bluuebunny/crossref_metadata_2025_split huggingface dataset:
The use of mouse/human chimaeric antibodies to investigate the roles of different antibody isotypes, including lgA2, in the killing of Schistosoma mansoni schistosomula by eosinophils
Authors: DUNNE DAVID W. , RICHARDSON BRIAN A. , JONES FRANCES M. , CLARK MICHAEL , THORNE KAREEN J. I. , BUTTERWORTH ANTHONY E. 
Published: October 2007

SummaryWe report the use of a matched set of mice/human chimaeric antibodies, directed against the 5‐iodo‐4‐hydroxyl‐3‐nitrophenacetyl (NIP) hapten, to investigate the roles of different human isotypes in antibody‐mediated eosinophil‐dependent killing of schistosomula. The chimaeric antibodies consist of mouse VH, VL and CL regions with human γ1, γ2, γ3 (2 allotypes), y4, α2, or e CH regions and were used in in vitro assays with human eosinophils and NIP‐coated S. mansoni schistosomula. Some anti‐NIP isotypes mediated high levels of killing, which was specific for NIP‐coated larvae, and we suggest that these antibodies will be a valuable tool for studies on the role of antibody isotypes in anti‐schistosome immune effector mechanisms. In particular, this method directly demonstrated, for the first time, that IgA is highly effective in mediating the killing of metazoan parasites by human eosinophils.
Soluble (s)CD23 levels in a parasitized population from Papua New Guinea
Authors: PRITCHARD D. I. , KUMAR SANJEEV , EDMONDS P. 
Published: October 2007

SummaryLevels of sCD23, total and specific IgE were found to be considerably elevated in the plasma of a helminth infected population from Papua New Guinea. Using age‐corrected data, a significant negative correlation was seen between sCD23 and total IgE in the young, at a time when hookworms are being rapidly acquired, and total IgE levels are rising most dramatically. It is suggested on the basis of this data that this inverse correlation is due to the stabilizing effect of IgE on the FceRII receptor in vivo, and that the high levels of sCD23 seen in hookworm infected individuals are partly responsible for the high levels of IgE recorded in these patients.
Induction of complement resistance in cloned pathogenic Entamoeba histolytica
Authors: HAMELMANN CHRISTOPH , FOERSTER BIRGIT , BURCHARD GERD D. , SHETTY NANDINI , HORSTMANN ROLF D. 
Published: October 2007

SummaryThe lytic effect of complement activated through the alternative pathway (AP) was studied on pathogenic and nonpathogenic Entamoeba histolytica recently isolated from stool samples. Recent nonpathogenic isolates were nearly unaffected by exposure to AP whereas recent pathogenic stool isolates were highly susceptible to AP dependent complement‐mediated lysis. Complement susceptible pathogenic stool isolates developed complement resistance in vivo during hamster liver passage and in vitro during cultivation in the presence of increasing concentrations of normal human serum (NHS). Since a clone of pathogenic HM‐l.IMSS which initially was highly susceptible also acquired complement resistance during cultivation in the presence of NHS, it is concluded that complement resistance was caused by induction rather than by selection alone. Because cultivation in the presence of heat‐inactivated NHS did not affect complement susceptibility of the cloned HM‐l.IMSS, complement activation itself might induce complement resistance in pathogenic E. histolytica.
Pulmonary inflammation and immune responses during the course of Nippostrongylus brasiliensis infection: lymphocyte subsets in bronchoalveolar lavage fluids of rats
Authors: RAMASWAMY K. , BEFUS D. 
Published: October 2007

SummaryQuantitative measurements were made of different phenotypes of lymphocytes in bronchoalveolar lavage fluid (BALF) of rats during the course of a primary or secondary infection with Nippostrongylus brasiliensis. These changes were compared with those in the peripheral blood to understand the site‐specificity of the responses. Following infection, there was a significant increase in both B and T lymphocytes in BALF. The CD4: CD8 ratio was significantly altered with a decreased ratio on day 2 and increased ratio on days 16 and 32 post infection (p.i.). Two colour analysis showed that during larval migration through the lungs (day 2 p.i.) there was a significant increase in CD8+, CD4+ OX22+ and CD4+ OX22‐ cells in BALF. As infection progressed in time, CD4+ OX22 – cells were increased significantly. Compared to primary infection, a secondary infection resulted in increased recovery of CD4+ OX22– cells in BALF. These changes were not readily appreciated in the peripheral blood, suggesting site‐specific compartmentalization of lymphocyte responses in the lung. The functional significance of these dynamic changes in lymphocyte subsets in the airspaces following infection remains to be identified.
A longitudinal study of naturally acquired cellular and humoral immune responses to a merozoite surface protein (MSP1) of Plasmodium falciparum in an area of seasonal malaria transmission
Authors: RILEY E. M. , MORRIS‐JONES S. , BLACKMAN M. J. , GREENWOOD B. M. , HOLDER A. A. 
Published: October 2007

