bluuebunny/crossref_metadata_2025_split huggingface dataset:
A theoretical framework for the immunoepidemiology of blocking antibodies to helminth infection
Authors: WOOLHOUSE M. E. J. 
Published: October 2007

SUMMARYEpidemiological evidence is widely cited in support of the hypothesis that certain antibody responses to human helminth, especially schistosome, infection exhibit blocking activity. This evidence includes positive correlations between antibody levels and the rate of re‐establishment of infection following chemotherapy, antibody levels which peak in younger and more susceptible age classes, lower ratios of blocking antibodies to others in older and less susceptible age classes. In this paper simple mathematical models are used to explore expected age‐specific relationships between antibody levels, parasite burdens and re‐establishment rates for different combinations of protective, neutral and blocking immune responses. In general, all the above cited patterns may be generated without invoking blocking activity, especially if the abilities to produce different antibody responses have different immunological memories, i.e. persist for different lengths of time in the absence of continued exposure to antigen. None of these patterns, including a positive correlation between antibody levels and rates of re‐establishment following chemotherapy, offers unambiguous evidence for blocking activity. Blocking activity is also predicted to affect the shape of the age‐intensity curve and the relationship between susceptibility to infection and age in ways which are not necessarily consistent with the epidemiological evidence. The importance of the blocking activity, which has been convincingly demonstrated in vitro, to population level immunoepidemiological patterns in the field therefore remains uncertain.
Cytokine profile of protective anti‐Trichinella spiralis CD4+ OX22− and non‐protective CD4+ OX22+ thoracic duct cells in rats: secretion of IL‐4 alone does not determine protective capacity
Authors: RAMASWAMY K. , E. GOODMAN RICHARD , G. BELL ROBIN 
Published: October 2007

SUMMARYWe analysed the cytokine profile of a T cell subset (CD4+ CD45 RC−) that confers protection against Trichinella spiralis infection in rats. These CD4+ cells are generated in the gut and appear in the thoracic duct lymph within 72 h after infection. Cytokine mRNA levels for IL‐2, IL‐3, IL‐4, IL‐5, IL‐10 and IFN‐γ and functional cytokine secretion for IL‐4, IL‐5, IFN‐γ, TNF‐α and mast cell differentiation activity were tested in vitro following stimulation with T. spiralis antigens. Compared to a non‐protective T cell population (CD4+ CD45 RC+ or CD8+), also isolated from the same thoracic lymph, no significant differences were observed in the levels of mRNA for IL‐2, IL‐3, IL‐4, IL‐5, IL‐10 or IFN‐γ in the protective CD4+ CD45 RC− cells. However, analysis of the cytokine activities in culture supernatant of these T cell subsets following 24 h stimulation in vitro with T. spiralis antigens showed that significant IL‐4 and IL‐5 activity but little IFN‐γ or TNF‐α was secreted by the protective CD4+ CD45 RC− cells. Whereas the non‐protective CD4+ CD45 RC+ cells secreted significant levels of IL‐4, IFN‐γ, mast cell differentiating activity and TNF‐α but little IL‐5 activity. Nonprotective CD8+ cells were found to secrete IL‐4 but not IL‐5. Production of IL‐4 was essentially equal for both protective and non‐protective T cell subsets. These findings suggest that the presence or absence of IFN‐γ secretion, rather than IL‐4 alone, determines whether a T cell subset has protective activity against T. spiralis infection in rats.
Complex formation of human alpha‐1–antitrypsin with components in Schistosoma mansoni cercariae
Authors: MODHA JAY , DOENHOFF MICHAEL J. 
Published: October 2007

SUMMARYHuman alpha‐1–antitrypsin (α1‐AT) was incubated with an extract of Schistosoma mansoni cercariae or porcine pancreatic elastase and analysed by immunoelectrophoresis and Western blotting. The inhibitor was shown to form complexes with components in S. mansoni cercariae in the same way as elastase. The role of α1‐AT in S. mansoni infection is discussed.
Avian coccidiosis: changes in intestinal lymphocyte populations associated with the development of immunity to Eimeria maxima
Authors: ROTHWELL LISA , GRAMZINSKI ROBERT A. , ROSE M. ELAINE , KAISER PETER 
Published: October 2007

