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Biomedical subjects

W H Hildemann

Publications and source records attributed to W H Hildemann.

At least 19 recordsLinked to original sources
PubMed1986

Allograft rejection, autograft fusion and inflammatory responses to injury in Callyspongia diffusa (Porifera; Demospongia).

Sponges exhibit a variety of swift, cellular defence responses to protect self integrity. The sponge Callyspongia diffusa has been used to characterize the cytological changes that occur during allograft rejection, autograft fusion, and inflammation. Allogeneic contact results in fusion of the two exopinacoderms followed by an infiltration of mesohyl cells into the graft zone. As mesohyl cells accumulate, they form tissue bridges that span the graft interface. After a few days, the tissue bridges and the nearby cellular infiltrate become necrotic and slough off, which separates the allogeneic tissues. Autograft fusion begins similarly but cellular infiltration does not follow exopinacoderm fusion. Contacted exopinacocytes are redistributed, the endopinacoderms and choanosomes come into contact, and the grafted sponge tissues merge. Tissue damage exposes internal regions of the sponge to the external environment. In many areas of injury, exposed choanosome is sealed by infiltrating mesohyl cells. In other areas, exposed endopinacoderm appears to serve as new exopinacoderm. Cellular debris is removed by phagocytic archaeocytes and new exopinacoderm is regenerated over the damaged choanosome. No scars remain once the inflammatory infiltrate has dispersed. In general, mesohyl cells are involved in defence responses without an observed enrichment of any specific cell type. However, archaeocytes from rejecting sponges appear to line both sides of the allogeneic interface.

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PubMed1986

Allogeneic cell interactions during graft rejection in Callyspongia diffusa (Porifera, Demospongia); a study with monoclonal antibodies.

Many aspects of the cellular immune system in the marine sponge Callyspongia diffusa, have been defined by using artificially transplanted allogeneic tissues. Rejections show specificity of 'non-self' recognition, cytotoxic effector responses and short-term immunological memory. Histological investigations reveal a generalized mesohyl migration to the graft zone where archaeocytes line up at the allogeneic interface. Monoclonal antibodies (mAbs) raised to sponge cells have shown that little or no allogeneic cell mixing occurs at the graft interface and that certain mesohyl cell types do not appear to be directly involved in graft rejections. However, all mesohyl cell types are present in autograft fusion zones and in inflammatory responses to injury. The involvement of only some of the mesohyl cell types in graft rejections suggests specific interactions of an effector 'immunocyte'.

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PubMed1984

Preparation of mouse type I and type II insulins for immunologic studies.

Mouse pancreata contain comparatively meager amounts of two insulin species, types I and II. When these insulins are to be prepared for immunogenetic studies, it is desirable to obtain equivalent amounts of both in concentrations suitable for immunization. Standard methods, based on isolating single species, favor recovery of one type. Moreover, published methods for separation of type I from type II produce very dilute insulin solutions. Methods are suggested here to overcome these disadvantages.

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PubMed1984

Immunoglobulin-bearing blood leucocytes in the Pacific hagfish.

The occurrence of immunoglobulin (Ig) bearing leucocytes in the blood of the Pacific hagfish, Eptatretus stoutii , was examined using a murine monoclonal antibody (45.3) and a rabbit antiserum specific for hagfish serum Ig. Binding of antibody 45.3 to hagfish leucocytes assessed by radioimmunoassay was inhibited by preincubation of antibody with purified serum Ig thus verifying the presence of cell surface Ig cross reactive with serum Ig. The monoclonal antibody identified approximately 65% of blood leucocytes as Ig+ve while the rabbit antiserum indicated 81% Ig+ve cells. Both antibody preparations failed to react specifically with cells from mouse, horned shark, tunicate or sea star; this indicates the distinctive nature of hagfish Ig. The high percentage of blood cells bearing surface Ig in the hagfish raises the possibility that lymphocyte divergence to separate B and T pathways may not have occurred in this most primitive vertebrate. Alternatively, an Ig-like specificity characteristic of both "T" and "B" lymphocytes may have been detected. In any event, a subset of Ig negative leucocytes is evident in hagfish.

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PubMed1984

H-2 hierarchy in the IR-gene controlled responses to hapten-modified mouse serum albumin.

Five hapten-modified autogenous mouse serum albumins (MSA), TNP11MSA, FITC8MSA, DNP64MSA, DNP5MSA, and PC2MSA, were tested for their ability to induce hapten-specific antibody responses in H-2 congenic mice of the H2d, H-2b, H-2a, and H-2f haplotypes. Four of the five modified MSAs, TNP11MSA, FITC8MSA, DNP64MSA, and PC2MSA, stimulated responses found to be under H-2-linked Ir gene control, whereas DNP5MSA failed to induce responses in any strain tested. H-2d, H-2D, and H-2a mice responded to FITC8MSA; H-2d and H-2b responded to TNP11MSA; and only H-2d mice were high responders to DNP64MSA and PC2MSA. H-2f mice failed to respond to any of the stimulating antigens. Thus, a hierarchy of H-2 haplotypes was observed in the responsiveness to modified MSA with H-2d greater than H-2b greater than H-2a greater than H-2f. Primed lymph node cells from PC2MSA immunized H-2d mice were challenged with antigen in vitro to assess the nature of the determinant recognized by T cells in the response to modified MSA. Lymph node cells proliferated only when challenged with PC2MSA. Unmodified MSA or TNP11MSA did not stimulate a proliferative response, suggesting that the immune T cells recognize a neodeterminant present on the modified PC2MSA.

