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Biomedical subjects

S R Smithers

Publications and source records attributed to S R Smithers.

At least 73 records · Page 4Linked to original sources
PubMed1979

Murine Schistosomiasis mansoni: anti-schistosomula antibodies and the IgG subclasses involved in the complement- and eosinophil-mediated killing of schistosomula in vitro.

Protein A-sepharose affinity chromatography was used to isolate IgG subclasses from the serum of CBA mice chronically infected with Schistosoma mansoni. The subclasses were tested for the presence of two antibodies which are responsible for the death of young schistosomula in vitro; 'lethal antibody' (LA), which kills schistosomula in co-operation with complement and 'eosinophil adherence antibody' (EAA) which causes the death of schistosomula by promoting the adherence of eosinophils to the parasite. LA and EAA were detected only in the IgG fraction of the serum. LA was concentrated in the IgG2a fraction and EAA in the IgG1 fraction. The development of IgG subclasses specific for schistosomula was followed in mice exposed to twenty cercariae by the fluorescent antibody technique. IgG1, IgG2a and IgG2b antibodies were detected 2 weeks after infection and their titres rose steadily to reach high levels by weeks 12 or 14. IgM antibody was not detected until week 6 and IgA until week 10; both were present at lower concentrations than the IgG1 antibodies.

Animals↗
PubMed1978

Complement-mediated killing of schistosomula of Schistosoma mansoni by rat eosinophils in vitro.

Eosinophils from the peritoneal cavity of normal rats, in the presence of fresh normal rat serum (NRS), adhered to schistosomula of Schistosoma mansoni in vitro and killed the majority of parasites within 18 h. The reaction differed from the previously described antibody-mediated eosinophil adherence to schistosomula which occurs in heat-inactivated immune rat serum (IRS) and where adherence is mediated through Fc receptors. Adherence of eosinophils in fresh NRS was shown to be due to the activation of complement at the schistosomular surface by the alternative pathway, and it was effected through C3 receptors. The ability of eosinophils to kill in Fc-mediated adherence. This enhancement of killer activity may be due to the generation by complement activation of eosinophil chemotactic factors which increase the concentration of cells at the target surface. It is suggested that eosinophil adherence mediated through complement activation could be the principla mechanism of destroying schistosomula in the host.

Animals↗
PubMed1978

Mannosyl transferase activity in homogenates of adult Schistosoma mansoni.

Homogenates of adult Schistosoma mansoni contain enzymes which are capable of transferring [14C]mannose from GDP[U-14C]mannose to a lipid acceptor which migrates as a single peak on a silica gel thin-layer plate. This lipid may belong to the class of polyprenol monophosphates which are intermediate elements in the glycosylation of nascent proteins. The schistosome mannosyl transferase activity is associated with membranous particles and is dependent on the presence of Mn2+. However, other divalent metals such as Mg2+ or Ca2+ can, in decreasing order of efficiency, replace Mn2+. When UDP[U-14C]glucose was incubated with the homogenates in the same conditions, relatively little label was transferred to the lipid acceptor. Live worms incubated in a medium containing GDP[U-14C]mannose seem to incorporate the label preferentially on the tegument and on adjacent subtegumental structures. By adding foetal calf serum to the medium, incorporation of the label can be stimulated.

Animals↗
PubMed1977

Host antigens and parasite antigens of murine Schistosoma mansoni.

An indirect fluorescent antibody technique was used to detect mouse host antigens and parasite antigens on the surface of Schistosoma mansoni. A rabbit anti-mouse rbc antiserum to detect host antigens, and serum from mice immune to S. mansoni was used to detect parasite antigens. Schistosomula prepared after penetration of isolated mouse skin did not possess host antigens but bound antibody from immune serum (immune antibody); schistosomula recovered from the lungs of mice five days after infection possessed host antigens and failed to bind immune antibody. In contrast, schistosomula recovered from the skin of normal or immune mice three and 20 hours after cercarial penetration, adult worms, and cryostat sections of adult worms, were positive for host antigens but also bound immune antibody. Strong binding of immune antibody only occurred with the cryostat sections. Anti-schistosome antibody can therefore bind to schistosomes in the presence of host antigen. The lung forms of schistosomula however, may have different surface properties as there is no evidence that immune antibody binds to these forms.

Animals↗
PubMed1977

Schistosoma mansoni: a comparative study of artificially transformed schistosomula and schistosomula recovered after cercarial penetration of isolated skin.

A comparison was made of the ultrastructure, development and antigenic nature of the surfaces and of the viability of three types of Schistosoma mansoni: schistosomula formed after cercariae had penetrated isolated skin (SS) schistosomula produced after mechanical separation of cercarial tails from bodies (MS), and schistosomula transformed from cercariae after incubation in fresh rat serum (RS). Within 2h of transformation, the surface membranes of all three types of schistosomula had changed from trilaminate to heptalaminate structures and SS and MS had lost their cercarial glycocalyx. Initially a dense amorphous material was demonstrated on the surfaces of RS, which was thought to be the result of an interaction between a factor in rat serum and the glycocalyx; this material was greatly reduced within 2 h of transformation. The pre-acetabular glands of SS were emptied while those of MS and RS retained their contents. Immunofluorescent studies showed that all schistosomula bound serum from mice immune to S. mansoni, but the binding was stronger with MS and RS. The mixed agglutination reaction demonstrated the presence of human A and B blood group-like antigenic determinants on approximately 30% of 3h old SS; these determinants were not detected on MS or RS. In vitro, the development of MS and RS was similar to SS; the first schistosomula reached the "gut-closed" stage by day 10; 50-70% of SS reached this stage by day 12, in contrast to only 25-50% of MS and RS. Between 28 and 45% of all schistosomula developed to maturity when injected intravenously into mice. It was concluded that the two types of artificially prepared schistosomula fulfil the main criteria of transformation from cercaria to schistosomulum. Further, it is suggested that MS are the most appropriate source of material for immunochemical and physiological studies.

