Search PubMed⌕ Search

Biomedical subjects

B Morris

Publications and source records attributed to B Morris.

At least 127 records · Page 7Linked to original sources

The synthesis and secretion of immunoglobulins by lymphoid cells in the sheep. The primary response to salmonella lipopolysaccharide.

The primary response of the popliteal node to Salmonella lipopolysaccharide was studied in the sheep. All three classes of immunoglobulin IgG1, igG2, and IgM were produced by both free-floating cells in the lymph and by cells within the pymph node throughout the immune responce which extended over a period of at least 20 days.. Most of the immunoglobulins were found to be nonspecific for the antigen when tested by a binding assay. It was calculated from the binding assay that far more antigen-specific IgG molecules were produced than IgM molecules. The proportion of IgM and IgG1 which showed affinity for Salmonella organisms increased throughout the response. IgG2 had no affinity for the antigen until around 480 h after challenge. When a hemagglutination assay was used to measure antibody production, most of the specific antibody produced during the response was found to be IgM. Blast cells produced most of the immunoglobulin during the first 4 days of the response, and these cells were responsible for almost all of the IgM production. Differences were observed in the relative amounts of IgG and IgM produced by the cells within the node and by free-floating cells in the efferent lymph. The free-floating cells in lymph synthesized and secreted relatively more IgM and relatively less IgG than did cells within the lymph node. Both populations of cells, however, secreted much more IgG than IgM.

Animals↗

Lymphopoiesis and lymphocyte recirculation in the sheep fetus.

The production and the circulation of lymphocytes has been examined in the sheep fetus where neither foreign antigen nor immunoglobulins occur. It was found that as the lymphoid organs increased in size during fetal life, the numbers and the output of lymphocytes in the thoracic duct lymph increased. The recirculating pool of lymphocytes was estimated to be 5.5 +/- 1.5 X 10(8) cells in fetal lambs 95-100 days of age, 5.7 +/- 1.2 X 10(9) cells in fetuses 130-135 days of age, and 1.2 +/0 9.3 X 10(10) cells in fetuses near to term. The rate of addition of lymphocytes to the recirculating pool was 3.2 +/- 1.9 X 10(6) cells/h in fetuses of 100 days and 3.4 +/- 0.9 X 10(7) cells/h in fetuses of 130 days of age. Lymphocytes recirculated from blood to lymph in fetuses; labeled cells injected into the blood stream reappeared in the thoracic duct lymph promptly and reached maximum levels around 12-18 h after they were injected. Labeled lymphocytes were detected subsequently in greatest numbers in the lymph nodes, particularly in the mesenteric lymph nodes and in the interfollicular areas of the Peyer's patches. Chronic drainage of thoracic duct lymph from fetuses in utero for periods of up to 36 days had no obvious effects on the growth or development of the fetus and only minimal effects on the content of lymphocytes in the various lymphoid tissues even though the number of cells in the blood and lymph were reduced to between 20-30% of normal levels. Thymectomy done in fetuses about 2 mo befor cannulation of the thoracic duct reduced the output of cells in the thoracic duct to about 25% of normal levels and caused a significant reduction in the content of lymphocytes in the various lymphoid tissues. Thymectomized fetal lambs subjected to thoracic duct drainage for periods up to 2 wk in utero had a similar complement of lymphocytes in their lymphoid tissues to intact thymectomized fetal lambs. Lymphocytes obtained from the thoracic duct lymph of lambs thymectomized 2 mo previously recirculated from blood to lymph when they were injected intravenously, although they did this at a significantly slower rate than did lymphocytes from normal lambs.

Animals↗

The effects of corticosterone and cortisone on the uptake of polyvinyl pyrrolidone and the transmission of immunoglobulin G by the small intestine in young rats.

1. The distribution of polyvinyl pyrrolidone along the intestinal lumen and in the intestinal wall, following oral administration to normal and corticosterone treated rats, was found to be extremely variable. Valid comparisons between the two groups of animals could not be made using this technique. 2. Three, 4 and 5 days after corticosterone treatment there was no significant change in the uptake of 125I-labelled polyvinyl pyrrolidone from standard doses injected into ligated segments of the distal small intestine; nor did the treatment induce precocious replacement of the absorptive cells in this region. Cortisone induced precocious cell replacement, a process which took up to 4 days to complete, and also led to a marked reduction in the uptake of 125I-labelled polyvinyl pyrrolidone from ligated segments of the distal intestine. 3. Three days after treatment with corticosterone (5 mg I.P. at 12 days) there was a marked reduction of labelled immunoglobulin G transport into the blood. Four and 5 days after treatment there was some recovery of the immunoglobulin G transport function. Three days after treatment with cortisone (5 mg I.P. at 12 days) there was closure of the gut to labelled immunoglobulin G. 4. The relevance of these results to antibody transmission and the termination of immunoglobulin transport is discussed.

