H-2D-associated hybrid resistance to EL4.
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Biomedical subjects
Publications and source records attributed to W H Hildemann.
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Antibodies to group A streptococcal carbohydrate, demonstrable by radioimmunoassay, were elicited in Pacific hagfish, Eptatretus stoutii, after prolonged immunization with whole cell vaccine. This hagfish antibody, isolated by ion-exchange chromatography of immune serum, exhibited a single precipitin line after immunoelectrophoresis against rabbit antiserum to hagfish serum. The isolated antibodies retained high binding activity for the streptococcal carbohydrate, but lacked the natural hemagglutinating activity found in both nonimmune and immune sera. Analysis by gel filtration in neutral and dissociating buffers and by sodium dodecyl sulfate/polyacrylamide gel electrophoresis under nonreducing conditions indicated an intact molecule of molecular weight approximately 160,000 that may be noncovalently associated in a polymer of higher molecular weight. Heavy chains of mobility identical to that of murine mu chains and light chains of mobility significantly slower than murine lambda chains were obtained after sodium dodecyl sulfate gel electrophoresis under reducing conditions. Instability of the tertiary structure of the antibody molecule was indicated by partial dissociation in buffers containing sodium dodecyl sulfate and by dissociation at low concentrations of reducing agent. In contrast to its well-developed system of cell-mediated immunity, only a minimal system of circulating antibody production is evident in this primitive fish. No evidence for divergence of cyclostome lymphocytes into separate T- and B-cell systems has yet been discerned.
Tissue transplantation immunity with a specific memory component is demonstrated in populations of Montipora. This highly discriminating immunoreactivity derives from extensive allogeneic polymorphism of histocompatibility (H) markers. An H system of immunorecognition is postulated to have originated in multicellular invertebrates probably beginning with coelenterates.
Three in vivo techniques were used to establish the specificity of tumor immunity induced after sensitization of F344 rats to syngeneic MCA-induced sarcomas: (1) post-excision resistance to tumor challenge, (2) passive tumor neutralization (the Winn test), and (3) concomitant immunity. In general, these assays revealed unique non-cross-reactive antigens associated with each of three sarcomas, FMF1, FMM2, and FMM3. However, spleen cells from tumor-sensitized rats did not demonstrate cell-mediated cytotoxicity in vitro corresponding to the specificity of tumor resistance in vivo. In the (3H)-proline cytotoxicity assay, spleen cells from FMM3 tumor-bearing rats or from FMM3 tumor-immune rats were not selectively cytotoxic for cultured FMM3 target cells. Parallel analysis of spleen cells from normal or FMM3-sensitized rats using the Winn assay and the (3H)-proline assay revealed that (1) spleen cell cytotoxicity in vitro did not correlate with effective tumor protection in vivo; and (2) normal spleen cells were cytotoxic against cultured sarcoma target cells in vitro and inhibited tumor growth in vivo. Thus, passive tumor protection by normal spleen cells in vivo corresponded with the demonstration of natural cytotoxicity in vitro, but induced specific anti-tumor reactivity was observed only in vivo.
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Transplantation studies with the sea star Dermasterias imbricata revealed that this echinoderm rejected most first-set allografts after prolonged chronic reactions. All control autografts remained intact and fully viable. The greatly accelerated rejection of subsequent second- and third-set allografts demonstrated that these reactions were not only highly specific, but that these animals possess at least short-term immunological memory. The specific nature of the allograft response was confirmed by the prolonged survival of unrelated third party allografts placed at the same time as second- or third-set allografts. Animals in these experiments were maintained in sea water at temperatures of 14-16 C. Since this low temperature is required for successful maintenance of this species, temperature-dependence studies could not be undertaken. The rejection reaction was characterized by loss of pigmentation, edematous swelling, and necrosis. Histologically, the allograft tissue was heavily infiltrated by lymphocyte-like cells and phagocytic cells, causing disruption of the normal cytoarchitecture of the dermis. Deposits of fibrous material were also in evidence. Autografts, on the other hand, remained fully viable with no signs of rejection. We conclude that this asteroid, a representative of the echinoderms, has a well-developed, cell-mediated immune response analogous to that of vertebrates.
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Passive immunological enhancement of skin allografts was investigated in three donor-host combinations of congenic mice disparate at non-H-2 loci. Serum against the graft donor was derived from mice that had received donor strain lymphoid cells as neonates, and thereby were rendered specifically tolerant of a skin allograft. We refer to this serum as "allograft-tolerant" serum. Each strain combination was chosen to provide only two non-H-2 histoincompatibilities present in the donor and absent in the host. The differences are categorized as immunogenetically strong, moderate, or weak, on the basis of skin allograft survival times. With passively administered allograft-tolerant serum significantly prolonged graft survivals were noted for the weakest combination only. Combined treatment with sublethal X-irradiation and allograft-tolerant serum signigicantly prolonged graft survivals were noted for the weakest combination only. Combined treatment with sublethal X-irradiation and allograft-tolerant serum significantly prolonged graft survival in both the moderate and weak combinations, with the largest effect present in the weakest disparity. A hyperimmune alloantiserum (produced in adults) directed against the graft donor prolonged allograft survival in the strongest disparity when given in combination with irradiation. In this combination, graft survival time was increased in hosts exposed to X-ray alone, but joint treatment with X-ray and the alloantiserum gave the largest increment. In contrast, combined treatment with the serum and an antithymocyte alloantiserum did not affect graft survival times. Treatment with both radiation and antithymocyte serum did not prolong graft survival beyond that in mice given only X-radiation. Immunological enhancement with central inhibition is assumed as the mechanism underlying prolonged graft survival, and it is suggested that a population of thymus-derived "killer" cells, sensitive to X-irradiation, is required for normal graft rejection.
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