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D Wakelin

Publications and source records attributed to D Wakelin.

At least 109 records · Page 6Linked to original sources
PubMed1991

Gamma interferon-mediated inhibition of Eimeria vermiformis growth in cultured fibroblasts and epithelial cells.

The growth of Eimeria vermiformis within cultured murine fibroblastlike (L-929) or rat epithelial-like (RATEC) cells was inhibited by treatment of the cells with the appropriate recombinant gamma interferon. The effect was apparent as a reduction in both the initial numbers of intracellular sporozoites and, to a much greater extent, the numbers of subsequent developmental stages. Pretreatment of the host cells was more effective than treatment in the early postinvasive period, and recombinant gamma interferon had no effect on the development of the parasite if added 24 h or later after the inoculation of sporozoites. Incubation of sporozoites in medium containing recombinant gamma interferon in no way affected their ability to invade or to grow within host cells. These findings indicate that the inhibitory effects of recombinant gamma interferon on the growth of E. vermiformis are mediated via the host cell and are directed mainly against the transforming sporozoite, although the ability of the sporozoite to invade the host cell was also reduced to some extent. The later developmental stages were refractory to the effects of this lymphokine.

Animals↗
PubMed1991

Immunity and genetics: their relation to control of parasitic zoonoses.

Effective control of parasitic zoonoses will ultimately require a combination of several approaches, including hygiene/sanitation, pasture management, chemotherapy and immunoprophylaxis. Development of vaccines, and other approaches to improving protective immunity, require a detailed understanding of parasite immunogenicity and host immune responsiveness. It is increasingly recognized that there is considerable variation in both of these parameters, and that this variation is genetically determined. Recent studies in this area and the consequences for control are discussed.

Animals↗
PubMed1991

Heterogeneity of murine bone marrow-derived mast cells: analysis of their proteinase content.

The expression of granule proteinases by murine bone marrow-derived mast cells (BMMC) grown in vitro was compared with that of serosal mast cells (SMC) from the peritoneal cavity. The granules in a proportion of BMMC (0.4-13%) and in all SMC were labelled with fluorescent antibodies against rat mast cell protease I (RMCP I). The granules of 1-47% of BMMC and 100% of SMC were labelled with antibodies against a 30,000 molecular weight (MW) murine intestinal mast cell proteinase (MIMCP). Four antigens from BMMC, ranging in MW from 28,000 to 32,000 and a single 28,000 antigen from SMC were detected on Western blot using anti-MIMCP antibodies. Only the 28,000 MW antigens from BMMC and SMC were visualized in blots probed with anti-RMCP I. BMMC grown in the presence of conditioned medium from activated splenocytes or from the WEHI-3B myelomonocytic cell line contained 52-118 ng and 3-25 ng MIMCP/10(6) cells respectively, whereas SMC lacked detectable MIMCP. The selective labelling of the 28,000 MW antigens in BMMC and SMC with anti-RMCP I and the variable expression of this antigen in BMMC as detected by immunofluorescence indicates that BMMC are not a homogeneous population of cells.

Animals↗
PubMed1990

Eimeria vermiformis: differences in the course of primary infection can be correlated with lymphocyte responsiveness in the BALB/c and C57BL/6 mouse, Mus musculus.

BALB/c and C57BL/6 mice are high- and low-responders, respectively, to infection with Eimeria vermiformis, this genetically determined difference being immunologically mediated. In order to identify the level at which response phenotype is determined, the proliferation of mesenteric lymph node cells and their ability to transfer immunity adoptively were investigated in each strain; the development of circulating serum antibodies to E. vermiformis was also determined. In all respects BALB/c mice responded earlier than the C57BL/6 but peak values were similar in both strains. The relationship between the temporal differences noted and the characteristic, differing course of the primary infection in the two strains is discussed.

Animals↗
PubMed1990

Genetic influences upon eosinophilia and resistance in mice infected with Mesocestoides corti.

