bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduced infectivity of Nematospiroides dubius larvae after incubation in vitro with neutrophils or eosinophils from infected mice and a lack of effect by neutrophils from normal mice
Authors: PENTTILA I.A. , EY P.L. , JENKIN C.R.
Published: October 2007

Summary Neutrophils and eosinophils, isolated from the blood of mice infected with Nematospiroides dubius, were tested for their capacity to damage exsheathed third stage N. dubius larvae in vitro. In the presence of fresh serum from infected mice, both types of granulocyte caused a significant reduction in larval infectivity (up to 40–50%) whereas lymphocytes/monocytes prepared from the same blood samples were inactive. Neutrophils were at least as active as eosinophils, on a cell for cell basis. None of the cells exhibited larvicidal activity in the absence of serum and serum alone had no effect. The reduction in larval infectivity caused by neutrophils in the presence of fresh normal mouse serum (NMS) was only marginally less than that obtained using immune mouse serum (IMS), suggesting that complement, which is activated by the larvae via the alternative pathway and mediates the adherence of both cell types, was able to promote the larvicidal effect of these cells in vitro. In contrast to neutrophils, eosinophils were considerably less effective in NMS than in IMS. Both NMS and IMS were ineffective if they had been heat‐inactivated or incubated with methylamine at pH 8.0 to destroy complement activity. The immunoglobulin fraction of IMS was also ineffective in promoting neutrophil or eosinophil‐mediated larval damage. These results indicate that in this in vitro system antibodies are incapable of directing the activity of either cell type in the absence of complement. A novel finding of this study was that neutrophils from uninfected mice were unable to reduce larval infectivity in the presence of fresh NMS or IMS. ‘Altered’ neutrophils possessing larvicidal activity appeared in the blood of mice within 4 days of infection with N. dubius.
Lymphatic filariasis in man: demonstration of circulating antigens in Wuchereria bancrofti infection
Authors: DASGUPTA A. , BALA SHUKAL , DUTTA S.N.
Published: October 2007

Summary Five hundred and twenty‐nine sera obtained from people dwelling in an area endemic for bancroftian filariasis were analysed for the presence of soluble circulating antigens (SCA) of filarial origin by counter Immunoelectrophoresis and 303 were found positive. It, therefore, appears that 57.3% subjects could be diagnosed by the detection of SCA irrespective of their clinical status. Of the three groups investigated, microfilaraemic, amicrofilaraemic and clinical, SCA could be demonstrated in maximum number of sera obtained from clinical cases. The parasite specificity of the SCA was determined by enzyme linked immunosorbent assay (ELISA), immunofluorescent antibody test (IFAT), counter Immunoelectrophoresis (CIEP) and gel diffusion (GD) using antisera raised against Litomo‐soides carinii in rabbits and antigens derived from Wuchereria bancrofti microfilariae or antigens present in sera of patients with bancroftian filariasis. This anti‐carinii hyperimmune serum under study did not show positive reactions with parasites other than filaria, or with the sera obtained from pre‐immunized rabbits and non‐endemic controls. A demonstration of a distinct precipitin band in CIEP and GD indicates that either monospecific hyperimmune sera or monoclonal antibodies could be raised for the development of a simple method for immunodiagnosis of bancroftian filariasis.
Monoclonal antibody neutralizes the sporozoite stage of different Theileria parva stocks
Authors: DOBBELAERE D.A.E. , SPOONER P.R. , BARRY W.C. , IRVIN A.D.
Published: October 2007

Summary Monoclonal antibodies were raised against sporozoites of Theileria parva. One of these antibodies (MAbDi) neutralized the infectivity of sporozoites for lymphocytes in vitro and for cattle in vivo. Neutralization seemed to occur by blocking sporozoite entry into the cell. MAbDi neutralized sporozoites of four unrelated stocks of T. parva, indicating the presence of a common antigenic determinant which may be important in initiating protective immunity.
Increased macrophage migration inhibition factor production in hamsters sensitized by amoebic antigen and glucan
Authors: HAQ A. , SHARMA A. , AHMAD S.
Published: October 2007

Summary Well defined cell‐mediated immune responses were detectable following experimental immunization of hamsters with Entamoeba histolytica antigen, using glucan as an adjuvant. Peritoneal cells from amoeba antigen‐glucan sensitized animals, upon incubation with specific antigen in vitro, were found to release into the supernatant a macrophage migration inhibition factor (MIF). Such supernatant fluids inhibited the migration of macrophages from non‐sensitized hamsters. The production of MIF was found to be greatly increased if glucan is added to amoeba antigen when sensitizing animals. The optimal concentration for maximum inhibition was recorded at 10‐8 dilution of the supernatant.
Immunological and ultrastructural aspects of the cell‐mediated killing of Dirofilaria immitis microfilariae
Authors: RZEPCZYK CHRISTINE M. , BISHOP C. J.
Published: October 2007

