bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune responses of cattle to biochemically modified antigens from the midgut of the cattle tick, Boophilus microplus
Authors: LEE R.P. , JACKSON L.A. , OPDEBEECK J.P.
Published: October 2007

Summary Treatment of membrane antigens of the midgut (GM) of the cattle tick, Boophilus microplus with sodium metaperiodate (periodate). pronase and lipase significantly inhibited the reactivity of the GM with antibodies in the sera of 57 cattle vaccinated with GM. Treatment of GM with periodate only removed the correlation between antibody reactivity of sera and protection against infestation with licks. A monoclonal antibody (MoAb QU13). which recognises protective antigens solubilized from GM (Lee & Opdebeeck 1991), did not react with GM treated with penodate. Cattle vaccinated with GM extracts were significantly protected against infestation with cattle licks (P < 005), whereas cattle vaccinated with either GM extracts treated with periodate or with antigens precipitated from GM extracts with MoAb QU13 and also treated with periodate, were not protected against infestation. These studies provide preliminary evidence that protective antigens in the lick midgut membrane either are carbohydrate or arc dependent on carbohydrate for their specificity.
Determination of the immunization schedule for field trials with the synthetic malaria vaccine SPf 66
Authors: ROCHA C.L. , MURILLO L.A. , MORA A.L. , ROJAS M. , FRANCO L. , COTE J. , VALERO M.V. , MORENO A. , AMADOR R. , NUÑEZ F. , CORONELL C. , PATARROYO M.E.
Published: October 2007

Summary The synthetic malaria vaccine SPf 66 has been shown to be safe, immunogenic and effective in trials performed with controlled groups naturally and experimentally exposed to the disease. In order to continue the trials in open populations, it was necessary to standardize the vaccination characteristics. We have performed four field trials with soldier volunteers with the aim, among others, of defining the number of doses required, the intervals between applications, the protein concentration, and the adjuvant to be used. In these trials, the vaccinated individuals' immune responses were evaluated by assaying anti‐SPf 66 antibody titres, in vitro growth inhibition of the P. falciparum parasite, and the vaccinees' capacity to recognize P. falciparum native proteins. From these results we conclude that the best vaccination schedule, for adults, is three doses administered subcutaneously on days 0, 30 and 180, each containing 2 mg of the synthetic polymerized petide SPf 66 adsorbed to alum hydroxide.
Brugia pahangi infections in immune‐compromised rats demonstrate that separate mechanisms control adult worm and microfilarial numbers
Authors: LAWRENCE RACHEL , DENHAM D.A.
Published: October 2007

Summary The immunological basis of resistance to Brugia pahangi infection in rats was studied. Infections were investigated in athymic rnu/rnu rats and in rats treated with the immuno‐suppressive agents cyclosporin A (CsA) or cyclophos‐phamide (Cy). The recovery of adult worms in normal rats was 1–2% in comparison to 12.2% recovery in athymic rats. CsA and Cy treated rats did not have increased adult worm burdens. Microfilarial (Mf) levels (expressed as Mf per ml per adult worm) were highly elevated in both athymic and Cy treated rats but not in CsA treated rats. IgG and IgM levels to B. pahangi antigens were severely depressed in both athymic and Cy treated rats. IgG levels but not IgM levels were abrogated in CsA treated rats. These results implied that control of larval establishment or adult killing, and regulation of Mf levels are separate T‐cell dependent mechanisms and act independently of IgG antibody. Control of Mf levels is associated with a specific IgM response which is Cy sensitive but CsA resistant.
Transmission blocking immunity to human Plasmodium vivax malaria in an endemic population in Kataragama, Sri Lanka
Authors: GAMAGE‐MENDIS ASOKA C. , RAJAKARUNA JAGATH , CARTER RICHARD , MENDIS KAMINI N.
Published: October 2007

Summary Serum effects on gametocyte infectivity, that is, transmission blocking/enhancing immunity, were measured in the sera of 196 acute Plasmodium vivax patients who were residents of a malaria region in Kataragama, southern Sri Lanka. Direct mosquito feedings were also performed on 170 of these patients. Sera of about 48% of patients suppressed gametocyte infectivity significantly (by more than 75%) and of a smaller proportion (12%) had pronounced infectivity enhancing effects. Transmission immunity did not increase with age of patients, rather, immunity tended to be higher in younger patients. Data suggest that immunity levels are boosted by reinfections only if they occur within a period of 4 months from the previous infection, i.e., that immune memory for boosting does not last beyond 4 months. Enhancing effects in the sera of patients correlated with the absence of gametocytes at the time of investigation suggesting that enhancement occurs early during the course of a blood infection, and blocking later, when serum antibodies reach higher levels. The blocking and enhancing effects of a serum appears to depend not only on the antibody concentration in serum, but also on the intrinsic infectivity of the parasite isolate against which it is tested: thus, infectivity enhancing effects were potentiated by low intrinsic infectivities of the parasite isolate. The direct infectivity of patients to mosquitoes correlated with transmission immunity indicating that transmission immunity is an influential factor determining infectivity of malaria patients.
The influence of challenge dose, duration of immunity, or steroid treatment on mucosal mast cells and on the distribution of sheep mast cell proteinase in Haemonchus‐infected sheep
Authors: HUNTLEY J.F. , NEWLANDS G.F.J. , JACKSON F. , MILLER H.R.P.
Published: October 2007

