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Immunology May 1988Monoclonal antibodies were produced following immunization of mice with live infective larvae of Brugia malayi. One of these, 46.08.76, is an antibody that promotes...
Monoclonal antibodies were produced following immunization of mice with live infective larvae of Brugia malayi. One of these, 46.08.76, is an antibody that promotes adherence of mouse peritoneal macrophages and human peripheral blood leucocytes to the infective larvae of B. malayi and Wuchereria bancrofti, respectively, and kills them. Fresh normal serum, as a source of complement, augments this effect. The same monoclonal antibody conferred 89% protection to jirds (Meriones unguiculatus) against challenge infection of B. malayi stage-three larvae. This monoclonal antibody recognizes antigens of 80,000, 67,000, 52,000 and 36,000 MW proteins present among the antigens of larvae, as detected by an immunoblotting technique. The antibody also reacts with antigens of infective larvae of Litomosoides carinii, Dipetalonema viteae and B. pahangi, but to a smaller extent.
Topics: Animals; Antibodies, Monoclonal; Antibody Specificity; Antibody-Dependent Cell Cytotoxicity; Antigens, Helminth; Brugia; Cross Reactions; Filariasis; Gerbillinae; Immunization, Passive; Mice; Mice, Inbred BALB C; Microfilariae; Molecular Weight
PubMed: 3384450
DOI: No ID Found -
Immunology Dec 1986The anti-phosphoryl choline antibody responses of resistant and susceptible strains of mice infected with microfilariae of Dipetalonema viteae or the gastrointestinal...
The anti-phosphoryl choline antibody responses of resistant and susceptible strains of mice infected with microfilariae of Dipetalonema viteae or the gastrointestinal nematode parasite Trichinella spiralis were determined. The responses were characterized both in terms of their kinetics and the constituent role played by each immunoglobulin heavy-chain class. Infection with either parasite elicited detectable responses in all strains investigated. However, the kinetics of the response of each heavy-chain class within each strain could vary independently. Furthermore, differences were observed between the responses of inbred mouse strains that differ in their ability to control infection. It was not possible, however, to correlate these differences in the serological response with the ability of these animals to control infection. The results are discussed in relation to attempts to improve serological diagnostic assays.
Topics: Animals; Choline; Dipetalonema Infections; Filariasis; Immunoglobulins; Mice; Mice, Inbred Strains; Phosphorylcholine; Trichinellosis
PubMed: 3804381
DOI: No ID Found -
Infection and Immunity Jun 1986Jirds with prepatent Dipetalonema viteae infections develop an acquired immunity to challenge infections. The objective of the present study was to observe...
Jirds with prepatent Dipetalonema viteae infections develop an acquired immunity to challenge infections. The objective of the present study was to observe parasite-specific and nonspecific cellular and humoral immune responses in immune jirds. Splenic hyperplasia was observed in infected jirds during the first 5 weeks of infection. Antigen-reactive spleen cells were observed in the lymphocyte transformation assay at 3 weeks postinfection. A depressed response to concanavalin A (ConA) was seen at 1 week postinfection through week 5. Mitomycin C-treated cells from infected jirds were capable of suppressing the response of normal cells to ConA. Sephadex G-10-nonadherent spleen cells from infected jirds showed elevated responses to D. viteae antigen at 1, 3, and 5 weeks and elevated responses to ConA at 3 and 5 weeks. Filaria-specific antibodies were seen at 1 week postinfection, and titers rose through week 5. Plaque-forming cell production to sheep erythrocytes was not depressed in infected jirds. It was concluded that jirds react immunologically with both cellular and humoral responses during the prepatent period of D. viteae infection. A concurrent immune depression was seen. Its effect on resistance and tolerance remains to be determined.
