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D L Sacks

Publications and source records attributed to D L Sacks.

86 records · Page 5Linked to original sources
PubMed1983

Thermosensitivity patterns of Old vs. New World cutaneous strains of Leishmania growing within mouse peritoneal macrophages in vitro.

Infection of mouse peritoneal macrophages in vitro was used to examine the effect of elevated temperature on the intracellular replication of various strains of Leishmania. Of eight cutaneous strains examined, all grew optimally at 35 degrees C. At 37 degrees C the reduction in growth was most pronounced for the New World cutaneous strains, and at 39 degrees C three of four New World cutaneous strains were completely destroyed whereas all of the L. tropica strains survived and exhibited at least 100% growth after 3 days. The results of these in vitro studies correlate closely with the outcome of heat therapy on two patients with cutaneous disease, suggesting that, in general, cutaneous lesions due to L. tropica strains might be less responsive to heat therapy than lesions due to L. mexicana and related strains.

Animals↗
PubMed1983

Evidence that schistosome MHC antigens are not synthesized by the parasite but are acquired from the host as intact glycoproteins.

Schistosoma mansoni schistosomula recovered from the lungs of mice have previously been shown to express serologically detectable products of the major histocompatibility complex (MHC). To determine whether these determinants are products of the schistosome genome, DNA from cercariae and adult worms of the parasite was probed with a 32P-cDNA clone encoding a human class I MHC antigen. Although this probe hybridized to mouse DNA, no hybridization was observed with DNA isolated from schistosomes, indicating that there are no DNA sequences homologous to class I MHC antigens in the parasite genome. The class I MHC antigens found on schistosomes were characterized in a further series of experiments. Two monoclonal antibodies known to recognize spatially distinct determinants of H-2Kk both bound to lung-stage schistosomula recovered from mice expressing this haplotype, suggesting that a significant portion of the H-2K molecule is present at the larval surface. Furthermore, both antibodies precipitated from lysates of 125I-lactoperoxidase-labeled lung-stage schistosomula, a molecule of approximately 45,000 daltons similar in mobility to H-2Kk precipitated from 125I-labeled mouse spleen cells. These results support the hypothesis that the class I MHC antigens expressed on S. mansoni are not synthesized by the parasite but are acquired from the host as intact glycoproteins.

Animals↗
PubMed1983

Evidence that anti-idiotype induced immunity to experimental African trypanosomiasis is genetically restricted and requires recognition of combining site-related idiotopes.

The ability of anti-idiotypic (anti-Id) antibodies to immunize mice against African trypanosomiasis independent of antigen has been confirmed. Of three allogeneic anti-Id antibodies raised against three protective monoclonal antibodies, each with specificity for the variant surface antigen of a clone of Trypanosoma rhodesiense, only one (anti-7H11 Id) was effective in immunizing BALB/c mice against homologous challenge. The immunity was associated with the more rapid and enhanced expression of the corresponding Id after infection. The immunity was restricted to mice bearing genes linked to Igh-Ca, which appeared to control expression of this Id both in response to infection and anti-Id treatment. Another Id, 11D5, appeared to be under similar genetic control. Anti-11D5 Id, however, was ineffective in immunizing mice against infection despite inducing high levels of Id bearing molecules before challenge. The immunizing potential of the respective anti-Id antibodies appeared to be related to the relative concentrations of antibodies reactive with idiotopes near to or within the antigen-combining site, which, in turn, determined the relative proportion of Id-bearing clones activated that had antigen binding activity.

Animals↗
PubMed1982

Immunization of mice against African trypanosomiasis using anti-idiotypic antibodies.

Anti-idiotypic (anti-Id) antibodies were raised against three protective monoclonal antibodies, each with specificity for the variable antigen type (VAT) of a clone of Trypanosoma rhodesiense. The IgG1 fractions of each were pooled and administered to BALB/c mice 3-4 wk before homologous challenge. The course of primary parasitemia was altered in 19 of 30 anti-Id-treated animals. The immunity was manifested as either: (a) complete protection, (b) reduced parasitemia, or (c) selection against parasites bearing the original VAT. The three idiotypes (Id) were found in variable levels in serum during the course of infection in control animals. However, in all anti-Id-treated mice that displayed immunity, one Id in particular (7H11) was detectable much earlier in infection and in higher levels than in control mice or anti-Id-treated, nonimmune mice. Six of nine mice treated with the anti-7H11 Id alone also displayed immunity, manifested in this case exclusively as selection against parasites bearing the original VAT. The effect was again associated with the more rapid appearance of the Id after infection. Specificity of the anti-Id-induced immunity was supported by the failure of anti-7H11 Id treatment to alter the course of infection with a heterologous clone of T. rhodesiense. To our knowledge, this is the first report of the antigen-independent induction of antimicrobial immunity using anti-Id antibodies.

