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H K Ziegler

Publications and source records attributed to H K Ziegler.

At least 55 records · Page 3Linked to original sources
PubMed1987

T-2 toxin-enhanced resistance against listeriosis in mice: importance of gastrointestinal lesions.

The role of T-2 toxin-induced gastrointestinal lesions in T-2 toxin-enhanced resistance to listeriosis in mice was evaluated. The T-2 toxin-induced lesions did not cause a starvation effect sufficient to enhance resistance to listeriosis. Administration of polymyxin E markedly reduced the gram-negative intestinal microflora and did not eliminate the toxin-induced resistance to listeriosis. The T-2 toxin did not cause an increased expression of Ia surface antigens on peritoneal macrophages. Thus, toxin-induced anorexia and starvation or absorption of gram-negative intestinal bacteria and endotoxins through toxin-induced gastrointestinal lesions did not account for the enhancing effect of T-2 toxin on resistance to Listeria monocytogenes infection in mice.

Animals↗
PubMed1986

Cyclosporine inhibits macrophage-mediated antigen presentation.

The influence of cyclosporine on antigen-specific, macrophage-dependent T cell activation was analyzed in vitro. Murine T cell activation by antigens derived from Listeria monocytogenes was monitored by the production of interleukin 2. Pretreatment (2 hr, 37 degrees C) of macrophages with cyclosporine resulted in a cell population with a markedly diminished capacity to support the activation of T lymphocytes. When cyclosporine-pretreated macrophages were added to cultures of untreated T cells and antigen, the dose of cyclosporine that produced 50% inhibition (ID50) was 1.5 micrograms/ml, and if antigen was present during the drug pretreatment, the ID50 was 0.6 micrograms/ml. Pretreatment of T cells also inhibited their subsequent activation by antigen and untreated macrophages, but a higher dose of cyclosporine was required to produce similar inhibition (ID50 = 4.4 micrograms/ml). Additional experiments focused on the mechanism of inhibition of antigen presentation when macrophages were pretreated with the drug. The addition of interleukin 1 or indomethacin to the cultures did not alter the inhibitory effect of cyclosporine. Under conditions that produced greater than 90% inhibition of antigen presentation, macrophage surface Ia expression was not altered, and the uptake and catabolism of radiolabeled antigen remained normal. Thus, cyclosporine had profound effects on antigen presentation that appear to be unrelated to decreases in interleukin 1 production, increases in prostaglandin production, decreases in Ia expression, or changes in antigen uptake and catabolism.

Animals↗
PubMed1986

[Ichthyosis uteri. Case report on a rare clinical entity].

The present paper communicates an observation of a squamous cell carcinoma of the corpus uteri at the base of an ichthyosis uteri. The ichthyosis uteri developed over a period of just three years from a discrete squamous cell metaplasia of the endometrial body in the presence of slight nonspecific endometritis. It is recommended that when ichthyosis uteri is detected the uterus should be removed, since the changes cannot be eliminated by curettage and there is a risk of malignant degeneration within a relatively short time.

Aged↗
PubMed1985

Influence of the H-2u haplotype on immune function in F1 hybrid mice. I. Antigen presentation.

Previously, we reported that myelin basic protein (MBP) peptide 1-37 contains an encephalitogenic epitope for PL/J mice, and MBP peptide 89-169 is encephalitogenic for SJL/J mice. (SJPL)F1 hybrid mice do not respond to immunization with these peptides in a co-dominant manner because the encephalitogenic response to peptide 1-37 dominates. To examine this phenomenon more closely, we tested the ability of MBP-primed parental or F1 T cells to respond to MBP or MBP peptides in the context of PL, SJL, or F1 antigen-presenting cells (APC). It was found that the F1 T cells responded to either the protein or the peptides when these were presented in the context of F1 or PL APC. However, F1 T cells would not respond to MBP in the context of SJL APC, although the latter cells were functionally intact. This effect was not antigen-specific because SJL APC would not present ovalbumin or PPD to primed F1 T cells. F1 T cells from mice immune to the strongly antigenic bacterium Listeria monocytogenes responded to bacterial antigens presented by SJL APC, although at a significantly lower level compared to the results obtained when these antigens were presented by F1 or PL APC. This finding implied that unbalanced antigen presentation was a quantitative rather than a qualitative phenomenon. When F1 hybrid mice from other strain combinations were tested, a similar effect was observed whenever one of the parental strains was PL/J. This effect was mapped to the MHC in MHC-congenic B10 mice.