SummaryA longitudinal study of cellular and serological responses to the major merozoite surface protein of Plasmodium falciparum (PfMSP1) has been conducted in a malaria immune population living in The Gambia, where malaria transmission is seasonally endemic. Recombinant or native proteins representing the sequence of PfMSP1 from the Wellcome strain of P. falciparum were used in in vitro lymphocyte proliferation, cytokine and antibody assays. Cellular responses of individual donors fluctuated over time, independent of seasonal changes in malaria transmission whereas anti‐PfMSP1 antibody levels were remarkably stable. At a population level, IFNγ responses were both more prevalent and of greater magnitude at the end of the rainy (malaria transmission) season than during the dry season. Responses of individuals lving in a rural village were compared with those of individuals living in an urban area with much lower levels of malaria transmission. Malaria infections were more likely to be symptomatic in urban dwellers than in inhabitants of rural villages but no significant differences in the level or prevalence of cellular or serological responses were seen between the two groups. However, urban dwellers with current symptomatic malaria infections had somewhat lower anti‐PfMSP1 antibody levels than their healthy, non‐parasitaemic neighbours.
The profile of IgG1 and IgG2a antibody responses in mice exposed to Schistosoma mansoni
Authors: MOUNTFORD A. P. , FISHER A. , WILSON R. A. 
Published: October 2007

SUMMARYThe segregation of IgG2a and IgG1 immunoglobulin isotypes as markers for Th1 and Th2 lymphocytes respectively, was investigated in mice exposed to normal or optimally‐irradiated S. mansoni cercariae. Using a panel of ELISAs, soluble antigens from lung‐stage schistosomula, adult worms, or eggs, were probed with serum samples collected at biweekly intervals. Infected mice developed increased IgG1 responsiveness to all three antigens, especially between weeks five and seven, whereas IgG2a responses were lower, particularly to egg antigens. This confirms that Th2 responses are dominant after the onset of patency in infected mice. In comparison, vaccinated mice developed lower levels of IgG1, and higher levels of IgG2a to larval and worm antigens. Thus, they had balanced expression of IgG1 and IgG2a, despite having a dominant Th1 lymphocyte population. An elevated IgG1 response to egg antigens in vaccinated mice challenged with normal parasites, occurred two weeks later than in normal mice. Mice exposed to male‐only cercariae developed IgG1 and IgG2a antibodies to larval and worm antigens. However, they also had elevated IgG1 to egg antigens from week five, despite a total absence of eggs. Therefore, adult worm antigens may cross react with the egg and stimulate the switch to Th2 dominated responsiveness.
Passively transferable protection against Schistosoma japonicum induced in the mouse by multiple vaccination with attenuated larvae: the development of immunity, antibody isotype responses and antigen recognition
Authors: DUNNE D. W. , JONES F. M. , COOK L. , MOLONEY N. A. 
Published: October 2007

