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B W PAPERMASTER

Publications and source records attributed to B W PAPERMASTER.

17 recordsLinked to original sources
PubMed1964

EVOLUTION OF THE IMMUNE RESPONSE. I. THE PHYLOGENETIC DEVELOPMENT OF ADAPTIVE IMMUNOLOGIC RESPONSIVENESS IN VERTEBRATES.

1. The California hagfish, Eptatretus stoutii, seems to be completely lacking in adaptive immunity: it forms no detectable circulating antibody despite intensive stimulation with a range of antigens; it does not show reactivity to old tuberculin following sensitization with BCG; and gives no evidence of homograft immunity. 2. Studies on the sea lamprey, Petromyzon marinus, have been limited to the response to bacteriophage T(2) and hemocyanin in small groups of spawning animals. They suggest that the lamprey may have a low degree of immunologic reactivity. 3. One holostean, the bowfin (Amia calva) and the guitarfish (Rhinobatos productus), an elasmobranch, showed a low level of primary response to phage and hemocyanin. The response is slow and antibody levels low. Both the bowfin and the guitarfish showed a vigorous secondary response to phage, but neither showed much enhancement of reactivity to hemocyanin in the secondary response. The bowfin formed precipitating antibody to hemocyanin, but the guitarfish did not. Both hemagglutinating and precipitating antibody to hemocyanin were also observed in the primary response of the black bass. 4. The bowfin was successfully sensitized to Ascaris antigen, and lesions of the delayed type developed after challenge at varying intervals following sensitization. 5. The horned shark (Heterodontus franciscii) regularly cleared hemocyanin from the circulation after both primary and secondary antigenic stimulation, and regularly formed hemagglutinating antibody, but not precipitating antibody, after both primary and secondary stimulation with this antigen. These animals regularly cleared bacteriophage from the circulation after both the primary and secondary stimulation with bacteriophage T(2). Significant but small amounts of antibody were produced in a few animals in the primary response, and larger amounts in the responding animals after secondary antigenic stimulation. 6. Studies by starch gel and immunoelectrophoresis show that the hagfish has no bands with mobilities of mammalian gamma globulins; that the lamprey has a single, relatively faint band of this type; and that multiple gamma bands are characteristic of the holostean, elasmobranchs, and teleosts studied. By this method of study, the bowfin appeared to have substantial amounts of gamma(2) globulin. 7. We conclude that adaptive immunity and its cellular and humoral correlates developed in the lowest vertebrates, and that a rising level of immunologic reactivity and an increasingly differentiated and complex immunologic mechanism are observed going up the phylogenetic scale from the hagfish, to the lamprey, to the elasmobranchs, to the holosteans, and finally the teleosts.

Adaptation, Physiological↗
PubMed1962

The role of the thymus in development of immunologic capacity in rabbits and mice.

In rabbits, complete thymectomy before the age of 5 days produced immunologic deficiency in the adult animals, as indicated by reduced antibody production to bovine serum albumin and bacteriophage T(2). Homotransplantation immunity was unaffected, however. In an inbred strain of mice, complete neonatal thymectomy resulted in complete inability of the 60-day-old animals to form antibody to bacteriophage T(2). Inbred mice, completely thymectomized at birth, had a deficient homograft response, indicated by acceptance of skin homografts from strains differing in both the weaker and stronger (H-2) histocompatibility antigens. Tumor transplants (mammary adenocarcinoma) were also successful across the H-2 genetic barrier in mice thymectomized at birth. Neonatal thymectomy also eliminated the Eichwald-Silmser phenomenon, rendering female mice capable of accepting isografts of male skin. Transplantation immunity in mice was also affected by later thymectomy, at 30 days of age, in certain strain combinations involving weak histocompatibility differences. Spleen and lymph node cells from mice thymectomized at birth or at 6 days of age, and sacrificed 2 months later, did not produce a graft versus host reaction in appropriate F(1) hybrid recipients, indicating that such cells are immunologically inactive. Neonatal thymectomy of F(1) hybrid mice, and in one strain combination thymectomy at 40 days of age, produced animals with inordinate susceptibility to runt disease (homologous disease) following injection of parent strain spleen cells 35 days (neonatal surgery) and 10 days (surgery at 40 days) later. Mice thymectomized at birth also showed growth failure and were short-lived. Studies of newborn mice indicated that they have true lymphocytes only in the thymus, and lack such cells in the spleen, lymph nodes, and gut. In normal mice, adult lymphoid structure develops gradually, beginning during the 1st week of life and continuing for the next month. In contrast, mice thymectomized at birth do not develop mature lymphoid structure: the lymph nodes and spleens tend to be small and poorly organized, and show a quantitative deficiency in lymphoid cells. It is our current working hypothesis that the thymus makes a major contribution toward the centrifugal distribution of lymphoid cells which, in turn, is essential to the full expression of immunologic capacity.

