bluuebunny/crossref_metadata_2025 huggingface dataset:
Reconstitution by bone marrow grafting of the defective protective capacity at the migratory phase but not at the intestinal phase of Nippostrongylus brasiliensis infection in W/Wv mice
Authors: ISHIKAWA N. , HORII Y. , NAWA Y.
Published: October 2007

After a primary infection by subcutaneous inoculation with the infective larvae (L3) of Nippostrongylus brasiliensis, the intestinal worm burden was higher and expulsion was slower in W/Wv mice than in +/+ mice. When the course of infection was segregated into the migratory and intestinal phases, protection during the migratory phase examined by the larval recovery from the lungs and that during the intestinal phase measured by worm burden after intraduodenal implantation with adult worms were both defective in W/Wv mice. The higher susceptibility of W/Wv mice during the migratory phase was normalized by bone marrow re constitution. On the other hand, higher susceptibility of W/Wv mice during the intestinal phase, which was measured by worm burden 24 h after intraduodenal implantation of the larvae recovered from the lungs of rats, was not normalized by bone marrow grafting. Furthermore, slower expulsion seen in W/Wv mice after intraduodenal implantation with adult worms was not hastened by bone marrow reconstitution. These results indicate that the protective mechanisms against N. brasiliensis operating during the migratory phase and those during the intestinal phase were different in terms of bone marrow dependency and that nonmyeloid cells utilizing c‐kit ligand/receptor system to express their functions are involved in the rnucosal defence against N. brasiliensis.
Heterogeneity of IgG antibody responses to cloned Onchocerca volvulus antigens in microfiladermia positive individuals from Esmeraldas Province, Ecuador
Authors: TRENHOLME KATHARINE R. , TREE TIM I. M. , GILLESPIE ANDREW J. , GUDERIAN RONALD , MAIZELS RICK M. , BRADLEY JANETTE E.
Published: October 2007

The prevalence of IgG antibodies to three recombinant O. volvulus antigens, OvMBP/10, OvMBP/11 and OvMBP/29 was determined in a group of 94 microfilaria positive (mf+) individuals resident in the hyperendemic onchocercal area of Esmeraldas Province, Ecuador. Clone OvMBP/11 was the antigen most frequently recognized by patients sera followed by OvMBP/10 and OvMBP/29. When a cocktail of the three recombinant antigens was used the proportion of positive sera increased to 100%. Antibody responses to the fusion partner maltose binding protein (MBP) were low in comparison with those to the cloned antigens and no correlation of responses between individual antigens was observed. The relative level of antibody response to each of the clones in the cocktail varied between individuals. The distribution of IgG responses to OvMBP/11 was bimodal and those to OvMBP/29 and OvMBP/10 were positively and negatively skewed, respectively. When the three recombinant antigens were used in combination this variation was minimized and the pattern of responses showed a normal distribution as was also seen to crude O. volvulus antigen. The cocktail of recombinants thus offers excellent diagnostic sensitivity in combination with the parasite specificity demonstrated previously.
Recognition of Giardia lamblia cyst‐specific antigens by monoclonal antibodies
Authors: CAMPBELL J. D. , FAUBERT G. M.
Published: October 2007

Immunization of BALB/c mice with a sonicated extract of in vitro‐generated Giardia lamblia cysts produced six cystspecific monoclonal antibodies (MoAbs). Two MoAbs (8C5.C11 and 5A4.G6), which recognize proteinaceous cyst antigens, were selected for further study. In indirect immunofluorescence (IFA), MoAb 8C5.C11 reacted with encystation‐specific vesicles in trophozoites beginning 3 h after the induction ofencystation in vitro. This MoAb also recognized cysts which began to appear at 12 h. In contrast, MoAb 5A4.G6 stained only cyst walls. In Western blots, both MoAbs also reacted with cyst antigens, but not trophozoite antigens. MoAb 8C5.C11 first recognized cyst antigen from 3 h encysting cultures, reacting with 26, 28, 42 and 46 kD bands. MoAb 5A4.G6 reacted with a 38 kD band, beginning with 12 h encysting cultures. When added to G. lamblia encysting cultures before the appearance of cysts (0 to 9 h) and in the presence of a source of complement, MoAb 8C5.C11 caused a significant reduction in the numbers of water‐resistant cysts produced in vitro compared to the control. MoAb 5A4.G6 did not affect in vitro encystation. These findings confirm the heterogeneity of cyst antigens, and also indicate that the process of encystation in vitro can be interrupted by antibodies and complement.
Antibodies to the serine rich Entamoeba histolytica protein (SREHP) prevent amoebic liver abscess in severe combined immunodeficient (SCID) mice
Authors: ZHANG TONGHAI , CIESLAK PAUL R. , FOSTER LYNNE , KUNZ‐JENKINS CYNTHIA , STANLEY SAMUEL L.
Published: October 2007

Amoebic liver abscess caused by Entamoeba histolytica is a major cause of morbidity and mortality worldwide. We used mice with severe combined immunodeficiency (SCID mice) to study the role of antibody in protection from amoebic liver abscess, and to identify protective antigens of E. histolytica. Antisera to recombinant versions of two major surface antigens of E. histolytica, the serine rich E. histolytica protein (SREHP) and the 170 kDa adhesin were used in this study. We found that 100% of SCID mice passively immunized with antiserum to the recombinant SREHP molecule were protected from developing amoebic liver abscess after intrahepatic challenge with virulent E. histolytica trophozoites. In contrast, preimmune serum, antiserum to a portion of the 170 kDa adhesin, and antiserum to the trpE fusion partner of SREHP did not protect SCID mice from amoebic liver abscess. Our study demonstrates that antibodies to a recombinant version of the amoebic SREHP molecule can protect against amoebic liver abscess, and suggest the recombinant SREHP molecule should be considered as a possible vaccine candidate to prevent amoebic liver abscess.
Genetic control of the antibody repertoire against excretory/secretory products and acetylcholinesterases ofDictyocaulus viviparus
Authors: McKEAND J. B. , KNOX D. P. , DUNCAN J. L. , KENNEDY M. W.
Published: October 2007

