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Results for “Immunity, Humoral”

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PubMed1988

Changes in the profiles of circulating white blood cells, corticosterone, T3 and T4 during the initiation of humoral immunity in immature male chickens.

Eight-week-old male White Leghorn chickens were injected intravenously with either 0.1 ml of Brucella abortus (BA) or saline. Blood samples were collected before injection, 1 hr, 3 hr, 6 hr, 12 hr, 24 hr, and then daily for the following 6 days after the injection. Total white blood cells (WBC), differential counts and corticosterone (CS), T3 and T4 levels were measured in all blood samples. These data represented the results obtained from the primary response. To obtain data for the secondary response, the same birds were injected 4 weeks following the first challenge and the same procedure was followed. During primary and secondary responses, circulating lymphocytes and monocytes decreased significantly 3 hr following BA injection and then increased steadily and reached a peak approximately 5 days post-BA injection, however, circulating heterophils increased significantly 6-12 hr and returned to normal levels 2 days post-BA injection. Serum corticosterone increased significantly 3 hr following BA injection. Serum T3 decreased significantly 3 to 12 hr then increased significantly 2 days following BA injection. There were no significant changes in any of the measurements following saline injection. Correlations between circulating hormones and white blood cells were calculated and are reported. These results indicate that an early step in the initiation of humoral immunity is probably an increase in serum CS. This increase in CS is followed by a decrease in circulating lymphocyte and monocyte numbers. These decreases may be the result of lymphocyte trapping in secondary lymphoid organs. This series of events may occur to modulate and activate the immune response.

Animals↗

PubMed2006

The CD1d-binding glycolipid alpha-galactosylceramide enhances humoral immunity to T-dependent and T-independent antigen in a CD1d-dependent manner.

Specific interaction of class II/peptide with the T-cell receptor (TCR) expressed by class II-restricted CD4+ T helper (Th) cells is essential for in vivo production of antibodies reactive with T-dependent antigen. In response to stimulation with CD1d-binding glycolipid, Valpha14+ TCR-expressing, CD1d-restricted natural killer T (NKT) cells may provide additional help for antibody production. We tested the hypothesis that the CD1d-binding glycolipid alpha-galactosylceramide (alpha-GC) enhances production of antibodies reactive with T-dependent antigen in vivo. alpha-GC enhanced antibody production in vivo in a CD1d-dependent manner in the presence of class II-restricted Th cells and induced a limited antibody response in Th-deficient mice. alpha-GC also led to alterations in isotype switch, selectively increasing production of immunoglobulin G2b. Further analysis revealed that alpha-GC led to priming of class II-restricted Th cells in vivo. Additionally, we observed that alpha-GC enhanced production of antibodies reactive with T-independent antigen, showing the effects of NKT cells on B cells independently of Th cells. Our data show that NKT cells have multiple effects on the induction of a humoral immune response. We propose that NKT cells could be exploited for the development of novel vaccines where protective antibody is required.

Animals↗

PubMed2003

Cellular and humoral immune reconstitution after autologous peripheral blood stem cell transplantation (PBSCT).

Immune reconstitution after autologous peripheral blood stem cell transplantation (PBSCT) is of particular interest because of its importance for clinical outcome. Despite prolonged immunosuppression, especially of CD4(+) cells, few infections after neutrophil recovery occur. Only reactivation of varicella zoster virus (VZV) is more frequent in the first year after transplantation. From August 1997 to May 2001, we prospectively evaluated 38 patients prior to conditioning and during follow-up of 12 months post-transplant for virus antibodies [measles, mumps, rubella, polio, herpes simplex, varicella zoster, mononucleosis, cytomegalovirus (CMV)] and lymphocyte subpopulations by flow cytometry. CD3(+) T lymphocytes, CD8(+) T cells, and B-lymphocyte reconstitution in our study confirms previous reports. Complete CD4(+) lymphocyte reconstitution was not achieved in the 12 months post-transplant leading to a suppressed CD4/CD8 ratio. IgG antibody titers against measles, mumps, rubella, and polio were present in almost all patients pretransplant and during 12 months post-transplant, indicating persistent humoral immunity. CD3(+) and CD8(+) counts of patients with clinical VZV reactivation ( n=5) post-transplant were significantly higher (median: 1201/microl and 938/microl, respectively) than in patients without VZV reactivation (median: 594/microl and 482/microl, respectively) 6-12 months post-transplant. Positive CMV titers pretransplant ( n=19) were also correlated with higher CD3(+) and CD8(+) counts 3-6 months post-transplant (median: 1050/microl and 1056/microl, respectively) compared to CMV-negative patients (738/microl and 584/microl, respectively), although none of the patients suffered from CMV disease. Therefore, we conclude that persistent viral infections can contribute to the CD8(+) T-cell reconstitution after PBSCT by oligoclonal expansion of antigen-specific memory CD8(+) T cells.