SummaryThe effect of infection and subsequent challenge with Eimeria maxima on the populations of lymphocytes in the small intestine of Light Sussex chickens was assessed by immunohistochemistry. T cells were characterized for CD3, CD4, CD8, TCR1 (γδ heterodimer) or TCR2 (αβ1 heterodimer) markers, and B cells for the expression of IgM, IgA andlgG. After a primary inoculum there were, in both the epithelium and the lamina propria, two distinct increases in the numbers of T lymphocytes. The first peaked on days 3–5 and the second, greater influx, on day 11 after infection. CD4+ and CD8+ cells were represented in both peaks but, whereas CD4+ cells were found almost exclusively in the lamina propria, CD8+ cells were present in both sites. The area staining positive for CD8+ cells was somewhat greater than the value obtained for CD4+ cells. In the epithelium there was an early, small increase in TCR1+‐staining, followed by a larger rise to the second peak, at which time there was also an increase in the lamina propria. Staining for TCR2+ cells followed the same pattern with a reversed distribution between epithelium and lamina propria. Changes after challenge were minimal and confined to the epithelium. The most notable changes in the expression of immunoglobulins were, in the lamina propria, a biphasic increase in the amount ofIgM+‐staining in the course of primary infection (corresponding approximately to that of the T cells), and in IgA + cells shortly after challenge.
Antibodies to Pf155/RESA and circumsporozoite protein of Plasmodium falciparum in paired maternal‐cord sera from Nigeria
Authors: ACHIDI E. A. , PERLMANN H. , SALIMONU L. S. , ASUZU M. C. , PERLMANN P. , BERZINS K. 
Published: October 2007

SummaryPaired maternal‐cord serum samples were analysed for antibodies to the P/155/RESA and circumsporozoite protein (CSP) antigens of Plasmodium falciparum. Malaria parasites were found in 2–6% (3/117) of cord blood and 22–4% (26/116) of maternal samples. Immunofluorescence assays detected P. falciparum‐specific IgG antibodies in all paired samples while P. falciparum‐specific IgM was detected in 5–8% (7/121) of cord samples. The positivity rates for antibodies to Pfl55/ RESA and (NANP)6 but not (EENV)6, a C‐terminal repeat sequence of Pf155/REAS, were significantly higher in maternal as compared with cord samples. Seropositivity rates to Pf155/RESA and (EENV)6 were not related to maternal parity group while positivity rates to the (NANP)6 peptide were higher in primiparae and multi‐par ae of 4 parity. These data confirm the transplacental transfer of P. falciparum‐Specific antibodies and the higher incidence of malaria parasitaemia in primiparae. The presence of P. falciparum‐.specific IgM in some cord samples suggests intrauterine sensitization of the foetus to malarial antigens.
IL‐10 mediates immunosuppression following primary infection with Toxoplasma gondii in mice
Authors: KHAN IMTIAZ A. , MATSUURA TADASHI , KASPER LLOYD H. 
Published: October 2007

SummarySuppression of the host immune response by Toxoplasma gondii has been observed in both human and experimental murine infection. In this study, inbred mice were infected with T. gondii. At day 7 post‐infection, the lymphoproli‐ferative response to both mitogen and superantigen as well as parasite antigen were found to be significantly depressed. Using a transwell system, it was determined that the reduced proliferative response was due to soluble factor (s) being expressed by splenocytes from the infected mice. Isolation of the splenocytes into an adherent and nonadherent population suggested that both macrophages and T cells were able to produce at least one soluble factor. Tissue culture supernatant derived from the splenocytes of the infected mice contain increased levels of IL‐10, whereas measurable IL‐2 levels could not be quantitated. At day 7 post‐infection, both a biologic assay for IFN‐γ in culture supernatant and the expression of IFN‐γ mRNA in the splenocytes were reduced. Antibody to IL‐10 was able to partially neutralize (almost 50%) the in vitro immune downregulation of the tissue culture supernatant. Anti‐IL‐10 in combination with a nitric oxide (NO) antagonist was able to reverse the inhibitory activity of the culture supernatant by 85%. Since IL‐10 is a potent antagonist of IFN‐γ, it may represent a critical cytokine involved in mediating T. gondii induced immunosuppression in the infected host.
Comparison of antibody isotype responses to Schistosoma mansoni antigens by infected and putative resistant individuals living in an endemic area
Authors: VIANA IRAMAYA R.C. , CORREA‐OLIVEIRA RODRIGO , CARVALHO OMAR DOS SANTOS , MASSARA CRISTIANO LARA , COLOSIMO ENRICO , COLLEY DANIEL G. , GAZZINELLI GIOVANNI 
Published: October 2007

