PubMed Health⌕ Search

Biomedical subjects

D Wakelin

Publications and source records attributed to D Wakelin.

At least 199 records · Page 11Linked to original sources

Evidence for the involvement of a bone marrow-derived cell population in the immune expulsion of Trichinella spiralis.

When mice were irradiated immediately before infection with Trichinella spiralis there was a profound and long-lasting interference with their ability to expel adult worms from the intestine. Irradiation given after the fifth day of infection was progressively less effective in this respect. The ability to expel worms was not restored when mesenteric lymph node cells (MLNC) were transferred (a) on the day of infection in mice irradiated one day previously, or (b) on day 7 of an infection in mice irradiated on day 6, even though the MLNC transferred immunity to intact recipients. Transfer of bone marrow (BM) alone was also without effect. However, worm expulsion was restored if, following irradiation and injection of BM, 10 days were allowed for BM differentiation before transfer of MLNC. This restoration was effective even after lethal levels of irradiation and was clearly dependent upon a donor-derived BM component cooperating with, or responding to, the activity of the transferred MLNC. The possibility that the BM component is non-lymphoid in nature is discussed.

Animals↗

Effect of the expulsion phase of Trichinella spiralis on Hymenolepis diminuta infection in mice.

The rapid elimination of the intestinal phase of Trichinella spiralis in NIH mice is associated with progressive inflammation of the intestinal tract. The non-specific effects of this inflammation were studied in mice concurrently infected with an unrelated parasite, Hymenolepis diminuta, which does not stimulate a visible inflammatory response but is also immunologically rejected by this strain of mice. It was demonstrated that the rejection phase of T. spiralis infection had a marked effect upon the growth and survival of H. diminuta. The cestode either failed to establish or to grow; if the worms were already strobilate when inflammation developed then destrobilation occurred. There was no cross-immunity between the parasites, nor was the interaction a direct consequence of inter-specific competition.

Animals↗

Immune expulsion of Trichuris muris from resistant mice: suppression by irradiation and restoration by transfer of lymphoid cells.

Lethal irradiation (850 rads) of mice made resistant to Trichuris muris markedly depressed their ability to expel a challenge infection. Expulsion was restored within 7-10 days when MLNC from uninfected mice were transferred on the day of infection, but no significant restoration was evident after transfer of immune serum. Transfer of BM alone had no restorative effect within 10 days and no synergism was seen when both BM and MLNC were transferred. MLNC from uninfected donors did not restore challenge expulsion when transfer was delayed until day 7 and the mice were killed 3 days later, although MLNC from resistant donors were effective within this time. When irradiated mice were given BM and the challenge infection allowed to continue for 15 days expulsion was restored, as it was when challenge was delayed for 7 days after BM transfer in thymectomized mice. The results confirm that expulsion of T. muris involves both antibody-mediated and lymphoid cell-mediated phases and offer no evidence for the involvement of other cell types.

Animals↗

Immunity to primary and challenge infections of Trichinella spiralis in mice: a re-examination of conventional parameters.

In young (6- to 8-week-old) NIH strain inbred mice expulsion of a primary infection of Trichinella spiralis began on day 8 and was virtually complete by day 11-5. In older mice expulsion occurred 1 or 2 days earlier. Experience of a primary infection elicited strong immunity to challenge, whether the challenge was given immediately after worm expulsion (day 14) or delayed (day 42). Challenge infections were expelled rapidly the majority of worms being lost during the first day. Immunity to challenge was elicited by low-level primary infections and was effective against large ventionally accepted parameters of immunity to T. spiralis in mice which, it is considered, are applicable only to mice with a genetically determined low-level of responsiveness to the parasite.

Animals↗

Accelerated expulsion of adult Trichinella spiralis in mice given lymphoid cells and serum from infected donors.

