PubMed Health⌕ Search

Biomedical subjects

D Wakelin

Publications and source records attributed to D Wakelin.

At least 145 records · Page 8Linked to original sources
PubMed1987

Suppression of mucosal mastocytosis by infection with the intestinal nematode Nematospiroides dubius.

Mice exposed to primary infections with the parasite intestinal nematode Nematospiroides dubius failed to show the mucosal mast cell (MMC) response which is characteristic of infections with other species of intestinal nematode and which was readily induced in these mice by infections with Nippostrongylus brasiliensis or Trichinella spiralis. The failure to generate a mucosal mastocytosis was independent of host strain or sex. When infections with N. dubius were established before, or concurrently with, T. spiralis or N. brasiliensis, the MMC response elicited by these species was delayed and/or depressed as was expulsion of the worms themselves. Infection with N. dubius given when a MMC response was already established, by exposure to T. spiralis, had no effect on MMC numbers. The possibility that the effects of N. dubius upon MMC responses reflect a lack of mastocytopoietic potential, rather than an active interference, was excluded by showing that SJL mice, which expel primary infections with N. dubius and express strong immunity to reinfection, developed marked mastocytosis during secondary infections. The depression of MMC responses by N. dubius is discussed in relation to the known immunosuppressive properties of this parasite and in relation to the T cell mediated control of MMC development.

Animals↗
PubMed1987

Adoptive transfer of enhanced eosinophilia and resistance to infection in mice by an in vitro generated T-cell line specific for Mesocestoides corti larval antigen.

A T-cell line specific for tetrathyridial antigens of the cestode parasite Mesocestoides corti was generated in vitro. The T-cells expressed the L3T4+ Ly2- phenotype and secreted the lymphokines: interleukin-1 (IL-1), interleukin-2 (IL-2), gamma interferon (IFN-gamma), colony stimulating factor (CSF), mast cell growth factor (MCGF) and eosinophil differentiation factor (EDF) in response to antigen stimulation. The line was stable for up to 16 weeks and produced an enhanced peripheral eosinophil response and a reduced parasite burden (40-50%) when adoptively transferred into naive recipients undergoing a primary infection.

Animals↗
PubMed1987

Lymphokine production by T cells generated during infection with Trichinella spiralis.

Lymphokine production by mesenteric lymph node cells (MLNC) taken from mice during infection with the intestinal nematode parasite Trichinella spiralis was investigated. Upon stimulation in vitro with a protective crude antigen preparation of the infective L1 larvae, MLNC proliferated in a specific manner, and were observed to release the T-cell lymphokines IL-2, IL-3 and interferon. IL-2 and IL-3 release by MLNC was greatest when taken during the early intestinal phases of infection. Interferon was also released by cells taken from infected mice, with highest levels observed shortly after expulsion of the parasite from the gut. MLNC taken during the early intestinal phases of infection were also able to respond and proliferate to an exogenous source of IL-2, suggesting clonal expansion of T cells within the node. Lymphokine release from T. spiralis specific T-cell lines was also examined.

Animals↗
PubMed1987

Immunity to Dipetalonema viteae (Filarioidea) infections in resistant and susceptible mice.

The course of infection with Dipetalonema viteae in mice shows marked genetically-determined strain variation. Subcutaneous implantation of 5 female D. viteae into C57BL/10 (B10) mice results in a short term, low level microfilaraemia compared with that seen in similar infections in BALB/c mice. Adult worm survival is similar, thus the different patterns of infections reflect responses directed against the microfilariae larvae (mf). A number of immunological parameters have been monitored during infection in an attempt to identify strain differences which may be correlated with levels of resistance. Blast cell activity in the spleen and lymph nodes showed little strain difference, peaking on day 10 and declining as mf disappeared from the circulation. Total serum IgG levels doubled in both strains during infection, the response being more rapid in B10 mice. Serum IgM levels increased threefold in BALB/c mice but fourteen-fold in B10. Radiosorbent assays identified comparable anti-adult antibody and anti-mf homogenate IgM antibody responses in both strains. Immunofluorescent assay showed that the appearance of IgM antibodies directed against the mf surface correlated with the clearance of mf from the blood of B10 mice, whereas similar antibodies were not detected in BALB/c mice. It is proposed that the efficient clearance of mf in B10 is mediated through an IgM-dependent mechanism and that the chronic microfilariaemia seen in BALB/c mice is facilitated by the absence of a specific IgM response to mf surface antigens.

Animals↗
PubMed1987

Release of leukotrienes during rapid expulsion of Trichinella spiralis from immune rats.

