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Biomedical subjects

C L Geczy

Publications and source records attributed to C L Geczy.

88 records · Page 5Linked to original sources
PubMed1978

Suppression of reaginic antibody formation in guinea pigs by anti-idiotypic antibodies.

Syngeneic immunization of strain 2 and strain 13 guinea pigs with purified antibodies against benzyl-penicilloyl bovine IgG (BPO-BGG) produces anti-idiotypic antibodies which specifically inhibit antigen-induced T cell proliferation in vitro. In sensitized guinea pigs, passive administration (either intravenously or subcutaneously in complete Freund's adjuvant [CFA] of these anti-idiotypic antibodies has a reversible suppressive effect on IgG and IgM responses. In addition, preimmunization with idiotypes effects a long-term and specific suppression of the production of homocytotropic antibodies against a hapten-protein conjugate (BPO-BGG). The suppression of the homocytotropic antibody response in already sensitized outbred guinea pigs was attampted by immunization with autologous serum, autologous antibodies, or autologous lymphoid cells. With all immunization procedures used so far, no significant suppressive effects could be demonstrated. The significance of these findings, in terms of the practical potential of autoanti-idiotypic immunization for the management of allergic diseases, is briefly discussed.

Animals↗
PubMed1978

Guinea pig macrophage agglutination factor is antigenically distinct from migration inhibition factor and immunoglobulin.

Lymph node cells from guinea pigs with specific delayed hypersensitivity release macrophage agglutination (MAggF) and migration inhibition factors (MIF) upon exposure to antigen or concanavalin A in serum-free medium. MAggF in culture supernatants was absorbed neither by immunoabsorbents made with a rabbit anti-guinea pig lymphokine serum that removed MIF, nor by immunoabsorbents made with rabbit anti-guinea pig Ig. These results suggest that MAggF is antigenically distinct from MIF and Ig.

Absorption↗
PubMed1978

Antibodies to guinea pig lymphokines. VII. Reactivity with products of lymphoid and nonlymphoid cells.

It was shown previously, that an antiserum directed against highly purified fractions of migration inhibitory factor inhibits delayed hypersensitivity reactions in vivo and in vitro. Using radiolabeling techniques we determined that the anti-lymphokine serum reacted primarily with three lymphocyte activation products (m.w. 60,000, 45,000, and 30,000) all of which had a similar isoelectric point of 5.2. The cellular origin of this material was investigated. It was found that activated B cells, B leukemia cells (L2C), and growing fibroblasts produced material of a similar m.w. as analyzed on SDS-PAGE. No cross-reaction was found with radiolabeled products of activated murine and human lymph node cells and of SV 40-infected African green monkey kidney cells. The isoelectric point of the reactive material from B cells, leukemia cells, and fibroblasts was determined at 5.2. In addition to material with pI 5.2, lymph node cells also produced material with pI 3.5 to 4.5, which focused at pH 5.0 to 5.4. After neuraminidase treatment macrophage migration inhibitory activity in fibroblast culture supernatants could be absorbed specifically to insolubilized anti-lymphokine antibody. These findings suggests that lymphoid and nonlymphoid cells are capable of producing molecules whose physicochemical and functional properties appear to be identical.

Animals↗
PubMed1977

Characterization of guinea pig mitogenic factors. I. Evidence that antigen-induced mitogenic factor and mitogenic factor from mixed leukocyte cultures are distinct molecular entities.

Mitogenic factor from BCG-sensitized cells stimulated with antigen (PPD) was found to have a m.w. between 20 and 25,000 daltons and an isoelectric point of about 7.5. The blastogenic activity of this factor was not affected by L-fucose or heating at 56 degrees C for up to 1 hr. Mitogenic factor obtained from supernatants of allogeneic cell mixtures (MLC-MF) on the other hand, had a m.w. at 15 to 18,000 daltons and an isoelectric point of 6.5. The blastogenic activity of MLC-MF was inhibited by 0.1 M L-fucose. The factor was stable at 56 degrees C for 1 hr. An antibody prepared against MLC-MF inhibited the MLC reaction as well as the activity of MLC-MF on non-committed cells. This antibody, however, did not affect the response of lymphocytes to PHA or PPD and had no suppressive effect on PPD-MF. The antibody was not cytotoxic and its suppressive activity in the MLC response could not be absorbed out by lymphoid cells indicating that it is probably directed against a lymphocyte activation product (MLC-MF) rather than membrane antigens. The chemical and immunologic differences exhibited by PPD-MF and MLC-MF indicate that these two lymphokines are distinct molecular entities.

Animals↗
PubMed1976

Histocompatibility antigens and genetic control of the immune response in guinea pigs. III. Specific inhibition of antigen-induced lymphocyte proliferation by strain-specific anti-idiotypic antibodies.

