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The carriage of immunological memory by small lymphocytes in the rat
, 1966
"... Although it has been shown that antibody-forming cells arise during secondary responses from dividing precursors (1-3), the origin of these precursors is still a matter of debate. In general terms they may either originate from a line of dividing cells which is formed during primary immunization, or ..."
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Although it has been shown that antibody-forming cells arise during secondary responses from dividing precursors (1-3), the origin of these precursors is still a matter of debate. In general terms they may either originate from a line of dividing cells which is formed during primary immunization, or from long-lived cells, also formed during primary immunization, but which only begin to divide after secondary challenge. Attempts have been made to distinguish between these alternative explanations of "immunological memory " by giving a pulse of tritlated thymidine immediately before secondary challenge and determining whether or not the antibody-forming cells become labeled. Experiments of this kind led Nossal and M~ikel ~ (4) to conclude that the cells which formed antibody after challenge with Salmonella adelaide in rats arose from large lymphocytes which were already dividing in the animal before the antigen had been given. On the other hand, Cohen and Talmage (5) concluded that the cells which synthesized antibody in response to a secondary challenge with bovine gamma globulin in mice were not dividing in the animal before the challenge; they questioned the conclusions of Nossal and M~ikela on the grounds that reutilization of
Thymus-dependent areas in the lymphoid organs of neonatally thymectomized mice
, 1966
"... Intravenously injected syngeneic thymus cells are less efficient than the same number of spleen cells in reducing the lymphocyte deficit, preventing the wasting syndrome, and restoring the impaired immunological responses of neonatally thymectomized mice (1-5). This apparent paradox led us to invest ..."
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Intravenously injected syngeneic thymus cells are less efficient than the same number of spleen cells in reducing the lymphocyte deficit, preventing the wasting syndrome, and restoring the impaired immunological responses of neonatally thymectomized mice (1-5). This apparent paradox led us to investigate the possibility that the injected cells differed in efficiency because they reached different destinations within the lymphoid organs of the thymectomized recipients. The destinations of comparable numbers of syngeneic thymus and spleen cells, labeled in vitro with tritiated adenosine and injected into neonatally thymectolnized C3H/Bi and Fl(C57BL X C3H/Bi) mice, were determined by autoradiography. A dose of 30 million cells was selected because previous experiments had shown that this number of spleen cells would restore the immunological competence of thymectomized recipients but the same number of thymus cells would be without effect (3). In the course of the autoradiographic investigations described below specific areas of severe lymphocyte depletion
Electron microscopic observations on antibody-producing cells in lymph and
, 1966
"... The direct demonstration by McMaster and Hudack (1) of the production of antibody in lymph nodes led to a long search for the cell in the lymph node which synthesized antibody. Early evidence by Harris, Grimm, Mertens, and Ehrich (2), Dougherty, Chase, and White (3), and Harris and Harris (4) that t ..."
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The direct demonstration by McMaster and Hudack (1) of the production of antibody in lymph nodes led to a long search for the cell in the lymph node which synthesized antibody. Early evidence by Harris, Grimm, Mertens, and Ehrich (2), Dougherty, Chase, and White (3), and Harris and Harris (4) that the lymphocyte was the cell of synthesis was followed by the studies of BjSrnehoe and Gormsen (5), and Fagraeus (6) indicating the plasma cell as the cell which produced antibody. The following years produced studies of the cellular source of antibody by at least six experimental approaches, each of which led some authors to conclude that the plasmacytic series of cells was involved, and others, the lymphocytic series (7). The culmination, in 1955, of this decade and a half of intensive research was the actual finding of antibody within plasma cells, by Coons and his colleagues (8-10), using the indirect fluorescent antibody technique. These cells were found in antibody-producing lymph nodes; antibody-containing plasma cells were soon also found in other situations, i.e., in sites of deposition of transferred
Mechanism of eosinophilia. II. Role of the lymphocyte
- J. Exp. Med
, 1970
"... The preceding article describes findings which are compatible with the thesis that the eosinophil response to inoculation by a nematode parasite has char-acteristics of an immunologic phenomenon (1 a). Further evidence to this effect has been obtained in experiments employing various immunosuppressi ..."