Animals↗
PubMed1962

Antibody-producing capacity of adult chicken spleen cells in newly hatched chicks.

1. To evaluate the effect of primary in vitro antigenic stimulation on a population of immunologically competent cells, a homologous cell transfer system was used, with adult chickens as the spleen cell donors, killed Brucella abortus as the antigen, and newly hatched chicks as the recipients. 2. The distribution of antibody titers in recipients of cells from random donors was bimodal, with about 30 per cent showing no detectable titer and the remainder distributed normally. 3. Variability of titer was reduced significantly in subgroups receiving cells from a single donor, indicating that the primary source of variability was the genetic capacity of discrete cell populations to respond to antigen. 4. In serial passage studies, activity of donor cell populations was lost rapidly: antibody was not demonstrated after the second passage, and the graft versus host reaction (splenomegaly) was not demonstrated after the third passage. Results were similar with in vitro antigenic stimulation at the time of the first passage only and with additional stimulation at the time of subsequent transfers. 5. The thesis that,the homograft reaction of the newly hatched recipients had contributed significantly to the variability in the single transfer studies and to the rapid loss of activity in the serial transfer experiments was confirmed by the results of transfers following alteration of the lymphoreticular system of the host by thorotrast administration, splenectomy, and treatment with 19-nortestosterone during embryogenesis. All three favored the survival and function of transferred cells, raising the average antibody titer and virtually eliminating the no-response category. The inhibition of homograft immunity was most pronounced in the 19-nortestosterone group.

Animals↗
PubMed1959

Aminonucleoside nephrosis. I. Electron microscopic study of the renal lesion in rats.

Experimental renal disease was produced in young rats by daily subcutaneous injections of 6-dimethylamino purine, 3-amino-d-ribose (aminonucleoside). The physiologic, biochemical, and light microscopic changes were similar to those observed in human nephrosis. Electron microscopy of the glomeruli from animals which received seven or more daily injections of aminonucleoside revealed characteristic abnormalities of the epithelial cells of the glomerular capillaries. These changes consisted of swelling, coalescence, and eventual obliteration of the epithelial cell foot processes and an increase in the number and the size of epithelial cytoplasmic vacuoles. The serial development of the ultramicroscopic pathologic changes in the epithelial cells, as observed by study of animals through the course of the disease, indicated that the smudging of the foot processes occurred at the time of onset of severe proteinuria. Further changes, consisting of hypercellularity due primarily to an increase in the number of endothelial cells and an increase in the amount of basement membrane-like material, were regularly observed by the 12th day after injections were begun. These abnormalities were correlated with the development of uremia in the later stages of the disease process. The distal and proximal renal tubules were abnormal by the 7th day after injections were begun, and showed localized swelling between the cristae of the mitochondria and a decrease in over-all cytoplasmic density, described as hydropic change. Electron microscopy of glomeruli from animals which had partially recovered from aminonucleoside nephrosis revealed areas of normal epithelial cell morphology. This observation was interpreted as evidence of partial reversal of the ultramicroscopic changes in the recovery phase of the disease. These observations of the fine structure of pathologically altered glomeruli and tubules in aminonucleoside nephrosis are similar to our findings in human nephrosis as revealed by electron microscopy of serial renal biopsies.

Animals↗