bluuebunny/crossref_metadata_2025 huggingface dataset:
Thymocyte‐dependent immunity to toxoplasmosis in the normal and immunocompromised guinea‐pig host
Authors: PAVIA CHARLES S.
Published: October 2007

Summary Guinea‐pigs made T‐cell deficient by thymectomy and irradiation, and protected with syngeneic bone marrow cells (TXB) have a greatly reduced capacity to express normal cell‐mediated immune functions, based on their poor responses to T‐cell mitogens, prolonged acceptance of skin allografts, and susceptibility to the lethal effects of graft‐versus‐host disease. Further evidence for impaired T‐cell activity in TXB guinea pigs was based on their inability to be fully sensitized to mycobacterial antigens, and increased susceptibility to an intradermally induced infection with the intracellular protozoan parasite, Toxoplasma gondii (RH strain). After challenge at multiple sites with 106 or 105 parasites, toxoplasmosis in thymus‐intact, fully immunocompetent guinea pigs is a self‐limiting and survivable infection, whereas the disease takes an acutely lethal course in the majority of TXB guinea‐pigs. The latter also had more parasites disseminating to various tissues sites than their euthymic counterparts. The reduced capacity of TXB guinea‐pigs to respond to mycobacterial products, and to generate anti‐Toxoplasma immunity can be restored by an intravenous infusion of normal syngeneic thymocytes. These findings provide substantial direct evidence strengthening the concept that protection against toxoplasmosis is heavily dependent upon an intact T‐cell component of the host's immune response.
Antibody‐dependent in‐vitro cytotoxicity of newborn Trichinella spiralis larvae: nature of the cells involved
Authors: GANSMULLER ANNIE , ANTEUNIS ANNY , VENTURIELLO STELLA M. , BRUSCHI FABRIZIO , BINAGHI RUBEN A.
Published: October 2007

Summary The cytotoxic reaction of normal peritoneal mouse cells, containing less than 3% eosinophils, against newborn Trichinella spiralis larvae, in the presence of antibody, was studied using newborn worms less than 2 h of age, or newborn worms that had been maintained in culture at 37°C for 20 h.

Newborn worms 2 h old were killed, whereas 20 h newborn worms were not. The cells that initially adhered to the larvae were examined by electron microscopy. Only eosinophils adhered to 2 h newborn worms and only macrophages to 20 h ones. The attached eosinophils degranulated and died after a few hours. The macrophages that adhered to, but did not kill the 20 h newborn worms were morphologically in good state and no lysis of the larvae was observed.

These results suggest that different antibody classes are involved in eosinophil and macrophage adherence, and strongly support the hypothesis that eosinophils mediate larval destruction. They also show that rapid changes are taking place after birth in the structure of the larval cuticle and that the age of Trichinella newborn worms is a major factor in the antibody‐dependent cellular cytotoxicity reaction.
Induction of protective immunity against Schistosoma mansoni by a non‐living vaccine. VI. Antigen recognition by non‐responder mouse strains
Authors: JAMES STEPHANIE L. , SALZMAN CAROL , PEARCE EDWARD J.
Published: October 2007

Summary Previous studies have shown that many strains of mice develop partial resistance to Schistosoma mansoni as a result of intradermal vaccination with soluble schistosome antigens plus BCG. However, P and BALB/c mice are non‐responsive to this intradermal vaccination protocol. In this study, humoral and cellular responses to schistosome antigens in vaccinated P and BALB/c mice were compared to those in protected C57BL/6 mice to identify an immune correlate to resistance in this model. Levels of circulating IgG and IgM antibodies to soluble adult worm antigens, as measured by ELISA. were comparable between strains. Moreover, Western blot analysis revealed no qualitative differences in antibody reactivity, with sera from vaccinated animals of all three strains recognizing the antigen previously identified as Sm‐97 (paramyosin). However, vaccinated P and BALB/c mice showed specific defects in cell‐mediated immunity to schistosome antigens, including decreased production of macrophage‐activating lymphokines and an inability to produce activated macrophage effector cells in vivo at the site of antigen challenge. These observations strengthen our hypothesis that the intradermal vaccine acts through induction of T‐cell‐mediated immune resistance mechanisms.
Surface‐associated proteins and host IgG on early and late metacestode stages of Taenia pisiformis
Authors: Craig P. S.
Published: October 2007

Summary
125I‐labelled proteins associated with the surface of the oncosphere and metacestode stages of Taenia pisiformis were investigated, together with the presence of host immunoglobulin G on the parasite surface. Rabbit IgG was detected by enzyme‐linked immunosorbent assay (ELISA) in the acid washes (pH 3.0) of viable 3‐week migratory metacestodes and 8‐week mature cystic metacestodes from the liver and peritoneal cavity, respectively, of rabbits orally infected with eggs of T. pisiformis. However, specific anti‐ T. pisiformis IgG antibodies could not be detected in these washes using ELISA. When intact and washed hatch‐activated oncospheres and 3‐week and 8‐week metacestode stages were iodinated with Bolton‐Hunter 125 reagent and examined by SDS‐PAGE and autoradiography, there appeared to be a marked loss and/or reduction of labelled proteins on the mature cystic metacestode compared to the oncosphere and 3‐week juvenile metacestode stages. Six‐week post‐infection rabbit sera strongly immunoprecipitated a 43 kD iodinated protein from oncospheres together with others including a 65 kD polypeptide. Only the 65 kD polypeptide, which is the major iodinated protein on 3‐week liver metacestodes, was immunoprecipitated from these juvenile or the mature metacestode stages. The results are discussed in relation to survival of metacestodes in the host, and as to how acquired resistance might result from both frequent egg challenge and concomitant immunity.
Evaluation of cytotoxic lymphocytes and their parasite strain specificity from African buffalo infected with Theileria parva
Authors: BALDWIN C.L. , MALU M.N. , GROOTENHUIS J.G.
Published: October 2007