Adult↗

PubMed2004

Activation of humoral immunity and eosinophils in neuromyelitis optica.

OBJECTIVE: To study immunologic alterations in patients with neuromyelitis optica (NMO). METHODS: The authors studied 8 patients with NMO together with 16 healthy subjects, 16 patients with relapsing remitting multiple sclerosis (RRMS), and 16 patients with secondary progressive MS (SPMS), matched for age and sex, as controls. Because recent histopathologic studies have demonstrated that active NMO lesions consist of perivascular immunoglobulin (Ig) deposition and eosinophil infiltration, IL-5, IL-6, IL-12, IgG, and IgM production by anti-myelin oligodendrocyte glycoprotein (MOG) mononuclear cells in peripheral blood and CSF were selected for study using ELISPOT. Eotaxin-2 (Eo-2) and eotaxin-3 (Eo-3) levels were also assessed using ELISA and eosinophil cationic protein (ECP) levels by radioimmunoassay. RESULTS: MOG-specific responses in CSF showed significant increase in IL-5, IL-6, IgG, and IgM secreting cells in NMO patients compared with patients with RRMS, SPMS and healthy subjects. Interestingly, numbers of IgM secreting cells were significantly higher than identical specificity IgG secreting ones. Moreover, CSF Eo-2, Eo-3, and ECP levels were also significantly higher in NMO patients compared to all three control populations. Anti-MOG IL-12 secreting cells were increased in CSF and peripheral blood from NMO, RRMS, and SPMS patients when compared to healthy subjects. CONCLUSIONS: These observations suggest that neuromyelitis optica is associated with a major humoral immune response (particularly anti-MOG IgM production) and eosinophil activation present exclusively in CSF.

Adult↗

PubMed1994

Humoral immune responses to Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans in adult periodontitis and rapidly progressive periodontitis.

The relationships between various forms of periodontal disease and the avidities of serum antibodies of all 3 immunoglobulin (Ig) classes (IgG, IgM and IgA) to Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans were investigated. Twenty-four patients with untreated adult periodontitis and twelve untreated patients diagnosed as suffering from the early-onset form of periodontitis, rapidly progressive periodontitis, were studied. The latter group were matched for age and sex to healthy controls. Antibody titres were measured and avidity (expressed as molarity) was further assayed using the thiocyanate elution method. Avidity has previously been shown to relate to the biological function of antibody. IgM avidities to P. gingivalis were lower in the rapidly progressive periodontitis group than in the adult periodontitis group (0.54 M vs 0.74 M). IgG avidities tended to be lower in the former than in the latter group (0.58 M vs 0.92 M). In accordance with other workers, seropositivity was defined as an immunoglobulin titre more than twice the median level of control sera. Only 2 of the rapidly progressive periodontitis group were seropositive. Interestingly, the seronegative rapidly progressive periodontitis patients were significantly different (0.53 M vs 0.92 M). The data that patients with various forms of periodontal disease appear to produce antibodies of differing avidity to P. gingivalis suggest that the quality of the humoral immune response to suspected periodontopathogens may have a bearing on the aetiology of periodontal disease.

Adult↗

PubMed2006

Efficacy of protein A-HRP in an immunological study of black rockfish (Sebastes schlegeli Higendorf) humoral immune responses.

