bluuebunny/crossref_metadata_2025 huggingface dataset:
Site potential for challenge attrition in mice, rats and guinea pigs vaccinated with irradiated cercariae of Schistosoma mansoni
Authors: McLAREN DIANE J. , PEARCE E. J. , SMITHERS S. R.
Published: October 2007

Summary The potential sites of attrition of a challenge population of schistosomes have been investigated in mice, rats and guinea pigs vaccinated with irradiated cercariae of Schistosoma mansoni, by the use of challenge regimens that permit sequential site elimination. Vaccinated mice showed significant immunity to a percutaneous cercarial challenge, but were only marginally resistant to an i.v. challenge with healthy lung stage worms. Vaccinated rats and guinea pigs differed from mice, in that they were able to mediate significant challenge attrition at post‐skin sites. Healthy lung worms were subject to immune elimination by rats in the lungs, or perhaps en route to the liver, but not in the liver itself. In contrast, guinea pigs had the capacity to kill challenge lung worms injected into either the lungs or the liver. Interestingly, lung worms harvested by extended incubation were shown to be sub‐optimal in terms of viability, since they were eliminated in significant numbers when injected i.v. into vaccinated mice. These data show that different hosts vaccinated in essentially the same manner differ in terms of their site potential for challenge attrition. It is emphasised however, that sites implicated by these experiments as having the capacity to mediate immune elimination are not necessarily the sites at which challenge attrition occurs under normal circumstances.
Sex‐influenced response in the pathogenesis of cutaneous leishmaniasis in mice
Authors: GIANNINI M. S. H.
Published: October 2007

Summary Male B10–129 (10M) ScSn mice were relatively resistant to cutaneous leishmanisis, while females frequently developed non‐healing expanding ulcers, leading to loss of infected extremities, metastasis to distal skin sites, and in some animals, death. Anti‐leishmanial antibody titers were higher, and delayed‐type hypersensitivity responses to parasite antigens, lower, in infected females than in males. Sex differences in response to cutaneous infection were not marked in BALB/cJ mice, a highly susceptible strain, and both males and females ultimately lost infected extremities, developed metastases, and died.
Antigenic diversity and size diversity of Plasmodium falciparum antigens in isolates from Gambian patients. I. S‐antigens
Authors: HOWARD RUSSELL J. , PANTON LINDSEY J. , MARSH KEVIN , LING IRENE T. , WINCHELL J ELLEN J. , WILSON R. J. M.
Published: October 2007

Summary Ring‐stage asexual parasites of P. falciparum were collected from six Gambian children and the S‐antigens radiolabeled by 3H‐glycine uptake during in vitro culture up to rupture of infected cells and merozoite release. Ouchterlony double diffusion of boiled culture supernatants against a panel of adult Gambian sera identified one S‐antigen precipitin arc for five isolates and two precipitin arcs for one isolate. Five of the six isolates were serologically distinct. Analysis of S‐antigens by comparison of SDS‐polyacrylamide gel electrophoresis patterns of heat‐treated soluble proteins revealed a more complex pattern of 3H‐labelled S‐antigens that was different for each isolate. There were between two and six different 3H‐labelled bands for each isolate in the size range of molecular weight 137 000 to 285 000. This result confirms the large size range of S‐antigens identified with culture adapted P. falciparum. Several bands were relatively weakly labelled with 3H‐glycine, suggesting that natural isolates contain one or two predominant S‐antigen phenotypes and several other S‐antigen phenotypes expressed by minor parasite subpopulations. Immunoprecipitation was performed using a panel of sera from Gambian adults, or, acute and 3 week convalescent sera from the same patients used for S‐antigen radiolabelling. Adult sera generally immunoprecipitated some of the S‐antigens in each isolate, including antigens that must represent extremely minor parasite subpopulations since they could not be seen in the patterns of non‐immunoprecipitated heat‐stable proteins. Sera from convalescent children were generally negative on immunoprecipitation, even with the homologous isolate. In one case we observed the acquisition of specific immuoprecipitating antibody to one of the homologous S‐antigens during the convalescent period. The antigenic and structural complexity of S‐antigens in natural isolates that have not been submitted to the selection pressure of adaptation for in vitro culture is clearly greater than for culture adapted P. falciparum.
Evidence that the reduced surface antigenicity of developing Schistosoma mansoni schistosomula is due to antigen shedding rather than host molecule acquisition
Authors: PEARCE EDWARD J. , BASCH PAUL F. , SHER ALAN
Published: October 2007

