bluuebunny/crossref_metadata_2025 huggingface dataset:
Zinc deficiency impairs T cell function in mice with primary infection of Heligmosomoides polygyrus (Nematoda)
Authors: SHI HAI NING , E. SCOTT MARILYN , M. STEVENSON MARY , G. KOSKI KRISTINE
Published: October 2007

This study was designed to determine whether severe zinc deficiency would prolong the course of a primary Heligmosomoides polygyrus infection in mice, and whether this could be related to impaired T cell function. Female BALB/c mice were fed a zinc‐sufficient (Zn+; 60 mg/kg), a zinc‐deficient (Zn‐; 0.75 mg/kg) or an energy restricted (PF; 60 mg zinc/kg) diet. After four weeks, some mice in each dietary group were given a primary infection with 100 larvae; nutritional, parasitological and immunological parameters were assayed over the following five weeks. Liver zinc concentrations were significantly reduced in Zn‐ mice compared with Zn+ mice. In certain cases, PF mice also had reduced liver zinc concentrations, showing the negative effects of restricted food intake on zinc status. Zinc deficiency prolonged the course of a primary infection, with the effects being most evident five weeks post‐infection when Zn+ mice had only 40% as many worms as Zn‐ mice. Parasite infection induced strong immunological responses in Zn+ mice in contrast to Zn‐ mice. The reduced production of IL‐4 and IFN‐γ, the reduced peripheral eosinophilia and reduced serum levels of IgE and IgG1 in Zn‐ mice were attributed to the zinc deficiency, whereas the reduced delayed type hypersensitivity response to parasite antigen and reduced production of IL‐5 were in certain instances attributed to reduced energy intake rather than zinc deficiency. These results show that zinc deficiency significantly impairs functions normally attributed to both Th1 and Th2 cell populations, and that these alterations are associated with elevated worm numbers in zinc‐deficient mice.
The role of CD4 cells in protective immunity to Brugia pahangi
Authors: BANCROFT A. J. , GRENCIS R. K. , ELSE K. J. , DEVANEY E.
Published: October 2007

The BALB/c mouse immunized sub‐cutaneously (s.c.) with 45 kRad attenuated third stage larvae (L3) of the lymphatic filarial nematode Brugia pahangi is strongly immune to a challenge infection (75–100% reduction in recovery at day six post challenge). Analysis of spleen cell supernatants from immunized mice re‐stimulated in vitro, with parasite antigen or the non specific T cell mitogen Con‐A reveals a cytokine profile (IL‐4, IL‐5 and IL‐9) which indicates that the Th2 subset of CD4 cells has been expanded. In an attempt to formally prove a critical role for CD4 cells in immunity in this model system, immunized mice were given either anti‐CD4 or anti‐CD8 neutralizing antibodies. Administration of anti‐CD4 antibody had a significant and detrimental effect on the immune response whereas anti‐CD8 antibody had a negligible effect on immunity. The efficacy of antibody in neutralizing their target cells was determined by fluorescence activated cell sorting analysis (FACS). Spleen cells from anti‐CD4 treated immunized mice, when re‐stimulated with parasite antigen had a significantly reduced potential to secrete IL‐4, IL‐5 and IL‐9 in vitro and serum from these mice had reduced levels of parasite specific IgG and IgE. These results demonstrate a critical role for CD4 T cells in host protective immunity to B. pahangi in vivo and strongly suggest that some component of the Th2 response plays an important role in the immune response elicited in this model system.
Vaccination of goats against the trematode Schistosoma bovis with a recombinant homologous schistosome‐derived glutathione S‐transferase
Authors: BOULANGER D. , TROTTEIN F. , MAUNY F. , BREMOND P. , COURET D. , PIERCE R. J. , KADRI S. , GODIN C. , SELLIN E. , LECOCQ J. P. , SELLIN B. , CAPRON A.
Published: October 2007

We assayed the vaccine potentialities of a recombinant S. bovis‐derived glutathione S‐transferase (rSb28GST), member of a molecular family already shown to have protective capacities in the S. mansoni and S. japonicum models. Injection of the rSb28GST in Freund's Complete Adjuvant resulted in good specific IgG responses allowing all the animals to display high antibody titres on the day of experimental challenge with S. bovis cercariae. No statistically significant differences were observed in the faecal egg output. Although tissue egg counts in vaccinated animals were lower than in controls, the difference was not statistically significant, apart from the number of eggs trapped in the liver (P<0·05). Likewise, PCV values remained parallel between the two groups. However, immunized goats gained 1·4 kg of body weight throughout the experiment whereas controls lost 1·2kg (P<0·05). In addition, the mean worm burden, assessed by perfusion 20 weeks after infection, was significantly reduced by 48% in the vaccinated group, the sex ratio being unaffected. It appears that a recombinat homologous protein can affect, in a natural host, the course of an experimental infection with a local strain of S. bovis, by affecting worm viability but not fecundity. These results also point to the striking differences in the effect of vaccination according to animal species. Because it has the capacity to prevent growth impairment due to schistosome pathogenicity, the molecule can be proposed as a valuable tool in the development of vaccine‐based control programs in endemic areas.
A theoretical framework for the immunoepidemiology of blocking antibodies to helminth infection
Authors: WOOLHOUSE M. E. J.
Published: October 2007

