bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunogenic proteins of Leishmania major during mouse infection
Authors: NGUYEN T.V. , MAUEL J. , ETGES R.J. , BOUVIER J. , BORDIER C.
Published: October 2007

Summary Mice of different strains (C3H/He, A/Jax, DBAy2, BALB/c and CBA/Ca) were infected intracutaneously with Leishmania major. Antibody production was analysed on the antigens of the promastigote form of the parasite which had previously been separated by SDS‐polyacrylamide gel electrophoresis and transferred to nitrocellulose sheets. The kinetics of IgG antibody production were determined and the major immunogenic proteins of the parasite were identified for each strain of mouse. It was found that: 1 Antibody directed against parasite proteins appeared in the blood of all mouse strains tested soon after the first week of infection and rose steadily for 5 to 12 weeks. 2 Qualitative individual variation within a given strain was commonly observed in the response to the various antigens. Each mouse strain synthesized IgG directed against a somewhat different spectrum of parasite proteins. Homologies in antigen recognition by pooled sera of five mice ranged from 54% to 79% from one mouse strain to another. Hybrid mice from a BALB/c × CBA cross (Fi generation) recognized essentially all antigens recognized by the two parents. Proteins of L. major with apparent molecular weights of 19 kD, 60 kD, 65 kD, 70 kD and > 100 kD were immunogenic in all strains of mice tested.
Protection against Trichinella spiralis induced by a monoclonal antibody that promotes killing of newborn larvae by granulocytes
Authors: ORTEGA‐PIERRES G. , MACKENZIE C.D. , PARKHOUSE R.M.E.
Published: October 2007

Summary Mouse monoclonal antibodies directed against biochemically defined surface antigens of Trichinella spiralis were selected and tested for their ability to destroy parasites in vivo and in vitro. One of these (NIM‐M5; IgGl), which recognised a surface component of approximately 64 K molecular weight in newborn larvae (NBL), bound to a surface component of this stage (as shown by fluorescence), and mediated the adherence of rodent eosinophil leucocytes to the surface of living NBL. Following cell adherence mediated by this monoclonal antibody, the worms were killed. This effect was enhanced by fresh normal serum suggesting a role for complement in this phenomenon. A monoclonal antibody directed against a surface component of infective larvae (NIM‐M1; IgM) did not promote adherence of cells nor killing of NBL in vitro. The effect of NIM‐M5 on the development of NBL to the intramuscular stage was examined. Treatment of NBL with the NIM‐M5 monoclonal antibody prior to their injection into mice, together with passive transfer of NIM‐M5 for 3 days, significantly reduced (36–51%) the proportion of larvae recovered by digestion 28 days later. Thus a single monoclonal antibody to NBL was able to mediate eosinophil‐dependent destruction of worms in vitro and reduce infectivity in vivo. These observations suggest that antibodies capable of mediating eosinophil‐induced destruction of nematodes in vitro may also be important in protection against infection.
T cell‐mediated immunity in murine malaria. II. Induction of protective immunity to P. chabaudi by antigen fed macrophages and antigen educated lymphocytes
Authors: CHEMTAI A. K. , HAMERS‐CASTERMAN C. , HAMERS R. , BAETSELIER P. DE
Published: October 2007

Summary We previously described assay systems for generating antigen specific proliferating T cells to P. chabaudi antigens. In the present study we examine whether the various sensitization approaches confer immunity against a cloned virulent strain IP‐PCI of P. chabaudi. We present data indicating that effective specific protective immunity can be induced through P. chabaudi antigen fed macrophages and antigen educated spleen cells (initiator lymphocytes). The expression of this protective immunity is proposed to depend on (a) antigen presentation and/or accessory function of macrophages and (b) the subsequent activation of T cell functions related to protection. Indeed analysis of different macrophage populations revealed a correlation between the expression of la molecules and IL‐1 secretion with their capacity to induce antigen specific T cells in vivo and subsequent protective immune mechanisms. Thus these results emphasize the critical functions of accessory cells in determining the outcome of malaria infections.
ACTH‐dependent modulation of malaria immunity in mice
Authors: van ZON A. A. J. C. , ELING W. M. C. , SCHETTERS T. P. M. , HERMSEN C. C.
Published: October 2007

Summary Tetracosactrin, a synthetic adrenocorticotrophic hormone (ACTH) analogue delivered by osmotic minipumps implanted s.c. in mice induced a dose‐dependent increase of plasma corticosterone levels. In mice with an established immunity to Plasmodium berghei the increase of the plasma corticosterone level due to tetracosactrin treatment correlated with loss of immunity against this malaria parasite. The observed plasma corticosterone levels associated with loss of malaria immunity were of the same order as those in mice that lost their immunity during pregnancy. Adrenalectomy before administration of the ACTH analogue prevented both the increase of plasma corticosterone and loss of malaria immunity. Adrenalectomized mice still lost their malaria immunity when treated with the synthetic corticoid dexamethasone. The effector function of malaria immunity is sensitive to corticoids, and. at least during pregnancy, the naturally occurring serum corticosterone level appears to be an important regulator of malaria immunity.
Complement activation by antigenic fractions of Entamoeba histolytica
Authors: MERI S. , RICHAUD GHYSLAINE , LINDER E.
Published: October 2007

