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N M Almond

Publications and source records attributed to N M Almond.

14 recordsLinked to original sources

Nematode antigens in protection, diagnosis and pathology.

A thorough study of parasite antigens is a prerequisite for control programmes based on protection by vaccination, accurate serodiagnosis and perhaps immune modulation to diminish pathological sequelae. Stage specific surface secreted and somatic antigens may be of particular value in proceeding towards these goals. The design of vaccines is most appropriately focused on surface antigens. With respect to pathology, certain antigens must stimulate humoral and, or cellular immune responses which are responsible for the undesirable immunopathologic consequences of the disease. The ultimate objective, therefore, is identification of those particular antigens followed by appropriate down regulation of the immune system in order to delete such potentially harmful immunological reactions. The relevant illustration presented in this context is an interesting correlation between one particular clinical condition of onchocerciasis ("sowda") and the serological response, defined both in terms of the parasite antigen and an immunoglobulin class restricted antibody response. Current parasitological methods of diagnosis consistently underestimate parasite prevalence. Failure to detect low level patent infections incurs the risk of having a reservoir capable of perpetuating infections. There is, then, an urgent requirement for accurate serodiagnosis, to be used in association with, and for the evaluation of, drug treatment and vector elimination in parasite control programmes. Given the high sensitivity of current immunoassay technology, the only bar to establishing the necessary immunological tests is the choice of suitably specific antibody-antigen systems. Once these are identified, a combination of recombinant nucleic acid biochemistry and hybridoma technology should provide the necessary reagents for inexpensive, robust and specific diagnostic tests. In addition, it may not be many years before the ubiquitous RIA and ELISA technology gives way to the newly developing biosensor systems. Finally, given the sensitivity and specificity of today's nucleic acid hybridization techniques, we may soon expect to see specific identification of infective larvae in their vectors of this, a cloned DNA probe specific for Onchocerca volvulus, and with potential for the detection of infective larvae in blackflies is described.

Animals↗

Variation in class-specific humoral immune responses of different mouse strains to microfilariae of Dipetalonema viteae.

The class-specific antibody responses of 3 strains of mice (C57/Bl10, BALB/C and CBA/N) known to vary in their ability to control the microfilaraemia which follows the subcutaneous transplantation of adult female Dipetalonema viteae has been investigated. The 3 mouse strains showed significant variation (a) in total levels of immunoglobulins and (b) in ability to recognize individual radio-isotope-labelled antigens as measured by coprecipitation. Within each mouse strain it was noted that antigens could vary with respect to the nature of the isotype of the antibody response which they elicited. Furthermore, by comparing results obtained from class-specific coprecipitation with surface ELISA it was found that a similar variation between responses to individual epitopes was also likely. No differences were observed in the humoral response of the 3 mouse strains which could explain the known resistance of the C57/Bl10 strain; reasons for this are discussed.

Animals↗

Repetitive DNA as a tool for the identification and comparison of nematode variants: application to Trichinella isolates.

DNA prepared from four isolates of Trichinella was compared by genomic DNA cross-hybridisation, by electrophoresis following restriction endonuclease digestion and by hybridisation studies using a cloned repetitive DNA sequence from T. spiralis. The DNA from T. spiralis, T. nelsoni and T. pseudospiralis isolates was distinct and the interrelationships of these isolates were inferred. In contrast to previous work on T. nativa and T. spiralis, our work suggests that these two isolates are very similar.

Animals↗

A comparison of the surface and secretions of Trichinella pseudospiralis and T. spiralis.

