bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunity to coccidiosis: genetic influences on lymphocyte and cytokine responses to infection with Eimeria vermiformis in inbred mice
Authors: WAKELIN D. , ROSE M. E. , HESKETH P. , ELSE K. J. , GRENCIS R. K.
Published: October 2007

Cellular and cytokine responses to infection with Eimeria vermiformis were compared in BALB/c (resistant) and C57BL/6 (B6‐susceptible) inbred mice. Cellular responses in the mesenteric lymph node (MLN) occurred sooner after primary infection in the resistant BALB/c strain. In contrast, proliferative responses occurred earlier after challenge in B6 mice. Resting levels of CD4 + ve and CD8 + ve T‐lymphocytes in the MLN differed between the two strains but the relative numbers of each subset remained relatively constant throughout primary infection. MLN cells taken at intervals after infection were assayed for release of the cytokines IFN‐gamma, IL‐5 and IL‐10 after culture in vitro with the mitogen Concanavalin A (Con‐A) or with parasite antigen. With either stimulus cells from resistant BALB/c mice released IFN‐gamma and IL‐5 earlier after infection than did B6 cells. The strains had a comparable absolute ability to produce IFN‐gamma but BALB/c cells released more IL‐5 than did B6, levels declining, rather than increasing, during primary infection in the latter. Only cells from BALB/c mice released IL‐10 during infection. Cells taken after a secondary infection released relatively little cytokine after pulsing in vitro. These data suggest that the difference in response phenotype between the two strains when infected with E. vermiformis reflect a kinetic, rather than a qualitative, difference in ability to mount protective T‐helper (Th) cell subset responses. No evidence was found for a Th2‐mediated interference with ability to release IFN‐gamma, the cytokine most closely associated with protective immunity.
The role of reactive nitrogen intermediates in modulation of gametocyte infectivity of rodent malaria parasites
Authors: MOTARD ANNIE , LANDAU IRENE , NUSSLER ANDREAS , GRAU GEORGES , BACCAM DOANH , MAZIER DOMINIQUE , TARGETT GEOFFREY A. T.
Published: October 2007

Direct feeding of Anopheles stephensi mosquitoes on mice infected with Plasmodium vinckei petteri showed that, during the periods of schizogony in the blood, the infectivity of gametocytes was markedly reduced. This could be prevented by prior injection of the L‐arginine analogue, Nw‐nitro‐L‐arginine (NwNLA) showing that the altered infectivity was due to reactive nitrogen intermediates (RNI). Similar effects on transmission of P. yoelii nigeriensis were demonstrated in vitro by membrane feeding of the mosquitoes. The in vitro reduction in infectivity could be reversed by injecting the L‐arginine analogue either into the infected mouse donor of serum, or into the membrane feeding chamber. Elevated levels of TNF and IL‐6 were demonstrated during the course of infection but did not correlate well with nitrogen radical activity. Similarly, direct measurements of NO2‐ and NO3‐ did not reflect the nitrogen radical activity revealed by addition of the specific L‐arginine analogue.
Stage‐specific surface antigens of the cattle lungworm Dictyocaulus viviparus
Authors: BRITTON COLLETTE , CANTO GERMINAL J. , URQUHART GEORGEM. , KENNEDY MALCOLM W.
Published: October 2007

Immunofluorescence on live Dictyocaulus viviparus parasites revealed a significant antibody response by vaccinated and patently infected bovine hosts to the sheath of infective larvae (L3), a structure which is generally thought to be shed from the parasite surface prior to invasion of host tissue. In contrast, surface‐exposed antigens of the adult, egg and pulmonary L1 stages were recognized only by serum antibody from calves exposed to a patent lungworm infection. Radioiodination of sheathed L3 identified a restricted set of components while a more complex pattern of labelled material was observed with adult parasites. Many more components of adult worms were labelled by the Bolton‐Hunter than by the lodogen reagent, probably reflecting the more penetrative labelling propensities of the former. Stage‐specificity of surface‐associated antigens of adult parasites was demonstrated by their immunoprecipitation by antibody from patently‐infected, but not from vaccinated, calves. There was no in vitro release of the major iodinatable surface‐associated antigens of adult parasites nor any binding of antibody raised against adult excretory‐secretory (ES) products to the surface of living adult worms, suggesting that surface components do not contribute to adult ES products in this species. Antibody responses to the surface of adults. L1 and eggs were specific to patently‐infected animals and may provide a useful indicator of exposure to patent infection.
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