Summary Complement (C) activation induced by Entamoeba histolytica in normal non‐immune human serum was studied by testing in vitro the ability of different fractions of the trophozoites to cause C3 breakdown. Whole trophozoites were found to activate both alternative and classical C pathways. The antibody‐independent classical pathway (MgEGTA inhibitable) C activating capacity was found to greatly increase after disruption of the cell membrane by sonication. Subsequent analysis after differential centrifugation and ion exchange chromatography of the membrane/particulate fractions showed, that this activity was not due to DNA, which has been shown to have the similar characteristics, but to other, as yet unidentified components. A rather homogenous membrane fraction obtained by elution with 0·4 M Tris‐HCl, pH 8·1 (described as 4M) and some cytoplasmic constituents obtained after gel chromatography retained a moderate degree of alternative pathway C3 activating capacity seen with intact trophozoites. Thus, it seems, that serum contact to the outer surface of E. histolytica trophozoites leads to C activation via both pathways with cell death as the result and to subsequent release of more efficiently classical pathway activating components. These phenomena probably have an important role in the inflammatory process in invasive amoebiasis.
Purification and characterization of a specific antigen from Echinococcus multilocularis
Authors: GOTTSTEIN B.
Published: October 2007

Summary A polypeptide (Em2a) purified by affinity chromatography from the Echinococcus multilocularis metacestode showed a high degree of purity as assayed by SDS‐PAGE and analytical isoelectrical focusing. A minor contamination with host albumin was revealed. Estimation of relative mol. mass gave a value of 54,000. The isoelectric point was found to be 4·8. Antigenic activity of the polypeptide was demonstrated by immunoprecipitation and western blotting. In these assays the protein was recognized only by homologous sera from patients infected with larval E. multilocularis. This antigen (Em2a) did not react in the ELISA with sera from patients infected with heterologous helminths; these sera were highly cross‐reacting with antigen from E. granulosus hydatid fluid. Seventy‐three (94%) from 78 investigated patients (alveolar echinococcosis) showed a seropositive reaction with the polypeptide Em2a.
Impaired macrophage leishmanicidal activity at cutaneous temperature
Authors: SCOTT P.
Published: October 2007

Summary Temperature is one of the primary influences upon the pathogenesis of cutaneous leishmaniasis. In this study, we measured the temperature of murine leishmanial lesions and determined the ability of lymphokine (LK) activated macrophages to kill Leishmania major at these temperatures. The temperature of leishmanial lesions in BALB/c and C3H/HeN mice ranged from 27°C to 32°C. We found that LK activated resident or inflammatory macrophages exhibited significantly less leishmanicidal activity in vitro at temperatures closer to those measured in vivo. The decrease in microbicidal activity was not due to the enhanced growth of the parasites at lower temperatures, since impaired killing was also observed against non‐replicating radiation attenuated amastigotes. Finally, the tumoricidal activity of macrophages was found to be significantly depressed at temperatures below 37°C, indicating a generalized impairment of macrophage function at these temperatures. These findings suggest that impaired macrophage microbicidal activity at cutaneous temperatures may contribute to parasite survival, and imply that healing of leishmanial lesions, as well as other cutaneous infections, may require an exceptionally potent local LK response.
Maternally derived immunity in young mice to infection with Trypanosoma brucei and its potentiation by Berenil chemotherapy
Authors: WHITELAW D. D. , URQUHART G. M.
Published: October 2007

Summary Young mice which were allowed to suckle, from birth, a mother infected with Trypanosoma brucei, or a mother whose infection had been cured before parturition with Berenil chemotherapy, were themselves immune to homologous trypanosome challenge. This immunity extended until approximately 25 days of age, and was transmitted in the colostrum/milk of the mother. Mice born of infected mothers, but transferred at birth to normal foster mothers, were susceptible to trypanosome infection. Drug prophylaxis in normal newborn mice was also effective for approximately 25 days, but in mice which, in addition, received colostral antibody from the mother, combined immunochemoprophylaxis protected the offspring for 40–50 days. Since the combination of protective strategies continued to resist challenge beyond the stage when, on its own, each component's efficacy had decayed, it may be of practical value as an approach to improved disease control under certain field conditions where trypanosomiasis prevails.
The genetic control of host responses to Dipetalonema viteae (Filarioidea) infections in mice
Authors: STOREY N. , WAKELIN D. , BEHNKE J. M.
Published: October 2007

Summary Dipetalonema viteae (Filarioidea) infections were established in inbred strains of mice by the s. c. implantation of adult female worms and the resulting microfilaraemia and adult worm survival monitored. BALB/c mice were the most susceptible strain examined, showing a high level microfilaraemia of approximately 6 month's duration. C57B1 10. CBA/Ca and C3H/He mice were all equally resistant to infection, showing a low level of microfilaraemia of approximately 1 month's duration. The response of NIH mice was intermediate. Relatively little strain difference was seen in adult worm survival although worms lived slightly longer in C57B1/10 mice than in BALB/c mice. The adult females became depleted of microfilariae over a period of approximately 1 month before becoming encapsulated in host tissue. Challenge infections given to mice previously implanted with worms resulted in lower level, shorter lasting microfilaraemias than those seen in the initial primary infections. All strains showed immunity when challenged. High responsiveness (resistance) was inherited as a dominant trait in F1 hybrids produced by crossing high and low responder strains. Genes linked with the major histocompatability complex (H‐2) were found to have no effect on the response phenotype as demonstrated by the similar responses of H‐2 congenic mice on the BALB/c or C57B1/10 backgrounds. The response phenotype of radiation chimaeras was determined by the phenotype of the donor from which bone marrow (BM) cells were taken for reconstitution. Susceptible BALB c mice reconstituted with resistant B10D2/n BM behaved identically to the donor strain, indicating that the genetic variation which exists between mouse strains in their responses to D. viteae is expressed through a population of BM derived cells and is not simply a consequence of host structure or physiology.
Systemic release of mucosal mast cell protease during infection with the intestinal protozoal parasite, Eimeria nieschulzi. Studies in normal and nude rats
Authors: HUNTLEY J. F. , NEWLANDS G. F. J. , MILLER H. R. P. , McLAUCHLAN M. , ROSE M. ELAINE , HESKETH PATRICIA
Published: October 2007