Summary The distribution of granule‐specific sheep mast cell proteinase (SMCP). was assayed by immunocytochemistry and quantified by immunoassay in sheep immune to Haemonchus contortus. Repeated infection with Haemonchus larvae over 10–12 weeks induced a pronounced mucosal mastocytosis, including intraepithelial globule leukocytes (GL), which. 7 days after ceasing this dosing regime, was associated with the inability of incoming larvae to establish within the abomasal mucosa. Loss of this resistance, due to the cessation of stimulation with Haemonchus larvae 84 days previously or to treatment of sheep with cortico‐steroid. was associated with a marked decline in mast cell density and concentrations of SMCP in abomasal mucosal tissues. Nevertheless, larvae also failed to establish in immune sheep rested from challenge 42 days previously and in which mast cell counts were not significantly different from those of control sheep. A small, but significant, release of SMCP was demonstrated in gastric mucus from immune sheep following larval challenge, whereas little or no SMCP was detected in mucus from naïve animals.
Demonstration of Leishmania specific cell mediated and humoral immunity in asymptomatic dogs
Authors: CABRAL M. , O'GRADY J. , ALEXANDER J.
Published: October 2007

Summary An ELISA and a lymphocyte proliferation assay were used for the detection of anti‐Leishmania antibodies and parasite specific cellular immunity respectively in a preliminary study of canine leishmaniasis in Oporto, Portugal. A high rate of infection was found considering the comparatively small group sampled. Of 34 dogs examined two had anti‐leishmanial antibodies but their lymphocytes did not proliferate in the presence of Leishmania infantum. Conversely two dogs demonstrated antigen specific lymphocyte proliferation in the absence of any detectable anti‐parasite antibodies. To our knowledge this is the first time that cellular immunity and presumably resistance of dogs to leishmanial infection has been demonstrated. These results suggest that there may be a spectrum of canine leishmaniasis similar to that observed in the human disease.
The influence of adjuvant on humoral responses to glutathione‐S‐transferase fusion proteins
Authors: VARLEY C.A. , DUNNE D.W. , HAVERCROFT J.C.
Published: October 2007

Summary Mice were immunized with one of two Schistosoma mansoni antigens, Sm20 and Sm50, expressed as fusion proteins with Schistosoma japonicum 26 000 Dalton glutathione‐S‐transferase (GST) or with GST alone. Antibody responses to GST were shown to be critically dependent on the adjuvant used. In Sm20‐GST immunized mice, we noted a striking bias to respond either to Sm20 or to GST according to the adjuvant used and responses to both in the same individual were rare. Fusion with Sm50, which is relatively non‐immunogenic, appeared to down‐regulate responses to GST.
The destruction of virulent Entamoeba histolytica by activated human eosinophils
Authors: LÓPEZ‐OSUNA MARTHA , ARELLANO JORGE , RETSCHMER ROBERTO R.K
Published: October 2007

Summary Unlike normal (i.e., non‐activated) human eosinophils that are unable to destroy virulent Entamoeba histolytica even in the presence of antibodies and complement, activated eosinophils effectively destroy the parasite in vitro without the help of opsonins, yet increase this capacity with their assistance. Many activated eosinophils succumb in the process as well, probably victims of toxic products released by dying amoebae. Human activated eosinophils thus behave more like activated macrophages than like neutrophil polymorphonuclear leucocytes that are notoriously incompetent in dealing with virulent amoebae. As a regular constituent of early inflammatory reactions, and notwithstanding the absence of blood and tissue eosinophilia in invasive amoebiasis, the activated eosinophil may play a role in the defence against E. histolytica.
Potent immunosuppression by secretory/excretory products of larvae from the sheep blowfly Lucilia cuprina
Authors: KERLIN ROY L. , EAST IAIN J.
Published: October 2007

Summary Secretory/excretory products (sec/ex) of parasitic larvae of the sheep blowfly Lucilia cuprina potently inhibited proliferation of peripheral blood leucocytes stimulated by mitogens in vitro. Suppression of proliferation was not due to irreversible damage because cells cultured for 24 h in high concentrations of sec/ex appeared viable (assessed by Trypan blue exclusion) and did not show impaired proliferation after washing. Furthermore, suppression induced by sec/ex could be overcome by increasing concentrations of mitogen. The inhibitory activity could be demonstrated in cultures where sec/ex was added at different times during the culture period. Inhibitory activities in sec/ex were heat‐labile and sensitive to treatment with trypsin. In addition to effects in vitro, sec/ex was strongly immunosuppressive in vivo. Sheep given combined injections of myoglo‐bin and sec/ex had markedly lower anti‐myoglobin antibody levels in sera than sheep that received injections of myoglobin alone. There was no significant antibody response to sec/ex itself. Immunosuppressive moieties in sec/ex produced by blowfly larvae may promote parasite survival by inhibiting the immune response of host sheep.
Isotypic variation in antibody responses in a community in Papua New Guinea to larval and adult antigens during infection, and following reinfection, with the hookworm Necator americanus
Authors: PRITCHARD D.I. , WALSH E.A. , QUINELL R.J. , RAIKO ANDREW , EDMONDS P. , KEYMER A.E.
Published: October 2007