Summary Antibody and lectin binding characteristics of Schistosoma mansoni schistosomula maturing in vivo and in vitro were quantitatively assessed and compared in order to investigate the basis of the reduced surface antigenicity of host derived larval schistosomes. Quantitative indirect immunofluorescence assays showed that schistosomula recovered from mice at 24 h and 5–10 days post infection bound low or insignificant amounts of a variety of anti‐schistosome antibodies including those from chronically infected and radiation attenuated cercariae‐vaccinated mice, a vaccinated rabbit and rabbits hyper‐immunized with non‐living larval and adult schistosome antigen preparations. In contrast, parasites maturing in vitro continued to bind highly significant levels of each of these antibody preparations until at least 10 days post transformation. To investigate the basis of the decreased surface antigenicity of parasites maturing in vivo, 6‐day‐cultured parasites were injected intravenously into mice and recovered from the lungs at various times thereafter and examined for their ability to bind both anti‐parasite and anti‐host antibodies. After 30 min in vivo, cultured schistosomula exhibited a significantly decreased capacity to bind anti‐parasite antibodies and concanavalin A (Con A), and by 16 h had lost their binding sites for fucose binding protein (FBP) as well. That this reduction in antigenicity was due to shedding of surface antigens was suggested by the observation that the reduced ability of these parasites to bind anti‐parasite antibodies coincided closely with the loss of 125I‐labelled surface proteins. Furthermore unlike 6 day schistosomula which had developed wholly in vivo, 6‐day‐cultured parasites recovered after 30 min in vivo failed to bind anti‐host antibodies suggesting that in these organisms parasite antigens were not masked by host molecules. These data argue that surface antigen shedding may explain the reduced surface antigenicity of schistosomula developing in vivo. While this surface modulation apparently independently of host antigen uptake, it is dependent upon an as yet unindentified host factor.
Schistosoma mansoni: characterization of two protective monoclonal antibodies
Authors: BICKLE Q. D. , ANDREWS B. J. , TAYLOR M. G.
Published: October 2007

Summary Two monoclonal antibodies against the surface of S. mansoni schistosomula were found to confer significant passive protection to mice (M7B3A, range 28–70%; M22H12C, range 14–58%). No additive effect was observed when both were transferred together. Neither McAb bound to the cercarial surface but both bound to the surface of in vitro derived schistosomula and schistosomula recovered from mouse skin up to 3 days after infection. The McAbs were species specific, but not S. mansoni strain specific. M22H12C immunoprecipitated an 125I‐labelled surface antigen of relative molecular weight (mol. wt) 32 000. In Western blotting of an NP40 schistosomular extract, M7B3A recognized an antigen smear of 13000–18000 with a dominant band at 16000. This 16000 antigen was recognized by serum from demonstrably immune mice and rats vaccinated with highly irradiated carcariae but not by sera from mice with chronic single sex or bisexual infections.
Detection of specific circulating antigen, immune complexes and antibodies in human hydatidosis from Turkana (Kenya) and Great Britain, by enzyme‐immunoassay
Authors: CRAIG P. S.
Published: October 2007

Summary Circulating antigen, specific immune complexes (IgG and IgM) and specific antibodies (IgG, IgM, IgE and IgA) were detected by enzyme‐linked immunosorbent assay (ELISA) in the sera of hydatid (Echinococcus granulosus) patients from Turkana (Kenya) and the UK. Specific IgG and IgM antibodies predominated in current UK hydatid infections, while all classes of specific antibodies were lower in the Turkana patients. Circulating antigen, detected in 3% polyethylene glycol (PEG) precipitated complexes, using peroxidase conjugated hyperimmune human hydatid IgG (Fab) was more specific in ELISA than either antibody or immune complex assays where peroxidase conjugated anti‐human IgG was used. Anti‐human immunoglobulin (‘rheumatoid’ factor) was not detected in hydatid sera. Serum antigen, specific IgM immune complexes and specific IgM antibodies were associated with UK cases of current hydatid infection in contrast to patients with previous histories of hydatidosis. In 3 hydatid patients (from UK) levels of circulating antigen and specific IgM immune complexes rapidly declined within 1–4 months after surgical cyst removal. The detection of specific IgG and antigen in PEG precipitated immune complexes from false‐negative/lowresponder Turkana hydatid sera, suggests that antibody ‘mopping’ by specific antigen may be occurring. After SDS‐PAGE/immunoblot‐ting analysis, antigen of mol. wt 67 000, present in hydatid cyst fluid and protoscoleces, was identified as putative circulating antigen in 3% PEG precipitates of sera from albendazole treated hydatid patients.
Interference between different serodemes of Trypanosoma congolense in the establishment of superinfections in goats following transmission by tsetse
Authors: WINGER R. H. D. , LUCKINS A. G. , MURRAY MAX , RAE P. , MOLOO S. K.
Published: October 2007

Summary When domestic ruminants cyclically infected with Trypanosoma congolense are superinfected with a different serodeme of the same species, an interference phenomenon occurs which delays the development of the second cyclical infection. Experiments were carried out to investigate the influence of the time interval between the two infections on the degree of interference and to follow the course of the superinfection clinically, serologically and histologically. Goats infected with tsetse‐transmitted T. congolense IL 1587 were either infected simultaneously or 7, 14, 18, 28 or 35 days later with a different serodeme, T. congolense IL 1180. Skin reactions due to superinfection were either absent or smaller in size and delayed in onset compared with control animals undergoing a primary infection with T. congolense IL 1180 which had been initiated by tsetse fly bites. All animals were treated with the trypanocidal drug Berenil 21 days after superinfection and 3 weeks later challenged with T. congolense IL 1180 using tsetse flies. The goats that had been infected simultaneously with the two serodemes were immune to the homologous challenge, but 11 (85%) of the animals that had been superinfected were not. The effect of interference on the host immune response to T. congolense IL 1180 was most marked in animals superinfected at day 7; thereafter there was evidence that the ability to respond immunologically against secondary infection was gradually recovered. Histological examination of skin removed 7 days after a simultaneous infection of goats with two serodemes, showed trypanosomes and a cellular reaction similar to that following infection with a single serodeme. In skin removed 7 days after superinfection of goats that had been infected for 7 days, the cellular response was less pronounced and trypanosomes were not seen, although by 14 to 16 days numerous trypanosomes were present and there was a marked cellular infiltrate. It is postulated that the presence or absence of a factor induced shortly after initiation of a trypanosome infection in the skin of goats might delay parasite development when metacyclic trypanosomes are deposited by tsetse following superinfection.
Passive protection against Taenia saginata infection in cattle by a mouse monoclonal antibody reactive with the surface of the invasive oncosphere
Authors: HARRISON L. J. S. , PARKHOUSE R. M. E.
Published: October 2007

