bluuebunny/crossref_metadata_2025 huggingface dataset:
Ookinete antigens of Plasmodium berghei. Appearance on the zygote surface of an Mr 21 kD determinant identified by transmission‐blocking monoclonal antibodies
Authors: WINGER L.A. , TIRAWANCHAI N. , NICHOLAS J. , CARTER H.E. , SMITH J.E. , SINDEN R.E.
Published: October 2007

Summary Zygotes and ookinetes of the rodent malaria Plasmodium berghei can be enriched 50‐fold, from whole blood cultures by ammonium chloride lysis. Three monoclonal antibodies (MoAbs) raised against such enriched preparations specifically bind to a determinant of Mr 21 kD as assessed by 125I‐labelled goal anti‐mouse IgG probed immunoblots of Western transfers of SDS‐PAGE gels. Indirect immunofluorescence indicates that the 21 kD determinant bound by specific MoAbs. whilst not detectable on gametocytes or gametes, appears on the parasite surface within 2 h of exflagellation/fertilization and increases thereafler. The three MoAbs specifically binding the 21 kD determinanl block oocys! development in mosquitoes by at least 90%, as assessed either by in‐vitro membrane feeds or by live feeds on passively immunized mice. These MoAbs reduce ookinete formation in vitro by between 52 and 100%. Possible mechanisms of action of these MoAbs are discussed.
Antibodies to Plasmodium falciparum gamete surface antigens in Papua New Guinea sera
Authors: GRAVES PATRICIA M. , CARTERS RICHARD , BURKOT THOMAS R. , QUAKYI ISABELLA A. , KUMAR NIRBHAY
Published: October 2007

Summary Sera from individuals living in malaria endemic areas of Papua New Guinea were tested for their effect on inactivity of Plasmodium falciparum gametocyles grown in culture to Anopheles freeborni mosquitoes. Consistent reduction of infectivity to less than 5% of control was observed with nine out of the 41 sera from the endemic area tested and also with three out of seven sera tested from individuals rarely exposed to malaria infection. Gamete surface antigens recognized by the sera were investigated by immunoprecipitation from 125I surface‐labelled gametes extracted in SDS and Triton X‐100. The main antigens recognized were of the same mol. wt (230, 48 and 45 kD) as those known to be targets of transmission‐blocking monoclonal antibodies. A significant negative correlation was observed between the total ct/min immunoprecipitated from surface‐labelled gametes by the sera and the average number of oocysts per gut observed in membrane feeding experiments with these sera. Spearmann's rank correlation coefficient indicated that suppression of infectivily correlated strongly with the presence of antibodies against the 230 kD protein; there was no significant correlation between suppression and antibodies to the 48/45 kD proteins. The antibody response to the different gamete surface antigens varied greatly in sera from the endemic areas suggesting that individuals respond differently to each gamete antigen.
Analysis of antibody responses to Hymenolepis nana infection in mice by the enzyme‐linked immunosorbent assay and immunoprecipitation
Authors: Ito A. , Honey R.D. , Scanton T. , Lightowlersr M.W. , Rickard M.D.
Published: October 2007

Summary Serum antibody responses in two strains of mice infected with embryonated eggs of Hymenolepis nana were analysed by the enzyme‐linked immunosorbent assay (ELISA) and immunoprecipitation (TP) using sodium deoxycholate (DOC)‐solubilized antigens prepared from embryonaled eggs (eggs), mouse‐derived cysticercoids (cysts) and adult tapeworms with immature segments only (adults). Highly susceptible dd mice, which harbour mature tapeworms for a long period (> 70 days), produced high levels of antibodies to all three different stages of H. nana. BALB/c mice, almost all of which expel adult tapeworms by 30 days after infection, produced high levels of antibody against egg antigens only. The high antibody titres to cyst and adult antigens in dd mice did not lead to expulsion of the worms. However, worms are rejecled early in BALB/c mice when there is little or no detectable serum antibody. The antibody responses to eggs seen in BALB/c mice which had long since shed their adult worms were probably due to ingestion of eggs from faeces of other infected mice. Antibodies to eggs were not detected in BALB/c mice which were initially inoculated with eggs (day 0) and then treated with praziquantel on day 6 after the tissue phase of infection only. The different antibody responses to egg antigens and the other two antigens (cyst and adult) in BALB/c mice suggest a difference in antigen specificity between eggs and both cysts and adults. A major antigen component with Mt 32 000 appears to be specific to the egg (or oncosphere) stage of H. nana. Antibody to this major component of eggs was absorbed only with intact eggs, but not with intact cysts nor adults with immature segments only, so that the antigen appears to be on the surface of the oncosphere.
Macrophage activation in vitro by lymphocytes from Leishmania major infected healer and non‐healer mice
Authors: PHAM THANH‐VAN , MACDONALD H. ROBSON , MAUËL JACQUES
Published: October 2007