The efficacy of protein A-horse radish peroxidase (HRP), as compared to that of mouse polyclonal antibody raised against purified Ig, in detection of black rockfish (Sebastes schlegeli Higendorf) immunoglobulin (Ig) was examined. Protein A affinity chromatography successfully purified Ig from black rockfish serum; the purified-Ig could be visualised as two protein bands (MW 70 and 25kDa) following resolution with sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions. In SDS-PAGE immunoblot profiles of the purified-Ig, the mouse polyclonal antibody recognised both the light chain and heavy chains of rockfish Ig, whereas protein A-HRP immunostained only the heavy chain of rockfish Ig. These results suggest that protein A-HRP may be used to detect rockfish antibody-antigen complexes in immunoassays. In a 2-DE immunoblot assay for exploring antigenic profiles of Lactococcus garvieae KG9408, protein A-HRP successfully detected specific antibodies to antigenic proteins of L. garvieae in the rockfish Ig. In addition, enzyme linked immunosorbent assay (ELISA) showed a high correlation between the results obtained for positivity of L. garvieae when protein A-HRP and the mouse polyclonal antibody-was used to analyse samples from 25 diseased rockfish. These results collectively indicate that protein A-HRP has a high affinity for Ig, and may be useful for new investigations into the humoral immune responses of rockfish.

Animals↗

PubMed2002

Persistent rat cytomegalovirus (RCMV) infection of the salivary glands contributes to the anti-RCMV humoral immune response.

The salivary glands are the major sites of persistent replication of rat cytomegalovirus (RCMV). At several months post infection (pi), infectious RCMV is usually still produced in the salivary glands but not in any other organ or tissue of the rat. To investigate whether the persistence of RCMV in the salivary glands is crucial to the pathogenesis of viral infection, we monitored the progression of RCMV-induced disease in rats from which the salivary glands had been surgically removed (desalivated) as well as in sham-operated rats, both after a lethal and sublethal challenge with RCMV. Desalivation did not have a significant effect on either RCMV-induced morbidity or mortality. As expected, at 1 year pi, relatively high levels of infectious virus were detected in the salivary glands of sham-operated rats, whereas neither infectious virus nor RCMV DNA could be detected in liver, spleen and lungs of these animals. Infectious virus and viral DNA were also undetectable in organs from desalivated animals at 1 year pi. Surprisingly, a difference was found between desalivated and sham-operated rats in the titers of anti-RCMV IgG antibodies, which were significantly higher in sham-operated rats than in desalivated animals at 183, 295 and 365 days pi. This finding indicates that the persistence of RCMV in the salivary glands may contribute significantly to the anti-RCMV humoral immunity of infected rats.

Animals↗

PubMed2002

Human herpesvirus-6 infection in neonates: Not protected by only humoral immunity.

BACKGROUND: Infants are usually protected from various viral infections, including human herpesvirus-6 (HHV-6) and human herpesvirus-7 (HHV-7) infections, during the early infantile period by antibodies transferred from their mothers. However, rare cases of exanthem subitum (ES) in neonates have been described in published reports. METHODS: From the infantile patients of febrile illness, HHV-6 and HHV-7 DNA were examined by the polymerase chain reaction method. Antibodies to HHV-6 and HHV-7 were detected by indirect immuno-fluorescence assay and neutralization test. Viral isolation was attempted from the patient's peripheral blood mononuclear cells (PBMC) during the acute phase of febrile illness. RESULTS: Human herpesvirus-6 was verified virologically in two neonates who were clinically diagnosed as ES within the first month of life. Although high copies of HHV-6 DNA were detected in their PBMC during the acute phase, the isolation of HHV-6 from their PBMC was not successful. Neutralizing antibodies to HHV-6 were detected in sera of the acute phase, and those antibodies were considered to be transferred from their mothers. Antibody titers showed fourfold elevation in sera of the convalescent phase. The HHV-6 infection occurred despite the presence of pre-existing maternal antibody. Human herpesvirus-7 and HHV-7 DNA were not detected from their clinical samples. CONCLUSIONS: This observation suggests that HHV-6 infection could not be protected by only humoral immunity.