SummaryThe isotypic patterns of antibodies against Schistosoma mansoni antigenic preparations from eggs (SEA), adult worms (SWAP) andcercariae (CERC) have been studied in sera from two groups of individuals living in an area endemic for S. mansoni. One of the groups was comprised of individuals diagnosed as having S. mansoni infections based on their patency, i.e. those passing eggs in their faeces (patent infections, PI). The other group has been consider ‘putatively resistant’ due to their residence in an endemic area, their documented exposure to positive transmission sites, and their repeated negativity upon stool examinations (endemic normals, EN). There are strong specific responses oflgGl, IgG4 and IgM, particularly to SEA and CERC, by both groups. The reactivities of all isotypes were lower to SWAP. The responses of IgG4, IgM and IgE anti‐CERC in EN and PI are higher than those found in normal individuals from outside endemic areas. In general, EN individuals express a relative higher level of anti‐STEG IgE as compared to IgG4. On the other hand the pool of sera from PI showed the opposite pattern of higher IgG4 as compared to IgE. Several correlations are seen between isotypic responses to SEA, SWAP and CERC based on comparisons to the anti‐SWAP IgE responses of the individuals in the two groups. These comparisons indicate the presence of distinct immunologic differences between individuals in the PI and the EN groups.,
Immunogens containing sequences from antigen Pf332 induce Plasmodium falciparum‐reactive antibodies which inhibit parasite growth but not cytoadherence
Authors: AHLBORG NIKLAS , IQBAL JAMSHAID , HANSSON MARIANNE , UHLÉN MATHIAS , MATTEI DENISE , PERLMANN PETER , STAHL STEFAN , BERZINS KLAVS 
Published: October 2007

SummaryImmunogens based upon sequences from the P. falciparum asexual blood stage antigen Pf332 were assessed for their capacity to induce antibodies inhibiting parasite growth or cytoadherence of infected erythrocytes in vitro. Selection of the Pf332 sequences was based on their reactivity with the human monoclonal antibody (MoAb) 33G2 which inhibits parasite growth as well as cytoadherence in vitro. Octameric multiple antigen peptides (MAP) were assembled based upon either a trimer of the minimal epitope recognized by the MoAb, VTEEI, or a Pf332 sequence including that motif, SVTEE1AEEDK. A dimer of SVTEEIAEEDK was also expressed in Escherichia coli, genetically fused to ZZ, two IgG‐binding domains of staphylococcal protein A. Rabbit antibodies elicited by the immunogens reacted with Pf332 in immunofluorescence and in ELISA with Pf332 peptides which were also recognized by MoAb 33G2. The MAP with branched (VTEEI)3 peptide induced the highest litres of P. falci‐pamm‐reactive antibodies. In contrast to MoAb 33G2, none of the polyclonal Pf332 reactive sera cross‐reacted with repeat sequences of the malaria antigen Pf155jRESA. The polyclonal Pf332‐reactive antibodies inhibited parasite growth efficiently but had no or very low inhibitory effect in a cytoadherence assay. Thus, while Pf332 may be an important target for parasite neutralizing antibodies its involvement in cytoadherence is unclear.
Reactive nitrogen intermediates implicated in the inhibition of Encephalitozoon cuniculi (phylum microspora) replication in murine peritoneal macrophages
Authors: DIDIER ELIZABETH S. 
Published: October 2007

SummaryEncephalitozoon cuniculi (phylum microspora) is a protozoan parasite that can replicate within parasitophorous vacuoles in macrophages. Thioglycollate‐elicited BALBjc peritoneal macrophages treated with murine recombinant interferon‐γ (rIFN‐γ; 10u/ml) in combination with lipopolysaccharide (LPS; 10ng/ml) for 24 h killed E. cuniculi as determined by significant reductions in the number of parasites and percent of infected macrophages 48 h later compared with cultures treated with medium only. Treatment of the elicited macrophages with murine rIFN‐γ (10u/ml or 100u/ml) only, resulted in microbistatic activity. Significantly higher levels of nitrite (NO2) were detected in supernatants from macrophage cultures treated with rIFN‐γ (10 u/ml or 100 u/ml) which induced microbistatic macrophage activity as well as from macrophage cultures treated with LPS + rIFN‐ when compared with levels of nitrite detected in supernatants of infected macrophages treated with medium only. Addition of the L‐ariginine analogue, N3 monomethyl‐L‐arginine (NMMA) at concentrations of 50, 100 or 250 uM significantly inhibited nitrite synthesis and prevented microsporidia killing. Addition of exogenous L‐arginine at concentrations of 5mM or 10 mM reversed the NMMA‐induced inhibition of parasite killing. These results indicate that reactive nitrogen intermediates contribute to the killing of E. cuniculi by LPS + rIFN‐γ‐activated murine peritoneal macrophages in vitro.
The combined epidermal growth factor‐like modules of Plasmodium yoelii Merozoite Surface Protein‐1 are required for a protective immune response to the parasite
Authors: LING I.T. , OGUN S.A. , HOLDER A.A. 
Published: October 2007