Summary Neutrophils in the presence of serum from dogs with occult Dirofilaria immitis infections were shown to be cytotoxic to D. immitis microfilariae recovered from the blood of microfilaraemic dogs. This cytotoxicity was correlated with the presence of IgM and IgG antibodies on the cuticular surface of microfilariae incubated in the sera from occult dogs. Such antibodies were not observed on the surface of microfilariae incubated in sera from microfilaraemic or normal dogs. The neutrophil attack was directed at the cuticular crypts, at which sites the worms appeared to be structurally most vulnerable because of the absence of the outer layer of the cuticle. The IgM antibodies were shown to be bound preferentially to these sites. Our data suggested that the neutrophil‐mediated toxicity involved both hydrogen peroxide release and degranulation.
Changes in the haemolytic activity of bovine serum complement by Hypoderma lineatum (insect oestridae) larval proteinases in naive and immune cattle
Authors: BOULARD CHANTAL , BENCHARIF FIFI
Published: October 2007

Summary Three serine proteinases (hypodermin A, B and C) of the first instar larvae of Hypoderma lineatum have been assayed for their ability to deplete seric complement of naive or immune cattle. In naive cattle complement consumption is initiated by hypodermin B through the sequence C1‐C3 at a concentration of 5 pg/ml of serum, and by hypodermin A through the sequence of C3‐C9 at a higher concentration of 150 μg. The third enzyme presenting a collagenolytic activity has no anti‐complementary activity even on C1 q. In immune cattle a 70% complement depletion through the classical pathway is observed with 15 μg of hypodermin B per ml of serum. The two enzymes A and C appear to play a minor role in the complement depletion via the classical pathway. The biological role of each of these enzymes in the parasite‐host interrelationships is discussed. The participation of these enzymes in the immediate hypersensitive reactions following systemic treatment of cattle infested by this endoparasite is considered.
Towards molecular vaccines against parasites
Authors: MITCHELL G. F.
Published: October 2007

Summary A strategy is outlined for the identification of'host protective antigens' of parasites using batteries of polyspecific sera from clinically and parasitologi‐cally denned individuals of the host population. Together with monospecific antibodies and gene cloning techniques, the approach aims to identify, characterize and produce defined antigens that, through active immunization, are necessary or sufficient for expression of host protective immunity on subsequent contact with the parasite population. The availability of a relevant mouse model system greatly increases the rate at which progress is made in the testing of vaccinating efficacy. Advantages and limitations of molecular, defined‐antigen vaccines are discussed as are integral components of the strategy such as probes for the analysis and quantitation of parasite population heterogeneity and antigenic variability, identification of principal mechanisms of ‘immune evasion’ utilized by invasive and resident parasites, reliable diagnostic procedures, and predictable antigen delivery systems and adjuvants. Emphasis is placed on the value of combining epidemiological and clinical studies with immunochemical and molecular cloning approaches in achieving the molecular vaccine objective.
Immunity to Brugia pahangi in athymic nude and normal mice: eosinophilia, antibody and hypersensitivity responses
Authors: VICKERY ANN C. , VINCENT A. L.
Published: October 2007

Summary Congenitally athymic nude (nu/nu) mice, immunologically reconstituted by thymus grafting before inoculation with infective larvae, and mice heterozygous for the nu gene (nu/+), mounted potent protective humoral and cellular immune responses to Brugia pahangi. Although responses were not identical, both groups of mice produced IgM, IgG and IgE antibodies specific for adult worm antigen (S‐Ag) present in a crude aqueous extract, made immediate and delayed hypersensitivity footpad swelling responses when challenged with S‐Ag and eliminated their infection in the early larval stages. Heterozygotes also exhibited a marked eosinophilia which peaked coincident with larval killing. In contrast, thymus grafting of patent nudes had no effect upon microfilaraemias or adult worm burdens and did not completely protect against a challenge larval inoculum although antibodies specific for S‐Ag were produced. With the occasional exceptions of moderate immediate footpad swelling and very low titres of IgM specific for S‐Ag, no specific immune responses to B. pahangi were found in ungrafted nude mice which allowed full development of adult worms and supported patent infections.
Antibody responses to the antigen Sj26 of Schistosoma japonicum worms that is recognized by genetically resistant 129/J mice
Authors: MITCHELL G. F. , BEALL J. A. , CRUISE K. M. , TIU W. U. , GARCIA E. G.
Published: October 2007

Summary Serum antibody responses of mice exposed to Philippine isolates of Schistosoma japonicum have been analysed by immunoprecipitation of exogenously radiolabelled antigens extracted from adult worms. Attention was focused on labelled protein antigens differentially recognized by sera of mice that differ genetically in their resistance status. Mice of the inbred strain 129/J can show high level resistance to first or repeated infection with S. japonicum. Even after six percutaneous administrations of 25 cercariae, approximately 50% of 129/J mice remain healthy with no or very feu worms present in the portal system. Sera from 129/J mice exposed to S. japonicum consistently and differentially recognise an antigen of adult worms of mol. wt. 26,000. This antigen, termed Sj26, is not immunoprecipitated from S. mansoni adult worms by sera from resistant 129/J mice. Serum antibodies to Sj26 are present in at least some patients with a history of schistosomiasis japonica. Whether immune responses to SJ26 are involved directly in expression of resistance to S. japonicum remains to be determined. However, this antigen produced by cloned DNA in expression vectors, or isolated from adult worms, is an obvious candidate to be tested for vaccination efficacy in mice.
Antibody‐dependent cellular cytotoxicity of Trypanosoma theileri mediated by purified bovine isotypes and subisotypes
Authors: TOWNSEND JACKIE , DUFFUS W. P. H.
Published: October 2007