Summary Peritoneal macrophages from CBA/T6 (healer) and BALB/c (non‐healer) mice were infected with Leishmania major (LV39) in vitro. The microorganism replicated at the same rate in macrophages from either strain. Exposure of infected cells to lymph node cells (LNC) from infected syngeneic animals led to intracellular killing of the parasite by macrophages from both strains, provided LPS was present in the incubation medium. In vitro‐propagated L.major‐specific T‐cell blasts activated macrophages from either strain in the absence of LPS. On a per cell basis, lymphoid cells from BALB/c mice were less efficient, however, than cells from CBA/T6 mice. Lysis of parasitized macrophages was also more marked in CBA/T6 than in BALB/c cell mixtures. LNC exposed to parasite antigen or to infected macrophages secreted macrophage‐activating factor (MAF); incubation with antigen also induced lymphocyte proliferation. MAF production and LNC proliferation decreased with progression of the infection of BALB/c mice, but always remained significant. The reduction in relative T‐cell numbers in the lymph nodes of infected animals was moderate; the absolute number of T‐cells increased markedly in the lymphoid organs of both strains, however. These results suggest that failure to heal may coexist together with active cell‐mediated immune response in non‐healer mice.
Theileria parva (Muguga) infects bovine T‐lymphocytes in vivo and induces coexpression of BoT4 and BoT8
Authors: EMERY D.L. , MACHUGH N.D. , MORRISON W.I.
Published: October 2007

Summary During the course of a lethal infection with Theileria parva (Muguga), the surface phenotypes of efferent lymphatic lymphocytes (ELL) were analysed to determine whether the parasite preferentially infected any particular subpopulation of cells. In the second week of infection, when the proportion of lymphoblasts and parasitized cells increased to 50% of the total ELL, > 99% of infected cells expressed T‐lymphocyte markers including both BoT4 and BoT8. From day 10, a population of T‐lymphocytes coexpressing BoT4 and BoT8 appeared in ELL, reaching 33% by day 14. Similar changes were observed in peripheral blood mononuclear cells (PBM) and lymph node cells (LNC). Analysis of ELL sorted into populations differing on the basis of expression of BoT4 and BoT8, revealed a higher level of parasitosis in the BoT4+ and BoT8+ lymphocytes than in the BoT4+ BoT8− or BoT4− BoT8+ populations. For comparison, the phenotypes of 28 cloned cell lines, obtained by infection of PBM with sporozoites in vitro, were examined. All of these clones exhibited T‐cell markers. Nine of the clones expressed both BoT4 and BoT8; within each of these lines, BoT4 was expressed on all cells, whereas BoT8 was expressed at variable concentrations on 20‐70% of cells. That BoT4+ cells were induced by T. parva (Muguga) to coexpress BoT8 was demonstrated directly by the finding that a BoT4+ BoT8− T‐cell clone expressed BoT8 following infection with the parasite.
The surfaces of the parasitic nematodes Trichinella spiralis and Toxocara canis differ in the binding of post‐C3 components of human complement by the alternative pathway
Authors: KENNEDY MALCOLM W. , KUO YIEN‐MING
Published: October 2007

Summary The binding of human complement components C3, C5 and C9 to the surface of the infective larvae of the nematode parasites Toxocara canis and Trichinella spiralis, by the alternative pathway, was examined by direct and indirect immunofluorescence on the intact parasites. This showed that although C3 bound to both nematodes they differed markedly in the binding of C5 and C9; C5 bound only minimally to T. spiralis, and C9 binding lo this parasite was barely detectable. In contrast, both early and late components bound to T. canis to a high density, comparable to, or in excess of, the binding of these components to the infective larvae of the trematode Schistosma mansoni. The lack of binding of the post‐C3 components to T. spiralis did not correlate with enhanced binding of the control protein, Factor H.
Parasite glycoconjugates: towards the exploitation of their structure
Authors: FERGUSON MICHAEL A.J. , HOMANS STEVEN W.
Published: October 2007

Summary The parasitic protozoa express many unusual complex carbohydrates at the cell surface in the form of glycoproteins and glycophospholipids. In several cases, such molecules have been shown to be involved in parasite survival, infectivity and host‐cell recognition. The carbohydrate chains of these glycoconjugates are often highly immunogenic, and can in some cases elicit protective immunity. The immunogenicity of some parasite glycans is a function of their unusual chemical structure as compared with mammalian glycans. This suggests differences in the glycosylation pathways between host and parasite due to their evolutionary distance. This article describes how a combination of biophysical and biochemical techniques can be used to determine the primary and three‐dimensional structures of parasite carbohydrate and how this information might be exploited towards the development of new selective chemotherapeutic agents and synthetic vaccines.
The cross‐reactive immune response between infective larvae and adult worms of Acanthocheilonema (Dipetalonema) viteae is dominated by phosphorylcholine
Authors: GUALZATA M.D. , RUDIN W. , WEISS N. , HEUSSER CH. H.
Published: October 2007

Summary The immune response of BALB/c mice against living L3 or adult extract of Acanthocheilonema viteae induces three antibody populations, namely antibodies which cross‐react between the two forms of A. viteae, and either (i)do, or (ii) do not express specificity for phosphorylcholine (PC), and (iii) antibodies which do not cross‐react between the two stages. In the anti‐L3 serum, almost all cross‐reactive antibodies to adult antigen arc PC specific and of the IgM isotype, apart from a minor non‐PC‐reactive IgE response. On the other hand, the cross‐reactive antibodies in the anti‐adult scrum are not PC reactive and of the IgG3 isotype. The non‐cross‐reactive antibodies in the two sera were predominantly IgM and IgG2/IgG1 for the anti‐L3 and anti‐adult respectively. Immunofluorescence and immunocytochemical studies on third‐stage larvae and female worms revealed that antigens expressing PC determinants were mainly found on certain internal structures, whereas the cuticles of adults and the outer cuticle part of L3 are PC negative. Topographical analyses revealed distinct differences in labelling patterns by the two antisera, in the different areas. Thus the cross‐reactive and non‐cross‐reactive antibodies induced by BALB/c mice to the two stages of A. viteae are different in nature. Since the antibody response induced by the L3 form and cross‐reactive to the adult form is directed towards an ubiquitous antigen, namely PC, which is not present on cuticula of either the L3 or adult worms, this response may not contribute to protection against the parasite.
The influence of protein deficiency on immunity to Heligmosomoides polygyrus (Nematoda) in mice
Authors: SLATER A.F.G. , KEYMER A.E.
Published: October 2007

