PubMed Health⌕ Search

Biomedical subjects

D Wakelin

Publications and source records attributed to D Wakelin.

At least 55 records · Page 3Linked to original sources
PubMed1997

Intra-abdominal sepsis: an immunocytochemical study of the small intestine mucosa.

AIM: To investigate immunocytochemical changes in intestinal tissues from patients with intra-abdominal sepsis, and to relate the changes to the possibility of enhanced bacterial adhesion and translocation. METHODS: Tissues from 17 patients suffering from intra-abdominal sepsis and from controls were sectioned and stained immunocytochemically for IgA, IgM, secretory component, J chain, and HLA-DR. Differences in the distribution and characteristics of positively staining cells between the patient groups were assessed. RESULTS: Patients with intra-abdominal sepsis had noticeable reductions in numbers of IgA and IgM plasma cells, reduced J chain staining, and had little immunoglobulin on the surfaces of enterocytes. In contrast, HLA-DR positive cells were increased in the sepsis compared with the control group. The plasma cells present showed cytological changes suggestive of apoptosis. CONCLUSIONS: Stress associated with sepsis and its immediate causes might result in increased plasma glucocorticoid levels that bring about apoptosis of mucosal plasma cells (or their precursors). The consequent reduction in expression of IgA and IgM may favour bacterial adhesion to the enterocytes and facilitate bacterial translocation into the tissues.

Adult↗
PubMed1997

Immune responses to intestinal parasites: protection, pathology and prophylaxis.

Aspects of the immune responses made by hosts to infection with intestinal parasites are discussed in relation to data from experimental systems in mice involving infections with the protozoans Eimeria vermiformis and Cryptosporidium spp., and the nematodes Nippostrongylus brasiliensis and Trichinella spiralis. The focus of the review is our knowledge and understanding of the roles played by the intestinal mucosa and the epithelial cells of the mucosa in the induction, regulation and expression of the immune and inflammatory responses that provide the host with protection but which may also lead to pathology. Emphasis is placed on current knowledge of T helper cell and cytokine involvement in these responses. The relationship between pathology and protection is discussed briefly, as are some aspects of the development of vaccines effective against intestinal parasites.

Animals↗
PubMed1997

Immune response to Echinococcus infection: parasite avoidance and host protection.

The life cycles of Echinococcus spp, involve two phases that have quite different immunological relationships with the host--the parenteral metacestode and the enteral adult. Immune control of the metacestode (at least of E. granulosus) by vaccination is now a real possibility, but there seems little prospect of similar control of the adult worms. Vaccination against metacestodes must not only induce effective responses but also prevent the parasite modulating these in such a way as to render them ineffective. This requires a much fuller understanding of the basis of parasite avoidance mechanisms, in particular an understanding of the balance of parasite- and host-protective mechanisms that involve the activity of T lymphocyte subsets. Protective responses against adult worms in the intestine appear weak and ineffective, although it is clear that the worms are immunogenic and there is some evidence that the host can become immune. Again, a more complete insight into the nature of the worm's association with the mucosal immune system is required, and a fuller understanding of the variables that influence this association; host genetic variation may prove to be an important factor that determines the outcome of adult worm infections.

Animals↗
PubMed1996

Trichinella isolates: parasite variability and host responses.

The genus Trichinella has the widest geographical distribution and the largest range of host species of all parasitic nematodes. It remains a significant human pathogen. More than 300 isolates of the genus are now available for laboratory study. The taxonomy of the genus, which has only recently achieved some stability, depends upon the use of a variety of biological, biochemical and genetic criteria. The biological characteristics of isolates, particularly those relating to infectivity and pathogenicity, can show considerable variation because they are subject to strong host influences, notably those associated with immune and inflammatory responses. Comparative studies of different isolates in different hosts, particularly strains of inbred mice, have helped to define these influences and to identify the relative contributions of isolate immunogenicity and host immune response capacity to the outcome of infection. Data from such studies can not only contribute to a better understanding of the biology of this genus but can also throw light on fundamental aspects of host-parasite interactions.

Animals↗
PubMed1996

Immunology and genetics of zoonotic infections involving parasites.