SummaryWe have reported previously that immunization with a bacterial recombinant protein containing the two epidermal growth factor (EGF)‐like modules of Plasmodium yoelii Merozoite Surface Protein‐1 (MSP‐1) protected miced against challenge with this malaria parasite. Bacterial plasmids containing sequences coding for the individual modules fused to glutathione S‐transferase (GST) have now been made. The fusion protein containing the combined EGF‐like modules was recognized by anti‐parasite antibodies and was immunogenic, producing high litre anti‐parasite and anti‐GST antibodies. In contrast, fusion proteins containing the two individual EGF‐like modules reacted poorly with the natural antibodies and their proteins, as well as a simple mixture of them, induced low levels of anti‐parasite antibodies despite producing high levels of anti‐GST antibody. Antibodies raised to the recombinant proteins recognized the 230 kDa MSP‐1. Groups of mice immunized with the different recombinant proteins were challenged with parasites: protection was observed in the group which had received the recombinant protein containing both modules but not in those groups immunized with the individual modules, either alone or as a mixture. These results suggest that there are important structural determinants formed by the two modules together, which are not present in either of the individual domains alone, and which are responsible for the immunogenicity of the protein or are the target of protective antibodies.
Comparative phenotypic analysis of lymph node cells in mice after infection or vaccination with normal or ultraviolet‐attenuated cercariae of Schistosoma japonicum or S. mansoni
Authors: LÜ F.L. , GUI M. , FILSINGER S. , HANSCH G.M. , RUPPEL A. 
Published: October 2007

SummaryMice were infected with 200 untreated or vaccinated with 500 ultraviolet‐attenuated cercariae of either Schistosoma japonicum or S. mansoni. For three weeks, cell numbers in axillary and mediastinal lymphnodes were counted and cell populations typed by cytofluorometry. In the axillary lymphnodes, numbers of B‐cells and CD3+CD4+ T‐cells but not CD3+CD8+ T‐cells increased. Following vaccination with either species, parasite migration was apparently delayed in the skin and interrupted at the lungs, the lymphnodes gained weight, and cell numbers of axillary lymph nodes increased more than after infection. In mediastinal lymphnodes, only immunization with S. japonicum but not S. mansoni cercariae led to an increase of CD3+CD4+ T‐cells. Following infection, both schistosome species induced higher CD3+CD4+, but not CD3+CD8+ T‐cells in mediastinal nodes, and the peak was earlier with S. japonicum (about seven days after infection) than with S. mansoni (about 10 days). In analogy to T‐cell observations by others using a gamma‐attenuated cercarial vaccine in S. mansoni, the present results suggest that CD3+CD4+ cells also play a role in the ultraviolet‐attenuated vaccine against S. japonicum.
Susceptibility to Plasmodium berghei infection in rats is modulated by the acute phase response
Authors: VREDEN STEPHEN G.S. , BROEK MARIES F. VAN DEN , OETTINGER MARIA C. , BOERS WILLEM , ROOIJEN NICO VAN , MEUWISSEN JOEP H. E. T. , SAUERWEIN ROBERT W. 
Published: October 2007

SummaryBrown Norway (BN) and Sprague Dawley (SD) rats are known to differ in their susceptibility to infection with sporozoites of Plasmodium berghei, as measured by the density of liver schizonts. Because of the known inhibitory effect of non‐specific immunomodulators on schizont development, we compared some aspects of the acute phase response in these two rat strains. LPS induced IL‐6 production was measured in supernatants of spleen cells and peritoneal macrophages of both strains. SD rats, which are the least susceptible to P. berghei sporozoites, showed significantly higher IL‐6 production by macrophages from both sources. When LPS was administered in vivo, SD rats also had a significantly higher IL‐6 response. Hepa‐tocytes from both strains were cultured in the presence of IL‐6. After three days of culture, α2‐Macroglobulin concentrations in the supernatants of SD hepatocytes were much higher than those from BN rats. Kupffer cell depletion in both BN and SD rats was correlated with a significant increase in liver schizont density, but did not abrogate the difference in susceptibility. From these results we conclude that the higher cytokine production capacity of SD rats compared to BN rats, may contribute to the difference in susceptibility to P. berghei sporozoites between these strains, but that other yet unknown factors are also involved.
Specific lgG1 and lgG2 antibody responses of dogs to Leishmania infantum and other parasites
Authors: DEPLAZES P. , SMITH N. C. , ARNOLD P. , LUTZ H. , ECKERT J. 
Published: October 2007

