PubMed Health⌕ Search

Biomedical subjects

D Wakelin

Publications and source records attributed to D Wakelin.

At least 163 records · Page 9Linked to original sources
PubMed1985

L3T4-positive T lymphoblasts are responsible for transfer of immunity to Trichinella spiralis in mice.

The characteristics of lymphocyte subpopulations involved in mediating immunity to the intestinal nematode Trichinella spiralis in vivo have been examined using adoptive transfer in conjunction with accurate cell-sorting and cell-depletion techniques. Positive selection of cell subsets, using FACS sorting and velocity sedimentation at unit gravity, confirm that rapidly dividing T blasts are the major population that mediates expulsion of the worm from the gut. Furthermore, cell-depletion studies demonstrated that the T-cell subset involved is of the L3T4 + ve Lyt 2-ve phenotype. This phenotype suggests class II MHC restriction in recognition of T. spiralis antigens by T cells in vivo. The roles that such T cells play in immunity to T. spiralis are discussed in terms of lymphokine release.

Animals↗
PubMed1985

Genetic control of immunity to Trichinella spiralis in mice: capacity of cells from slow responder mice to transfer immunity in syngeneic and F1 hybrid recipients.

Mice of the C57BL/10 (B10) strain are slow responders to infection with T. spiralis in terms of ability to expel worms from the intestine. Compared with rapid-responder NIH mice, infection stimulates a slower and reduced blast cell response in the draining mesenteric lymph node (MLN). Transfer of immune cells from the MLN (MLNC) does not accelerate worm expulsion from naive B10 recipient mice, even though MLNC from this strain effectively transfer immunity to (B10 X NIH) F1 recipients. In common with other B10 background mice C57BL/10 show an infection-dose related suppression of immunity to T. spiralis. Such suppression does not appear to determine the response to MLNC, as adoptive transfer into B10 recipients was not enhanced by reducing the level of challenge infection given, and transfer into F1 recipients was unaffected by simultaneous transfer of lymphocyte populations from donors infected at a level which would induce suppression. A hypothesis is proposed which relates slow response status to (i) the inherent capacity of the intestinal inflammatory component of worm expulsion, and (ii) the outcome of infection-dose related stimulatory and suppressive influences acting on the two interacting lymphocyte components of expulsion. The relevance of H-2-linked and non-H-2 genes to the control of the response is discussed.

Animals↗
PubMed1984

Transfer of immunity against Hymenolepis nana in mice with lymphoid cells or serum from infected donors.

Immunity to Hymenolepis nana was adoptively transferred to recipient mice of 4 strains using mesenteric lymph node cells (MLNC), spleen cells (SC), and/or serum taken from infected donor mice. Donor cells capable of transferring immunity appeared in the mesenteric lymph nodes and spleen at an early stage (5 days) after infection. Immunity was most effectively transferred with MLNC and immune serum did not enhance this effect. It is suggested that effective immunity to H. nana involves both antibody and T cell-mediated inflammatory events.

Animals↗
PubMed1984

Evasion of the immune response: survival within low responder individuals of the host population.

It is proposed that, for many species of parasites, evasion of the host immune response may be achieved passively through enhanced survival within host individuals that have a genetically determined low responsiveness to infection. Evasion by this means may contribute significantly to continued transmission of infection in man and domestic animals and influence the severity of pathology. Low responsiveness plays an important role in determining over-dispersion of parasites within host populations, and the common occurrence of this form of distribution is seen as supporting evidence for the proposition, although few of the examples available provide conclusive proof. The extensive individual and strain variation in response to parasitic infection in laboratory strains of mice is taken as a homologue of the natural situation and allows analysis of the mechanisms underlying low responsiveness. Two examples are considered in detail. In Leishmania infections both non-H-2 and H-2-linked genes influence resistance, but the primary expression of genetically determined low response is at the level of the macrophage. Genetic influences upon acquired immunity regulate macrophage-T-cell interactions. In Trichinella spiralis H-2-linked and non-H-2 genes influence development of the intestinal responses necessary for expulsion of the adult worm, the former through the response of helper T-cells to worm antigen and the amplification of this response through other T-cells, the latter through an effect upon the response of myeloid stem cells to T-cell signals. Modification of genetically determined low responsiveness is discussed in terms of improving host responsiveness through vaccination or non-specific immunostimulation and altering host genotype through selective breeding or the introduction of resistance alleles into a population.

Animals↗
PubMed1984

Genetic control of immunity to Trichinella spiralis infections of mice. Hypothesis to explain the role of H-2 genes in primary and challenge infections.