Summary Bovine neutrophils, eosinophils and macrophages mediated in vitro cytotoxicity against Trypanosoma theileri in the presence of purified IgM, IgGl and IgG2 from immune bovine serum. When the immunoglobulin fractions were assayed at similar concentrations, IgM was the most effective isotype mediating killing with all three effector cell types. Using the ELISA with monospecific antisera against the different bovine isotypes and subisotypes, IgM was shown to be contaminated by < 1%. The addition of 0·08 M 2‐mercaptoethanol inhibited IgM‐mediated ADCC but not that of IgGl or IgG2, and the cytotoxicity occurred in the absence of complement. The presence of isotype and subisotype specific Fc receptors on the bovine effector cells was investigated using a totally homologous erythrocyte‐antibody (EA) resetting technique. FC receptors for bovine IgM, IgG1 and IgG2 were detected on bovine neutrophils. Very few FcM receptors were detected on either eosinophils or macrophages, but FcG2 receptors were detected on both cell types, and FcG1 receptors on macrophages. However, eosinophils showed very few FcG1 receptors. The failure to detect all types of Fc receptor on the three different effector cells is discussed.
Further studies on genetic variation of hepatosplenic disease and modulation in murine schistosomiasis mansoni
Authors: FANNING MARY M. , KAZURA J. W.
Published: October 2007

Summary The influence of genetic factors on the modulation of hepatosplenomegaly. portal venous pressure and granuloma size in chronic murine schistosomiasis mansoni was studied. Experiments with congenic mice confirmed previous observations that after 8 weeks of infection these disease manifestations are influenced by non‐H‐2 genes. During chronic infection (20 weeks compared to 8 weeks of infection), hepatosplenomegaly was minimally altered. Portal venous pressure was found to increase in 129/J and BALB/cJ mice, did not change in C57BL/6J and DBA/2J and decreased in CBA CaJ mice. Simultaneous measurements of granuloma size delineated two groups: decrease of >40%—C57BL/6J, DBA/2J and CBA/CaJ strains and decrease of ≤ 20%—129/J, BALB/cJ and C3H/HeJ mice. There was no consistent correlation between the magnitude or direction of alterations in portal pressure and granuloma size among the various strains studied. Furthermore, these alterations were independent of changes in parasite burden (adult worms or hepatic eggs). This amelioration of disease (modulation) was found to be influenced by a small number of non‐H‐2 genes.
Inhibition of lymphocyte invasion by sporozoites and the transformation of trophozoite infected lymphocytes in vitro by serum from Theileria annulata immune cattle
Authors: PRESTON PATRICIA M. , BROWN C. G. D.
Published: October 2007

Summary Serum from calves immune to Theileria annulata inhibited sporozoite‐induced infection and transformation of peripheral blood leucocytes (PBL) into macroschizont infected lymphoblastoid cells in vitro. Invasion by sporozoites was suppressed by some sera, especially that obtained after challenge, but in many instances suppression of infection could be attributed only to retardation of development of PBL infected with intracellular trophozoites into proliferating macroschizont infected cells. Suppression occurred both in cultures of PBL from susceptible calves and in cultures of PBL from T. annulata immune calves. More uninfected than infected blast cells were found both in cultures of PBL from susceptible calves and in cultures of PBL from immune animals. Results suggested that proliferation of uninfected PBL from susceptible calves was initiated by the transformation of sporozoite infected cells, whilst proliferation of uninfected PBL from immune calves also incorporated a component which was a mitotic response of sensitised lymphocytes to sporozoites (i.e. parasite antigen). Thymidine incorporation by cultures was a measure of proliferation of both uninfected and infected blast cells. It could be used, therefore, to monitor parasite development only where proliferation of total blast cells was directly related to proliferation of infected blasts, as in cultures of PBL from susceptible calves. This study suggests that resistance of cattle to tick derived challenge with sporozoites is mediated initially by serum factors acting both on sporozoites and on the development of intracellular trophozoites to schizonts; that the proliferation of uninfected lymphocytes in naive cattle infected with tropical theileriosis is a direct response to the proliferation of Theileria infected cells and that the proliferation of uninfected lymphocytes in Theileria immune cattle is a combined response to the proliferation of Theileria infected cells and parasite antigen.
The serum antibody response of infected rats, rabbits, lambs and calves to Fasciola hepatica adult antigen fractions separated by preparative flatbed iso‐electrofocussing
Authors: WASSALL D. A. , SINCLAIR I. J.
Published: October 2007

Summary Electrofocussing of F. hepatica adult antigen in granulated gels separated the material into 22 arbitrary fractions. Polyacrylamide gel analysis demonstrated groups of proteins with similar iso‐electric points in 19 of the fractions. A microplate ELISA detected antigens in all 22 fractions and was used to test the serum antibody response in infected rats, rabbits, lambs and calves to these antigen fractions. The results indicated that rat and calf sera gave a much stronger response than rabbit and lamb sera to the antigens which separated above pH 7·0. It is possible that the greater efficiency of the rat and bovine immune systems in combating re‐infection with F. hepatica may be related to this response.
The use of aldehydes to show a relationship between host and parasite antigens at the surface of adult male Schistosoma mansoni
Authors: HARNETT W. , KUSEL J. R. , BARROWMAN M. M.
Published: October 2007