The in vitro T-cell proliferation induced by penicilloylated bovine IgG (BPO-BGG) in sensitized strain 2 and strain 13 guinea pigs could be specifically blocked by strain-specific antisera presumably directed against cell membrane-associated immunoglobulin idiotypes. The anti-idiotypic antisera were prepared in strain 2 and strain 13 guinea pigs against immunoadsorbent purified anti-BPO-BGG antibodies which had been raised in strain 2 and strain 13 animals. Strain 13 antistrain 13 anti-BPO-BGG (a strain 13 BPO-BGG) suppressed the in vitro BPO-BGG response of cells from immunized strain 13 animals but did not inhibit the response of cells from immune strain 2 animals. Conversely, the corresponding antiserum raised in a strain 2 combination (a strain 2 BPO-BGG) only inhibited the in vitro BPO-BGG response of strain 2 cells. Furthermore, the inhibitory activity of the antisera could only be absorbed by immune cells from the syngeneic strain. The activity of the a strain 13 BPO-BGG serum was highly specific; the inhibitory activity could only be absorbed by BPO-BGG-sensitive strain 13 cells. The inhibitory activity of the anti-idiotypic sera was predominantly associated with the 19S fraction. The data suggest that immune cells and in particular T lymphocytes from strain 2 and strain 13 guinea pigs possess strain-specific recognition structures from BPO-BGG with the same idiotypes as the corresponding strain-specific immunoglobulins. Furthermore, the production of such inhibitory anti-idiotypic sera was restricted to syngeneic combinations, which suggests a potential role of autoanti-idiotypic antibodies in the regulation of the immune response. The anti-idiotypic antisera used here are apparently directed against gene products not associated with the strain 2 or strain 13 major histocompatibility complex.

Animals↗
PubMed1976

Antibodies to guinea pig lymphokines. III. Reactions with radiolabeled lymphocyte activation products.

An antiserum raised against a purified fraction of guinea pig lymphokines exhibits marked in vivo properties; it suppresses delayed hypersensitivity reactions and binds migration inhibition factor (MIF) from supernatants of activated lymphocyte cultures in vitro. This serum was analyzed for specificity using a radioactive double labeling technique which distinguishes products synthesized either de novo or in increased amounts by stimulated lymphocytes. Combined supernatants of stimulated (concanavalin A or PPD) and unstimulated cultures labeled with either tritiated or [14C]leucine, respectively, were fractionated on Sephadex G-75. Pooled fractions were precipitated using the antibody sandwich technique, and solubilized precipitates were analyzed using sodium dodecyl sulfate polyacrylamide gel electrophoresis. Using this procedure the anti-lymphokine serum recognized primarily three newly sythesized lymphocyte activation products with molecular weights of approximately 60 000, 45 000 and 30 000 daltons. By contrast, these molecules could not be detected in radiolabeled lymph node cells which had been solubilized with NP-40 detergnt. The isoelectric point of all three molecules was found to be 5.2 +/- 0.3. The previously determined characteristics (mol.wt. 45 000, pI 5.2) of MIF and the property of the anti-lymphokine serum to absorb MIF activity suggest an identity between MIF and one of the molecules. In view of the previously described in vivo effects of the anti-lymphokine serum it is concluded that at least one of these three molecules plays an important role in the early events of delayed-type hypersensitive reactions in vivo.

Animals↗
PubMed1976

Antibodies to guinea pig lymphokines. II. Suppression of delayed hypersensitivity reactions by a "second generation" goat antibody against guinea pig lymphokines.

A "second generation" antibody to a highly purified lymphocyte product was raised in a goat against material eluted from a rabbit anti-guinea pig lymphokine immunoadsorbent column. This anti-lymphokine serum, in constrast to anti-lymphocyte serum (ALS) did not appear to contain cytotoxic antibodies directed against membrane antigens on guinea pig lymph node lymphocytes. Furthermore, the anti-lymphokine serum did not inhibit the formation of spontaneous T rosettes nor significantly depress lymphocyte response to mitogens. The anti-lymphokine serum totally suppressed the delayed skin reactivity to PPD and contact sensitivity to DNCB when injected intradermally around the site of antigen challenge. By contrast, intradermally injected ALS did not appear to suppress the PPD response in sensitized guinea pigs. Intravenously and i.p. administered anti-lymphokine serum was somewhat less effective in suppressing the delayed skin response to PPD. The intradermal injection of the antiserum had no effect on nonspecific inflammation evoked by turpentine-olive oil or on the extravasation of circulating Evans blue evoked by intradermally injected histamine. Histologic examination of 24-hr DNCB-induced skin lesions from sensitized guinea pigs treated with intradermally injected anti-lymphokine serum showed marked reduction of mononuclear infiltration of the dermis and of epidermal lesions, as compared with skin sites taken from sensitized animals pretreated with normal goat serum. The anti-lymphokine serum injected i.v. also markedly reduced the perivascular infiltration of the dermis and subcutis in skin reaction sites from sensitized animals challenged with PPD. Intravenous treatment with ALS for 3 consecutive days caused extensive depletion of the paracortical areas of peripheral lymph nodes whereas treatment with normal serum and anti-lymphokine serum caused no such depletion. It is proposed that the anti-lymphokine serum is directed against activated lymphocyte products, one of them being MIF. These products are involved in the mediation of delayed hypersensitivity reactions. This is in marked contrast to ALS, the suppressive action of which appears to be central rather than peripheral.