Summary Theileria parva‐reactive cytotoxic lymphocytes and their precursors were examined in the blood of African buffalo infected with T. parva and uninfected African buffalo. Peripheral blood mononuclear cells (PBM) from eight of 11 infected buffalo were found to have potent cytotoxic activity after stimulation with autologous parasitized cells for 6 days in vitro, while PBM from uninfected buffalo or PBM from infected buffalo not stimulated in vitro had no cytotoxic activity. The cytotoxic activity was specific for parasitized cells and genetically restricted since there was no killing on uninfected autologous lymphoblasts and a lower percentage of killing on parasitized allogeneic lymphocytes than on targets of autologous parasitized cells. The cytotoxic cells tested for parasite strain specificity were shown to kill autologous cells transformed with different stocks of both cattle‐derived (T. parva parva) and buffalo‐derived (T. parva lawrencei) parasites.
Genetic variation in the humoral immune responses of mice to the nematode Trichuris muris
Authors: ELSE K. , WAKELIN D.
Published: October 2007

Summary Genetically based differences in the antibody responses to the large intestinal nematode Trichuris muris were studied in two groups of H–2 congenic strains of mice that differed in their relative resistance to infection with this parasite. The primary antibody response to parasite excretory/secretory (E/S) antigen was predominantly an IgG response with the strains forming two distinct groups, defined by their genetic background. The more susceptible B10 genetic background mice had strikingly higher antibody levels than mice of the BALB genetic background. Superimposed upon these background effects were clearly defined influences attributable to H–2–linked genes, strains which differed genetically only at H–2 loci exhibiting differences in the kinetics of the antibody response. Only B10.G and B10.BR mice showed any great increase in IgM levels post–infection. No IgA specific to E/S antigen was detected in the peripheral circulation of any strain at any time post–infection. Antibody responses to a 40–43 kD antigen revealed clear H–2–linked gene effects, with mice sharing the H–2k haplotype (B10.BR, BALB/K) exhibiting considerably higher total antibody levels than strains expressing other haplotypes; mice of the H–2d haplotype (BALB/c, B10.D2/n) responded very weakly to this antigen. A Western blot analysis of antigen recognition by antibody revealed similarities between the mouse strains in their total antibody responses to T. muris E/S antigen. However, immunoprecipitation studies showed that in general the more susceptible B10 congenic strains had wider spectra of antigen recognition than the BALB congenics. Strains sharing the same H–2 haplotype had dissimilar antigen recognition profiles, but strains sharing the H–2b haplotype (B10, BALB/B) recognized a low mol. wt antigen (20–23 kD) not recognized by any other strain, suggesting an exclusively H–2b restriction in the recognition of this antigen. These results support the conclusion that both H–2–linked and background genes play important roles in controlling the humoral immune response to T. muris infection.
Lymphocyte subpopulations of sheep in protective immunity to Taenia hydatigena
Authors: MEEUSEN E. , GORRELL M. D. , RICKARD M. D. , BRANDON M. R.
Published: October 2007

Summary Lymphocyte subpopulations entering the liver and surrounding the rejection sites during a 9–day period after infection of immune sheep with Taenia hydatigena were identified with the aid of monoclonal antibodies against lymphocyte cell surface markers. Viable lymphocytes were isolated from the liver tissue and stained by indirect immunofluorescence for subsequent flow cytometry analysis. Over the first 6 days after challenge infection a marked increase in the ratio of T–helper to T–suppressor/cytotoxic lymphocytes was observed. SBU–T19+ lymphocytes, a CD5+ T–cell subpopulation uniquely identified in the sheep, were present in small numbers in sheep liver both before and after infection. There was a large, continuous increase ofslg+ B–cells over the 9–day observation period after infection. Eosinophils were the predominant granulocytes in the liver of infected sheep. The exact location of the leucocyte subpopulations in respect to the rejection sites in infected liver was determined by in–situ immunoperoxidase staining of frozen liver sections. The evolution of the parasite–induced leucocyte response was characterized by the appearance of a central core of eosinophils surrounded by increasing numbers of CD4+ helper T–cells. CD8+ (suppressor/ cytotoxic) and SBU–T19+ T–lymphocytcs were present in much smaller numbers and by day 9 after infection were located predominantly around the periphery of the lesions. Distinct foci of tightly packed B–cells developed within the lesions and increased dramatically in size over the 9–day observation period. At this time, lesions appeared as compact aggregations of leucocytes encircled by a second band of eosinophils. Both T– and B–lymphocytes within the lesions stained positive for class II major histocompatibility antigens.
Development of metacyclic Leishmania promastigotes is associated with the increasing expression of GP65, the major surface antigen
Authors: KWEIDER M. , LEMESRE J. L. , SANTORO F. , KUSNIERZ J. P. , SADIGURSKY M. , CAPRON A.
Published: October 2007

