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D Wakelin

Publications and source records attributed to D Wakelin.

At least 181 records · Page 10Linked to original sources
PubMed1982

Cortisone-induced immunotolerance to nematode infection in CBA/Ca mice. I. Investigation of the defect in the protective response.

The parasitic nematode Trichuris muris is expelled from the large intestine of CBA/Ca mice after approximately 20 days of infection. Short term treatment with cortisone acetate prevented expulsion and allowed the establishment and survival of an adult worm population for at least 70 days. This tolerance to the primary infection persisted after removal of the adult worms by chemotherapy and allowed the full development of a secondary infection. High levels of blast activity were seen in the mesenteric lymph node on days 30 and 40 of a primary infection in tolerant mice. Serum taken from tolerant mice passively conferred immunity on naive mice, but cells transferred from such donors were ineffective. Cells from immune mice were not capable of eliciting expulsion of an established primary infection in tolerant mice but did cause a significant reduction in worm numbers when given on the same day as a secondary infection. Cells from naive mice had no effect upon infections in tolerant mice. It is suggested that, in this system, corticosteroid treatment deletes an accessory cell population causing tolerization of immunocompetent T cells.

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PubMed1982

Genetic factors controlling the intestinal mast cell response in mice infected with Trichinella spiralis.

Inbred strains of mice showed marked variation in their mast cell (MC) response to infection with Trichinella spiralis. Variation was under genetic control, the ability to respond to infection being inherited as a dominant trait. MHC-linked genes may influence the absolute level of response, but overall response kinetics appear to be controlled by genes which are not linked to the MHC. An enhanced MC response was transferred adoptively with immune mesenteric lymph node cells (IMLNC), but reciprocal adoptive transfers between H-2 compatible rapid (NIH) and slow (B10.G) responder strains showed that the degree of enhancement was determined by the response phenotype of the recipient, not that of the donor. Similarly, in bone marrow (BM) chimaeras, produced by reconstituting lethally irradiated F1 (B10.G x NIH) mice with parental BM, the MC response to T. spiralis was determined by the response phenotype of the BM donor, whether or not rapid responder IMLNC were transferred. The data are discussed in terms of a T lymphocyte regulated, bone marrow stem cell origin of mucosal MC and interpreted as showing that genetic regulation of the MC response is expressed at the level of stem cell or precursor response to T cell derived mastopoietic factors.

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PubMed1981

Immunity to Strongyloides ratti in rats. 1. Adoptive transfer with mesenteric lymph node cells.

Adoptive transfer of immunity against the enteral phase of Strongyloides ratti was monitored using four parameters; namely, number of worms recovered, position occupied in the host's small intestine, worm length and fecundity. When immune mesenteric lymph node cells (IMLNC) were transferred from donors infected for 20, 26 or 32 days into recipients infected for 3 days, a marked acceleration of worm expulsion was evident by day 16 post-infection (p.i.). IMLNC from day-16 p.i. donors did not transfer expulsion. In an experiment in which recipients were given 2 x 10(8) or 1 x 10(8) IMLNC from donors infected for 26 days, accelerated worm expulsion occurred only with the higher inoculum, although manifestations of direct worm immunity, i.e. altered position and reduced length and fecundity, were evident in both cases. Transfer of IMLNC appeared to have no effect upon worm establishment; when cells were transferred on the day of infection a period of 16 days was necessary to effect both direct anti-worm immunity and expulsion, although the former was evident on day 14 p.i. However, when IMLNC were transferred to rats already infected for 6 days, a very significant reduction of their worm burden was apparent 10 days after IMLNC transfer.

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PubMed1981

Genetic control of immunity to Trichinella spiralis. Donor bone marrow cells determine responses to infection in mouse radiation chimaeras.