Summary The natural infection of a community with the hookworm Necator americanus induces a vigorous humoral response to both larval and adult parasite antigens. This response occurs in all five human antibody isotypes, and data are presented to show that, at the population level, isotypes respond differently, following chemotherapy and during reinfection, to changes in antigen stimulation. The differential response probably reflects the fact that the parasite, during the course of its life cycle, presents different amounts of antigens at different anatomical locations. It is suggested that IgG and IgM responses against adult excretory‐secretory (ES) products most accurately reflect the efficacy of chemotherapy, and the load of resident adult infection, while IgG responses against larval somatic antigens reflect continuous exposure to infection. These hypotheses should now be tested, at the level of the individual, in a longitudinal manner using more closely spaced sampling intervals. This repetitive sampling, and the inclusion of a measure of the exposure of the population to infective stages, will allow more definitive conclusions to be made about the role of the immune response in controlling worm burdens.
Fasciola hepatica in the rat: immune responses associated with the development of resistance to infection
Authors: KEEGAN P.S. , TRUDGETT A.
Published: October 2007

Summary F. hepatica infections were established in rats and immune responses were monitored during primary and challenge infections. Antibody levels peaked at 3 weeks post‐primary infection and at 6 days post‐challenge infection. No significant correlation was found between antibody titre and number of flukes recovered at autopsy. Immunoblotting revealed a limited number of immunoge‐nic polypeptides. When antibodies from these reactive bands were eluted and tested by IFA they all gave identical binding patterns: on juvenile fluke sections tegumental syncytium. tegumental cells and gut cells were labelled, while on adult sections the same antibodies labelled gut cells, reproductive tissue, excretory ducts and flame cells. This suggested that these tissues shared a common epitope or range of epitopes. A pronounced eosinophilia was observed throughout the infection period studied and infected liver sections showed massive cellular infiltration. Histochemical and immunocytochemical investigation of infected liver revealed the presence of large numbers of eosinophils, neutrophils, lymphocytes and phagocytes. The implications of these findings, to an understanding of concomitant immunity in the rat are discussed.
Cytokines inhibit the development of trophozoite‐infected cells of Theileria annulata and Theileria parva but enhance the proliferation of macroschizont‐infected cell lines
Authors: PRESTON PATRICIA M. , BROWN C.G.D. , RICHARDSON WENDY
Published: October 2007

Summary The following bovine (Bo) and human (Hu) cytokines—Bo rTNF‐a, Bo rIFN‐g, Hu IFN‐a, Hu rIL‐1, Hu rIL‐2—significantly inhibited the in vitro development of trophozoite‐infected cells of three stocks of Theileria annulata and of Theileria parva (Muguga). However, none of these cytokines inhibited the proliferation of established T. annulata or T. parva macroschizont‐infected cell lines. Indeed, Bo rTNF‐a and Hu rIL‐2 consistently enhanced the proliferation of macroschizont‐infected cell lines of both species and the blastogenesis of uninfected lymphocytes in trophozoite‐infected cultures. These results suggest that cytokines could help in resistance to challenge infections by preventing the further development of trophozoite‐infected cells but provide no evidence that any of the above cytokines directly help to resolve primary infections by inhibiting the growth of macroschizont‐infected cells. These findings also suggest that both TNF‐a and IL‐2 could play a role in the pathogenesis of Theileria infections by promoting the proliferation of macroschizont‐infected cells and the associated lymphoid hyperplasia.
Nutrition, immunity and helminth infection: effect of dietary protein on the dynamics of the primary antibody response to Trichuris muris (Nematoda) in CBA/Ca mice
Authors: MICHAEL E. , BUNDY D. A. P.
Published: October 2007

Summary The effect of dietary protein on the specific antibody responses (total immunoglobulins, IgGI and IgA) to the intestinal nematode Trichuris muris was studied in CBA/Ca mice fed isocaloric diets containing 16% or 4% protein. Mice fed the 16% diet and given a high infection dose of 650 eggs expelled almost their entire primary infection by day 21 post infection. In similarly infected animals fed the 4% protein diet, there was prolonged survival of adult worms. At a low infection dose of 10 eggs, there was no evidence of an expulsion response in either dietary group. The primary antibody response to parasite excretory/secretory (E S) antigen was time‐dependent, regardless of dietary protein or infection dose, and was predominantly an IgGI response. Within each dietary group, antibody production and antigen recognition occurred earlier and the antibody responses were more intense in mice given the higher infection dose. The principal finding was that the specific antibody response was more vigorous, both quantitatively (serum titres) and qualitatively (antigen recognition by IgGI), in mice on a low protein diet, even though worm expulsion did not occur in these hosts. This result suggests that serum antibody level or antigen recognition is not related simply to protective immunity against T. muris in CBA/Ca mice.
Analysis of the specificity of the salivary antigens of Ornithodoros erraticus for the purpose of serological detection of swine farms harbouring the parasite
Authors: PÉREZ‐SÁNCHEZ R. , OLEAGA‐PÉREZ A. , ENCINAS‐GRANDES A.
Published: October 2007

Summary In Spain, considerable efforts are currently being devoted to the eradication of Ornithodoros erraticus from the swine farms harbouring this parasite, the European vector of African swine fever (ASF). However, to do so, a preliminary requirement is to determine on which farms it is present. Of all possible methods for discovering this, the only one feasible for large scale application is the serological detection of swine bearing anti‐O. erraticus antibodies. To apply serology it was necessary to check the specificity of extracts from the salivary glands (SGE) from O. erraticus. For this, indirect ELISA, competitive ELISA and Western blot were used to assay the SGE from O. erraticus and their corresponding antisera against the SGE and respective antisera from 4 ixodidae, one mange mite, one louse and a mosquito. The results obtained show that only the anti‐ixodidae sera are able to react against the SGE from O. erraticus. The cause of this reaction are the somatic antigens present in the SGE of the argasid but not its soluble (secretory) antigens. It is proposed that the anti‐cement antibodies present in the anti‐ixodidae sera are those that react with the somatic antigens of O. erraticus.
T lymphocyte dependent enteropathy in murine Trichinella spiralis infection
Authors: GARSIDE P. , GRENCIS R. K. , MOWAT A. McI.
Published: October 2007

