thymus appears to be required for this phenomenon.

Animals↗

A study of cell mediated and humoral immunity in haemophilia and related disorders.

Helper (OKT4) and suppressor (OKT8) T lymphocyte populations and functional assays of cellular immunity were studied in 37 patients with haemophilia and related disorders in parallel with age matched control subjects. The study included 26 patients with factor VIII (FVIII:C) deficiency, eight patients with factor IX deficiency and three patients with severe von Willebrand's disease (vWd). In patients with factor VIII deficiency low helper T lymphocyte counts, low T helper: suppressor ratios and a diminished response to the lymphocyte mitogen phytohaemagglutinin with decreased natural killer cell activity were observed. Individuals with factor IX deficiency had low absolute T lymphocyte (OKT3) counts and T helper cell counts. Patients with severe factor VIII deficiency (FVIII:C less than 1 u/dl) had lower T helper suppressor ratios and lower killer cell and natural killer cell activity in comparison to mildly affected individuals and all of the severely affected factor IX deficient cases. Studies of humoral immunity revealed a generalized increase in immunoglobulin levels in patients with coagulation disorders of any type. The total haemolytic complement activity was reduced in a significant proportion of haemophilic subjects. Levels of alpha-1-interferon were elevated in the groups of haemophilic subjects studied. The abnormalities of cellular and humoral immunity observed did not correlate with the amount or type of coagulation factor administered to individual patients in the preceding 2 years. The most marked abnormalities of immune function occurred in the one patient diagnosed as suffering from AIDS on clinical grounds.

Adolescent↗

Effects of supplemental vitamin E on performance, health, and humoral immune response of beef cattle.

Three experiments were conducted to examine the effect of dietary vitamin E on receiving performance and health and on finishing performance of beef cattle. One hundred twenty beef steers (Exp. 1; initial BW = 173 kg) and 200 beef heifers (Exp. 2; initial BW = 204 kg) were assigned randomly to one of three treatment diets formulated to supply 285, 570, or 1,140 IU/animal daily of supplemental vitamin E during the receiving period. Average daily gain, gain:feed, and DMI were calculated every 14 d, with pen as the experimental unit. Morbidity and retreatment data were analyzed using a nonparametric procedure. After the receiving period, cattle were assigned to a grazing period followed by a finishing program and fed until slaughter. In Exp. 3, 17 beef steers were used to evaluate effects of the same three vitamin E levels on humoral immune response to an ovalbumin vaccine given on d 0 and 14. Jugular blood samples were collected on d 0, 7, 14, and 21. In Exp. 1, vitamin E did not affect (P > 0.10) ADG, DMI, or gain:feed for d 0 to 14, 14 to 28, or 0 to 28. No effects were noted for percentage of morbidity; however, cattle receiving 1,140 IU/d had a numerically (P = 0.15) lower incidence of retreatment. During the 91-d finishing phase, a quadratic effect (P < 0.08) was noted for DMI, ADG, backfat thickness, longissimus muscle area, and yield grade. In Exp. 2, a tendency for a linear (P = 0.10) increase in ADG was observed for the first 14 d of receiving; however, ADG decreased linearly (P = 0.06) with vitamin E concentration thereafter. For the 28-d period, ADG and DMI did not differ among treatments, but gain:feed decreased linearly (P < 0.05) for d 14 to 28 and for d 0 to 28. No effects on percentage morbidity were noted in Exp. 2, and no differences were detected for ADG, gain:feed, or DMI for the 98-d finishing period. There was a linear increase in yield grade (P < 0.05) and a linear (P < 0.08) decrease in longissimus muscle area with increasing vitamin E. Heifers receiving 570 IU of vitamin E during the receiving period tended to have a higher (P < 0.09) dressing percentage at slaughter. In Exp. 3, no significant differences were detected in serum IgG titers to ovalbumin on d 0, 7 or 14; however, on d 21, a linear increase (P = 0.07) in serum IgG titers was noted with supplemental vitamin E. Supplemental vitamin E had limited effects on performance; however, effects on humoral immune response and recovery from respiratory disease warrant further research.