Animals↗
PubMed1982

Incubation of trypanosome-derived mitogenic and immunosuppressive products with peritoneal macrophages allows recovery of biological activities from soluble parasite fractions.

This report describes further attempts to define the nature of the parasite product(s) responsible for the extensive changes in lymphoid tissue in mice during infection with Trypanosoma brucei. As previously described, potent mitogenic and immunosuppressive effects are induced by a trypanosome-derived crude membrane fraction in vivo. There was no enrichment in these activities when purified parasite surface membranes were used. Mitogenic activity can be recovered from soluble trypanosome material only when it is incubated with peritoneal macrophages before transfer into syngeneic recipients. Thus, by encouraging association with a critical target cell, soluble parasite products can be studied, and their active components can be separated by conventional methods. Preliminary fractionation of high-spin trypanosome supernatant over Sepharose 4B confined the mitogenic activity to the high-molecular-weight fraction, which is a macromolecular complex of proteins, glycoproteins, and lipid. Extracted lipid from this material was able to significantly suppress a primary immunoglobulin G anti-sheep erythrocyte response. The activity was periodate sensitive and pronase resistant. The use of macrophages in vitro may be a general method whereby important biological activities lost as a result of fractionation procedures can be recovered and the active components studied in greater detail.

Animals↗
PubMed1980

Trypanosome-induced suppression of anti-parasite responses during experimental African trypanosomiasis.

The effect of Trypanosoma brucei infections on parasite-specific antibody responses was examined by immunization of infected mice with radio-attenuated trypanosomes of a noncross-reacting clone. Antibody titers (total Ig) against variant surface antigen were determined by indirect immunofluorescence. The suppression resulting from acute infection was virtually complete, and is associated with the failure to control the first relapse variant of the acute clone. The suppression resulting from chronic infection was much less severe, and subsequently variant populations of the chronic clone are successfully controlled. Antibody collected 10 days after each of the first 3 peaks of parasitemia during chronic infection was titrated on the homologous parasite preparations isolated from each wave in individual mice. As the infection progressed, both IgG and IgM antibody responses to each successive wave declined However, the decline of IgG antibody was more rapid than IgM, so that by the third parasite wave the mice responding with predominantly, if not exclusively, low levels of IgM antibody. We conclude that the severity of trypanosome-induced suppression of the anti-parasite response and IgM response in particular, determines the course of infection by trypanosomes varying in virulence.

Acute Disease↗
PubMed1980

Trypanotolerance in inbred mice: an immunological basis for variation in susceptibility to infection with Trypanosoma brucei.

Previous studies have suggested that the suppression of IgM responses induced by different strains of trypanosomes can be related to the virulence of the parasite in a defined mouse strain (Sacks et al. 1980). This study has examined immunosuppression induced by Trypanosoma brucei NIM7 in two mouse strains (C3H/He and [CBA/H x C57B1/6]F1) which differ considerably in their ability to survive infections. The results confirm our previous studies in that mice were able to survive infection whilst they maintained at last a residue of their ability to mount an IgM response to DNP-Ficoll, a T-independent antigen. Complete abrogation of the IgM response coincided with fulminating parasitaemia, resulting in the death of the host.

Animals↗
PubMed1979

Membrane fractions of trypanosomes mimic the immunosuppressive and mitogenic effects of living parasites on the host.

African trypanosomiasis in mice leads to profound changes in lymphoid tissues. In an attempt to define the nature of the trypanosome stimulus, we have studied the effect of radio-attenuated trypanosomes and their subcellular fractions in vivo. We find that relatively low doses of irradiated Trypanosoma brucei S42 injected into (CBA/H x C57B1/6)F1 mice mimicked the previously reported effects of infective parasites. 2 x 10(7) irradiated trypanosomes caused a greater than two-fold increase in spleen weight accompanied by a roughly 10-fold increase in background plaque forming cells (PFC) to sheep red blood cells (SRBC). The primary response to SRBC was significantly enhanced when priming was carried out on the day of trypanosome injection, but significantly suppressed when carried out 3 days later. Disruption of trypanosomes by freeze-thawing did not destroy their mitogenic or immunosuppressive activities. A membrane fraction collected by high speed centrifugation (150 000 x g) after removal of larger organelles at 12 000 x g retained both mitogenic and suppressive activities. The high speed supernatant lost the ability to enhance background PFC, but still caused partial immunosuppression with a much lower potency than the membrane pellet. Whether immunosuppression and enhanced PFC levels relate to the same parasite product is not clear as yet, but both effects can be ascribed to a membrane fraction of the parasite.

