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Biomedical subjects

M J Stear

Publications and source records attributed to M J Stear.

At least 55 records · Page 3Linked to original sources

Genetic resistance to parasitic infection.

The ability of animals to resist infections with parasites is genetically determined and therefore variable between individuals or breeds of a given host species. Such variation may involve innate (non-immunological) and acquired (immunologically mediated) resistance mechanisms, and is determined by both major histocompatibility complex (MHC)-linked and non-MHC genes. Resistance is inherited as a dominant trait, with heritability often exceeding 0.3. Genetic variation can be exploited to improve the capacity of domestic animals to resist parasitic infection. Methods to achieve this exploitation are discussed in relation to gastrointestinal nematode infections in sheep.

Animals↗

Resistance of four sheep breeds to natural and subsequent artificial Haemonchus contortus infection.

The response of Red Maasai sheep to natural and artificial Haemonchus contortus infections was compared with sheep of Blackheaded Somali, Dorper and Romney Marsh breeds. Significant breed differences in egg count, packed cell volume (PCV), and mortality rates showed that the Red Maasai sheep were more resistant to natural H. contortus infection than sheep from the other three breeds. Of the initial groups of 15 wethers of each breed, two animals from each of the Dorper and Blackheaded Somali groups and nine from the Romney Marsh group died with haemonchosis during a 12 month field study. Following artificial infection of the Red Maasai, Dorpers and Blackheaded Somalis, with 10000 H. contortus L3, the Red Maasai sheep maintained a lower egg output and a higher PCV than animals of the other two breeds. The results clearly showed that breed substitution with the Red Maasai is a control option in areas where sheep are kept for meat and H. contortus is endemic.

Animals↗

Response to artificial and subsequent natural infection with Haemonchus contortus in red Maasai and Dorper ewes.

Maiden Red Maasai and Dorper ewes were kept indoors and artificially infected with a single oral dose of 5000 infective larvae of Haemonchus contortus. Their faecal egg counts (FEC) and packed red cell volumes (PCV) were monitored for 9 weeks. They were then treated with an anthelmintic and turned out to graze together on a pasture contaminated with H. contortus. They grazed this pasture for 14 months and were allowed to mate and lamb. While at pasture the ewes were monitored for FEC, PCV and peripheral eosinophilia. Red Maasai ewes had significantly lower FEC, and for certain periods, significantly higher PCV and peripheral eosinophilia. During the periparturient period, FEC were about twice as high in the Dorper breed as the Red Maasai. These results confirm and extend previous reports on the superiority of the Red Maasai breed in East Africa.

Animals↗

The genetic basis of resistance to Ostertagia circumcincta in lambs.

The relationship between Ostertagia (Teladorsagia) circumcincta and sheep is one of the best understood host-parasite relationships in any species. The key components of resistance have been quantified, the extent of genetic control has been established for lambs, and methods now exist to breed lambs which will be both more resistant to worms and more productive than unselected lambs. A major gene for resistance has been identified within or around the major histocompatibility complex, and this gene appears to be the strongest yet identified for resistance to any parasite species. The most important mechanisms of resistance are local IgA responses which regulate worm fecundity and immediate hypersensitivity responses which regulate worm burdens. IgA responses develop before effective immediate hypersensitivity responses. Good simulation models now exist to predict, for example, outbreaks of disease and the response of sheep to selection. The challenge now is to use our improved understanding of the population biology to develop even better simulation models and to produce expert systems based on these models which can be used by veterinarians and others to determine optimal procedures for individual farms to control disease and reduce sub-clinical economic losses.

Animals↗

Heterogeneity in the recognition of Ostertagia circumcincta antigens by serum antibody from mature, infected sheep.

The recognition of parasite molecules from third-stage and adult Ostertagia circumcincta by serum antibody was studied in a group of matched, mature Scottish Blackface sheep that had been naturally and then deliberately infected. A total of 20 molecules was recognized in somatic extracts from third-stage larvae and 31 molecules in somatic extracts from adult parasites. However, no sheep recognized all immunogenic molecules and no molecule was recognized by all sheep. There was no obvious relationship between recognition of any parasite antigen and polymorphism at class I loci or at the DRBI class II locus of the major histocompatibility complex in these outbred animals. Only 15 molecules from third-stage larvae were present at a frequency suitable for statistical analysis and recognition of three of these 15 molecules was associated with differences in worm burdens. Recognition of two of five molecules from adult parasites was associated with differences in worm length. These results indicate that variation in the recognition of specific, identifiable parasite molecules may be partly responsible for variation among sheep in resistance to O. circumcincta.

Animals↗

Sequence polymorphism in the bovine major histocompatibility complex DQB loci.