Animals↗

Quantitative assessment of the transmission of labelled protein by the proximal and distal regions of the small intestine of young rats.

1. The plasma volume in rats aged 15-16 days was measured by dilution analysis using homologous, 125I-labelled immunoglobulin G. A mean plasma volume of 5-53 ml./100 g and a mean blood volume of 8-01 ml./100 g were obtained.2. After the injection of labelled immunoglobulin G into the heart, homogenates of various abdominal organs and of the carcass were prepared. Labelled immunoglobulin G left the vascular compartment at a rate of about 9-10%/hr over a 3 hr period. About 11% of the labelled immunoglobulin G was catabolized in 2 hr. 3. The data obtained from these studies was used to make quantitative estimates of the amount of intact immunoglobulin G transmitted from the proximal intestine and from the ileum after the intra-intestinal injection of 1000 mug of labelled immunoglobulin G. Homogenates of the experimental animals were prepared and it was estimated that over 40% of the labelled immunoglobulin G was transmitted as intact protein from the proximal intestine. The results suggest that no intact immunoglobulin G was transmitted from the ileum, but about 15% of the protein removed from the ileum was recovered in the whole body as degraded fragments precipitable with trichloroacetic acid. 4. These observations are discussed in the context of the transmission of antibodies, and their relevance to the receptor hypothesis is considered.

Animals↗

Cytotoxic mechanisms detected in vitro following sheep renal allografts.

Cytotoxic effects of lymph and blood components, removed from sheep following renal allografting were determined by in vitro assay using 51Cr labelled donor sheep lymphocytes as target cells. Lytic antibodies were detected in lymph efferent from the node draining the graft site and at lower concentrations in blood serum and in lymph leaving the graft. The cytotoxic antibodies had both complement-dependent and leucocyte-dependent functions; the complement-dependent antibodies were fractionated and shown to be of IgM and IgG1 subclasses. Cytotoxic cells were found in lymph leaving the graft but not in blood or in lymph efferent from the draining node; those detected in the renal lymph were non-specific in action and their appearance correlated with increased numbers of macrophages.

Animals↗

The response of the lymphoid system to renal allografts in sheep.

The immunological events which occur in lymph nodes situation regional to renal allografts have been studied by collecting lymph from these nodes and monitoring the changes in its cellular and humoral antibody content. Simultaneously, reactions occurring in the renal allograft and in lymph nodes distant to the graft were also monitored in the lymph from these organs throughout thelife of the graft. Large basophilic lymphoid cells appeared first in lymph from the renal allograft at around 48 hr postgrafting, whereas these cells did not appear in the lymph from the regional node until 80-100 hr after the graft was installed. Lymphoid blast cells were not seen inany significant numbers in lumph from nodes situated at a distance from the graft. The first detectable antibody was produced by the regional lymph node between 110 and 175 hr postgrafting, andin other undetermined sites within the next 80 hr. Antibody was not synthesized in any detectable amounts by the graft or by lymph nodes situated at a distance from the graft. The antibody which was present in the lymph from the regional node was produced primarily by fixed cells which remained in the node, and very little antibody was produced by the lymphoid cells which migrated from the node in efferent lymph. The cells in the lymph from the renal allograft produced only small amounts of immunoglobulin. Cells present in lymph from the renal allograft and in lymph from the regional lymph node actively synthesized and secreted significant amounts of nonimmunoglobulin proteins which were separated on Sephadex G-200 columns into peaks which coincided with 19S, 7S, and 4S proteins. The identities and biological activities of these proteins have not yet been determined.

Animals↗

The transmission of -125-I-labelled immunoglobulin G by proximal and distal regions of the small intestine of 16-day-old rats.