Outbred Dunkin‐Hartley and inbred strain 2 and strain 13 guinea pigs were immunized withDictyocaulus viviparusadult ES products prior to challenge with third stage larvae. Antibody responses of the three strains to adult ES products and the acetylcholinesterase (AChE) isoforms which they contain were examined. Using immunoprecipitation and ELISA, it was observed that responses in the three strains to adult ES products were distinct: considerable heterogeneity in the antibody repertoire was observed between outbred Dunkin‐Hartley animals, with only slight variation occurring amongst the inbred individuals. Responses to the AChE isoforms were heterogeneous amongst individual outbred guinea pigs but were more consistent in inbred strain 2 and 13 animals in which strain‐specific patterns of recognition were observed. Previous studies with nematode infections have indicated a role for the major histocompatibility complex in determining the nature and level of the immune response. As the inbred strains bear different alleles at the Class II region but are identical at the Class I region, the differences observed are likely to be due to genes mapping to the Class II locus. This is therefore the first report of genetic restriction of the antibody repertoire to secreted AChEs of a parasitic nematode.
Severe cryptosporidiosis in children with normal T‐cell subsets
Authors: MØLBAK KARE , LISSE IDA M. , HØJLYNG NIELS , AABY PETER
Published: October 2007

Though Cryptosporidium spp. is considered to cause only a self‐limiting illness in immunocompetent children, data from Guinea Bissau suggest that cryptosporidiosis may be a significant cause of deaths in developing countries. An impaired cellular immune function could explain the severe course of cryptosporidiosis in these children. We therefore investigated in a community study whether pre‐infectious CD4/CD8 status had an impact on incidence and severity of cryptosporidiosis. Of 168 children below two years of age 21 experienced Cryptosporidium‐infection within 156 days after blood sampling, but no tendencies of pre‐infectious impaired cellular immune function was found in the cases compared with controls, nor did nine children who acquired persistent diarrhoea or three who died have impaired CD4/CD8 status.
Temporal differences in the expression of mRNA for IL‐10 and IFN‐γ in the brains and spleens of C57BL/10 mice infected with Toxoplasma gondii
Authors: BURKE JOANNE M. , ROBERTS CRAIG W. , HUNTER CHRIS A. , MURRAY MAX , ALEXANDER JAMES
Published: October 2007

C57BL/10 Sc Sn (B10) mice infected orally with Toxo‐plasma gondii tissue cysts were killed at regular intervals up to day 116 post infection (p.i.) and their brains excised. These were used either to count the total number of cysts in the brain, for RNA purification or histopathological studies. Mortality levels in a parallel group of T. gondii infected B10 mice were also monitored and regular plasma samples taken to measure specific antibody production. Seventy per cent of mice died within the first 35 days of infection. Thereafter deaths were infrequent. Inflammation in the brain was apparent from day 10 onwards and by day 25 there was widespread astrocyte activation, perivascular cuffing, meningitis and extensive encephalitis. Total cyst numbers increased rapidly from day 15 to day 35 when they peaked. By day 60, however, cyst numbers had dropped dramatically and this decrease continued through to day 116. Using the polymerase chain reaction mRNA transcripts for IFN‐γ were detected from the first time point sampled, day 25 p.i., until the end of the study. Transcripts for IL‐10, an inhibitor of IFN‐γ production, release and activity, were not detected until day 70. The predominant antibody detected against T. gondii was IgG2a but not IgG1. Significantly transcripts for IFN‐γ were found in the spleens of infected but not noninfected animals. Our results suggest that an inflammatory response associated with IFN‐γ production in B10 mice eventually controls T. gondii infection. After the cyst burden has dropped dramatically transcripts for IL‐10 are detected in the brain, perhaps to suppress inflammation, and limit pathology.
Bancroftian filariasis‐differential reactivity of anti‐sheath antibodies in microfilariae carriers
Authors: RAVINDRAN B. , SATAPATHY A. K. , SAHOO P. K.
Published: October 2007

Anti‐sheath antibodies have been detected using an immunofluorescent assay (IFAT) in the sera of microfilariae carriers (AS cases) residing in areas endemic for Bancroftian filariasis. Microfilariae (mf) of Wuchereria bancrofti purified from five different mf carriers were used separately as antigen to identify anti‐sheath antibodies. The reactivity of sera from AS cases to mf sheath was found to be variable to the five different mf preparations. While as high as 25% of the sera reacted with mf purified from one individual, none of them reacted with mf purified from two other individuals. Such a differential reactivity to the sheath was found to be a feature of antibodies in AS cases only. Sera of seven amicrofilaraemic patients with elephantiasis reacted uniformly with all five mf preparations. The possible existence of polymorphic antigen (s) on the sheath of W. bancrofti mf has been proposed.
Neutralization of the activity of a Fasciola hepatica cathepsin L proteinase by anti‐cathepsin L antibodies
Authors: SMITH ANGELA M. , CARMONA CARLOS , DOWD ANDREW J. , McGONIGLE SHARON , ACOSTA DANIEL , DALTON JOHN P.
Published: October 2007