Epidemiological 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

We 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

Human 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

The 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

Paired 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

Suppression 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

The 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

Immunogens 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

Encephalitozoon 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

We 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

Mice 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

Brown 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

Sera 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

This 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

Immune 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.
Identification and characterization of excreted/secreted products of Trichuris trichiura
Authors: LILLYWHITE J. E. , COOPER E. S. , NEEDHAM C. S. , VENUGOPAL S. , BUNDY D. A. P. , BIANCO A. E.
Published: October 2007

This study provides the first description of the range and immunogenicity of proteins excreted and/or secreted by living T. trichiura adult worms following their recovery from the human large intestine. Metabolic labelling ofT. trichiura excretory/secretory (ES) products with [35S]‐methionine revealed a range of proteins with prominent components at 52–54 kDa, 35–45 kDa & 17 kDa. In contrast, the major component of unlabelled T. trichiura ES, somatic whole worm and isolated stichosome extracts, and of [35S]‐methionine labelled somatic extracts, was present at approximately 47 kDa. Similarly, the major 43 kDa protein present in unlabelled T. muris ES, somatic worm extract and [35S]‐methionine labelled somatic worm extract, was only weakly detected in labelled T. muris ES. Pulse chase experiments demonstrated that after 20 h, the 43 kDa was a prominent component of T. muris ES. These data suggest that the 43/47 kDa protein of Trichuris adult worms is not a major constituent of newly synthesized ES but is either synthesized at a slower rate than other proteins, or sequestered or stored, most likely in the stichocytes, before release. Immunoprecipitations using a range of sera from T. trichiura‐infec ted individuals demonstrated that many of the ES components are immunogenic. Antibody responses were vigorous in children with intense infections and negligible in parasitologically negative children. There was marked heterogeneity in responses to a 17 kDa antigen, with the age profile of anti‐17 kDa antibody levels reflecting age‐dependent infection intensities at the population level.
Immunity in humans toNecator americanus‐.IgE, parasite weight and fecundity
Authors: PRITCHARD D. I. , QUINNELL R. J. , WALSH E. A.
Published: October 2007

The effect of the humoral immune response on the weight and fecundity of the hookworm Necator americanus was examined in an endemically‐infected human population. There was a highly significant negative correlation between total IgE levels and parasite weight and fecundity, after controlling for any effects of host age and hookworm burden. This correlation was present both at initial treatment and after 2 years' reinfection. There was a similar negative correlation between the number of eosinophils and hookworm weight and fecundity at initial treatment. Correlations with levels of specific antibodies to N. americanus excretory‐secretory products were weaker and not significant, although there was a trend towards negative correlations with anti‐ES IgE. This is the first field evidence for an effective human immune response to N. americanus. Although the mechanism of this effect is not clear, we suggest that total IgE levels reflected the level of Th2 cell activation.
Immunity to Trichinella spiralis transferred by serum from vaccinated mice not protected by immunization
Authors: ROBINSON K. , BELLABY T. , WAKELIN D.
Published: October 2007

Serum antibody responses to infection with the intestinal helminth Trichinella spiralis in mice remain at low levels for the first ten to 12 days, slowly increasing to high litres around day 20. It is thought that antibody, therefore, has a limited role in the primary immune response raised against this infection and this is confirmed by the inability of primary infection serum to transfer immunity adoptively. High‐responder NIH and low‐responder B10 mice were vaccinated with T.spiralis antigen in Freund's complete adjuvant prior to challenge. This procedure conferred significant protection on NIH mice but not B10. Sera from these mice were transferred into recipients before and during challenge infection. Significant levels of protection were obtained in both strains with both homologous and heterologous sera, even though vaccination itself had not resulted in protection of the B10 donor mice. These data indicate that the B10 strain is potentially capable of making a protective immune response against the intestinal phase of T.spiralis.
Nitric oxide inhibits establishment of macroschizont‐infected cell lines and is produced by macrophages of calves undergoing bovine tropical theileriosis or East Coast fever
Authors: VISSER ASTRID E. , ABRAHAM A. , SAKYI LESLEY J. BELL , BROWN C. G. D. , PRESTON PATRICIA M.
Published: October 2007

