PubMed Health⌕ Search

Biomedical subjects

G H Mitchell

Publications and source records attributed to G H Mitchell.

At least 55 records · Page 3Linked to original sources
PubMed1982

Circulating immune complexes in Plasmodium knowlesi infected Kra, and merozoite vaccinated Rhesus monkeys.

The presence of circulating soluble immune complexes that bind the C1q component of complement has been determined in the sera of two monkey species showing different degrees of clinical immunity to Plasmodium knowlesi infection. Material binding C1q was found in the serum of both primarily infected Kra monkeys and post-vaccinated immune Rhesus monkeys following the onset of parasitaemia. The complexes then disappeared from the circulation of Kra monkeys despite continuing low-grade parasitaemia, but in Rhesus monkeys C1q binding material remained detectable for up to 3 weeks after apparent elimination of parasites. The ability of complexes to bind C1q was removed by reduction and alkylation and binding material was absorbed by staphylococcal protein A suggesting the presence of Ig. Further analysis of the binding material is required to fully establish its constitution and possible immunoregulatory function at different stages of infection in the two monkey species.

Animals↗
PubMed1980

Long term cultivation of a simian malaria parasite (Plasmodium knowlesi) in a semi-automated apparatus.

An apparatus is described and illustrated for the continuous semi-automated cultivation of Plasmodium knowlesi. The change of medium was automated and involved six operations. Parasites were maintained for 12 weeks, at which time the experiment ended. During this period, parasite density, morphology and serological specificity were monitored. Parasites retained synchromy and normal morphology only for the first cycle in culture. The maximum degree of morphological abnormality (90%) was reached at three weeks. Lysis of infected erythrocytes seemed to occur before full maturation of the parasites. Infected cells cultured for 31 days produced a normal, fulminating infection in a rhesus monkey.

Animals↗
PubMed1979

Nor-MDP, saponin, corynebacteria, and pertussis organisms as immunological adjuvants in experimental malaria vaccination of macaques.

Vaccination of primates against malaria using antigen derived from erythrocytic parasite stages has been most successful where Freund's complete adjuvant has been employed. Since this adjuvant is clinically unacceptable its replacement is a matter of urgency.In the present work a muramyldipeptide derivative (nor-MDP) given in mineral oil has proved to be partially effective as an adjuvant for merozoite vaccination of Macaca mulatta against Plasmodium knowlesi, and saponin has proved to be effective in similar vaccination of M. fascicularis.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1978

Antibody mediated mechanisms of immunity to malaria induced by vaccination with Plasmodium knowlesi merozoites.

Rhesus monkeys vaccinated with merozoites in FCA are protected against challenge with several strains and variants of Plasmodium knowlesi. Vaccination induces sterilizing immunity which is species specific. Merozoite-blocking (inhibitory) antibody usually correlates with clinical immunity and protection can be passively transferred with immune sera provided these contain high levels of inhibitory antibody. However, vaccination using adjuvants other than FCA may induce inhibitory antibody without clinical protection. In addition, vaccinated animals may become susceptible to challenge 4-5 weeks after splenectomy, although inhibitory antibody levels are not reduced. These observations indicate that immunity induced by merozoite vaccination involves: (i) merozoite blocking (inhibitory) antibody, (ii) specific antibody or immune complexes acting synergistically with cytotoxic splenic cells stimulated by FCA.

Animals↗
PubMed1977

Merozoite vaccination of douroucouli monkeys against falciparum malaria.

Erythrocytic merozoites of Plasmodium falciparum (Gambia) were isolated from cultures of schizont-infected human red cells on CF 11 cellulose columns. Douroucouli monkeys vaccinated with such preparations stored in liquid nitrogen and then emulsified in Freund's complete adjuvant (F.C.A.), were resistant to successive challenges with West African (Lagos) and East African (Uganda Palto-Alto) strains of P. falciparum. The induced immunity is specific since vaccination with P. knowlesi merozoites in F.C.A. does not modify the course of P. falciparum infections in douroucouli monkeys.

Animals↗
PubMed1977

A review of metozoite vaccination against Plasmodium knowlesi malaria.

Techniques for the isolation of merozoites of Plasmodium knowlesi malaria have allowed their use in experimental vaccines. Rhesus monkeys were protected to a very great extent from otherwise lethal challenge with this malaria when Freund's Complete Adjuvant was a vaccine component.

Animals↗
PubMed1977

Recent advances in understanding the invasion of erythrocytes by merozoites of Plasmodium knowlesi.