Fasciola hepatica secretes a cathepsin L proteinase that is suggested to play an in vivo role in immunoprotection since the enzyme can cleave host immunoglobulin. In the present report, rabbit anti‐cathepsin L IgG was shown to bind to the cathepsin L enzyme and inhibit its ability to cleave IgG molecules. Cathepsin L can prevent the antibody‐mediated attachment of eosinophils to newly excysted juveniles in in vitro assays; however, if anti‐cathepsin L IgG are mixed with the cathepsin L prior to the addition of the enzyme to the assay, eosinophils attach to the newly excysted juveniles. Thus it is possible to prepare antibodies that can bind and disrupt the biological activity of the F. hepatica cathepsin L.
Inhibitory effects of concurrently present ‘normal’Nippostrongylus brasiliensis worms on expulsion of ‘damaged’worms and associated goblet cell changes in rats
Authors: ISHIKAWA N. , HORII Y. , NAWA Y.
Published: October 2007

Nippostrongylus brasiliensis worms obtained from the stable phase of a primary infection (‘normal’worms) are able to establish and survive in naïve recipient rats into which they have been adoptively transferred, whereas those obtained at the time of expulsion (‘damaged’worms) are rapidly expelled. Expulsion is associated with quantitative/ qualitative goblet cell changes. Thus, N. brasiliensis adult worms seem to stimulate the expulsion process only after being ‘damaged’by the host's immunity, whereas it is possible that ‘normal’worms may inhibit the expulsion process. To see whether ‘normal’worms have such inhibitory effects, the fate of concurrently implanted ‘normal’and ‘damaged’worms was examined with reference to goblet cell changes in the intestine. By using either male or female worms as ‘normal’or ‘damaged’populations, it was possible to determine the origin of worms remaining in the intestine. The results show that not only ‘normal’worms but also ‘damaged’worms, which would normally be expelled, remained in the intestines of the recipients on Day five. Goblet cell hyperplasia and alteration of terminal sugars of mucins, which was induced within five days after implantation of ‘damaged’worms, were completely inhibited by the concurrent presence of ‘normal’worms. The inhibitory effects of ‘normal’worms were destroyed when they were killed by heating before implantation. Possible mechanisms leading to expulsion of N. brasiliensis are discussed.
Antigenic diversity of the asexual developmental stages of Eimeria tenella
Authors: TOMLEY FIONA
Published: October 2007

Total polypeptides from unsporulated and sporulated oocysts, sporozoites and the first two generations of merozoites of Eimeria tenella were fractionated by electrophoresis through polyacrylamide gels. The parasites are complex and the arrays of polypeptides differ for each of the developmental stages indicating that there is stagespecific control of gene expression. In particular, first generation merozoites display a markedly different polypeptide profile to that of either sporozoites or second generation merozoites. Changes in antigenicity during sporulation and the antigenic relationships between the three asexual zoite stages were examined by probing electroblotted polypeptides with a panel of antisera raised in rabbits to purified preparations of each stage. Antigenic cross‐reactivity is well maintained throughout sporulation even though the sizes of antibody‐reactive polypeptides change. In contrast there is a marked lack of cross‐reactive epitopes between sporozoites, first and second generation merozoites.
Resistance and disease in Brugia malayi infection of ferrets following prior infection, injection of attenuated infective larvae and injections of larval extracts
Authors: CRANDALL R. , CRANDALL C. , NAYAR J. , DOYLE T.
Published: October 2007

A partial resistance expressed by a 53% to 78% reduction in lymphatic filariae from a challenge infection was induced in ferrets (Mustela putorius furo) by a prior infection and by injection of radiation attenuated infective larvae (L3) but not by injections of lyophilized microfilariae (mf) or L3. Equivalent acquired resistance was demonstrated with and without overt filarial disease. A prior infection resulted in peripheral lymphoedema in approximately one‐third of the amicrofilaraemic resistant ferrets following challenge infection and injection of attenuated larvae resulted in inflammatory responses characteristic of a hyper‐responsive syndrome in one‐half of the amicrofilaraemic ferrets. Injections of lyophilized mf inhibited microfilaraemia and promoted development of lymphostatic disease. A limited examination of immune responses and histopathology suggested that disease in partially resistant ferrets was associated with high TH2 dependent responses directed, at least in part, to mature filariae and to mf. Mechanisms of resistance were not identified.
Protective antibodies against Taenia taeniaeformis in rats infected with eggs or injected with non‐viable oncospheres or recombinant antigens of oncospheres
Authors: ITO AKIRA , ASANO KAZUHITO , OKAMOTO KEN‐ICHI
Published: October 2007

Antibody responses against Taenia taeniaeformis in rats infected with eggs or injected with non‐viable oncospheres or recombinant antigens of oncospheres were analysed by passive transfer of serum and Western blotting. When recipient rats were injected with 1 ml serum from donors infected with eggs (infected serum), they all showed complete resistance to oral egg challenge, whereas those injected with 1 ml serum from donors injected with either oncospheres or recombinant antigens (vaccinated serum) showed no resistance. IgG and IgG subclass responses detected by Western blotting revealed that antibody responses to oncosphere antigens in infected serum thoroughly differed from those in vaccinated serum. It is suggested that IgG2a responses in infected serum should be used for screening of epitopes for candidate vaccine.
Detection of Bm86 antigen in different strains of Boophilus microplus and effectiveness of immunization with recombinant Bm86
Authors: PENICHET MANUEL , RODRIGUEZ MANUEL , CASTELLANO ORLANDO , MANDADO SARA , ROJAS YOLANDA , RUBIERA ROGER , SANCHEZ PEDRO , LLEONART RICARDO , FUENTE JOSE DE LA
Published: October 2007