The genetic influences upon host variation in eosinophilia and resistance to helminth infection, and the relationship between these parameters, was investigated in 9 inbred and 3 hybrid strains of mice infected with Mesocestoides corti. Blood, bone marrow, spleen and peritoneal fluid eosinophilia were far higher in SJL mice than in any other inbred strain. SWR, NIH, C3H and BALB/c mice were high responders to M. corti whereas CBA and 3 congenic strains sharing the B10 background (C57BL/10, B10.S, B10.G) were low responders. Some of the genes for high eosinophil responsiveness appeared to be dominant, as F1 hybrids from high and low response parental strains were intermediate to high in response to infection. SJL and NIH strains were highly susceptible to infection with M. corti, larval burdens at 21 days after infection with 100 tetrathyridia being considerably higher (greater than 1000) than all other strains. BALB/c (congruent to 700 larvae) were designated susceptible, SWR (greater than 400 larvae) were resistant and the B10 congenics (less than 400 larvae) were highly resistant. Genes influencing resistance also appeared to be dominant, as F1 hybrids between resistant and susceptible parental strains were intermediate to resistant on infection. The overall response patterns indicate a direct correlation between susceptibility to infection and high eosinophil responsiveness, but this relationship is not consistent in all strains.

Animals↗
PubMed1990

Genetically-determined influences on the ability of poor responder mice to respond to immunization against Trichuris muris.

Strains of mice poorly (B10) or non-responsive (B10.BR) to a primary infection with Trichuris muris were protected against infection by vaccination with excretory/secretory (E/S) antigen in Complete Freund's Adjuvant (CFA). Protection in these mice was slow to be expressed compared to that in good responder strains. Vaccination boosted the IgG and IgG1 antibody responses to E/S antigen and altered the antigen recognition profiles, three high molecular weight antigens (80-85, 90-95, 105-110 kDa) being recognized by antibodies in sera from vaccinated but not control mice. B10.BR mice which had experienced a patent primary infection could not be protected against challenge infections by vaccination and this was correlated with depressed levels of IgG1, but not total IgG, to E/S antigen early post-challenge compared with vaccinated infected mice which had not seen an adult primary infection. There was also lack of recognition of the three high molecular weight antigens recognized by antibodies in sera from mice infected after vaccination. It is suggested that the rapid development of high levels of IgG1 antibodies, and the recognition of the three high molecular weight antigens, may reflect events that are important in protective immunity. Immunomodulation of host immunity by T. muris may therefore be achieved, at least in part, by the suppression of specific IgG1 levels, the production of an irrelevant IgG isotype and prevention of the recognition of critical antigens.

Animals↗
PubMed1990

Infectivity, antigenicity and host responses to isolates of the genus Trichinella.

Comparisons were made of the infectivity and antigenicity of 4 Trichinella spiralis isolates (S, D, Y, W), of quite different geographical origins, and T. pseudospiralis (P) in rapid- and slow-responder inbred mice. Infectivity was measured by the Index of Reproductive Capacity (ICR) expressed as the ratio between the number of muscle larvae recovered on day 30 post-infection (p.i.) and the numbers of larvae given at infection. Antigen recognition was measured by the degree of proliferation of mesenteric lymph node cells (MLNC) to in vitro stimulation with crude muscle larvae antigen (CMLA) and by the total antibody responses to CMLA at day 25 p.i. as measured by ELISA. Regarding infectivity the isolates fell into two groups, high infectivity (S, D and Y) and low infectivity (W and P). Analysis of CMLA, detergent-stripped (CTAB) and 125I-labelled surface larval proteins was made by SDS-PAGE under reducing conditions. Differences in antigen profiles were seen in all antigen preparations, being most noticeable in CTAB and 125I-labelled proteins from W and P isolates. Antigen recognition by polyclonal infection-derived antisera and by monoclonal antibodies raised against the T. spiralis London strain (L) was studied in the W (Arctic) and S (Spanish) isolates. Polyclonal antisera recognized different antigens in the S and W isolates, as did the monoclonal antibody, although recognition was more restricted. Neither antibody recognized a 64 kDa band in the W isolate which was clearly visible in the others tested.