Radiation chimaeras, prepared from NIH (rapid-responder) mice or from the F1 progeny of a cross between H-2 compatible B10.G (slow-responder) and NIH mice, were tested for their ability to respond to infection with the intestinal nematode parasite Trichinella spiralis. Mice reconstituted with bone marrow (BM) from NIH donors showed the rapid response characteristic of this strain, i.e. expelled worms from the intestine before day 12 of infection; those given BM from B10.G mice showed a show expulsion pattern, losing worms after day 12. There was no evidence that the environment of the recipient exerted any influence on the ability of the BM cells to express the response characteristic of the donor. When chimaeras were given immune mesenteric lymph node cells (IMLNC) from infected NIH donors there was successful adoptive transfer of immunity, resulting in an accelerated loss of worms. As before, the time course of the accelerated response was determined by the genotype of the BM used. These results confirm that genetic control of the process of worm expulsion is expressed at the level of a bone marrow-derived cell population and is independent of lymphocyte responsiveness. They further show that the factors involved are an inherent property of the cells concerned. The possibility that these cells are myeloid in nature is discussed.

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PubMed1980

Genetic control of immunity to parasites: adoptive transfer of immunity between inbred strains of mice characterized by rapid and slow immune expulsion of Trichinella spiralis.

Adoptive transfer of immunity with immune mesenteric lymph node cells (IMLNC) was used to analyse the roles of immune and inflammatory events in determining the strain-characteristic time of expulsion of Trichinella spiralis from mice. Transfer of IMLNC within and between three rapidly responding strains (NIH, SWR, DBA1-all H-2q) resulted in accelerated worm expulsion, worm loss commencing before day 8 in each case. When NIH cells were transferred to slow-responder B10 congenic mice (B10G-H-2q) mice, immunity was evident at 8 days as a reduction in worm fecundity and only by 12 days as a reduction in worm numbers. A similar result was obtained when B10G cells were given to B10G recipients. In the reciprocal transfer, IMLNC from B10G transferred immunity to NIH as effectively and as rapidly as did NIH cells. Cells capable of transferring immunity were present in B10G mice as early as 4 days after infection, even though worm expulsion in this strain does not occur until after day 12. Thus following heterologous transfers of IMLNC, the time of worm expulsion was determined by the response of the recipient, and presumably by the ability to generate intestinal inflammatory changes. Earlier work has shown that the strain-characteristic time of worm expulsion is genetically determined, but not by H-2 linked genes. A corollary of the present work is that non-H-2 linked genes control the generation of intestinal inflammatory changes in T. spiralis infections. H-2 genes may control lymphocyte responsiveness to infection and the haplotype H-2q may determine a rapid response. Comparisons are made with the genetic control of resistance to Listeria monocytogenes and possible mechanisms are discussed.

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PubMed1979

Transplantation of adult Trichinella spiralis between hosts: worm survival and immunological characteristics of the host--parasite relationship.

A technique for the transplantation of Trichinella spiralis worms directly into the host intestine is described. Infections established by the direct transfer of adult worms were essentially normal both in terms of their survival and reproduction and in their stimulation of, and susceptibility to, host immune responses. Worms transplanted from NIH mouse donors at intervals after infection had an equal ability to survive in the recipient, even when taken from the donor shortly before or during the process of worm expulsion, showing that expulsion does not require worms to be irreversibly damaged. It was noted, however, that after 7 days in the donor the ability of the worm to reproduce in the recipient was temporarily impaired.

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PubMed1979

The effect of the expulsion phase of Trichinella spiralis on Hymenolepis diminuta infection in rats.

The effect of the intestinal changes brought about by the expulsion of Trichinella spiralis in rats was studied in relation to the growth and survival of a concurrent infection with Hymenolepis diminuta, a cestode not normally rejected by the rat in low-level infections. Growth of H. diminuta was stunted in rats given T. spiralis just before, or after, infection with H. diminuta, the stunting being more pronounced when the cestode was given closer to the period of inflammation. There was no loss of the cestode from dual-infected rats and no evidence for destrobilation was found. Lower T. spiralis burdens had a correspondingly weaker effect on growth of H. diminuta, and stunting was abolished by administration of the anti-inflammatory drug cortisone acetate. It is concluded that the stunting of H. diminuta is probably due to the non-specific inflammatory component of the rat's response to T. spiralis infection.

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PubMed1979

T and B cells in the transfer of immunity against Trichinella spiralis in mice.