Summary An indirect radiolabelled antibody method has been developed to measure the effects of aldehydes on the amount of antigen detectable at the surface of adult male Schistosoma mansoni. Incubation of schistosomes in formaldehyde (0·01–10% wt/vol.) or glutaraldehyde (0·01–0·1% wt/vol.) was found to result in increased exposure of parasite antigens with a concomitant decrease in the amount of surface located host RBC antigens. Those concentrations of formaldehyde or glutaraldehyde which were most effective in removing or displacing host antigens were also most able to expose parasite antigens. These findings are consistent with the hypothesis that host antigens mask parasite antigens at the surface of the adult schistosome.
Defective protective capacity of W/Wv mice against Strongyloides vatti infection and its reconstitution with bone marrow cells
Authors: NAWA Y. , KIYOTA M. , KORENAGA M. , KOTANI M.
Published: October 2007

Summary The susceptibility of congenitally anemic, and mast cell deficient W/Wv mice to infection with Strongyloides ratti was examined. After a primary infection, W/Wv mice showed greater and more persistent peak larval counts than did normal littermates. Worm expulsion was also slower in W/Wv mice than in +/+ mice. Furthermore, difference in susceptibility was expressed as early as 24 h after infection, suggesting not only that protective mechanisms of the gut but also of the connective tissue were defective in W/Wv mice. Reconstitution with bone marrow or spleen cells from +/+ mice was effective in restoring the protective response in W/Wv mice, whereas thymocytes or mesenteric lymph nodes had no effect. Both connective tissue and mucosal mast cells were repaired in W/Wv mice after marrow reconstitution and infection. Since relatively long incubation period was required for the expression of such reconstituting activities, bone marrow cells seem to contain precursor cells of the effector and/or regulator cells.
A limiting dilution assay for quantifying Leishmania major in tissues of infected mice
Authors: TITUS R. G. , MARCHAND M. , BOON T. , LOUIS J. A.
Published: October 2007

Summary A limiting dilution assay for the quantification of Leishmania major in infected mouse tissue was developed. The assay was found to be both sensitive and reliable, and, due to its design, could be scored either visually or following the incorporation of 3H‐thymidine by the growing parasites. Results are presented in which the assay was employed to enumerate L. major in the tissues of susceptible (BALB/c) and resistant (CBA) mice at intervals after infection with L. major. It was found that parasites could be detected at the site of injection with L. major as early as 3 days after infection. By day 8, a substantial increase in the number of parasites at the lesion site had occurred in both strains of mice. Subsequently, whereas the number of parasites decreased in the lesions of CBA mice, their number steadily increased in the lesions of BALB/c mice. Parasites were detected in lymph nodes draining the lesion site in both BALB/c and CBA mice by 28 days after infection. Interestingly, a low number of L. major was found in the lymph nodes of CBA mice at 100 days after infection, a time when no parasites could be detected at the lesion site. Previous results from this laboratory have demonstrated that the adoptive transfer of L. major‐specific L3T4‐positive T‐cell populations exacerbated cutaneous lesions induced by L. major in BALB/c mice. Experiments presented here indicate that the adoptive transfer of L. major‐specific T‐cells also exacerbated cutaneous leishmaniasis in CBA mice. Using the sensitive limiting dilution assay presently described, it was found that this unexpected exacerbative effect of L. major‐specific T‐cells on lesion development was accompanied by a substantial increase in the number of parasites in the lesions of the adoptively transferred mice.
Protective immunity to malaria: studies with cloned lines of Plasmodium chabaudi and P. berghei in CBA/Ca mice. I. The effectiveness and inter‐and intra‐species specificity of immunity induced by infection
Authors: JARRA W. , BROWN K. N.
Published: October 2007

Summary CBA/Ca mice were immunized by infection with cloned lines of Plasmodium berghei (isolates ANKA, KSP‐11). Plasmodium chabaudi chabaudi (AS, CB) or Plasmodium chabaudi adami (DS) and then challenged with either homologous or heterologous parasites. Protective responses were assessed in immune mice relative to the controls by their ability to (i) extend the time taken for the mean parasitaemia to reach a predetermined level (1% or 0·1%) (ii) reduce peak parasitaemia (iii) resolve the parasitaemia sooner and/or (iv) control or eliminate recrudescences. At both the inter‐ and intra‐species level, immunity appeared largely specific for the cloned line inducing it. At the interspecies level marginally effective cross‐immunity was sometimes evident, thus P. berghei KSP‐11 immune mice displayed some immunity against P. c. chabaudi AS, although immunity to this parasite was relatively ineffective against P. berghei ANKA or KSP‐11. Cross‐immunity was more apparent between the subspecies P. c. adami and P. c. chabaudi and between cloned lines of the latter parasite derived from the AS and CB isolates. These data reflect considerable inter‐ and intra‐species structural and immunogenic differences in certain antigens of parasitized erythrocytes and merozoites, which have been identified in a number of murine malarias and associated with protective immunity. Similar differences recently identified in the equivalent antigens of the human parasite P. falciparum may therefore have important implications for protective immunity in man.
In‐vitro antibody‐dependent killing of schistosomula of Schistosoma haematobium by human eosinophils
Authors: HAGAN P. , MOORE P. J. , ADJUKIEWICZ A. B. , GREENWOOD B. M. , WILKINS H. A.
Published: October 2007

