Colin Dobson

Hereford cattle immunized and protected against Boophilus microplus with soluble and membrane‐associated antigens from the midgut of ticks

Summary Hereford cattle were immunized with membranes and soluble components extracted from the midgut of Boophilus microplus. Membrane vaccines protected cattle (91%) against challenge with 3 × 20 000 larval ticks administered at intervals of 7 days. Vaccines made from soluble antigens did not protect cattle. Antibody levels measured by enzyme‐linked immunosorbent assay (EL1SA) related to the levels of protection induced by vaccination.

Certain aspects of the host-parasite relationship of Nematospiroides dubius (Baylis). I. Resistance of male and female mice to experimental infections.

1. It has been shown that there is a difference between the resistance of male and female mice to infection with Nematospiroides dubius . 2. More parasites were harboured, during both the larval and adult parasitic phases, by male mice. 3. These worms were found to occupy a similar relative length of the intestine between the stomach and the caecum in male and female mice infected for either 5 or 10 days. 4. The relative length of the intestine infected on the fifth day was significantly greater than that infected on the tenth day. This investigation was carried out during the tenure of a Research Studentship from the Department of Scientific and Industrial Research. I should like to thank Professor I. Chester Jones, in whose department the work was done, for the facilities provided and Dr E. T. B. Francis for his helpful and critical supervision.

Passive transfer of immunity with serum in mice infected with Nematospiroides dubius: Influence of quality and quantity of immune serum

Dobson C. 1982. Passive transfer of immunity with serum in mice infected with Nematospiroides dubius: influence of quality and quantity of immune serum. International Journal for Parasitology 12: 207-213. The passive transfer of protective immunity to mice with immune serum against Nematospiroides dubius infection was directly proportional to the number of infections experienced by the serum donor mice and the antibody titre and quantity of serum transferred to each recipient. These effects were seen as decreased parasite survival, stunting of growth and reduced parasite fecundity. Male worms were more susceptible to the effects of immune serum than female worms. Immune serum from female donors was more efficacious than that from males in protecting mice against infection. Passively immunized male mice harboured more worms than females given the same serum. Antibody appeared to debilitate the parasite both directly, by influencing its biology and indirectly by reducing its survival.

Predicting resistance of sheep to Haemonchus contortus infections

In vitro cultures of lymphocytes from worm-free sheep responded to larval and adult H. contortus antigens by undergoing blast transformation. The level of response varied considerably between animals but was heritable and positively correlated with resistance to subsequent primary, secondary and trickle infection by the parasite, but not with age of the sheep older than 5 months. Lymphocyte responses to phytohaemagglutinin and H. contortus antigens were not present at birth in lambs but developed during the first 5 months in the absence of infection. The proportion of the infecting dose of larvae which was inhibited at the early fourth stage correlated with age of the sheep and with the increase in lymphocyte response to H. contortus antigens during primary infections with H. contortus. Sheep which were most susceptible to infection had the lowest lymphocyte responses to H. contortus antigens but had the highest rate of weight gain during infection. It is suggested that man has selected the most productive animals at the expense of resistance to H. contortus. The definition of genetically controlled markers on lymphocytes is seen as a means by which disease resistant strains of animals may be selected.

Influence of serial passage on the infectivity and immunogenicity of Nematospiroides dubius in mice

Dobson C. and Owen M. E. 1977. Influence of serial passage on the infectivity and immunogenicity of Nematospiroides dubius in mice. International Journal for Parasitology 7: 463-466. The infectivity of Nematospiroides dubius was increased for Quackenbush (Q) mice by ten serial passages through this host. At the same time C(In3)H mice became more refractory to infection with successive Q generations of the parasite. Both strains of mice rejected the most highly selected parasites more readily than parasites from the earlier generations. These responses were shown to be immunological in nature by infections in hypothymic Balb/c CBA nu/nu and nu/+ mice and to be dose dependent. The selection of N. dubius for increased infectivity in Q mice enhanced its immunogenicity in this and other mouse strains possibly because of increased genetic homogenicity in the selected populations. N. dubius selected for Q mice showed a degree of immunologieal adaptation to Q but not to C3H mice.

Effect of host sex on passive immunity in mice infected with Nematospiroides dubius