Summary The systemic secretion of rat mucosal mast cell protease (RMCPII), a major product of rat mucosal mast cells (MMC), was examined during primary infections with the protozoan parasite, Eimeria nieschulzi in CFH/B, athymic (rnu/rnu) and euthymic (rnu/+) rats. Release of RMCPII into the blood stream (2·9 μg/ml of serum) of normal rats occurred within 1 day after infection. This response developed 3–6 hours after inoculation with oocysts, was dose‐dependent, and was found in both naive and immune rats. Maximal release of RMCPII (4·5 μg/ml of serum) in naive rats occurs 9 days after primary infection, whereas the numbers of MMC and concentrations of mucosal RMCPII were maximal 14 days after infection, by which time the systemic RMCPII response had begun to decline. The numbers of MMC and concentrations of mucosal RMCPII in uninfected nude rats were similar to those in the heterozygous (rnu/+) litter‐mates. After infection, the numbers of MMC and concentrations of mucosal RMCPII increased in the heterozygotes but not in nude rats. Similarly, RMCPII was detected systemically only in the heterozygotes.
Cell mediated immunity to liver fluke antigens during experimental Fasciola hepatica infection of cattle
Authors: OLDHAM G. , WILLIAMS LINDA
Published: October 2007

Summary Cell mediated immunity (CMI) to Fasciola hepatica antigens was detected by lymphocyte proliferation and interleukin‐2 (IL‐2) production tests in cattle during the first 4 weeks following liver fluke infection. From the fifth week of infection onwards peripheral blood lymphocytes were unresponsive to fluke antigens by these in vitro tests. Investigations into the cause of this unresponsiveness found no evidence to suggest a selective loss of the IL‐2 producing lymphocyte sub‐population or that macrophages were responsible for the suppression or that antigen responsive cells were being sequestered in the spleen and mesenteric lymph nodes. Tests carried out on culture supernatants demonstrated the production during this unresponsive period of factors capable of suppressing in vitro responses to PHA. Although further tests failed to show antigen specific suppressor factors the presence of MHC restricted suppressor factors could not be ruled out. The early and transient appearance of CMI during F. hepatica infection of cattle indicates that delayed type hypersensitivity is unlikely to be important in protective immunity in cattle.
Effects of anethole dithiolthione and 2(3)‐tert‐butyl‐4‐hydroxyanisole on schistosome granuloma formation
Authors: FELDMAN GERALD M. , NAPLES JEAN M. , SEED JOHN L. , BUEDING ERNEST
Published: October 2007

Summary Administration of the antioxidants 2(3)‐tert‐butyl‐4‐hydroxyanisole (BHA) or 5‐(P‐methoxyphenyl)‐3H‐1.2‐dithiol‐3‐thione (ADT) to female CD‐1 mice starting 4 weeks after infection with 70 cercariae of Schistosoma mansoni resulted in a decrease in the size of the inner fibrotic region of the hepatic granuloma. The cellular composition of the granuloma was not altered by treatment with these two compounds. The administration of the specific superoxide scavenger copper diisopropylsalicylate (CuDIPS) resulted in a similar decrease in granuloma size, suggesting a role of superoxide radicals in the granulomatous response.
Multinucleate giant cells in murine and rat lungs during Nippostrongylus brasiliensis infections. A study of the kinetics of the response in vivo, cytochemistry, IgG‐ and C3‐mediated functions
Authors: EGWANG T. G. , RICHARDS C. D. , STADNYK A. W. , GAULDIE J. , BEFUS A. D.
Published: October 2007

Summary The cytochemical and functional characteristics of broncho‐alveolar multinucleate giant cells and the kinetics of the giant cell response in the lungs of mice and rats during Nippostrongylus brasiliensis infection were studied. Primary infections resulted in significantly increased numbers of recoverable giant cells for up to 30 and 50 days in rats and mice, respectively. During secondary infections in the rat the giant cell response was more rapid and greater in magnitude than in a primary infection, suggesting that it was immunologically mediated. The giant cells displayed decreased C3‐ and IgG‐dependent binding or phagocytic potential compared with mononucleate alveolar macrophages. Fusion of mononucleate alveolar macrophages into giant cells may therefore compromise complement and antibody dependent helminthocidal activity of these cells.
Antigenicity and immunogenicity of the tegumental outer membrane of adult Schistosoma mansoni
Authors: PAYARES G. , McLAREN DIANE J. , EVANS W. H. , SMITHERS S. R.
Published: October 2007