Summary The influence of dietary protein on the efficiency with which mice could be immunized against infection with the nematode Heligmosomoides polygyrus was investigated. Immunization with irradiated larvae did not protect outbred mice fed synthetic diets containing 2% or 4% protein against a challenge infection, while animals fed a diet containing 8% protein were significantly resistant. In further experiments with high‐responder NIH mice, protein malnutrition was again found to cause a significant depression in immunity. Immunization primed all mice for an intense production of antibody against larval worms in a challenge infection, and although a slightly higher litre of antibody was detected in the plasma of mice fed a 16% compared with a 2% protein diet it seemed unlikely that this was sufficient to account for the reduced resistance of the malnourished mice. The development of eosinophilia in the blood of immunized mice was significantly delayed in malnourished animals following challenge, and it is suggested that a reduction in the number of granulocytes attacking larval worms contributed to the low level of resistance observed in these animals. Protein malnutrition thus markedly suppresses the effectiveness of immunization of mice against an intestinal nematode, and it is suggested that this result may be of general significance with regard to the potential for widespread immunization of people against infections of this type.
Vaccination trials in rhesus monkeys with a minor, invariant, Plasmodium knowlesi 66 kD merozoite antigen
Authors: DEANS J.A. , KNIGHT A.M. , JEAN W.C. , WATERS A.P. , COHEN S. , MITCHELL G.H.
Published: October 2007

Summary A minor Plasmodium knowlesi 66 kD antigen, which plays an essential role in merozoite invasion, has been shown to be stable in distinct variants and strains of the parasite, and in the face of a specific immune response from the host. Parasites were unable to produce novel molecule(s) to replace it functionally, even in the presence of specific immune pressure. Rhesus monkeys immunized with the purified 66 kD antigen, with saponin as adjuvant, produced antibody which inhibited merozoite invasion of red cells in vitro. Four out of six immunized rhesus monkeys demonstrated clinically effective immunity when challenged at a time of known or presumed high inhibitory antibody titre. When immunization failed to protect, it was ascribed to insufficient levels of specific antibody attributable either to a suboptimal dose of antigen or the use of an inadequate adjuvant.
Immune response to minor variant antigen types (VATs) in a mixed VAT infection of the African trypanosomes
Authors: SEED JOHN RICHARD , SECHELSKI JOHN B.
Published: October 2007

Summary It has been shown that soon after the onset of acute infection with Trypanosoma brucei gambiense, mice are able to detect immunologically small numbers of minor variant antigen types (VATs) within the population. However, in more longstanding infections, considerably larger populations of minor VATs are required to stimulate an effective immune response. As a result, larger populations of minor VATs evade immune detection and, following a decrease in parasitaemia, become part of the relapse population. We hypothesize that the development of immunosuppression increases the effectiveness of antigenic variation as an escape mechanism.
Enhancing and suppressive effects of tumour necrosis factor/cachectin on growth of Trypanosoma musculi
Authors: KONGSHAVN PATRICIA A.L. , GHADIRIAN ESFANDIAR
Published: October 2007

Summary The effect of human recombinant TNF on the growth of T. musculi has been investigated. When added to parasites cultured in vitro, TNF inhibited their growth. In the presence of thioglycollate‐elicited peritoneal exudate cells, the opposite effect was seen and TNF enhanced the growth of trypanosomes in vitro. Similarly, administration of TNF in vivo during the course of infection led to a net increase in the parasite population. It is suggested that TNF exerts a direct anti‐trypanosomal effect while simultaneously promoting the growth of the parasite through an indirect effect mediated via the host's cells, possibly the macrophages.
Demonstration of soluble Plasmodium falciparum antigens reactive with Limulus amoebocyte lysate and polymyxin B
Authors: JAKOBSEN P. H. , BAEK L. , JEPSEN S.
Published: October 2007

Summary To investigate whether soluble Plasmodium falciparum antigens possess endotoxin‐like properties, the interaction of Limulus amoebocyte lysate (LAL) with defined soluble antigens from Plasmodium falciparum was studied by various crossed immunoelectrophoretic methods and immunoblotting. The soluble P. falciparum antigens were purified by affinity chromatography using human IgG from malaria‐immune adults as ligand. Of eight possible antigens, at least three were affected by LAL, as indicated by disappearance of these antigens in the precipitation pattern, after the reaction with LAL. One of the LAL‐reactive antigens is a heat‐stable glycoprotein with the presence of both hydrophilic and hydrophobic regions in its structure. This antigen shows a strong reaction with polymyxin B, and antibodies against it have been shown to be inhibitory to the growth of P. falciparum in culture. It is concluded that LAL reacts with several soluble antigens from P. falciparum and it is suggested that these antigens participate in the induction of protective immunity to malaria, and consequently that one or more of the soluble antigens are candidates for a malaria vaccine.
Immunization against Plasmodium falciparum with recombinant polypeptides produced in Escherichia coli
Authors: HOLDER ANTHONY A. , FREEMAN ROBERT R. , NICHOLLS STEPHEN C.
Published: October 2007