Animals↗
PubMed1984

Modulation of macrophage Ia-expression by lipopolysaccharide. I. Induction of Ia expression in vivo.

Experiments were performed to analyze the modulation of macrophage Ia expression and biosynthesis by Salmonella minnesota-derived lipopolysaccharide (LPS) in vivo. The i.p. injection of LPS into LPS-responder mice caused a dramatic increase in the Ia expression of the peritoneal macrophage population harvested 1 wk after injection. As little as 1 ng of lipid-rich Re595 LPS per mouse caused a significant I-Ak increase, and 1 microgram was optimal; wild-type S. minnesota LPS was less active. No I-Ak induction by LPS was observed in the LPS-nonresponder strain C3H/HeJ. LPS-induced macrophages showed a 6- to 16-fold increase in I-Ak expression by radioimmunoassay (RIA), a 3- to 10-fold increase in the proportion of I-Ak-positive cells, and a 10- to 15-fold increase in I-Ak biosynthetic capacity. The magnitude of this induction by LPS was comparable to increases observed after injection of live Listeria monocytogenes. The kinetics of I-Ak induction by LPS and by L. monocytogenes were different: LPS caused an initial decrease in I-Ak expression 1 day after injection, and I-Ak induction by LPS occurred more slowly and maintained heightened expression longer. Several H-2 gene products (H-2Kk, I-Ak, and I-Ek) were augmented in LPS-induced macrophages. In keeping with increased I-A and I-E expression, LPS-induced macrophages were more effective than normal macrophages in presenting antigen to T lymphocytes. We suggest that the modulation of macrophage Ia expression is one important mechanism contributing to the immunoregulatory activity of LPS.

Animals↗
PubMed1984

Analysis of Listeria monocytogenes antigens with monoclonal antibodies.

Hybridomas secreting antibodies directed against Listeria monocytogenes were produced by the fusion of a drug sensitive tumor cell line with splenic B cells from mice immunized with L. monocytogenes. A solid phase radioimmunoassay (RIA) screening procedure was performed with three forms of listerial antigens: (i) heat killed L. monocytogenes (HKLM); (ii) isopycnic gradient purified soluble listerial proteins (SLP) and (iii) syngeneic macrophages which had ingested HKLM (MAC-LM). Ninety-three hybridoma lines were identified which showed antibody reactivity to at least one of the antigenic forms. The predominant isotypes of hybridoma derived antibodies were IgG2 and IgM. Of those antibodies reactive with HKLM 70% appeared species specific and did not react with L. grayi, L. denitrificans or L. murrayi. The others (30%) showed several cross-reactivity patterns with bacteria such as Staphylococcus aureus, Escherichia coli, and Bacillus subtilis. Interestingly, of those positive on MAC-LM (27), 13 lines were reactive only with HKLM, 8 with all three antigenic forms, and 6 were reactive only with MAC-LM. Three lines were also identified which reacted with SLP alone. We anticipate that these antibody reagents will prove extremely useful in the identification and purification of antigenic structures and in the study of macrophage functions relating to antigen processing and presentation.

Antibodies, Monoclonal↗
PubMed1984

The processing and presentation of Listeria monocytogenes antigens by macrophages.