Zoonoses involving parasites are both common and important, some causing serious diseases. The abilities of such parasites to pass between humans and a variety of vertebrates facilitates their use as experimental model systems. Much can be learned about the host-parasite relationships of zoonotic infections from laboratory-based studies, particularly where it is possible to make use of defined parasite isolates in a variety of host species or in genetically defined strains of a given host. This review focuses on our current understanding of the immunological influences upon host-parasite interactions involving zoonotic parasites and on how such influences are modified by the genetic variability found n populations of both hosts and parasites. Particular emphasis is given to data arising from work with the intestinal parasitic nematode Trichinella spiralis and other isolates of the genus Trichinella.

Animals↗
PubMed1996

The serum immune response of young lambs to a primary infection with Nematodirus battus.

Young lambs (6-8 weeks of age) were infected with 50000 infective stage larvae of the trichostrongyle nematode Nematodirus battus. Initial mean adult worm burdens of 23884 +/- 1678 (S.E.M.) at day 14 post-infection (p.i.) were reduced significantly (P < 0.01) to a mean burden of 5383 +/- 1397 by day 21 p.i. Blood samples were taken and serum analysed using ELISA and Western blotting techniques for IgG antibodies specific for N. battus. Pre-infection serum from young naive animals showed IgG recognition of adult and larval N. battus whole worm homogenate. Recognition of adult antigens became reduced during the first 14 days after infection, followed by a subsequent increase beginning between days 14 and 18 p.i. and peaking at day 28 p.i. IgM recognition of N. battus antigens showed a single response peak, starting between days 14 and 18 p.i., without the pre-infection elevated titre as observed with IgG. These results show that young lambs can mount a significant serum response to a primary infection with N. battus during rejection of adult worms and that lambs receive from their dams IgG antibodies that are capable of recognizing adult and larval N. battus during the first few weeks of life.

Animals↗
PubMed1996

Responses to vaccination in strains of mice that differ in susceptibility to coccidiosis.

BALB/c mice are normally resistant to infection with Eimeria vermiformis than C57BL/6 (B6) mice, but these phenotypes were reversed by prior vaccination with crude antigens prepared from developmental stages of the parasite: B6 mice were protected, and BALB/c mice were made more susceptible. Infections with a heterologous species, E. pragensis, were unaffected when this was given either alone or together with E. vermiformis. In both strains of mice, vaccination induced serum antibody responses to E. vermiformis and the levels were boosted by superimposed infection, the highest values being found in BALB/c mice. Cellular responses in the mesenteric lymph nodes (MLN), as indicated by cellularity and proliferation, either unstimulated or restimulated in vitro with E. vermiformis antigen, were decreased in both strains, but markedly more in BALB/c than B6. The capacity of MLN cells to transfer immunity to naive recipients was lowered by vaccination of BALB/c donors but unimpaired in vaccinated B6 mice. Responses to the mitogen, concanavalin A, and to unrelated antigens (human erythrocytes and fowl gamma globulin) were unaffected. Thus, parenteral vaccination, which increased the susceptibility of BALB/c mice to infection with E. vermiformis, had a depressing effect on some specific immune responses in the MLN. It was surprising to find some reduction in the cellular responses of the MLN of B6 mice also, although they were protected by vaccination.

Animals↗
PubMed1996

Comparison of antibody and cytokine responses to primary Giardia muris infection in H-2 congenic strains of mice.

The course of primary infections with Giardia muris differs between BALB and B10 H-2 congenic strains of mice. In the first 3 weeks of infection, there is a more rapid decline in intestinal trophozoite and fecal cyst counts in B10 strains than in BALB strains. To determine whether this difference could be explained by variation in specific antibody responses, both secretory immunoglobulin A (IgA) and serum antibody responses were compared between these strains. No significant differences in the timing, titer, or specificity of secretory or serum antibodies were found. However, on comparing specific anti-G. muris serum IgG subclass responses, we found that B10 strains produced IgG2a while BALB strains produced IgG1, suggesting differential involvement of T helper 1 and 2 subsets of lymphocytes. When cells harvested from mesenteric lymph nodes were stimulated with concanavalin A in vitro, both gamma interferon and interleukin-5 were secreted by cells from B10 mice, but only interleukin-5 was secreted by cells from BALB/c mice. Specific blockade of gamma interferon by monoclonal antibody administered to B10 mice resulted in an enhanced intensity of infection.

Animals↗
PubMed1996

Induction of differential T-helper-cell responses in mice infected with variants of the parasitic nematode Trichuris muris.