Antibodies, Viral↗

PubMed2001

Adventitial infiltrates associated with advanced atherosclerotic plaques: structural organization suggests generation of local humoral immune responses.

Advanced atherosclerotic lesions often contain adventitial lymphoid infiltrates, which occasionally contain nodular aggregates resembling lymphoid follicles. The structural organization suggests that local maturation of B cells may take place at these sites, as described for the mucosa-associated lymphoid tissue (MALT). This concept was evaluated by studying the micro-anatomy and cellular composition of adventitial infiltrates associated with advanced atherosclerosis of the aorta. Sections of 22 atherosclerotic aortas were stained immunohistochemically for cellular markers characteristic for lymphoid follicles, such as HECA-452-positive endothelial cells, CD20-positive B cells, CD21-positive follicular dendritic cells, and CD68-positive macrophages. Ki-67 was used as a proliferation marker. The TUNEL technique was used to study the presence of apoptotic cells. Specimens containing MALT served as comparison and positive controls. Seven of the 22 atherosclerotic aortas contained adventitial infiltrates resembling lymphoid follicles. The organized nodular centres were composed of CD45RA+ B cells, follicular dendritic cells (CD21+), a few T lymphocytes (CD3+) and 'tingible body' macrophages (CD68+). A large number of cells were Ki-67-positive; apoptotic bodies were numerous and phagocytosed by macrophages. The parafollicular area contained CD45RO-positive T cells and HECA-452-positive vessels. Vessels elsewhere were always HECA-452-negative. Specimens with MALT showed similar features. This study reveals a close resemblance between adventitial lymphoid infiltrates in advanced atherosclerotic aortic disease and MALT, suggesting local generation of a humoral immune response, likely to be initiated by antigens released during a process of long-standing tissue injury and inflammation as part of advanced atherosclerosis.

Adult↗

PubMed1997

The Mycoplasma hominis P120 membrane protein contains a 216 amino acid hypervariable domain that is recognized by the human humoral immune response.

In the antigenically heterogeneous species Mycoplasma hominis a monoclonal antibody, mAb 26.7D, was previously found to recognize a 120 kDa polypeptide from M. hominis 7488. This antibody did not react with the type strain PG21. The homologous gene from M. hominis PG21 was cloned and sequenced and found to have a sequence identity of 91% with the gene of strain 7488. One hypervariable and two semivariable regions were detected. The epitope for mAb 26.7D was mapped to the hypervariable domain by expression of various parts of this domain in Escherichia coli using expression vector systems. A polyclonal antiserum (pAb 121) generated against the hypervariable region of P120 from PG21 identified the P120 homologue in M. hominis PG21. Fusion proteins of the hypervariable and constant parts of the proteins were constructed and tested for reactivity with 21 human sera. Twelve sera reacted with the 7488 hypervariable fusion protein, but only four reacted with PG21 hypervariable fusion protein. No reactivity was seen with a fusion protein containing part of the constant region of P120. Gene fragments amplified from 18 M. hominis isolates by PCR confirmed the heterogeneity of the hypervariable domain. Based on restriction endonuclease cleavage patterns of the hypervariable domain the 18 isolates could be divided into four cases. Reactivity with both mAb 26.7D and pAb 121 confirmed these classes. The hypervariable, but not the constant, part of P120 was recognized by the human humoral immune response. Such a variable domain may be important in evasion of the host's immune response, and thus aid survival of the micro-organism.

Amino Acid Sequence↗

PubMed1992

The variable C-terminal region of the Mycobacterium leprae 70-kilodalton heat shock protein is the target for humoral immune responses.