Summary Mice infected with Trichinella spiralis developed significant enteropathy, comprising villus atrophy, crypt hyperplasia, goblet cell hyperplasia and a decrease in intra‐epithelial lymphocyte numbers by 10 days post‐infection, when most of the parasites had been expelled from the gut. However, worm expulsion was prevented by treatment with cyclosporin A and, despite a continued parasite burden, cyclosporin A treated animals had no villus atrophy or changes in inflammatory cell numbers. These results confirm that the expulsion of T. spiralis from the mouse gut is accompanied by a significant intestinal lesion and that both of these phenomena are T‐cell mediated.
Cats with single Brugia pahangi infections: relationship between parasitological status and humoral responses to somatic and surface parasite antigens
Authors: FLETCHER C. , BIRCH D. W. , DENHAM D. A.
Published: October 2007

Summary Cats given a single inoculation of Brugia pahangi infective larvae (L3) were retrospectively allocated into three groups according to parasitological outcome of infection. Recognition of somatic and surface antigens of B. pahangi by sera from each group was compared by ELISA, immunoelectroblotting, and immunoprecipitation techniques.

In cats that never became microfilaraemic mean serum IgG antibody levels against somatic extracts from adult male worms. L3, and microfilariae (mf) were higher than levels in cats that initially became microfilaraemic (mf+ve) then spontaneously became nonmicrofilaraemic (mf‐ve). The lowest levels of antibody against each stage were found in cats that remained persistently mf+ve.

Antigenic components of 18 kD and 22 kD in somatic extracts of adult worms and L3 were recognized by sera from cats that never became mf+ve and by spontaneously mf‐ve cats, but not by sera of persistently mf+ve cats.

When radioiodinated surface antigens of mixed adult worms and microfilariae were immunoprecipitated by sera from cats in the three groups, no correlation was observed between recognition of individual antigen components and parasitological outcome of infection.
Arginine‐dependent generation of reactive nitrogen intermediates is instrumental in the in vitro killing of protoscoleces of Echinococcus multilocularis by activated macrophages
Authors: KANAZAWA T. , ASAHI H. , HATA H. , MOCHIDA K. , KAGEI N. , STADECKER M. J.
Published: October 2007

The interaction between protoscoleces of Echinococcus multilocularis and activated murine macrophages was examined in this study. Marked protoscolicidal activity was displayed by peritoneal macrophages (PM) activated with interferon‐γ (IFN‐γ), or IFN‐y plus lipopolysaccharide. Pretreatment of the parasites with heat‐inactivated specific murine infection serum, but not with normal serum rendered them more susceptible to PM killing. NG‐monomethyl‐Larginine, a competitive inhibitor of L‐arginine completely inhibited the killing activity of activated PM. while reconstitution of arginine‐free medium with L‐arginine restored the killing properties of the activated PM. The results show that activated PM have the ability to kill E. multilocularis protoscoleces in vitro and suggest that reactive nitrogen intermediates (RNl) play an important role in the mechanism. An oxygen‐mediated mechanism did not appear to play a role because scavengers of reactive oxygen species did not reduce the killing activity. The arginine‐dependent killing mechanism was enhanced by superoxide dismutase (SOD), probably because SOD might prolong the effect of nitric oxide. Secretion of RNI by activated macrophages may be capable of a significant role in preventing of the dissemination of E. multilocularis infection in vivo.
Antibody responses to invariant antigens of Trypanosoma congolense in cattle of differing susceptibility to trypanosomiasis
Authors: AUTHIÉE EDITH , MUTETI DAVID K. , WILLIAMS DIANA J. L.
Published: October 2007

Five trypanotolerant N'Dama (Bos taurus) and five susceptible Boran (Bos indicus) cattle were challenged by tsetse flies infected with Trypanosoma congolense IL 13‐E3. These animals had experienced five previous infections with T. congolense, each terminated by drug therapy. Immunoblotting and ELISA were used to determine isotype and specificity of antibody responses to trypanosome invariant antigens. Both IgM and IgG1 were elicited, but the IgG1 responses were directed against a greater diversity of antigens. A 69 kD antigen was the major invariant antigen which elicited IgM antibodies in both breeds, but the N'Damas also responded with high levels of specific IgG1. Analysis of isotypic responses to whole trypanosome extract also revealed lower levels of IgG1 and higher levels of IgM in the Borans than in the N'Damas, suggesting that a dysfunction in the switch from IgM to IgG might occur in infected Boran cattle. A 33 kD antigen appeared to elicit only IgG1. Sera from all five N'Damas and the two Borans which were most resistant to the disease reacted with this antigen prior to and following re‐infection. Furthermore, during the primary T. congolense infection in the same animals, anti‐33 kD antibodies were detectable in all five trypanotolerant N'Damas, but in none of the five susceptible Borans. Thus, the presence of antibodies to the 33 kD antigen ofT. congolense appeared to be associated with a capacity to control the disease.
Host genetics and resistance to acute Trypanosoma cruzi infection in mice. I. Antibody isotype profiles
Authors: POWELL MALCOLM R. , WASSOM DONALD L.
Published: October 2007