The control of tick populations by using conventional strategies poses several problems, including the appearance of organophosphate resistant strains, among others. The possibility of using alternative strategies such as vaccination with tick antigens has been suggested by several authors. One particular antigen (Bm86) has been described and shown to be able to induce a protective immunity against the cattle tick Boophilus microplus. In this paper we demonstrate by means of immunohistochemical staining that this antigen is conserved among several strains of this species. These results correlate with those showing that animals vaccinated with a preparation of recombinant Bm86 were protected against challenge with the four different strains tested, including one resistant to organophosphates. These results favour the immunization with recombinant Bm86 for the control of the cattle tick B. microplus.
Vaccination against gastrointestinal nematodes of sheep using purified secretory acetylcholinesterase from Trichostrongylus colubriformis– an initial pilot study
Authors: GRIFFITHS G. , PRITCHARD D. I.
Published: October 2007

Purified secretory acetylcholinesterase (sAChE) from Trichostrongylus colubriformis was used as a candidate vaccine against mixed T. colubriformis, Haemonchus contortus and C. oncophora challenge infections of sheep. Cross species protection was achieved with an average reduction in worm burden of all species of 31%, rising to 58% in individual cases. There was no consistent reduction in faecal egg counts and increases in anti‐T. colubriformis sAChE IgG antibody levels following vaccination were modest. We suggest that improved antigen delivery systems will result in increased host protection.
Immunoglobulin G binding proteins in male Rhipicephalus appendiculatus ticks
Authors: WANG HUI , NUTTALL PATRICIA A.
Published: October 2007

Three abundant immunoglobulin G binding proteins (IGBPs) of29kDa (IGBP‐MA), 25kDa (IGBP‐MB), and 21 kDa (IGBP‐MC) were isolated from partly fed male Rhipicephalus appendiculatus ticks using an agar‐ose‐IgG column. After separating the proteins by SDS‐PA GE, each individual IGBP band was cutou tfrom the gel and used to raise antiserum in guinea pigs. Using immuno‐blotting, each of the three IGBPs was shown to be antigenically distinct, and specific for feeding male R. appendiculatus ticks. They were detected in the salivary glands of male ticks that had been feeding in either the presence of absence of female ticks, and appeared to be glycoproteins. The smallest protein, IGBP‐MC, bound to guinea pig IgG (on which species the ticks were fed) and also bound to human and bovine IgG, whereas IGBP‐MA and possibly IGBP‐MB only bound to guinea pig IgG. The function of IGBPs in tick salivary glands and their significance in male ticks are discussed.
Expression of the Plasmodium berghei ookinete protein Pbs21 in a baculovirus‐insect cell system produces an efficient transmission blocking immunogen
Authors: MARGOS GABRIELE , KURTENBACH KLAUS , POSNETT ELSA , BARKER GUY C. , MATSUOKA HIROYUKI , PATON MICHAEL G. , SINDEN ROBERT E.
Published: October 2007

A surface protein of Plasmodium berghei ookinetes, Pbs21, was expressed in a baculovirus‐insect cell system in cell culture and in Heliothis virescens larvae. Groups of BALB/c mice received two intraperitoneal inoculations of either i) Tris‐buffer or homogenized H. virescens larvae infected with wild‐type baculovirus; ii) enriched, homogenized ookinetes, or Hi) homogenizedH. virescens larvae expressing recombinant Pbs21 (rPbs21). All animals immunized with ookinetes or with rPbs21 had high litres of antibodies (IgG isotype) that bound to native Pbs21. The large majority of antibodies in immune sera of both groups recognized the antigen under non‐reducing but not under reducing conditions. The predominant IgG‐sub‐classes in mice immunized with ookinetes was IgGl and in mice immunized with rPbs21, the subclasses were IgGl and IgG2a. Immunization with rPbs21 reduced the infec‐tivity of P. berghei to mosquitoes by 91% compared to a 99% reduction following immunization with ookinetes. This preliminary data indicate that rPbs21 expressed in this eukaryotic system induces a transmission‐blocking immunity which is more effective than that achieved using rPbsll expressed in Escherichia coli (Matsuoka et al. 1994).
Trypanosoma cruz/‐induced decrease in the level of interferon‐7 receptor expression by resting and activated human blood lymphocytes
Authors: KIERSZENBAUM F. , LOPEZ H. MEJIA , TANNER M. K. , SZTEIN M. B.
Published: October 2007

A substantial proportion of human peripheral blood mononuclear cells (PBMC) manifested a decreased capacity to express membrane interferon‐γ receptors (IFN‐γR) when co‐cultured with Trypanosoma cruzi. Among the lymphocytes, B cells accounted for the bulk of this effect, evidenced by a marked drop in the proportion of CD19+ or CD20+ cells expressing IFN‐γR. Decreased IFN‐γR expression by B lymphocytes was seen as early as 3 h after co‐culture with T. cruzi and persisted for at least 24 h. The parasite had no detectable effect on CD19, CD20 or DR antigen expression by B lymphocytes. Neither the proportion ofB cells expressing these markers nor the membrane density of these molecules varied significantly in the presence of T. cruzi. In PBMC cultures stimulated with Staphlyococcus aureus Cowan I (SACI), T. cruzi decreased the percentages of both IFN‐γR+ and IFN‐R +bnght (cells expressing above‐normal levels of surface IFN‐γR) B lymphocytes. Cell‐free filtrates of T. cruzi suspensions reproduced the suppressive effects of living parasites on IFN‐γR expression by B cells. When T. cruzi was present, the intracellular levels of IFN‐γR molecules in resting or SACI‐activated B lymphocytes, represented by fluorescence intensity, were well below control values, suggesting that decreased surface expression resulted from suppressed IFN‐γR synthesis. Among T (CD3+) cells, 10–8% to 39–6% (7 donors) expressed surface IFN‐γR and did so at a very low level. These percentages were also reduced by T. cruzi. If occurring in the host, downregulated expression of IFN‐γR could curtail the utilization of IFN‐γ, known to play a critical role in host defence against T. cruzi infection.
Lack of an association between hydatid disease and autoimmunity
Authors: COLEBROOK AMANDA L. , LIGHTOWLERS MARSHALL W.
Published: October 2007