SummarySera from dogs naturally infected with Leishmania infantum were analysed for the IgG subclass specificity of their antibody response by ELISA. Dogs infected with L. infantum produced both IgGl and IgG2 antibodies with IgG2 being associated with asymptomatic infections and IgGl being associated with disease (symptomatic dogs, non‐ or low‐responsive to chemotherapy). The differential responses of IgG] and IgGl serum antibodies in asymptomatic and symptomatic dogs may indicate a dichotomous immune response to infection with L. infantum. To confirm this, on a broader scale, sera from dogs naturally exposed to an asymptomatic protozoan infection, Toxoplasma gondii, were also analysed as were sera from dogs exposed to the helminths, Dirofilaria immitis and Toxocara canis. Antibodies specific for T. gondii antigen detected in sera from 17 dogs were of the IgG2 subclass only. Both IgGl and IgG2 antibodies to D. immitis andl. canis were present in the sera of naturally infected dogs but IgGl appeared to be the predominant subclass. Furthermore, in dogs experimentally infected with T. canis, selective regulation ofIgG2 and IgGl responses was apparent since production of the two subclasses occurred at different times following infection, with IgGl levels declining as IgGl levels rose. Thus, the analysis of IgG subsets in parasitized dogs provides evidence of a dichotomous response to infection: IgGl is associated with asymptomatic protozoan infections and IgGl is associated with helminth infections and disease caused by protozoan infection.
Resolution of Cryptosporidia! infection in mice correlates with parasite‐specific lymphocyte proliferation associated with both Th1 and Th2 cytokine secretion
Authors: TILLEY M. , MCDONALD V. , BANCROFT G. J. 
Published: October 2007

SummaryThis study was designed to investigate and characterize T‐cell responses which lead to elimination of a primary infection of Cryptosporidium muris in BALBjc mice. The proliferative response of spleen cells to parasite antigen was measured by uptake of 3H‐thymidine and, in parallel, supernatants were removed from cells to measure levels oflFN‐γ, TNF, IL‐2 and IL‐4 by ELISA. Oocyst excretion in faeces was first detected on day 10 post infection (p.i.); the level of shedding subsequently increased until day 14 and then declined until no oocysts were detected by day 25. The proliferative response of spleen cells from infected animals was similar to control levels up to day 14p.i. but increased significantly on day 21 and was even greater on day 26. IFN‐γ and IL‐2 were detected initially on day 14 p.i. and significantly higher concentrations were found on days 21 and 26. IL‐4 secretion was also detected, but not until day 21 p.i., and production of TNF was not found at any time. Depletion of T‐cells or CD4 + cells from spleen cells cultured with antigen resulted in a significant decrease in the levels of cytokine detected. These results indicated, therefore, that in BALB/c mice there was a correlation between the development of immunity to C muris infection and both a parasite antigen‐specific proliferative response and Thl and Th,2 cytokine production by spleen cells
Relationships between maternal malaria and malarial immune responses in mothers and neonates
Authors: RASHEED F. N. , BULMER J. N. , DE FRANCISCO A. , JAWLA M. F. B. , JAKOBSEN P. H. , JEPSON A. , GREENWOOD B. M. 
Published: October 2007

SummaryImmune responses of 97 Gambian women and their neonates were studied. New methods distinguished between active and previous placental malaria, were used to examine relationships between maternal malaria and neonatal immune responses. Many placentas (61%) had active or previous malarial infection. Maternal and cord malarial IgG levels correlated (P < 0–001). Malarial IgG was raised in cord blood in active placental malaria; IgM was not detected. Mean lymphoproliferation and the proportion of responders to soluble P. falciparum antigens (F32) and conserved regions of p190 expressed on trophozoites and schizonts (190L and 190N) were higher in neonates than mothers. There was no clear relationship between maternal malaria and neonatal mean lymphoproliferation to malarial antigens, although fewer neonates responded when mothers were actively infected. Matched maternal and neonatal lymphoproliferation responses did not correlate. However, first born neonatal lymphoproliferation to PPD and malarial antigens appeared lower than other neonates, in agreement with lower lymphoproliferation in primigravidae compared with multigravidae. Also in common with mothers, autologous plasma suppressed neonatal lymphoproliferation to PPD and malarial antigens, suggesting common immunoregulation. Higher Cortisol or other circulating factors in first pregnancies may be implicated. The relevance of cell‐mediated malarial immune responses detected at birth remains to be established.