Summary Schistosomula of S. haematobium have been shown to be susceptible to in vitro killing by eosinophils in the presence of serum from an infected individual. The highest level of killing was found after 48 h in culture. Killing was related to the eosinophil to schistosomula ratio, being highest at 5000:1. Killing was also related to serum concentration, being highest at a 1/10 final dilution, falling to background levels at a 1/120 final dilution. At a cell: target ratio of 2000:1 and at a serum dilution of 1/10 eosinophils from subjects with high peripheral blood eosinophil counts were, cell for cell, more active in killing S. haematobium schistosomula than were eosinophils from subjects with lower counts. Sera taken from adults resident in an endemic area gave higher levels of killing in the presence of eosinophils than did sera taken from adults with no history of exposure.
Eosinophilia and resistance to Schistosoma haematobium in man
Authors: HAGAN P. , WILKINS H. A. , BLUMENTHAL U. J. , HAYES R. J. , GREENWOOD B. M.
Published: October 2007

Summary We have measured the levels of infection with Schistosoma haematobium in children resident in an endemic area of The Gambia before and 3 months after successful chemotherapy and following reinfection. An exposure index was calculated from data collected on water contact, cercarial densities and infected snail densities at water contact sites. Peripheral blood eosinophil levels were recorded and the ability of serum (heat inactivated) from the children to allow killing of schistosomula of S. haematobium was examined. Of 50 children with a post‐treatment egg count of < 1 ovum/10 ml urine, 26 were classified as reinfected, acquiring > 1 ovum/10 ml urine over the transmission season. Twenty‐four were classified as not reinfected, acquiring < 1 ovum/10 ml of urine over the same period. These two groups did not differ with respect to their estimated age, weight or pretreatment egg counts. Children who were reinfected had significantly higher levels of exposure and significantly lower peripheral blood eosinophil counts than children who were not reinfected. At all levels of exposure children with high eosinophil counts were less likely to be reinfected than those with lower counts. But antibody‐dependent, complement‐independent killing of schistosomula of S. haematobium by eosinophils was barely detectable and did not differ between reinfected and non reinfected groups. These observations suggest that subjects with elevated counts are less susceptible to reinfection but the mechanisms involved are not apparent.
Fasciola hepatica: comparison of immature and mature immunoreactive glycoproteins
Authors: DALTON JOHN P. , TOM TIMOTHY D. , STRAND METTE
Published: October 2007

Summary A comparison of the 35S‐methionine metabolically labelled immunoreactive glycoproteins of immature and mature F. hepatica was carried out by one‐and two‐dimensional sodium dodecyl sulfate‐polyacrylamide gel electrophoresis. Sera of rabbits infected for 3 weeks reacted much more strongly with glycoproteins of immature flukes than with glycoproteins of mature flukes as compared to sera of rabbits infected for 9 weeks. Several of the immunoreactive glycoproteins were also released by immature F. hepatica into the culture medium. At least one was a component of the T1 type granules. Analysis of the in vitro translation products of mature F. hepatica indicated that the initial humoral immune response of rabbit hosts may be directed against carbohydrate moieties.
Natural resistance to African trypanosomiasis
Authors: ROELANTS G. E.
Published: October 2007

Glossina infected with African trypanosomes infest 107 Km2 of intertropical Africa. Ten thousand cases of human sleeping sickness are officially recorded each year and 35 times 106 human beings are at risk. Animal trypanosomiasis impedes the use of 7times 106 Km2 of land adequate for cattle raising and constitutes a major constraint to increasing protein production in Africa.

Several approaches are used to combat trypanosomiasis (a) vector eradication has been successful in certain denned situations but cannot be realistically extended to the whole area at risk, (b) prophylactic drugs, which are too toxic for humans, are widely used to protect cattle. This practice has led to field resistance to many drugs used in the past (reviewed in Holmes & Scott 1982) and the appearance of resistance to the last available prophylactic drug, isometamidium, is being reported (Bourn & Scott 1978, Kiipper & Wolters 1983, Pinder & Authie 1984), (c) the hope for a vaccine has been largely abandoned, in the present state of knowledge, due to the considerable extent of antigenic diversity in trypanosomes (reviewed in Doyle 1977, Turner 1982, Roelants & Pinder 1984), (d) consequently, the possible use of certain West African breeds of cattle, which appear resistant to trypanosomiasis, has been emphasized as a solution to this problem in domestic animals. The analysis of this natural resistance is the subject of the present essay.
Antigenic diversity and size diversity of P. falciparum antigens in isolates from Gambian patients. II. The schizont surface glycoprotein of molecular weight ˜ 200 000
Authors: HOWARD R. J. , McBRIDE J. S. , ALEY S. B. , MARSH K.
Published: October 2007