The prolonged survival of Echinococcus granulosus within the human host indicates that some mechanism is operating to permit parasite evasion of the host immune response. Several publications have described autoimmune phenomena in patients infected with hydatid cysts. The aim of this study was to test the postulate that there is a higher prevalence of autoantibodies in serum from patients with hydatid disease than in control samples, and this may provide some evidence of an association between autoimmunity andE. granulosus infection. Sera from 70 patients with hydatid disease and 45 control subjects were assayed for the presence of antinuclear antibodies (ANA), tissue specific autoantibodies and rheumatoid factor. All patients were aged between 20 and 80 years of age with no known history of autoimmune disease. Hydatid patients were surgically confirmed cases. Control subjects were chosen on the basis that they were age and sex matched to the test sera and had no known illness at the time blood samples were obtained. On the basis of an ANA autoantibody litre of > 1:40 being regarded as positive, 19 (27%) of the hydatid patients, 13 (28%) of the controls were positive. Low levels of tissue specific autoantibodies and rheumatoid factor were detected in sera from 5 (7%) and 2 (11%) hydatid patients and 4 (8%) and 3 (16%) of control subjects respectively. No significant differences (P > 0–05) were found between autoantibody levels in the hydatid patient sera and the controls. These findings suggest that there is no association between hydatid infection and the level of autoantibodies to a broad range of self antigens.
Immunoprophylactic potential of a 120 kDa Brugia malayi adult antigen fraction, BmA‐2, in lymphatic filariasis
Authors: CHENTHAMARAKSHAN V. , REDDY M.V.R. , HARINATH B.C.
Published: October 2007

A 120 kDa antigen containing SDS‐PAGE fraction BmA‐2 isolated from Brugia malayi adult parasite was highly reactive with normal sera from filarial endemic area. BmA‐2 was analysed for its propylactic potential in in vitro and in vivo. Sera collected from BmA‐2 immunized jirds induced a significant level (80 to 90%) of protection against infective larvae and microfilariae in in vitro ADCC assay as well as in in situ micropore chamber implantation studies. Mastomys natalensis immunized with BmA‐2 showed a significant level of protective response against circulating microfilariae by clearing 90% of them from circulation by fifth day after challenge infection. Immunization of jirds with BmA‐2 resulted in an enhanced level of antibody response against BmA‐2 and 88% reduction in the development of the parasites to the adult stage. Passive transfer of immunesera from jirds immunized with BmA‐2 to naive jirds resulted in 71% reduction in adult worm recovery as observed 90 days after challenge infection with B. malayi. On the other hand the passive transfer of nonadherent spleen cells from immune jirds did not show any significant effect on the development of parasite. Administration of jirds anti BmA‐2 serum to microfilaraemic jirds showed a temporary decrease in micrqfilarial count which was increased to pretherapeutic level within 100 days and there was no effect on the adult worms. This implies that the immune protective effect of BmA‐2 is mainly antibody dependent and active immunization with BmA‐2 is effective against filarial infection.,
Further characterization of the 38 kDa antigen from Echinococcus granulosus (hydatid disease) cyst fluid: evidence for antigenic heterogeneity and reactivity with anti‐P1 antibodies
Authors: ZHANG LI‐HUA , LEGGATT G.R. , McMANUS D.P.
Published: October 2007

A panel of 5 IgM and 6 IgG1 monoclonal antibodies (MoAbs) was produced against a band, eluted from a reducing SDS‐PAGEgel, containing the 38 kDa subunit of antigen 5 (Ag5) from Echinococcus granulosus cyst fluid; seven of the MoAbs were shown subsequently to bind epitopes on Ag5 but none recognizedphosphorylcho‐line or periodate‐sensitive carbohydrate epitopes. Differences in the fine specificity of the MoAbs were apparent and, upon reduction, heterogeneity in 38 kDa components from hydatid cyst fluids of different intermediate host origin was revealed by peptide fingerprinting and immuno‐blotting using the MoAbs. One of the IgGl MoAbs (ED9) was able to distinguish a reduced 38 kDa molecule in cyst fluids from two distinct genotypes–the horse/dog and sheep/dog strains–of E. granulosus and this may have implications for hydatid serology, immunoepidemiology and strain typing. Furthermore, epitopes on this 38 kDa component or on a different molecule with the same or similar Mr are reactive with anti‐P1 blood group antigen antibodies and this could result in false‐positive reactions where sera from P2 patients with suspected hydatid disease are tested by immunoblot or immunoprecipitation analysis.,
The effects of H2 and non‐H2 genes on the survival of Onchocerca lienalis microfilariae in the mouse
Authors: FOLKARD SHELLEY G. , BIANCO ALBERT E.
Published: October 2007