Immunity to the adult stage of Trichinella spiralis, assessed by an acceleration of worm expulsion, was transferred to recipient mice with mesenteric lymph node cells (MLNC) or serum taken from infected donors. Immunity was transferred most effectively by MLNC taken from donors infected for 8 days, i.e. donors actively responding to infection. Transfer of both MLNC and serum brought about a marked acceleration of worm expulsion in all cases, even where MLNC or serum given separately failed to transfer a significant degree of immunity.

Animals↗

Genetic control of immune responses to parasites: selection for responsiveness and non-responsiveness to Trichuris muris in random-bred mice.

Populations of Schofield strain, random-bred mice were shown to have a bimodal variation in ability to bring about immune expulsion of the nematode Trichuris muris. This variation was genetically determined and independent of the size of infection experienced. The proportion of mice unable to achieve worm expulsion (non-responders) was relatively constant in various populations of the strain but was increased by selective breeding from mice of known status. Crosses made between non-responder and responder mice produced progeny that were almost all (92%) of responder phenotype, showing that the ability to achieve worm expulsion was inherited as a dominant characteristic. It is suggested that the genetic control involves a small number of genes; the possible immunological mechanisms by which control is mediated are briefly discussed.

Animals↗

Immune expulsion of Trichuris muris from mice during a primary infection: analysis of the components involved.

Immune serum accelerated the expulsion of Trichuris muris when transferred into normal mice on days 0 and 3 after infection, but had no effect when the recipient mice had been immunosuppressed by sublethal irradiation or by cortisone treatment. Delaying serum transfer until days 7 and 8 in normal mice failed to accelerate expulsion, although immune mesenteric lymph node cells (MLNC) accelerated expulsion whether transferred early or late in infection. Expulsion from NIH mice, normally complete by 12 days, was prevented by sublethal irradiation given as late as 9 days after infection, but could be restored by subsequent transfer of immune MLNC or, to a lesser degree, non-immune MLNC. Immune MLNC were unable to restore worm expulsion in mice irradiated before infection. These results are interpreted as showing that the immune expulsion of T. murius from mice during a primary infection requires the sequential activities of antibody-mediated and lymphoid cell-mediated components.

Animals↗

Genetic control of immune responses to parasites: immunity to Trichuris muris in inbred and random-bred strains of mice.

A comparison has been made of the responses of random-bred CFLP and inbred NIH mice to infection with Trichuris muris. Random-bred mice showed greater variation in worm burdens and less uniformity in worm expulsion. Irradiation prior to infection reduced variation, but did not increase the mean level of infection above that shown by the most susceptible unirradiated mice. In NIH mice, however, irradiation raised the level of infection in all mice. The factors responsible for variation between CFLP mice and for the level of infection in NIH mice came into play after the fifth day of infection and were inactivated by cortisone acetate. It is suggested that these factors are immunologically mediated and under direct genetic control. Uniformity of infection and expulsion in NIH mice is therefore seen as a consequence of genetic uniformity; variability in CFLP mice as a consequence of genetic variation. The time of worm expulsion was found to differ markedly between inbred strains of mice. Hybrid progeny showed the expulsion time characteristic of the parental strain with the most rapid expulsion; greater resistance was therefore inherited as a dominant characteristic. The genetic control of immunity to T. muris is discussed in the context of the antibody- and cell-mediated components of the expulsion process.

Animals↗

Suppression of the immune response to Trichuris muris in lactating mice.

Mice infected with Trichuris muris during lactation were unable to expel the infection at the normal time, but expulsion occurred when lactation was terminated. Suppression of expulsion was uniform in mice suckling more than five young but variable with smaller litters. Mice exposed to a primary infection while lactating were shown to have serum antibodies capable of passively transferring immunity to recipient mice and showed near normal immunity to a secondary infection given after lactation had ceased. Acquired immunity to T. muris was also suppressed by lactation, but the worms which became established in lactating resistant mice were fewer and smaller than those in non-lactating, non-resistant controls. It is suggested that the suppressive effect of lactation in this host-parasite relationship is exerted on the second, lymphoid cell-mediated phase of worm expulsion.

Animals↗