Nitric oxide (NO) was produced when bovine peripheral blood mononuclear cells (PBMC) or purified, adherent PBMC (macrophages) were incubated in vitro with bovine recombinant interferon gamma (Bo rIFN‐γ). NO was produced by cells from naive, uninfected calves as well as by cells from cattle either infected with or recovered from infection with Theileria annulata or Theileria parva. PBMC of cattle undergoing tropical theileriosis (T. annulata infection) or East Coast fever (T. parva infection) synthesized NO spontaneously in vitro. NO was also induced when PBMC of immune, but not of naive, cattle were cultured with T. annulata macroschizont‐infected cell lines. Macrophages alone were not stimulated to produce NO by such infected cells. In vitro establishment of macroschizont‐infected cell lines was suppressed either by incubating sporozoites with S‐nitroso‐N‐acetyl‐DL‐penicillamine (SNAP), a NO releasing molecule, prior to invasion of PBMC or by pulsing developing cultures of trophozoite‐infected cells with SNAP. Proliferation of established macroschizont‐infected cell lines was not affected by SNAP. Taken together with the well documented roles of NO in neurotransmission, vasodilatation, cell and tissue damage and immunosuppression, the results presented here indicate that NO may not only protect cattle against T. annulata and T. parva but, if produced in excess, play a prominent role in the pathogenesis of tropical theileriosis and East Coast fever.
Specific T cell unresponsiveness in human filariasis: diversity in underlying mechanisms
Authors: SARTONO ERLIYANI , KRUIZE YVONNE C.M. , PARTONO FELIX , KURNIAWAN AGNES , MAIZELS RICK M. , YAZDANBAKHSH MARIA
Published: October 2007

In an attempt to overcome T cell unresponsiveness to filarial antigens, 65 individuals belonging to the three clinical groups of elephantiasis patients, microfilaraemics, and asymptomatic amicrofilaraemics who exhibited unresponsiveness to Brugia malayi adult worm antigen (BmA) were studied. Peripheral blood mononuclear cells were co‐cultured with antigen and one of the following reagents that have been reported to be effective in reconstituting T cell proliferation: interleukin‐2 (IL‐2), interleukin‐7 (IL‐7), anti‐interleukin‐4, anti‐interleukin‐10, anti‐CD2, anti‐CD27, anti‐CD28, indomethacin, phorbol myristate acetate (PMA), or calcium ionophore (A23I87). We were able to overcome antigen‐specific unresponsiveness in only a minority of the individuals studied. Co‐culture with IL‐2, IL‐7, indomethacin and PMA were the only conditions which resulted in enhanced proliferation to BmA in these individuals. In general, unresponsiveness in elephantiasis patients was easier to reverse than in other clinical groups: in 50% of elephantiasis patients, in 12.5% of microfilaraemics and in 20% of asymptomatic amicrofilaraemics. The results indicate that more than one distinct immunological mechanism may account for the antigen‐specific unresponsiveness in individuals exposed to and infected with brugian filariasis.
Acquisition and expression of humoral reactivity to antigens of infective stages of filarial larvae
Authors: BAILEY JOSEPH W. , HIGHTOWER ALLEN W. , EBERHARD MARK L. , LAMMIE PATRICK J.
Published: October 2007

Measurement of anti‐larval responses in filaria‐exposed populations may shed light on the natural history of exposure to Wuchereria bancrofti. Using serum samples obtained by a cross‐sectional survey of 172 individuals from two neighbourhoods in Leogane, Haiti, antibody responses directed against infective stage filarial larvae (L3) were assayed by enzyme‐linked immunosorbent assay (ELISA), immunofluorescence (IFA), and immunoblot for the presence of anti‐larval antibodies. ELISA results indicated that virtually all members of both neighbourhoods mounted an anti‐larval antibody response within the first five years of life, suggesting that exposure to infection is universal. In a multiple linear regression analysis that modelled antibody levels as a function of age, gender, microfilaria status, and neighbourhood (as a proxy for transmission intensity), isotype‐specific antibody levels were found to be significantly influenced by both age and neighbourhood. Antibodies directed against the surface of L3 also were age‐dependent; the prevalence of IgG antibodies detected by IF A was significantly higher in children than in adults. The prevalence of antibody recognition of 16–7 and 72–3kDa L3 antigens on immunoblots was significantly greater for serum samples from microfilaraemic than amicrofilaraemic persons. These results suggest that antibody responses to larval antigens are influenced to varying degrees by age, transmission intensity, and microfilaremia status.
Effect of chemotherapy on immune response to egg antigens of Schistosoma mansoni in chronically infected children from areas of low transmission
Authors: NOYA O. , LOSADA S. , NOYA B. ALARCÓN DE , GONZÁLEZ S. , HERMOSO T. , BALZAN C. , CESARI I.M.
Published: October 2007