Summary The tegumental membranes of adult Schistosoma mansoni have been isolated and purified and shown to function as potent immunogens; they elicit an essentially identical immune response in rabbits, rats and mice. Anti‐membrane antisera harvested from these animals consistently recognized common antigens, of relative molecular weight (mol. wt) 32000 and 20000, on the surface of young schistosomula, 5 day old lung worms and adult worm purified membranes. An additional molecule of 25 000 mol. wt was present on the surface of lung worms and adult worm membranes and was specifically recognised by serum from chronically infected mice and by serum from rabbits inoculated with adult worm purified membranes. The concept of antigenic identity between developmental stages that parasitize the mammalian host was further substantiated by the observation that anti‐membrane antiserum bound to live schistosomula, lung worms and adult parasites as measured by indirect immunofluorescence. In complement‐mediated in vitro cytotoxicity assays, the sera from rabbits inoculated with either adult worm purified membranes, or the 32000 mol. wt antigen partially purified from adult worm membranes, mediated levels of schistosomula killing as high as those obtained with sera from chronically infected mice. These rabbit antisera also promoted eosinophil adherence and killing of newly transformed schistosomula, but lung stage parasites, despite binding the anti‐membrane antiserum, were refractory to both humoral and cellular cytotoxicity. The significance of antigenic identity is discussed in relation to the concept of concomitant immunity.
The role of humoral immune responses in determining susceptibility of A/J and C57BL/6 mice to infection with Trypanosoma congolense
Authors: MORRISON W. I. , MURRAY M.
Published: October 2007

Summary The relative resistance of C57BL/6 mice to infection with Trypanosoma congolense as compared to A/J mice was found to be independent of the infective dose of trypanosomes and required an intact immune system, as sublethal levels of gamma irradiation abolished the differences in susceptibility between the two strains. C57BL/6 mice produced earlier and quantitatively superior antibody responses both to the variable surface glycoprotein and to common membrane antigens on the trypanosome than A/J mice. No difference was observed in the class of antibody produced. In parallel with the specific response, C57BL/6 mice also generated higher levels of antibody to an unrelated antigen (TNP) and developed higher levels of total serum IgM. However, despite the low levels of both specific antibody and antibody to TNP in A/J mice, these animals developed massive increases in total serum IgG2a. The role of this selective activation of IgG2a producing cells in the susceptibility of the A/J mice was unclear. Although susceptibility was closely correlated with specific antibody responses during infection, the two strains of mice showed a similar capacity to respond to fixed doses of irradiated trypanosomes. This indicates that an inherent difference in immune responsiveness to the trypanosomal antigens is not the major factor determining susceptibility. Moreover, the finding that a proportion of A/J mice which received infective and irradiated trypanosomes simultaneously showed depressed antibody responses to the trypanosome, suggests that active infection of A/J mice with T. congolense impairs their ability to initiate an appropriate immune response to the trypanosome.
Isolation and characterization of salivary antigens from Hyalomma anatolicum anatolicum
Authors: GILL H. S. , BOID R. , ROSS C. A.
Published: October 2007

Summary This study demonstrates the involvement of a large number of salivary proteins in the acquisition of resistance to Hyalomma anatolicum anatolicum. Using immunoblotting, sera from hypersensitized rabbits were shown to react with nine proteins in the saliva and 17 in salivary gland extracts (SGE) from 96 h fed female ticks. The salivary antigens had molecular weights in the range of 14 400 to 130000. All the antigens identified in the saliva and 12 of the SGE antigens were glycoprotein in nature and a majority of them appeared to be common to different stages of feeding. In addition antigen I (molecular weight 130000) showed acid phosphatase and antigen III (molecular weight 96000) showed both non‐specific esterase and aminopeptidase activity. Three high molecular weight proteins isolated from saliva (antigen I, antigen II–molecular weight 103 000 and antigen III), gave immediate hypersensitivity reactions in intradermal inoculation into rabbits which had previously been exposed to ticks. Antigens II and III also elicited a strong delayed hypersensitivity reaction. These results may help to explain the nature of the immune mechanisms which effect resistance against H. a. anatolicum.
Identification of infection‐associated antigens in Theileria annulata transformed cells
Authors: SHIELS B. R. , McDOUGALL C. , TAIT A. , BROWN C. G. D.
Published: October 2007

Summary The protozoan parasite Theileria annulata causes a severe disease of cattle in tropical countries; one stage in the parasite life cycle involves the transformation of bovine lymphocytes leading to rapid lymphoproliferation. Immunity to this disease is largely cell mediated and directed against the infected lymphocyte. In this paper we report the identification of three classes of infection specific antigen (using monoclonal antibodies) one of which is found on the surface of the lymphocyte. Such antigens can be used in parasite strain typing, in providing an understanding of the molecules involved in immunity and in providing the basis for a vaccine.
IgE antibody against surface antigens of Leishmania promastigotes in American cutaneous leishmaniasis
Authors: LYNCH NEIL R. , MALAVE CARIDAD , TURNER KEVEN J. , INFANTE BENITO
Published: October 2007

Summary As IgE‐mediated immune mechanisms participate in the host defence against some types of parasites, we evaluated sera from American cutaneous leishmaniasis (ACL) patients for the presence of this antibody against Leishmania. Using monoclonal antibodies against human IgE and an immunoperoxidase staining technique, 48% of the patients sera tested were found to contain IgE antibody that bound strongly to Leishmania promastigotes. A much lower proportion of sera from non‐symptomatic subjects from either endemic or non‐endemic areas of the disease contained significant levels of and‐Leishmania IgE antibody (6–5% and 0% respectively). The results indicated that the IgE antibody bound predominantly to surface components of the promastigotes, and reactivity against the intracellular amastigote form of the parasite was rarely detected. Somewhat unexpectedly, in a small proportion of the sera, the IgE antibody showed apparent specificity for L. mexicana or L. braziliensis.