Topics: Animals; Antibody Formation; Antigens, Helminth; Dipetalonema; Dipetalonema Infections; Filariasis; Gerbillinae; Immunity, Cellular; Lymphocyte Activation; Male; Spleen; Splenomegaly
PubMed: 3710584
DOI: 10.1128/iai.52.3.742-747.1986 -
Immunology Jan 1986In vivo and in vitro experiments were performed to study immune protective mechanisms against larval Dipetalonema viteae. Jirds infected with 30 third-stage larvae (L3)...
In vivo and in vitro experiments were performed to study immune protective mechanisms against larval Dipetalonema viteae. Jirds infected with 30 third-stage larvae (L3) of D. viteae for 1, 3 or 5 weeks showed significant killing of challenge larvae implanted for 2 weeks in diffusion chambers. A retardation of larval growth was seen 7 days after larval implantation, and larval death was observed beginning at 10 days. When L3 were placed in vitro with peritoneal exudate cells (PEC) from normal jirds, cellular adherence was seen starting on Day 4, and larval death was seen on Day 10. It was concluded that larvae had to undergo some development in vitro, that would allow cellular adherence to larval surface. Larvae, recovered after 7 days in vivo or in vitro, were placed in culture with normal PEC; cell adherence and worm death occurred at equal rates for both groups of worms. Larvae which had been in culture for 7 days were implanted in immunized jirds for 7 days. Significant killing of these worms was observed, whereas larvae recovered from ticks prior to implantation were not killed. In vivo and in vitro results therefore show that larval development is required for generating susceptibility to specific and/or non-specific immune reactions. A hypothesis is suggested for the function of larval retardation.
Topics: Animals; Ascitic Fluid; Cell Adhesion; Dipetalonema; Dipetalonema Infections; Filariasis; Gerbillinae; Immunity, Innate; In Vitro Techniques; Larva; Male; Ticks
PubMed: 3943876
DOI: No ID Found -
The Biochemical Journal Dec 1985The present study deals with the discovery and partial characterization of specific binding proteins for retinol and retinoic acid from filarial parasites (worms of the...
The present study deals with the discovery and partial characterization of specific binding proteins for retinol and retinoic acid from filarial parasites (worms of the superfamily Filarioidea), including those from two species of Onchocerca. These binding proteins, which are distinct in their physicochemical properties and in the mode of ligand interactions from the host-tissue retinoid-binding proteins, may be involved in the mediation of the putative biological roles of retinoids in the control of parasitic growth, differentiation and reproduction. Parasite retinol-binding protein and retinoic acid-binding protein exhibited specificity for binding retinol and retinoic acid respectively. Both the binding proteins showed an s20,w value of 2.0 S. On gel filtration, both proteins were retarded to a position corresponding to the same molecular size (19.0 kDa). On preparative columns, the parasite binding proteins exhibited isoelectric points at pH 5.7 and 5.75. Unlike the retinoid-binding proteins of mammalian and avian origin, the parasite retinoid-binding proteins showed a lack of mercurial sensitivity in ligand binding. The comparative amounts of retinoic acid-binding protein in five parasites, Onchocerca volvulus, Onchocerca gibsoni, Dipetalonema viteae, Brugia pahangi and Dirofilaria immitis, were between 2.7 and 3.1 pmol of retinoic acid bound/mg of extractable protein. However, the levels of parasite retinol-binding protein were between 4.8 and 5.8 pmol/mg, which is considerably higher than the corresponding levels of cellular retinol-binding protein of mammalian and avian origin. Both retinol- and retinoic acid-binding-protein levels in O. volvulus-infected human nodules and O. gibsoni-infected bovine nodules were similar to their levels in mammalian tissues. Also, these nodular binding proteins, like the host-binding proteins, exhibited mercurial sensitivity to ligand interactions.