Summary A panel of monoclonal antibodies has been shown previously to identify both serologically diverse and serologically conserved epitopes on a major polymorphic surface protein of P. faliparum schizonts from culture‐adapted isolates. The molecular nature of the antigen recognized by eight of these monoclonal antibodies was studied with three isolates analyzed directly from patients in The Gambia. Malarial (glyco) proteins were labelled by biosynthetic uptake of 3H‐glucosamine or 3H‐leucine during culture of ring‐stage parasites from infected blood to the late‐trophozoite/early‐schizont stage (26–30 h). Those monoclonal antibodies which reacted positively with an isolate by indirect immunofluorescence also immunoprecipitated a single 3H‐leucine or 3H‐glucos‐amine labelled antigen of mol. wt ˜200 000 from Triton X‐100 extracts of the same isolate. Monoclonal antibodies which did not react by indirect immunofluorescence failed to immunoprecipitate this antigen. Although each of the three isolates studied in detail was very similar serologically with the panel of monoclonal antibodies specific for this mol. wt ˜200 000 antigen, this protein could be distinguished with each isolate on the basis of its apparent size on SDS‐polyacrylamide gel electrophoresis. The specifically immunoprecipitated antigen had a mol. wt of 204 000, 197 000 or 202 000, depending on the isolate. Size diversity of this malarial glycoprotein was also detected with seven other Gambian P. falciparum isolates. We conclude that natural isolates of P. falciparum express a major 3H‐glucosamine labelled glycoprotein of mol. wt Mr˜200 000 which exhibits size diversity and expresses antigenically conserved as well as diverse epitopes as defined by the panel of monoclonal antibodies.
Immunoglobulin class specific responses to biochemically defined antigens of Trichinella spiralis
Authors: ALMOND N. M. , PARKHOUSE R. M. E.
Published: October 2007

Summary A comparison of the humoral response to resistant (NIH) and susceptible (C3H) strains of mice, which reject adult worms at different rates during a primary infection, was made following infection with Trichinella spiralis. The serum concentration of immunoglobulins of the heavy chain classes IgM, IgGl, IgG2, IgG3 and IgA were determined by single radial immunodiffusion. Antibodies of the same immunoglobulin isotypes to biochemically defined, stage specific surface and secreted components of three stages of parasite development were also determined using an isotype specific immuno‐coprecipitation assay. Independent variation of the responses of each immunoglobulin isotype was observed. The specific anti‐parasite response did not reflect total serum immunoglobulin levels in all immunoglobulin classes, and this is discussed in relation to basic mechanisms of immunoglobulin class switching. Finally a close correlation was observed in resistant (NIH) mice between the production of IgA antibody to surface components of adult worms and accelerated expulsion of this stage of the worm from the gastrointestinal tract. The possible relevance of this IgA response is further indicated by the failure of susceptible mice to synthesise IgA antibodies to the same surface antigens.
Regulation of parasite‐specific antibody responses in resistant (C57BL/6) and susceptible (C3H/HE) mice infected with Trypanosoma (trypanozoon) brucei brucei
Authors: BLACK S. J. , SENDASHONGA C. N. , WEBSTER P. , KOCH G. L. E. , SHAPIRO S. Z.
Published: October 2007

Summary After infection with 103T. brucei GUTat 31, C57BL/6 mice produced antibody responses and controlled the first parasitaemic wave whereas C3H/Hemice did not. The inability of C3H/He mice to control parasitaemia resulted from an impaired ability of parasite‐induced antibody‐containing cells to secrete immunoglobulin. Antibody‐containing cells in infected C3H/He mice regained the ability to secrete antibody within 24 h after trypanosome elimination by treatment with Berenil, suggesting that the block in antibody secretion was maintained by living parasites or short‐lived components of degenerating parasites. Infected C3H/He mice also had an impaired ability to produce a rabbit erythrocyte‐specific antibody response on challenge with rabbit erythrocytes and this response recovered when parasites were eliminated from the blood 24 h before analysis. It was not possible to inhibit secretion of antibody by rabbit erythrocyte‐induced plasma cells either by incubating them with serum from infected C3H/He mice or by injecting large numbers of living trypanosomes into C3H/He mice already responding to rabbit erythrocytes. The process leading to failure of parasite and rabbit erythrocyte‐induced antibody‐containing cells to become high rate antibody‐secreting cells was not identified but did not appear to correlate with any obvious change in the intra‐cellular morphology of the antibody‐containing cells.
Analysis of B cell and T cell proliferative responses induced by monomorphic and pleomorphic Trypanosoma brucei parasites in mice
Authors: SENDASHONGA CYRIAQUE N. , BLACK S. J.
Published: October 2007

Summary Cells collected from C57B1/6 mice infected with monomorphic and pleomorphic clones of Trypanosoma brucei parasites (ILTat 1 ‐4 and GUTat 3–1) were analysed for the incorporation of 125I‐Iododeoxyuridine into DNA of total splenic lymphocytes and of B and T lymphocytes isolated on a fluorescence activated cell sorter. The monomorphic T. brucei ILTat 1–4 parasites triggered delayed and low splenic DNA synthetic responses in comparison to those arising in mice infected with the pleomorphic T. brucei GUTat 3–1 organisms. Mice infected with both parasite clones mounted splenic DNA synthetic responses similar to those arising in animals infected with the pleomorphic organisms alone and similar responses were induced by lethally irradiated T. brucei GUTat 3–1 and T. brucei ILTat 1 ‐4 parasites. In mice infected with the pleomorphic parasites, DNA synthesis was first detected in the Tcell population and Bcell DNA synthetic responses were detected between 1 and 2 days later. In contrast only T cell DNA synthetic responses were detected after infection with the monomorphic T. brucei ILTat 1–4 parasites. It is suggested that the previously reported failure of monomorphic T. brucei parasites to trigger antibody production in infected mice is a result of their inability to stimulate B lymphocytes.
Opisthorchis viverrini: pathogenesis of infection in immunodeprived hamsters
Authors: FLAVELL D. J. , FLAVELL S. U.
Published: October 2007