Some strains of inbred mice survive acute infection with Trypanosoma cruzi while others die within a few weeks after infection. Mice which express B10 background genes and either the H‐2q or H‐2d haplotypes are resistant and survive. However, mice which share the B10 genetic background but express H‐2k alleles die, usually within 4 weeks following infection. These data confirm that at least 1 gene in the major histocompatibility complex can determine whether an animal lives or dies during the acute phase. Expression of the H‐2q haplotype on the B10 genetic background or in DBA/l mice is associated with resistance, but H‐2q mice expressing the C3H background are susceptible. Therefore, at least I gene in the genetic background also influences resistance. Our data suggest that genes associated with resistance must be present in both the MHC and the genetic background or the animal will die. The isotypes and specificities of parasite reactive antibodies found in the serum of different inbred mouse strains were assessed during acute infection. Levels of IgM were higher in sera from mice which express the resistant B10 background than in sera from mice expressing the susceptible C3H background. Conversely, mice which share the C3H background genes produced high levels of anti‐parasite IgG2a when compared to B10 congenic strains. Antigen specificity, however, may be influenced by both background and MHC genes, as congenic strains expressing different MHC haplotypes recognized different constellations of T. cruzi antigens. These data suggest a correlation between genes which influence antibody specificity or isotype and the genes which determine the ability of various inbred mouse strains to survive acute infection with T. cruzi.
Synthetic peptides based on conserved Plasmodium falciparum antigens are immunogenic and protective against Plasmodium yoelii malaria
Authors: CHAUHAN VIRANDER S. , CHATTERJEE SHYAMA , JOHAR PARAMJEET K.
Published: October 2007

Two synthetic polypeptides containing multiple B‐ and T‐cell epitopes derived from the conserved regions of two vaccine candidate antigens namely MSA‐1 and RESA of human malarial parasite P. falciparum were studied for immunogenicity and protectivity. Both constructs elicited strong antibody and lymphocyte proliferation responses in BALB/c mice immunized with the carrier‐free peptides. In an ELISA, these peptides also bound antibodies present in the sera from the P. vivax infected humans as well as from the P. yoelii infected mice. Significantly, our data showed that immunization of mice with these P. falciparum peptide could impart partial protection against P. yoelii challenge infection. Our finding that synthetic peptides representing portions of P. falciparum antigens were capable of stimulating protective immune responses against rodent malaria suggests that murine malaria model P. yoelii may provide a suitable system for primary screening of potentially protective synthetic immunogens.
Anisakis simplex: antigen recognition and antibody production in experimentally infected mice
Authors: IGLESIAS R. , LEIRO J. , UBEIRA F. M. , SANTAMARINA M. T. , SANMARTÍN M. L.
Published: October 2007

The kinetics of antibody response to intraperitoneal infection of mice with third stage larvae of Anisakis simplex was investigated by ELISA. Maximum antibody response to excretion‐secretion (ES) antigens was reached before maximum response to somatic (SA) antigens. Total immunoglobulin (Ig) production (consisting mainly of IgM and IgG1 isotypes) was very similar in both cases. Immunoblotting was used to characterize the antigens recognized by the host in the presence or absence of the metabolic products released by the parasite in vivo. Sera from mice infected with live larvae (anti‐L3 L serum) and immunized with dead larvae (anti‐L3 D serum) recognized a similar pattern of bands in immunoblots of ES and SA antigen preparations. In the latter, however, three bands at 14, 17 and 18 kD were only recognized by the anti‐L3 L serum. A possible explanation is that these low molecular weight antigens are ES products released only in vivo. Finally, the immune response in mouse was compared using ELISA and immunoblotting with the response of a human anisakiasis reference serum, and was found to display considerable similarities. This suggests that the mouse may be a useful model for studying the immunobiology of A. simplex in man.
IgE responses in cats infected with Brugia pahangi
Authors: BALDWIN C. I. , DE MEDEIROS FILOMENA , DENHAM D. A.
Published: October 2007

Passive cutaneous anaphylaxis tests were used to examine the IgE responses of cats repeatedly infected with the filarial nematode Brugia pahangi. Specific IgE was usually detected only in those cats that killed their adult worms and rarely in those cats in which adult worms survived for long periods. We suggest that this specific IgE is actively involved in killing adult worms in the lymphatics.
Influence of genes within the MHC on mortality and brain cyst development in mice infected with Toxoplasma gondii: kinetics of immune regulation in BALB H‐2 congenic mice
Authors: BLACKWELL JENEFER M. , ROBERTS CRAIG W. , ALEXANDER JAMES
Published: October 2007

Previous work has shown that genes within the major histocompatibility complex (MHC) of the mouse influence resistance and susceptibility to Toxoplasma gondii infection. Initial studies presented here using B10 H‐2 congenic and recombinant haplotype mice inoculated via the oral route with the low virulence Beverley strain of T. gondii confirm the D region localization of MHC‐linked control of brain cyst number. All B10 mice were, however, exquisitely sensitive to minor changes in virulence of the parasite inoculum resulting in high mortality during the early acute phase of infection. Further experiments examining mortality and brain cyst number in BALB MHC congenic mice inoculated via different routes indicated that the BALB background would provide a more favourable genetic environment in which to analyse kinetics of MHC controlled immune regulation following infection via the natural (oral) route. In studies comparing d and k haplotype mice a dramatic inverse relationship between splenic CD4:CD8 T cell ratios and brain cyst number was observed, particularly in the strain (BALB/K; H‐2k) most susceptible to high brain cyst numbers and subsequent toxoplasmic encephalitis. Of particular interest was the observation that splenomegaly and the relative increase in the splenic CD8 T cell population preceded and accompanied the very dramatic and rapid increase in brain cyst formation. The results suggest that the too rapid development of a potent anti‐parasite response in the viscera may drive the parasite to encyst in the brain.
Ablation of eosinophils with anti‐IL‐5 antibody enhances the survival of intracranial worms of Angiostrongylus cantonensis in the mouse
Authors: SASAKI OSAMU , SUGAYA HIROKO , ISHIDA KAZUTO , YOSHIMURA KENTARO
Published: October 2007