H-2 congenic strains of mice were compared for their ability to expel T. spiralis infections from the small intestine and for their ability to limit the reproduction of adult female worms. B10.M mice (H-2f) expelled both primary and challenge infections more quickly than did the strains B10.Q(H-2q) and B10.BR(H-2k). During a primary infection, expulsion of worms from B10.M mice began before Day 9 post-infection and worm counts differed significantly (P less than .05 Student's t-test) from counts in B10.BR mice on each of Days 12 and 15.B10.Q mice expelled worms more rapidly than B10.BR but worm counts did not differ significantly until Day 15. Whereas B10.M mice responded most quickly to expel worms from the gut, B10.Q mice were most effective in limiting worm reproduction. Female worms harvested from B10.Q mice and cultured for 24 hr in vitro produced significantly fewer newborn larvae than did worms from B10.M or B10.BR mice. Worms from B10.M mice were less fecund than worms from B10.BR, but this difference was not apparent before Day 9 post-infection, and worms from B10.M were always more fecund than worms from B10.Q. Challenge infections 21 days following a priming dose of 200 T. spiralis muscle larvae were rejected very quickly. B10.M mice expelled 65% of their worms during the first 24 h. By Day 6 after challenge, B10.M mice had expelled 84% of their worms; B10.Q and B10.BR expelled 75% and 37% respectively. These results suggest that a rapid expulsion response may be expressed in many different strains of mice depending on how the mice are immunized and the size of the infecting dose. Fecundity of female worms 6 days following a challenge infection was reduced for all strains tested when compared to primary infection controls; however, worms from B10.Q mice were less fecund than worms from B10.M or B10.BR. Results of these experiments demonstrate that H-2 genes play an important role in controlling the immune response which expels worms from the gut and the response which limits worm reproduction. These H-2-controlled differences are expressed during both primary and challenge infections. As the present results conflict somewhat with results published elsewhere, we have proposed a new hypothesis to explain the data collected in our laboratories thus far. According to this hypothesis, the anti-adult response, the anti-fecundity response, and the rapid expulsion response are under independent genetic control and influenced by the interacting products of both H-2 and non-H-2 genes.

Animals↗
PubMed1983

Functional antigens of Trichuris muris released during in vitro maintenance: their immunogenicity and partial purification.

The immunogenicity of the secretory exo-antigen (EXA) originating in the stichosome of Trichuris muris has been investigated. High levels of immunity to challenge were produced using EXA (100 micrograms) by subcutaneous administration. Vaccination with a range of doses of EXA in Freunds' Incomplete Adjuvant (FIA) showed a dose response; 1 microgram of EXA reduced the worm burden by 50% and doses of 10 micrograms or more reduced the worm burden by 80-90% at Day 9 post-infection. Worms recovered from vaccinated mice were significantly smaller than those from controls. A precipitin line identifiable with EXA was shown to immunize mice against T. muris challenge by vaccination. The protective antigen contained in EXA has been partially isolated using gel filtration, ion exchange filtration and isoelectric focusing and has been shown to be a protein of 30000 molecular weight having a pI of 6.8-7.3.

Animals↗
PubMed1983

Cortisone-induced immunotolerance to nematode infection in CBA/Ca mice. II. A model for human chronic trichuriasis.

Treatment of CBA/Ca mice with cortisone acetate for a short period after infection with Trichuris muris induces a state of immunotolerance which allows the development and survival of a chronic infection. Mice harbouring such infections were found to be less capable of responding to a primary infection with Trichinella spiralis or of producing humoral responses to lipopolysaccharide and sheep red blood cells. Mesenteric lymph node T cells, however, were as responsive to the polyclonal activator phytohaemagglutinin as those from normal mice. Homing to the intestinal tract of activated mesenteric lymph node cells from helminth-infected donors was not impaired in the animals harbouring chronic infections. The results are discussed in terms of antigenic competition and with respect to their relevance to chronic human trichuriasis.

Animals↗
PubMed1983

Genetic control of eosinophilia. Mouse strain variation in response to antigens of parasite origin.

Strain variation in capacity to develop peripheral blood eosinophilia was observed in inbred NIH and C57BL/10 (B10) mice exposed to parasite antigens by infection or by parenteral injection in Freund's complete adjuvant. NIH mice were good responders, showing rapid development of high eosinophil counts, B10 mice were low responders. The difference in response phenotype was independent of the parasite used for infection (Trichinella spiralis or Nematospiroides dubius) and of the antigen used for injection (T. spiralis larval antigen or Limulus haemocyanin). Pre-treatment of T. spiralis infected mice with low doses of cyclophosphamide (150 mg/kg) or restriction of the duration of infection to 7 days by anthelmintic treatment did not enhance the response of B10 mice. Thus no evidence was found that the poor response phenotype of B10 during T. spiralis infection reflected any active suppressive mechanisms developed during the adult or muscle larval phases of infection. Demonstration that eosinophilia is induced primarily by the intestinal phase allows comparison with other parameters of the immune response induced by the adult worms, namely intestinal mastocytosis and worm expulsion. From this comparison it is concluded that the low eosinophil response phenotype of B10 mice may reflect a generalized deficiency in the response of bone marrow derived precursor cells to factors of T lymphocyte origin. The significance of genetically determined variation in eosinophil responsiveness is discussed in relation to the development of protective immune or pathological responses to parasite infection.

