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Biomedical subjects

A Sher

Publications and source records attributed to A Sher.

At least 307 records · Page 17Linked to original sources
PubMed1980

Studies of the antibody-dependent killing of schistosomula of Schistosoma mansoni employing haptenic target antigens. I. Evidence that the loss in susceptibility to immune damage undergone by developing schistosomula involves a change unrelated to the masking of parasite antigens by host molecules.

A method was developed for coupling a hapten, trinitrophenyl (TNP), to the surface of schistosomula of Schistosoma mansoni which results in a minimal loss in their viability as judged by morphological examination in vitro and survival after injection in vivo. Skin-stage (3-h-old) and lung-stage (5-d-old) schistosomula surface labeled in this manner were then compared for their susceptibility to killing by anti-TNP antibody-dependent effector mechanisms both in vivo and in vitro. TNP skin-stage larvae were readily rejected in mice actively immunized against TNP bovine gamma globulin and were highly susceptible to anti-TNP-dependent killing mediated either by complement or purified human eosinophils in vitro. In contrast, TNP-lung-stage schistosomula, which were shown by microfluorimetry to bind anti-TNP antibody to approximately the same extent as skin-stage schistosomula, were found to be resistant to killing by the same in vivo and in vitro mechanisms. These findings suggest that the insusceptibility of postskin-stage schistosomula to antibody-dependent killing must result at least in part from an intrinsic structural change in the integument of the parasite and cannot be caused solely by the masking of parasite antigens by acquired host molecules, a mechanism of immune evasion previously proposed for schistosomes.

Animals↗
PubMed1980

Cell mediated immune responses in experimental amebiasis.

Cell migration was inhibited when Entamoeba histolytica antigen-sensitized peritoneal exudate cells were cultured in the presence of specific antigen. The inhibition of cell migration was caused due to interaction of antigen with sensitized lymphocytes. This migration inhibition was well correlated with cell mediated immune responses, but not with circulating antibody levels. Peritoneal cells obtained from animals immunized with 70.5 microgram of antigen gave a better response in capillary tube tests. It was further found that 0.88 microgram antigen constitutes an optimum dose for studying migration inhibition reaction. The results obtained from the capillary and agarose plate technics show a slight disparity due to a difference in the respective specificities of the two tests. Agarose plate technic appears to be rather specific for pure antigen samples, while the capillary tube test is more appropriate for crude type antigens.

Amebiasis↗
PubMed1980

Specificity of alloreactive T lymphocytes that adhere to lung stage schistosomula of Schistosoma mansoni.

Alloreactive T lymphocytes generated against MHC antigens have previously been shown to adhere to lung stage schistosomula of S. mansoni because of the host MHC products known to be present on the surface of the parasites. In experiments reported here, the cells in this adherent population were shown to consist of Ly-2 positive, Thy-1 positive lymphocytes and to react specifically with products of the K and D but not the I region of the MHC. These results strengthen previous findings suggesting that the adherent lymphocytes are CTL.

Animals↗
PubMed1980

Newly transformed schistosomula spontaneously lose surface antigens and C3 acceptor sites during culture.

The binding of rat anti-schistosome antibody and rat C3 to the surface of newly transformed schistosomula of S. mansoni was measured by quantitative immunofluorescence during the first 48 hr of their development in vitro. Schistosomula, cultured in media either with or without serum, lost antibody or C3 from their surface exponentially with a halftime of 5 hr for both labels. The loss of the surface molecules is seen in parasites that are labeled and then cultured as well as in parasites cultured and then labeled, indicating that the labeling procedure itself is not inducing the observed change. This immunochemical modification in the schistosomulum surface appears to be independent of host molecule adsorption and intrinsic to the development of the parasite.

Animals↗
PubMed1979

Purification of rodent eosinophils on discontinuous metrizamide gradients.

Methods are described for the purification of rat and mouse eosinophils. Peritoneal exudate cells obtained from Schistosoma mansoni- or Trichinella spiralis-infected mice were plated on plastic dishes, and the nonadherent cells were centrifuged over discontinuous hypertonic metrizamide gradients. Approximately 41% of those eosinophils present in the original preparations were recovered from the interfaces between 20% and 22% metrizamide at an average of 88% purity. Peritoneal cells obtained from either uninfected or S. mansoni-infected rats were placed directly onto metrizamide gradients. After centrifugation, essentially all eosinophils present in the original preparations were recovered at the interface between 18.5% and 22.5% metrizamide, with an average of 80% purity. These methods for eosinophil purification have proven to be reproducible and to yield cells which are morphologically preserved and functional, as demonstrated by their ability to respond to a chemotactic stimulus.

Animals↗
PubMed1979

Major histocompatibility complex products restrict the adherence of cytolytic T lymphocytes to minor histocompatibility antigens or to trinitrophenyl determinants on schistosomula of Schistosoma mansoni.

We have previously shown that schistosomula passaged through mice acquire histocompatibility (H) antigens that can be recognized either by alloantibody or by alloreactive cytolytic T lymphocytes (CTL). The latter specifically adhere to but fail to damage the parasite. In this paper we describe the use of trinitrophenyl (TNP)-labeled schistosomula to show that the adherence of CTL with specificity for TNP-modified syngeneic cells is restricted by the major histocompatibility complex (MHC) in a fashion similar to that seen in the lysis of TNP-labeled tumor targets. Thus, these CTL adhere only to schistosomula that have both the appropriate H antigens and TNP determinants on their surface, and not to schistosomula bearing either of these antigens by themselves. We note a significant degree of adherence to schistosomula bearing TNP determinants and H antigens allogeneic to the CTL. Anti-minor H antigen CTL are also restricted by the MHC in their adherence; thus, they only adhere to schistosomula that carry both the major and minor H antigens of the stimulator cells. These antigens can be acquired either by a single passage in vivo of schistosomula through congenic strains that possess both the relevant antigens or by sequential passage through two different strains, each contributing one of the antigens in question.