Effects of depressed eosinophilia on the development of Angiostrongylus cantonensis in the mouse were studied using monoclonal rat anti‐mouse‐interleukin‐5 antibody (anti‐IL‐5). The administration of anti‐IL‐5 strongly depressed peripheral, cerebrospinal fluid (CSF) and medullary eosinophilic responses in mice infected with A. cantonensis, when compared with groups treated with phosphate‐buffered saline solution (PBS) alone or isotype‐matched rat IgG. There was no significant difference in A. cantonensis antigen specific IgG and IgE antibody responses between rat IgG treated and anti‐IL‐5 treated mice. Intracranial worm recovery in anti‐IL‐5 treated mice was consistently high throughout the course of the study and some worms migrated from the brain to the lungs. By contrast, almost all the intracranial worms in the mouse groups treated with PBS alone or rat IgG died before day 32. These data clearly indicate that IL‐5 is essential for eosinophil responses in A. cantonensis infected mice and also that eosinophils serve as a potential effector cell in the killing of the intracranial worms in mice.
Epitope specificity and capacity to inhibit parasite growth in vitro of human antibodies to repeat sequences of the Plasmodium falciparum antigen Ag332
Authors: AHLBORG NIKLAS , FLYG BIRGITTA WÅHLIN , IQBAL JAMSHAID , PERLMANN PETER , BERZINS KLAVS
Published: October 2007

It has earlier been shown that the Plasmodium falciparum‐reactive human monoclonal antibody 33G2 inhibits parasite growth in vitro as well as cytoadherence of infected red blood cells to melanoma cells in vitro. MoAb 33G2 recognizes an epitope of the P. falciparum antigen Ag332 and cross‐reactive determinants in Pf 155/RESA and Pf 11.1 located in repetitive regions containing sequences of regularly spaced pairs of glutamic acid. To study whether antibodies of this specificity frequently occur in human immune sera and if they could be of importance for protective immunity, antibodies were affinity purified on MoAb 33G2 reactive Ag332 peptides. The epitope specificity of the affinity purified antibodies, determined by the Pepscan method, resembled that of MoAb 33G2, but showed differences in fine specificity. The antibodies cross‐reacted to some extent with Pf 11.1 and Pf 155/RESA repeat peptides as detected by peptide ELISA and Pepscan. In indirect immunofluorescence all purified antibodies displayed a dotted pattern of staining of late stage infected red blood cells of two lines of the P. falciparum strain FCR3, including a Pf 155/RESA deficient line. The in vitro growth of these two lines was efficiently inhibited by the affinity purified antibodies, indicating that their inhibitory effect was mainly due to reactivity with antigens other than Pf 155/RESA. This, and the fact that Pf 11.1 has been shown not to be expressed by the asexual stages suggests that Ag332 may be an important target for potentially protective antibodies in vivo and that Ag332 based immunogens are of interest for development of malaria subunit vaccines.
Immunological relationships during primary infection with Heligmosomoides polygyrus (Nematospiroides dubius): downregulation of specific cytokine secretion (IL‐9 and IL‐10) correlates with poor mastocytosis and chronic survival of adult worms
Authors: BEHNKE J. M. , WAHID F. N. , GRENCIS R. K. , ELSE K. J. , BEN‐SMITH A. W. , GOYAL P. K.
Published: October 2007

Mice were infected either with Trichinella spiralis (day 0). Heligmosomoides polygyrus (day – 14) or concurrently with both species and were killed in groups, together with naïve control mice, on 2 occasions (day 8 and 15 post infection with T. spiralis, corresponding to days 22 and 29 p.i. with H. polygyrus). The expulsion of T. spiralis was slowed significantly in concurrently infected mice and this was associated with a reduced mastocytosis and lower serum mucosal mast cell protease levels. Mesenteric lymph node (MLN) lymphocytes from all three experimental groups secreted IL‐3 and IL‐4 in copious amounts when stimulated in vitro by Concanavalin A (Con‐A), but the secretion of high levels of IL‐9 and IL‐10 was essentially confined to mice infected with T. spiralis alone. It is suggested that adult H. polygyrus selectively modulate cytokine secretion by Th2 cells within the MLN during infection and that this is brought about as a direct consequence of the mechanism employed by H. polygyrus to depress mucosal inflammatory responses in order to facilitate its own survival.
The effect of irradiation on the third stage larvae of Brugia pahangi
Authors: DEVANEY E. , BANCROFT A. , EGAN A.
Published: October 2007