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PubMed1984

Alloimmune memory is absent in Hymeniacidon sinapium, a marine sponge.

The southern California sponge Hymeniacidon sinapium can recognize and reject transplanted allogeneic tissues. This species reveals a complex rejection response that involves cellular infiltration into the graft interface and a deposition at that site of a fibrous wall. The response then proceeds to a cytotoxic reaction in which the cells in the graft zone become necrotic and slough off, resulting in allogeneic tissue separation. The rate and intensity of this response varies with the genetic constitutions of the paired sponges and the temperature of the water. In experiments employing pre-sensitized second-set and unrelated third-party graftings, with changes in temperature, sensitization times, intervals before regrafting, and experimental sites, this species did not exhibit alloimmune memory (i.e., accelerated second-set rejection). When the allorejection described here for H. sinapium is taken in conjunction with rejection responses reported for other sponge species, it is apparent that sponges have two major methods for responding to allogeneic contacts: barrier formation or cytotoxicity. The rejection method seems to correspond with the presence or absence of immune memory, and may, in part, be correlated with habitat and frequency of contacts with "non-self." The development of the rudimentary immune system in metazoans is discussed in relation to the rejection of naturally transplanted tissues in addition to challenges from pathogens.

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PubMed1983

Cytotoxic transplantation immunity in the sponge Toxadocia violacea.

The Hawaiian sponge, Toxadocia violacea, exhibited discriminating transplantation immunity in an extensive series of allogeneic and xenogeneic parabioses. Cytotoxic alloincompatibility occurred without exception, but with differing degrees of severity. The allorejection reactions developed more rapidly than has been observed in any other animal species. An intense tissue-bridging reaction in allogeneic contact zones preceded acute soft tissue destruction; the cytotoxic reactivity was usually restricted to the immediate zone of direct contact. The median reaction times were closely temperature-dependent and much accelerated at higher temperature. Specific, short-term alloimmune memory was revealed by second-set and third-party graftings. Extensive allogeneic polymorphism was evident from the invariable rejection observed among more than 140 different pairings. Xenograft reactions between Toxadocia violacea and Callyspongia diffusa were characterized by acute cytotoxicity, immune memory, and a qualitative change in secondary versus primary responses.

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PubMed1982

Characterization of alloimmune memory in a sponge.

Alloimmune memory, revealed by consistently accelerated second-set graft rejection in contrast to unrelated third-party reactions, has been reported in four species of marine sponge. Allogeneic tissue of the marine sponge, Callyspongia diffusa was grafted/parabiosed to examine critically the essential features of alloimmune memory in this member of the least complex major metazoan phylum. Although sponges lack an organized circulatory system, the immunologic memory spreads rapidly through body tissues. Heightened reactivity persisted for only 3 yo 4 wk after primary sensitization. This appears to constitute a major difference from the long-term alloimmune memory found among vertebrates. This limited duration of memory, however, is apparently sufficient for the individual sponge to cope with repeated challenges to its integrity.

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PubMed1981

Two distinct high immune response phenotypes are both controlled by H-2 genes mapping K or I-A.

Murine responses to immunization with 2, 4, 6-trinitrophenyl (TNP) conjugated to autogenous mouse serum albumin (MSA) in complete Freund's adjuvant (CFA) are controlled by a gene(s) in the K or I-A region of H-2 complex. High immune responses of both H-2d and H-2b mice have been mapped to this region of the major histocompatibility complex. No modifying effects were observed from genes to the right of I-A in either responder haplotype. High responsiveness controlled by Kb or I-Ab is inherited with complete or partial recessivity, depending on the route of immunization and the sex of the responder. However, high responsiveness controlled by Kd or I-Ad is inherited dominantly. This unusual pattern of inheritance of immune responsiveness to TNP-MSA is consistent with the genetic mapping to K or I-A. TNP-MSA-specific T-cell reactivity following immunization with TNP-MSA in vivo was examined utilizing a T-cell-dependent proliferation assay in vitro with cells obtained from high or low responder mice. Genetic mapping and mode of inheritance in this assay for antigen-specific T-cell reactivity corresponded with results obtained from a plaque-forming cell (PFC) assay measuring antibody production by B cells. Both the proliferative and PFC responses are probably under the same Ir gene control. Both gene dosage effects and Ir-gene-product interaction could influence the generation of specific immune responsiveness in F1 hybrids between high and low responders to TNP-MSA.