Abstract Dobson C. & Owen M. E. 1978. Effect of host sex on passive immunity in mice infected with Nematospiroides dubius. International Journal for Parasitology 8 : 359–364. Female C 3 H but not Quackenbush (Q) mice harboured fewer Nematospiroides dubius than male C 3 H and Q mice. Both strains lost worms 21 days after infection. C 3 H and Q mice became progressively immune to infection following 4 sequential doses of N. dubius larvae and showed a sex resistance to infection. Hypothymic nu/nu CBA Balb/c mice did not show these effects on N. dubius infection. The reciprocal transfer of male and female immune mesenteric lymph node cells (IMLNC) to syngeneic male and female recipients showed that the female environment enhanced the protective qualities of both male and female IMLNC but the male environment suppressed these effects. Gonadectomized male and female recipients of male and female IMLNC had levels of infection similar to the entire female recipients. Serum from immune female donor mice protected both male and female recipients better than immune serum from male donors, but female mice in each treatment group were better protected than male mice. Immune serum transferred greater levels of protection then IMLNC to recipient mice against N. dubius infections. These data are consistent with the conclusion that the male environment suppresses lymphocyte activity and the production of protective antibodies and additionally may depress the effectiveness of sensitized lymphocytes and antibodies in ejecting N. dubius . On the other hand the female environment does not appear to adversely affect the mobilization of the protective immune response and may enhance immune effector mechanisms in protecting mice against N. dubius infections.

Certain aspects of the host-parasite relationship of Nematospiroides dubius (Baylis). II. The effect of sex on experimental infections in the rat (an abnormal host).

1. The male rat is more susceptible to infections of Nematospiroides dubius than the female. As the rat grows older the resistance of the female rat to infection increases at a greater rate than that of the male. 2. The course of the infection is modified by the sex of the host. 3. More larvae penetrated the intestinal mucosa to encyst in the male than in the female. More larvae, however, formed cysts in the female than in the male rat by the fifth day. 4. The male harboured more adult worms than the female rat, although this difference was not significant in the immature animals. 5. The sex resistance of the rat to N. dubius infections was removed by bilateral gonadectomy. Castration decreased the susceptibility of the male rat, while spaying increased it in the female compared with the susceptibility in the respective normal hosts. 6. Subsequent replacement of the homologous sex hormone in the gonadectomized rat restores the sex resistance, and may even increase it (particularly in the immature animals). Oestradiol increased the resistance of the spayed female rat, while testosterone increased the susceptibility of the castrate male rat to infection. 7. Oestradiol implanted in castrate male rats increased the resistance of these hosts to a greater level than was shown in the normal male rat. 8. The rat shows a marked age resistance over which the sex resistance is superimposed. 9. The relationship between the sex of the host and its resistance to infection is discussed. This work was done during the tenure of a Department of Scientific and Industrial Research Studentship. My thanks are due to Dr E. T. B. Francis for his helpful and critical supervision and to Professor I. Chester Jones, in whose department the work was done, for the facilities he provided.

HOST ENDOCRINE INTERACTIONS WITH NEMATODE INFECTIONS. I. EFFECTS OF SEX, GONADECTOMY, AND THYROIDECTOMY ON EXPERIMENTAL INFECTIONS IN LAMBS.

Male lambs were more susceptible to Oesophagostomum columbianum infections, harboring more and larger worms and producing fewer nodules than females. Gonadectomy removed these differences by increasing the susceptibility and worm growth in the female lamb. Thyroidectomy did not affect host resistance, as measured by nodule numbers, but did increase adult worm survival, particularly in the female host. This was attributed to decreased mucus production allowing more adult worms to survive in the thyroidectomized lambs. On first infection, many nodules were formed around the larvae by all the lambs, rather than around secondary bacterial infections. The average daily egg output per female worm was 11,300. Worms from normal female lambs produced more eggs than worms from other hosts. This was attributed to loss of worms, over the period of observation, giving an exaggerated result. Haemonchus contortus, a superficial migrator, did not show the same responses to the host endocrines as O. columbianum. Thus the conclusion was reached that parasites which have extensive somatic migrations in their life cycles are more likely to be affected by the hormone balance of the host than worms which do not have this somatic phase.

Low molecular weight immunosuppressors secreted by adult Nematospiroides dubius

Adult Nematospiroides dubius excretory-secretory products (ES) were collected from worms cultured in vitro, separated by sodium dodecyl sulphate--polyacrylamide gel electrophoresis (SDS-PAGE) into four fractions (FI-IV), electroeluted and assessed for their ability to inhibit the proliferation of mouse lymphocytes stimulated by mitogens in vitro. The proliferation of mitogen- and ES-stimulated mouse spleen lymphocytes from normal and infected mice was inhibited by low mol. wt ES F-IV (less than 26,000).

Genetic variation and host-parasite relations : Nematospiroides dubius in mice

Our work deals with aspects of the genetics and immunology of host-parasite relationships as they influence the development of protective immunity and the phenomenon of coevolution. The aim is to understand parasitism through analyses of host specificity. In earlier studies we examined the inheritance of resistances in mice to infections with Nematospiroides dubius (=Heligmosomoides polygyrus) and established the predominant role played by antibodies in protective immunity. Here we report information concerning the selection of lines of N. dubius that differ in their ability to survive antagonistic immunological reactions from mice. Challenge infections with groups of these mice, immunized and protected by previous repeated infections, show that worms selected to survive the immunity that kills other worms do so by inhibiting the effectiveness of the cellular rather than humoral elements of protective immunity.