Summary Two proteins produced in recombinant Escherichia coli and containing ammo acid sequences from the Plasmodium falciparum precursor to major merozoite surface antigens (PMMSA) have been partially purified. These proteins, together with a preparation of merozoites, have been used to immunize animals. The antibody response and the degree of protection were compared. Animals immunized with merozoites produced antibodies reacting with many P. falciparum proteins. whereas a response specific for PMMSA was detected in those receiving the recombinant material. Incomplete protection was conferred to both groups and there was no apparent correlation between antibody levels and protection.
Bovine mononuclear cell lines transformed by Theileria parva or Theileria annulata express different subpopulation markers
Authors: SPOONER R. L. , INNES E. A. , GLASS E. J. , MILLAR P. , BROWN C.G.D.
Published: October 2007

Summary Bovine mononuclear cell lines infected with the protozoan parasites Theileria annulata and T. parva have been studied with a panel of monoclonal antibodies reacting with bovine lymphocyte subpopulation markers. All infected lines are MHC class II positive, though the amount of class II antigen expressed varied between lines, and within individual lines there was variation in the proportion of positive cells from 100% with many, to less than 10%. All lines were negative for a macrophage/monocyte marker and for surface IgM. The T. parva lines tested were all positive for BoT4 or BoT8 or both, whereas T. annulata lines were uniformly negative for both of these markers. These results suggest that the two parasites preferentially infect different lymphocyte subpopulations.
Lymphocyte phenotypes in the abomasal mucosa of sheep infected with Haemonchus contortus
Authors: GORRELL M. D. , MILLER H. R. P. , BRANDON M. R.
Published: October 2007

Summary Lymphocyte subpopulations in the abomasal mucosa of worm‐free and parasitized sheep were assessed in situ. A preponderance of T‐lymphocytes, with approximately equal numbers of cells expressing CD5, CD4 and CD5 antigens, was found. Most of the lymphocytes expressing CD8 lacked CD5. Using a panel of 15 monoclonal antibodies to ovine leucocyte antigens, abomasal lymphoid follicles in the mucosa were shown to resemble lymph node follicles phenotypically. Abomasal epithelial cells contained major histocompatibility complex (MHC) class II antigen. Infection or hyperimmunization of pasture‐reared sheep with the gastric nematode Haemonchus contortus increased the numbers of mucosal mast cells and eosinophils but did not alter the phenotypic composition or number of mucosal lymphocytes or the pattern of expression of MHC class II antigens.
Identification of protein components of Echinococcus granulosus protoscolex antigens for specific serodiagnosis of E. granulosus infection in dogs
Authors: GASSER ROBIN B. , LIGHTOWLERS MARSHALL W. , RICKARD MICHAEL D.
Published: October 2007

Summary Proteins of Echinococcus granulosus protoscolex excretory/secretory or deoxycholate solubilized somatic antigens were radiolabelled with 125I and immunoprecipitated with sera from dogs naturally or experimentally infected with E. granulosus and various control dog sera. Analysis of immunoprecipitates was performed using one‐ and two–dimensional gel electrophoresis to identify antigenic protein components specific for E. granulosus. Using both electrophoretic techniques, a basic component of Mr 27000 and an acidic component of Mr 94000 were defined in both excretory /secretory and somatic protoscolex antigens, and were specifically identified by 95% and 62% of 21 sera from E. granulosus‐infected dogs, respectively. An abundant component of Mr 35000 was identified by 100% of these dogs, parts of which were E. granulosus specific. Results of this study should allow identification of specific recombinant antigens for routine serodiagnosis of E. granulosus infection in dogs.
Impaired immune responsiveness in Plasmodium berghei immune mice
Authors: SCHETTERS T. P. M. , BREDA J. H. J. VAN RUN–VAN , WIEL TH. VAN DE , HERMSEN C. C. , CURFS J. , ELING W. M. C.
Published: October 2007

Summary Mice immunized against Plasmodium berghei parasites by drug–controlled infection exhibited decreased immunoresponsiveness against rabbit red blood cells (RRBC). Increasing RRBC antigen dose increased responsiveness, but agglutinating anti–RRBC antibodies of the IgG class remained undetectable. Clearance of colloidal carbon from the bloodstream of malaria–immunized mice was not different from controls. Removal of all the persistent parasites from immune mice did not restore responsiveness until 140 days after treatment, suggesting that the parasite per se did not influence responsiveness directly. Because of this, and because of the fact that priming of mice with RRBC before P. berghei immunization was not more effective than priming after immunization, it was concluded that antigen uptake and subsequent presentation were not impaired in P. berghei immune mice, in contrast to infected mice. Anti–RRBC antibodies were detected in serum of P. berghei immune mice, but regulation of responsiveness to RRBC by transfer of such immune mouse serum was not found. Immunoglobulin levels, especially of the IgG2 and IgG3 subclass were elevated in sera of P. berghei immune mice, which indicated an LPS–like polyclonal activation. The results also suggest that during drug–controlled infection, which leads to immunity against infection, a state of B–cell tolerance is induced.
Limiting dilution analysis of the T cell response to Plasmodium chabaudi chabaudi in mice
Authors: LANGHORNE JEAN , SIMON BIRGIT
Published: October 2007