Summary Opisthorchis viverrini infections were established in immunologically intact and T cell deprived hamsters. T cell deprivation appeared to have no effect on worm establishment or egg production. Histopathologically, intact and deprived animals showed similar degrees of bile duct hyperplasia and periductular fibrosis, though there was a marked reduction in the intensity of the periportal inflammation in the majority of T cell deprived animals. Serum transaminase levels were significantly raised in intact animals by 25 days after infection, whilst levels remained within normal limits throughout the infection period for the majority of the T cell deprived animals. The antibody response to parasite antigens as determined by immunoelectrophoresis, was impaired in T cell deprived animals. Attempts to correlate the serological picture with transaminase levels at three time points after infection and also with the extent of periductular inflammation seen on killing, proved largely unsuccessful. These results indicate that T cell deprivation of the hamster host ameliorates the periductular inflammatory response provoked by O. viverrini in this species. It is suggested that such inflammatory responses are evoked by parasite antigens which gain access to portal tract and surrounding areas, and that such reactions are immunopathologi‐cal in their outcome to the host, resulting in liver cell death and subsequent replacement of resolving inflammatory and necrotic areas with fibrotic tissue.
Immunization of mice with surface antigens from the muscle larvae of Trichinella spiralis
Authors: GRENCIS R. K. , CRAWFORD C. , PRITCHARD D. I. , BEHNKE J. M. , WAKELIN D.
Published: October 2007

Summary Surface antigens of muscle larvae of Trichinella spiralis were stripped from the cuticle of live worms by the cationic detergent cetyltrimethylammonium bromide (CTAB). Such antigen preparations were shown to contain surface antigens of approximate molecular weights 100000, 90000, 69000, 55000, 46000 and 35000. Immunoprecipitation experiments confirmed that the surface of muscle larvae share antigenic epitopes with antigens contained within and secreted by the stichosome. CTAB antigen preparations were shown to be protective in NIH mice against a challenge infection as assessed by reduction in intestinal worm burden, worm fecundity, worm length and muscle larvae burden. The role of surface antigens in protective immunity to T. spiralis is discussed.
Surface properties of developing stages of Trichuris muris
Authors: PRESTON CHRISTINE M. , JENKINS T. , McLAREN DIANE J.
Published: October 2007

Summary Surface properties of developing stages of Trichuris muris were investigated by analysis of binding affinities for specific anti‐parasite antibodies present in a range of infection sera; in vitro eosinophil adherence studies; and binding of the fluorescent‐labelled lectins, Con A, WGA, PNA and RCA. In general, larvae of any one particular stage did not bind anti‐parasite antibodies present in serum collected at an earlier stage of the infection, thus indicating a considerable degree of antigenic stage‐specificity. Forty day and older parasites displayed similar binding properties and it is suggested that no major changes in surface antigenicity occur after the final moult at day 25–30 after infection. Surface properties were also examined by means of complement and antibody‐mediated eosinophil adherence assays. Attachment of eosinophils was maximal with day 5 larvae, although even at this stage not all of the parasite surface was covered with attached cells. Despite adherence, eosinophils were unable to effect parasite killing, even after 48 h of incubation. These studies showed that eosinophil adherence‐promoting antibodies were present in immune sera; that the larval parasite surface was able to activate complement by the alternate pathway with subsequent generation of C3b molecules, and that the parasite was able to withstand eosinophil adherence and secretion by an as yet unidentified evasive stratagm. Studies with fluorescent‐labelled lectins showed that all larval stages (days 5–25 after infection) were positive for Con A binding. Early larval stages (days 5–10 after infection) also bound PNA and WGA. Interestingly, recently moulted individuals rarely exhibited fluorescence, but cast cuticles fluoresced brightly.
Protection of mice against intestinal amoebiasis with BCG, Corynebacterium parvum and Listeria monocytogenes
Authors: GHADIRIAN E. , KONGSHAVN P. A. L.
Published: October 2007

Summary Treatment with Corynebacterium parvum or BCG, or infection with live Listeria monocytogenes was found to protect mice against subsequent infection with Entamoeba histolytica. Complete protection was obtained in mice treated with 107 (colony forming units) of BCG but not with 105. Partial protection was achieved with 106 of BCG. These data provide evidence that non‐specific immunity plays an important role in host defense against amoebic infection
Reconstitution of mucosal mast cells in W/Wv mice by adoptive transfer of bone marrow‐derived cultured mast cells and its effects on the protective capacity to Strongyloides ratti‐infection
Authors: ABE T. , NAWA Y.
Published: October 2007