Summary Using immunofluorescence techniques and flow microfluorometry analysis, we have demonstrated that the binding of a monoclonal antibody (VD5/ 25) produced against GP65, the major surface antigen of Leishmania braziliensis, increased on the surface of stationary‐phase promastigotes from all the New World Leishmania species causing mucocutaneous or cutaneous disease as compared with the log‐phase parasites. In addition, a sequential development of Leishmania amazonensis promastigotes from a non‐infective to an infective stage was demonstrated. Indeed, promastigotes in the stationary phase (days 6–7) were found to be far more infective than those in the logarithmic phase of growth (day 3) both in vitro for mouse peritoneal macrophages and in vivo for BALB/c mice. The intracellular survival and multiplication of L. amazonensis were significantly inhibited when infective promastigotes were treated with the VD5/25 monoclonal antibody. The increasing expression of GP65 on the promastigote surface may thus contribute to Leishmania infectivity. This seems to represent a characteristic mechanism applicable to all New World Leishmania species studied.
Mechanisms of resistance/susceptibility to murine encephalitozoonosis
Authors: LIU JIUAN J. , GREELEY ELIZABETH H. , SHADDUCK JOHN A.
Published: October 2007

Summary Mechanisms of resistance/susceptibility to the obligate intracellular protozoan Encephalitozoon cuniculi were studied in resistant BALB/c and susceptible C57BL/6 mice. Three immunological functions were examined: the production of lymphokine(s) (LK) by T‐lymphocytes, the proliferative response of spleen cells to parasite spore fragments, and the ability of splenic and thioglycollate‐induced peritoneal macrophages to act as accessory cells in antigen‐induced T‐cell proliferation. The two strains showed differences in the time required for LK production in vitro but not in their ability to generate LK. Spore fragment‐induced lymphoblastogenesis was found in spleen cells of infected BALB/c and C57BL/6 mice. There was no difference between the two strains in dose response and time of maximal response, but the magnitude of maximal response was significantly less in C57BL/6 mice. Indomethacin was found to augment the lymphoproliferative response of C57BL/6 but not BALB/c mice, suggesting that prostaglandin production may be involved in immunosuppression in C57BL/6 mice. C57BL/6 mice required more splenic adherent cells to achieve the same proliferative response as found in BALB/c mice. The ability of thioglycollate‐induced peritoneal macrophages to act as accessory cells in antigen‐induced T‐cell proliferation was less in C57BL/6 mice than in BALB/c mice. Thus, it appeared that the relative susceptibility of C57BL/6 mice to encephalitozoonosis may be due to defective accessory cell function of splenic and peritoneal macrophages, depressed lymphoproliferation against spore fragments (possibly due to prostaglandin‐mediated suppression) and a delay in LK production. There was no significant difference between the survival times of BALB/c‐nu and C57BL/6‐nu mice, suggesting that non‐immune mediated resistance did not play a role in determining resistance/susceptibility.
Schistosoma mansoni: enhanced efficacy of Praziquantel treatment in immune mice
Authors: FLISSER ANA , DELGADO VICTOR S. , MCLAREN DIANE J.
Published: October 2007

Summary Naive CBA/Ca mice and CBA/Ca mice vaccinated 4 weeks previously with radiation‐attenuated cercariae of Schistosoma mansoni were challenged with normal cercariae and then treated with 500 mg/kg body weight of Praziquantel (Pzq). The drug was administered intramuscularly or intradermally on day 1, but intramuscularly only on day 6. The results show clearly that in naive mice skin‐stage larvae were susceptible to Pzq provided the drug was given intradermally on day 1. Lung worms were susceptible to Pzq given intramuscularly on day 6. Drug efficacy in naive mice is thus dependent upon treatment being given at the correct time and via the optimal route. The efficiency of Pzq treatment was enhanced in vaccinated mice, but was again affected by the treatment regime. Analysis of the data revealed a highly significant synergistic effect between drug treatment and vaccination when Pzq was given intramuscularly on day 6. Synergy was detectable but only marginally significant when the drug was administered intradermally on day 1, and could not be demonstrated when Pzq was given via the intramuscular route on day 1. These findings are discussed in the light of known sites and mechanisms of vaccine resistance in mice, as well as in relation to the mode of action of Pzq against schistosome parasites.
Specific cross‐protection between Schistosoma bovis and S. haematobium induced by highly irradiated infections in mice
Authors: AGNEW ALISON M. , MURARE H. M. , DOENHOFF M. J.
Published: October 2007

Summary Significant levels of resistance against Schistosoma haematobium challenge were developed by mice exposed to highly irradiated (20 krad) cercariae of the homologous species (46–53%) or of the closely related species, S. hovis (34–56%) but not of S. mansoni (– 6–28%). This ability to cross‐protect reflects the phylogenetic relationships between these species; S. mansoni and S. bovis, as well as S. mansoni and S. haematobium, failed to cross‐protect. The cross‐protection demonstrated between S. bovis and S. haematobium in mice was non‐reciprocal.
Changes in the superoxide anion generating capacity and respiratory burst enzymes of peripheral blood monocytes of monkeys during acute Plasmodium knowlesi infection
Authors: JAYSHREE R. S. , GANGULY N. K. , SETHI A. K. , MAHAJAN R. C.
Published: October 2007

Summary The superoxide anion generation profile of peripheral blood monocytes of rhesus monkeys was investigated during the different stages of an acute Plasmodium knowlesi infection. An initial increase in superoxide anion was followed by a significant decline (P < 0001), paralleled by a drop in NADPH oxidase activity; there was no alteration in the activity of the hexose monophosphate shunt enzymes. This lowered activity of the NADPH oxidase, with the resulting decreased Ö2‐ generation, might be responsible for the failure of the animals to control the parasitaemia; as a result they succumbed to the infection.
Schistosoma mansoni: histological analysis of the synergistic interaction between vaccine immunity and praziquantel therapy in the lungs of mice
Authors: PIPER KAREN P. , MOTT RICHARD F. , McLAREN DIANE J.
Published: October 2007

Summary Naive CBA mice and mice vaccinated 4 weeks previously with gamma‐irradiated cercariae of 5. mansoni were challenged percutaneously with normal cercariae and then treated with 500 mg/kg body weight of Praziquantel (Pzq). The drug was administered intradermally on day 1 or intramuscularly on day 6, thus targeting against skin stage or lung stage challenge larvae respectively. The skin site of challenge and/or the lungs were removed at various time points to provide samples for histological examination. As reported elsewhere (Flisser, Delgado & McLaren 1989) the efficacy of Pzq was significantly enhanced in vaccinated mice and was influenced by the treatment regime. Histological analysis revealed that when Pzq was administered I/D on day 1 to vaccinated mice, the inflammatory response to challenge differed in extent but not nature from that seen in vaccinated but untreated cohorts. This correlates with worm recovery data showing no (this study), or only marginal synergy between drug treatment and immunity using this regimen of drug treatment (Flisser et al. 1989). Following the day 6 protocol of drug delivery, however, lungs from treated vaccinated mice exhibited many large inflammatory reactions containing trapped challenge larvae. In contrast, lungs from untreated vaccinated mice had only few foci which were small and rarely contained trapped larvae. These data again correlate well with worm recovery data showing that there is a highly significant synergy between vaccination and drug treatment administered at this time (Flisser et al. 1989; this study). It would seem, therefore, that Pzq exacerbates lung phase immunity in the NIMR vaccine mouse model where skin phase immunity predominates and pulmonary attrition is normally minimal. The results are discussed in the light of published data concerning the effector mechanisms thought to characterize skin and lung phase vaccine resistance in the murine model.
Novel cross‐reactive epitopes on asexual blood stage antigens of Plasmodium falciparum
Authors: RAMASAMY RANJAN , MARIO GEYSEN H.
Published: October 2007

Summary An IgM monoclonal antibody that reacts with the merozoite membrane and internal merozoite antigens was shown to recognize several previously characterized asexual blood stage antigens of Plasmodium falciparum as well as new antigens. Among the reactive antigens identified were FIRA, GYMSSA, RESA and the S‐antigen. Analysis of the cross‐reactions between FIRA and GYMSSA by epitope scanning was performed. The most reactive peptides in GYMSSA had the common sequence STNS. The cross‐reactive epitopes in FIRA could, in many cases, be explained by the results of a replacement net analysis performed on the STNS epitope. It is proposed that the cross‐reactive epitopes, which in several cases have no obvious linear homology but possess high S, T and N content, may be present as loops or coils on the surface of the molecules.
MHC‐restricted antibody responses to Trichuris muris excretory/secretory (E/S) antigen
Authors: ELSE K.J. , WAKELIN D. , WASSOM D.L. , HAUDA K.M.
Published: October 2007

Summary Two panels of H‐2 recombinant mice were used in a detailed serological study to analyse the role of H‐2‐linked genes in the control of the antibody response to excretory/secretory (E/S) antigens of Trichuris muris. An apparent H‐2q (1‐Aq) restriction on the early development of high levels of IgGl antibody to E/S antigen was revealed by ELISA. No such restriction was demonstrated for the specific IgG2a response patterns. Recognition of two high molecular weight antigens (90–95 kDa, 105–110 kDa) by IgG antibodies was also shown to be almost exclusively H‐2q restricted and may be related at least in part to the high antibody levels seen for H‐2q strains of mice. Immune serum from resistant (B10.BR × B10.G) Fl hybrid mice (H‐2qk) containing high levels of IgGl antibodies specific for T. muris E/S and IgG antibodies which recognized the 90–95 kDa and 105–110 kDa E/S antigens was effective in transferring protection to the non‐responsive B10.BR mouse strain as seen on day 35 post‐infection (p.i.). It is suggested that the IgG responses described for the generally very resistant H‐2q mouse strains may contribute to, but not be an absolute requirement for. protective immunity, antibody‐mediated damage facilitating a subsequent cellular attack in certain strains of mice.
The expression of the Mr 30 000 antigen in the third stage larvae of Brugia pahangi
Authors: DEVANEY EILEEN , JECOCK ROWENA M.
Published: October 2007

Summary The expression of the Mr 30 000 surface antigen in the third stage larvae (L,3) of Brugia pahangi has been investigated. The antigen could be detected only with great difficulty in the mosquito derived Li externally labelled with 125I but was more easily labelled in 24 and 48 h post‐infective larvae harvested from the vertebrate host. Labelling of a detergent extract of mosquito derived L3 with 125I demonstrated that the Mr 30 000 antigen was indeed present in this life cycle stage, presumably in an internal localization. It seems likely that the Mr 30 000 antigen is not fully expressed in the parasite cuticle until after infection of the vertebrate host. The data presented also suggest that there arc major differences in the surface properties of the mosquito derived Li compared to the p.i. L3 harvested from the vertebrate host.
Antigenic components of Paragonimus heterotremus recognized by infected human serum
Authors: MALEEWONG W. , WONGKHAM C. , NONDA S.PARIYA , INTAPAN P. , PIPITGOOL V. , DAENSEEGAEW W. , MORAKOTE N.
Published: October 2007

Summary The antigenic components of a Paragonimus heterairemus saline extract were revealed by SDS‐PAGE and Western blot analysis using sera from 32 patients with P. heterotremus infection. 60 with other helminthiasis, and 15 normal human sera. It was found that the worm extract was comprised of more than 13 polypeptides. among which 5 components were strongly recognized by paragonimiasis sera. These components had approximately showed molecular weight of < 12‐3. 12 3, 18‐5, 31,‐5 and 38 kD. Only the 31.5 kD component was recognized by all 32 paragonimiasis sera. Sera from other helminth infections and from uninfected did not produced detectable bands with the worm extract. The present findings suggested that the 31.5 kD component may be sensitive and specific for the diagnosis of human paragonimiasis heierotremus.
Circulating filarial antigen in cats infected with Brugia pahangi is indicative of the presence of adult worms
Authors: KUMAR H. , BALDWIN C. , BIRCH D.W. , DENHAM D.A. , DE MEDEIROS F. , MIDWINTER I.T.C. , SMAIL A.
Published: October 2007

Summary Using counterimmunoelectrophoresis with rabbit antisera raised against soluble extracts of adult females of Brugia pahangi parasite antigen was detected in the serum of all cats repeatedly infected with B. pahangi. Antigen was never delected in uninfected cats. The antigen was associated with the presence of adult worms. Antigen was detected consistently in a cat that was amicrofilaraemic but at autopsy harboured only two or three adult worms. Conversely, some cats showed slowly declining numbers of microfilariae and, in these, circulating antigen declined before the number of microfilariae. Eventually no antigen was detectable in circulation whereas microfilariae, although in diminishing numbers, were still present. At autopsy no adult worms were found in these cats. Antigen also appeared in several cats before they became microfilaraemic.
Evidence of subjects sensitized to Leishmania infantum on the French Mediterranean coast: differences in gamma interferon production between this population and visceral leishmaniasis patients
Authors: MELLER‐MELLOUL C. , FARNARIER C. , DUNAN S. , FAUGERE B. , FRANCK J. , MARY C. , BONGRAND P. , QUILICI M. , KAPLANSKI S.
Published: October 2007

Summary The Marseilles region is an endemic area for visceral mediterranean leishmaniasis, but although the number of dog cases, the parasite's main host, is very high, only a few people develop the disease. We looked for sensitized healthy subjects among 25 healthy individuals living in this area by studying their in vitro lymphoproliferative response to Leishmania infantum antigens and gamma interferon synthesis. We found that 65% of tested subjects were sensitized against L. infantum. We compared their cell mediated immunity to that of 13 active Kala‐Azar patients and 13 controls from non‐endemic areas. In patients, results showed a specific cellular immuno‐deficiency in the lymphocyte response to L. infantum antigens and a global deficiency of gamma interferon production. Interestingly, the healthy individuals from the endemic area who responded to L. infantum antigens were found to produce high γ interferon levels after L. infantum antigen stimulation. After healing, the cell mediated‐immunity of the 3 patients we followed up was similar to that of the sensitized tested healthy subjects, but the former were still producing antibodies at the time of study.
Schistosoma mansoni: immuno‐localization of the calcium binding protein Sm20
Authors: HAVERCROFT J.C. , SMITH A.L. , WILLIAMS R.H.
Published: October 2007

Summary The 20 kDa calcium binding protein of Schistosoma mansoni, Sm20. is expressed in all stages of the life cycle from the cercaria to the adult worm and in the egg, with equal levels of Sm20 present in adult male and female worms. Localization of Sm20 by immuno‐electron microscopy using Sm20‐specjric antisera and the protein A gold technique demonstrated that the majority of Sm20 is expressed in muscle but that it may also be expressed at low levels in the tegument. These results suggest that Sm20 plays a role in the calcium mediated regulation of muscle contraction. However, it is not clear whether Sm20 acts as a reservoir for calcium in muscle or is directly involved in the regulatory mechanisms of contraction.
Cytokine control of Leishmania infection in the BALB/c mouse: enhancement and inhibition of parasite growth by local administration of IL‐2 or IL‐4 is species and time dependent
Authors: LEZAMA‐DAVILA CLAUDIO M. , WILLIAMS DENISE M. , GALLAGHER GRANT , ALEXANDER JAMES
Published: October 2007

Summary The therapeutic potential of locally injected interleukin‐2 (IL‐2) or interleukin‐4 (IL‐4) was studied in the footpads of Leishmania mexicana or Leishmania major infected BALB/c mice. The disease state was measured both pathologically, by measuring lesion size, and parasitologically, by counting total parasite numbers from infected footpads. IL‐2 (0.5 μg/dose) or IL‐4 (0.1 μg/dose) was administered either early, 1 day and/or 15 days after infection, or late, after palpable lesions had developed. Results differed markedly depending on which Leishmania species was used and at what time during the course of disease that therapy commenced. Both L. major and L. mexicana infections, as measured by footpad thickness and parasite number, were exacerbated if IL‐4 was injected into the infected footpads early, during the first two weeks of infection. Paradoxically, late intralesional injection (i.e. after measurable lesions had developed) of IL‐4 markedly inhibited both lesion size and parasite growth in L. major, though not L. mexicana, infected mice. IL‐2 had no measurable effect on the course of L. major infections no matter when or how often, the infected footpads of mice were treated. However, early administration of IL‐2 did exacerbate L. mexicana lesion and parasite growth while late treatment had no effect. Generally, but not always, increases in footpad size correlated with increases in parasite number.
Temporal variation in the carbohydrate and peptide surface epitopes in antibody‐dependent, eosinophil‐mediated killing of Schistosoma mansoni schistosomula
Authors: LANGLEY JANE G. , DUNNE DAVID W.
Published: October 2007

Summary Changes in the surface antigenicity and susceptibility to eosinophil‐dependent killing during in vitro development of schistosomula of Schistosoma mansoni, were examined using sera from rabbits and mice immunized with antigens that are shed from the schistosomulum in vitro (shed antigen), a carbohydrate extract of shed antigen (SAg/CHO) or a periodate‐insensitive fraction of shed antigen (SAg/PEP). Anti‐SAg/CHO antisera recognised mainly carbohydrate epitopes on the parasite surface, whilst anti‐SAg/PEP antisera bound to periodate‐insensitive, putative peptide, surface epitopes. Anti‐SAg/PEP antibodies failed to recognise the surface of newly transformed schistosomula unless the parasite was first treated with sodium periodate, suggesting that these epitopes may be masked by periodate sensitive (i.e., carbohydrate) epitopes. There was an increase in anti‐SAg/PEP antibody binding to the larval surface with age of the parasite in vitro; five‐day‐old lung schistosomula were also recognised by anti‐SAg/PEP antisera. In contrast, anti‐SAg/CHO antibody binding declined with parasite age, and failed totally to recognise lung schistosomula. This change in epitope expression was reflected in eosinophil‐dependent cytotoxicity assays, with anti‐SAg/CHO antisera killing young larvae and anti‐SAg/PEP antisera only killing older larvae. Lung worms were not killed by either antisera. The difference in epitopes recognised by the antisera was also reflected in the antigens identified by immunoprecipitation and SDS‐PAGE.
Persistent infection of Strongyloides venezuelensis and normal expulsion of Nippostrongylus brasiliensis in Mongolian gerbils, Meriones unguiculatus, with reference to the cellular responses in the intestinal mucosa
Authors: HORII Y. , KHAN A. I. , NAWA Y.
Published: October 2007

The kinetics of daily faecal egg count, worm burdens, and intestinal cellular responses were examined in Mongolian gerbils after infection with either Strongyloides venezuelensis or Nippostrongylus brasiliensis alone, or concurrently with both parasites. The results show that, both in individual and concurrent infections, S. venezuelensis infection persisted for over 10 weeks and elicited a gradual increase in number of mast cells in the jejunal mucosa. On the other hand, N. brasiliensis worms were expelled by 3 weeks in association with goblet cell hyperplasia. These results suggest that effector/regulator cells involved in worm expulsion are different and highly selective depending on the genus of intestinal helminths.
The use of mouse/human chimaeric antibodies to investigate the roles of different antibody isotypes, including lgA2, in the killing of Schistosoma mansoni schistosomula by eosinophils
Authors: DUNNE DAVID W. , RICHARDSON BRIAN A. , JONES FRANCES M. , CLARK MICHAEL , THORNE KAREEN J. I. , BUTTERWORTH ANTHONY E.
Published: October 2007

We report the use of a matched set of mice/human chimaeric antibodies, directed against the 5‐iodo‐4‐hydroxyl‐3‐nitrophenacetyl (NIP) hapten, to investigate the roles of different human isotypes in antibody‐mediated eosinophil‐dependent killing of schistosomula. The chimaeric antibodies consist of mouse VH, VL and CL regions with human γ1, γ2, γ3 (2 allotypes), y4, α2, or e CH regions and were used in in vitro assays with human eosinophils and NIP‐coated S. mansoni schistosomula. Some anti‐NIP isotypes mediated high levels of killing, which was specific for NIP‐coated larvae, and we suggest that these antibodies will be a valuable tool for studies on the role of antibody isotypes in anti‐schistosome immune effector mechanisms. In particular, this method directly demonstrated, for the first time, that IgA is highly effective in mediating the killing of metazoan parasites by human eosinophils.
Soluble (s)CD23 levels in a parasitized population from Papua New Guinea
Authors: PRITCHARD D. I. , KUMAR SANJEEV , EDMONDS P.
Published: October 2007

Levels of sCD23, total and specific IgE were found to be considerably elevated in the plasma of a helminth infected population from Papua New Guinea. Using age‐corrected data, a significant negative correlation was seen between sCD23 and total IgE in the young, at a time when hookworms are being rapidly acquired, and total IgE levels are rising most dramatically. It is suggested on the basis of this data that this inverse correlation is due to the stabilizing effect of IgE on the FceRII receptor in vivo, and that the high levels of sCD23 seen in hookworm infected individuals are partly responsible for the high levels of IgE recorded in these patients.
Induction of complement resistance in cloned pathogenic Entamoeba histolytica
Authors: HAMELMANN CHRISTOPH , FOERSTER BIRGIT , BURCHARD GERD D. , SHETTY NANDINI , HORSTMANN ROLF D.
Published: October 2007

The lytic effect of complement activated through the alternative pathway (AP) was studied on pathogenic and nonpathogenic Entamoeba histolytica recently isolated from stool samples. Recent nonpathogenic isolates were nearly unaffected by exposure to AP whereas recent pathogenic stool isolates were highly susceptible to AP dependent complement‐mediated lysis. Complement susceptible pathogenic stool isolates developed complement resistance in vivo during hamster liver passage and in vitro during cultivation in the presence of increasing concentrations of normal human serum (NHS). Since a clone of pathogenic HM‐l.IMSS which initially was highly susceptible also acquired complement resistance during cultivation in the presence of NHS, it is concluded that complement resistance was caused by induction rather than by selection alone. Because cultivation in the presence of heat‐inactivated NHS did not affect complement susceptibility of the cloned HM‐l.IMSS, complement activation itself might induce complement resistance in pathogenic E. histolytica.
Pulmonary inflammation and immune responses during the course of Nippostrongylus brasiliensis infection: lymphocyte subsets in bronchoalveolar lavage fluids of rats
Authors: RAMASWAMY K. , BEFUS D.
Published: October 2007