Summary A limiting dilution assay system was developed in order to measure the in–vitro T cell response to antigens of the erythrocytic stages of Plasmodium chabaudi. The conditions of the assay are such that only CD4+ T cells are able to respond. The assay allows the determination of the frequencies of T cells which proliferate and/or which develop into helper cells for antibody production during a primary infection. A specific response from splenic T cells can be measured as early as 7 days after infection, and is still significant 3 months after injection of P. chabaudi. At all times the frequency of proliferating cells was greater than the precursor frequency of T helper cells. This suggests that a proportion of CD4+ T cells in this assay, although they respond to malarial antigen, do not develop into helper cells for antibody production. This limiting dilution assay will be a useful method by which to evaluate the functional heterogeneity of the CD4+ T cell response to malaria antigens.
In–vitro lysis of sensitized Trypanosoma cruzi by platelets: role of C3b receptors
Authors: UMEKITA LILIA F. , MOTA I.
Published: October 2007

Summary Incubation of Trypanosoma cruzi bloodstream trypomastigotes (Btrys) with C5–deficient blood in the presence of anti–T. cruzi immune mouse serum (IMS) or its IgG fraction resulted in an immediate formation of small clumps in which one could easily see platelets adhered to the parasites. After 4 h of incubation most of the clumps had disappeared and the number of the parasites was considerably reduced. Twenty–four hours later there were only a few remaining parasites. This same sequence of events was also observed when the parasites were incubated with isolated platelets in presence of IMS or its IgG fraction. When the parasites were incubated with plasma in the presence of IMS or its IgG fraction but in the absence of platelets there was strong agglutination of the parasites but no reduction in their number. Incubation of the parasites with platelets and IMS or its IgG fraction in C3–depleted plasma prevented adherence of the platelets to the parasites and their subsequent lysis. It is concluded that platelets are able to induce in–vitro lysis of the Btrys and that this phenomenon is dependent on the platelet' receptor for C3b.
Genetic control of immune response to a purified Schistosoma mansoni antigen. I. Effect of MHC class II antigens on the cellular, humoral and protective responses
Authors: MENDLOVIC F. , TARRAB–HAZDAI R. , PURI J. , ARNON R.
Published: October 2007

Summary The influence of the I region of the major histocompatibility complex (MHC) on T–dependent immune responses against a purified schistosome antigen (9B antigen) was investigated. H–2 congenic mice expressing both I–A and I–E antigens (I–E+) showed a higher in–vitro proliferation to 9B antigen as compared to the recombinant strains expressing only I–A (I–E–). These two strains of mice differed both qualitatively and quantitatively in the humoral responses elicited by the purified antigen. Furthermore, in–vivo protection experiments showed that mice which do not express I–E molecules can be partially protected against the disease by prior immunization with the 9B antigen in contrast to their I–E expressing counterparts. The possible role of the I–E molecule in the immune responses elicited during Schistosoma mansoni infection is discussed.
Early appearance of variant parasites in Plasmodium chabaudi infections
Authors: MCLEAN SHEILA A. , MACDOUGALL LYNNE M. , PHILLIPS R.S.
Published: October 2007

Summary Previous studies have shown that the recrudescence parasitaemias seen in mice infected with Plasmodium chabaudi AS strain are antigenically different from the infecting parent population. Antigenic differences between recrudescent and parent populations were demonstrated in a passive transfer assay. In the present study, using the same assay system, it has been shown that in some mice, variant parasites (i.e. different from the parent population) can be detected at a time when the primary parasitaemia is still patent but in remission. This is the first report in Plasmodium of variant parasites being detected during the course of a patent primary parasitaemic episode of an infection initiated with a cloned line.
Injection of microfilariae induces resistance to Brugia malayi infection in ferrets and accelerates development of lymphostatic disease
Authors: CRANDALL R.B. , CRANDALL CATHERINE A. , NAYAR J.K.
Published: October 2007

Summary Ferrets injected intravenously with living microfilariae or cutaneously with microfilariae followed by intravenous injection developed partial resistance to a challenge infection as measured by recovery of adult filariae from lymphatics. Following a challenge infection, the ferrets injected with microfilariae developed lymphatic pathology characteristic of a chronic infection or that observed following multiple infections. There was disruption of lymphatic drainage of the infected limb and lymphoedema. The results suggest that immune responses to antigens of microfilariae, presumably antigens shared with other developmental stages, effected both increased resistance and enhanced lymphatic pathology.
Suppressive macrophages occurring in murine Trypanosoma brucei infection inhibit T‐cell responses in vivo and in vitro
Authors: BOROWY NORBERT K. , STERNBERG JEREMY M. , SCHREIBER DAGMAR , NONNENGASSER CHRISTINA , OVERATH PETER
Published: October 2007

Summary Intraperitoneal injection of Trypanosoma brucei AnTat 1.1 into mice of the C3H.He, BALB/c or C57BL/6 strains resulted in impaired immune responses from day 3 onwards, as measured by the reduction in DNA synthesis in spleen cell populations stimulated with concanavalin A (Con‐A) in vitro. Adherent cells from the peritoneum (PC) or from the spleen of infected mice, consisting predominantly of macrophages, caused a 60–80% reduction of the Con‐A response in spleen cells from syngeneic recipients 3–4 days after transfer in vivo. Adherent PC from irradiated or athymic mice were equally suppressive. Spleen cells from infected mice reduced the proliferative response of spleen cells from uninfected mice upon co‐cultivation in vitro. This dominant suppressive effect was abolished after the selective removal of macrophages from the spleen cell population by treatment with L‐leucine methylester. Moreover, the macrophage‐depleted spleen cells from infected mice responded normally to Con‐A provided they were supplemented with splenic adherent cells from naive mice as a source of accessory cells. Both the cell transfer and co‐cultivation experiments suggest that infection with African trypanosomes changes the properties of macrophages to a state which allows them actively to suppress immune responses.
The humoral response to heat shock protein 70 in human and murine Schistosomiasis mansoni
Authors: MOSER DORIS , DOUMBO OGOBARA , KLINKERT MO‐QUEN
Published: October 2007