SUMMARYVaccination of mice with attenuated S. japonicum cercariae induces protection against secondary infection which can be transferred to naive mice with serum (VMS). The presence of antibody does not per se impart protection as serum from mice carrying non‐attenuated infections (CIS), contains high levels of specific antibody, but confers no protection. Here we describe the increased protection transferred (20 to 68%) with increased number of vaccinations (one to five) given to the donors, and its decline with time after the final vaccination. We also describe the development of IgM, IgA, IgE, total IgG and IgG subclass responses in VMS, giving different levels of protection and CIS, directed against sodium periodate‐sensitive and ‐resistant epitopes in ‘skin‐stage’, ‘lung‐stage’and ‘liver‐stage’schistosomula, adult worms and eggs. In addition, antibody affinity maturation, development of S. japonicum species‐specific responses, and vaccination‐specific responses were examined. No response developed in parallel with serum‐mediated immunity, suggesting immunity may be due to responses against individual antigens. Preliminary examination of antigens recognized in Western blot showed that two schistosomal membrane antigens, of 13 and 40 kDa, were recognized by VMS from mice vaccinated five times (68% protection), but not by twice vaccinated VMS (27% protection). Neither antigen was recognized by non‐protective CIS.
Evidence for limited activation of distinct CD4+ T cell subsets in response to the Plasmodium falciparum circumsporozoite protein in Papua New Guinea
Authors: DOOLAN DENISE L. , BECK HANS‐PETER , GOOD MICHAEL F. 
Published: October 2007

SUMMARYBoth CD4+ and CD8+ T cells, as well as antibody, are known to be important in sporozoite immunity. Data from animal studies suggest that cytokines, in particular γ‐interferon and interleukin‐6, are involved. The interplay of these various factors and their importance in vaccine development has, however, not yet been elucidated. In this study, we have studied cellular and humoral responses of individuals naturally exposed to malaria in a highly endemic region of Papua New Guinea to the circumsporozoite protein of Plasmodium falciparum, a prime vaccine candidate antigen. A paucity of any CD4+ lymphoproliferative response to this protein by Papua New Guineans was notable which parallels our recent observation of a paucity of CD8+ T cell response and contrasts markedly with the responses of other endemic populations. There was nevertheless a significant antibody response to the central conserved B cell epitope, (NANP)n, as well as to other critical epitopes. An inverse relationship between γ‐interferon production and interleukin‐6 production and a positive correlation between γ‐interferon production and CS peptide‐specific lymphoproliferation was observed. High levels of peptide‐specific IL‐6 production were associated with high levels of peptide‐specific serum antibodies. Our data provide evidence for the limited activation of distinct CD4+ T cell subsets and for the existence of functionally distinct subpopulations of human CD4+ T cells with respect to cytokines known to be important in sporozoite immunity.
Expression of an Onchocerca volvulus Ov33 homolog in Dirofilaria immitis: potential in immunodiagnosis of heartworm infection
Authors: MEJIA J. SANTIAGO , NKENFOU CELINE , SOUTHWORTH MAURICE W. , PERLER FRANCINE B. , CARLOW CLOTILDE K. S. 
Published: October 2007

SUMMARYIn this study, the expression of an Onchocerca volvulus Ov33 homolog was demonstrated in Dirofilaria immitis. Rabbit antiserum raised against a recombinant fusion protein of O. volvulus, MBP/OvD 5B (Ov33), was found to react with a 31–33 kDa glycoprotein (DiT33) of adult worms of D. immitis. An antibody response to MBP/OvD 5B was observed in dogs, as early as 11 weeks post infection with infective larvae of D. immitis, and in dogs with occult infection. Cats both experimentally and naturally infected with D. immitis also reacted strongly with the recombinant antigen. In contrast, sera from dogs receiving chemically‐abbreviated infection or from animals harbouring a variety of other helminths failed to react. These data suggest that antibody responses generated by DiT33 may have potential in immunodiagnosis of heartworm infection in cats and dogs.
Resistance against Taenia hydatigena in sheep after passive transfer of serum or colostrum
Authors: JACOBS H. J. , MORIARTY K. M. , CHARLESTON W. A. G. , HEATH D. D. 
Published: October 2007

SUMMARYThe role of antibody in the resistance of sheep to infection with Taenia hydatigena metacestodes was examined using passive transfer of immunoglobulin. The immunoglobulin either was experimentally transferred in serum, or was transferred from immune ewes to their new‐born lambs in colostrum. Pooled serum from donor lambs which had received one, light, oral infection did not protect recipients although the donors themselves were immune. However, transfer of pooled serum from donors which had either received three oral infections, or three immunizations with solubilized T. hydatigena oncospheres in a water‐in‐oil adjuvant, resulted in 70–80% fewer cysts in the recipients. Colostrum from ewes infected with three high or low doses of T. hydatigena eggs was transferred to their lambs. A short acting protection (one to three weeks) was observed in the lambs. Comparisons by ELISA and Western blot, of the anti‐T. hydatigena oncosphere antibody content of the donor sera, the sera of the recipients collected 24 h and seven days after transfer, the sera of the lambs and ewes, and the colostrum of the ewes, indicated that resistance to the challenge infection depends upon a critical level of antibody.
A theoretical framework for the immunoepidemiology ofPlasmodium falciparummalaria
Authors: GUPTA SUNETRA , P. DAY KAREN 
Published: October 2007