Quantitative measurements were made of different phenotypes of lymphocytes in bronchoalveolar lavage fluid (BALF) of rats during the course of a primary or secondary infection with Nippostrongylus brasiliensis. These changes were compared with those in the peripheral blood to understand the site‐specificity of the responses. Following infection, there was a significant increase in both B and T lymphocytes in BALF. The CD4: CD8 ratio was significantly altered with a decreased ratio on day 2 and increased ratio on days 16 and 32 post infection (p.i.). Two colour analysis showed that during larval migration through the lungs (day 2 p.i.) there was a significant increase in CD8+, CD4+ OX22+ and CD4+ OX22‐ cells in BALF. As infection progressed in time, CD4+ OX22 – cells were increased significantly. Compared to primary infection, a secondary infection resulted in increased recovery of CD4+ OX22– cells in BALF. These changes were not readily appreciated in the peripheral blood, suggesting site‐specific compartmentalization of lymphocyte responses in the lung. The functional significance of these dynamic changes in lymphocyte subsets in the airspaces following infection remains to be identified.
A longitudinal study of naturally acquired cellular and humoral immune responses to a merozoite surface protein (MSP1) of Plasmodium falciparum in an area of seasonal malaria transmission
Authors: RILEY E. M. , MORRIS‐JONES S. , BLACKMAN M. J. , GREENWOOD B. M. , HOLDER A. A.
Published: October 2007

A longitudinal study of cellular and serological responses to the major merozoite surface protein of Plasmodium falciparum (PfMSP1) has been conducted in a malaria immune population living in The Gambia, where malaria transmission is seasonally endemic. Recombinant or native proteins representing the sequence of PfMSP1 from the Wellcome strain of P. falciparum were used in in vitro lymphocyte proliferation, cytokine and antibody assays. Cellular responses of individual donors fluctuated over time, independent of seasonal changes in malaria transmission whereas anti‐PfMSP1 antibody levels were remarkably stable. At a population level, IFNγ responses were both more prevalent and of greater magnitude at the end of the rainy (malaria transmission) season than during the dry season. Responses of individuals lving in a rural village were compared with those of individuals living in an urban area with much lower levels of malaria transmission. Malaria infections were more likely to be symptomatic in urban dwellers than in inhabitants of rural villages but no significant differences in the level or prevalence of cellular or serological responses were seen between the two groups. However, urban dwellers with current symptomatic malaria infections had somewhat lower anti‐PfMSP1 antibody levels than their healthy, non‐parasitaemic neighbours.
The profile of IgG1 and IgG2a antibody responses in mice exposed to Schistosoma mansoni
Authors: MOUNTFORD A. P. , FISHER A. , WILSON R. A.
Published: October 2007

The segregation of IgG2a and IgG1 immunoglobulin isotypes as markers for Th1 and Th2 lymphocytes respectively, was investigated in mice exposed to normal or optimally‐irradiated S. mansoni cercariae. Using a panel of ELISAs, soluble antigens from lung‐stage schistosomula, adult worms, or eggs, were probed with serum samples collected at biweekly intervals. Infected mice developed increased IgG1 responsiveness to all three antigens, especially between weeks five and seven, whereas IgG2a responses were lower, particularly to egg antigens. This confirms that Th2 responses are dominant after the onset of patency in infected mice. In comparison, vaccinated mice developed lower levels of IgG1, and higher levels of IgG2a to larval and worm antigens. Thus, they had balanced expression of IgG1 and IgG2a, despite having a dominant Th1 lymphocyte population. An elevated IgG1 response to egg antigens in vaccinated mice challenged with normal parasites, occurred two weeks later than in normal mice. Mice exposed to male‐only cercariae developed IgG1 and IgG2a antibodies to larval and worm antigens. However, they also had elevated IgG1 to egg antigens from week five, despite a total absence of eggs. Therefore, adult worm antigens may cross react with the egg and stimulate the switch to Th2 dominated responsiveness.
Passively transferable protection against Schistosoma japonicum induced in the mouse by multiple vaccination with attenuated larvae: the development of immunity, antibody isotype responses and antigen recognition
Authors: DUNNE D. W. , JONES F. M. , COOK L. , MOLONEY N. A.
Published: October 2007

Vaccination of mice with attenuated S. japonicum cercariae induces protection against secondary infection which can be transferred to naive mice with serum (VMS). The presence of antibody does not per se impart protection as serum from mice carrying non‐attenuated infections (CIS), contains high levels of specific antibody, but confers no protection. Here we describe the increased protection transferred (20 to 68%) with increased number of vaccinations (one to five) given to the donors, and its decline with time after the final vaccination. We also describe the development of IgM, IgA, IgE, total IgG and IgG subclass responses in VMS, giving different levels of protection and CIS, directed against sodium periodate‐sensitive and ‐resistant epitopes in ‘skin‐stage’, ‘lung‐stage’and ‘liver‐stage’schistosomula, adult worms and eggs. In addition, antibody affinity maturation, development of S. japonicum species‐specific responses, and vaccination‐specific responses were examined. No response developed in parallel with serum‐mediated immunity, suggesting immunity may be due to responses against individual antigens. Preliminary examination of antigens recognized in Western blot showed that two schistosomal membrane antigens, of 13 and 40 kDa, were recognized by VMS from mice vaccinated five times (68% protection), but not by twice vaccinated VMS (27% protection). Neither antigen was recognized by non‐protective CIS.
Evidence for limited activation of distinct CD4+ T cell subsets in response to the Plasmodium falciparum circumsporozoite protein in Papua New Guinea
Authors: DOOLAN DENISE L. , BECK HANS‐PETER , GOOD MICHAEL F.
Published: October 2007