Summary We have expressed two cDNA sequences encoding 121 and 230 amino acids of the C‐terminus of the Schistosoma mansoni Hsp70 in Escherichia coli. The products were synthesized as polypeptides fused to the RNA polymerase of bacteriophage MS2, and their reactivities were tested in ELISAs, using sera from human and murine infections. Anti‐Hsp70 antibodies were detected in a significant number of individuals suffering from chronic schistosomiasis mansoni, but not in patients with known recent infections. This, together with the finding that antibodies directed at S. manoni‐specific Hsp70 determinants during the course of infection of experimental mice were not detectable until 5–6 weeks postinfection, suggests that the protein may be a useful marker for distinguishing late and early infections. The diagnostic specificity of Hsp70 was evaluated with sera from humans infected with different schistosome species and other parasitic diseases. While some subjects infected with 5. haematobium produced antibodies which recognized the S. mansoni Hsp70, no such antibodies were generated in 5. japonicum infected individuals. However, cross‐reactive antibodies were elicited in donors with other parasitic diseases such as filariasis and malaria. The absence of antibodies in early infection and the observed cross‐reactivities led us to conclude that Hsp70 will be of limited value in the diagnosis of schistosomiasis.
Cysticercosis: cellular immune responses during primary and secondary infection
Authors: MEEUSEN E. , BARCHAM G. J. , GORRELL M. D. , RICKARD M. D. , BRANDON M. R.
Published: October 2007

Summary Immune reactions to cysticercosis have been extensively studied in mice. The lack of significant lymphocyte infiltration into the livers of infected mice and the obvious role of antibodies in rejection has led to the general conclusion that cellular reactions do not play a role in protection against this disease. In contrast, the present study examining the immune response to cestode infections in a large animal model (sheep) revealed the presence of a massive and highly organized cellular infiltration in the livers after a secondary Taenia hydatigena infection. The majority of the infiltrating lymphocytes were of the CD4+ phenotype with much fewer CD8+ cells present. While most γδ‐TCR+ cells in peripheral blood are SBU‐T19+, the majority of γδ ‐TCR+ lymphocytes in the liver lesions are SBU‐T19‐ suggesting selective migration of these cells into the lesions. In contrast to the diffuse distribution of T cells in the lesions, B cells were present as distinct aggregates.

In primary T. hydatigena infections, host class I and class II MHC antigens were shown, for the first time in cestode infections, to be absorbed onto the surface of the metacestode bladderwall indicating their possible involvement in parasite survival. No immune reactions were observed close to the parasite although lymphocytes and eosinophils were infiltrating the adjacent portal tract areas. Most lymphocytes in both primary and secondary infections were positive for MHC class II antigens suggesting selective recruitment of activated cells to the site of infection.

Significant changes in relative and absolute numbers of lymphocyte subpopulations were also observed in the draining hepatic lymph nodes dominated by a massive increase of B cells. In contrast, at the peak of local cellular infiltration, no changes in lymphocyte subpopulations were observed in peripheral blood showing the limited usefulness of this compartment in studying cellular changes in localized infections.

The vigorous cellular response observed in the livers of sheep contrasts sharply with the lack of lymphocyte infiltration reported in mice indicating that small animal models may not be appropriate to study cellular responses to cysticercosis in large animals and man.
Monoclonal antibodies against Opisthorchis viverrini antigens
Authors: BILLINGS P.B. , UTSAKHIT N. , SIRISINHA S.
Published: October 2007

Summary Monoclonal antibodies (MoAb) were produced against somatic antigens of adult human liver fluke Opisthorchis viverrini. Earlier studies attached diagnostic potential to an 89–90 kD antigen present in both somatic extracts and in vitro culture supernatants as well as to the abundant 16–17 kD tegumental protein doublet. Mice made excellent immune responses to low dose somatic extract adsorbed onto nitrocellulose or to the 80–95 kD region of SDS gel Western blots. The antigen specificities of hybridomas reactive with somatic antigen by ELISA were determined by radioimmunoprecipitation or immunoblotting. Six MoAb reacted with the desired 16 kD tegumental protein. A 90 kD somatic protein was identified by 9 clones. By indirect immunofluorescence, monoclonals reactive with the 16 kD polypeptide identified the outermost surface of the tegument. The 90 kD antigen was associated with all major muscle systems, most strikingly the crossed subtegumental layers, oral and ventral suckers, pharynx and a thin layer surrounding caeca. The biochemical identity of this muscle‐associated antigen is unknown, but it is clearly distinct from the previously identified species‐specific 89 kD exoantigen. The 16 kD tegumental protein shares epitopes with a number of related flukes. However, 2 MoAb which react with this protein show no crossreaction.
Lectin binding characteristics of haemocytes and parasites in the oyster, Crassostrea virginicd, infected with Haplosporidium nelsoni (MSX)
Authors: KANALEY SHEILA A. , FORD SUSAN E.
Published: October 2007