Immunosuppressed 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

The 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

The 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

Experiments 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

The 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

The 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

Adherent 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

Using 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

Free‐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

Rabbits 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

The 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

Two 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

Monospecific 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

It 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

Trypanosoma 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

Mice 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

Human 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.
Toxocara canis‐induced murine pulmonary inflammation: analysis of cells and proteins in lung tissue and bronchoalveolar lavage fluid
Authors: BUIJS J. , LOKHORST W. H. , ROBINSON J. , NIJKAMP F. P.
Published: October 2007

The pulmonary immuno‐inflammatory reaction and its effect on microvascular integrity was studied in Toxocara canis infected BALB/c mice. The investigation aimed to compare changes in lung histology and composition of bronchoalveolar lavage fluid (BALF) caused by T. canis infection with those described to occur in allergic asthma. Groups of (non)‐infected mice (1000 ova) were investigated until 90 days post infection (p.i.). Migration of the larvae through the lungs was followed by a rapidly progressing multifocal interstitial and alveolar inflammation. Eosinophils and lymphocytes formed perivascular and partially peribronchial mixed cellular infiltrates. Lymphocytes with plasma cell morphology staining intracellularly for either α, ɛ or γ immunoglobulins were demonstrated. BALF, collected from mice infected with either 250, 500 or 1000 ova was analysed at 14 and 28 days p.i. A dose‐related increase in cell numbers and in albumin and IgA concentration was observed. IgE increase was independent of the infective dose. Peak values were measured at 14 days p.i. Albumin increase in lung homogenate was highest at 28 days p.i. 30% of the lymphocytes consisted of T cells carrying Thy‐1.2 and L3T4 surface antigens. It is concluded that T. canis‐induced pulmonary inflammation affects the permeability of the microvasculature. This is expressed by interstitial oedema and plasma exudation in the airway lumen. Both phenomena occur also in allergic asthma. It is suggested that increased permeability of the microvasculature is mediated by T cells and eosinophils.
Cross‐protection between species of the Schistosoma haematobium group induced by vaccination with irradiated parasites
Authors: NAVARRETE S. , ROLLINSON D. , AGNEW A. M.
Published: October 2007

Mice vaccinated with irradiated cercariae of Schistosoma haematobium, S. bovis and S. margrebowiei showed good levels of resistance (38–62%) against an homologous challenge, and varying degrees of resistance (19–46%), against challenges with closely related species. No protection against S. mansoni was induced by vaccination with any of these species. This restricted cross‐protection reflects the close phylogenetic relationship between species of the S. haematobium group and indicates that immunologically important epitopes are conserved within this species complex.
Plasmodium falciparum malaria transmission‐blocking immunity under conditions of low endemicity as in Sri Lanka
Authors: PREMAWANSA SUNIL , GAMAGE‐MENDIS ASOKA , PERERA LAKSHMAN , BEGARNIE STEVEN , MENDIS KAMINI , CARTER RICHARD
Published: October 2007

Sera from acute primary Plasmodium falciparum patients in Sri Lanka were tested for the presence of antibodies against gamete antigens and for their functional effects of transmission blocking activity. Comparisons were made with corresponding data from a previous study from sera of patients from Papua New Guinea where malaria is more highly endemic. Although the prevalence of anti‐gamate antibodies in the two groups were broadly similar, the prevalence of infectivity suppressive effects in the Sri Lankan sera (56%) was less than in Papua New Guinea sera (75%), suggesting that the generation of functionally effective transmission blocking antibodies requires prolonged exposure to multiple inoculations of malaria. In Papua New Guinea sera there was a good correlation between transmission blocking effects and antibody responses to Pfs 230, a known target of transmission blocking antibodies. Among the Sri Lankan sera no strong correlation was found between transmission blocking effects and the presence of antibodies to gamete surface antigens Pfs 230 nor Pfs 48/45 as detected by immunoprecipitation of radio‐iodinated gamate proteins; a strong correlation was however, found between the intensity of response to gamete surface antigens by IFA and transmission blocking effects of these sera. It is possible therefore, that the antigens identified by IFA include non‐protein moieties and that these may be the targets of transmission blocking antibodies in sera from acute primary infections of P. falciparum.
Tumour necrosis factor production by monocytes from cattle infected with Trypanosoma (Duttonella) vivax and Trypanosoma (Nannomonas) congolense: possible association with severity of anaemia associated with the disease
Authors: SILEGHEM MAARTEN , FLYNN J. NORMAN , LOGAN‐HENFREY LINDA , ELLIS JOHN
Published: October 2007

