bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of the hepatoprotective effects of immune cells and serum in Schistosoma mansoni‐infected immunosuppressed mice
Authors: HASSOUNAH O. A. , DOENHOFF M.J. 
Published: October 2007

SummaryImmunosuppressed mice with heavy Schistosoma mansoni infections suffer from a severe hepatotoxicity reaction soon after the onset of infection patency, and this may be directly consequent upon the failure of the hosts to mount adequate granulomatous responses to embolized parasite eggs. Immune serum or immune peripheral lymphocytes from normal S. mansoni‐infected immunologically intact donor mice were transferred to homologously‐infected syngeneic T‐cell deprived recipients to test the respective capacities of the transferred humoral or cellular immune effector elements to prevent hepatocellular damage and to reconstitute granuloma formation. Transferred immune serum was very effective in preventing liver cell damage, but did not significantly reconstitute the capacity to form granulomas in the recipients. In contrast, mice receiving immune spleen and mesenteric lymph node cells had their capacity to form granulomas around liver‐bound eggs reconstituted, but lymphoid cell transfer was less effective in protecting against hepatocyte damage than serum transfer. Protection of host tissues may therefore not be the main role of the T‐cell mediated S. mansoni egg granuloma.
Age‐dependency of serum isotype responses and antigen recognition in human whipworm (Trichuris trichiura) infection
Authors: NEEDHAM C. S. , LILLYWHITE J. E. , DIDIER J. M. , BIANCO A. E. , BUNDY D. A. P. 
Published: October 2007

SummaryThe present study examines the age‐dependency of parasite‐specific isotype responses and antigen recognition profiles of individuals within a Trichuris trichiura endemic community, in order to evaluate the significance of serum antibodies as determinants of observed age‐related patterns of infection intensity. A high degree of individual heterogeneity is observed in isotype responses to separated T. trichiura antigens by Western blot. Recognition by IgG1 antibodies exhibits marked age‐dependency. The age‐profiles of IgG1 responses to selected antigens of 16–17 kDa and 90 kDa molecular weight reflect the age‐related changes in current infection intensity at the population level. Similarly, mean age patterns of IgG2 responses to a 90 kDa antigen, and mean IgG4 responses to a 16–17 kDa antigen reflect mean infection levels. IgG3 responses are negligible, and for methodological reasons, both IgE and IgM specificities are not presented. IgA responses to separated antigens of 16–17 kDa and 90 kDa, exhibit age‐profiles which may suggest the development of an IgA‐mediated acquired resistance to T. trichiura with age. IgA levels remain elevated throughout early adulthood, when infection intensity levels markedly decrease, supporting the hypothesis that IgA antibodies may be significant in generating the convex nature of the age‐infection profile of T. trichiura.
Isotype‐specific antibody responses to Haemonchus contortus in genetically resistant sheep
Authors: GILL H. S. , GRAY G. D. , WATSON D. L. , HUSBAND A. J. 
Published: October 2007

SummaryThe kinetics of anti‐Haemonchus antibody responses in serum and faecal extracts of pasture‐reared, genetically resistant and random‐bred sheep infected with Haemonchus contortus were examined using an isotype‐specific ELISA. Anti‐Haemonchus antibodies of IgA, IgG1, IgG2 and IgM isotypes were detected in serum and faecal extracts of both resistant and random‐bred sheep after challenge infection. Serum IgG1 and IgA levels in resistant sheep were significantly higher than in random‐bred sheep between 10 and 31 days after infection. However, there were no differences in IgG2 and IgM antibody responses between the two genotypes. Faecal antibody responses to H. contortus showed a clear genetic effect with resistant sheep exhibiting higher IgA levels throughout infection and higher IgG1 levels between 24 and 31 days after infection. Furthermore, serum IgG1 and IgA, and faecal IgA responses were negatively correlated with faecal egg counts in both genotypes on 17, 24 and 31 days after infection. Together, these results are taken to indicate that anti‐parasite IgA and IgG1 antibodies may play an important role in genetically determined resistance of sheep to haemonchosis
Vaccine development against cutaneous leishmaniasis. Subcutaneous administration of radioattenuated parasites protects CBA mice against virulent Leishmania major challenge
Authors: RIVIER D. , SHAH R. , BOVAY P. , MAUEL J. 
Published: October 2007