Summary The surface, excretory/secretory and intracellular compartments of Taenia saginata oncospheres were analysed by a combination of immunochemical techniques and by the use of selected hybridoma antibodies. The surface proteins of the oncospheres were directly iodinated by the lactoperoxidase technique and the intracellular and excretory/secretory components were labelled biosyntheti‐cally by culture in vitro with 35S‐methionine. Analysis of radiolabeled proteins by SDS‐PAGE revealed a restricted number of components in all of these three compartments. Mouse derived monoclonal antibodies directed against the oncospheral stage of this parasite demonstrated both stage specific and common determinants on the surfaces of the oncospheres and the metacestodes. One monoclonal (IgM) antibody, reactive with the oncosphere surface, which had a half life of 4–1 days when injected into calves, conferred protection against oral infection with T. saginata eggs. A monoclonal antibody reactive with a major secreted component did not confer passive protection.
Brugia pahangi infections in cats: antibody responses which correlate with the change from the microfilaraemic to the amicrofilaraemic state
Authors: FLETCHER C. , BIRCH D. W. , SAMAD R. , DENHAM D. A.
Published: October 2007

Summary The humoral responses of eight cats infected with Brugia pahangi to somatic antigens from all life‐cycle stages were examined quantitatively by ELISA and qualitatively by immunoblotting for almost a year post infection. Six cats spontaneously became amicrofilaraemic: their production of IgG antibodies against somatic antigens of microfilariae, adults, and infective larvae was not statistically higher than that of the two cats which remained microfilaraemic. However, immunoblotting revealed that those cats which spontaneously became amicrofilaraemic selectively recognized certain microfilaria!, adult and infective larval somatic antigens prior to disappearance of microfilariae from the peripheral circulation. The data suggest that selective recognition of antigens by some cats is responsible for the production of antibodies which may then promote microfilarial death.
Eimeria tenella: quantitative in vitro and in vivo studies on the effects of mouse polyclonal and monoclonal antibodies on sporozoites
Authors: CRANE MARK ST. J. , NORMAN DEBORAH J. , GNOZZIO MARK J. , TATE ANN C. , GAMMON MAUREEN , MURRAY P. KEITH
Published: October 2007

Summary Murine, polyclonal and monoclonal antibodies, raised against sporozoites of Eimeria tenella, were tested for their ability to neutralize sporozoite infectivity in vitro and in vivo. Neutralization was effected via three mechanisms. Firstly, sporozoites fixed complement, at low titres, and lysis occurred by the alternative pathway of complement activation. Secondly, in the absence of complement activity, the murine heat‐inactivated, hyperimmune antiserum neutralized sporozoites at relatively low titres. At high titres, even though sporozoites were agglutinated, neither the heat‐inactivated hyperimmune antiserum nor the monoclonal antibody neutralized sporozoites. Finally, in the presence of complement and specific antibodies, at titres which by themselves would not neutralize sporozoites, neutralization was effected due to lysis via the classical pathway of complement activation.
Limit dilution analysis of mast cell precursor frequency in the gut epithelium of normal and Trichinella spiralis infected mice
Authors: DILLON SUSAN B. , MACDONALD THOMAS T.
Published: October 2007

Summary Previous studies have established that the gut nematode Trichinella spiralis induces a dramatic thymus dependent intestinal mastocytosis which peaks within 6 to 12 days after primary oral infection. It is not known, however, if the increase in gut mast cells results from the influx of mast cells or their precursors, or from the expansion and differentiation of mast cell precursors (MCP) that are normally present in the small intestinal epithelium. In the present study, the number of mucosal MCP in the intraepithelial lymphocyte (IEL) population and in bone marrow (BM) cells from normal and 4 day T. spiralis infected mice was compared by culturing the cells at limiting dilutions in medium containing interleukin‐3 (IL‐3). While the MCP frequency in IEL from infected mice was found to be significantly increased in comparison with that found in normal mice, the numbers of MCP in BM from the two groups were equivalent. Resident intraepithelial mucosal MCP therefore undergo a local expansion before the occurrence of an overt T dependent intestinal mastocytosis. This finding lends support to the view that local mucosal T cells are involved in regulating mast cell numbers in response to intestinal helminth infection.
The immunodominant epitope of the major membrane tachyzoite protein (P30) of Toxoplasma gondii
Authors: SANTORO F. , CHARIF HALEH , CAPRON A.
Published: October 2007

Summary Several physicochemical characteristics of the repeated epitope of the major surface protein (P30) of Toxoplasma gondii were investigated with an anti‐P30 mAb by two different methods: (a) a one‐site/inhibition assay that detects molecules containing single or multiple epitopes and (b) a two‐site/one antibody radiometric assay that is only effective with antigenic molecules containing two or more identical epitopes. Using both techniques, the repeated epitope within purified P30 was stable after 1 h at 63°C, but labile at 100°C. It was also resistant to successive freezing and thawing, and not affected after one year at – 70°C. Lyophilization and acidic or basic treatment had no effect. This epitope was also resistant to 20% trichloroacetic acid precipitation (activity recovered in the pellet) and to precipitation with cold acetone.