Rapid expulsion of the nematode Trichinella spiralis from immune rats is associated with an increase in volume of intestinal exudate and the presence of large numbers of tissue mucosal mast cells (MMC) and eosinophils. We have measured the concentrations of leukotrienes (LT) C4 (LTC4) and B4 (LTB4) in gut perfusates and mucosal homogenates at 30 min, 1, 3, 6 and 20 hr after challenge with larvae. Leukotrienes were identified by radioimmunoassay (RIA) combined with reverse-phase high-pressure liquid chromatography (RP-HPLC). There were significant elevations at 30 min and 1 hr in the concentrations of LTC4 in the perfusates from the gut of challenged immune rats compared to controls (infected unchallenged and uninfected naive rats). Similar increases in immunoreactive LTC4 and LTB4 were observed in mucosal homogenates from the gut of immune challenged animals. A second peak of LTB4 was also observed at 20 hr in both immune and naive challenged rats. There were also elevations in serum concentration of the MMC-associated specific serine protease, rat mast cell protease II (RMCPII). Since LTC4 causes smooth muscle contraction, increased vascular permeability and stimulation of mucus hypersecretion, and LTB4 recruits and activates inflammatory cells, leukotrienes may participate in the process of rapid expulsion of T. spiralis.

Animals↗
PubMed1987

Characterization and mast cell origin of a chymotrypsin-like proteinase isolated from intestines of mice infected with Trichinella spiralis.

A proteinase was purified by cation exchange and affinity chromatography from the small intestines of mice infected with Trichinella spiralis. The enzyme was highly soluble and was chymotrypsin-like in its substrate specificities and susceptibility to inhibitors. It had a MW of 26,000, as determined by SDS-PAGE electrophoresis. Antibodies raised against the proteinase were affinity purified and their specificity confirmed by Western blot analysis. When used to localize the enzyme immunohistochemically, they reacted with granules of mast cells in the epithelium and lamina propria of the parasitized small intestine. The antibodies also bound to mast cell granules in a number of other sites, including tracheal epithelium, gastric mucosa, skin and tongue. Affinity-purified antibodies raised against rat mast cell proteinase II (RMCPII) cross-reacted with the mouse mast cell proteinase on Western blots.

Animals↗
PubMed1986

Genetic and other constraints on resistance to infection with gastrointestinal nematodes.

Infections with gastrointestinal (GI) nematodes are among the most prevalent infections of man. Not only are they common and widespread in populations throughout the world, but they are frequently chronic and occur repeatedly throughout the lifetime of an individual. It is now well established that such parasites can be highly immunogenic and that their environment, the gastrointestinal tract, is well equipped to mount potent immune and inflammatory responses. The abundance and long-term survival of GI nematodes therefore present a paradox. This review takes the standpoint that man as a species has the capacity to produce effective and protective responses against GI infections, but that this capacity is subject to a number of powerful constraints, arising from parasite evasion, depression of response capacity and deficiency in response capacity. These constraints are discussed in the light of evidence drawn from experimental studies with animal models.

Age Factors↗
PubMed1986

Blast cell activity in mice infected with Hymenolepis nana, H. diminuta and Trichinella spiralis: in vivo uptake of 125IUdR in lymphoid tissues and gut.

The kinetics of the lymphoblast response in mice during the course of a primary infection with Hymenolepis nana was measured by the in vivo uptake of 125IUdR. The response was most marked in tissues local to the site of infection, involving the nodes draining the small intestine but not other areas, e.g., inguinal lymph nodes. A close correlation between these responses and the course of infection was observed. Uptake of 125IUdR was greatest in the mesenteric lymph node (MLN) but the peak reached in this organ was later than that in Peyer's patches (PP), small intestine (SI) and spleen (S). The increase in lymphoblast activity of the MLN was similar with Trichinella spiralis; no significant blast cell response to infection with H. diminuta was found till day 9 after injection, the results being similar to those obtained when H. nana infections were established using cysticercoids rather than eggs. It has been shown that the increase in lymphoblast activity was closely correlated with the presence of cells which are most effective in adoptive transfer immunity. A dose-dependent effect was detected in blast cell activity of MLN in different infection levels with T. spiralis and H. nana.

Animals↗
PubMed1986

Genetic control of immunity to Trichinella spiralis in mice. Response of rapid- and slow-responder strains to immunization with parasite antigens.