This study demonstrates that ACL patients can develop anti‐Leishmania IgE antibody responses, that seem to be directed peferentially against surface antigens of promastigotes, and that can be strain specific. This raises the question as to the possible contribution of this antibody to the immune defence mechanisms against the parasite.
In vitro antibody‐mediated macrophage activity on Breinlia macropi microfilariae. I. Adherence and cytotoxicity
Authors: YEN P. K. F. , HOLT P. G. , STANLEY N. F. , TURNER K. J.
Published: October 2007

Summary Intense adherence accompanied by cytotoxicity, which initially occurred at 4 h of interaction was observed when the microfilariae of Breinlia macropi were introduced to cultures of quokka peritoneal macrophages previously sensitized in 20% immune serum. No significant difference in the adherence or cytotoxic effects was observed among macrophages from normal, microfilaraemic and amicrofilaraemic quokkas. However, the serum component mediating these effects was found only in microfilaraemic and seropositive amicrofilaraemic quokkas. This mediator was heat‐labile and its mediation of the adherence and cytotoxic effects was independent of complement. Because of its apparent dissociation from IgG and its heat lability, the possibility that the mediator resides in the previously‐described reaginic antibody of the quokkas was discussed.
Genetic control of immunity to Trichinella spiralis in mice. Response of rapid‐ and slow‐responder strains to immunization with parasite antigens
Authors: WAKELIN D. , MITCHELL L. A. , DONACHIE A. M. , GRENCIS R. K.
Published: October 2007

Summary Slow‐responder C57BL/10 (BIO) mice responded poorly to immunization with muscle larval antigen of Trichinella spiralis showing no accelerated loss of worms from a subsequent challenge infection. In contrast, rapid‐responder NIH mice and (BlOxNIH) F, mice developed high levels of immunity after immunization. Lymphocyte proliferation studies showed that immunized BIO mice did respond to in vitro restimulation with antigen, though less well than NIH mice. Failure of B10 mice to respond to immunization did not therefore reflect a failure to recognize larval antigen, a view confirmed by the fact that immunization was achieved using abbreviated enteral infections and, to a smaller extent, by parenterally administered muscle larvae.
Study of T cell subsets in patients with cutaneous leishmaniasis
Authors: JAROSKOVA LYDIE , SELIM M. M. , VLASIN Z. , AL‐TAQUI MUNA
Published: October 2007

Summary The proportion of T lymphocyte populations was assessed using monoclonal antibodies (OKT 3, OKT 4, OKT 8) and spontaneous E‐rosette tests with SRBC (for total and active TE cells) in 36 patients with cutaneous leishmaniasis subdivided according to the clinical variety. The T cell profile was normal in patients with simple cutaneous leishmaniasis of early ulcerative type whereas active TE cells and OKT 4 positive cells were reduced in some cases of late ulcerative type. A significant reduction of active TE cells and of OKT 4 positive cells (helper/inducerphenotype) and increase of OKT 8 positive cells (suppressor/ cytotoxic phenotype) was observed in peripheral blood of all patients with persistent active lesions and leishmaniasis recidivans. In patients with highly ulcerated persistent lesions a low proportion of active TE cells was also demonstrated in cellular extracts from dermal tissue. The results support the data obtained in experimental leishmaniasis that lack of helper/inducer cells and generation of suppressor T cells may be responsible for the development of chronic leishmaniasis.
Suppression of blood monocyte and neutrophil chemotaxis in acute human malaria
Authors: NIELSEN HENRIK , KHARAZMI ARSALAN , THEANDER THOR G.
Published: October 2007

SummaryThe host response toPlasmodiaincludes the production of enlarged populations of peripheral blood monocytes and tissue macrophages in the spleen and the liver. Since the hyperplasia of the mononuclear phagocyte system is believed to arise as a consequence of an enhanced blood monocyte influx, we tested monocyte chemotactic responsiveness in 19 patients with acute primary attack malaria. In addition, the neutrophil chemotaxis was measured in 12 patients. Before the initiation of antimalarial treatment a significant depression of monocyte chemotaxis was observed in approximately half of the patients when compared with healthy control subjects. The depression was found inPlasmodium falciparummalaria as well as inP. vivaxorP. ovalemalaria patients. The defective responsiveness was not receptor specific, since the responses towards casein and zymosan activated serum proved to be equally suppressed. The monocyte chemotaxis was followed in 14 of the patients, during treatment and after complete recovery. After 3 days of treatment the response had improved in most of the patients, and after 7 days all patients had a normal monocyte chemotaxis, which remained normal after one month. No significant differences betweenP. falciparumandP. vivax/ovalemalaria was observed with respect to blood monocyte chemotactic responsiveness. Neutrophil chemotaxis in patients withP. falciparuminfections was similarly suppressed before treatment (54% of controls), was still defective after 3 days of treatment, and nearly normalized after 7 days (87% of controls). Furthermore, monocyte phagocytic and candidacidal activities were assessed in the same patients on admission and during the follow‐up. In contrast to chemotaxis, these functions were normal in all of the patients whenever measured. In conclusion, not all cell functions were altered in concert, and the previously unreported suppression of chemotactic migration might reflect a change in blood leucocyte subpopulations, deactivationin vivoor a direct suppressive effect of Plasmodia induced products.
Regional specialization of the surface of a parasitic nematode
Authors: ORTEGA‐PIERRES GUADALUPE , CLARK N. W. T. , PARKHOUSE R. M. E.
Published: October 2007