Animals↗
PubMed1990

The influence of genes mapping within the major histocompatibility complex on resistance to Trichuris muris infections in mice.

Two panels of H-2 recombinant strains of mice were used in an attempt to map the H-2-linked genes which control resistance to infection with Trichuris muris. Response phenotypes could be related to the presence of 'resistance' (q,b) or 'susceptibility' (k,d) alleles at I-A. The influence of these genes was modulated by other alleles, particularly q or d alleles, at the D end of the H-2. Absence of I-E molecules correlated with resistance to infection in some but not all strains studied. Thus the (B10.BR x B10.G) F1 strain which expressed I-Ek gene products was resistant to infection. A study of the time-course of infection in strains of mice expressing q alleles throughout the H-2 on 4 different genetic backgrounds (NIH, SWR, DBA and B10) revealed that most strains were resistant to infection. However, the DBA/1 strain exhibited differential responsiveness, 4 out of 6 individuals harbouring mature adult parasites on day 35 post-infection.

Alleles↗
PubMed1990

Zinc deficiency and zinc repletion: effect on the response of rats to infection with Trichinella spiralis.

The expulsion of a primary infection of Trichinella spiralis was studied in rats fed diets containing (per kg diet) either 3 mg Zn [zinc deficient (Zn-)] or 40 mg Zn [zinc adequate (Zn+)]. A dose of 2000 muscle larvae (ML) impaired weight gain (mg/g body wt) in all groups compared with uninfected controls [eg, 0-7 d postinfection (dpi): infected Zn-, -105 +/- 10 (means +/- SEM); uninfected Zn-, 54 +/- 19 (p less than 0.001)]. In a study with 20.5 ML/g body wt, some Zn- rats were transferred at the time of infection to the zinc-adequate diet. [This was the zinc-repleted group (ZnR).] Both groups retained a group of pair-fed controls (Zn-PF and ZnRPF). The percentage dose established at 7 dpi was similar in all groups (32.5-39.3%) but at 13 dpi recoveries were 19.4 +/- 2.2% for Zn-, 0.1 +/- 0.1% for Zn-PF, 1.6 +/- 0.9% for ZnR, 0.6 +/- 0.2% for ZnRPF, and 4.1 +/- 2.2% for Zn+ (p less than 0.001). Up to 13 dpi, all groups except ZnR lost weight. These results show that zinc deficiency impairs the expulsion of T spiralis in rats.

Animals↗
PubMed1990

Zinc deprivation and zinc repletion: effect on the response of rats to infection with Strongyloides ratti.

The course of a subcutaneous weight-related infection with Strongyloides ratti was followed in rats fed diets containing either 3 mg Zn/kg diet [zinc deficient (Zn-)] or 40 mg Zn/kg diet [zinc adequate (Zn+)]. At 19 d postinfection (dpi) the proportions of larvae persisting in the intestines as adult worms were 52 +/- 2% (means +/- SEM) for Zn-, 39.5 +/- 2.5% for pair-fed Zn- (Zn-PF), and 31.6 +/- 3.2% for Zn+ (p less than 0.001, analysis of variance); some Zn- rats were then transferred to the zinc-adequate diet [This was the zinc-repleted group (ZnR).] Both groups retained a group of pair-fed controls (Zn-PF and ZnRPF). Between 19 and 28 dpi ZnR animals gained weight faster than did Zn- animals and had heavier thymuses relative to body weight. Zinc deficiency enhances the establishment of S ratti larvae in the intestine of rats and alters the characteristics of intestinal expulsion of the nematodes; however, spontaneous cure was achieved by 38 dpi in both Zn- and control groups.

Animals↗
PubMed1990

Distribution of intestinal mast cell proteinase in blood and tissues of normal and Trichinella-infected mice.