Topics: 4-Chloromercuribenzenesulfonate; Animals; Carrier Proteins; Centrifugation, Density Gradient; Filarioidea; Isoelectric Focusing; Macromolecular Substances; Molecular Weight; Protein Binding; Receptors, Retinoic Acid; Retinol-Binding Proteins; Retinol-Binding Proteins, Cellular; Tretinoin; Vitamin A
PubMed: 3004410
DOI: 10.1042/bj2320577 -
Parasite Immunology Jul 1985Dipetalonema viteae (Filarioidea) infections were established in inbred strains of mice by the s.c. implantation of adult female worms and the resulting microfilaraemia...
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.
Topics: Animals; Dipetalonema; Female; Filariasis; Genes, MHC Class II; Heterozygote; Host-Parasite Interactions; Mice; Mice, Inbred Strains; Radiation Chimera
PubMed: 3929210
DOI: 10.1111/j.1365-3024.1985.tb00081.x -
Immunology Mar 1984Neutrophils from the peripheral washings of normal rats in the presence of sera obtained from rats immune to circulating microfilariae adhered to and killed the...
Neutrophils from the peripheral washings of normal rats in the presence of sera obtained from rats immune to circulating microfilariae adhered to and killed the microfilariae of Dipetalonema viteae in vitro within 16-24 hr. No significant adherence or cytotoxicity was mediated by sera collected from animals with a high microfilaraemia or from normal rats. Ultrastructural studies show that neutrophils, which are bigger than microfilariae, can easily internalize the small larvae resulting in the disintegration of the parasite. Immunoadsorption and inhibition experiments showed that the adherence-promoting activity resides both in IgG and IgE classes of antibody. However, the mere participation of these two antibodies is not sufficient to effect neutrophil adherence towards microfilariae, the presence of complement is also required. Samples of fresh immune rat serum (fIRS) depleted in alternative pathway components of complement by treatment with zymosan A failed to mediate cell adherence to the parasite. fIRS inactivated for the classical pathway of complement by the chelating agent EGTA partially retains its activity in mediating cytotoxicity to microfilariae. The striking antigenic specificity of D. viteae antibodies was shown by their ability to mediate cytotoxicity only to D. viteae but not towards Brugia malayi microfilariae.
Topics: Animals; Cell Adhesion; Cells, Cultured; Complement System Proteins; Cytotoxicity, Immunologic; Dipetalonema; Immunoglobulin E; Immunoglobulin G; Microfilariae; Microscopy, Electron; Neutrophils; Rats; Rats, Inbred Strains; Time Factors
PubMed: 6538183
DOI: No ID Found -
Clinical and Experimental Immunology Dec 1982The present study reports the presence of Onchocerca volvulus specific IgE in the sera obtained from onchocerciasis patients. About 70% of onchocerciasis patients showed...
Detection of IgE antibodies in onchocerciasis. Possibility of using allergens from Dipetalonema viteae extracts that cross-react with allergenic determinants in crude extracts of Onchocerca volvulus.
The present study reports the presence of Onchocerca volvulus specific IgE in the sera obtained from onchocerciasis patients. About 70% of onchocerciasis patients showed a raised level of O. volvulus specific IgE compared to patients infected either with other human filarids (Loa loa, Wuchereria bancrofti, Brugia malayi) or with other helminths (Schistosoma mansoni, Ascaris lumbricoides, Fasciola hepatica). The O. volvulus specific IgE level was significantly higher in patients exhibiting 'gale filarienne' than in microfilaremic patients or in endemic controls. The total IgE level was significantly raised in the serum samples of all groups of subjects from endemic areas compared to European controls. There was no significant increase in the level of IgE in the onchocerciasis sera when O. volvulus antigen was replaced by the antigens from various helminths in the present assay system (radioallergosorbent test). However, there was a clear evidence of the presence of cross-reacting allergens in the crude extracts from adults of O. volvulus and Dipetalonema viteae (a rodent filarial parasite) because there was a significant reduction in IgE level in onchocerciasis sera following absorption with either O. volvulus or D. viteae sorbents. Moreover, the IgE antibodies in onchocerciasis patients sera recognized the allergens which were present in the somatic extracts of O. volvulus and D. viteae as revealed by radiolabelled anti-IgE.