Summary A monoclonal antibody (NIM‐M7) has been prepared which reacts with a major surface antigen of adult males and females of Trichinella spiralis. This specificity is only demonstrable when the antigen is liberated by detergent solubilization of surface‐labelled worms. When reacted with living adults, on the other hand, NIM‐M7 reacts well with only the eversible cloaca, or copulatory bell, of the male, binding weakly, if at all, to other surface areas of male or female worms. A similar staining pattern is also given by Concanavalin A. The differential staining given by NIM‐M7 must indicate a molecular difference between the organization of the same surface antigen on the cuticular surface of the copulatory bell and other areas of the worm surface. This example of regional specialization demonstrates that the nematode cuticle is not necessarily chemically uniform.
Phosphorylcholine‐bearing antigens in filarial nematode parasites: analysis of somatic extracts, in‐vitro secretions and infection sera from Brugia malayi and B. pahangi
Authors: MAIZELS R. M. , BURKE J. , DENHAM D. A.
Published: October 2007

Summary A set of cross‐reactive antigens is described which are present in somatic extracts and in‐vitro secretions of the filarial nematodes Brugia pahangi and B. malayi. A monoclonal antibody reactive with a repeating epitope on these molecules readily detects circulating antigen in the serum of animals infected with lymphatic filariae, using either an immunoradiometric assay or enzyme‐linked immunosorbent assay (ELISA). This epitope has the immunological reactivity and chemical characteristics of the phosphorylcholine (PC) hapten. The anti‐PC monoclonal has been used to define the antigens bearing this epitope, and in chromatographic studies on material from extracts of Brugia adult worms, a heterogeneous profile of PC‐positive molecules are found. In sera from Brugia‐infected jirds, an antigen with a native molecular weight of approximately 500000 is observed, which displays limited sensitivity to protease degradation. However, denatured samples on Western blots show a major parasite circulating antigen of Mr 90000. The detection of this antigen in the presence of excess host antibody is also demonstrated, taking advantage of the stability of the target epitope to a range of treatments designed to dissociate and eliminate immune complexes.
Dipetalonema viteae infection in three species of rodents: species specific patterns of the antibody response
Authors: LUCIUS R. , KAPAUN A. , DIESFELD H. J.
Published: October 2007

Summary Groups of jirds (Meriones unguiculatus), multimammate rats (Mastomys natalensis) and golden hamsters (Mesocricetus auratus) were infected with third stage larvae (L3) of Dipetaloneam viteae and the course of infection was followed until 20 weeks post infection. Worm growth was best and microfilaraemia was high and long lasting in jirds and in multimammate rats, whereas golden hamsters were poor hosts as measured by these parameters. The IgG and IgM antibody responses of the species were compared by immunoblotting and ELISA using proteins of D. viteae, separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS‐PAGE). The levels of antibodies against most proteins of high molecular weight declined during infection in jirds and in multimammate rats, whereas an increase was observed in golden hamsters. In contrast, several antigens of low molecular weight induced increasing antibody levels in all species. Species specific antigen recognition was observed for a number of protein bands of L3, microfilariae and female worms. The data suggest that susceptibility to immunesuppression and the species specific pattern of antigen recognition might determine the qualities of a rodent species as host for D. viteae.
Variants with reduced virulence derived from Leishmania major after mutagen treatment
Authors: MARCHAND M. , DAOUD S. , TITUS R. G. , LOUIS J. , BOON T.
Published: October 2007

Summary After several in vitro treatments of a virulent population of Leishmania major with the mutagen, N‐methyl‐N'‐nitro‐N‐nitrosoguanidine (MNNG), five clones (vir‐) were obtained that did not produce cutaneous lesions after subcutaneous injection of 106 promastigotes. All the control clones (vir+) obtained from the non‐mutagenized parasite population produced progressive cutaneous lesions with as few as 103 parasites. Late lesions were observed occasionally after injection of 107 vir‐ parasites. These late lesions appeared to result from the selection of virulent revertants, since parasites isolated from these lesions produced progressive lesions in BALB/c mice almost as readily as the control parasites.

Two vir‐ clones, one vir+ clone and one revertant clone were examined for survival in BALB/c macrophages in vitro. All clones were taken up by the macrophages and transformed into amastigotes. However, vir‐ clones failed to multiply inside the macrophages.

A vir‐ clone was found to protect mice against a subsequent challenge with vir+ parasites.
Depression of virus‐specific cytotoxic T‐cell responses during murine malaria
Authors: NICKELL S. P. , FREEMAN R. R. , COLE G. A.
Published: October 2007