Summary Lectin‐binding surface receptors on haemocytes from host oysters were compared with those on plasmodial stages of the ascetosporan parasite Haplosporidium nelsoni (MSX). Haemocytes were agglutinated, in descending order of strength, by WGA, HPA, LPA, ConA, and CFA. GMA, PHA, and RMA lectins failed to agglutinate at 100 μg/ml, the highest concentration tested. These results indicate that haemocytes contain surface receptors resembling N‐acetyl‐D‐glucosamine and α‐methylmannopyranoside. Fluorescent (FITC) labelled ConA and WGA also bound to H. nelsoni plasmodia, but parasites were commonly excluded from clumps of agglutinated haemocytes, except for those that were apparently trapped passively in large aggregates. Although seasonal variations existed, agglutination titres for all reacting lectins were 2‐ to 8‐fold higher for cells from systemically infected oysters compared to control oysters not manifesting systemic infections. Preincubation of lectins in serum from control animals reduced agglutination titres 6‐ to 9‐fold, whereas incubation in serum from systemically infected oysters reduced titres only 4‐ to 6‐fold. The loss of lectin‐like molecules from the serum of systemically infected animals, and the concurrent increase of lectin receptors in the haemocyte population, is probably related to known changes in haemocyte composition and the loss of serum glycoproteins in diseased animals. Antigenic similarities were detected between surface receptors on oyster haemocytes and those on H. nelsoni plasmodia, which may help explain the failure of oyster haemocytes to phagocytose this parasite.
Antigenic variation in Giardia lamblia: cellular and humoral immune response in a mouse model
Authors: GOTTSTEIN BRUNO , HARRIMAN GREGORY R. , CONRAD JOHN T. , NASHf THEODORE E.
Published: October 2007

Summary Neonatal mice (CR:NIH:S) were infected with a cloned human isolate of Giardia lamblia (GS/M‐83‐H7) and the surface antigens of the intestinal trophozoites, as well as the cellular and humoral immune responses, were analysed during the course of infection. Infections in mice peaked 2–3 weeks after inoculation and were self‐cured by day 42 post‐infection (p.i.). The proportion of trophozoites expressing the Mr 72 000 surface antigen of the initial inoculum had decreased by day 12 and approached zero by day 22 p.i., similar to infections in humans. The predominant parasite‐specific humoral response was an IgM‐ and IgG‐isotype directed to the original Mr 72 000 surface antigen as well as other antigens. T‐lymphocytes (predominantly LY4(CD4)+) isolated from Peyer's patches 12 days p.i. and later showed a significant proliferative response to Giardia lamblia antigens. Spleen and lymph node cells showed no lymphoproliferative response. T‐cell blot analysis revealed the presence of dominant T‐cell epitopes in the areas of Mr 200 000–75 000 and < 50 000 polypeptides. No response was demonstrated in the Mr 72 000 region (migration site of the major surface antigen), suggesting T‐cell dependent mechanisms are most likely not responsible for the surface antigen switch which occurred during the course of infection. This model infection can be used to study the role of immunological mechanisms in Giardia lamblia variant antigen switching and in the control of infections.
Cysticercosis vaccine: cross protecting immunity with T. solium antigens against experimental murine T. crassiceps cysticercosis
Authors: SCIUTTO E. , FRAGOSO G. , TRUEBA L. , LEMUS D. , MONTOYA R.M. , DIAZ M. L. , GOVEZENSKY T. , LOMELI C. , TAPIA G. , LARRALDE C.
Published: October 2007

Summary Vaccination of mice with an antigen extract from Taenia solium cysticerci induced protection against challenge with T. crassiceps cysticerci as successfully as did antigen extracts from T. crassiceps. Vaccination was more effective in male than in female mice and in the resistant strain (BALB/B) more so than in the susceptible strain (BALB/c). While only the resistant strain was completely protected by vaccination, the parasite load of the susceptible strain was significantly reduced by vaccination. Cross immunity between the human and murine parasites establishes murine T. crassiceps cysticercosis as a convenient laboratory model in which to test promising T. solium antigens aimed at vaccine development against T. solium cysticercosis. Further, results point to strong interactions of the immune system with sexual and histocompatibility factors in the host's dealing with cysticercosis.
Administration of β‐glucan following Leishmania major infection suppresses disease progression in mice
Authors: GOLDMAN RACHEL , JAFFE CHARLES L.
Published: October 2007

Summary The potential of β‐glucan (glucan) to suppress the progression of lesions caused by virulent strains of Leishmania major in genetically susceptible BALB/c mice when administered post challenge was evaluated. Glucan particles (glucanp) prepared from Saccharomyces cerevisiae were injected i.v. at 7‐day intervals starlins 7 days after parasite challenge. Four injections gave a more rapid and a higher extent of suppression than 1, 2 or 3 injections. Mice receiving only parasites, a glucose solution, starch particles or glucanp by the i.p. route showed a progressive increase in footpad thickness and developed ulcerating lesions. An alkali solubilized glucan (glucanas) was injected (50 μg, 200 μg and 400 μg/mousc) 4 times at 4 day intervals either i.v. or i.p. starling four days post parasite challenge. Glucanas injection by either route blocked lesion development; the 50 μg treatment had already substantial effects and 400 μg in the i.p. route prevented even the initial stages of lesion formation. Touch prints from the lesion area and from the liver of mice receiving 200 μg glucanas were amasiigote free. The anti Leishmania antibody litre of glucanas treated mice was lower and their sera recognized fewer antigens than that of control Leishmania bearing mice.
Characterization of the thoracic duct T‐helper cells that co‐mediate, with antibody, the rapid expulsion of Trichinella spiralis in adult rats
Authors: AHMAD A , BELL R.G. , WANG C.H. , SACUTO F.R.
Published: October 2007