SummaryExperiments described in this paper were aimed at determining whether subcutaneous inoculation of live, avirulent Leishmania major would protect mice against infection by the virulent parasite. To this effect, promastigotes or amastigotes of a highly virulent strain of L. major (MRHO/IR/76), used in human trials of leishmanization, and which induces non‐healing skin lesions in both CBA and BALB/c mice, were rendered non‐pathogenic by gamma irradiation. A dose of 150 krad was required to abrogate the virulence of the parasite as tested on BALB/c mice. Strikingly, however, not all leishmanias were completely inactivated by this procedure since live parasites were detected in the footpads and/or the inguinal lymph nodes as long as 28 days (CBA) or 18 weeks (BALB/c) after injection. Furthermore, 150 krad‐irradiated promastigotes retained the capacity to transform into amastigotes intracellularly in vitro. Subcutaneous inoculation of this irradiated ‘vaccine’ confered onto CBA mice a high degree of protection against challenge by both the homologous and a heterologous (MRHO/SU/59/P) strains of L. major. Lymph node cells from protected animals acquired the capacity to activate infected macrophages in vitro to kill intracellular L. major. To allow for maximum development of immunoprotection, the irradiated promastigotes had to remain viable, perhaps reflecting a requirement for transformation into amastigotes in the vaccinated host.
Dynamic interaction between Leishmania infection in mice and Th1‐type CD4+T‐cells: complexity in outcome without a requirement for Th2‐type responses
Authors: SCHWEITZER A. NICOLA , SWINTON JONATHAN , ANDERSON ROY M. 
Published: October 2007

SummaryThe interaction between Leishmania parasites and Th1 cells is investigated using a simple mathematical model of immunological responses and parasite population growth within the host. The model generates patterns of resistance and susceptibility to infection that mirror observed trends in experimental infections of mice and of humans exposed to infection in areas of endemic transmission. The heterogeneity in outcome predicted by the model can arise either through differences in the values of the parameters that characterize the genetic background of the host or as a consequence of differences in the size of the infecting inoculum of the parasite. Detailed analyses of equilibrium states and of the time course of infection within a host suggest that a limitation in the availability of precursor T‐cells, as a consequence of high levels of recruitment into the activated pool, may play a signficant role in the progression of infection in susceptible hosts. A brief discussion is presented of the implications of model prediction for therapeutic intervention.
Anti‐Thy‐1 treated and irradiated spleen cells from (BALB/cXC57Bl/6) F1 mice infected with Plasmodium chabaudi chabaudi can transfer protection into irradiated hosts
Authors: LEGORRETA‐HERRERA M. , FIALLOS‐LEON C. , CEDILLO‐BARRON L. , MARTINEZ‐GOMEZ F. , FOSTER‐CUEVAS M. , FAVILA‐CASTILLO L. 
Published: October 2007

SummaryThe transfer of spleen cells from (BALB/cXC57Bl/6) F1 mice recovered from a Plasmodium chabaudi chabaudi AS infection into irradiated syngeneic recipients conferred protection. Neither elimination of Thy‐1+ cells nor in vitro irradiation of immune cells before transfer affected protection while both anti‐Thy‐1 treatment and irradiation abolished the appearance of anti‐P. c. chabaudi antibodies in the recipients. Superinfection of immune spleen cell donors did not improve their capability to transfer protection which was also unaffected by anti‐Thy‐1 treatment. The serum of mice after one infection was only marginally protective when transferred into irradiated recipients and a second infection improved the protective activity of serum which was not further improved by six infections. The cotransfer of immune serum and immune cells did not result in any synergistic effect. On the other hand, when P. c. chabaudi AS (BALB/cXC57B1/6)F1 infected mice were challenged with a high dose of Plasmodium yoelii 17XL at crisis, the mice were unable to control the heterologous parasite. When mice were challenged with P. yoelii 17XL several weeks after infection with P.c. chabaudi AS, a good degree of cross‐protection was observed.
Enhancement of eosinophil‐mediated cytotoxicity to schistosomula of Schistosoma mansoni by autologous mononuclear cells from patients
Authors: KIMANI G. , MKOJI G. M. , RASHID J. R. , MBUGUA J. M. , KOECH D. , KAMAU T. , MUNGAI B. 
Published: October 2007