To investigate the immunodominance of this repeated epitope during the humoral immune response against T. gondii, competition binding assays between anti‐P30 mAb and polyclonal antibodies, from rabbits immunized with either purified P30 or total Toxoplasma extract and from patients with toxoplasmosis, have been used. We found that the mAb inhibited 50–95% of the binding of the IgG antibodies from both rabbits to purified P30. In addition, the binding of both human IgG and IgM antibodies to P30 was significantly inhibited by the mAb. It appears, therefore, that a single region of P30 contains most of the immunogenic activity.
Immune‐mediated adherence of eosinophils to Toxocara canis infective larvae: the role of excretory‐secretory antigens
Authors: BADLEY JANE E. , GRIEVE ROBERT B. , ROCKEY JOHN H. , GLICKMAN LAWRENCE T.
Published: October 2007

Summary The participation of Toxocara canis larval excretory‐secretory antigens in immune‐mediated adherence was determined in vitro. Adsorption of immune sera with excretory‐secretory antigens removed some complement components, removed IgG antibody directed against larval surfaces, and abrogated all adherence observed with untreated immune serum. At least four antigens could be implicated in adherence, by Western blot analysis of adherence mediating sera.

Scanning and transmission electron microscopic examination of larvaleosinophil interactions revealed that eosinophils adhered to a membranous sheath‐like layer that was frequently detached from the larval epicuticle. The layers appeared to be composed of surface antigens and antibody, and may provide larvae with protection against antibody and eosinophil toxins by preventing their contact with the epicuticle. The release of surface antigens also may be important in allowing larvae to evade the host's immune response by facilitating the removal of antibody and eosinophils from the larval surface.
Activation by synergism between endotoxin and lymphokines of the mouse macrophage cell line J774 against infection by Trypanosoma cruzi
Authors: ALCINA ANTONIO , FRESNO MANUEL
Published: October 2007

Summary The mouse macrophage cell line J774 was easily infected by T. cruzi epimastigotes which were transformed to amastigotes that multipled inside the cells. Spleen‐T‐cells from T. cruzi immune mice stimulated with Concanavalin A or T. cruzi, but not with unrelated antigens, released lymphokines into the supernatants that when added to J774 cells were unable to induce complete trypanocidal activity, although they were able to delay the rate of infection by protecting the cells from being infected. Addition of bacterial lipopolysacharide (LPS), although inactive by itself, acted synergistically with the supernatants in inducing complete trypanocidal activity without affecting the susceptibility of J774 cells to infection. Gamma‐interferon (γ‐IFN) activity was detected in the supernatants, however, but was not solely responsible for the trypanocidal inducing activities, since: (1) there was no correlation between the levels of γ‐IFN and macrophage activation; (2) γ‐IFN alone was less effective than the supernatants alone; and (3) two active fractions of 100 000–150 000 mol. wt and 30 000 mol. wt were separated by gel filtration chromatography of the lymphokine preparations. The latter, which showed the characteristics of γ‐IFN with respect to size, pH 2 sensitivity and antiviral activity, had some trypanocidal activity alone. However, the 100 000–150 000 mol. wt fraction was active only in the presence of LPS. Finally, this trypanocidal inducing activity of the supernatants was not due to the induction of synthesis of γ‐IFN by the J774 cells.
Antigen expression during development of the human hookworm, Necator americanus (Nematoda)
Authors: CARR A. , PRITCHARD D. I.
Published: October 2007

Summary Summary The accumulated and de novo synthesized antigens expressed by L3, L4 and adult Necator americanus. recognized by both the natural host, man, and the experimental host, the hamster, were identified by immunoblotting and immunoprecipitation analysis. Following infection of neonatal hamsters serum samples were taken on days 17, 35 and 117. Only serum taken 117 days after infection showed significant reactivity in immunoblotting experiments, recognizing adult epitopes of 30000, 33000, 48000 and 69000 mol. wt thereby suggesting that few accumulated antigens are shared between developmental stages. By contrast, immunoprecipitation analysis of metabolically labelled proteins suggested that L3 and in particular L4 larvae synthesize some antigens which comigrate with those synthesized and accumulated by adult worms. In addition, L4 larvae synthesize a 41000 mol. wt excretory/secretory (ES) stage specific antigen.

Parallel experiments using serum samples from infected humans, demonstrated that hamsters and man recognize many antigens of identical molecular weight. Notable in this respect are accumulated adult antigens of 30000, 33000, 48000 and 69000 and de novo synthesized antigens of 30000, 33000, 44000, 46000 and 69000 mol. wt. Some individual human sera mainly recognized L3 antigens of 47000–69000 mol. wt in immunoblotting experiments whilst others simultaneously recognized adult epitopes. This differential recognition of developmental stages by individual human sera suggests that genetic or epidemiological factors are operative and warrants further study.