The effect of H2 and non‐H2 genes in a mouse model of protective immunity against Onchocerca lienalis microfilariae have been investigated. Non‐H2 effects were determined using CBA, BALB/c, B10, SJL and TO strains. All were permissive for establishment of a primary infection with microfilariae, although significant differences in parasite recoveries were evident amongst the various strains. The effect of H2 genes upon a primary infection was investigated using H2 congenic B10 and BALB strains, B10, B10.S, B10.BR, B10.D2/n, BALB/c, BALB.B, and BALB.K. Significant H2 effects were seen among the relatively weak responder B10 strains, but were not present among the relatively strong responder BALB strains. These results support a dominant effect of non‐H2 genes following primary exposure to microfilariae, and a ‘fine tuning’ effect of H2 genes that is apparent only in weaker responding strains. Upon reinfection of all the strains investigated, a gradation of protection was detected that appeared to be exclusively dependent upon H2.,
Vaccination of patas monkeys experimentally infected with Schistosoma haematobium using a recombinant glutathione S‐transferase cloned from S. mansoni
Authors: BOULANGER D. , WARTER A. , TROTTEIN F. , MAUNY F. , BREMOND P. , AUDIBERT F. , COURET D. , KADRI S. , GODIN C. , SELLIN E. , PIERCE R.J. , LECOCQ J.P. , SELLIN B. , CAPRON A.
Published: October 2007

The capacity of a recombinant glutathione S‐transferase from Schistosoma mansoni (rSm28GST) to vaccinate primates fErythrocebus patas,) against a heterologous infection with Schistosoma haematobium has been tested. Two injections of the purified molecule with Muramyl‐Di‐Peptide (MDP) as adjuvant resulted in a high level antibody response in the five immunized animals and in a significant reduction in worm fecundity compared to the controls which received adjuvant alone. Mean levels of daily egg excretion in urine and faeces were reduced by respectively 55% and 74% although perfusion revealed that worm burdens were similar in both groups. The protective effect was long lasting since it was maintained up to the end of the experiment, 42 weeks after infection. Hatching rates and the numbers of intra‐uterine eggs were also significantly affected by the vaccination. Tissue eggs were also drastically diminished in the urogenital system (–80%) but the reduction was not statistically significant. One animal was not protected by the immunization. There was a good correlation between parasitological data and the intensity of bladder lesions assessed by microscopic examination. Polypoid formations together with an intense exudation of the lamina propria were frequently seen in the controls but rarely in the vaccinated group where formation of scar tissue was predominant. These results underline the vaccine potential of the recombinant Sm28GST as a possible valuable prophylactic tool for the control of egg‐induced pathology and transmission of African schistosomes.
Immunoregulation in human lymphatic filariasis: the role of interleukin 10
Authors: MAHANTY SIDDHARTHA , NUTMAN THOMAS B.
Published: October 2007

In humans with lymphatic filariasis microfilaremia is associated with a parasite antigen‐specific hyporesponsive‐ness when assessed by cell proliferation and secretion of interleukin‐2 and interferon‐γ. Hyporesponsiveness in these individuals is not only parasite antigen‐specific but appears to be limited to Th1‐type responses. Th2 mediated responses such as IL‐5 secretion and IgE antibody production to parasite antigens are generally strong and usually no different than those seen in immunologically more reactive amicrofilaremic individuals with chronic lymphatic pathology. The mechanisms by which Th1 responses are inhibited have not yet been elucidated, but some studies suggest that down‐regulatory cytokines such as IL‐10 may be involved in this process. Mononuclear cells from microfilaremic individuals have been found to secrete greater quantities of IL‐10 spontaneously and in response to parasite antigens. In this review, mechanisms by which IL‐10 may be induced by the parasite and the mode by which IL‐10 may regulate parasite antigen‐specific Th1 responses in these individuals are discussed.
Reduced amount of intestinal mucus by treatment with anti‐CD4 antibody interferes with the spontaneous cure of Nippostrongylus brasiliensis‐infection in mice
Authors: KHAN W. I. , ABE T. , ISHIKAWA N. , NAWA Y. , YOSHIMURA K.
Published: October 2007

Mechanism of spontaneous cure was studied in mice infected with mouse‐nonadaptive Nippostrongylus brasiliensis. Adult BALB/c mice were cured spontaneously of infection with this strain of N. brasiliensis by Day 7 post‐infection. Expulsion of intestinal worms was delayed dose‐dependently by a treatment with anti‐CD4 antibody. However, the treatment had no significant effect on larval recovery from the lungs. Treatment of mice with anti‐IL‐5 antibody suppressed intestinal tissue eosinophilia induced by the infection, but did not affect intestinal worm recovery. Antigen specific IgE antibody was not detected in the sera obtained from Days 5 to 15. Therefore, IL‐5 and specific IgE antibody are probably not important in the spontaneous cure. Treatment of mice with anti‐CD4 antibody had no significant effect on number of intestinal goblet cells or on expression of terminal sugars of goblet cell mucins. However, histological and quantitative analyses revealed that significantly less intestinal mucus was released in anti‐CD4 antibody treated mice than in control mice. These results suggest that CD4+ lymphocytes control the amount of intestinal mucus and consequently the reduced mucus interferes with the spontaneous cure. Quantity of mucus released in the intestinal lumen may have an essential role in the spontaneous cure ofN. brasiliensis‐in/fcfio/i of mice.
Human immune recognition of recombinant proteins representing discrete domains of the Plasmodium falciparum gamete surface protein, Pfs230
Authors: RILEY ELEANOR M. , WILLIAMSON KIM C. , GREENWOOD BRIAN M. , KASLOW DAVID C.
Published: October 2007

