摘要:

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 establis

ISSN:0141-9838    

DOI:10.1111/j.1365-3024.1995.tb00960.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryThe 230 kD gamelocyte/gamete‐specific surface protein of Plasmodium falciparum, Pfs230, is a target of antibodies which inhibit the development of the parasite inside the mosquito vector. A transmission blocking vaccine based on Pfs230 may be a powerful tool for malaria control. As a first step, Pfs230 has been expressed in E. coli as a series of recombinant proteins, fused to maltose binding protein. We have used the fusion proteins to assess cellular and humoral immune responses to Pfs230 in malaria‐immune adult Gambian blood donors; responses to the fusion proteins have been compared with responses to native Pfs230. The tetrapeptide repeat region of the molecule appears to be immunodominant for both antibody‐producing cells and peripheral blood T cells. We postulate that this may represent a mechanism for immune evasion since the N‐terminal repeat region of the molecule is cleaved from the mature protein and shed into the plasma. Responses to fusion proteins representing the seven‐cysteine motifs were correlated within individual donors, suggesting that cross‐reactive epitopes occur within the motifs. Antibody responses to recombinant proteins were poorly correlated with responses to native Pfs230 suggesting that dominant epitopes of the native protein are not adequately represented in the recombinant proteins. Although prokaryotic expression products may be suitable for induction of cellular immune responses to Pfs230, alternative expression systems may be needed for creation of appropriate B ce

ISSN:0141-9838    

DOI:10.1111/j.1365-3024.1995.tb00961.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryCD8+T cells and lysis of parasitized macrophages seem to be important in the resistance to murine leishmaniasis. In the present study, we evaluated peripheral blood mononuclear cell (PBMC) from patients with either cutaneous (CL) or mucosal (ML) leishmaniasis in cell lysis assays using51‐Cr‐labeled Daudi or K562 cells, or autologous antigen‐pulsed macrophages as targets. Results are reported as lytic units (number of cells required for 30% lysis) per million PBMC. Exposure of patient PBMC (n= 12) to lysate from Leishmania amazonensis promastigotes led to an increase in cytotoxic activity compared to unstimulated patient cells against Daudi (81.8 ± 14.9 vs 13.6 ± 5 lytic units (LU) per million PBMC; mean ± SEM) and K562 (65.7 ± 8.4 vs 13.1 ± 5 LU/106PBMC). ML had higher responses than CL in both targets (80–4 ± 11.0 vs 46.4 ± 11.6 LU/106PBMC for K562, and 104.3 ± 23.8 vs 59.3 ± 14.3 LU/106PBMC for Daudi). Normal control PBMC, stimulated with L. amazonensis antigen had 6.32 ± 3.72 LU/106PBMC against Daudi cells and 9.06 ± 2.78 LU/106PBMC against K562. The cell responsible for lysis of the K562 cells was characterized as NK, by means of cell separation employing magnetic beads coupled to antibodies. Addition of recombinant TGF‐β or recombinant human IL‐10 reduced L. amazonensis‐mdwcec? cytotoxicity by 90% and 70%, respectively. Cytotoxicity of antigen‐stimulated PBMC was also demonstrated against autologous L. amazonensis antigen‐pulsed macrophages in the range of 6.7 to 41.7LU/106PBMC. In this system TGF‐β and IL‐10 also decreased the

ISSN:0141-9838    

DOI:10.1111/j.1365-3024.1995.tb00962.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryHuman eosinophilic enteritis (EE) may result from hypersensitivity to the excretory I secretory (ES) antigens of adult Ancylostoma caninum. The origin of several antigens were identified by probing adult A. caninum with mouse monoclonal antibodies (MoAbs), sera from mice vaccinated with ES antigens and sera from human EE patients. Six MoAbs (AC/ES1–6) were produced against ES antigens, two being IgG3 and four IgM. Western blots demonstrated four different antigen specificities: MoAb AC/ES 1 bound strongly to an ES product at about 30kDa; AC/ES 2 recognized a broad band ranging from 50–200kDa; AC/ES 3, AC/ES 5 and AC/ES 6 reacted at about 68 kDa, and AC/ES 4 at about 97kDa. Sections of formalin‐fixed, paraffin embedded adult A. caninum were then incubated with these MoAbs and immunostained by the peroxidase‐anti‐peroxidase (PAP) technique. The target epitope of MoAb AC/ES 1 was found mainly in the oesophageal, amphidial and excretory glands; AC/ES 2 reacted weakly with many structures in the sections; AC/ES 3, AC/ES 5 and AC/ES 6 were specific for excretory glands only, and AC/ES 4 bound to amphidial glands. Sera from immunized mice reacted with all three (especially the excretory) glands and the cuticle. In an indirect assay, worm sections probes with three human EE patient sera demonstrated maximal staining in the amphidial glands. Our findings confirm that ES products of A. caninum include immunogenic glandular secretions which may be involved in the pathogenesis of

ISSN:0141-9838    

DOI:10.1111/j.1365-3024.1995.tb00963.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryThe cellular immune response in sheep to an acute and chronic primary and an acute secondary liver fluke infection were examined by immunohistology of liver tissue and flowcytometry of lymphocytes from the draining hepatic lymph nodes. Ten days after primary infection, portal tract areas surrounding migratory tunnels were infiltrated with CD4+and CD8+lymphocytes with fewer B cells and T19+T cells. Micro abscesses were distributed sporadically in the liver parenchyma and young flukes could be easily observed in the liver tissue free from inflammatory cells. More intensive infiltration of the portal tract areas was observed during a secondary liver fluke infection characterized by a pronounced increase in eosinophils, B cells and CD4+T cells. In addition, there was an increase in MHC class II+fibroblastic‐like cells surrounding the migratory tracts. In contrast to the primary infection, no young flukes were observed in the same tissue areas during the secondary infection. Chronic primary infections were characterized by perilobular fibrosis and a predominance of CD8+and γδ‐TCR+T19‐T cells distributed within fibrotic strands. Distinct B cell follicles were observed in the fibrotic strands and near major bile ducts and necrotic patches. Pronounced lymphocyte infiltration could occasionally be observed surrounding liver fluke eggs lodged in liver tissue. A progressive increase in lymph node weight, cell number and CD4/CD8 ratio was observed in the acute and chronic primary infections. The role of the infiltrating cell populations and possible mechanisms of immune evasion by the parasite are di

ISSN:0141-9838    

DOI:10.1111/j.1365-3024.1995.tb00964.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryThis 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 p

ISSN:0141-9838    

DOI:10.1111/j.1365-3024.1995.tb00965.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY