Biomedical subjects

J B Dixon

Publications and source records attributed to J B Dixon.

At least 19 recordsLinked to original sources

PubMed1997

Echinococcosis.

Hydatids, the intermediate stages, or metacestodes, of the tapeworm genus, Echinococcus, present a major immunological problem; they survive, grow and metastasize in immunized hosts which are protected against reinfection and possess effector mechanisms capable of killing the parasite. Explanations for this state of concomitant immunity have been made from investigations of avoidance strategies, genetics and quantitative hydatid growth. The latter study suggests that the host-parasite relationship is sustained as a dynamic equilibrium between parasite growth and acquired immunity, the balance being subject to mutual regulation and including the possibility of spontaneous rejection of the parasite. Two immunoregulatory, or cytokine-like, factors have been detected in hydatids of Echinococcus spp. One appears to be a mediator of the previously reported mitogenic effects of hydatids. Recent evidence has linked these effects to generation of T-suppressor populations. The second factor interferes with the interaction of macrophages and T-cells, mimics the effect of metacestode infection in impairing the accessory action of macrophages in lymphoproliferative responses, and is suppressive for rosette-forming cell responses against third-party antigens. It is suggested that these factors form part of a primary homeostatic mechanism regulating hydatid growth and immunity.

Animals↗

PubMed1997

Immunological activities of a lymphocyte mitogen isolated from coenurus fluid of Taenia multiceps (Cestoda).

The purification of a mitogen from Taenia multiceps coenurus fluid has been previously reported. In the present study, this activity, which was independent of endotoxin, stimulated the expression of lymphocyte IL-2 and Fc receptors, enhanced mitotic response to phylohaemogglutinin and concanavalin A and antagonised the previously described suppressive effects of the macrophage modifying fraction of coenurus fluid. The mitogen also increased peritoneal macrophage count and viability, Fc receptor expression and Fc receptor-mediated phagocytosis. The mitogenic activity could be destroyed by a combination of protease and amylase, but not by either enzyme alone. It is suggested that the mitogen forms part of a homeostatic mechanism for the preservation of a balanced host-parasite relationship.

Animals↗

PubMed1996

Macrophage modifying factor secreted by the tetrathyridia of Mesocestoides corti (Cestoda): monoclonal antibody to the modifying factor antagonizes its immunological activity.

Immunomodulation of macrophage activity by in vitro secretions of Mesocestoides corti has been previously demonstrated. The modifying activity secreted by M. corti had the effect of reducing the normal accessory function of macrophages in a Con-A-activated lymphocyte proliferation assay. This paper describes the purification of the modifying activity by FPLC techniques and the generation of a monoclonal antibody (MoAb) to this molecule in mice. The MoAb bound immunomodulatory FPLC fractions of M. corti in an ELISA. When MoAb was applied in conjunction with immunomodulatory parasite secretions to macrophages in vivo or in vitro, the modifying effect of the secretions was abolished. This profound effect of the MoAb should help to elucidate the mechanisms by which metacestode parasites avoid host immune responses and may enable therapeutic intervention.

Adjuvants, Immunologic↗

PubMed1996

Taenia multiceps (Cestoda): Ia antigen expression and prostaglandin secretion by parasite-modified, murine peritoneal macrophages.

Taenia multiceps secretions modify accessory cell activity in macrophages. The present experiments were designed to elucidate the cellular mechanisms involved. While normal, murine peritoneal macrophages amplified mitogen-activated T-cell proliferation, macrophages modified by exposure to parasite secretions inhibited this proliferation. The modified behaviour was shown by glutaraldehyde-fixed as well as living macrophages, and modification was inducible by FPLC fraction 24 of coenurus fluid and was associated with an expanded population of 1a- macrophages. Secretory products of parasite-activated macrophages also inhibited T-cell proliferation, and secretion was prevented by indomethacin. The measurement of modified accessory activity was not influenced by the concentration of tritiated thymidine in lymphocyte proliferation assays. Consequently there is no evidence that the reported events are affected by macrophage-derived, cold thymidine secretion. It is concluded that T. multiceps si able to manipulate macrophage accessory function by mechanisms which involve altered histocompatibility antigen expression and the secretion of prostaglandin.

Animals↗

PubMed1994

Modification of macrophage -T cell interaction during infection of mice with Mesocestoides corti (Cestoda).

Peritoneal macrophages from Mesocestoides corti-infected mice showed a marked and progressive loss of ability to act as accessory cells for syngeneic Con A-stimulated mesenteric lymph node lymphocytes. The same effect on the macrophages could be induced by intraperitoneal injection of M. corti culture supernatant, despite a concurrent increase in numbers of peritoneal adhesive macrophages. The findings are used to compare and contrast the known immunomodulatory effects of M. corti and taeniid metacestodes, the latter differing chiefly in their potential for modifying T-cell as well as macrophage behaviour.

Animals↗

PubMed1994

Level of nutrition and age at weaning: effects on humoral immunity in young calves.

Thirty-two calves were studied to determine the effects of level of nutrition (400 and 1000 g (air-dry matter) milk substitute per d) and age at weaning (5, 9 and 13 weeks) on humoral immune responses measured in serum and bronchoalveolar washings (BAW). All calves were immunized with Keyhole limpet haemocyanin (KLH) at 3 weeks of age, and with horse erythrocytes (HRBC) 1 d after weaning. Feeding the higher level of nutrition compared with the lower level decreased anti-HRBC titres and serum IgG2 and IgA responses to KLH (P < 0.05). Weaning at 5 compared with 9 weeks of age decreased serum anti-HRBC responses (P < 0.05), but weaning age had no effect on anti-KLH responses (P > 0.05). Feeding the higher level of nutrition increased total protein (P < 0.05) and IgG2 concentrations (P < 0.01) in BAW. The results showed that variation in husbandry conditions that is within conventional limits affects humoral immune responses in young, artificially-reared calves.

Aging↗

PubMed1993

Alteration of cellular immune responses by nutrition and weaning in calves.

The effects of two levels of nutrition (400 g and 1000 g air dry matter milk substitute powder per day) and three ages of weaning (five, nine and 13 weeks) on cellular immune responses were determined in 32 calves. The lower level of nutrition was found to increase skin sensitivity responses to keyhole limpet haemocyanin (KLH) and decrease lymphocyte blastogenesis test (LBT) responses to ConA and pokewood mitogen (P < 0.05). Weaning at five weeks old resulted in increased KLH skin responses at nine weeks old compared with unweaned calves and decreased LBT responses to ConA and phyto-haemagglutinin at 10 weeks old compared with calves weaned at nine weeks old (P < 0.05). Weaning at five weeks old also increased peripheral blood concentrations of BoCD2+ and BoCD8+ lymphocytes (P < 0.05). The results show that the choice of husbandry conditions alters cellular immune responses in young calves and suggest that early weaning effects are essentially nutritional.

Age Factors↗

PubMed1992

Modification of accessory activity of sheep monocytes in vitro by a coenurus antigen from Taenia multiceps.

A factor in Taenia multiceps coenurus fluid (TMCF) has previously been shown to modify the accessory activity of murine macrophages in vivo and in vitro. The factor (TMCF-F24) has been purified by ion exchange in a fast protein liquid chromatography (FPLC) system. This study was conducted to determine whether TMCF-F24 is an antigen in naturally occurring cerebral coenuriasis, and whether it can also modify normal sheep blood monocytes. Specific IgG antibodies to TMCF-F24 were detected, using ELISA, in serum and cerebrospinal fluid of sheep with clinical coenuriasis. Alterations in monocyte accessory activity were detected by an assay which measured the rate of increase in mitogen-induced lymphocyte transformation caused by addition of increasing numbers of the monocytes. Normal monocytes caused a positive increase in lymphocyte transformation. Monocytes incubated with TMCF-F24 caused progressive inhibition of transformation. This factor may therefore modify monocyte-T cell interaction in natural infection.

Animals↗

PubMed1992

Effects of weaning on antibody responses in young calves.

Two experiments were performed to investigate the effects of cessation of feeding milk substitute (weaning) on antibody responses to Keyhole Limpet haemocyanin (KLH) in young calves. In the first experiment, 47 calves were weaned at 42 days of age, while a further 47 calves remained unweaned until 84 days of age. All calves were immunized with KLH at 43 and 85 days of age. Serum IgG1, IgG2 and IgA responses to KLH were increased in the early weaned calves compared with the late weaned calves following both primary and secondary immunizations. In the second experiment, 24 calves were immunized with KLH at 21 days of age. Subsequently, at 35 days of age, eight calves were weaned, eight calves were sham-weaned and eight calves remained unweaned. Sham-weaning involved continuing to feed milk substitute of greatly decreased nutritional value in an attempt to isolate nutritional from behavioural effects of weaning. No effects of treatments on antibody responses were detected. It was concluded that weaning affects antibody responses to antigens given near weaning but not to antigens given 2 weeks before weaning.

Aging↗

PubMed1992

Modulation of calf immune responses by Ostertagia ostertagi: the effect of diet during trickle infection.

The effects of Ostertagia ostertagi infection and diet on antibody responses to O. ostertagi third stage larval (L3) antigen and to an unrelated antigen, Keyhole Limpet Haemocyanin (KLH) were determined in calves experimentally infected with 3000 L3 on alternate days for 6 weeks. Calves were given one of two diets, and were either infected or not infected with O. ostertagi L3. The diets were either high (H) or low (L) in protein/energy and were within the range of normal husbandry practice in the UK. Both IgG1 and IgG2, but not IgA, responses to L3 antigen were increased in the L-diet compared with the H-diet. IgA responses to L3 antigen were not affected by dietary treatment. The effects of diet and infection on anti-KLH IgG1 were independent of each other; IgG1 anti-KLH responses were decreased by infection and by the L-diet compared with the H-diet. The data suggest that there is a strong interrelationship between diet and immunity during nematode infections.

Animals↗

PubMed1992

The effects of tumour necrosis factor on host-parasite relations in murine Mesocestoides corti (Cestoda) infection.

The regulatory role of tumour necrosis factor (TNF) was investigated in murine infection with tetrathyridia of Mesocestoides corti. Recombinant TNF alpha reduced macrophage larvicidal activity in vitro. M. corti primed mice for TNF release in response to bacterial lipopolysaccharide (LPS) in vivo. TNF activity was amplified 100-fold at 14 days post-infection (p.i.), with a further rise at day 28 p.i. Maximal inflammatory reaction was observed histologically in the liver at the height of TNF activity. Hepatic necrosis was located within inflammatory foci, but not within the vicinity of the parasite itself, suggesting that TNF may contribute to the pathogenesis of infection. Peritoneal cells from infected mice, when stimulated with tetrathyridia in vitro, showed a 4-fold increase in TNF alpha activity at day 14 p.i. However, when peritoneal cells were stimulated with LPS in vitro, a marked increase in TNF alpha secretion was observed at 2 months post-infection followed by a slow decline. It is suggested that impaired macrophage effector function, previously attributed to endogenous endotoxin, which gains access to peritoneal macrophages through an inability of the liver to detoxify endotoxin, may be mediated through TNF alpha.

Animals↗

PubMed1991

Interleukin-1-like activity in synovial fluids and sera of horses with arthritis.

Synovial fluid samples of horses with osteoarthritis were investigated to detect interleukin-1 (IL-1) activity which could contribute to the disease pathogenesis. Of the 32 samples tested, 12 (37.5 per cent) showed an augmented phytohaemagglutinin induced proliferation of C3H/HeJ mouse thymocytes. Positive results were also seen in horses with infected arthritis, osteochondritis, traumatic arthritis and undefined synovial effusions. Normal synovial fluid and sera from all groups failed to show any detectable IL-1 activity. Fractionation of synovial fluid showed that the IL-1 activity was in the 15 to 20 Kd fractions. In the absence of mitogen, synovial fluid failed to stimulate thymocytes and did not stimulate the growth of an interleukin-2 (IL-2) dependent CTLL cell line, but synovial fluid stimulated IL-2 release by mouse spleen cells incubated with suboptimal doses of lectin. Evidence of an IL-1 inhibitor in synovial fluid from osteoarthritic horses was provided by ultrafiltration experiments and by the inhibitory activity of synovial fluid at particular dilutions in the thymocyte assay. The presence of IL-1-like activity could be relevant in the pathogenesis of arthritis in horses.

Animals↗

PubMed1991

Estimation of immunity in the developing calf: cellular and humoral responses to keyhole limpet haemocyanin.

The efficacy of keyhole limpet haemocyanin (KLH) as a test antigen was determined in calves. Humoral and cellular (in vivo and in vitro) responses were compared. Calves were immunized with KLH at either 3 weeks or up to 5 months of age and immune responses were subsequently tested. Class and subclass antibody responses were detected by ELISA, lymphocyte blastogenesis was measured using a whole blood culture technique (LTT) and skin sensitivity responses were measured as an increase in skin thickness following intradermal injection. In young calves, skin test responses were maximal at 24 h and were found to correlate with IgG1 and IgG2 responses (P less than 0.01), with IgA (P less than 0.05) but not with IgM or LTT. Histological examination of skin swellings found a sequence of cellular events, with polymorphonuclear cells dominating until 48 h after intradermal injection, when mononuclear cells became involved. However, in older calves, skin test responses correlated not only with IgG1 and IgA responses but also with lymphocyte transformation (P less than 0.05). These findings suggest that, while immune responses to KLH may be a useful indicator of immune competence in calves, interpretation should be made with caution particularly in young calves.

Animals↗

PubMed1991

Immune modulation by Ostertagia ostertagi and the effects of diet.

IgG1 antibody responses to Ostertagia ostertagi third stage larvae (L3) and the third party antigen, keyhole limpet haemocyanin (KLH), and faecal egg counts were determined in calves infected with a single dose of O. ostertagi and in uninfected, pair-fed calves. The infected and uninfected calves were given diets either high (H) or low (L) in protein and energy. The diets were within the normal range of husbandry practice in the UK. IgG1 antibody responses to L3 antigen were significantly greater from 6 weeks post-infection in infected calves given the L diet than in infected calves given the H diet (P less than 0.05). The effects of diet and infection on anti-KLH IgG1 responses were independent of each other. IgG1 responses to KLH were decreased by infection and by the L diet compared with the H diet.