The effect of irradiation on the third stage larvae of the filarial nematode Brugia pahangi was investigated. Labelling with 33S methionine of control or irradiated L3, post‐infective L3 or L4 revealed no consistent alterations in the pattern of proteins synthesized. The only significant difference observed was in 125I labelling, where the specific activity of labelling of soluble cuticular proteins was lower in irradiated than in control parasites. This difference may be related to the reduced size of irradiated parasites rather than to a specific effect of irradiation on the expression of cuticular proteins. Irradiated parasites recovered on day 14 post‐infection were significantly shorter than control parasites. Irradiation also appeared to have a lethal effect on male parasites, as no recognizable males were recovered from animals given irradiated L3, nor were microfilariae ever observed in these animals. The mechanisms by which irradiation may enhance the immunogenicity of L3 of filarial nematodes are discussed.
Antibody responses to a 33 kDa cysteine protease of Trypanosoma congolense: relationship to ‘trypanotolerance’ in cattle
Authors: AUTHIÉ EDITH , DUVALLET GÉRARD , ROBERTSON CHRIS , WILLIAMS DIANA J. L.
Published: October 2007

A cysteine protease of Trypanosoma congolense (congopain) elicited IgG1 antibodies in those cattle which exhibited a degree of resistance to disease during experimental infections (Authié et al. 1992, 1993). The aim of the present study was to investigate further the association between anti‐congopain antibodies and resistance to trypanosomiasis, and to provide a lead into the mechanisms responsible for the differential responses to congopain in cattle. Isotype characteristics and kinetics of the antibody response to congopain were studied in three N'Dama (trypanoresistant) and three Boran (susceptible) cattle during primary infection with T. congolense ILNat 3.1. In both groups an IgM response to congopain was elicited, thus demonstrating that congopain is antigenic in both types of cattle. Most of the IgM appeared to be incorporated into immune complexes. IgG was detected as free antibody; IgG1 but not IgG2 was detected. All three N'Dama, but none of the three Boran cattle, mounted a significant IgG response to congopain. Sera from 70 primary‐infected cattle belonging to five breeds of differing susceptibility were tested for their reactivity to congopain. High levels of IgG to congopain were observed in the two trypanotolerant breeds, whereas the three susceptible breeds had lower levels of these antibodies. Crosses between N'Dama and Boran cattle, which exhibit an intermediate susceptibility, had intermediate levels of antibodies. Thus, the results from experimental infections confirmed our initial observations. However, under natural tsetse challenge, repeated infections and trypanocidal treatments in Zebu cattle stimulated as high anti‐congopain antibody levels as in non‐treated trypanotolerant taurine cattle.
Salivary gland material from the sand fly Lutzomyia longipalpis has an inhibitory effect on macrophage function in vitro
Authors: THEODOS CYNTHIA M. , TITUS RICHARD G.
Published: October 2007

Previous work from our laboratory demonstrated that the infectivity of the protozoan parasite Leishmania major was enhanced in mice if the infecting inoculum contained salivary gland lysates from the sand fly vector Lutzomyia longipalpis. The present study was designed to address the hypothesis that sand fly salivary gland material may function by inhibiting the host immune response. Results indicated that sand fly saliva inhibited the ability of macrophages to present leishmanial antigens to parasite‐specific T cells.
Mechanisms of eosinophilia in Toxocara canis infected mice: In vitro production of interleukin 5 by lung cells of both normal and congenitally athymic nude mice
Authors: TAKAMOTO MASAYA , SUGANE KAZUO
Published: October 2007

Mechanisms of eosinophilia were compared between in vitro bone marrow cell cultures of congenitally athymic (nu/nu) mice and their heterozygous littermates (nu/+). Cultures of 5 × 104bone marrow cells using interleukin 3 (IL‐3), IL‐5 and granulocyte‐macrophage colony‐stimulating factor showed that nu/nu and nu/+ mice mimicked each other in eosinophil production both before and after infection with Toxocara canis. Eosinophil differentiating activity (EDA) was detected in media conditioned by spleen cells and lungs of T. canis infected nu/+ mice, although nu/nu mice showed EDA only in lung‐conditioned medium. EDA, detected both in infected nu/nu and nu/+ mice, was inhibited by an anti‐IL‐5 monoclonal antibody. These results indicate that IL‐5 may be produced by lung cells of both nu/nu and nu/+ mice as well as by spleen cells of nu/+ mice infected with T. canis, which is the reason why nu/nu mice infected with T. canis exhibit blood eosinophilia.
Praziquantel‐induced exposure of Schistosoma mansoni alkaline phosphatase: drug‐antibody synergy which acts preferentially against female worms
Authors: FALLON P. G. , SMITH P. , NICHOLLS T. , MODHA J. , DOENHOFF M. J.
Published: October 2007

The efficacy of praziquantel‐treatment of murine Schistosoma mansoni‐infections can be enhanced by concurrent administration of rabbit anti‐sera with specificity for parasite antigens. Monospecific rabbit serum raised against S. mansoni worm alkaline phosphatase, that was reactive with the enzyme on the drug‐treated female surface, was found to significantly and preferentially increase the mortality of female worms by PZQ. Immunoglobulins purified from the anti‐alkaline phosphatase antiserum inhibited 54% of schistosome alkaline phosphatase enzymatic activity on the surface of praziquantel‐treated worms. We propose that synergistic antibody‐mediated death of drug‐damaged worms is a consequence of the inhibition of drug‐exposed alkaline phosphatase on the female worm surface by passively transferred antibody.
Goblet cell mucins of four genera of the subfamily Cricetinae with reference to the protective activity against Strongyloides venezuelensis
Authors: SHI B.‐B. , ISHIKAWA N. , ITOH H. , IDE H. , TSUCHIYA K. , HORII Y. , UCHIYAMA F. , NAWA Y.
Published: October 2007