Animals↗
PubMed1979

Potentiation of schistosome granuloma formation. By lentinan--a T-cell adjuvant.

Lentinan is a fungal polysaccharide which acts as a T-cell adjuvant. When this glucan was administered to thymus-intact mice by intraperitoneal injection, conspicuously enlarged lung granulomas formed in response to either Schistosoma mansoni or S japonicum eggs or to antigen-coated polyacrylamide beads. Liver granulomas in cercaria-induced S mansoni infection were augmented up to eight-fold in volume. By contrast, nude mice showed a complete absence of hypersensitivity granulomas, regardless of whether they received lentinan. Lentinan-potentiated granulomas show a distinctive histopathologic picture characterized by abundant, large, pale-staining macrophages; reduced and redistributed eosinophil populations; and frequent, extensive central necrosis, uncommon in unpotentiated schistosome foci. They also differ in their distributions of egg antigen and of host immunoglobulins. Optimal lentinan effects followed a single 1-mg dose when given to sensitized mice on the day of intravenous challenge with S mansoni eggs rather than at the time of intraperitoneal sensitization or following challenge. This adjuvant appears to act on effector T cells or on macrophages interacting with T cells; its effect on macrophages in a latex bead foreign body granuloma was minimal. A number of other lentinan-associated systemic effects on parasite and host were noted and described, including reduced female schistosome egg output.

Adjuvants, Immunologic↗
PubMed1978

Acquisition of murine major histocompatibility complex gene products by schistosomula of Schistosoma mansoni.

Schistosoma mansoni schistosomula recovered from the lungs of inbred mice were shown to possess serologically detectable alloantigens on their tegumental surfaces. Using appropriate antisera and infected congenic and recombinant mice as worm donors, gene products of the K and I subregions of the major histocompatibility complex were demonstrated among these alloantigens acquired by the parasites. In contrast, other cell surface alloantigens, such as Thy 1, Ly 1, and H-Y and the serum proteins albumin, C3 and Ig, could not be detected on the surface of lung schistosomula by means of comparable techniques. In another series of experiments, schistosomula recovered from the lungs of mice and reinjected into allogeneic recipients were shown to exchange their alloantigens during an 87-h period of examination. Similarly, lung schistosomula cocultured with allogeneic lymphocytes were shown to acquire major histocompatibility complex (MHC) coded antigens from the cells. It is possible that as acquired host molecules, MHC gene products may disguise the surface of schistosome parasites thereby rendering them insusceptible to immune attack.

Animals↗
PubMed1978

Early developmental changes of the schistosomula of Schistosoma mansoni in vitro and in mouse lung.

Fresh (3 h) schistosomula of Schistosoma mansoni were obtained by the skin penetration method and injected intravenously into groups of mice either immediately or after 48 h incubation in tissue culture. Schistosomula were then recovered from the lungs 1 to 2 days after injection. The recovery results showed that the ability of uncultured schistosomula to emerge from lung tissue increased with time, became maximal on the 3rd day and diminished thereafter. In contrast, cultured schistosomula were able to emerge from chopped lung at a much earlier time after injection. Fresh schistosomula, as well as those recovered from mouse lungs, were assayed by indirect immunofluorescence for the presence of parasite and host antigens. Similarly, fresh schistosomula which had been incubated in foetal calf serum, with or without mouse red blood cells, were assayed for parasite and host antigens after 3-24 h of culture. Fresh schistosomula expressed parasite antigen with greater intensity than those recovered from mouse lungs and showed no trace of host antigen. Lung schistosomula, on the other hand, expressed less parasite antigen but more red blood cell antigen with increasing time in the host. Schistosomula cultured in the absence of mouse red blood cells expressed only parasite antigen throughout the period in culture, while those cultured in the presence of mouse red blood cells also expressed parasite antigen during the entire period in culture but, in addition, by 24 h host antigen could also be detected. These developmental and adaptational changes may play a role in determining the survival of parasites in the normal or immune host.

Animals↗
PubMed1977

Host antigens and parasite antigens of murine Schistosoma mansoni.

An indirect fluorescent antibody technique was used to detect mouse host antigens and parasite antigens on the surface of Schistosoma mansoni. A rabbit anti-mouse rbc antiserum to detect host antigens, and serum from mice immune to S. mansoni was used to detect parasite antigens. Schistosomula prepared after penetration of isolated mouse skin did not possess host antigens but bound antibody from immune serum (immune antibody); schistosomula recovered from the lungs of mice five days after infection possessed host antigens and failed to bind immune antibody. In contrast, schistosomula recovered from the skin of normal or immune mice three and 20 hours after cercarial penetration, adult worms, and cryostat sections of adult worms, were positive for host antigens but also bound immune antibody. Strong binding of immune antibody only occurred with the cryostat sections. Anti-schistosome antibody can therefore bind to schistosomes in the presence of host antigen. The lung forms of schistosomula however, may have different surface properties as there is no evidence that immune antibody binds to these forms.

Animals↗