Slow-responder C57BL/10 (B10) mice responded poorly to immunization with muscle larval antigen of Trichinella spiralis showing no accelerated loss of worms from a subsequent challenge infection. In contrast, rapid-responder NIH mice and (B10 X NIH) F1 mice developed high levels of immunity after immunization. Lymphocyte proliferation studies showed that immunized B10 mice did respond to in vitro restimulation with antigen, though less well than NIH mice. Failure of B10 mice to respond to immunization did not therefore reflect a failure to recognize larval antigen, a view confirmed by the fact that immunization was achieved using abbreviated enteral infections and, to a smaller extent, by parenterally administered muscle larvae.

Animals↗
PubMed1986

Immunization of mice with surface antigens from the muscle larvae of Trichinella spiralis.

Surface antigens of muscle larvae of Trichinella spiralis were stripped from the cuticle of live worms by the cationic detergent cetyltrimethylammonium bromide (CTAB). Such antigen preparations were shown to contain surface antigens of approximate molecular weights 100,000, 90,000, 69,000, 55,000, 46,000 and 35,000. Immunoprecipitation experiments confirmed that the surface of muscle larvae share antigenic epitopes with antigens contained within and secreted by the stichosome. CTAB antigen preparations were shown to be protective in NIH mice against a challenge infection as assessed by reduction in intestinal worm burden, worm fecundity, worm length and muscle larvae burden. The role of surface antigens in protective immunity to T. spiralis is discussed.

Animals↗
PubMed1986

Antigen-specific T-cell lines transfer protective immunity against Trichinella spiralis in vivo.

T-cell lines specific for infective muscle larvae antigens of the intestinal nematode Trichinella spiralis have been generated in vitro. These antigen-specific T-cell lines express the L3T4+ Ly2- phenotype and secrete the lymphokines IL-2, IL-3 and gamma-IFN. They are stable in culture for up to 15 weeks and are protective when adoptively transferred into naive recipients. As few as 2 x 10(5) T. spiralis-specific tract. In addition, intestinal mastocytosis and peripheral blood eosinophilia were accelerated after adoptive transfer of T. spiralis-specific T-cell lines.

Animals↗
PubMed1985

The genetic control of host responses to Dipetalonema viteae (Filarioidea) infections in mice.

Dipetalonema viteae (Filarioidea) infections were established in inbred strains of mice by the s.c. implantation of adult female worms and the resulting microfilaraemia and adult worm survival monitored. BALB/c mice were the most susceptible strain examined, showing a high level microfilaraemia of approximately 6 month's duration. C57Bl/10, CBA/Ca and C3H/He mice were all equally resistant to infection, showing a low level of microfilaraemia of approximately 1 month's duration. The response of NIH mice was intermediate. Relatively little strain difference was seen in adult worm survival although worms lived slightly longer in C57Bl/10 mice than in BALB/c mice. The adult females became depleted of microfilariae over a period of approximately 1 month before becoming encapsulated in host tissue. Challenge infections given to mice previously implanted with worms resulted in lower level, shorter lasting microfilaraemias than those seen in the initial primary infections. All strains showed immunity when challenged. High responsiveness (resistance) was inherited as a dominant trait in F1 hybrids produced by crossing high and low responder strains. Genes linked with the major histocompatibility complex (H-2) were found to have no effect on the response phenotype as demonstrated by the similar responses of H-2 congenic mice on the BALB/c or C57bl/10 backgrounds. The response phenotype of radiation chimaeras was determined by the phenotype of the donor from which bone marrow (BM) cells were taken for reconstitution. Susceptible BALB/c mice reconstituted with resistant B10D2/n BM behaved identically to the donor strain, indicating that the genetic variation which exists between mouse strains in their responses to D. viteae is expressed through a population of BM derived cells and is not simply a consequence of host structure or physiology.

Animals↗
PubMed1985

Susceptibility to coccidiosis: contrasting course of primary infections with Eimeria vermiformis in BALB/c and C57/BL/6 mice is based on immune responses.

The effects of three immunosuppressive treatments--whole body irradiation and injections of cortisone acetate or cyclophosphamide, on the course of primary infections with Eimeria vermiformis were investigated in 'resistant' BALB/c and 'susceptible' C57BL/6 mice. Immunosuppression (and the nude athymic mutation in BALB/c mice) resulted in increased reproduction of the parasite in both strains of mice, indicating some immunological control of primary infections. The effect was, however, very much more marked in the BALB/c mice, resulting in an alteration in the relative susceptibilities of the two strains. The findings are discussed and it is suggested that the basis for the differences observed in the course of infection in normal BALB/c and C57BL/6 mice lies in their immune responses to this parasite.

Animals↗