The resistance or susceptibility of mice to infection with the intestinal nematode parasite Trichuris muris is closely correlated with polarization of T helper (Th) cell responses to the type 2 (Th2) or type 1 (Th1) subset. Comparison of infections with three isolates of T. muris (E/K, E/N, and S) in three inbred strains of mice (CBA, C57BL/10, and B10.BR) has shown that host Th response phenotype can be parasite determined. Although the mouse strains used show genetically determined variation in ability to respond to T. muris (CBA > C57BL/10 > B10.BR), the speed of worm expulsion in a given strain depended upon the isolate used for infection (E/K > E/N > S). The two isolates that induced the most effective resistance (E/K and E/N) elicited parasite-specific host antibody responses that were dominated by immunoglobulin G1 (IgG1), and antigen-stimulated T cells from infected mice released interleukin-5 in vitro. With the isolate that induced the least host resistance (S), the dominant antibody response was IgG2a, and T cells released gamma interferon in vitro. These data show clearly that parasite variant-specific factors play a major role in Th subset polarization during infection.

Animals↗
PubMed1996

Immunocytochemistry of mucosal changes in patients infected with the intestinal nematode Strongyloides stercoralis.

AIM: To investigate the immunopathological changes in duodenal tissues induced by strongyloidiasis and to relate these to degrees of clinical severity. METHODS: Tissues taken from 21 patients showing mild, moderate or severe symptoms of strongyloidiasis, and from non-infected controls, were sectioned and stained immunocytochemically for IgA, secretory component (SC) and HLA-DR. Immunopathology was assessed by changes in numbers, intensity and distribution of stained cells. RESULTS: Parasitised individuals showed villous atrophy and crypt hyperplasia. There was notable infiltration of the lamina propria by IgA positive plasma cells and of the epithelium by intraepithelial lymphocytes. Infection was also associated with increased expression of SC and decreased expression of HLA-DR in epithelial cells. Changes in all parameters correlated with degree of clinical severity. CONCLUSIONS: Profound mucosal changes are induced by strongyloidiasis. Some are analogous to those seen in coeliac disease, but others seem quite unusual. It is likely that these changes are functionally related to the immunopathophysiological consequences of infection seen in patients with severe disease.

Adult↗
PubMed1996

The mycobacterial component of complete Freund's adjuvant induces expulsion of the intestinal nematode Trichinella spiralis in mice.

Expulsion of T. spiralis adult worms was accelerated in high-responder NIH mice vaccinated previously with complete Freund's adjuvant (CFA) emulsified in PBS, whereas the expulsion of this parasite from low-responder C57 BL/10 mice was unaffected. Incomplete Freund's adjuvant (IFA) did not induce protection and it was concluded that the mycobacterial component, present in CFA but absent from IFA, was responsible for inducing these non-specific protective effects. CFA did not induce T. spiralis-specific B- or T-cell responses, but high levels of IFN gamma from Con A-stimulated mesenteric lymph node cells of CFA-vaccinated NIH mice were detected. Such cytokine release was not produced by cells from the C57 BL/10 strain. It is therefore proposed that IFN gamma production is related to the mode of adjuvanticity and non-specific protective effects of CFA in this system.

Animals↗
PubMed1996

Lung eosinophilia in response to intravenously injected Trichinella spiralis.

Mice were injected intravenously with killed muscle-stage larvae of the parasitic nematode Trichinella spiralis. This induced eosinophilic lung inflammation, the degree of eosinophilia was detected and measured by broncho-alveolar lavage. Subsequent in vivo restimulation by Trichinella antigens produced an enhanced lung response, showing that exposure to killed larvae generated an effective immunological memory. The kinetics and characteristics of the eosinophil response suggested that it was locally rather than systemically controlled. This conclusion is based on the fact that, in contrast to the situation seen after oral infection with T. spiralis, there was little change in bone marrow eosinophilopoiesis, blood eosinophil numbers or in serum interleukin-5 levels.

Animals↗
PubMed1996

Immunocytochemical demonstration that human duodenal Brunner's glands may participate in intestinal defence.

The immunocytochemical demonstration of IgA and IgM in some secretory units of human Brunner's glands, associated with the presence of secretory component in all secretory cells, indicates the possibility that these glands assist the function of the intestinal crypts in transporting immunoglobulins into the gut lumen. In addition, the presence of muramidase (lysozyme) in the cells of the secretory units suggests that Brunner's glands continuously secrete bactericidal enzyme, thus reinforcing the function of the Paneth cells as contributors to nonspecific defence (innate immunity) in the intestinal tract.