Intact, viable adults, infective and newborn larvae of Trichinella pseudospiralis were surface labelled with 125I by the chloramine T method and labelled proteins were compared with those obtained from equivalent stages of T. spiralis. Electron-microscope autoradiography determined that labelled proteins were restricted to the cuticle for all stages of both isolates. Comparative polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate (SDS-PAGE), using thin gradient gel slabs, of proteins obtained from each stage, demonstrated that the profile of surface-labelled proteins of T. pseudospiralis were restricted in number, stage specific, and similar to equivalent proteins of T. spiralis both in size and in their organization into aggregates. The stage-specific profiles of surface-labelled proteins derived from newborn larvae were indistinguishable, but differences were noted between adults and infective larvae of the two isolates. These differences in protein structure were confirmed by two dimensional mapping of tryptic peptides. Stage-specific profiles were also obtained when [35S]methionine biosynthetically labelled secretions of the 3 stages of T. pseudospiralis were compared by SDS-PAGE. Comparison of the profiles obtained with secretions for respective stages of T. spiralis again failed to distinguish newborn larvae, but adults and infective larvae of T. spiralis and T. pseudospiralis displayed a mixture of common and species-specific proteins. These findings are discussed in relation to the different pathology associated with infection with two isolates.

Animals↗

Immunoglobulin class specific responses to biochemically defined antigens of Trichinella spiralis.

A comparison of the humoral response to resistant (NIH) and susceptible (C3H) strains of mice, which reject adult worms at different rates during a primary infection, was made following infection with Trichinella spiralis. The serum concentration of immunoglobulins of the heavy chain classes IgM, IgG1, IgG2, IgG3 and IgA were determined by single radial immunodiffusion. Antibodies of the same immunoglobulin isotypes to biochemically defined, stage specific surface and secreted components of three stages of parasite development were also determined using an isotype specific immuno-coprecipitation assay. Independent variation of the responses of each immunoglobulin isotype was observed. The specific anti-parasite response did not reflect total serum immunoglobulin levels in all immunoglobulin classes, and this is discussed in relation to basic mechanisms of immunoglobulin class switching. Finally a close correlation was observed in resistant (NIH) mice between the production of IgA antibody to surface components of adult worms and accelerated expulsion of this stage of the worm from the gastrointestinal tract. The possible relevance of this IgA response is further indicated by the failure of susceptible mice to synthesise IgA antibodies to the same surface antigens.

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Relationship between non-antigen-specific immunodepression and persisting immune complexes induced by pertussis in mice.

A temporal relationship has been demonstrated between persisting immune complexes and non-antigen-specific immunodepression. Mice were given intraperitoneal injections of Bordetella pertussis at weekly intervals. After 7 weeks they developed circulating immune complexes, the levels of which increased with continued administration of pertussis. The increase in immune complex levels was accompanied by a diminished primary immune response to intraperitoneally injected sheep erythrocytes (SRBC) as judged by a reduction in their direct and indirect plaque-forming cell response and serum agglutination titres. Spleen cells from immunodepressed pertussis-treated mice were transferred to irradiated normal recipients and displayed a normal response to SRBC. By contrast, spleen cells transferred from normal donors to irradiated pertussis-treated recipients had an impaired response to SRBC. Thus, the immunodepression caused by pertussis treatment is a property of the environment and not the lymphocytes themselves. It is considered that chronic circulating immune complexes induced by pertussis administration may cause non-antigen-specific immunodepression.

Animals↗

The response of humans to surface and secreted antigens of Trichinella spiralis.

Biochemically characterised surface and secreted stage specific antigens were used to analyse the response of humans to infection with Trichinella spiralis. Immuno-coprecipitation and SDS-PAGE of labelled proteins were used to dissect the humoral response of Mexican and European infected sera to each component antigen. The results demonstrate that in man, like laboratory rodents, the response to each protein varies independently. In addition, they permit a more rational approach to the development of improved immuno-diagnostic techniques.

Animals↗

The Ig class distribution of anti-phosphoryl choline responses in mice infected with parasitic nematodes.

The anti-phosphoryl choline antibody responses of resistant and susceptible strains of mice infected with microfilariae of Dipetalonema viteae or the gastrointestinal nematode parasite Trichinella spiralis were determined. The responses were characterized both in terms of their kinetics and the constituent role played by each immunoglobulin heavy-chain class. Infection with either parasite elicited detectable responses in all strains investigated. However, the kinetics of the response of each heavy-chain class within each strain could vary independently. Furthermore, differences were observed between the responses of inbred mouse strains that differ in their ability to control infection. It was not possible, however, to correlate these differences in the serological response with the ability of these animals to control infection. The results are discussed in relation to attempts to improve serological diagnostic assays.

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