Overall, these studies confirm the pronounced immunogenicity of Necator americanus in both man and an animal model and pave the way for analysis of the relevance of these antigens to field situations.
Potential value of localized skin reactions (chancres) induced by Trypanosoma congolense transmitted by Glossina morsitans centralis for the analysis of metacyclic trypanosome populations
Authors: DWINGER R. H. , MURRAY MAX , MOLOO S. K.
Published: October 2007

Summary Goats infected with Trypanosoma congolense transmitted by Glossina morsitans centralis and then treated with the trypanocidal drug diminazene aceturate are immune to tsetse‐transmitted infection with a homologous, but not heterologous trypanosome clone. Immune animals fail to develop localized skin reactions (chancres) and do not become infected, whereas on heterologous challenge chancres appear followed by parasitaemia. In this study, the feasibility of using chancre reactions to characterize several different metacyclic populations of T. congolense was evaluated. Provided goats were immunized, it was found that the chancre reaction could be used to distinguish different populations of T. congolense. However, problems were encountered when attempts were made to induce immunity against more than one trypanosome population. When goats were infected by tsetse flies with four antigenically unrelated metacyclic populations of T. congolense, either simultaneously or at 4 day intervals, adequate immunological priming was not always achieved. In fact, goats exposed to superinfection 8 to 12 days after a primary infection did not develop chancres or an immune response to the second infection (although they were immune to the organism used for primary infection). Following trypanocidal treatment these animals were subsequently completely susceptible to homologous infection with the metacyclic population used for superinfection, indicating that some form of interference phenomenon effective at the level of the skin appears to prevent or delay the development of the second trypanosome population following superinfection of infected animals.
Trypanolytic activity and antibodies to metacyclic trypomastigotes of Trypanosoma cruzi in non‐Chagasic human sera
Authors: YOSHIDA NOBUKO , ARAGUTH MARCIA F.
Published: October 2007

Summary Metacyclic trypomastigotes of Trypanosoma cruzi, derived either from triatomid vectors or axenic cultures, were found to be extensively lysed by sera of some non‐Chagasic healthy individuals through activation of the alternative complement pathway. Antibodies to T. cruzi metacyclics were detected by direct agglutination test in normal human sera (NHS) containing trypanolytic activity. Absorption of lytic NHS with metacyclic trypomastigotes, but not with non pathogenic Herpetomonas samuelpessoai promastigotes, abolished the trypanolytic effect. Natural antibodies to trypomastigotes were not found in NHS devoid of trypanolytic activity. Precipitation of 131I‐labelled metacyclic surface proteins with lytic NHS revealed as the major band a polypeptide with an apparent molecular weight of 75 000.
Species‐specific and common epitopes on the secreted and surface antigens of Toxocara cati and Toxocara canis infective larvae
Authors: KENNEDY M. W. , MAIZELS R. M. , MEGHJI M. , YOUNG L. , QURESHI F. , SMITH H. V.
Published: October 2007

Summary It is widely accepted that the major cause of visceral larva migrans (VLM) in man is Toxocara canis infection. This has been largely based on the detection of antibodies to this species. We have compared the antigens of T. canis and Toxocara cati in order to establish whether assay for the former might be compromised by infection with the latter. Comparisons were made by radioiodination of the surface and excretory/secretory (ES) glycoproteins of the infective larvae of both species. immunoprecipitation with poly‐ and monoclonal reagents, and SDS‐PAGE. The SDS‐PAGE profiles of surface antigens of the two species showed few similarities. whereas that of the ES material indicated considerable homology. Serum from infected animals and a human VLM patient exhibited complete cross reactivity, although there was evidence in the mouse of a specific response to one of the components of T. cati ES. Testing of ES against a panel of monoclonal antibodies (MoAbs) confirmed the similarity; all but one of the MoAbs recognized several of the components of both sources of ES. The only exception was MoAb Tcn‐2, which did not react with T. cati surface, somatic or ES antigens. This antibody is known to recognize a carbohydrate determinant which is widespread on T. canis glycoproteins. This species‐specific determinant, therefore, represents a reversal of the consensus that peptide determinants tend to be the more specific. Finally, the MoAbs were used to examine the exposure of shared epitopes on the surface of intact larvae of T. cati. Again, fine differences in binding by anti‐carbohydrate monoclonals were observed when the two species of Toxocara were compared, reflecting a distinction in exposure or orientation of surface molecules on these nematodes. Moreover, these epitopes were absent or variably present on the surface of freshly hatched larvae, and full exposure did not occur until about 24 h post‐hatching. This delay in the presentation of epitopes
Associations between clinical disease, circulating antibodies and C1q‐binding immune complexes in human onchocerciasis
Authors: SISLEY B. M. , MACKENZIE C. D. , STEWARD M. W. , WILLIAMS J. F. , O'DAY J. , LUTY A. J. F. , BRAGA M. , EL H. , SHEIKH H.
Published: October 2007

Summary Onchocerciasis is a disease where often there are high levels of serum antibodies and high parasitic loads. The role of immune complexes in the development of the disease is investigated here by studying non‐specific and Onchocerca volvulus specific immune complex levels, as well as the antibody concentrations, in the sera of 372 people living in either Southern (199) or Northern (173) Sudan; sera from Sudanese individuals (31) and Caucasians (21) living outside the onchocerciasis endemic area were also tested.