Animals↗
PubMed1982

Specific cross-immunity between Trichinella spiralis and Trichuris muris: immunization with heterologous infections and antigens and transfer of immunity with heterologous immune mesenteric lymph node cells.

Infections with either 300 infective Trichinella spiralis larvae or 400 embryonated eggs of Trichuris muris were infective in eliciting accelerated expulsion of heterologous challenge infections given 20 days after the primary infection. Accelerated expulsion could also be achieved by the administration of soluble crude worm antigen given 12 days prior to heterologous challenge or by adoptive transfer of mesenteric lymph node cells taken from mice infected with the heterologous parasite. Each species is capable of eliciting an accelerated secondary expulsion response in hosts that have been actively or adoptively immunized against the other species and these results are taken to indicate that there is a specific cross-immunity between T. spiralis and T. muris due to shared antigens. It is postulated that these shared antigens are derived from stichocyte granules.

Animals↗
PubMed1982

The use of host strain variation to assess the significance of mucosal mast cells in the spontaneous cure response of mice to the nematode Trichuris muris.

A proportion of DBA/2 mice do not reject the large intestinal nematode parasite Trichuris muris. In this strain and the early rejecting NIH and the late rejecting CBA/Ca strains the kinetics of the mast cell accumulation in a primary infection were similar with peak mast cell numbers being recorded on day 20 post-infection. Comparisons between rejector and non-rejector DBA/2 mice showed no differences in the mast cell accumulation. There was no rise in mast cell numbers in response to a secondary infection, in either the NIH or CBA/Ca strains, for at least 3 days after the infection had been expelled. It is suggested that mucosal mast cell accumulation is not induced by a simple response to parasite factors, that the cells are not directly involved in the expulsion of T. muris and that any role they play in the spontaneous cure response is subject to more complex control.

Animals↗
PubMed1982

Short lived, dividing cells mediate adoptive transfer of immunity to Trichinella spiralis in mice. I. Availability of cells in primary and secondary infections in relation to cellular changes in the mesenteric lymph node.

After a primary infection with the parasitic nematode Trichinella spiralis NIH mice showed a short lived increase in cellularity of the mesenteric lymph node (MLN), which began between days 2 and 4 peaked at day 8 and had declined by day 21. The majority of cells contributing to this increase were Ig-ve and presumed to be T cells. Coincident with the increase in cell number there was an increase in lymphoblast activity, again largely in the T-cell fraction. MLN cells taken at intervals from mice during a primary infection successfully transferred immunity, i.e. accelerated worm expulsion in recipients, on days 4 and 8, but not on day 21. It was shown that the effective cells in transferring immunity were present in the T-enriched fraction. When mice were present in the T-enriched fraction 21 days after a primary infection the same sequence of changes was apparent in the MLN, but the time course was accelerated, i.e. peak cellularity and lymphoblast activity occurred on day 4 post challenge. Cells capable of transferring immunity were present in the MLN on days 2 and 4 post challenge but not thereafter. As in the primary infection the effective cells, and those responsible for the cellular changes in the MLN, were T cells.

Animals↗
PubMed1982

Short lived, dividing cells mediate adoptive transfer of immunity to Trichinella spiralis in mice. II. In vivo characteristics of the cells.

The in vivo characteristics of mesenteric lymph node cells (MLNC) capable of mediating the adoptive transfer of immunity to Trichinella spiralis have been examined. Mediator cells were diverted into the peritoneal cavity of infected donor mice following the induction of a peritoneal exudate and its was shown that these were nylon-wool, non-adherent (T) cells. After density gradient separation of [125I]-UdR-labelled MLNC, the fractions that were most effective in transferring immunity were those containing a small proportion of cells but the largest proportion of incorporated activity. Treatment of the donors of MLNC with the mitotic inhibitor vinblastine effectively prevented both the transfer of immunity and increased incorporation of [125I]-UdR characteristic of the mediator population. In vitro irradiation of MLNC failed to affect their ability to transfer immunity. Collectively these findings support the conclusion that mediator cells are T lymphoblasts, and suggest that mediation of immunity is effected directly by this population and not by their progeny.

Animals↗