Macrophages play a requisite role in the induction and expression of T lymphocyte responses to Listeria monocytogenes. For effective T cell-macrophage interaction to occur, macrophages must perform at least two fundamental functions. They must take up and handle the antigen, and they must express appropriate membrane glycoproteins encoded for by the I-region of murine major histocompatibility gene complex (Ia molecules). Data collected in a murine model suggests that the following sequential events are involved in the Listeria-macrophage-T cell interaction. Listeria interaction with macrophage cell surface via trypsin sensitive structures. Interiorization within phagosomes. Phagosome-lysosome fusion. Partial degradation of Listeria. Transfer of protein antigen fragments to macrophage cell surface. Recognition of macrophage surface antigen and I-region associated (Ia) molecules by the T cell receptor. The essential feature of this model is that: antigen handling occurs intracellularly and independently of macrophage cell surface Ia molecules. With regard to the survival advantage of this mechanism, one may speculate that the degradation of pathogens by macrophages may serve to increase the number of different structural moieties which can act as antigens. Thus, bacterial components normally sequestered in the interior of organisms could conceivably serve as antigens, and the multiplicity of such antigenic determinants would make it less likely that a nonresponder status with respect to I-region gene function would be generated. This mechanism may be especially relevant to host defense against intracellular pathogens such as Listeria monocytogenes.

Animals↗
PubMed1982

Decrease in macrophage antigen catabolism caused by ammonia and chloroquine is associated with inhibition of antigen presentation to T cells.

This paper describes the effects of two lysosomotropic compounds, ammonia and chloroquine, on the interaction of mononuclear phagocytes with immune T cells. The uptake and ingestion of Listeria monocytogenes by macrophages were not affected by the drugs; however, the macrophage catabolism of 125I-labeled Listeria was reduced in a dose-dependent way. The macrophage presentation of Listeria to T cells, an I-region-dependent phenomenon, was also inhibited. The degree of inhibition of catabolism paralleled that of antigen presentation. The inhibition of antigen presentation took place if the macrophages were treated before and during Listeria uptake; minimal inhibition took place if the macrophages were treated 30 min after Listeria ingestion, at which time a significant amount of bacteria was already catabolized. Our previous studies had shown that the macrophage-associated antigen recognized by T cells became apparent 30-60 min after uptake of Listeria. We conclude that ammonia and chloroquine affected an intracellular handling step required for the expression of the immunogen relevant for T-cell recognition.

Ammonium Chloride↗
PubMed1979

[Lobar pneumonia (author's transl)].

129 cases of lobar pneumonia were analysed. The frequency of occurrence in autopsy material was 2.5%, and has not increased or decreased appreciably in the past 20 years. Men and women were affected with approximately the same frequency up to the age of 40, thereafter male mortality is considerably higher. The diagnosis of a lobar pneumonia was made clinically in only 16 percent of the cases. The anatomical appearance of the illness has not changed compared to the findings of earlier studies, however chronic clinical courses are common, occurring in about 15% of the cases. The lobar pneumonia was the direct or indirect cause of death in all instances. There has been a remarkable change in the causative agents in favor of gram negative organisms.

Adolescent↗
PubMed1978

[Autopsy findings in a case of fatal dextran reaction (author's transl)].

A report of fatal dextran reaction is presented. A patient who had had a stable circulatory status developed massive systemic venous congestion and irreversible cardiac arrest after receiving an infusion of approximately 50 ml of dextran solution. Autopsy showed total occlusion of the pulmonary circulation as a result of precipitation of the dextran-blood mixture. Similar occlusion was demonstrated in capillaries in the kidneys, spleen and cardiac musculature. Death occurred during acute, right-sided heart failure. Pathogenetically a type III allergic reaction with precipitation of antigen antibody complexes in the presence of excess antibody is suspected. In cases such as this one, with no history of prior exposure to dextran, sensitization may have occured with a substance sharing antigenic properties with dextran.

Aged↗
PubMed1978

Liposomes as model membrane systems for immune attack. I. Transfer of antigenic determinants to lymphocyte membranes after interactions with hapten-bearing liposomes.