Polymorphism in DQB sequences of the bovine major histocompatibility complex was investigated in 22 British Friesian cattle. The first domain exon was amplified, cloned and sequenced. Eight different sequences were identified, six of which had not been identified previously. The high proportion of novel sequences suggests that additional polymorphisms within the DQB loci remain to be discovered in this breed. One sequence was present in at least 21 of the 22 cattle. This sequence, or a closely related sequence, has also been found in American Holstein Friesian, Swedish Red and White and Japanese Black cattle. The remarkably high sequence conservation suggests that the bovine DQB region may contain a locus with a low level of polymorphism and be more similar to the human DQB region than previously supposed. One sequence with three widely spaced frameshift insertions appeared to be a pseudogene.

Animals↗

Natural scrapie in a closed flock of Cheviot sheep occurs only in specific PrP genotypes.

Natural scrapie in a closed flock of South Country Cheviot sheep has resulted in 45 deaths between 1986 and 1995. Of these cases, 35 sheep have been analysed for disease-linked PrP gene polymorphisms and all encode valine at codon 136 on at least one allele with 77% homozygous (VV136) and 23% valine/alanine heterozygotes (VA136). Mean survival time was 907 and 1482 days for VV136 and VA136 scrapie affected animals respectively. VV136 animals were all at great risk of disease if allowed to live long enough. However scrapie occurred only in a specific subgroup of VA136 sheep, survival advantage depending on VA136 animals being heterozygous for other polymorphisms at codons 154 or 171. The flock history has been recorded in great detail since its foundation in 1960 however there was no strong evidence for simple maternal or paternal transmission of disease other than inheritance of PrP genotype.

Animals↗

Class I and class II major histocompatibility complex alleles are associated with faecal egg counts following natural, predominantly Ostertagia circumcincta infection.

During a previous investigation an association was found between major histocompatibility complex (MHC)-DRB1 alleles and faecal egg counts following natural infection predominantly involving Ostertagia circumcincta in a flock of Scottish Blackface sheep. To localise the disease-resistance locus we screened the same flock for an MHC class I microsatellite and a newly developed microsatellite for the DY locus located in the class IIb subregion. Some alleles at both additional loci were associated with resistance to infection. Least-squares analysis of variance indicated that in 6-month-old lambs, substitution of the most common alleles by the alleles associated with resistance would result in an 8- and a 218-fold reduction in faecal egg counts for MHC class I and DY, respectively. These results indicate that genes within the MHC genes play a large and significant role in the development of resistance to a widespread, important and natural parasite.

Alleles↗

An ovine lymphocyte antigen is associated with reduced faecal egg counts in four-month-old lambs following natural, predominantly Ostertagia circumcincta infection.

Ovine lymphocyte antigen is associated with reduced faecal egg counts in 4-month-old lambs following natural, predominantly Ostertagia circumcincta infection. International Journal for Parasitology 26: 423-428. Ten lymphocyte antigens were defined in a flock of Scottish Blackface sheep known to be naturally exposed to infection with Ostertagia circumcincta. Population and family studies suggested that the 10 antigens were products of class I loci. Antigen G13br was in linkage disequilibrium with allele g2 at the DRB1 locus. The g2 allele has previously been associated with reduced faecal egg counts in a different crop of lambs from the same farm. In this study antigen G13br was also associated with a reduction in faecal egg counts. The results provide partial confirmation of the role of the major histocompatibility complex in resistance to natural, predominantly O. circumcincta infection.

Alleles↗

The likelihood of detecting differences between groups of sheep following deliberate infection with Ostertagia circumcincta.

An examination of variation following deliberate infection with Ostertagia circumcincta suggested that even large parasitological differences among groups have little chance of being detected unless the number of sheep in each group is quite large. Tables that give the probability for various sample sizes are presented; these tables should aid the interpretation of previously published results and may assist in the design of future experiments.

Abomasum↗

Evidence for genetic control of vaccine-induced antibody responses in cattle.

The purpose of our study was to identify evidence for genetic control of immune responses in cattle. To address this question, we evaluated the variation of antibody responses induced by vaccination with Brucella abortus Strain 19, a live attenuated bacterial vaccine, in large half-sibling families. The data were analyzed using a parametric statistical model that incorporated the effects of sire, bovine major histocompatibility complex (BoLA) types and parameters related to the experimental design. The BoLA types represented a readily identifiable marker, analogous to those known to be associated with genetic control of immune responses in other mammals. Variation between individual animals within our test population was significant but we were able to identify both individual animals and families with high or low antibody production phenotypes. In several cases, these traits were significantly correlated with individual bulls, suggesting the existence of sire effects, or with individual BoLA types. These findings are consistent with the theory that at least two separate genes or genetic systems contribute to the control of bovine antibody responses to B. abortus vaccination. These genetic effects are likely to be analogous to those identified in several species of laboratory rodents and humans.