In an attempt to identify antigenic molecules from Schistosoma mansoni eggs, a serological study was performed on children of a Venezuelan town (Carabal‐leda) in which the transmission of schistosomiasis had been interrupted two years prior to sera sampling. Infected children received treatment with Praziquantel and, based on the disappearance of eggs in the stools plus negativiza‐tion of the circumoval precipitin test (COPT) one year after treatment, they were classified as either responders or non‐responders to chemotherapy. Western blots of soluble egg antigen (SEA) with a very sensitive chemiluminescent substrate were performed. Sera from responder children recognized a 25kDa band of SEA which diminished significantly after treatment. This was less frequent in non‐responder children. When the sera of responder and non‐responder children were compared before treatment, we found that the recognition of the 40 and 41 kDa proteins could be predictive of response to chemotherapy. All these antigens, used in ELISA‐type techniques, might be of importance in the evaluation and follow‐up of large scale schistosome control programmes.
Suppressor macrophages in Trypanosoma brucei infection: nitric oxide is related to both suppressive activity and lifespan in vivo
Authors: MABBOTT NEIL A. , SUTHERLAND IAN A. , STERNBERG JEREMY M.
Published: October 2007

African trypanosome infections cause immunosuppression in both experimental rodent and natural hosts. One characteristic of this is an eliciting of suppressor macrophages which results in an unresponsiveness in lymphocytes. Macrophages from Trypanosoma brucei‐infected mice have previously been shown to produce high levels of nitric oxide (NO). Using model systems based on in vivo macrophage transfer and drug cure, we have sought to determine the relationship between NO and suppressed lymphocyte responses. Peritoneal macrophages from T. brucei‐infected mice inhibited the Concanavalin A (Con‐A) response of spleen cells from syngeneic recipients 3–4 days after transfer in vivo due to the activity of suppressor macrophages. When macrophage NO synthesis was inhibited either in vitro or in vivo the suppressive effects were partially abrogated. These data provide evidence of a role for NO in mediating immunosuppression during murine T. brucei infection. Suppression in spleens of mice receiving suppressor macrophages was transient, with total recovery of spleen cell mitogen responses six days after transfer. Suppression and recovery was found to coincide with the presence or absence (respectively) of donor macrophages in recipient spleens. When T. brucei‐infected mice were treated with a curative dose of a trypanocide there followed a recovery of lymphocyte responsiveness after a period of 4–5 days, and this directly correlated with a reduction of macrophage NO synthesis to control levels both in vivo and in vitro. The apparent loss of suppressor macrophage activity after 4–6 days in both drug cured animals and recipients of macrophage transfer was shown to be due to NO‐mediated apoptosis of these cells.
Induction of CD4+ and CD8+ T cell responses in efferent lymph responding to Toxoplasma gondii infection: analysis of phenotype and function
Authors: INNES ELISABETH A. , PANTON WENDY R.M. , SANDERSON ANDREW , THOMSON KATHERINE M. , WASTLING JONATHAN M. , MALEY STEPHEN , BUXTON DAVID
Published: October 2007

The kinetics of induction of T cell responses were examined in efferent lymph from a node draining the site of a primary inoculation of Toxoplasma gondii. The numbers of T cells increased after infection, due initially to an expansion of the CD4+ T cell population followed by an increase in the number of CD8+ T cells which coincided with the peak lymphoblast response. Proliferative responses of CD4+ T cells to T. gondii antigen were detectable from day six after infection and immune efferent lymph cells inhibited the intracellular multiplication of T. gondii in vitro. Optimum inhibition was achieved using CD8+ T cells restimulated in vitro, and the effector function appeared to be directed preferentially against the autologous rather than the allogeneic infected target cell. The results provide unique information on the induction of immune responses to T. gondii in vivo and provide evidence that both CD4+ and CD8+ T cells are necessary for the development of protective immunity induced by the S48 strain of T. gondii which is used as a live vaccine in sheep.
Protective effect of low doses of an anti‐IL‐4 monoclonal antibody in a murine model of acute toxoplasmosis
Authors: VILLARD O. , CANDOLFI E. , DESPRINGRE J. L. , DEROUIN F. , MARCELLIN L. , VIVILLE S. , KIEN T.
Published: October 2007