Brunner Glands↗
PubMed1995

Oral and parenteral vaccination against Trichinella spiralis infections in high- and low-responder mice.

Vaccination by different routes and with different adjuvants is known to influence profiles of immune responses and may be used to overcome genetically determined low-responsiveness to infection. A mouse model of infection with the intestinal nematode Trichinella spiralis was used to investigate the effect of mode of vaccination upon immune responsiveness and worm expulsion phenotype in high- (NIH) and low- (C57 BL/10) responder strains of mice. Muscle larval homogenate antigen was given subcutaneously in Freund's complete adjuvant (FCA) to induce a systemic immune response or with cholera toxin (CT) orally to stimulate mucosal immunity. Both approaches significantly protected NIH mice. Vaccination with FCA was correlated with elevated serum IgG after infection, whereas oral CT-vaccination resulted in increased levels of intestinal IgA. Neither type of vaccination successfully protected the low-responder C57 BL/10 strain and there were no effects on the low antibody levels that infection induced in this strain.

Administration, Oral↗
PubMed1995

Immune response profiles in vaccinated and non-vaccinated high- and low-responder mice during infection with the intestinal nematode Trichinella spiralis.

NIH and C57 BL/10 (B10) mice show genetically determined differences in their response to Trichinella spiralis infection. This study examines the influence of these on parameters of the immune response to infection after vaccination using muscle-larval excretory-secretory antigen in Freund's complete adjuvant. Serum antibody levels were greatly elevated when mice of both strains were vaccinated prior to infection; however, NIH produced significantly higher-level antibody responses than B10. Vaccination accelerated and increased the capacity of mesenteric lymph node T-cells to proliferate in vitro in response to specific antigen stimulation in both mouse strains but, in general, the stimulation indices of NIH cells were higher than those of the B10. The capacity of mesenteric lymph node cells (MLNC) and spleen cells (SC) to produce IL-5 and gamma IFN was measured after specific in vitro stimulation and early gamma IFN secretion was noted in the supernatants of NIH MLNC and SC, but not in B10 SC. Concentrations of IL-5 rose steadily over the first 10-14 days after infection in cell cultures from both strains. Prior vaccination of these animals appeared to enhance cytokine levels. It is postulated that the efficacy of vaccination in NIH mice is a consequence of their genetically determined capacity to produce early and high-level responses to the antigens of T. spiralis and to express these in intestinal effector mechanisms.

Animals↗
PubMed1995

Isolates of Trichuris muris vary in their ability to elicit protective immune responses to infection in mice.

Much of what is currently known of the host-parasite interaction between mice and the parasitic nematode Trichuris muris has come from experiments using a single parasite isolate (E/N). This isolate has been compared with 2 others which, on morphological criteria, belong to the same species. In 3 inbred strains of mouse that show distinct, genetically determined response phenotypes, there was a consistent pattern in terms of parasite survival time regardless of host strain, E/K worms being expelled early, E/N expelled later and S worms very late or not at all. High-responder CBA mice expelled E/K and E/N worms earlier than low-responder C57 B1/10 mice. B10.BR mice were permissive to S isolate infection, mounted a very late response to E/N worms but expelled E/K worms effectively by day 25. The differential response of mice to these isolates provides an experimental system for identifying the basis of variation in this host-parasite relationship.

Adaptation, Physiological↗
PubMed1995

Genetic variation in neutrophil accumulation in mice is not mediated through immigrant regulatory cells.

Genetic variation of induced peritoneal neutrophilia in mice was accompanied by parallel variation in macrophage responses. The timing of the macrophage responses in high responder (C57B1/10) mice indicated a potential role for these cells in mediating the enhanced neutrophil response. However, adoptive transfer of inflammatory macrophages did not induce neutrophilia. Analysis of peritoneal cytokine levels in high and low responder mice further indicated that IL-1, IL-3, GM-CSF, G-CSF and interferon-gamma (IFN-gamma) were not involved in mediating the genetic variation observed. Exogenous tumour necrosis factor-alpha (TNF-alpha) was effective in inducing the high responder phenotype, despite the absence of detectable TNF-alpha in either peritoneal fluid or serum. A role for genetically determined differential expression of endothelial adhesion molecules in high and low responders is suggested.

Animals↗