SUMMARYMolecular genetic analyses ofP. falciparumhave led to the cloning and sequencing of a number of antigens that are potential candidates for vaccination against malaria. Seroepidemiological studies in endemic areas have attempted to assess the relative importance of these antigens in protection against malaria. In this paper, we attempt to evaluate the relative contributions of conserved and strain‐specific immune responses by modelling their influence of age‐specific patterns of infection and disease. The modelling exercises in this paper clearly demonstrate that the observed patterns of age‐prevalence are best explained by proposing that the accumulation to a threshold of an immune response against a conserved determinant is required for protection against infection, while ‘anti‐disease’ immunity develops more linearly with exposure. This is compatible with the conjecture that the parasite population is structured into several independently transmitted strains, that each confers some degree of ‘anti‐disease’ immunity, but does not protect against further infection by the same strain. Within this framework, the average duration of parasitaemia increases with age, as previously encountered strains endure for longer periods at a subclinical level. Indirect evidence for the increase in duration of parasitaemia with age may be obtained from a comparison of age‐prevalence curves between dry and rainy seasons. By using mathematical methods to structure epidemiological and immunological information, we provide a coherent theoretical framework for the dissection of the important components of naturally acquired immunity to malaria.
Eimeria maxima: ELISA and Western blot analyses of protective sera
Authors: WALLACH MICHAEL , C. SMITH NICHOLAS , M. D.MILLER CATHERINE , ECKERT JOHANNES , ROSE M.ELAINE 
Published: October 2007

SUMMARYInfection of chickens with Eimeria maxima induces the production of parasite‐specific antisera which can be used passively to protect naïve chickens against infection. Globulin fractions of these antisera can also be used passively to protect chickens. Similarly, intramuscular injection of soybean lectin affinity purified gametocyte antigens of E. maxima in Freund's Complete Adjuvant induces production of antibodies which are maternally transferred and thereby protect hatchlings against E. maxima. ELISA analyses of serum pools having varying protective capacities revealed good correlations between passive protection and levels of anti‐unsporulated oocyst, anti‐sporulated oocyst, anti‐merozoite and anti‐gametocyte antibodies. Western blotting demonstrated that the sera mainly recognized a number of high molecular weight antigens in all developmental stages and that the intensity of the reactions reflected the degree of protection induced by the sera. Sera from birds immunized with gametocyte antigens also recognized high molecular weight antigens from all the developmental stages, with banding patterns remarkably similar to those observed for sera from infected birds. Taken together, these results indicate that antibodies can protect against infection with E. maxima and these antibodies may recognize and act against asexual and/or sexual stages of the parasite.
Effect of testosterone on the mucosal defence against intestinal helminths in Indian soft‐furred rats, Millardia meltada with reference to goblet and mast cell responses
Authors: TIURIA RISA , HORII Y. , MAKIMURA S. , ISHIKAWA N. , TSUCHIYA K. , NAWA Y. 
Published: October 2007