A sensitive and specific enzyme-linked immunosorbent assay (ELISA) was developed for mouse intestinal mast cell proteinase (IMCP). Specificity was demonstrated by the absence of immunoreactivity with extracts of isolated serosal mast cells (SMC), or with high concentrations (50 micrograms/ml) of the antigenically similar rat mast cell proteinases I or II. The small and large intestines in normal mice were the major sources of IMCP, there being little or no IMCP in non-mucosal tissues. Concentrations of IMCP in normal (non-parasitized) mice were low, but were increased 100-1000-fold intestines of mice infected 10 days earlier with Trichinella spiralis. The kinetic response of secreted IMCP into the blood of mice following infection with T. spiralis was also studied. Systemic release of IMCP coincided with the immune expulsion of adult worms from the intestine, and peak concentrations (9.45 micrograms/ml IMCP) occurred 9 days after infection. The tissue distribution of IMCP, its secretion into blood, and its enteric accumulation during parasite infection, are consistent with a mucosal mast cell (MMC) source for IMCP. The results are discussed in the context of similar findings for rat mast cell proteinase II.

Animals↗
PubMed1990

MHC-restricted antibody responses to Trichuris muris excretory/secretory (E/S) antigen.

Two panels of H-2 recombinant mice were used in a detailed serological study to analyse the role of H-2-linked genes in the control of the antibody response to excretory/secretory (E/S) antigens of Trichuris muris. An apparent H-2q (I-Aq) restriction on the early development of high levels of IgG1 antibody to E/S antigen was revealed by ELISA. No such restriction was demonstrated for the specific IgG2a response patterns. Recognition of two high molecular weight antigens (90-95 kDa, 105-110 kDa) by IgG antibodies was also shown to be almost exclusively H-2q restricted and may be related at least in part to the high antibody levels seen for H-2q strains of mice. Immune serum from resistant (B10.BRxB10.G) F1 hybrid mice (H-2q/k) containing high levels of IgG1 antibodies specific for T. muris E/S and IgG antibodies which recognized the 90-95 kDa and 105-110 kDa E/S antigens was effective in transferring protection to the non-responsive B10.BR mouse strain as seen on day 35 post-infection (p.i.). It is suggested that the IgG responses described for the generally very resistant H-2q mouse strains may contribute to, but not be an absolute requirement for, protective immunity, antibody-mediated damage facilitating a subsequent cellular attack in certain strains of mice.

Animals↗
PubMed1990

Functional correlations between mucosal mast cell activity and immunity to Trichinella spiralis in high and low responder mice.

Levels of intestinal mast cell protease (IMCP) were quantified in serum, gut tissue and in intestinal fluids taken from mice infected with Trichinella spiralis during primary and secondary infections. The ability to generate a mast cell response was dependent on the response phenotype of the mouse strain used. The mast cell response in rapid responder mice (NIH) occurred sooner and was more pronounced than in either intermediate (SWR) and low responder (B1O) mice. This pattern was also reflected in the concentration of IMCP found in various tissues examined. The correlations between IMCP concentrations in blood, and worm expulsion, are discussed.

Animals↗
PubMed1989

Acanthocheilonema viteae (Dipetalonema viteae) in mice: attempts to correct the low responder phenotype of the BALB/c host.

Attempts were made to correct the low responder phenotype of microfilaraemic Acanthocheilonema viteae (Dipetalonema viteae) infected BALB/c mice through the transfer of immune spleen cells and immune serum from amicrofilaraemic B10 background mice. The transfer of immune cells and serum prior to infection failed to influence development of microfilaraemia in BALB/c recipients. Attempts to alter the course of an established microfilaraemia in BALB/c mice through the transfer of 3 x 10(7) immune spleen cells were unsuccessful but transfer of 3 x 10(8) cells reduced microfilaraemia temporarily. Treating microfilaraemic BALB/c mice with immune serum brought about a rapid reduction in microfilaraemia. This effect was only temporary and numbers of circulating microfilariae returned to control levels within a short time. Repeated serum transfers reduced the microfilaraemia only during the period of treatment. Similar results were obtained when immune serum was given to microfilaraemic, immunodeficient CBA/N mice.