The levels of non‐specific immune complexes (NS‐IC) in these sera were measured by a solid phase radio‐immunoassay and those of O. volvulus‐specific immune complexes (OV‐IC) by an assay measuring antibody‐excess complexes using Clq‐coated plates. The concentrations of O. volvulus IgG antibodies were measured by ELISA. Immune complex and antibody levels of the serum donors were compared with regard to their clinical status due to onchocerciasis. These clinical changes were classified according to onchocercal lesions related to either (a) the active destruction of microfilariae (acute changes), or (b) the long term tissue alterations (chronic changes). Data was analysed using the Odds Ratio method.

A negative association between microfilarial load and immune complex level was found, with the higher levels of OV‐IC present in patients with the lower levels of dermal microfilariae (i.e., less than 10 mf/mg). Significant associations between immune complex levels and the severity of onchocercal disease were also found. Levels of OV‐IC specific immune complexes were higher in infected individuals carrying dermal onchocercal lesions than in those without such clinical changes; there was no apparent relationship between these levels and the
Antibody isotypes of immune complexes in schistosomiasis mansoni in Sudan
Authors: JASSIM A. , CATTY D. , HASSAN K.
Published: October 2007

Summary From a panel of monoclonal antibodies to Schistosoma mansoni, one that is specific to a shared cercarial and schistosomular antigen, and does not react with other major parasite species including Fasciola hepatica, was selected for use as an antigen‐capture layer in a sandwich ELISA for detection of specific circulating immune complexes in the blood of S. mansoni‐infected subjects from Sudan. The test, which identifies immune complexes of only a single antibody‐bound antigen, is developed using human Ig class‐ and IgG subclass‐specific enzyme (HRP)‐antibody conjugates. European blood donor sera and those with rheumatoid factor and/or anti‐nuclear antibody are negative in this test. The prevalence and distribution of the different antibody isotypes in antigen‐specific complexes was determined in 276 subjects of four infection groups; primary school children, adult irrigation canal cleaners with chronic infections, an equivalent group of Praziquantel cured canal cleaners, and hospital‐referred cases with severe hepatosplenic symptoms. The isotype profiles of antibodies in the specific complexes were compared with those in the total serum complexes prepared by polyethylene glycol precipitation.

In chronic infections and in children there is a high prevalence of IgG and IgM specific complexes, the IgG being predominantly IgG1, with little or no IgG3 and IgG4. Treated chronic infections show reduced specific complexes in all classes of antibody. Compared with chronic and children's infections, a large proportion of the patients with severe infections have in addition to high IgM, high levels of IgG2, IgG3 and IgG4 specific complexes, a fact which suggests a causal relationship between antibody production in one or more of these subclasses to the circulating antigen and symptoms of hepatosplenic disease.

Although all subjects have significant amounts of total serum complexes with IgG, untreated chronic infections have much higher concentrations than other infected groups. This group also has the highest levels and prevalence of IgM and IgE complexes. In treated chronic cases IgG and IgM total complexes are greatly reduced. The significant finding in patients with severe symptoms is the relatively high IgA immune complex level compared with other groups.

Taken overall the results suggest that screening of populations in endemic regions for serum immune complexes by specific and non‐specific means could offer valuable data on the significance of antibody responses to circulating antigens in different isotypes in relation to pathogenesis. In addition the loss of complexes after chemotherapy may be of special value in determining the success of treatment regimens.
Inbred mice infected with Plasmodium yoelii differ in their antimalarial immunoglobulin isotype response
Authors: TAYLOR DIANE W. , PACHECO ELAINE , EVANS CHARLES B. , ASOFSKY RICHARD
Published: October 2007

Summary Antibodies are known to be important in mediating malarial immunity, but the influence of the various immunoglobulin isotypes on parasite elimination is unclear. The purpose of this study was to provide basic information on the induction of isotype expression in genetically different mice during primary malaria. Parasitaemias and the serum antimalarial IgM. Igd1, IgG2, IgG3 and IgA antibody titres measured in a radioimmunoassay were followed in outbred and 11 inbred strains of mice infected with 17XNL Plasmodium yoelii. Severity of infection, as judged by length of infection, peak parasitaemias and death, was found to differ between the strains. All strains developed rapid IgM responses, but only 3/11 inbred strains produced significant antimalarial IgG1 levels during primary infection. All strains produced an IgG3 response, which developed slightly more quickly in strains with the least severe courses of malaria. A large variation in the IgG3 response was noted between strains. In general, IgG3 antibodies were the first IgG‐isotype to appear in serum. They were detected as early as day 8 in strains that developed mild infections but were not present until around day 20 in strains with the most severe cases of malaria. Only one strain produced detectable antimalarial IgA antibodies. These results show that different patterns of isotype expression are induced in inbred strains of mice during primary P. yoelii infection.
Immunity to coccidiosis: adoptive transfer in NIH mice challenged with Eimeria vermiformis
Authors: ROSE M.ELAINE , WAKELIN D. , JOYSEY H.S , HESKETH PATRICIA
Published: October 2007