Summary Mice with self‐limiting P. yoelii or fatal P. berghei infections exhibited a markedly impaired ability to mount specific splenic cytotoxic T‐lymphocyte responses to immunization with infectious ectromelia (EV), vaccinia (VAC), or lymphocytic choriomeningitis viruses (LCMV). Lymph node responsiveness, however, was not impaired. Primary CTL responses were depressed in mice immunized 7 days after P. berghei infection, while in P. yoelii‐infected mice, depressed responses were detected only during the period corresponding with maximal parasitemia (days 9–12). Secondary VAC‐specific CTL responses in vitro by spleen cells of mice previously immunized during P. yoelii infection were also depressed if UV‐inactivated rather than infectious VAC was used for immunization. In addition, spleen cells of mice already immune to VAC failed to yield normal secondary CTL responses in vitro during the period of maximal P. yoelii parasitaemia. Collectively, these findings indicate that, during patent malaria infections, priming for and expression of virus‐specific CTL responses may be inhibited.
Plasmodium falciparum‐inhibitory monoclonal antibodies produced by human hybridomas
Authors: FINE EDARD , INSELBURG JOSEPH , OBEING JOSHUA , HANSON ALOYSIOUS
Published: October 2007

Summary Stable human hybridomas were generated that produced inhibitory anti‐Plasmodium falciparum monoclonal antibodies. Peripheral blood lymphocytes, obtained from adults in Liberia, a malaria endemic area, were immortalized with Epstein‐Barr virus and then fused with KR4, a human, lymphoblastoid cell line. Stable hybridmoas that produced anti‐P. falciparum monoclonal antibody were identified by an ELISA assay that used the trophozoite and schizont antigens of both the Honduras I and FCR3 parasite strains. Monoclonal antibodies produced by selected hybridomas derived from lymphocytes of two individuals were subsequently studied. The anti‐parasite antibodies were produced at 1–3 μg/ ml in culture supernatants. All of the monoclonal antibodies bound specifically to trophozoites and schizonts of both strains of parasite in an indirect immunofluor‐escence assay and inhibited production of ring stage parasites by more than 90% when added to trophozoite or schizont containing erythrocytes in culture. Western immunoblot analysis of antigens obtained from trophozoites and schizonts (parasite age span of 36 to 48 h) was performed using either affinity purified or ammonium sulfate‐concentrated monoclonal antibody. Antibody from three hybridomas which bound primarily to antigens of the Honduras 1 strain had Mr of approximately 140000, 130000 and 123000.
Peripheral blood leucocytes subpopulation dynamics during Trypanosoma congolense infection in Boran and N'Dama cattle: an analysis using monoclonal antibodies and flow cytometry
Authors: ELLIS J. A. , SCOTT J. R. , MACHUGH N. D. , GETTINBY G. , DAVIS W. C.
Published: October 2007

Summary A panel of monoclonal antibodies (MoAb) with specificities for bovine leucocyte subsets were used in conjunction with routine haematological procedures to analyse sequential changes in peripheral blood leucocyte populations during the course of tsetse fly‐transmitted Trypanosoma congolense infection in trypanotolerant N'Dama and trypanosusceptible Boran cattle. Subsequent to the first parasitaemic wave, the N'Dama cattle maintained packed cell volumes (PCV) above 22 and lower levels of parasitaemia than Boran throughout the 160 days of the experiment. In contrast, the Borans developed severe anaemia and required curative drug therapy (i. e., PCV dropped to less than 15) by 55 days (range: 22–55 days) post infection. There were significant (P < 0±05) decreases in total white blood cells and total lymphocytes from pre‐infection levels to the first peak of parasitaemia (day 16 post‐infection) in both groups. Flow cytometric analyses using MoABs revealed that this change was due to an absolute decrease in T cells expressing BoT2 and either BoT4 or BoT8, surface immunoglobulin M‐positive (sIgM+) B cells, and null cells which did not express T cell, B cell or monocyte markers. During this period there was significant variation over time, but no overall increase or decrease, in the number of cells expressing class II major histocompatibility (MHC) molecules or monocyte markers, or in the number of circulating neutrophils or eosinophils. The BoT4/BoT8 ratios were significantly (P < 0±01) increased in both groups of infected animals at the first peak of parasitaemia. After day 22 in the infected N'Damas and in the Borans which required drug therapy, there was a leucocytotic response characterized by an increase in the total number of B cells, T cells, and null cells. Prior to infection and throughout the course of the experiment N'Dama cattle had significantly (P < 0±01) higher numbers of B cells and null cells than Boran.
Localization of mucosal mast cells in W/WV mice after reconstitution with bone marrow cells or cultured mast cells, and its relation to the protective capacity to Strongyloides ratti infection
Authors: ABE T. , NAWA Y.
Published: October 2007

Summary Localization of mast cells in the intestinal epithelium, villous lamina propria and basal lamina propria of mast cell‐deficient WBB6F1 (W/Wv) mice reconstituted with either bone marrow cells or with cultured mast cells (BMMC) was compared to that of mast cell‐sufficient C57 BL/6 or C57 BL/6‐bgj/bgj (beige) mice after infection with Strongyloides ratti. In mast cell‐sufficient C57 BL/6 or beige mice, the maximum number of intestinal mucosal mast cells (MMC) was more than 160 MMC/10 villus crypt units (VCU) and more than 90% of MMC were located in the intestinal epithelium. When W/WV mice were reconstituted with bone marrow cells of beige mice, worm expulsion was hastened and the MMC response became comparable to that of mast cell‐sufficient mice in terms of cell numbers and their intra‐epithelial localization. On the other hand, when W/Wv mice were reconstituted with BMMC of beige mice, only a few donor type MMC were detected in the intestine. The proportion of intra‐epithelial MMC was lower than that of mast cell‐sufficient mice or of marrow‐reconstituted W/Wv mice. Even repeated injection of BMMC could not fully restore the number of intra‐epithelial MMC to the level of that observed in mast cell‐sufficient mice. Since mast cell‐growth factor‐producing activity of W/Wv mice was comparable to that of mast cell‐sufficient mice, the ineffectiveness of BMMC‐transfer in restoring protective activity or MMC responses in W/WV mice seems to be attributed to the functional immaturity or inactivity of BMMC.
Adoptive transfer of enhanced eosinophilia and resistance to infection in mice by an in vitro generated T‐cell line specific for Mesocestoides corti larval antigen
Authors: LAMMAS D. A. , MITCHELL L. A. , WAKELIN D.
Published: October 2007