Animals↗

PubMed1991

Modification of cellular immunity by Taenia multiceps (Cestoda): accessory macrophages and CD4+ lymphocytes are affected by two different coenurus factors.

Taenia multiceps coenurus fluid was analysed by fast protein liquid chromatography in order to separate the factors responsible for previously reported modification of immunological activity in macrophages and T-cells. One factor, F7, was found to be mitogenic for murine L3T4+ T-cells, to be macrophage dependent, to require macrophage compatibility at the I region of the H2 complex, to increase the sensitivity of T-cells to regulatory signals from macrophages and to increase the rate of generation of splenic rosette-forming cells (RFC) against sheep red cells. A second factor, F24, was found to alter macrophages so as to render them suppressive, rather than stimulatory, for parasite-activated and Con A-activated lymphocyte transformation, to depress the rate of generation of RFC and to antagonize the mitogenic effect of F7. The combined actions of these two factors are, therefore, sufficient to explain the known immunomodulatory effects of the metacestode.

Animals↗

PubMed1991

Differential regulation of murine Mesocestoides corti infection by bacterial lipopolysaccharide and interferon-gamma.

Many liver-invasive parasites cause extensive liver damage which may result in an impaired ability to catabolize endotoxin. The influence of endogenous endotoxin on the progress of liver-invasive parasitic diseases has been investigated in murine Mesocestoides corti infection. Invasion of liver tissue by tetrathyridia resulted in extensive parenchymal destruction with fibrosis. In association with this, undetoxified endotoxin, in potentially biologically active concentration, was found on peritoneal macrophages, 5 months post-M, corti infection. Host susceptibility was influenced by the Lps gene for responsiveness to lipopolysaccharide (LPS). The parasite burden of LPS-responsive (C3H/HeN) mice was significantly increased in the livers of these mice when compared to LPS-resistant (C3H/HeJ) mice. LPS reduced the ability of normal peritoneal macrophages to kill tetrathyridia, when co-cultured in vitro. LPS also abrogated the ability of recombinant interferon-gamma (r.IFN-gamma) to enhance macrophage larvicidal activity. These in vitro findings were confirmed in vivo. Daily intraperitoneal administration of LPS, at low concentration, caused a 4-fold increase in parasite burden in the liver, while r.IFN-gamma at optimal concentration reduced parasite burden by 57%. Post-infection macrophages have previously been shown to be refractory to cytokine-activation for larval killing. In this report, we conclude that (1) this refractoriness may be due to the presence of undetoxified endotoxin on post-infection macrophages and (2) endotoxin may reduce host resistance by abrogating effector macrophage response to IFN-gamma.

Animals↗

PubMed1991

Lymphoreticular responses to metacestodes: Taenia multiceps (Cestoda) can modify interaction between accessory cells and responder cells during lymphocyte activation.

This study was designed to test the accessory function of macrophages after activation with products of Taenia multiceps coenuri. Activation was carried out by intraperitoneal injection of mice with coenurus fluid or protoscolex culture supernatant, and function was assessed by adding these macrophages in progressively increasing numbers to macrophage-depleted lymphocyte cultures transforming under the influence of plant mitogens or coenurus-fluid mitogen. In contrast to normal macrophages, which have a progressively enhancing action on the above reactions, parasite-activated macrophages at similar concentrations were progressively inhibitory. However, low concentrations of the activated macrophages enhanced mitosis as well as, or better than, normal. Lymph node cells from injected mice showed abnormal response to macrophage-derived signals. In particular there was subnormal reaction to macrophages in the presence of coenurus mitogen. These results suggest that T. multiceps coenuri may survive in the host because of their ability to reduce effective interaction between lymphocytes and accessory cells.

Animals↗

PubMed1991

Echinococcus multilocularis antigens modify accessory cell function of macrophages.

Peritoneal macrophages and splenic lymphocytes were collected from BALB/c mice, normal or previously infected with Echinococcus multilocularis. In an accessory cell function assay, peritoneal macrophages, in increasing numbers, were added to cultures of splenic lymphocytes. Cultures were stimulated by concanavalin A (Con A) or E. multilocularis culture supernatant (EMSN). Post-infection macrophages, unlike normal macrophages, suppressed Con A- and EMSN-driven lymphocyte transformation. Modification of accessory cells could also be repeatedly induced in vivo by EMSN or a single FPLC fraction of EMSN. Lymphocytes were made more sensitive to accessory cell signals following incubation with EMSN.

Animals↗