Summary Thoracic duct cells that act synergistically with immune serum or antibody to transfer rapid expulsion of a challenge infection with Trichinella spiralis muscle larvae were characterized as OX38+, OX8−,OX22− T helper cells. Protective capacity was confined to the dividing T helpers that appeared on days 3–5 in the thoracic duct of rats during a T. spiralis infection. To realize their intestinal priming potential in recipient rats, MHC‐compatibility between donor and recipient rat was required. Fractionation of immune serum with 40% saturated ammonium sulphate left transferable protective activity in both the precipitate and supernatant fractions. Absorption of immune serum with muscle larvae antigen removed the capacity to transfer protection.
Reconstruction of immune‐mediated ion secretion in gut mucosa of the athymic rat
Authors: HARARI YAEL , CASTRO GILBERT A.
Published: October 2007

Summary A defect in an immune‐mediated, physiological reaction in the small intestine of congenitally immunosuppressed rats has been identified and corrected by recouping the immunological trigger in the mucosa with epithelial effector cells. Antigenic challenge of jejunum from euthymic rats sensitized by infection with Trichinelta spiralis evoked an anaphylactic response in vitro that was characterized by an elevation in transmural short‐circuit current (Isc) and caused by net Cl‐ secretion. In contrast, jejunum from previously infected athymic counterparts failed to respond electrophysiotogically to antigenic stimulation. Passive immunization of athymic rats with anti‐Trichinella serum restored jejunal responsiveness to antigen. Jejunal unresponsiveness to anligcnic challenge in the athymic rat compared with the euthymic rat was not due to a difference in the duration of exposure to the sensitizing antigens, mast cell numbers, inflammation‐related hislological changes nor to reduced responsiveness of epithelium to Cl‐ sccretagogues. Because the transduction of the antigenic signal into epithelial ion transport changes in euthymic rais requires IgE, mucosal mast cells, mast cell‐derived mediators and enteric nerves, the results support the conclusion that an antibody deficiency is the only functional defect preventing the antigen‐induced change in mucosal ion transport in the athymic host.
Genetic control of the immune response to Trichinella spiralis: recognition of muscle larval antigens
Authors: ROBINSON M. , KRCO C.J. , BEITO T.G. , DAVID C.S.
Published: October 2007

Summary Host antibody recognition of muscle larval (ML) antigens of Trichinella spiralis was examined. Monoclonal antibodies (MoAbs) to known host protective ML antigens have been produced in order to aid this examination. Eleven strains of mice with independent MHC haplotypes and seventeen T. spiralis infected human patients were all found to recognize the same three major antigens as the monoclonal antibodies; i.e., of mw 41, 46 and 55 kD. However all scrum samples tested also recognized further ML antigens and this recognition varied with the individual or strain. This variation in antigen recognition also applied to the MoAb. Mutual inhibition studies demonstrated that even where the MoAb apparently recognized the same antigens, specific epitope recognition was disparate. Hence some of the major antigens recognized by hosts of T. spiralis, regardless of whether vaccinated or infected, correspond with antigens which have considerable host protective properties. There also appear to be a number of epitopes upon these antigens and the biological implications of this are discussed.
Immunization of mice and baboons with the recombinant Sm28GST affects both worm viability and fecundity after experimental infection with Schistosoma mansoni
Authors: BOULANGER D. , REID G.D.F. , STURROCK R.F. , WOLOWCZUK I. , BALLOUL J.M. , GREZEL D. , PIERCE R.J. , OTIENO M.F. , GUERRET S. , GRIMAUD A. , BUTTERWORTH A.E. , CAPRON A.
Published: October 2007

Summary A member of the glutathione S‐transferase family. Sm28GST has previous! demonstrated a good ability to protect rodents against experimental infection with Schistosoma mansoni. In order lo evaluate its efficacy in a model closer to man, two different protocols of immunization with recombinant Sm28GST were tested on baboons in a large‐scale trial. Three injections in the presence of aluminium hydroxide as adjuvant resulted in a significant 38% reduction in the adult worm burden together with a trend for a lower percentage of inflammatory tissue in the liver. Individual levels of protection, ranging from 0 to 80%, underlined the heterogeneity of the immune response to this purified molecule in outbred primates. On the other hand, two injections of Sm28GST in the presence of aluminium hydroxide and Bordetella pertussis reduced female schistosome fecundity by 33%, with a more pronounced effect (66%) on faecal egg output; there was also a trend, in this protocol, for decrease of the mean granuloma surface in the liver. Individual anti‐Sm28GST IgG antibodies were apparently unrelated to levels of immunity, but there was partial evidence that cytophilic IgE might play a role in the immune mechanisms affecting worm viability, but not fecundity. In the mouse model, Sm28GST vaccination resulted in a lower hatching ability of tissue eggs recovered from immunized mice whereas passive transfer of specific anti‐Sm28GST T‐lymphocytes, one day before infection, significantly reduced the number of eggs in the liver of mice. We propose that different protocols of immunization with a recombinant molecule can impede Schistosoma mansoni worm viability and fecundity, but can also affect miracidium