Summary Bone marrow‐derived cultured mast cells (BMMC) were transferred intravenously into W/Wv mice to examine if they could reconstitute defective mucosal mast cell response or defective protective capacity against infection with Strongyloides ratti. When mast cell growth factor‐producing activity of W/Wv mice were examined, mesenteric lymph node cells obtained at 7 to 14 days after infection could produce this factor in vitro by stimulation with S. ratti‐adult worm antigen. A single injection of BMMC (1 ± 107) on day 7 post‐infection (p.i.) neither caused an increase in number of intestinal mucosal mast cells not altered the kinetics of faecal larval output (LPG). On the other hand, serial injections of BMMC (5 ± 106) from day 5 to 10 p.i. (total 3 ± 107 cells) resulted in the significant increase in number of intestinal mucosal mast cells. However, this treatment too could not alter the kinetics of LPG. Therefore, adoptive transfer of BMMC could cause the increase in number of histologically detectable‐mucosal mast cells, but these cells are, by themselves, not sufficient to cause the expulsion of S. ratti adult worms from the intestine.
The correlation between delayed hypersensitivity, lymphocyte activation and protective immunity in experimental murine leishmaniasis
Authors: DE ROSSELL RAIZA ARAGORT , BRAY R. S. , ALEXANDER J.
Published: October 2007

Summary The growth of Leishmania major and Leishmania mexicana lesions and the concomitant development of delayed‐type hypersensitivity (DTH) to homologous or heterologous soluble antigen was studied in BALB/c and CBA/Ca mice. Although CBA/Ca mice are highly susceptible to L. mexicana, developing non‐healing lesions, they are resistant to L. major; while BALB/c mice develop non‐healing lesions when infected with either species. The development of resistance was associated with the acquisition of DTH which peaked at 48 h (L. major infected CBA/Ca mice). Non healing lesions were associated with either negative DTH (L. major infected BALB/c mice) or DTH that peaked at 24 h but had significantly subsided by 48 h (L. mexicana infected CBA Ca and BALB/c mice). The latter response was associated with basophilic infiltration of the skin test site. Pre‐irradiating (600 rad) CBA/Ca and BALB/c mice induced resistance against L. mexicana and L. major respectively in conjunction with the appearance of 48 h DTH to the homologous antigen. There was clear dissociation in the skin reactivity produced by the heterologous antigen. Thus L. major‐derived antigen failed to produce DTH in L. mexicana infected mice of either strain. L. mexicana‐derived antigen on the other hand produced a quicker response and of greater magnitude than the homologous antigen in L. major infected CBA/Ca mice. This correlated well with the strong cross‐immunity induced by L. major in these mice to L. mexicana infection.
Live oral Salmonella vaccines: potential use of attenuated strains as carriers of heterologous antigens to the immune system
Authors: DOUGAN G. , HORMAECHE C. E. , MASKELL D. J.
Published: October 2007

Summary Live attenuated strains of salmonellae are showing promise as live oral vaccines against human typhoid fever and other Salmonella infections of man and animals. Attenuation can be achieved by introducing genetically defined, non‐reverting mutations into specific genes on the Salmonella chromosome. Mutations in the gal E or aro A genes of Salmonella inhibit the ability of the bacteria to grow in vivo, and strains carrying such lesions are effective vaccines against salmonellosis. Genetic determinants encoding for the expression of potentially protective antigens from heterologous, non‐Salmonella pathogens can be readily introduced into these attenuated Salmonella strains. Expression of the heterologous antigen does not affect the ability of the Salmonella host to be used as a Salmonella vaccine. Mice infected orally with a Salmonella typhimurium aro A vaccine expressing the Escherichia coli heat‐labile toxin B subunit developed both a secretory and serum antibody response to this antigen. These serum antibodies were able to neutralise the activity of E. coli heat‐labile toxin in tissue culture assays. A humoral and cell‐mediated (DTH) immune response was detected against beta galactosidase, an intracellular antigen, in mice infected with an aro A vaccine expressing this cloned antigen. The prospects for the development of live Salmonella vaccines as a method for delivering heterologous antigens derived from bacteria, viruses and parasites is discussed.
Schistosoma mansoni: interactions of adult parasites with the complement system
Authors: RASMUSSEN KATHLEEN R. , KEMP WALTER M.
Published: October 2007

Summary The interaction of the mouse complement system with adult male Schistosoma mansoni was studied by immunocytochemical localization procedures and in‐vitro assays for complement mediated tegument damage. Mouse C3 was demonstrated to be associated with the parasite's tegument, but was localized only in the infoldings of the tegument and not on its free surface. Freshly harvested parasites manifested no detectable tegumental modification when incubated in normal mouse serum or in immune mouse serum. However, parasites which had been allowed to lose their adsorbed host components by elution (incubation in serum free media for 3 h at 37°C) were severely damaged by incubation in normal mouse serum, but not by incubation in immune mouse serum. This damage was shown to be mediated by the alternative complement pathway and appeared to be initially limited to the tubercles of the adult male parasite. Tegument disruption could be blocked by pre‐incubation of the eluted worms in either immune mouse serum or an IgG fraction of immune mouse serum. An IgG fraction of normal mouse serum did not protect the parasite, and infected mouse serum (IMS) which had been depleted of IgG produced tegument damage equivalent to that observed with normal mouse serum (NMS). The addition of I‐IgG to NMS abrogated tegument damage. These data suggest that while adult schistosomes possess surface molecules bearing alternative pathway complement activation sites, these sites are masked by adsorbed host components in vivo. These results further indicate that in the absence of these masking host molecules anti‐schistosome IgG may play a role in protecting the adult worm from alternative pathway activation, perhaps by binding to and blocking the activation sites on the tegument associated molecules.