Summary The development of a reliable model for the adoptive transfer of immunity to coccidiosis (infection with Eimeria vermiformis in NIH mice) is described. More than 108 of a mixture of spleen and mesenteric lymph node(MLN) cells, given either intravenously or intraperitoneally, were required to transfer a significant degree of protection. Dividing cells, present in the donors at 10 or 14 days after priming, but not at 5 or 19 days, were shown to be the effectors. When examined separately. MLN cells were found to be superior to spleen cells, and the injection of as few as 5 × 107 was capable of substantially reducing the oocyst output from a challenge inoculum. The recipients of cells from primed mice had earlier, and sometimes higher, titres of specific antibodies in the serum but, overall, there was no correlation between these titres and protection. Further characterization of the cells responsible for adoptively transferring immunity to this infection should now be possible.
A role for elevated plasma corticosterone in modulation of host response during infection with Trichinella pseudospiralis
Authors: STEWART GEORGE L. , MANN MARTHA A. , UBELAKER JOHN E. , McCARTHY JOHN L. , WOOD BEVERLY G.
Published: October 2007

Summary Suppression of host inflammatory response in mice infected with Trichinella pseudospiralis was associated with host plasma corticosterone levels significantly higher than those seen in uninfecled mice or in mice infected with T. spiralis. Increases in the population of mitochondria and depletion of lipid droplets in cells of the zona fasciculata were seen in the adrenals of mice infected with T. pseudospiralis. Elevations in enteritis, myositis and myocarditis accompanied 100% mortality in adrenalectomized mice infected with T. pseudospiralis, while lower levels of inflammation and no mortality were observed in sham operated or intact animals infected with this parasite. The severe myositis normally accompanying infection with T. spiralis was suppressed by concurrent infection with 1000 or 2000 T. pseudospiralis to levels equivalent to those seen in animals receiving 015 and 0‐41 mg cortisone acetate/25 g mouse/day, respectively.
Characterization of Schistosoma mansoni monoclonal antibodies which block in‐vitro killing: failure to demonstrate blockage of immunity in vivo
Authors: BICKLE Q.D. , ANDREWS B.J.
Published: October 2007

Summary We have characterized various anti‐schistosomular surface MoAbs previously shown to partially block in‐vitro killing of schistosomula by human sera and eosinophils (Dunne et at. 1987). Immunodiffusion analysis showed that four IgM and one IgG3 MoAbs recognized periodate sensitive epitopes on the same molecular species present in schistosomular antigen but their patterns of reactivity with soluble egg antigen demonstrated that at least three distinct epitopes were involved. SDS‐PAGE analysis showed the TgMs to react with 125I‐labelled surface antigens of Mr 35 000‐38 000 and Mr 20 000, and the IgG3 to react with an Mr 38 000 antigen. In spile of their effect in vitro, transfer of the IgM MoAbs at the time ofchallenge of mice vaccinated with irradiated cercariae or of mice injected with an unrelated (anti‐Mr 16 000) protective MoAb failed to produce in‐vivo blocking. Similarly, injection of Schistosoma mansoni eggs, prior infection with worms of one sex, or passive transfer of serum from single‐sex infected mice failed to influence the resistance conferred by vaccination with irradiated cercariae.
Hereford cattle immunized and protected against Boophilus microplus with soluble and membrane‐associated antigens from the midgut of ticks
Authors: OPDEBEECK J.P. , WONG J.Y.M. , JACKSON L.A. , DOBSON C.
Published: October 2007

Summary Hereford cattle were immunized with membranes and soluble components extracted from the midgut of Boophilus microplus. Membrane vaccines protected cattle (91%) against challenge with 3 × 20 000 larval ticks administered at intervals of 7 days. Vaccines made from soluble antigens did not protect cattle. Antibody levels measured by enzyme‐linked immunosorbent assay (EL1SA) related to the levels of protection induced by vaccination.
Ultrastructural and morphometric analyses of eosinophils from the cerebrospinal fluid of the mouse and guinea‐pig infected with Angiostrongylus cantonensis
Authors: YOSHIMURA KENTARO , SUGAYA HIROKO , KAWAMURA KOICHI , KUMAGAI MASAHIRO
Published: October 2007

Summary Guinea‐pigs infected with Angiostrongylus cantonensis developed pleocytosis and eosinophilia in the cerebrospinal fluid (CSF) at day 12 post‐infection (p.i.). showing a peak response at day 20 p.i., followed by a gradual reduction. Ultrastructural observations on CSF eosinophils from infected mice and guinea‐pigs revealed various signs of eosinophil degranulation after day 14 p.i., suggesting the exocytosis of lysosomal material. Morphometric analysis indicated that CSF eosinophils after day 22 p.i. contained fewer granules as well as smaller granules than those at days 14‐20 p.i. These data suggest that CSF eosinophils release granule constituents into the outside of the cells and these secretion products could interact with the intracranial worms and are probably related to worm death. As degenerative atrophy or partial loss of Purkinje cells and the spongy vacuolation of the white matter were noted in the cerebellum of infected mice, it was suggested that CSF eosinophils could be a possible cause of neurological disorders in angiostrongyliasis cantonensis.
Acquired resistance to the human hookworm Necator americanus in mice
Authors: WELLS CATHERINE , BEHNKE JERZY M.
Published: October 2007