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PubMed1981

Afferent sensitization and efferent cytotoxicity in allogeneic tissue responses of the marine sponge Callyspongia diffusa.

Allogeneic branches of the marine sponge Callyspongia diffusa were paired either in parabiosis or as allografts. To examine the specificity of the allogeneic rejection process, naive second sets and third parties were substituted in the midst of primary allogeneic tissue responses. Other experiments were conducted with 0.2-, 0.8-, 3.0-, and 5.0-micron pore size membrane barriers separating various combinations of naive and presensitized allogeneic paired sponges. The results of these experiments demonstrate that both the afferent and efferent phases of allograft rejection in Callyspongia diffusa depend on direct allogeneic cell contact. Cytotoxic reactivity does not involve a readily diffusible cytotoxic molecule. Moreover, the specificity of allogeneic sponge graft rejections resides in the early recognition or afferent phase; once the effector response is generated or turned on, subsequent allogeneic cytotoxicity is nonspecific.

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PubMed1980

Allogeneic polymorphism and alloimmune memory in the coral, Montipora verrucosa.

Populations of the coral Montipora verrucosa exhibited very extensive allogeneic polymorphism revealed by parabiotic incompatibility amont 890 different pairings of colonies (clones) without exception. More than 1,400 reciprocal histoincompatibilities were actually recorded because bilateral cytotoxicity was observed among most of the the alloparabionts tested. This "uniqueness of the individual" in terms of cell surface histocompatibility (H) markers is manifest in the whole spectrum of possible incompatibilities from strong to moderate to weak. The directionality, severity, and rate of rejection were mainly determined by the genetic constitutions of the interclonal parabionts. Allograft reaction times were closely temperature dependent and inversely related to the strength of the H barrier. Heightened alloimmunity or early memory was demonstrable after only 2 days of presensitization and became maximal after 4 to 8 days. After prolonged primary immunization, potent alloimmune memory persisted for 4 weeks, but disappeared after 8 to 16 weeks. Immunological primitiveness in corals may therefore be reflected in the lack of long-lived memory as found among vertebrates.

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PubMed1980

Characteristics of the second-set kidney allograft reactions in rats.

Unlike skin allografts in rats, accelerated rejection of second-set kidney allografts was a rare occurrence. Host reactivity was generally suppressed as a consequence of first-set kidney rejection, resulting in prolonged survival of a second-set kidney bearing the same alloantigens. Three variables with potentially important clinical implications were critical for induction of extended survival of the second kidneys: (1) Longer first-set kidney retention or sensitization periods promoted prolonged second-set allograft survival; the longer the period (tested up to 50 days), the greater was the observed immunosuppression. (2) Shorter intervals between first set removal and second-set grafting greatly prolonged second-set survival times; the shorter the interval, the greater the immunosuppressive effect. The optimal timing for facilitation of second kidney survival may be assumed as the time of first kidney removal. (3) Lesser or weaker histoincompatibility of the second kidney clearly promoted prolonged or indefinite survival. Thus, the second kidney from semiallogeneic F1 hybrids survived far longer than fully allogeneic parental kidneys. Prolongation of second-set F1 kidney survival could be achieved under less strict conditions. Spleen lymphocytes from second kidney recipients showed suppressed alloreactivity in the popliteal lymph node graft-versus-host (GVH) assay. Prolonged survival of repeated renal allografts is attributable to intervention of an active immunoblocking process rather than acquired tolerance.

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PubMed1980

Characteristics of transplantation immunity in the sponge, Callyspongia diffusa.

Very extensive polymorphism of histocompatibility (H) molecules in the sponge Callyspongia diffusa was revealed by the incompatibility found among 480 different allogeneic pairings without exception. This represents some 960 individual clones utilized as alloparabionts or sources of fitted allografts. Consistent cytotoxic reactivity provoked by allogeneic cell surface contact in Callyspongia is manifest in a continuum of strong to weak histoincompatibilities; however, strong reactions are most frequent at normal temperatures of 23 to 27 C. The directionality, vigor, and timing of alloparabiotic rejection in this species all depend mainly on the genetic constitutions of the interacting clones. Replicate interclonal combinations yield essentially identical rejection reactions, and differences in graft dosage had no effect on either the direction or intensity of allocytotoxicity. Alloreaction times are inversely proportional to the strength of the H barrier. Maximal allosensitization indicated by accelerated second-set reactivity was gradually achieved, as a function of the interclonal combination, after 2 to 8 days of primary contact. Heightened transplantation immunity or memory persists for at least 2 to 3 weeks after contact sensitization.

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PubMed1979

Immunocompetence in the lowest metazoan phylum: transplantation immunity in sponges.

Isografts of Callyspongia diffusa fuse compatibly, but allografts are invariably incompatible. Extensive polymorphism of cell-surface histocompatibility markers is evident. The histocompatibility barriers range from strong to weak depending on the interclonal combination, but early rejection with conspicous cytotoxic sequelae is typical. Reaction times of first-set, second-set, and third-party grafts indicate highly discriminating transplantation immunity with a specific memory component.

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