Treatment with an anti‐IL‐4 monoclonal antibody protected susceptible C57BL/6 mice against challenge with an avirulent strain of T. gondii. Antibody therapy with 100 [ig on days 0 and 7 post infection resulted in 100% survival of C57/BL6 mice infected orally. Survival was dose‐dependent. Treatment prolonged parasitaemia but did not alter tissue parasite load. Increased serum IgG2a and IFN‐γ levels, together with low levels of IgG1, in mice treated with anti‐IL‐4 or an isotype control, indicated a trend towards a predominant Thl response in all survivors. The persistence of an IgE response after treatment suggests that endogenous IL‐4 was only partly neutralized or that other factors can induce the production of IgE in murine toxoplasmosis.,
Physician and patient survey of allergic rhinitis: methodology
Authors: Higgins V. , Kay S. , Small M.
Published: October 2007

Methodology for Disease Specific Programme (DSP©) surveys designed by Adelphi Group Products is used each year to survey patients and physicians on their perceptions of treatment effectiveness, symptoms and impact of diseases. These point‐in‐time surveys, conducted in the USA and Europe (France, Germany, Italy, Spain and UK), provide useful information on the real‐world management and treatment of diseases. This paper describes the methodology for the DSP survey in allergic rhinitis, detailing the preparation of materials, recruitment of physicians, data collection and data management.
A survey of the burden of allergic rhinitis in the USA
Authors: Schatz M.
Published: October 2007

Background:  A prospective, cross‐sectional, international survey was conducted among patients and physicians to identify symptom perception and the impact of allergic rhinitis (AR) on health‐related quality of life (HRQoL). This paper presents the results from the USA.

Methods:  Data were recorded by 447 patients and matched with data collected on these patients by primary care physicians or specialists. Tests to confirm a diagnosis of AR had been performed on 345 (77.2%) patients. Because of the intermittent nature of the disease, both physicians and patients recorded the presence, severity and impact of symptoms at the time of consultation, in addition to symptoms frequently, but not currently, present. Health‐related quality of life was assessed using the Mini Rhinoconjunctivitis Quality of Life Questionnaire.

Results:  According to the physicians’ assessment, a large proportion of patients had moderate or severe disease (62.6%; n = 280), persistent disease (47.0%; n = 213) and comorbidities such as asthma (28.4%; n = 127). Comparison of the physicians’ and patients’ assessment of disease severity found that patients rated their disease as more severe than physicians across all three types of AR (P < 0.001). At the time of the consultation, 44.0% (n = 197) of patients were suffering from nasal and ocular symptoms, and 23.7% (n = 106) of all patients reported that their current nasal and ocular symptoms were moderate or severe in nature. More than 50% of the patients surveyed (56.4%; n = 252) were using two or more medications for their AR. Health‐related quality of life correlated negatively with the number of symptom‐free days in the previous 4 weeks. Allergic rhinitis had a significantly greater impact on patients with more persistent disease compared with those with intermittent disease (2.3 ± 1.3 vs 1.4 ± 1.1; P < 0.001); nevertheless, approximately two‐thirds of patients with intermittent disease reported some impairment of their professional or daily life as a result of AR.

Conclusions:  The results of this survey highlight the unmet needs of the many patients in the USA who present during routine care with moderate or severe and/or persistent disease and an associated high symptom burden and impaired HRQoL.
Fungal skin infections among prison inmates in Abakaliki, Nigeria
Authors: Oyeka C. A. , Eze I. I.
Published: October 2007

Of 402 prison inmates screened for fungal skin lesions, 79 (19.7%) showed skin lesions, which proved mycologically positive by microscopy and culture. Dermatophytes were responsible for skin lesions in 61 (77.2%) of the inmates, while non‐dermatophytes accounted for 18 (22.8%) of the lesions. The dermatophytes recovered were mostly anthropophilic and included Trichophyton rubrum 33 (41.8%); T. mentagrophytes var. interdigitale 3 (3.8%); T. tonsurans 3 (3.8%); T. violaceum 2 (2.5%); Epidermophyton floccosum 10 (12.7%). A zoophilic dermatophyte, Microsporum canis, was recovered from 10 (12.7%) cases. The non‐dermatophytes were Candida albicans 15 (19%) and Candida spp. 3 (3.8%). Trichophyton rubrum was the most frequently recovered dermatophyte (41.8%) and caused infections in a variety of sites. The groin was the most common site of infection being infected in 50% of the cases by both the dermatophytes and non‐dermatophytes. Younger inmates (17–24 years) recorded the highest prevalence of infection (45.6%). Newer inmates (>2 years) were found to be more infected than older ones.