SummaryAdherent mononuclear cells (monolayer), when co‐cultured with autologous peripheral blood eosinophils isolated from patients treated for Schistosoma mansoni infections, enhanced the eosinophil‐mediated killing of antibody coated schistosomula. The monolayer increased the activity of the eosinophils by 225%, and was observed in 80% of the patients studied. Heat labile factors other than complement, present in immune serum, further enhanced the ability of eosinophils to kill schistosomula in the presence of the monolayer. On their own the adherent cells did not mediate obvious damage to the parasite. Eosinophils that had been pre‐incubated with the monolayer (100 mins) and tested separately, killed equal numbers of schistosomula as in the co‐culture assay; this excludes the possibility of concurrent schistosomula cytotoxicity by the two cell populations. The ability of the monolayer to activate eosinophils was not altered by inhibitors of protein synthesis. The monolayer was largely consistent of monocytes as demonstrated by an over 96% positive staining for non‐specific esterases.
The sheath of the microfilaria of Wuchereria bancrofti has albumin and immunoglobulin on its surface
Authors: KAR SHANTANU K. , MANIA JAYANTI , BALDWIN C. I. , DENHAM D. A. 
Published: October 2007

SummaryUsing direct fluorescent antibody analysis it was shown that the sheath of live microfilariae of Wuchereria bancrofti has human albumin and the immunoglobulin G subclasses IgG1 and IgG4 on its surface.
Immobilization of Schistosoma mansoni miracidia by activation of the alternate complement pathway at unusually high serum dilution
Authors: KNOPF PAUL M. , PETZKE MARY M. , McLAREN DIANE J. 
Published: October 2007

SummaryFree‐swimming Schistosoma mansoni miracidia were immobilized by adding normal mammalian serum to the water. Miracidial immobilizing activity (MIA) was shown to result from activating the alternate pathway of complement (APC). MIA in normal sera was heat‐sensitive and anibody independent; it was greatly reduced in factor B‐depleted or C6‐depleted, but not in C1‐depleted, human serum. Addition of purified factor B to B‐depleted serum totally restored MIA. Half‐maximal MIA in normal human, rabbit, and guinea pig sera was detectable at final dilutions exceeding 1/100, 1/200, and 1/500, respectively, and normal rat serum was particularly potent, with MIA at dilutions exceeding 1/2000. Detection of APC activity at such high dilutions is quite extraordinary and attributed to the hypotonic conditions. We confirmed and extended previous findings that heat‐inactivated infection sera also display MIA. Immobilizing activity in irradiated‐cercarial vaccine rat serum cofractionated with rat IgG and anti‐SWAP antibody activity. Antibody‐dependent MIA titres were much lower than for APC‐dependent MIA. Based upon light microscope and transmission EM studies, immobilization of miracidia by APC activation was attributed to severe tegumental damage. Miracidia within egg shells were insensitive to MIA.
Immunogenicity in rabbits and monkeys of influenza ISCOMs conjugated with repeated sequences of the Plasmodium falciparum antigen Pf155/RESA
Authors: SJÖLANDER ANDERS , HANSSON MARIANNE , LÖVGREN KARIN , WÅHLIN BIRGITTA , BERZINS KLAVS , PERLMANN PETER 
Published: October 2007

SummaryRabbits and monkeys were immunized with two fusion proteins, ZZ‐M3 and ZZ‐M5, coupled to pre‐formed influenza virus membrane glycoprotein ISCOMs. The fusion proteins comprise two IgG‐binding domains from staphylococcal protein A (ZZ) and repeated amino acid sequences from the C‐terminal (M3) or central (M5) repeat regions of the Plasmodium falciparum antigen Pf155/RESA. The induced antibody responses were of long duration, could be efficiently boosted and were comparable to those obtained with Freund's Adjuvant. The produced antibodies reacted with M3, M5, protein A and the influenza glycoprotein, recognized Pf155/RESA and inhibited merozoite invasion in vitro. These results suggest that coupling of immunogens to pre‐formed ISCOMs may be a basis for construction of multivalent subunit vaccines.
Localization of the A1.12/9 antigen family to the neurones, putative sensory receptors and tegument of Schistosoma mansoni
Authors: HAVERCROFT J. C. , SMITH A. L. 
Published: October 2007