Animals↗
PubMed1979

Isolation of a type-specific antigen from Chlamydia trachomatis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

This report describes the isolation of a type-specific antigen of a serotype A strain of Chlamydia trachomatis. The antigen could be identified in sodium dodecyl sulfate-polyacrylamide electrophoretic (SDS-PAGE) analysis of immunoprecipitates of homologously reacted lysates from Bolton-Hunter 125I-labeled elementary bodies, solubilized by sonication and treatment with Nonidet P40. The electrophoretic pattern of this precipitate revealed a peak of unique mobility that was not reproduced by heterologous or control precipitates. Immunoadsorbtion of test antigen with purified IgG fractions from homologous antisera completely removed this peak, whereas similar adsorbtion wth heterologous IgG had minimal effect. Comparison of this antigen in SDS-PAGE with protein standards revealed an approximate m.w. of 27,000.

Animals↗
PubMed1978

Cell-mediated immune responses in owl monkeys (Aotus trivirgatus) with trachoma to soluble antigens of Chlamydia trachomatis.

The first temporal study of the cell-mediated immune responses (CMI) following ocular infections with Chlamydia trachomatis is presented. We examined the CMI of owl monkeys infected with trachoma to soluble antigens of C. trachomatis by leucocyte migration inhibition (LIF) and delayed hypersensitivity skin testing. Delayed hypersensitivity of a systemic nature developed after a local eye infection in owl monkeys; clearance of inclusions from conjunctival cells coincided with the onset of this response. The association of eye secretion and circulating antibodies with recovery from primary infection was not so striking. Both cellular and humoral immune responses persisted for at least 2 months, at which time all test animals were completely resistant to re-infection. The elicitation of cell-mediated immune reactions with solubilized chlamydial antigens may permit the isolation of specific antigens involved in the generation of protective immunity in the owl monkey model.

Animals↗
PubMed1978

Separation and partial characterization of a type-specific antigen from Chlamydia trachomatis.

Type-specific antigens of Chlamydia trachomatis have been demonstrated by the mouse toxicity prevention test and a variety of immunofluorescent techniques. In addition, biologic activity has been associated with these antigens in terms of type-specific immunity to trachoma infections. This report is the first to describe the detection of a soluble type-specific antigen of C. trachomatis and its separation from those antigens that cross-react among different immunotypes. Test antigens were prepared by labeling the surface components of purified, yolk sac grown organisms with a radioiodinated intermediate (Bolton-Hunter reagent, 125I). The organisms were solubilized with Triton X-100 and gel filtered through Sepharose 6B. All fractions were then tested in radioimmunoassay for binding with rabbit antisera raised against solubilized immunogens prepared from homologous and heterologous strain organisms propagated in BHK-21 cells. A fraction demonstrating homologous binding only was used in subsequent modified procedures for the preparation of quantities of type-specific antigen sufficient for analysis. The antigen appears to be a heat labile, cell surface protein associated with apparent immunogenic activity during the course of actual chlamydial eye infection.

Antigen-Antibody Complex↗
PubMedDate not supplied

Developmental modification of the lipophosphoglycan from Leishmania major promastigotes during metacyclogenesis.

Lipophosphoglycan was isolated from the dividing, noninfective stage and from the nondividing metacyclic stage of Leishmania major promastigotes. The lipophosphoglycans were characterized by SDS-PAGE and by chromatographic and quantitative analysis of phosphatidylinositol-specific phospholipase C- and mild acid-generated fragments. The results revealed two stage-specific structural differences: (i) an increase in size of the metacyclic form of the glycoconjugate due to an approximate doubling in the number of its salient phosphorylated saccharide units; and concomitantly, (ii) a subtle compositional change in these units. Gas-liquid chromatographic analysis indicated that the phosphatidylinositol lipid anchor was developmentally conserved. These developmental modifications suggest important roles for the lipophosphoglycan which have not been previously considered, such as promoting complement resistance within the vertebrate host, and midgut attachment and release within the sand fly vector.

Animals↗