Animals↗
PubMed1989

Infectivity of Trichinella isolates in mice is determined by host immune responsiveness.

A comparison was made of the development, survival and reproduction of 5 isolates of Trichinella spiralis in inbred mice. Low responder C57BL/10 mice allowed worms of all isolates to survive longer and reproduce more successfully than did high responder NIH mice, suggesting that host immunity exerted a dominant influence upon infectivity. One isolate (Is-5 (W) -an arctic isolate) had a markedly lower infectivity than all other isolates, and was selected for more detailed study, together with isolate Is-1 (S) (a temperate isolate) which showed high infectivity. The lower infectivity of Is-5 (W) reflected a more rapid onset of immunity in mice infected with this parasite, immunity reducing the reproductive potential of female worms and causing an early expulsion from the intestine. No evidence of a dose-dependent suppression of immunity was found to explain the higher infectivity of Is-1 (S). Is-5 (W) provided a very rapid mucosal mastocytosis Is-1 (S) elicited higher levels of circulating parasite-specific antibodies than did Is-5 (W). These results are discussed in relation to the interplay of parasite immunogenicity and host immune responsiveness in determining infectivity, and point to the importance of identifying those immunodominant parasite molecules which control the balance of the host-parasite relationship.

Animals↗
PubMed1989

Host predisposition to trichuriasis: the mouse--T. muris model.

Predisposition to trichuriasis in mice is reflected in the inability of certain strains, or certain individuals within strains, to express protective immunity. Poor responders fail to expel worms and harbour chronic patent infections. The mechanisms underlying this phenomenon were studied in poor responder mice challenged after abbreviated or prolonged primary infections. Mice exposed to a complete primary infection were fully susceptible when challenged after the removal of the primary infection by anthelmintic. Failure to expel either infection suggests (a) that non-responsiveness to a primary infection does not reflect an inability to expel worms of a certain size, i.e. is not a consequence of the speed of the immune response in relation to parasite growth and (b) that non-responsiveness is long-lasting. Challenge after abbreviation of primary infections at different stages of worm development showed that persistence of larvae beyond day 21 was critical in determining poor response to reinfection. By inference the same conclusion can be drawn about the inability of such mice to expel primary infections. Serological analysis suggested a relationship between low antibody titres, restricted antigen recognition profiles and resistance to infection. It is suggested that the later stages of parasite development are immunosuppressive; the implications for human trichuriasis are discussed.

Animals↗
PubMed1989

Nature and nurture: overcoming constraints on immunity.

Parasitic infections in man and domestic animals exhibit two striking characteristics (a) their prevalence is high, but infections are unequally distributed among individuals within populations and (b) immunity is often slow to develop and appears, at best, only partially effective. Recent immunological and epidemiological studies suggest that effective immunity can develop, but that high prevalence within populations reflects the operation, not only of socio-economic and climatic factors, or husbandry practices, but also of powerful environmentally induced constraints upon the development of resistance. Immunogenetic studies suggest the operation of additional constraints upon the development of resistance. Immunogenetic studies suggest the operation of additional constraints which reflect individual genetic characteristics, and which influence the ability to develop and express effective immunity. A full understanding of all constraints is necessary before levels of population and individual resistance to infection can be increased; the need for such understanding has become more pressing with the prospect that anti-parasite vaccines may become available. Two aspects of environmentally induced constraints are considered, those arising from nutritional inadequacies and those resulting from exposure to infection in early life. Both are discussed primarily in terms of helminth parasites. Genetically determined constraints are discussed with reference to MHC-restricted recognition of malarial peptide vaccines and in terms of Class II molecule-directed control of T-cell function in Leishmania infections. Genetic influences are also considered from the standpoint of inflammatory cell function, in immunity against intestinal nematodes and in vaccine-induced immunity against Schistosoma. Finally, parasite-induced constraints, particularly those which down-regulate protective responses are discussed briefly.

Age Factors↗