The 70-kDa heat shock protein of Mycobacterium leprae has a high degree of homology with the human hsp70 protein, yet it still elicits T-lymphocyte responses in subjects infected with M. leprae or vaccinated with the related Mycobacterium bovis BCG. We examined the serological responses to this protein by using recombinant protein fragments expressed from mutants with deletions of the M. leprae p70 gene. Monoclonal antibodies raised against either M. bovis or M. leprae p70 reacted with the C-terminal fragments but not the N-terminal fragments in a solid-phase enzyme-linked immunosorbent assay and an immunoblot assay. Inhibition enzyme-linked immunosorbent assays confirmed that two separate epitopes were defined by these monoclonal antibodies. Murine polyclonal sera also showed stronger binding to the C-terminal fragments. Sera from 33 and 48% of lepromatous leprosy patients reacted with M. leprae and M. bovis p70. This reactivity was mycobacterium specific, since few sera from control subjects in the same leprosy-endemic region were seropositive. The levels of anti-mycobacterial hsp70 antibodies were higher in patients with lepromatous leprosy than in those with tuberculoid leprosy or tuberculosis. The reactivity of sera from patients with leprosy was maximal with the C-terminal fragments. Therefore the C-terminal portion of M. leprae hsp70, which includes the region of maximum divergence from human hsp70, is the major target for the humoral immune response to the protein.

Animals↗

PubMed2001

The impact of H2-DM on humoral immune responses.

H2-DM (DM, previously H2-M) facilitates the exchange of peptides bound to MHC class II molecules. In this study, we have used H2-DM-deficient (DM(-/-)) mice to analyze the influence of DM in the priming of B cell responses in vivo and for Ag presentation by B cells in vitro. After immunization, IgG Abs could be raised to a T-dependent Ag, 4-hydroxy-5-nitrophenylacetyl-OVA, in DM(-/-) mice, but closer analysis revealed the IgG response to be slower, diminished in titer, and composed of low-affinity Abs. The Ab response correlated with a vast reduction in the number of germinal centers in the spleen. The presentation of multiple epitopes by H2-A(b) from distinct Ags was found to be almost exclusively DM-dependent whether B cells internalized Ags via fluid phase uptake or using membrane Ig receptors. The poor B cell response in vivo could be largely, but not completely restored by expression of a H2-Ea(d) transgene, despite the fact that Ag presentation by H2-E(d/b) molecules was found to be highly DM dependent. Hence, while substantial Ab responses can be raised in the absence of DM, this molecule is a crucial factor both for Ag processing and for the normal maturation of T-dependent humoral immune responses in vivo.

Animals↗

PubMed1995

Effects of the whole extract and the chromatographic fractions of the pig placenta on lymphocyte proliferation and humoral immune response.

The immunoregulatory properties of pig fetal placenta extracts (PE) from 1 st, 2nd and 3rd month of pregnancy and five fractions (F1 to F5), isolated on Sephadex G-200 and additionally characterized by fast performance liquid chromatography, FPLC (Superose 12 HR) were studied in order to clarify the local immune regulation in diffuse epitheliochorial placentation. The obtained substances were added at 6.25 to 100 microg in cultures of Concanavalin A-stimulated mouse splenocytes and Phytohemagglutinin-stimulated pig and human PBL to monitor their influence on [(3)H]Thimidine uptake in proliferating lymphocytes. Their effects on the number of plaque-forming cells in spleen cell suspensions from mice treated ip simultaneously with sheep red blood cells and with 100 microg protein of PE, respectively, of each fraction were also investigated: PE and F1 had no effect while F4 and F5 suppressed the mitogen-induced lymphocyte proliferation in all studied species. F2 and F3 stimulated mouse and pig lymphocyte proliferation. The effects were dose-dependent and the suppression was not due to cytotoxic effects. The FPLC data allowed the suggestion that 110 kD protein(s) were involved in stimulation and 7 kD substance(s) - in suppression of cell proliferation. The PE from the 3 studied periods as well as the 5 fractions increased significantly the primary humoral immune response against T-dependent antigen. The results revealed that trophoblast of epitheliochorial placenta produces simultaneously immuno-stimulatory and -suppressive factors acting across the species barrier. Their presence at the feto-maternal interface may contribute to the regulation of local immune reactions and survival of the allogenic fetuses despite the morphological specificities of this type of placentation.

Journal Article↗

PubMed2004

Benzo[a]pyrene-induced immunotoxicity in Japanese medaka (Oryzias latipes): relationship between lymphoid CYP1A activity and humoral immune suppression.