Plasma of cattle infected with Trypanosoma vivax IL2337 was analysed for the presence of bovine tumour necrosis factor (TNF) by EIA in which TNF was captured by a monoclonal antibody (MoAb BC9) and detected by a rabbit polyclonal antiserum. At week 2–3 post infection (p.i.) only a low activity was detected. Therefore, an alternative approach was used in which TNF production was measured ex vivo. Monocytes from T. vivax IL2337‐infected cattle manifested a strong TNF production which peaked around week 2½ p.i. Monocytes from pre‐infection controls did not produce significant concentrations of TNF. In contrast to the strong production of TNF by monocytes from cattle infected with T. vivax IL2337, TNF production was not detected from monocytes of cattle infected with Trypanosoma congolense ILNat 3.1. Trypanosomiasis due to these parasites differs in the degree if anaemia as indicated by packed cell volume (PCV). T. vivax IL2337 causes a severe, acute PCV fall whereas T. congolense ILNat 3.1. causes a more gradual fall in PCV.
Transmission‐blocking antibodies against multiple, non‐variant target epitopes of the Plasmodium falciparum gamete surface antigen Pfs230 are all complement‐fixing
Authors: READ D. , LENSEN A. H. W. , BEGARNIE S. , HALEY S. , RAZA A. , CARTER R.
Published: October 2007

We have studied the properties of 16 newly derived monoclonal antibodies (MoAbs) against Pfs230, a gamete surface protein of Plasmodium falciparum and a target of transmission‐blocking antibodies. All 16 MoAbs recognized Pfs230 by immunoprecipitation from non‐ionic detergent extracts of the protein radio‐labelled with 125Iodine. The MoAbs also recognized this protein on Western blots under non‐reducing conditions but none of them recognized the protein under reducing conditions. Using an immunoradiometric assay the MoAbs appear to define nine different epitope regions. The MoAbs were tested for their ability to lyse extra‐cellular female gametes of P. falciparum isolate 3D7. Eight of the MoAbs, all of isotype IgG2a, mediated complement‐dependent lysis of the gametes; seven of the MoAbs, all isotype IgG1, failed to lyse the gametes in the presence of active complement. The eight complement‐fixing MoAbs mediated almost total suppression of infectivity of gameto‐cytes of P. falciparum 3D7 to mosquitoes; where tested this suppression was mainly complement‐dependent. The seven non‐complement‐fixing MoAbs had no significant effect on the infectivity of gametocytes of P. falciparum 3D7 to mosquitoes. When tested by immunofluorescence the target epitopes of all the MoAbs were conserved in each of the five different isolates of P. falciparum which were tested.
Heterogeneity of antigen‐specific CD4+ T cell clones from a patient with Schistosomiasis mansoni
Authors: HIRAYAMA KENJI , S. ABRAMS JOHN , J. QUINN JOHN , A. HARN DONALD
Published: October 2007

Two subsets of differentiated murine helper T cells, Th1 and Th2, based on secretion products in response to antigen have been described (Cher & Mosmann 1987, Coffman et al. 1988, Lopez et al. 1988, Paliard et al. 1988, Patel et al. 1988, Mosmann & Coffman 1989). To analyse immunological function of antigen‐specific CD4+ T cells in human schistosomiasis, we produced schistosomal egg antigenspecific T cell clones from a former patient. We identified four different types of CD4+ T cell clones by analysis of cytokine production. Two of the four types of the clones corresponded to murine Th1 or Th2 subsets; a third type was of the Th0 subset (Th1 + 2) and a fourth type produced IL‐5 dissociated from IL‐4. Analysis of the antigen(s) recognized by these T cell clones showed that all of the clones proliferated in response to soluble egg antigen(s) (SEA) found within a pl fraction whose pH was 5·2. T cell Western blot analysis of the stimulatory pl fraction demonstrated that the apparent Mr of the relevant antigens recognized by the clones were 38 kDafor the Th2 homologue, and 45–55 kDa for the Th1 homologue.
The effect of treating with anti‐interleukin‐1 receptor antibody on the course of experimental murine cutaneous leishmaniasis
Authors: M. THEODOS CYNTHIA , SHANKAR ANURAJ , L. GLASEBROOK ANDREW , D. ROEDER WILLIAM , G. TITUS RICHARD
Published: October 2007