Both CD4+ and CD8+ T cells, as well as antibody, are known to be important in sporozoite immunity. Data from animal studies suggest that cytokines, in particular γ‐interferon and interleukin‐6, are involved. The interplay of these various factors and their importance in vaccine development has, however, not yet been elucidated. In this study, we have studied cellular and humoral responses of individuals naturally exposed to malaria in a highly endemic region of Papua New Guinea to the circumsporozoite protein of Plasmodium falciparum, a prime vaccine candidate antigen. A paucity of any CD4+ lymphoproliferative response to this protein by Papua New Guineans was notable which parallels our recent observation of a paucity of CD8+ T cell response and contrasts markedly with the responses of other endemic populations. There was nevertheless a significant antibody response to the central conserved B cell epitope, (NANP)n, as well as to other critical epitopes. An inverse relationship between γ‐interferon production and interleukin‐6 production and a positive correlation between γ‐interferon production and CS peptide‐specific lymphoproliferation was observed. High levels of peptide‐specific IL‐6 production were associated with high levels of peptide‐specific serum antibodies. Our data provide evidence for the limited activation of distinct CD4+ T cell subsets and for the existence of functionally distinct subpopulations of human CD4+ T cells with respect to cytokines known to be important in sporozoite immunity.
Expression of an Onchocerca volvulus Ov33 homolog in Dirofilaria immitis: potential in immunodiagnosis of heartworm infection
Authors: MEJIA J. SANTIAGO , NKENFOU CELINE , SOUTHWORTH MAURICE W. , PERLER FRANCINE B. , CARLOW CLOTILDE K. S.
Published: October 2007

In this study, the expression of an Onchocerca volvulus Ov33 homolog was demonstrated in Dirofilaria immitis. Rabbit antiserum raised against a recombinant fusion protein of O. volvulus, MBP/OvD 5B (Ov33), was found to react with a 31–33 kDa glycoprotein (DiT33) of adult worms of D. immitis. An antibody response to MBP/OvD 5B was observed in dogs, as early as 11 weeks post infection with infective larvae of D. immitis, and in dogs with occult infection. Cats both experimentally and naturally infected with D. immitis also reacted strongly with the recombinant antigen. In contrast, sera from dogs receiving chemically‐abbreviated infection or from animals harbouring a variety of other helminths failed to react. These data suggest that antibody responses generated by DiT33 may have potential in immunodiagnosis of heartworm infection in cats and dogs.
Resistance against Taenia hydatigena in sheep after passive transfer of serum or colostrum
Authors: JACOBS H. J. , MORIARTY K. M. , CHARLESTON W. A. G. , HEATH D. D.
Published: October 2007

The role of antibody in the resistance of sheep to infection with Taenia hydatigena metacestodes was examined using passive transfer of immunoglobulin. The immunoglobulin either was experimentally transferred in serum, or was transferred from immune ewes to their new‐born lambs in colostrum. Pooled serum from donor lambs which had received one, light, oral infection did not protect recipients although the donors themselves were immune. However, transfer of pooled serum from donors which had either received three oral infections, or three immunizations with solubilized T. hydatigena oncospheres in a water‐in‐oil adjuvant, resulted in 70–80% fewer cysts in the recipients. Colostrum from ewes infected with three high or low doses of T. hydatigena eggs was transferred to their lambs. A short acting protection (one to three weeks) was observed in the lambs. Comparisons by ELISA and Western blot, of the anti‐T. hydatigena oncosphere antibody content of the donor sera, the sera of the recipients collected 24 h and seven days after transfer, the sera of the lambs and ewes, and the colostrum of the ewes, indicated that resistance to the challenge infection depends upon a critical level of antibody.
A theoretical framework for the immunoepidemiology ofPlasmodium falciparummalaria
Authors: GUPTA SUNETRA , P. DAY KAREN
Published: October 2007

Molecular genetic analyses ofP. falciparumhave led to the cloning and sequencing of a number of antigens that are potential candidates for vaccination against malaria. Seroepidemiological studies in endemic areas have attempted to assess the relative importance of these antigens in protection against malaria. In this paper, we attempt to evaluate the relative contributions of conserved and strain‐specific immune responses by modelling their influence of age‐specific patterns of infection and disease. The modelling exercises in this paper clearly demonstrate that the observed patterns of age‐prevalence are best explained by proposing that the accumulation to a threshold of an immune response against a conserved determinant is required for protection against infection, while ‘anti‐disease’ immunity develops more linearly with exposure. This is compatible with the conjecture that the parasite population is structured into several independently transmitted strains, that each confers some degree of ‘anti‐disease’ immunity, but does not protect against further infection by the same strain. Within this framework, the average duration of parasitaemia increases with age, as previously encountered strains endure for longer periods at a subclinical level. Indirect evidence for the increase in duration of parasitaemia with age may be obtained from a comparison of age‐prevalence curves between dry and rainy seasons. By using mathematical methods to structure epidemiological and immunological information, we provide a coherent theoretical framework for the dissection of the important components of naturally acquired immunity to malaria.