SummaryThe A1.12/9 antigen family were localized to the periphery of vesicle‐like structures in neurones and in the putative sensory receptors of cercariae by immuno‐electron microscopy. After transformation into schistosomula, the antigens were rapidly lost until, after 18 h, no immunoreactivity could be detected. Expression resumed at approximately 36 h post‐transformation and had returned to high levels by 4 days post‐infection. This level was maintained through to the adult worm stage. In 4 day lung schistosomula and in 14 day and 21 day liver schistosomula immunolabelling was observed within the matrix of the tegument itself and also in association with the tegumental membrane and vesicles within the tegument. These properties suggest that the A1.12/9 antigens may be involved in neuropeptide processing pathways. In particular, this family may represent the schistosome homologue of the granin family with which they share common properties and some sequence homology.
Suppression of Schistosoma bovis egg production in cattle by vaccination with either glutathione S‐transferase or keyhole limpet haemocyanin
Authors: BUSHARA H. O. , BASHIR M. E. N. , MALIK K. H. E. , MUKHTAR M. M. , TROTTEIN F. , CAPRON A. , TAYLOR M. G. 
Published: October 2007

SummaryTwo of the antigens which have shown vaccine potential in animal experiments against Schistosoma mansoni are glutathione‐S‐transferase (GST) and GP38, protective epitopes of which are shared with keyhole limpet haemocyanin (KLH). We therefore tested S. bovis GST and KLH for vaccine efficacy against S. bovis in the natural Zebu cattle host. In a preliminary experiment three vaccinations with a total of 1.39 mg of native GSTs of S. bovis induced specific antibody at the time of challenge as detected by Western blotting and ELISA and mean faecal egg counts between weeks 6‐10 post‐challenge were reduced by 56.4 to 82.5% compared to non‐vaccinated controls. Mean adult worm recoveries and tissue egg densities in large intestine and liver samples were also reduced in the vaccinated group, but these differences were not statistically significant. In a subsequent experiment one group of calves was vaccinated with a similar schedule to that used above; a second group of calves was given only two injections of GST (total 0.48 mg protein); a third group of calves was vaccinated twice with a total of 2.0 mg KLH in PBS. All three vaccination schedules induced specific antibody. Both GST vaccination schedules induced significant reductions in faecal egg counts compared to non‐vaccinated controls and in this experiment tissue egg densities were also significantly reduced. A striking finding, however, was that adult worm counts were not reduced by vaccination. An essentially similar outcome resulted from KLH vaccination, since there were significant reductions in faecal and tissue egg counts in the absence of a reduction in adult worm numbers. This type of immunity mimics that induced by natural or experimental infections in the calf and clearly has implications for vaccine design.
Ultrastructural localization of major hydatid fluid antigens in brood capsules and protoscoleces of Echinococcus granulosus of human origin
Authors: SÁNCHEZ F. , GARCIA J. , MARCH F. , CARDEÑOSA N. , COLL P. , MUÑOZ C. , AULADELL C. , PRATS G. 
Published: October 2007

SummaryMonospecific rabbit antisera obtained through experimental immunization with previously purified proteins were used in the ultrastructural localization of two hydatid fluid antigens, in brood capsules and protoscoleces of Echinococcus granulosus of human origin. The antigen‐antibody reaction was revealed by a colloidal gold based method. Reaction was evident in the connective region of the germinal membrane and in the parenchyma of the protoscoleces. Both antigen 5 and antigen B were located in the interstitial material between the parenchymal cells and precisely associated with disorganized areas. The brood capsule wall and the brood capsule contents, the tegument of the protoscoleces, the parenchymal cells, the muscle cells, the calcareous corpuscles and the hooks did not contain antigen 5 or antigen B. Label was not observed in the lumen of the collecting ducts or in the flame cells, although antigen 5 was evident in the periluminal cytoplasm. The origin of the antigens and their release are discussed.
Specificity variants in monoclonal antibodies reactive with peptide epitopes of the ring‐infected erythrocyte surface antigen (RESA) of Plasmodium falciparum
Authors: VENN ALISON , FAIRBRIDGE DAVID , MASON TOM , MARBROOK JOHN , MURRAY LEECIA , ANDERS ROBIN , SHORTMAN KEN 
Published: October 2007

SummaryIt has been suggested that repeat sequence antigens of Plasmodium falciparum may serve the parasite in immune evasion by modifying the host antibody response and impairing the development of protective immunity. According to this proposal networks of cross‐reactive, repeat sequence malarial antigens have the ability to stimulate a high proportion of all somatically mutated B cells with altered antibody specificity, and thus to hinder the normal process of antibody affinity maturation. To determine the rate at which immunoglobulin mutations produce new reactivities with repeat sequence antigens, hybridoma cell lines specific for the ring‐infected erythrocyte surface antigen (RESA) were examined for the incidence of specificity variants that arose naturally or as a result of treatment with the chemical mutagen ethylmethane sulphonate (EMS). From one of the cell lines variants were readily isolated having reactivity towards a very closely related repeat sequence epitope within the same RESA antigen. However, the other hybridoma/antigen combinations revealed no variants. In general, mutations giving rise to antibodies with altered specificity for related repetitive antigens were not readily induced and only limited support of the hypothesis was obtained.
Comparison of the effects of immune killing mechanisms on Trypanosoma brucei parasites of slender and stumpy morphology
Authors: McLINTOCK L. M. L. , TURNER C. M. R. , VICKERMAN K. 
Published: October 2007