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The preceding article describes findings which are compatible with the thesis that the eosinophil response to inoculation by a nematode parasite has char-acteristics of an immunologic phenomenon (1 a). Further evidence to this effect has been obtained in experiments employing various immunosuppressive agents (i b). The present paper reports on tests for both humoral and cellular mediators of the reaction. Particular emphasis is placed on evidence that the lymphocyte plays a role, as it does in other expressions of immunity. Materials and Methods Unless stated, the experimental procedures in this work were those described in the preceding article (1 a). Inbred Rats.--Two inbred rat strains were found to be suitable for this work. One, an SPF Wistar (WMp), was obtained from the Medical Research Council Laboratory Animal Centre at Carshalton, Surrey; the other, a parasite-free strain (WAG), came from the Glaxo Research Farm, Harefield, Middlesex. The criterion for histocompatibility within each strain was survival of skin grafts for at least 100 days.
Proliferative activity of the lymphatic tissues of rats as studied with tritium-labeled thymidine
, 1964
"... Isotopic labeling of the DNA of blood cells has provided an important technique for obtaining information about the cytokinetics of white cells. It has been assumed that the DNA label is stable within a given lineage of cells. However, several papers have indicated reincorporation of tritiated thymi ..."
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Isotopic labeling of the DNA of blood cells has provided an important technique for obtaining information about the cytokinetics of white cells. It has been assumed that the DNA label is stable within a given lineage of cells. However, several papers have indicated reincorporation of tritiated thymidine (H3Tdr)-labeled deoxyribonucleic acid (H3DNA) of cells during catabolism by other proliferating cells. The tritiated thymidine is originally incorporated during DNA synthesis (I-6). Most interpretations of this finding have assumed that it is not the result of radiobiological artifact due to the isotope. Aside from the significance of this finding in terms of interpretation of data pertaining to cell renewal, life span, and possible transformation of blood cells into different morphological entities (7), the possibility of the DNA within cells being unstable has many other implications. The biochemistry of the transfer of DNA label remains to be elucidated. Hamilton (8), whose work in leukemic subjects led him to propose that DNA reutilization might occur within lymphatic tissue, believed that his data favored
Initiation of antibody responses by different classes of lymphocytes. IV. Lymphocytes involved in the primary antibody response to a hapten-protein conjugate. Immunology
, 1971
"... Thymus-dependent, helper cells ("T " lymphocytes) 1 and thymus-independent, antibody-forming precursor cells ("B " lymphocytes) cooperate in the initiation of the primary antibody response of rodents to a variety of antigens (1-3). Both cell lines also cooperate in the initiation ..."
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Thymus-dependent, helper cells ("T " lymphocytes) 1 and thymus-independent, antibody-forming precursor cells ("B " lymphocytes) cooperate in the initiation of the primary antibody response of rodents to a variety of antigens (1-3). Both cell lines also cooperate in the initiation of the secondary antibody response, and both carry immunological memory (4, 5). Recent cell transfer studies indicate that B memory cells determine the changes in the proportion of immunoglobulin classes and affinity of antibodies produced in the secondary response (6-8). These changes suggest that B memory cells are not derived by a simple expansion of unprimed B lymphocytes, but rather by heterogeneous expansion of subpopulations of unprimed B lymphocytes or by a qualitative change in immunological function. On the other hand, the carriage of immunological memory by T lymphocytes could be explained by a homogeneous expansion of unprimed T cells. Miller et al. (5) and Mitchell et al. (4) have shown that both primed and unprimed T lymphocytes are able to cooperate with primed B lymphocytes in the adoptive secondary antibody response of mice to fowl gamma globulin and sheep red blood cells (SRBC), respectively.
Studies on the recovery of the immune response in irradiated mice thymectomized in adult
, 1964
"... It has been shown that mice thymectomized at 2 months of age have diminished numbers of lymphoeytes in their peripheral blood and lymphoid tissues (1) but no defects in immune responses (2). When, however, thymectomy was followed by a potentially lethal dose of ionizing irradiation and bone marrow t ..."
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It has been shown that mice thymectomized at 2 months of age have diminished numbers of lymphoeytes in their peripheral blood and lymphoid tissues (1) but no defects in immune responses (2). When, however, thymectomy was followed by a potentially lethal dose of ionizing irradiation and bone marrow therapy, the mice failed to respond, at 2 months postirradiation, to skin homografts and sheep erythrocytes. Sham-thymectomized control mice, on the other hand, had perfectly normal immune responses when tested 4 to 10 weeks after irradiation and marrow therapy. It was concluded that the recovery of the immune mechanism after total body irradiation is thymus-dependent (2). The present experiments were undertaken to study the effects of varying different parts of this system such as the number, source, and type of cells used for therapy and the age of the host at thymectomy. In addition, the growth of the mice and their immune response at later times after irradiation were studied.