Exposure to the environmental contaminant benzo[a]pyrene (BaP) results in suppression of immune function in both mammalian and fish species. This laboratory has previously demonstrated that a single intraperitoneal (IP) injection of BaP reduced lymphocyte proliferation, phagocyte-mediated superoxide generation, and antibody-forming cell (AFC) numbers in Japanese medaka (Oryzias latipes). The objective of the current study was to determine the role of BaP metabolism in the observed immunosuppression. Results from rodent studies have suggested that BaP elicits its immunotoxic effects via upregulation of cytochrome P4501A1 (CYP1A1) and the subsequent production of immunosuppressive BaP metabolites. In this study, exposure of medaka to 200 microg BaP/g BW significantly induced CYP1A expression or activity within lymphoid tissue 48 h post-IP injection; induction was observed specifically within distinct subpopulations of kidney mononuclear cells. Concurrent injection of fish with BaP and the CYP1A1 inhibitors alpha-naphthoflavone (ANF) or dehydroepiandrosterone (DHEA) resulted in inhibition of renal EROD activity and amelioration of BaP-induced suppression of medaka AFC numbers. Results of this study suggest that (1) BaP-induced suppression of medaka humoral immunity relies upon the CYP1A-catalyzed production of immunotoxic BaP metabolites and (2) BaP metabolites may be created in situ, directly by specific cells within kidney lymphoid tissue. Thus, apparently, mechanisms involved in BaP-induced immunosuppression have been phylogenetically conserved from fish to mammals.

Animals↗

PubMed2006

Dissociation of lung function changes with humoral immunity during inhaled human insulin therapy.

RATIONALE: Inhaled human insulin (INH; Exubera [human insulin (recombinant DNA origin) Inhalation Powder]) causes small changes in pulmonary function and increases in insulin antibodies compared with subcutaneous (SC) insulin. OBJECTIVES: To investigate the relationship between changes in pulmonary function and insulin antibodies and acute effects of INH on lung function. METHODS: In a 24-wk multicenter study, 226 patients with type 1 diabetes were randomized to receive daily premeal INH or SC insulin for 12 wk (comparative phase), followed by SC insulin for 12 wk (washout phase). MEASUREMENTS: Spirometry tests were conducted and insulin antibody levels were measured throughout the study. Acute insulin-induced changes in lung function were calculated as the difference between FEV1 before, and 10 and 60 min after, insulin. MAIN RESULTS: There was a temporal dissociation between pulmonary function changes and insulin antibody generation. Small treatment group differences in changes in FEV1 from baseline, favoring SC insulin, were fully manifest by 2 wk of INH therapy, did not increase during the remainder of the comparative phase, and resolved within 2 wk of INH discontinuation. By contrast, insulin antibody levels remained low for the first 2 wk with INH, increased during Weeks 2 to 12, and gradually declined during washout. There was no evidence of acute insulin-induced alterations in lung function 10 and 60 min postinhalation. CONCLUSION: The small lung function changes observed with INH therapy are not mediated by the humoral immune response, or associated with acute decrements in lung function immediately after insulin inhalation.

Administration, Inhalation↗

PubMed2005

Humoral immune response in acute hepatitis C virus infection.

BACKGROUND: There is little information on the timing, magnitude, specificity, and clinical relevance of the antibody response to acute hepatitis C virus (HCV) infection. We investigated the specificity, titer, and neutralizing potential of antibody responses to acute infection by examining 12 injection drug users before, during, and after infection. METHODS: Seroconversion was defined as incident detection of HCV-specific antibodies by using a commercially available enzyme-linked immuosorbent assay (ELISA). HCV protein-specific antibody responses were measured using recombinant antigens in an ELISA. For neutralization assays, plasma was incubated with human immunodeficiency virus (HIV)-HCV H77 or control HIV-murine leukemia virus (MLV) pseudotype virus and then allowed to infect Hep3B hepatoma cells. RESULTS: The mean time to HCV seroconversion was 6 weeks after the onset of viremia. Antibody responses to nonstructural proteins were detected before responses to the structural proteins, and antibodies to both were primarily restricted to the immunoglobulin G1 (IgG1) subclass. The maximum median end point titers for antibody responses to structural and nonstructural proteins were 1 : 600 and 1 : 6400, respectively. Antibodies that neutralized a retroviral pseudotype bearing HCV 1a envelope glycoproteins were detected at seroconversion in only 1 subject and at 6-8 months after seroconversion in 3 subjects. The delayed appearance of neutralizing antibodies was consistent with the late development of antibodies specific for the viral envelope glycoproteins, which are believed to mediate virus neutralization. CONCLUSION: The humoral immune response to acute HCV infection is of relatively low titer, is restricted primarily to the IgG1 subclass, and is delayed. A better understanding of why production of neutralizing antibody is delayed may improve efforts to prevent HCV infection.