SummaryEffects of testosterone on the mucosal defence mechanisms against intestinal helminths were examined in Millardia meltada. When female M. meltada were treated with testosterone at the pharmacological dose, Nippostrongy‐lus brasiliensis infection persisted for over seven weeks with prominent biphasic pattern of faecal egg production, whereas almost complete expulsion was observed by two weeks in untreated controls. In spite of a biphasic pattern of faecal egg production, the worm burden of testosterone‐treated animals remained constant up to three weeks and then slowly decreased by seven weeks. To see whether or not this delayed expulsion in testosterone treated animals was due to altered cellular responses of the intestinal mucosa, goblet and mast cell responses were examined histologically. At two weeks post‐infection, goblet cell responses at the infected site were significantly lower in testosterone‐treated animals than in controls. In contrast mast cell hyperplasia was comparable between testosterone‐treated and control animals. When Strongyloides venezuelensis, in which expulsion is dependent on mucosal mast cells, were infected concurrently with N. brasiliensis, testosterone‐treated animals could expel S. venezuelensis worms by Day 18, but failed to expel N. brasiliensis. Histologically, mast cell hyperplasia was associated with expulsion ofS. venezuelensis, while goblet cell responses were suppressed. From these results, testosterone seems to suppress proliferation/function of goblet cells but does not affect mast cells ofM. meltada.
Assessment of the role of the humoral response to Plasmodium falciparum MSP2 compared to RESA and SPf66 in protecting Papua New Guinean children from clinical malaria
Authors: Al‐YAMAN F. , GENTON B. , ANDERS R. , TARAIKA J. , GINNY M. , MELLOR S. , ALPERS M. P. 
Published: October 2007

SummaryThe prevalence and concentration of naturally acquired humoral response (IgG) to merozoite surface protein 2 (MSP2), RESA, SPf66 and crude schizont extract were measured in a population living in a malaria highly endemic area of Papua New Guinea. A prospective longitudinal study in 0–5–15 year old children was conducted for one year in order to examine the relationship between the humoral response to these antigens and subsequent susceptibility to clinical malaria using a series of clinical definitions. The prevalence and concentration of antibodies to all antigens increased with age. Such correlation with age was most marked for MSP2 recombinant proteins. When age and previous exposure were controlled for, only antibody levels to MSP2 recombinant proteins (3D7 andd3D7) and to RESA predicted a reduction in incidence rate of episodes of clinical malaria. Our results support the inclusion of the recombinant proteins of the 3D7 allelic family of merozoite surface antigen 2 and RESA into a subunit vaccine against malaria.,
The influence of the site of parasite inoculation on the development of Th1 and Th2 type immune responses in (BALB/c × C57BL/6) F1 mice infected with Leishmania major
Authors: NABORS GARY S. , NOLAN TOM , CROOP WILLIAM , LI JIAN , FARRELL JAY P. 
Published: October 2007

SUMMARYAlthough inbred strains of mice are classified as genetically resistant or susceptible to Leishmania major based upon their ability to control infection, other factors such as the strain, dose, and site of parasite inoculation can also affect the outcome of the disease. Here we used the Fl progeny of BALB/c (susceptible) and C57BL/6 (resistant) mice (designated CB6F1) to investigate whether mice or intermediate susceptibility to infection differed from the parental strains in their ability to control infections at different cutaneous sites. CB6F1 mice developed progressive disease when inoculated in the dorsal skin, but healed infections in the footpad. Consistent with these observations, mice inoculated in the footpad ultimately developed Th1 responses, known to be required for healing, while Th2 responses developed in mice inoculated in the dorsal skin. However, IL‐4 and IFN‐γ production during the first few weeks of infection was similar in CB6F1 mice inoculated at either site, suggesting that factors in addition to the relative levels of these cytokines produced early in infection may influence the nature of the antileishmanial immune response, and the eventual disease outcome. Infection in CB6F1 mice provides a model for the study of immunity to L. major in genetically identical animals, in which a prolonged mixed Thl/Th2 cytokine pattern initially develops, but ultimately diverges into more defined Th1 and Thl type responses.
Accelerated clearance of Onchocerca microfilariae and resistance to reinfection in lnterleukin‐4 gene knockout mice
Authors: HOGARTH P. J. , FOLKARD S. G. , TAYLOR M. J. , BIANCO A. E. 
Published: October 2007

SUMMARYImmunity to Onchocerca microfilariae (mf) in mice is associated with CD4+ Th2 cells and is dependent on IL‐5. In view of the role ofIL‐4 in the development of Th2 cells, we have utilized IL‐4 gene knockout mice (IL‐4‐1‐) to investigate microfilarial clearance and resistance to reinfection. Paradoxically, in the absence of IL‐4 there is accelerated clearance of microfilariae during a primary infection and unimpeded expression of resistance to reinfection. IL‐4‐1‐ mice showed a lack of an IgE response although peripheral eosinophilia was equivalent to wildtype controls. The data presented here suggest that elimination ofmfcan occur independent of IL‐4 and that in this model it may even be detrimental to the host.