To assess the role of interleukin‐1 (IL‐1) in cutaneous leishmaniasis, Leishmania major‐infected mice were treated with an anti‐IL‐1 receptor monoclonal antibody, LA‐15.6. MoAb LA‐15.6 prevents binding of IL‐1 to both the T cell and B cell/macrophage forms of the IL‐1 receptor. We found that treating with LA 15.6 inhibited the development of cutaneous lesions of L. major in both genetically‐susceptible and resistant mice. Interestingly, this treatment had little or no effect on parasite numbers in the lesions or on the cytokines (interferon‐gamma, interleukin‐4) that the animals produced in response to infection with the parasite. These results suggest that although IL‐1 plays a detrimental role in cutaneous leishmaniasis, it does not mediate this effect by altering the parasite‐specific T cell response.
Antibody‐dependent neutrophil‐mediated parasite killing in non‐lethal rodent malaria
Authors: WAKI S.
Published: October 2007

The effects of administrating recombinant human granulocyte colony‐stimulating factor (rhG‐CSF) and passively transferring immune serum on infection with an attenuated variant of Plasmodium berghei XAT (Pb XAT), in severe combined immunodeficiency (SCID) mice were examined. In immune competent (C.B‐17) mice, the attenuated parasite infection was inevitably self‐resolving and degenerating forms inside erythrocytes appeared, coinciding with the drop in parasitaemia, whereas SCID mice were unable to control parasite growth and all the mice died. Continuous administration with rhG‐CSF caused neutrophilic granulocytosis in both SCID and C.B‐17 mice. The effect of rhG‐CSF on the infection in C.B‐17 mice was to suppress the course of the parasitaemia at an early phase whereas it had no effect in SCID mice. When immune serum was transferred on the day of infection, the prepatent period was prolonged two days in both SCID and C.B‐17 mice. When administration with rhG‐CSF was combined with transfer of immune serum, SCID mice showed four days delay in patency and degenerating parasites were seen during the course of parasitaemia, although the infection was ultimately fatal. C.B‐17 mice similarly treated showed a seven day delay in the onset of the patent parasitaemia which was of a lesser magnitude and shorter in duration compared with control mice. On the other hand, when C.B‐17 mice were splenectomized three weeks before infection and then treated with rhG‐CSF and immune serum, no degenerating parasites were seen during the infection and all mice died with high parasitaemias. These results show that antibody‐dependent neutrophil‐mediated parasite killing may occur in the spleen of mice infected with P. berghei XAT.
An analysis of the humoral immune response of dogs following vaccination with irradiated infective larvae of Dirofilaria immitis
Authors: MEJIA J. SANTIAGO , CARLOW CLOTILDE K. S.
Published: October 2007

In this study, dogs were immunized with irradiated L3 larvae of Dirofilaria immitis. Following challenge with non‐irradiated L3, vaccinated dogs had an average of 71% fewer adult worms compared to non‐vaccinated animals. A comparative analysis of eosinophil and antibody responses of these two groups of dogs is presented. Vaccinated dogs preferentially recognized several larval (14, 20, 30, 34, 39 kDa), adult worm (20 kDa) and microfilarial (36, 38, 71, 84 kDa) antigens. To characterize these antigens, the extent of glycosylation was assessed. The data suggest that an earlier response to these antigens may be important in the protection induced in dogs by administration of irradiated L3 of D. immitis.
Restricted heterogeneity of T cell receptor variable alpha chain transcripts in hearts of Chagas’disease cardiomyopathy patients
Authors: CUNHA‐NETO EDÉĈAIO , MOLITERNO RICARDO , COELHO VERÔNICA , GUILHERME LUIZA , BOCCHI EDIMAR , HIGUCHI MARIA DE LOURDES , STOLF NOEDIR , PILEGGI FULVIO , STEINMAN LAWRENCE , KALIL JORGE
Published: October 2007

The role of autoimmunity in the pathogenesis and progression of heart lesions in the chronic phase of Chagas’disease is controversial. In the absence of parasites in situ, the T cell infiltrate seen in heart lesions may be the primary determinant of tissue damage ultimately leading to heart failure and death. We used the polymerase chain reaction to amplify each known T cell receptor (TCR) Vα and Vβ subfamily‐specific sequence in transcripts derived from heart samples obtained from Chagas’cardiomyopathy patients. The average number of TCR Vα. subfamilies (7·1 per tissue sample) was significantly lower than that for TCR Vβ subfamilies (15·1 per sample). The average percentage of tissue samples positive per TCR Vα. and Vβ subfamily was respectively 39·6% vs. 73·5%. These data suggest that, in Chagas’heart lesions, the detectable TCR Vα. repertoire is significantly narrower than TCR Vβ repertoire. On the other hand, in normal heart tissue, diversity of Vα. and Vβ TCR is similar among the scarce circulating T cell population. Such evidence of restricted TCR V region repertoire has been described in experimental and human autoimmune diseases. Our results are consistent with the possibility that T cells responsible for heart damage in chronic Chagas’cardiomyopathy may be recognizing a few heart‐specific antigenic targets.
Release of nitric oxide during the experimental infection with Trypanosoma cruzi
Authors: PETRAY PATRICIA , ROTTENBERG MARTÍN E. , GRINSTEIN SAUL , ÖRN ANDERS
Published: October 2007