Summary A T‐cell line specific for tetrathyridial antigens of the cestode parasite Mesocestoides corti was generated in vitro. The T‐cells expressed the L3T4+ Ly2‐ phenotype and secreted the lymphokines: interleukin‐1 (IL‐1), interleukin‐2 (IL‐2), gamma interferon (IFN‐γ), colony stimulating factor (CSF), mast cell growth factor (MCGF) and eosinophil differentiation factor (EDF) in response to antigen stimulation. The line was stable for up to 16 weeks and produced an enhanced peripheral eosinophil response and a reduced parasite burden (40–50%) when adoptively transferred into naive recipients undergoing a primary infection.
Schistosoma mansoni: evidence that immunity in vaccinated and chronically infected CBA/Ca mice is sensitive to treatment with a monoclonal antibody that depletes cutaneous effector cells
Authors: McLAREN DIANE J. , STRATH M. , SMITHERS S. R.
Published: October 2007

Summary Naive mice, mice vaccinated 4 weeks previously with radiationattenuated cercariae of Schistosoma mansoni and mice infected 16 weeks previously with normal S. mansoni cercariae were treated with a rat monoclonal antibody (NIMP‐R14), that has been reported elsewhere to recognize neutrophils selectively. The establishment of a primary schistosome population in naive mice was not affected by the administration of this reagent. In contrast, immunedependent challenge elimination was reduced in both vaccinated and chronically infected mice following treatment with NIMP‐R14. Maximal suppression of resistance in both vaccinated (67% mean reduction) and chronically infected (44% mean reduction) mice was achieved when NIMP‐R14 was injected intraperitoneally on the day of challenge. The monoclonal was markedly less effective when administered on or after day 3. Analysis of the blood leucocyte profiles of vaccinated/NIMP‐R14 treated mice showed that the monoclonal totally abrogated neutrophils from the peripheral circulation between days 1 and 6. Histological examination of the skin site of challenge revealed, however, that NIMP‐R14 treatment had reduced the number of eosinophils and macrophages as well as neutrophils in the cutaneous tissues of vaccinated mice. The reaction site thus more closely resembled that of naive/challenged mice than that of untreated vaccinated/challenged mice. Although we have not been able to identify a specific effector cell from these studies, we have demonstrated clearly that a skin‐located cellular effector mechanism contributes to immune resistance in both murine models.
HLA antigens associated to amoebic abscess of the liver in Mexican mestizos
Authors: ARELLANO J. , ISIBASI A. , MIRANDA R. , HIGUERA F. , GRANADOS J. , KRETSCHMER R. R.
Published: October 2007

Summary Worldwide prevalence of amoebiasis is estimated at 4 ± 108 cases/year, yet only one of about 300 individuals harbouring Entamoeba histolytica suffers tissue invasion and these cases are mostly concentrated in certain areas of Asia, Africa and Latin America. Patients with amoebic abscess of the liver (AAL) represent only a small fraction of that. These contrasting figures have been tentatively explained on the one hand through variations in sex, immunocompetence. nutritional and other socioeconomic features of the host, and on the other hand through differences in parasite virulence. In order to explore a possible association between the major histocompatibility complex (MHC) and AAL susceptibility, we studied the HLA profile in 31 Mexican mestizos with AAL and compared it to race and socioeconomically matched controls. Mexican mestizo patients with AAL revealed a significant increase in HLA‐Bw16 and HLA‐DR3 which could suggest an HLA‐related susceptibility to liver invasion by E. histolytica.
Biliary antibody response in rats infected with rodent Giardia duodenalis isolates
Authors: SHARMA AGNES WAIGHT , MAYRHOFER GRAHAM
Published: October 2007

Summary Using a sensitive ELISA, specific serum and bile anti‐Giardia IgM and IgA responses were studied in rats infected with two strains of Giardia duodenalis: a rat isolate which produces a chronic infection and a mouse isolate which produces a self‐limiting infection. Paired samples of scrum and bile were collected from groups of DA (RTlavl) rats at various times during primary and secondary infections. Antibody responses to both organisms were similar. Only IgA anti‐Giardia antibodies were detected in bile whereas both IgM and IgA antibodies were detected in serum. Biliary IgA antibody litres increased throughout the course of the primary infection and remained at high levels for at least 10 weeks. Biliary IgA titres increased 16‐fold during the secondary infection with both isolates. Serum IgA anti‐Giardia titres also increased but more slowly than the titres in bile. Serum IgM antibody responses were observed against both organisms during the primary and secondary infections. Trophozoites harvested from the intestinal lumen during primary infections were examined for surface‐bound IgA by immunofluorescence microscopy. IgA was detected on 3% of trophozoites on day 7 after infection but on over 70% of trophozoites by the 10th day. The data demonstrate the occurrence of a secretory IgA immune response in rats infected with both G. duodenalis isolates, some of which is directed against surface antigens of the trophozoites.