Animals↗
PubMed1976

Antibodies to guinea pig lymphokines. IV. Suppression of the mixed leukocyte culture reaction by anti-lymphokine globulin.

An antiserum, (anti-lymphokine globulin, ALyG) directed against highly purified products of activated lymphocytes, inhibits the proliferation of responding cells in guinea pig mixed leukocyte cultures ((MLC). This serum recognizes three newly synthesized lymphocyte products (one of them being migration inhibition factor (MIF) which are involved in the mediation of delayed hypersensitivity reactions in vivo. Since ALyG does not appear to contain cytotoxic antibodies against guinea pig lymphocyte antigens and its inhibitory activity cannot be removed by absorption with lymphoid cells it seems likely that the inhibition of MLC reactivity is not mediated by the lysis of stimulator or responder cells and its target is not the lymphocyte per se but possibly some factor elaborated during MLC response. By contrast, antisera with specificity for histocompatibility (H) antigens can inhibit the MLC when the appropriate H antigens are present on the responding and/or stimulating cell population. However, this inhibitory of the antisera can be effectively absorbed with lymphoid cells bearing the appropriate H antigens. The addition of ALyG even 48 hr after the initiation of culture results in a marked inhibition of MLC reactivity. This finding is consistent with the elaboration of a mitogenic factor or signal during the first 48 hr of culture and the delivery of this signal to the responding cell population. Thus, ALyG does not appear to interfere with the synthesis of this factor but must be present after its release in order to block responder cell proliferation. Furthermore, the stimulatory effect of this MLC mitogenic factor, but not of PPD-induced mitogenic factor on "third party" cells can be completely inhibited when the cells are cultured in the presence of ALyG. These findings suggest that the MLC-mitogenic factor in this system is identical to or cross-reactive with one or both of the newly synthesized molecules recognized by the ALyG.

Animals↗
PubMed1975

Histocompatibility antigens and genetic control of the immune response in guinea pigs. II. Specific inhibition of antigen-induced lymphocyte proliferation by anti-receptor alloantisera.

The in vitro recognition of acetylsalicilyl ovalbumin, penicilloylated bovine IgG (BPO-BGG) and the multichain copolymer poly-L-(Tyr, Glu)-poly-D L-Alapoly-L-Lys [(T, G)-A-L] by primed (2 x 13) F1 cells could be markedly and specifically blocked by alloantisera directed against "receptors" (R) or recognition structures for these antigens. The antisera were raised against lymphoid cells from various F2 hybrid guinea pigs of (2 x 13) histocompatibility type in which responsiveness to low doses of acetylsalicylic acid anhydride, BPO-BGG and (T, G)-A-L segregated independently of each other. One of the genes required for the expression of high responsiveness appears to be linked to the 13 MHC genes. The anti-R antisera did not contain antibodies capable of interacting directly with the stimulating antigen since passage of the sera through antigen-immunoadsorbent columns did not remove antibodies capable of suppressing in vitro recognition. Furthermore, the antisera did not appear to contain cytotoxic antibodies directed against specific antigen-sensitive cells. The activity of the anti-R sera was highly specific: their inhibitory activity could only be absorbed by lymphoid cells bearing the specific recognition structures for the appropriate antigen. Preliminary experiments yield no indication that the anti-R antisera are specific for immunoglobulin idiotypes.

Animals↗
PubMedDate not supplied

Chemotactic responses of hagfish (Vertebrata, Agnatha) leucocytes.

The chemotactic responses of hagfish leucocytes were tested using a variety of chemoattractants. Leucocyte migration was significantly enhanced by purified mammalian complement anaphylotoxin (C5a) and LPS-activated hagfish plasma. Checkerboard analyses confirmed that the responses of leucocytes to both of these chemoattractants were directed along concentration gradients (chemotaxis) and did not result from accelerated random movement (chemokinesis). Chemotaxis was undertaken by leucocyte fractions that were enriched in granulocytes, the predominant phagocytic cells of hagfish. The data suggest that chemotactic mechanisms may have been conserved during evolution to such a degree that mammalian chemoattractants can bind and activate chemotactic receptors on hagfish leucocytes. Moreover, hagfish appear to express plasma proteins that are structurally and functionally homologous to mammalian complement anaphylotoxins.

Animals↗