Age Factors↗

Pseudomonas aeruginosa chromosomal beta-lactamase in patients with cystic fibrosis and chronic lung infection. Mechanism of antibiotic resistance and target of the humoral immune response.

The intensive antibiotic treatment of cystic fibrosis (CF) patients with chronic lung infection with Pseudomonas aeruginosa has improved the survival rate and the clinical condition of Danish patients. Acquirement of resistance to anti-pseudomonal antibiotics is one of the main drawbacks of this therapeutic strategy and our results showed the development of resistance of P. aeruginosa to several antibiotics during 25 years of intensive antibiotic treatment. Our studies have been concentrating on the development of resistance to beta-lactam antibiotics. We have shown an association between the development of resistance to beta-lactam antibiotics and the occurrence of high beta-lactamase producing strains and between the MIC of the beta-lactams and the levels of beta-lactamase expression. Partially derepressed mutants, characterized by high basal levels of beta-lactamase with the possibility of induction to even higher levels during treatment with beta-lactam antibiotics, were the most frequent phenotype found among resistant Danish P. aeruginosa CF isolates. We have also shown that the high alginate producing P. aeruginosa isolates, that characterize the chronic lung infection in CF patients, are more susceptible to antibiotics and produce less beta-lactamase than the non-mucoid paired isolates. We propose that the non-mucoid isolates are exposed to a relatively higher antibiotic pressure than the mucoid isolates and therefore, they become easily antibiotic resistant and in consequence produce high levels of beta-lactamase. The beta-lactamase produced by the non-mucoid isolates might play a protective role in the biofilm, defending the mucoid isolates from the action of beta-lactam antibiotics and helping them to maintain their antibiotic susceptibility. We have also shown that beta-lactamase, which is a periplasmic enzyme, can be secreted extracellulary packed in membrane vesicles liberated by high beta-lactamase-producing P. aeruginosa. The continuos presence in the CF lungs of bacteria producing high basal levels of beta-lactamase (partial derepressed) induces a humoral immune response to beta-lactamase. We have shown that antibodies against the chromosomally encoded beta-lactamase (a beta ab) might be considered a marker of the development of resistance to beta-lactam antibiotics. We investigated the humoral immune response to beta-lactamase by quantifying a beta ab specific IgG and IgG subclass antibodies, by investigating the influence of the allotypes on the IgG subclass response and by measuring the avidity of the IgG a beta ab. We found that CF patients with good lung function had in the early stages of the chronic lung infection higher titers of a beta ab of good avidity than patients with poor lung function. Therefore, we raised the hypothesis that some of the a beta ab might have beta-lactamase neutralizing effect, playing a beta-lactamase inhibitor role and improving the effect of the treatment with beta-lactam antibiotics. Finally, we tested our hypothesis in the rat model of chronic lung infection by assessing the effect of a beta ab raised by vaccination with purified chromosomal beta-lactamase on the outcome of the treatment with ceftazidime of bacteria resistant to beta-lactam antibiotics. Our results showed that significantly lower bacterial load and better lung pathology were found in rats with neutralizing antibodies compared to non-immunized rats or rats without neutralizing antibodies. Our findings might be of potential importance for the improvement of the treatment with beta-lactam antibiotics of resistant P. aeruginosa hyperproducing chromosomal beta-lactamase that represent a threat especially for patients with CF and chronic lung infection.

Animals↗

Evaluation of the humoral immune response of CD rats following a 2-week exposure to the pesticide carbaryl by the oral, dermal, or inhalation routes.

