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Biomedical subjects

A F Geczy

Publications and source records attributed to A F Geczy.

At least 91 records · Page 5Linked to original sources
PubMed1977

Linkage of guinea pig Bf and C4 TO THE GPLA.

Inbred and partially inbred strains of guinea pigs were typed for their polymorphic Bf and C4 patterns. In crosses and backcrosses of inbred strains of guinea pigs the inheritance of Bf, C4, and GPLA phenotypes was studied. The presented data indicate linkage of the structural Bf and C4 loci to the major histocompatibility complex (MHC) of the guinea pig, the GPLA system. Evidence for a GPLA-B-Ia crossover was obtained. Bf and C4 typing contributes to the characterization of the GPLA region in some inbred strains thus providing a simple method for determining the state of inbreeding on the one hand and providing the necessary third or fourth region within the GPLA for the detection of informative meiosis, on the other.

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

Induction of specific anti-guinea pig T cell sera in rabbits.

In an attempt to increase the specificity of antisera raised in rabbits against strain 2 guinea pig thymocytes and brain, the rabbits were screened for titres of natural antibodies to thymocytes and other lymphocytes. Although unimmunized rabbits commonly had moderate titres of cytotoxic antibodies to guinea pig thymocytes, occasional animals had low titres to thymocytes and moderate titres to bone marrow cells. Intravenous immunization of this latter group of rabbits with thymocytes led to the production of high titred anti-thymocyte sera which were easily made specific for thymus-derived lymphocytes (T cells) by absorption with L2 C lymphoma, a bone marrow-derived lymphoma of strain 2 guinea pigs. Sera raised against guinea pig brain in complete Freund's adjuvant which had high titres of antibodies to both thymocytes and bone marrow cells could be made specific for T cells only with great difficulty. The cytotoxic activity of the anti-T cell serum could be absorbed by strain 2 thymocytes and brain homogenates, while high dilutions of this serum inhibited the formation of spontaneous rosettes between guinea pig lymphoid cells and normal rabbit erythrocytes.

Absorption↗
PubMed1976

Guinea pig histocompatibility antigens. I. Serological and genetic characterization of GPLA antigens.

Lymphocytotoxic alloantisera were obtained by cross immunization among outbred guinea pigs from a closed colony. Groups of antisera recognizing the same specificities were established by panel analysis, cross immunization among appropriate phenotypes, and absorption studies. Three antigens designated B1, B2, and B3 (perviously B, C, and D) were detected in our outbred colony and also found to be present in a wide variety of guinea pig strains. These antigens were shown by population and breeding studies to be allelic gene products of a first guinea pig locus (GPLA) (designated locus B). Four new guinea pig families homozygous for their B locus antigens are now in the seventh generation of inbreeding. NIH guinea pig strains 2 and 13, which share the B1 antigen, differ by a number of other antigens which have been designated I1, I2, I3 (previously A), and I4. These antigens differ from the B locus gene products in their molecular size and tissue distribution and it is, therefore, postulated that they represent an equivalent of the Ia antigens in mice (designated I region). Cross immunizations among inbred or outbred guinea pigs identical for currently known B locus and I region antigens yield further antisera, possibly recognizing additional Ia specificities and/or a second GPLA locus designated locus S. Whereas the conventional eosin lymphocytoxicity technique easily permits the detection of the widely distributed antigens (such as the B locus antigens), a more sensitive 51Cr release technique is required to demonstrate the "Ia equivalent" antigens of the guinea pig, possibly due to their restricted presence on the membrane of only some lymphoid cell populations.

Absorption↗
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↗
PubMed1976

The major histocompatibility complex of the guinea-pig. II. Relationship between mixed leucocyte reactivity and serologically-defined phenotypes of the GPLA B locus and I region.

The relationship between the mixed leucocyte reaction (MLR) and the serologically-defined antigens controlled by genes in the guinea-pig B locus (equivalent to the murine D or K region) and I region was investigated in various inbred and partially inbred strains and in guinea-pig families homozygous for their GPLA alleles. No MLR reactions could be detected among guinea-pig families of a closed colony which had been bred to homozygosity for their GPLA antigens. By contrast, animals which differed in their I region showed strong MLR reactivity. Animals with identical I regions as judged by four serologically-defined specificities only, but differ with respect to B locus determinants, yield appreciably lower MLR responses. It appears that in the guinea-pig, as in other mammalian species, the antigenic systems responsible for MLR reactivity are controlled primarily by genes identical with or closely linked to the I region of the major histocompatibility complex.

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↗
PubMed1975

The major histocompatibility complex of the guinea pig. I. Serologic and genetic studies.

Serologic and genetic studies of the antigens which comprise the guinea pig MHC have demonstrated three distinct but linked genetic regions. Antisera to the B region were raised by cross-immunization of random-bred animals; this region controls antigens B.1, B.2, B.3, and B.4 which behave as alleles at a single locus and which resemble the products of the murine D or K region genes in their tissue distribution and molecular characteristics. Cross-immunization of inbred strain 2 and strain 13 animals, both of which bear the B.1 antigen, leads to sera which identify antigens which resemble the products of the I region of the murine MHC. Specific absorption experiments have demonstrated four distinct I region antigens. In addition to the B and I regions, inbred strain 2, strain 13, and some outbred animals bear an antigen (S.1) which is the product of a third genetic region and which also resembles the murine D or K region gene products in molecular size. The results of these studies should facilitate the use of the guinea pig as an experimental model for studies of genetic control of the immune response and the function of the histocompatibility-linked Ir genes.

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