Previous observations on the process of invasion by P. knowlesi are briefly reviewed and new findings concerning the adhesion of parasites to erythrocytes and their intracellular passage are reported. Merozoites adhere to erythrocytes by means of a well-defined coat with the cytochemical characteristics of glycoprotein. This coat has receptors that engage in at least three distinct types of attachment. The ensuing invagination of the erythrocyte surface has two phases, the first consisting of an inward buckling of the membrane to form a vacuole and the second a rapid expansion to create the final parasitophorous vacuole inhabited by the trophic parasite. Some cytochemical evidence concerning the nature of the rhoptry complex is discussed in relation to these changes.

Adhesiveness↗
PubMed1976

The effect of human immune IgG on the in vitro development of Plasmodium falciparum.

Plasmodium falciparum parasites infecting Aotus trivirgatus erythrocytes were cultured in media (Harvard and TC199) augmented with human, foetal calf, or other sera. Conditions were established which supported growth of parasites and allowed cyclical multiplication when fresh erythrocytes (from Aotus or Homo) were added in sub-culture (mean multiplication rate: X3). Immunoglobulin G pools, prepared from plasma collected in endemic malarious areas in Africa and from unexposed Britons, were tested for effects on the in vitro growth (measured by incorporation of tritiated leucine) and multiplication of parasites. Whilst non-immune IgG was without effect, IgG from both East and West Africa inhibited the multiplication of East African (Uganda-Palo Alto strain) parasites.

Animals↗
PubMed1975

In vitro isolation of Plasmodium knowlesi merozoites using polycarbonate sieves.

A culture chamber fitted with a polycarbonate sieve has been used to isolate Plasmodium knowlesi merozoites as they are released from schizonts. A 3 mum pore-size sieve allows passage of normal erythrocytes and red cells containing rings and trophozoites and can be used to concentrate schizonts from a mixed cell population. A 2 mum pore-size sieve retains normal and parasitized cells and provides uncontaminated merozoites in high yield (5 x 10(10) merozoites per ml schizonts). Merozoite viability diminishes rapidly during 30 min after isolation. These preparations should prove valuable for studies of the biochemical, physiological and antigenic properties of this transient phase of the malaria parasite.

Animals↗
PubMed1975

Structure and invasive behaviour of Plasmodium knowlesi merozoites in vitro.

The structure and invasive behaviour of extracellular erythrocytic merozoites prepared by a cell sieving method have been studied with the electron microscope. Free merozoites contain organelles similar to those described in late schizonts of Plasmodium knowlesi. Their surface is lined by a coat of short filaments. On mixing with fresh red cells, merozoites at first adhere, then cause the red cell surface to invaginate rapidly, often with the formation of narrow membranous channels in the red cell interior. As the merozoite enters the invagination it forms an attachment by its cell coat to the rim of the pit, and finally leaves this coat behind as it is enclosed in a red cell vacuole. Dense, rounded intracellular bodies then move to the merozoite periphery, and apparently rupture to cause further localized invagination of the red cell vacuole. The merozoite finally loses its rhoptries, the pellicle is reduced to a single membrane and the parasite becomes a trophozoite. Invasion is complete by 1 min after adhesion, and the trophozoite is formed by 10 min.

Cell Membrane↗
PubMed1975

Merozoite vaccination against Plasmodium knowlesi malaria.

Free malarial merozoites isolated from in vitro cultures of P. knowlesi and emulsified with Freund's complete (FCA) or incomplete (FIA) adjuvant were used to vaccinate twelve Rhesus monkeys against the uniformly lethal infection caused by P. knowlesi. Initial challenge of six monkeys with the same parasite variant as used for vaccination produced no detectable infection in three monkeys, while three others developed low-grade parasitaemia (maximum 1.5 per cent), which terminated after 6-11 days. Vaccination with merozoites in either FCA or FIA induced protection against homologous variant challenge. Six other monkeys were challenged first with a parasite variant different from that used for vaccination. Two animals immunized with merozoites in FIA alone or in FCA on only one occasion developed fatal infections. The other four animals vaccinated at least twice with merozoites in FCA showed low-grade parasitaemia (maximum 1.5 per cent) which terminated after 8-12 days. Eight monkeys rechallenged on eleven occasions at intervals of up to 16 weeks were completely resistant to several variants and a distinct laboratory strain of P. knowlesi, but developed chronic malaria similar to that in unimmunized controls when challenged with a different species of malaria, P. cynomolgi bastianellii. It is concluded that merozoite vaccination of Rhesus monkeys induces immunity against the erythrocyte stages of P. knowlesi far greater in degree and significantly broader in variant specificity than that achieved by previous methods of immunization or by repeated drug-controlled infections.

Animals↗