The 230 kD gamelocyte/gamete‐specific surface protein of Plasmodium falciparum, Pfs230, is a target of antibodies which inhibit the development of the parasite inside the mosquito vector. A transmission blocking vaccine based on Pfs230 may be a powerful tool for malaria control. As a first step, Pfs230 has been expressed in E. coli as a series of recombinant proteins, fused to maltose binding protein. We have used the fusion proteins to assess cellular and humoral immune responses to Pfs230 in malaria‐immune adult Gambian blood donors; responses to the fusion proteins have been compared with responses to native Pfs230. The tetrapeptide repeat region of the molecule appears to be immunodominant for both antibody‐producing cells and peripheral blood T cells. We postulate that this may represent a mechanism for immune evasion since the N‐terminal repeat region of the molecule is cleaved from the mature protein and shed into the plasma. Responses to fusion proteins representing the seven‐cysteine motifs were correlated within individual donors, suggesting that cross‐reactive epitopes occur within the motifs. Antibody responses to recombinant proteins were poorly correlated with responses to native Pfs230 suggesting that dominant epitopes of the native protein are not adequately represented in the recombinant proteins. Although prokaryotic expression products may be suitable for induction of cellular immune responses to Pfs230, alternative expression systems may be needed for creation of appropriate B cell epitopes.
Cellular responses during liver fluke infection in sheep and its evasion by the parasite
Authors: MEEUSEN E. , LEE C. S. , RICKARD M. D. , BRANDON M. R.
Published: October 2007

The cellular immune response in sheep to an acute and chronic primary and an acute secondary liver fluke infection were examined by immunohistology of liver tissue and flowcytometry of lymphocytes from the draining hepatic lymph nodes. Ten days after primary infection, portal tract areas surrounding migratory tunnels were infiltrated with CD4+ and CD8+ lymphocytes with fewer B cells and T19+ T cells. Micro abscesses were distributed sporadically in the liver parenchyma and young flukes could be easily observed in the liver tissue free from inflammatory cells. More intensive infiltration of the portal tract areas was observed during a secondary liver fluke infection characterized by a pronounced increase in eosinophils, B cells and CD4+ T cells. In addition, there was an increase in MHC class II+ fibroblastic‐like cells surrounding the migratory tracts. In contrast to the primary infection, no young flukes were observed in the same tissue areas during the secondary infection. Chronic primary infections were characterized by perilobular fibrosis and a predominance of CD8+ and γδ‐TCR+ T19‐ T cells distributed within fibrotic strands. Distinct B cell follicles were observed in the fibrotic strands and near major bile ducts and necrotic patches. Pronounced lymphocyte infiltration could occasionally be observed surrounding liver fluke eggs lodged in liver tissue. A progressive increase in lymph node weight, cell number and CD4/CD8 ratio was observed in the acute and chronic primary infections. The role of the infiltrating cell populations and possible mechanisms of immune evasion by the parasite are discussed.
Immune cytotoxic activity of human eosinophils againstTrichinella spiralisnewborn larvae
Authors: VENTURIELLO S. M. , GIAMBARTOLOMEI G. H. , COSTANTINO S. N.
Published: October 2007

The ability of human eosinophils to kill the newborn larvae (NBL) of Trichinella spiralis of different maturation status, in the presence of antibody, was studied. A cytotoxic in vitro test was performed using NBL less than 2h of age (NBL2) or NBL maintained in culture at 37°C for 20 h (NBL20), peripheral blood eosinophils, anti‐Trichinella serum and human fresh serum as source of complement. Under these experimental conditions eosinophils from normal individuals attached to NBL2as well as to NBL2o but only the latter were killed. On the other hand, eosinophils from volunteers with eosinophilia killed NBL regardless of larval age. Neither adherence nor significant mortality was observed in the absence of immune serum. These results indicate that NBL maturation and eosinophil activation status are crucial for antibody‐dependent cellular cytotoxic reaction (ADCC).
The cachexia associated with Trypanosoma cruzi acute infection in mice is attenuated by anti‐TNF‐a, but not by anti‐IL‐6 or anti‐IFN‐7 antibodies
Authors: TRUYENS CARINE , TORRICO FAUSTINO , ANGELO‐BARRIOS ALCIRA , LUCAS RALF , HEREMANS HUBERTINE , BAETSELIER PATRICK DE , CARLIER YVES
Published: October 2007

BALB/c male mice acutely infected with Trypanosoma cruzi underwent a severe weight loss (around 20%, from day 18 to 31 post‐infection), when compared to age‐matched uninfected animals. Though mice regained weight later, when blood parasites were hardly detectable, wasting extended over the chronic phase of infection. The onset and the magnitude of weight loss were related to the mouse susceptibility to infection, since they were respectively earlier and higher in male mice which will die than in surviving ones, in males than in females, and in BALB/c than in B6D2 [(C57B1/6 × DBA/2)F1], a mouse strain more resistant to infection. Fat weight of infected mice (male BALB/c) was reduced by 60 to 80%, whereas lean mass was unaffected and water content rose by 6 to 10% in acute and chronic infection. Haematocrit was also decreased by 15–16% in acute infection. Animals failed to compensate their energetic loss since their food intake remained similar to that of uninfected animals. Injections of neutralizing anti‐TNF‐α monoclonal antibody into infected male mice, during the first two weeks but not later in infection, significantly attenuated the weight loss. Early administration of anti‐IL‐6 or anti‐IFN‐γ MoAbs did not improve the mouse wasting. Taken together, these data show that TNFis a key agent of cachexia occurring in the acute T. cruzi infection in mice.
Stem cell factor dependent hyperplasia of mucosal‐type mast cells but not eosinophils in Schistosoma mansoni‐infected rats
Authors: NEWLANDS G. F. J. , COULSON P. S. , WILSON R. A.
Published: October 2007