We analysed the production of nitric oxide (NO) intermediates by cells from BALB/c mice infected with either virulent (Tulahuén or RA) or avirulent (CA‐1) strains of Trypanosoma cruzi. Peritoneal or spleen cells from mice infected with T. cruzi released NO when incubated without further stimuli. Cells from mice during the acute stage of infection accumulated higher levels of inducible NO synthase mRNA and produced both, before and after lypopolysaccharide stimulation, higher amounts of NO than cells from mice chronically infected with T. cruzi. NO synthesis showed similar kinetics in connection with all three strains ofT. cruzi, but cells from mice inbred with the Tulahuén or RA strains released higher levels of IFN‐γ, an activator of the NO pathways, than cells from mice infected with the CA‐1 strain. In vivo administration of L‐Ng‐monomethyl‐L‐arginine (L‐NMMA), a competitive inhibitor of NO synthase, increased the susceptibility of mice to T. cruzi. We conclude that infection with T. cruzi induces NO production, and suggest that NO plays a role in the resistance against the parasite.
Cellular inflammatory responses in skin of sheep selected for resistance or susceptibility to fleece rot and fly strike
Authors: COLDITZ I. G. , LAX J. , MORTIMER S. I. , CLARKE R. A. , BEH K. J.
Published: October 2007

Leucocyte populations were examined in normal and inflamed skin of sheep bred for resistance (R) or susceptibility (S) to bacterial fleece rot and the common sequela, body strike caused by the dipteran parasite Lucilia cuprina. No differences between R and S lines were found in numbers of neutrophils accumulating in acute inflammatory lesions induced by activated complement, leukotriene B4, interleukin(IL)‐lβ, tumour necrosis factor‐α, IL‐8 orendotoxin from Pseudomonas aeruginosa. T19+ (a γδ T cell subset) lymphocytes and eosinophils were more prevalent in skin of sheep from the S line whereas IgE+ cells were more prevalent in skin of sheep from the R line. In an unrelated population of sheep, animals with low fleece rot scores had more intense neutrophil migration into inflammatory lesions induced by all the mediators examined than did animals with high fleece rot scores. IgE+ cells were more prevalent in animals with low fleece rot scores, although in contrast to R and S lines, T19+ cells tended to be elevated in this group of animals. The results suggest that defence mechanisms associated with IgE+ cells in skin may play an important role in resistance to fleece rot and fly strike.
Mechanisms of innate and acquired resistance to Cryptosporidium parvum infection in SCID mice
Authors: McDONALD V. , BANCROFT G. J.
Published: October 2007

SCID mice, which lack T and B cells, were used as hosts to investigate the nature of both T cell‐independent and T‐cell‐dependent immune responses to infection with Cryptosporidium parvum. We found previously that SCID mice developed chronic infections in which the level of oocyst excretion was low up to about eight weeks post‐infection but then increased significantly to cause morbidity and death after 13 weeks. In the present study, weekly administration of an anti‐IFN‐γ monoclonal antibody (MoAb) resulted in a shortened prepatent time, significant increase in oocyst excretion and early onset of disease and death. These results suggested an immunologically mediated resistance to C. parvum in the SCID host which required the production of IFN‐γ. Attempts to demonstrate a role for TNF in nonspecific immunity were unsuccessful as injection of mice at weekly intervals with an anti‐TNF MoAb failed to alter the course of infection. In contrast to the chronic infection observed in the mice above, SCID mice reconstituted with spleen cells from naïve BALB/c mice were able to recover. Depletion of CD4+ cells from the donor population abrogated this protective effect. Mice receiving spleen cells depleted of CD8+ cells were able to recover but the patent infection was prolonged compared with those obtained in mice receiving unfractionated cells. These results demonstrate that CD4+ cells are necessary for the development of immunity to C. parvum infection in reconstituted SCID mice, but, in addition, that CD8+ cells also make a significant contribution to this immunity.