Summary BALB/c mice were exposed to primary or secondary infection with the hamster‐adapted strain of Necator americanus, and the course of infection was monitored through worm recovery and immunological assays. Significantly fewer viable larvae were recovered from the skin site of reinfected mice on day 2 post‐infection, and fewer larvae resided in ihe lungs of challenged mice 3‐5 days after infection, suggesting that the skin was involved in resistance to secondary infection. The serum antibody response to L3 antigen was enhanced during secondary infection, peaking on day 9, and the bronchoalveolar leucocyte (BAL) response was more intense at this stage. Thus the secondary BAL response was initiated more promptly than the primary response, peaking on day 13 at twice the intensity of the primary response and five times above the resting level. Differential counts revealed that by far the most significant changes in cell populations were those observed for eosinophils in lavage fluid. At the peak of the response a 925‐fold increase over control levels was detected in mice undergoing a challenge infection. Some cellular and serological components of the secondary response were defined in the present work and it was concluded that reinfected mice have the capacity to trap parasites during their passage through the skin and development in the lungs.
Giardia muris infection in mice with concurrent graft‐versus‐host reaction
Authors: FERGUSON ANNE , MUNRO GRANT H.
Published: October 2007

Summary The effects of concurrent graft‐versus‐host reaction (GvHR) on the course of Giardia infection in CBA x BALB/c F1 mice have been examined, to test the hypothesis that T‐cell‐mediated immunity, in the form of a local DTH reaction, alters the host‐parasite relationship in favour of the host by changing the physical environment of the parasite. GvHR did not enhance immunity, indeed mice infected with Giardia at a late stage of GvHR had significantly higher faecal cyst excretion and prolongation of the plateau phase of infection, indicating a degree of immunodeficiency.
Trypanosoma cruzi metacyclic trypomastigotes: neutralization by the stage‐specific monoclonal antibody 1G7 and immunogenicity of 90 kD surface antigen
Authors: ARAGUTH MARCIA F. , RODRIGUES MAURICIO M. , YOSHIDA NOBUKO
Published: October 2007

Summary In this study we have investigated the ability of the stage‐specific monoclonal antibody (MoAb) 1G7 to neutralize the infectivity of Trypanosoma cruzi metacyclic trypomastigotes (Tulahuen strain). Mice inoculated with metacydics pre‐incubated with 1G7 or the corresponding Fab fragments were found to develop greatly reduced parasitaemias compared with control animals. Similar results were obtained when mice received 1G7 (0‐5 mg/mouse) before challenge with metacyclics. The 90 kD surface protein recognized by MoAb 1G7 was affinity purified and analysed for its immunogenic properties. Immunization of mice with 90 kD antigen induced antibodies that reacted with the native metacyclic surface antigen. The purified antigen was also capable of specifically stimulating the‘in‐vitro’ proliferation of 90 kD‐primed T‐cells. Furthermore, in a preliminary experiment in which mice were immunized with the purified polypeptide and challenged with Tulahuen metacyclics, low parasitaemia levels were observed in 60% of animals as opposed to non‐immunized controls. The iodinated 90 kD antigen, which has previously been shown to be ubiquitous among T. cruzi strains, was precipitated by different immune sera including various chagasic sera.
Enzyme‐linked immunosorbent assay for Giardia‐specific IgA in mouse intestinal secretions
Authors: HEYWORTH MARTIN F. , KUNG JACOB E. , CAPLIN ABIGAIL B.
Published: October 2007

Summary We describe an ELISA for trophozoite‐specific IgA in the intestinal secretions of mice infected with Giardia muris. Using this method, trophozoite‐specific IgA was demonstrated in intestinal secretions of Giardia‐infected immunocompetent BALB/c mice. Such antibody was undetectable in the intestinal secretions of Giardia‐infected athymic (nude) mice. Immunocompetent BALB/c mice are able to clear G. muris infection whereas nude mice are not. The study provides evidence that the chronicity of G. muris infection in nude mice results from lack of intestinal trophozoite‐specific IgA in these animals. By means of the ELISA, trophozoite‐specific IgA was demonstrated in intestinal secretions from immunocompetent mice in the absence of protease inhibitors.
Protective immunity to malaria: studies with cloned lines of rodent malaria in CBA/Ca mice. IV. The specificity of mechanisms resulting in crisis and resolution of the primary acute phase parasitaemia of. Plasmodium chabaudi chabaudi and P. yoelii yoelii
Authors: JARRA W. , BROWN K. N.
Published: October 2007

Summary Low numbers of parasites from cloned lines of the rodent malaria parasites, Plasmodium chabaudi chabaudi AS and P. yoelii yoelii A, injected into CBA/Ca mice produce acute but usually self–limiting infections. During crisis, i.e. 1–2 days after peak parasitaemia, ‘pre–immune’ mice experiencing such ‘background’ infections were reinfected intravenously with homologous parasites or parasites of heterologous strains or species. P. c. chabaudi AS pre–immune mice controlled an AS challenge with essentially the same kinetics as the background infection. Reinfection of AS pre–immune mice with the heterologous (CB and IP–PCI) P. c. chabaudi strains or P. chabaudi adami DS had little effect on the initial growth of these parasites, although eventually the parasitaemia was controlled. In contrast, a partial inhibitory effect on the growth of P. vinckei lentum DS was evident. Challenge with the non–lethal (A) or lethal (YM) variants of P. y. yoelii resulted in an increase in both the growth and virulence of these parasites. P. y. yoelii A pre–immune mice controlled a homologous challenge, but were less effective at controlling the YM variant. In addition, they were unable to clear rapidly a P. c. chabaudi AS or P. v. lentum DS challenge. Both the multiplication and virulence of P. berghei ANKA were enhanced. These findings demonstrate that resolution of the primary acute parasitaemia in P. c. chabaudi AS– and P. y. yoelii A–infected mice is predominantly mediated by species– and strain–specific mechanisms.