The interaction of human peripheral blood lymphocytes with liposomes containing DNP-aminocaproyl-phosphatidylethanolamine together with either egg yolk or dipalmitoylphosphatidylcholine has been investigated. When lymphocytes were incubated with liposomes at 37 degrees C, the aqueous compartment (86Rb+) and the lipid portion (3H-lipid) of the liposomes became cell associated to an equivalent extent. At 0 degrees C, however, the incorporation of 3H-lipid exceeded that of 86Rb+. Lymphocyte-liposome interactions were accompanied by the transfer of DNP to the surface of the lymphoid cell as measured by susceptibility to complement in the presence of anti-DNP antibody. Hapten transfer was not limited to liposome interactions with lymphocytes, but occurred also with other cells (e.g., Chang cells). Hapten transfer could also be demonstrated by susceptibility to K cell-mediated lysis. These findings suggest that liposomes may prove to be a useful vehicle for the transfer of new antigenic determinants onto cell surfaces. The implications of these findings are discussed in the context of using liposomes as targets for cell-mediated cytotoxic attack.

Animals↗
PubMed1977

Studies on the cytotoxic activity of human lymphocytes. II. Interactions between IgG and Fc receptors leading to inhibition of K cell function.

The inhibition of human K cell-mediated cytolysis by a variety of immunoglobulin preparations was studied. It was found that inhibition was not a simple function of IgG concentration but was dependent on the mode of immunoglobulin presentation. The relative inhibitory capacity of IgG preparations on a weight basis was as follows: cell associated Ig larger than or equal to immobilized immune complexes greater than insoluble immune complexes greater than soluble immune complexes greater than heat-aggregated Ig greater than monomeric Ig. These results imply that the inhibitory capacity of immunoglobulin is determined by ligand (Fc) multivalency. It was found that although interactions between immunoglobulin and Fc receptors occur at low temperatures, these interactions lead neither to lysis nor to K cell inactivation. A temperature-sensitive post-binding event was required both for lysis to occur and for K cells to be inactivated. These findings lead us to propose that an IgG-induced redistribution ("capping") of Fc receptors on the K cell surface may be required for cytolysis and for effector -ell inactivation.

Antigen-Antibody Complex↗
PubMed1975

[Anticonvulsant drugs and liver damage (Author's transl)].

540 autopsies of institutionalized epileptics who had been treated with anticonvulsant drugs were evaluated as to type and frequency of pathological changes in the liver and compared with a control series of 270 nonepileptics. A specific liver-toxicity of antiepileptic drugs, or combination of drugs, could not be established. Thus, only in 3 cases, one of which was fatal, was a relationship found between anticonvulsant drug therapy and liver damage. Therefore, there seems to be no reason to discontinue anticonvulsant therapy or to reduce the usual dose for fear of causing liver damage. On the other hand, it was found that tuberculosis may have adverse effects upon the liver of patients undergoing anticonvulsant drug therapy. From 41 cases of active tuberculosis we found 13 with severe liver damage, 3 of which were fatal. 10 patients had, and 3 had not, received antituberculosis chemotherapy.

Adult↗
PubMed1975

Antibody-dependent cytolytically active human leukocytes: an analysis of inactivation following in vitro interaction with antibody-coated target cells.

A leukocyte population consisting of approximately 85% lymphocytes, prepared from human peripheral blood by centrifugation through a Ficoll-Hypaque gradient, was studied for its capacity to destroy antibody-coated human liver (Chang) cells in vitro. Cytolysis was a rapid event: increased ionic flux (86Rb) from the target cell occurred within 10 min of the addition of effector cells. Kinetic analysis of target cell destruction (51 Cr release) was compatible with a "one hit" hypothesis, thereby indicating that cytolysis resulted from a single collision was an effector cell. The initial rate of cytolysis was linear and related to the number of leukocytes added, but lysis at all of the leukocyte to target cell ratios tested ceased after 5 hr. The number of target cells killed at that time was directly proportional to the number of leukocytes added. While the lytic capacity of the effector population was totally depleted after incubation with antibody-coated target cells, cytotoxicity was not affected by co-culturing leukocytes with Chang cells treated with pre-immune serum. The cytotoxic effector cells functioning in this antibody-dependent lytic system are thus to be contrasted with killer T cells, whose lytic activity is not compromised by interaction with homologous target cells. It was estimated that approximately 4% of the leukocyte population employed could kill antibody-coated Chang cells, a figure consistent with the estimated frequency of "null" cells within human peripheral lymphocytes.

Animals↗