Topics: Allergens; Antigens; Cross Reactions; Dipetalonema; Epitopes; Humans; Immunoelectrophoresis; Immunoglobulin E; Onchocerca; Onchocerciasis; Radioallergosorbent Test
PubMed: 6187503
DOI: No ID Found -
Immunology Jan 1982To explore the relative species specificities of the IgE and IgG antibody responses to helminth infections in man, we studied four pools of sera from patients infected...
To explore the relative species specificities of the IgE and IgG antibody responses to helminth infections in man, we studied four pools of sera from patients infected with Wuchereria bancrofti, Brugia malayi, Onchocerca volvulus or Ascaris lumbricoides and ten individual sera from patients with onchocerciasis. IgE antibodies were detected by radioallergosorbent test (RAST) analysis and IgG antibodies by a Staphylococcus protein A radioimmunoassay (Staph A-RIA). Analysis of the binding curves with four different immunosorbents (prepared from antigens of B. malayi, O. volvulus, Dipetalonema viteae and A. lumbricoides) in the RAST and the binding curves with these same four antigens in the Staph A-RIA confirmed the relative species specificities for both the IgE and IgG antibody responses. Then determination of these antibody levels after specific absorption of the sera with both homologous and heterologous antigens showed that in all instances there was significantly less cross-reactivity with heterologous parasite antigens (i.e. higher species specificity) in the IgE antibody response to filarial infection than in the corresponding IgG antibody response. Such findings imply that efforts toward developing techniques for specific immunodiagnosis of filarial infections are likely to be particularly successful if focused on the IgE antibody response of exposed individuals.
Topics: Antigens; Ascariasis; Brugia; Cross Reactions; Dipetalonema Infections; Filariasis; Humans; Immunoglobulin E; Immunoglobulin G; Onchocerca; Onchocerciasis; Radioimmunoassay; Species Specificity
PubMed: 7199027
DOI: No ID Found -
Clinical and Experimental Immunology Jan 1981Infective larvae of did not reach maturity in inbred Fischer rats. However, female adults of when transplanted surgically into Fischer rats established and the...
Dipetalonema viteae infective larvae reach reproductive maturity in rats immunodepressed by prior exposure to Schistosoma mansoni or its products and in congenitally athymic rats.
Infective larvae of did not reach maturity in inbred Fischer rats. However, female adults of when transplanted surgically into Fischer rats established and the resulting microfilaraemia from the transplanted worms persisted for about 120 days after infection. Sequential dissections showed that some of the female worms transplanted remained viable in rats for about 35 days after infection. After inoculation of infective larvae into rats a varying number transformed into stage-4 larvae but they did not develop into adult worms and were killed. However, when the rats were immunodepressed non-specifically by a pre-existing infection or by treatment with -derived substance(s), a number of stage-4 larvae renewed their development and reached sexual maturity. These worms produced microfilariae which were observed in the peripheral blood for about 40 days. The effect of previous infection with on the survival and growth of in Fischer rats depends greatly on the relative timing of infection because infective larvae of reached maturity only when rats were inoculated with infective larvae after 15 days of infection but not after 21 or 28 days of infection. will also develop to maturity in congenitally athymic rats. In congenitally athymic rats (Nu/Nu) each given 75 infective larvae, both the microfilaraemia and adult worm recovery at post-mortem were higher than those which resulted in Nu/Nu rats given an infection of 200 larvae. These experiments show that in rats innate immunity to this filarial nematode reflects a very rapidly induced acquired immunity which kills the parasite before it reaches maturity.
Topics: Animals; Dipetalonema; Dipetalonema Infections; Filariasis; Immune Tolerance; Larva; Male; Rats; Rats, Inbred Strains; Schistosoma mansoni; Schistosomiasis; T-Lymphocytes; Time Factors
PubMed: 6972836
DOI: No ID Found