Enriched populations of T or B cells, prepared by nylon wool filtration of mesenteric node lymphocytes from mice infected with Trichinella spiralis, were capable of transferring immunity to normal and irradiated syngeneic mice. In cell recipients there was an early loss of fecundity by the worms and an accelerated expulsion from the intestine. Treatment with anti-Thy 1.2 serum, to deplete contaminating T cells, severely reduced or abolished the protective activity of enriched B-cell fractions. Replacement of contaminating T cells by normal T cells restored the capacity of B-cell fractions to reduce worm fecundity but did not result in worm expulsion. As it was shown that comparatively small numbers of T cells (3 x 10(6)) alone were effective in transferring immunity to irradiated mice it is suggested that the T cells act not as helper cells, but are involved in the generation of changes in the intestinal environment that are detrimental to worm survival.

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PubMed1978

Immunity to intestinal parasites.

Intestinal parasites are common in man and animals and can cause severe disease. Knowledge of immunity to such infections is limited and comes largely from studies using laboratory host-parasite systems. Understanding how immunity can operate, and why it often does not, is not only of intrinsic interest but necessary for the development of immunological methods of control.

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PubMed1978

The effect of concurrent infection with Trichinella spiralis on Hymenolepis microstoma in mice.

The intestinal changes brought about by rejection of Trichinella spiralis from mice were studied in relation to their effects on a concurrent infection with Hymenolepis microstoma, a cestode not normally rejected from mice. The rejection phase of T. spiralis was associated with a marked stunting of growth of H. microstoma given just before, during, or just after rejection of the nematode. The survival of H. microstoma was affected only when rejection of T. spiralis coincided with the intestinal phase of the cestode: if T. spiralis rejection was timed to occur after the scolex of the cestode had entered the bile duct there was no loss of H. microstoma. It is suggested that the adverse effects on growth and establishment of H. microstoma were due to the non-specific inflammatory component of the host's response to infection with T. spiralis.

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PubMed1977

Nematospiroides dubius: stimulation of acquired immunity in inbred strains of mice.

The development of immunity to Nematospiroides dubius was studied in three strains of inbred mice (BALB/c, C3H and NIH). Although a primary infection in NIH mice persisted for two months without evidence of a reduction in worm numbers, female mice of this strain readily developed resistance to reinfection. The degree of resistance was enhanced when an immunizing infection of 600 larvae was administered as 6 separate doses of 100 larvae given between days 0 and 11, and the worms removed by anthelmintic treatment given on days 15, 21, 28 and 35. Immunity in mice immunized in this way was manifest both as a reduction in worm recoveries on days 9-14 after challenge and also as an expulsion of established worms from the intestine. BALB/c mice were initially less resistant, but expelled most of the worms which became established; C3H mice showed no evidence of expulsion. The finding that inbred NIH and BALB/c mice acquire resistance to N. dubius offers possibilites for the systematic analysis of lymphoid cell activity in initiating and expressing immunity to this parasite.

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PubMed1977

Transfer of immunity to Trichinella spiralis in the mouse with mesenteric lymph node cells: time of appearance of effective cells in donors and expression of immunity in recipients.

Cells capable of transferring immunity to Trichinella spiralis, i.e. of accelerating adult worm expulsion, were present in the mesenteric lymph nodes of mice infected for 4, 6 or 8 days, but not in mice infected for only 2 days. The time-course of worm expulsion in mice infected on the day of transfer was similar in recipients of day 4 or day 8 cells, expulsion becoming marked only when the recipients had been infected for at least 6 days. Transfer of cells 4 or 6 days after infection did not result in an accelerated worm expulsion; transfer 1 or 2 weeks before infection did not enhance the level of immunity in recipient mice. In contrast to the results obtained with mesenteric lymph node cells (MLNC) on immunity was transferred when recipients were given spleen cells taken from donors infected for 8 days. It is suggested that MLNC do not cause worm expulsion directly, but cooperate with another component of the host's defence mechanism. Accelerated expulsion in recipients of cells was accompanied by a premature decline in fecundity of female worms. Evidence is presented to show that worm expulsion and impaired reproduction may represent independent aspects of the immune response to T. spiralis.

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