THE EFFECTS OF THYMUS AND OTHER LYMPHOID ORGANS ENCLOSED IN MILLIPORE DIFFUSION CHAMBERS ON
, 1965
"... The possibility that the thymus produces a humoral substance with far reaching biological effects has been frequently considered. Support for the production of a hormone has been offered on morphological grounds by the description of secretory vesicles in the frog thymus (1), and colloid-containing ..."
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Cited by 9 (0 self)
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The possibility that the thymus produces a humoral substance with far reaching biological effects has been frequently considered. Support for the production of a hormone has been offered on morphological grounds by the description of secretory vesicles in the frog thymus (1), and colloid-containing cysts lined by ciliated cuboidal cells in normal mouse thymus (2, 3). Although there have been claims of the discovery of thymus-derived substances exhibiting anticancer properties (4, 5), with growth-promoting or growth-retarding effects (6), and with antibacterial (7) and antiviral activity (8), none of these claims has been widely substantiated. Meanwhile, the possibility that the thymus, e/a a humoral factor, exerts an effect on other lymphoid tissue has been receiving increasing support. Several authors have reported a transient lymphocytosis-stimulating effect following the injection of a variety of thymus extracts in guinea pigs (9) and mice thymectomized in adult life (10), in intact neonatal mice (11), and in young rabbits (12) and rats (13). Also, extracts and implants of heavily irradiated thymuses
Intestinal lymphangiectasia: a proteinlosing enteropathy with hypogammaglobulinemia,lymphocytopenia and impaired homograft rejection
- Journal of Clinical Investigation
, 1967
"... Abstract. Intestinal lymphangiectasia is a disease characterized by dilated intestinal lymphatics, protein-losing enteropathy, hypoalbuminemia, and edema. The immunologic status of 18 patients with intestinal lymphangiec-tasia was studied. Concentrations of IgG, IgA, and IgM were measured by immune ..."
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Abstract. Intestinal lymphangiectasia is a disease characterized by dilated intestinal lymphatics, protein-losing enteropathy, hypoalbuminemia, and edema. The immunologic status of 18 patients with intestinal lymphangiec-tasia was studied. Concentrations of IgG, IgA, and IgM were measured by immune precipitation and metabolism of these three immunoglobulins was studied using purified radioiodinated proteins. The serum concentration and total body pool of each immunoglobin were greatly reduced. The fraction of the intravascular protein pool catabolized per day was increased to 34 % for IgG, 59 % for IgA, and 66 % for IgM; these are in contrast with control values of 7%, 28%, and 17%, respectively. Synthetic rates of the immunoglobulins were normal or slightly increased. Primary circulating antibody response was tested in five patients with Vi and tularemia antigens. Titers elicited in patients with the Vi antigen were significantly lower than those seen in a control group, whereas no difference was seen between patient and control responses to the tularemia antigen.
Density distribution analysis of antigen sensitive cells in the rat. Nature
, 1967
"... Density distribution analysis is a convenient objective means of characterizing different cell populations (1-5, 28). With most populations a prominent feature of this technique is a reproducible heterogeneity of components which is apparently not an artifact (3, 5). Attempts to understand this hete ..."
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Density distribution analysis is a convenient objective means of characterizing different cell populations (1-5, 28). With most populations a prominent feature of this technique is a reproducible heterogeneity of components which is apparently not an artifact (3, 5). Attempts to understand this heterogeneity in terms of functional differences have been only partially successful; preliminary results have indicated that differences in density of 19S hemolysin-forming ceils reflect differences in physiological and metabolic properties (1, 5). Accordingly, it became of some interest to carry out density distribution analysis on the precursor cells of the 19S hemolytic antibody-forming cell (AS1 cell). It was hoped that, aside from possible metabolic and physiological dif ferences, it might be possible to detect AS cells differing in immunological func tion. Preliminary accounts of this work have been published elsewhere (2, 4)-Materials and Methods Animals.--Male Lewis rats (9-12 wk) bred in the Hall Institute were used as cell donors in all experiments except those involving newborn or very young animals, in which case rats of