Animals↗

The key components of resistance to Ostertagia circumcincta in lambs.

One of the most remarkable features of parasitic infections in general, and Ostertagia circumcincta infection of sheep in particular, is the extensive variation among hosts in resistance to infection, as assessed by parasite burdens and production of eggs or infective larvae. Here Mike Stear, Michael Park and Stephen Bishop describe the factors that account for the variation among animals within a flock, including dam, sire, sex, date of birth and history of exposure to infection. There are no detectable genetic effects in lambs less than three months old. Genetic control of an acquired response develops in two stages: first, a reduction in the average egg production per worm, which is associated with the development of a parasite-specific local IgA response; and second, control of worm burden, which is associated with the production of globule leukocytes in the abomasal mucosa.

Journal Article↗

Response of Dorper and red Maasai lambs to trickle Haemonchus contortus infections.

Six-month-old red Maasai lambs were more resistant than Dorper lambs to repeated infections at one to two week intervals with 1000 Haemonchus contortus infective larvae. Resistance after infection was assessed by means of faecal egg counts, packed cell volumes, eosinophil counts, total serum protein concentrations and mortality rates. The weight gains of the infected animals were only marginally lower than those of their uninfected controls, most probably because of their significantly higher feed consumption, and evidently the infected lambs were not utilising all of the extra feed for growth. This absence of anorexia in spite of the infection was probably due to the palatability of the high protein diet fed to the lambs.

Animals↗

The repeatability of faecal egg counts, peripheral eosinophil counts, and plasma pepsinogen concentrations during deliberate infections with Ostertagia circumcincta.

Faecal egg counts, peripheral blood eosinophil counts and plasma pepsinogen concentrations were monitored during 2 successive, deliberate infections in 24 Scottish Blackface sheep. For all 3 techniques, the repeatability of replicate counts or of measurements made at short intervals were high which suggests that all 3 assays were reliable. Within an infection the repeatability of different samples from the same animal decreased as the interval between samples increased. The repeatability between infections was only moderate for faecal egg counts but high for peripheral eosinophil counts and plasma pepsinogen concentrations. Of the 3 variables, faecal egg count was the most strongly associated with the worm burden. Together, the three variables accounted for, in a statistical sense, one half of the variation in worm burden. The three variables, if measured concurrently, should provide a more effective identification of resistant and susceptible lambs.

Animals↗

An ovine major histocompatibility complex DRB1 allele is associated with low faecal egg counts following natural, predominantly Ostertagia circumcincta infection.

Infection with Ostertagia circumcincta is a major constraint on sheep production in temperate areas of the world. A potential control strategy is the use of genetically resistant sheep. Therefore we examined the association between MHC-DRB1 alleles and faecal egg counts following natural, predominately O. circumcincta infection in a flock of Scottish Blackface sheep. Nineteen DRB1 alleles were identified by a combination of variation in the length of simple repetitive sequences within the intron between exons 2 and 3 and hybridisation of selected oligonucleotides to polymorphisms within exon 2. Faecal samples were taken from 200 lambs from one to six months of age at intervals of 4 weeks. Genetic effects were strongest at 6 months of age. Least-squares analysis indicated that substitution of the most common allele (I) by allele G2 would result in a 58-fold reduction in faecal egg counts in 6-month-old lambs and a 22-fold reduction in 5-month-old lambs. These results suggest that the major histocompatibility complex plays an important role in the development of resistance to O. circumcincta.

Alleles↗

Comparison of four methods for the determination of plasma pepsinogen concentration.

Four methods for estimating plasma pepsinogen concentrations were compared to determine the most suitable for routine use. Three of the methods were colorimetric assays which used glycine-buffered albumin, albumin, or haemoglobin as their substrates. The fourth method was a radial diffusion assay which used casein in agarose as its substrate. All four methods gave reproducible results when replicates were assayed on the same day. However, the first method had the least day-to-day variation and was the only method which gave a linear relationship with different concentrations of pepsinogen in a plasma pool.

Albumins↗

Influence of supplementation with dietary soyabean meal on resistance to haemonchosis in Hampshire down lambs.

The influence of dietary protein supplementation on resistance to haemonchosis was examined in Hampshire down lambs fed either a basal diet or a diet supplemented with soyabean. At seven months of age the lambs were challenged with an initial loading dose of Haemonchus contortus, followed by a trickle infection three times a week. Blood and faecal samples were collected three times a week and bodyweights were recorded weekly. After 10 weeks the lambs were slaughtered and their worm burdens and carcase composition determined. Although their mean worm burdens were similar, the lambs given the basal diet had higher faecal egg counts, lower packed red cell volumes and lower concentrations of total plasma protein and plasma albumin than the lambs given the supplemented diet. The dietary supplementation also improved the carcase composition of the lambs.

Animal Feed↗