Goblet and mast cell responses in the jejunum of four genera, Mesocricetus auratus (Syrian hamster), Phodopus campbelli, Cricetulus griseus (Chinese hamster), and Tscherskia triton, belonging to the subfamily Cricetinae, were examined after infection with Strongyloides venezuelensis. Parasite eggs became detectable in faeces of all four genera on Day 7. Faecal egg count peaked around Day 8 in C. griseus and T. triton and around Day 14 in M. auratus and P. campbelli. In M. auratus and P. campbelli, faecal egg production persisted over 40 days, whereas that in C. griseus and T. triton rapidly terminated within 14 days. In all four genera examined, goblet cell hyperplasia and mastocytosis were observed at the time of expulsion of S. venezuelensis. However, in the comparative study of all four genera, neither the degree of goblet or mast cell hyperplasia nor the phenotype of mast cells correlated to the rapidity of the expulsion of S. venezuelensis. On the other hand, the rapidity of expulsion closely correlated with the degree of sulphation of goblet cell mucins because two genera, C. griseus and T. triton, having highly sulphated goblet cell mucins showed faster expulsion of S. venezuelensis than the other two genera, P. campbelli and M. auratus, having less sulphated mucins. These results suggest that physicochemical nature of mucins is critical for the expulsion of S. venezuelensis from the subfamily Cricetinae.
The role of adult worms in suppressing functional protective immunity toHeligmosomoides polygyrus bakerichallenge infections
Authors: PLEASS R. J. , BIANCO A. E.
Published: October 2007

AdultHeligmosomoides polygyrus bakeri, radiolabelled with [35S]‐methionine were successfully transferred to naive NIH mice by oral gavage. Adult worms and radio‐label could be detected up to 45 days post‐infection. Adult worms gavaged into immune NIH mice, immunized with a drug abbreviated larval infection, were rejected within 45 days. These adult worms were unable to ablate the development of a functional protective response to a larval challenge infection in the NIH strain. In fact 50 adult worms were sufficient to significantly immunize NIH mice against a larval challenge infection. However, adult worms were able to suppress the development of a functional protective response in an outbred CFLP strain. Although a protective immune response could not be elicited to a challenge infection in CBA mice, the presence of gavaged adult worms was shown to increase the susceptibility of mice to a challenge infection. For all mouse strains, no significant difference in levels of L4 antigen‐specific serum IgG, IgG1, IgG2a, and IgA existed between immune mice and groups of mice immunosuppressed by adult worms. Levels of L4 antigen‐specific serum IgG1 were significantly lower in the poorly immunizable CBA strain compared to CFLP and NIH strains. No correlation was found across mouse strains between the intensity of the antibody response and the mean worm burdens per animal group. In addition, no correlation was found between levels of L4 antigen‐specific antibody within each mouse and the loss of worms by individual mice.
Histochemical characteristics of the goblet cell mucins and their role in defence mechanisms against Nippostrongylus brasiliensis infection in the small intestine of mice
Authors: ISHIKAWA N.
Published: October 2007

The histochemical characteristics of the small intestinal goblet cell mucins of mice and their protective role during the expulsion of Nippostrongylus brasiliensis adult worms were examined. Lectin histochemistry revealed that, before infection, strongly positive stainability of Helix pomatia agglutinin (HPA) and Limax flavus agglutinin (LFA) was observed in all of the small intestinal goblet cell mucins of mice. When ‘normal’or ‘damaged’N. brasiliensis adult worms were implanted separately into the small intestine of euthymic mice, 50% of them were established in the intestine on day one after implantation, but were subsequently expelled within one week in association with HPA and LFA positive goblet cell hyperplasia. On the other hand, in dexamethasone treated euthymic mice, 70% of implanted ‘normal’worms were expelled by day 7 and 80% of implanted ‘damaged’worms were expelled by day 4 in association with HPA and LFA positive goblet cell mucins but no goblet cell hyperplasia. This is consistent with the fact that, in spite of no increase in goblet cell number in hypothymic nu/nu mice, all of the implanted ‘damaged’worms were expelled within day 5 and 80% of implanted ‘normal’worms were expelled by day 14 post implantation, possibly associated with strngly expressed terminal GalNAc and sialic acid residues of the small intestinal goblet cell mucins prior to infection.
Hepatic recruitment of mast cells occurs in rats but not mice infected with Schistosoma mansoni
Authors: MILLER H. R. P. , NEWLANDS G. F. J. , McKELLAR A. , INGLIS L. , COULSON P. S. , WILSON R. A.
Published: October 2007

The pathogenesis of infection with Schistosoma mansoni in rats is distinct from that in mice. Rats are non‐permissive hosts and infection is terminated in the liver before egg laying commences whereas the parasite completes its life cycle in mice. Comparison of the mast cell responses in the two species reveals that a pronounced hepatic mastocytosis occurs in the rat and this is concomitant with the demise of the parasite. The majority of recruited hepatic mast cells contain the highly soluble granule chymase, rat mast cell protease‐II, which is released systemically into blood during the period of parasite elimination. In contrast, very few mast cells are found in livers of parasitized mice and none contain the soluble granule chymase mouse mast cell protease‐1. However, during egg deposition in the gut, an intraepithelial mastocytosis occurs in parasitized mice. These intraepithelial cells are typical mucosal mast cells as determined by their content of mouse mast cell protease‐1. Recruitment of mucosal mast cells occurs in the intestinal lamina propria of infected rats soon after the parasites migrate to the liver. These findings suggest that mast cells of the mucosal phenotype are involved in the pathogenesis of the hepatic response to infection in the rat but that, in the mouse, mucosal mastocytosis is associated with intestinal sensitization by egg antigens.