Agglutination Tests↗
PubMed1977

Antibody-mediated adherence of rat eosinophils to schistosomula of Schistoma mansoni in vitro.

Eosinophils from the peritoneal washings of normal rats adhered to live or formalin-fixed schistosomula of Schistosoma mansoni in vitro, in the presence of heat-inactivated serum from infected rats. Eosinophil adherence caused permeability changes in the schistosomula as revealed by 51Cr release and methylene blue uptake. The serum factor which mediated adherence resided in the 7S fraction after Sephadex G-200 gel filtration. Protein A from Staphylococcus aureus which binds specifically to the Fc piece of IgG inhibited adherence, thereby demonstrating that IgG was the antibody responsible for this reaction and that the Fc portion was the site of interaction between eosinophil and antibody; rat eosinophils were shown to possess Fc receptors. The antibody mediating adherence reached high titres in the sera of rats 5-8 weeks after exposure to 500 cercariae, but thereafter there was a gradual decline in titre. Surface membrane from adult S. mansoni inhibited adherence, indicating the presence of cross-reacting antigens in adult worms and schistosomula.

Animals↗
PubMed1976

Acquired resistance to Schistosoma haematobium in the baboon (Papio anubis) after cercarial exposure and adult worm transplantation.

Observations were made on the development of acquired resistance to Schistosoma haematobium in the baboon following immunization with cercariae by the percutaneous route and by the transplantation of adult worms into the mesenteric veins. In the first experiment six baboons were immunized with 1000 S. haematobium cercariae given percutaneously. They were challenged with 10 000 cercariae given 73 weeks later and the results were compared with a similar infection in non-immunized animals. The results showed that the baboon can develop a strong resistance to reinfection with S. haematobium. The manifestations of the immunity were (i) the absence of any increase in egg output after challenge (ii) the substantially lower level of adult worms and eggs in the tissues of the immunized baboons compared with the challenge control animals (iii) a reduction in the egg laying capacity of the residual worms and (iv) the virtual absence of gross pathology and the mild lesions seen in the tissue sections of all the immunized animals. The depression in egg laying of the worms was confirmed by transplanting them into non-immune baboons. This experiment indicated that the non-egg-laying worms in the immune baboons were not irreversibly damaged since they survived, some even migrating to the vesical and ureteric vessels, and egg-laying was rapidly resumed after transplantation. A further experiment was designed to see if a similar degree of immunity could be produced by an adult worm infection without previous exposure to cercariae or schistosomula. The immunization dose consisted of 50-100 S. haematobium worm pairs which were transplanted into the mesenteric veins of each of six baboons and the animals were challenged percutaneously with 7000 cercariae 35-55 weeks later. There was little difference in the worm burdens of the immunized and control animals but the worms in the immunized baboons produced fewer eggs and the pathology seen in these animals was much milder than in the challenge control animals suggesting that some degree of resistance to reinfection was produced by the transplanted worms.

Animals↗
PubMed1976

Acquisition of human blood group antigens by Schistosoma mansoni.

Juvenile forms of Schistosoma mansoni (schistosomula) have been cultured in human blood of various specificities and tested for the presence of blood group substances on their surfaces. The tests employed were survival following transfer into rhesus monkeys immunized against human blood substances, mixed agglutination reactions, and immunofluorescence. A, B, H AND Lewisb+ antigens were expressed at the surface when the parasites were cultured in blood of appropriate specificities. Rhesus, M N S, AND Duffy antigens could not be detected on the parasite surface following culture. The evidence suggests that the expressed blood group antigens are of host origin and are acquired by the parasite during culture, probably in the form of glycolipids or megaloglycolipids. It is likely that these substances are also acquired by parasites in the bloodstream of man. They may serve to mask surface parasite antigens, and so enable schistosomes to evade parasite-specific humoral or cellular immune responses.

ABO Blood-Group System↗
PubMed1976

T-cell helper response to antigens of Schistosoma mansoni in CBA mice.

It is believed that a T-cell helper response against the schistosome surface is a necessary prerequisite for the development of protective immunity in schistosomiasis. Accordingly, the carrier effect has been used to assay eleven antigenic preparations of Schistosoma mansoni for their helper T-cell priming against surface components of the schistosomula. Three weeks after i.v. injection of the preparation, CBA mice were injected with schistosomula coated with trinitrophenol (TNP) and 4 days later, their spleens were assayed for plaque-forming cells (PFC) against TNP. Formalin-fixed schistosomula and crude adult worm tegumental membrane induced the highest response; only thirty schistosomula or 10mug of crude membrane protein were needed to generate a T-cell helper response equivalent to that induced by a living infection. All other antigenic preparations, including formalin-fixed cercariae, live miracidia, eggs and adult worm culture fluid, generated some response indicating the presence of shared carrier components.

Animals↗