Stem cell factor (SCF) is a growth factor with multiple activities which acts on numerous cell types including primordial germ cells, haemopoietic stem cells, melanocytes and mast cells. SCF is critical for the development of the mast cell hyperplasia associated with infection with the intestinal parasites Nippostrongylus brasiliensis and Trichinella spiralis. In the present study we have assessed the role of SCF in the mast cell and eosinophil responses to Schistosoma mansoni in the rat by blocking its effects in vivo with polyclonal antibody to SCF. Rats treated with sheep anti‐SCF antibody on days 21, 24, 27 and 30 of infection with S. mansoni showed a rapid decrease in serum concentrations of the mucosal mast cell‐associated protease rat mast cell protease II (RMCP II) by day 24, compared with normal sheep IgG‐treated controls. Similarly, the number of mucosal mast cells and RMCP II levels in both small intestine and liver were also significantly reduced by day 32 of infection. In contrast with the depeletion of mast cells and mast cell proteases, eosinophil numbers in liver or intestine did not change significantly after anti‐SCF treatment compared with controls. These results confirm that mast cell survival and hyperplasia are dependent on the presence of SCF whilst demonstrating that the eosinophil recruitment to liver and intestine associated with S. mansoni infection is SCF‐independent.
Immunoglobulin and cytokine profile in murine secondary hydatidosis
Authors: HARALABIDIS S. , ARAGOUNI E. K. , FRYDAS S. , DOTSIKA E.
Published: October 2007

We have investigated specific immune responses in BALB/c mice with experimentally induced secondary hydatidosis. Following intraperitoneal inoculation of brood capsules containing Echinococcus granulosus‐protoscoleces, the course of the infection was followed for 513 days. The sera of the mice were screened for the presence of a number of cytokines, and for specific antibodies. During the first 129 days of infection, high levels of cytokines TNFα, IL‐α, IFNγ, IL‐6, andIL‐10 and specific IgGl andIgG3 isotypes were detected, as compared to uninfected controls. The levels oflgM and IgG2a were slightly increased following infection, and remained elevated throughout the period of observation. The levels of IL‐lα and specific immunoglobulin of all isotypes except IgM and IgG2α, were significantly decreased 103 days post infection fp.i.), whereas TNFα was sharply decreased 129 days p.i. During the period of 129 to 209 days of infection there was an increase in secreted IL‐10, and a slow decrease in the levels of IL‐6 andlFN‐γ. Levels of IgM, IgG, IgGl, and IgG2a plateaud during this period, whereas IgG3 and TNFα showed a peak at day 190 p.i. These data suggest the induction of Th2 antibody‐mediated immunity with a parallel expansion of Thl‐mediated inflammatory responses as important mechanism of host defence against the metacestode.
Regulation of egg production, worm burden, worm length and worm fecundity by host responses in sheep infected with Ostertagia circumcincta
Authors: STEAR M. J. , BISHOP S. C. , DOLIGALSKA M. , DUNCAN J. L. , HOLMES P. H. , IRVINE J. , McCRIRIE L. , McKELLAR Q. A. , SINSKI E. , MURRAY MAX
Published: October 2007

Following infection with Ostertagia circumcincta there was considerable variation in worm burdens, worm size and number of inhibited larvae even among sheep matched for age, sex, breed, farm of origin and history of parasite exposure. There was also substantial variation among sheep in the concentration of mast cells, globule leucocytes, eosinophils, IgA‐positive plasma cells and parasite‐specific IgA in the abomasal mucosa. With the exception of faecal egg counts over time, the parasitological and immunological traits were all continually distributed among animals and sheep did not fall into discrete high and low‐responder categories. The responses were correlated. Sheep with more mast cells also had more globule leucocytes, more eosinophils, more IgA plasma cells and greater amounts of parasite‐specific IgA in the abomasal mucosa. Female worm length was strongly and positively correlated with the number of eggs in utero. Faecal egg counts were associated with variation in worm number and with variation in the number of eggs in utero. The worm burden was negatively correlated with the number of globule leucocytes in the abomasal mucosa, suggesting that worm numbers are regulated by immediate hypersensitivity reactions. Decreased female worm length was associated with an increased local IgA response to fourth stage larvae. The number of inhibited larvae was positively associated with the size of the local IgA response and positively associated with the size of the worm burden. The results suggest that variation among mature sheep in faecal egg counts is due, at least in part, to variation in local IgA responses which regulate worm fecundity and to variation in local immediate hypersensitivity reactions which regulate worm burdens.
The role of CD4+ and CD8+ T cells in protective immunity to the murine nematode parasite Trichuris muris
Authors: KOYAMA KOICHI , TAMAUCHI HIDEKAZU , ITO YOICHI
Published: October 2007

The role ofCD4+ and CD8+ T cells in protective immunity to Trichuris muris was studied in CD4+ or CD8+ or both CD4+ and CD8+ T cell‐depleted BALB/c mice. To assess in vivo depletion of T‐cell subsets, CD4+ and CD8+ T cells in the Peyer's patches, the mesenteric lymph nodes (MLN), and the spleens of mice treated with T cell‐specific monoclonal antibodies (MoAbs) were analysed by FACS. CD4+ T cells were selectively depleted in mice injected with anti‐CD4 MoAb i.p. and injection of anti‐CD8 MoAb resulted in selective depletion ofCD8+ T cells. The expulsion ofl. muris was inhibited in CD4+ T cell‐depleted mice and numerous worms were detected in the large intestine on days 14 and 21 after infection, although no suppression of protective immunity to T. muris was observed in CD8+ T cell‐depleted mice. Moreover, there was no difference in suppression of protective immunity to T. muris between CD4+ T cell‐depleted and both CD4+ and CD8+ T cell‐depleted mice. These results indicate that CD4+ T cells play a central role in protective immunity to T. muris infection.