The objective of this study was to examine the immunotoxicological effects of the methyl-carbamate pesticide carbaryl via the oral, dermal, or inhalation routes. Male CD rats were exposed to carbaryl 5 d/wk for a 2-wk period. During nose-only inhalation exposures, rats received either 36, 137, or 335 mg/m3 carbaryl in acetone for 6 h. Air only and acetone/air controls were run concurrently. Orally exposed animals received either 1 ml corn oil or 10, 25, or 50 mg/kg carbaryl, while dermally exposed animals received either 2 ml acetone or 100, 500, or 1000 mg/kg carbaryl on their dorsal flank for 6 h. Four days prior to sacrifice, animals from all exposure groups were injected iv with 2 x 10(8) sheep red blood cells (SRBC). The primary immunoglobulin M (IgM) humoral immune response to SRBC was then assessed by measuring SRBC-specific antibody-forming cells (AFC) and levels of serum anti-SRBC IgM antibody, respectively, using the hemolytic plaque assay and an enzyme-linked immunosorbent assay. Individual body weights, spleen, thymus, and liver weights, spleen cell number, and red and white blood cell (RBC, WBC) counts were obtained for each animal. Following nose-only inhalation exposures, dose-dependent decreases in thymus weights, spleen cell number, AFC/spleen, AFC/10(6) splenocytes, and serum levels of SRBC-specific IgM antibody were observed. Significant decreases of 33, 57, and 22% in spleen cell number, AFC/spleen, and thymus weight, respectively, were found at the 335 mg/m3 exposure level. Animals exposed orally to 25 mg/kg carbaryl had a 34% decrease in WBC counts. A 34% decrease in WBC and a 13% increase in RBC counts were observed at the 50 mg/kg oral dose. Significant decreases in liver weights ranging from 11 to 13% were found at all oral exposure levels. Dermal exposure to carbaryl revealed no significant toxicological effects. Results indicate that humoral immune suppression was observed following inhalation, but not following oral or dermal exposures to carbaryl. Immunotoxicological studies evaluating pesticides need to consider relevant exposure routes and dosages for appropriate risk assessment procedures and exposure limits to be established.

Administration, Cutaneous↗

Pregnancy and humoral immune response in mice chronically infected by Trypanosoma cruzi.

The effect of pregnancy on the humoral immune response induced by Trypanosoma cruzi was studied in groups of chronically infected and pregnant mice (IP) or chronically infected and nonpregnant mice (INP) of strain BALB/c. Groups of noninfected and nonpregnant mice (NINP) or noninfected and pregnant mice (NIP) served as controls. The pregnant mice were killed on day 17 of pregnancy. Anti-T. cruzi immunoglobulin G (IgG) and IgM antibodies, detected by immunofluorescence or enzyme-linked immunosorbent assay or both, underwent a pregnancy-associated decrease of 20 to 40%, whereas complement-mediated lytic antibodies were unaffected by pregnancy. Immunoblotting analysis indicated identical specificities of the anti-T. cruzi antibodies in IP and INP groups. The levels of all the immunoglobulin isotypes (particularly IgG2a and IgG3), circulating immune complexes, rheumatoid-like factor, and anti-DNA antibodies were considerably increased during chronic infection (NINP versus INP), which could be related to the high degree of polyclonal B-cell activation occurring in T. cruzi infection. However, pregnancy significantly decreased (by 20 to 60%) such parameters. IgG levels were particularly affected (by 40 to 60%), and the decreases could be ordered as follows: IgG3 greater than IgG2a greater than IgG1 greater than IgG2b for IP versus INP. Comparisons between the noninfected groups indicated differences only in IgG levels. These results indicate the following. (i) The specific humoral anti-T. cruzi immune response is weakly affected by pregnancy, which is not sufficient to modify the course of the mother's infection. (ii) Pregnancy does not modify the expression of the anti-T. cruzi antibody repertory. (iii) Pregnancy reduces the polyclonal B-cell activation, particularly the levels of the IgG isotypes undergoing the greatest activation.

Animals↗

Cellular and humoral immune responses in Campylobacter pylori-associated chronic gastritis.

Gastric cellular and humoral immune response investigated by immunoperoxidase staining of 53 antral biopsies showed significant differences in Campylobacter pylori-associated gastritis as compared with non-bacterial chronic gastritis and normal controls. IgA, secretory component, and complement C3 coated bacilli were seen in all cases of active chronic gastritis. C3 was always associated with coating by IgA, IgM, or both, which were rarely seen in gastritis without polymorphonuclear neutrophil infiltration. Intraepithelial mononuclear cellular infiltration was seen in 18 of 26 cases of C. pylori-associated chronic gastritis. The intraepithelial mononuclear cells stained positively for T cells and histiocytes.

Antibody Formation↗