SummaryTrypanosoma brucei slender forms predominate over stumpy forms as the parasite population grows but at the peak of a parasitaemic wave and during remission of infection stumpy forms predominate. To determine whether this change in predominance might be caused by selective killing of slender forms, the fates of slender and stumpy form trypanosomes in two in vitro assays of immune‐mediated killing were compared. Parasite populations in which > 90% of cells were of slender morphology were observed to be killed by antibody‐dependent complement‐mediated lysis approximately five times faster than populations in which < 15% of cells were slender and most were of intermediate or stumpy morphology. Quantification of the relationship between the proportion of slender forms in the population and the rate of lysis indicated that slender forms were killed approximately 7.3 times faster than other forms. In an opsonization assay, no differences were observed between slender and stumpy forms in the extent to which they attached to macrophages in an antibody‐dependent manner. These results suggest that the change in proportions of slender and stumpy forms at the peak of a parasitaemic wave results from slender forms being more susceptible to complement‐mediated killing as the antibody response develops.
Antibody to interleukin 5 prevents blood and tissue eosinophilia but not liver trapping in murine larval toxocariasis
Authors: PARSONS J. C. , COFFMAN R. L. , GRIEVE R. B. 
Published: October 2007

SummaryMice previously sensitized by infective‐stage larvae of the canine nematode, Toxocara canis, trap large numbers of challenge larvae within the liver; trapped larvae are found within eosinophilic granulomas. To investigate the role of eosinophils in this phenomenon we examined larval trapping in mice depleted of blood and tissue eosinophils by treatment with a monoclonal antibody (MoAb) (TRFK‐5) produced against recombinant murine interleukin 5 (rmIL‐5). Control mice received either an isotype‐matched control MoAb or PBS. On day 0 test mice were given a sensitization dose of 125 infective T. canis eggs. Test and challenge control mice received 500 infective eggs on day 28. All mice were killed on day 42 and larval numbers within the liver were determined. Liver samples were also collected for histopathological and morphometric examination. When compared to test mice treated with PBS or the isotype control, the level of circulating eosinophils in anti‐IL‐5‐treated test mice was reduced by 94–96% on days 14 and 27,99% on day 35, and 100% on day 42; the level of tissue eosinophils within liver granulomas on day 42 was reduced by 92–95%. The total area of inflammation within the liver was similar among all test groups. However, the highly eosinophilic infiltrates, present in control sections, were replaced in anti‐IL‐5‐treated mice by lymphocytes, macrophages, and foreign‐body giant cells. No difference was found in larval trapping between antibody‐treated groups. These findings suggest that the eosinophil is not necessary for liver trapping in murine larval toxocariasis.
In vitro secretion of cytokines by human mononuclear cells of individuals during and after cutaneous leishmaniasis infection
Authors: FRANKENBURG SHOSHANA , KOFSKY YAEL , GROSS ANAT 
Published: October 2007

SummaryHuman peripheral blood mononuclear cells were incubated in the presence of Leishmania major promastigotes. The culture supernatants were collected after 24 and 72 h and the cytokine content was measured. It was found that mononuclear cells from cured individuals, in the presence of L. major promastigotes, had increased leishmanicidal activity and secreted increased levels of interferon gamma (IFNγ), interleukin‐2 (IL‐2) and tumour necrosis factor alpha (TNF). The levels of IL‐6, on the other hand, did not differ from the levels secreted by cells from unexposed individuals. The secretion of cytokines by cells from patients in the course of the disease was sometimes elevated, but the pattern they presented was more heterogeneous than that of cured individuals, and showed less correlation with leishmanicidal effector activity. Addition of IFN and IL‐2, but not TNF, to cultures from unexposed individuals caused increased leishmanicidal activity, suggesting that these factors play a role in controlling the parasite infection; the role of TNF is not yet clear, and is probably concentration‐dependent.