Acute Disease↗

PubMed2006

Humoral immune reaction of newborn calves congenitally infected with Neospora caninum and experimentally treated with toltrazuril.

Neospora caninum is widely recognized as one of the most important infectious organisms causing abortion and stillbirth in cattle. This parasite causes severe economical losses worldwide. Infection is mostly passed vertically from mother to calf during pregnancy. Under certain circumstances, an infection can lead to abortion, but in most cases it results in a chronically infected calf, which itself will represent the next endogenously infectious generation. So far, no reliable therapeutic or metaphylactic tool has been developed. One possibility to control the problem may consist of treating newborn calves that became vertically infected by a persistently infected mother. This may allow parasite-free offspring. The aim of the present study was to address the questions: (1) can serology be used to assess efficiency of treatment in toltrazuril-medicated animals? and (2) is a strategic prevention measure possible by means of producing N. caninum-free calves from positive cows? Calves from Neospora-seropositive cows and heifers were randomly split into two different medication groups: 36 calves were medicated with toltrazuril and 36 calves obtained a placebo. Medication (20 mg toltrazuril per kg bw) was administered three times, every second day, within the 7 days post natum. Three months after medication, there was no difference in antibody reactivity between the two groups. At later time points (4-6 months), however, significant differences were found, as explained by a strong humoral immunity after chemotherapeutical affection of parasites, while the placebo-treated animals only responded weakly to the persistent infection. In summary, we concluded that (1) serology was not an entirely appropriate tool to answer our initial question and (2) toltrazuril has the potential to eliminate N. caninum in newborn calves. As a consequence, we plan to follow up toltrazuril-medicated calves clinically and serologically over a longer period and investigate if they give birth to Neospora-free calves.

Abortion, Veterinary↗

PubMed1986

Genetic predisposition to diabetes mellitus is associated with impaired humoral immunity to coxsackievirus B4.

Experiments were performed to determine whether genetic predisposition to diabetes mellitus (DM) or clinical DM or both exert an influence on the production of neutralization antibodies to coxsackievirus B4 (CB4). The homozygous diabetic mutant mouse db+/db+, on the inbred C57BL/KsJ genetic background, develops a diabetes-like disease when maintained on ad libitum diet but restriction of excess food intake prevents overt disease. The doubly heterozygote db+/+m or the homozygote +m/+m misty coat color mutant, on the C57BL/KsJ genetic background, do not develop DM and served as controls. Animals infected with one-half a previously determined LD50 of CB4 were bled prior to infection and at 3, 5, 7, 14, 21 days and at 1, 2, 3, 4 and 5 months after infection. Serum neutralization antibody (NA) levels were determined from the percent CB4 plaque reduction. Until 2 months following infection, NA levels were not significant in either of the homozygous diabetic mutant groups, db+/db+. In the diabetic mutant group db+/db+, without overt disease, neutralization of CB4 when observed, was low, short-lived, and apparently not specific. However, in the homozygous diabetic mutants with spontaneous diabetes, CB4 NA became evident at 2 months after infection. By 3 months post-infection, serum NA levels were sufficient to cause 90% virus plaque reduction. These observations demonstrate that hereditary DM as characterized by the mutation diabetes, db, in the C57BL/KsJ mouse, is associated with a marked impaired humoral immune response to a diabetogenic human CB4. Specifically, there is an inability to develop an adequate level of anti-CB4 antibodies. The type and degree of immunological impairment are apparently different prior to and after onset of diabetes mellitus.

Animals↗