1. Standard doses of -125-I-labelled rat IgG were injected into the intestinal lumen of rats aged 16 days, and their sera were sampled 2 and 3 hr later. High concentration quotients were obtained after injection into the proximal small intestime, whereas very little immunoglobulin was transmitted from doses injected into the terminal 20 cm of the small intestine. 2. The villi of the terminal 18--20 cm of the small intestine of 16-day-old rats, the region from which very little transmission of IgG occurred, were lined by tall columnar absorptive cells with very larg supra-nuclear vacuoles. The extent of the terminal intestine, in which this cell type predominated in the absorptive epithelium, varied with age. The importance of defining the precise location of the region of the intestine under examination is stressed. 3. The experimental results and the histological observations are discussed in relation to (a) the results which have been obtained using PVP, which is unsuitable as an indicator of immunoglobulin transport in the rat and (b) the histological composition of the absorptive epithelium and the maturation changes which affect the epithelium between 18 and 21 days.

Age Factors↗

The role of humoral antibody in the rejection of primary renal allografts in sheep.

Antibody which had cytotoxic and agglutinating activity against donor lymphocytes appeared in the blood stream of primary renal allograft recipients usually within 48 h of the graft being finally rejected. Appearance of the antibody See PDF for Structure in the blood was associated with severe alterations in vascular permeability and this led to increases in the numbers of red cells and in the protein content of the lymph coming from the allograft. It was possible to elute cytotoxic and agglutinating antibody from renal allograft tissue, showing that this type of antibody was bound to graft antigens during the rejection process. The transfusion of whole serum or serum globulins obtained from sheep that had previously rejected allografts led to the destruction of recently installed renal grafts and the histological changes produced in these grafts and the alterations in the composition of the lymph coming from them were similar to those seen in the terminal stages of primary rejection. These findings have led us to the conclusion that in the sheep, at least the terminal stage of primary renal allograft rejection is mediated by humoral antibody.

Animals↗

The effects of cortisone acetate on stomach evacuation and the absorption of 125I-labelled globulins in young rats.

1. After short exposure (3-5 hr) to I.P. cortisone acetate (5 mg), the reduced transmission of labelled globulin to the circulation in 14-day-old rats is due to the slow release of the oral dose from the stomach. The ability of the small intestine to absorb and transmit globulin to the circulation is comparable in control and experimental animals.2. About 26 hr after cortisone acetate treatment (5 mg), the greatly reduced absorption of labelled globulin from oral doses administered to rats aged 15 days is due to the combined effects of the slower release of the dose from the stomach and to changes which have occurred in the small intestine.3. About 50 hr after the administration of 5 mg cortisone acetate the effect on the rate of stomach evacuation is minimal in rats aged 16 days. When labelled globulin is introduced directly into the duodenum of these animals virtually no absorption occurs.4. The results obtained from the experiments in which labelled globulin was injected into the duodenum support the contention that the proximal half of the small intestine is an important site for macromolecular transport.

Administration, Oral↗

The absorption of 125I-labelled immunoglobulin G by different regions of the gut in young rats.

1. (125)I-labelled homologous IgG was injected into different regions of the small intestine of rats aged 12, 16, 18, 20 and 22 days. At 12 days the proximal and middle regions of the intestine readily absorbed globulin and transmitted it to the circulation. The distal region of the intestine transmitted little to the circulation at all ages tested.2. The intestine loses its ability to transmit globulin to the circulation in a distal-proximal direction. At 16 and 18 days the ability of the middle region had declined significantly, and this decline continued so that little globulin was transmitted from this region at 20 and 22 days.3. The proximal intestine retained the ability to transmit globulin to the circulation in significant amounts up to 20 days.4. There is a close negative correlation between body weight and total radioactivity of the sera of rats which had received doses of labelled globulin into the proximal and middle regions of the intestine. There was no such correlation after injection into the distal intestine - suggesting a restricted throughput of radioactive material by the absorptive cells of this region.5. These results are discussed in the context of the termination of antibody absorption, and in relation to the results obtained using polyvinyl pyrrolidone.

Age Factors↗

Quantitative studies on the proliferation and differentiation of antibody-forming cells in lymph.

The transforming cells that appear in the efferent lymph from a lymph node responding to an antigenic challenge are part of a heterogeneous population which changes as the response progresses. Some cells containing small amounts of antibody appear early in the response and these cells have the cytologic characteristics of small and medium lymphocytes. They are, however, actively synthesizing DNA. As the immune response progresses, the antibody content of the cells in lymph increases. When incubated in vitro, cells in lymph appearing late in the response released 20 times more antibody per cell than those appearing early in the response. Large blast cells are the predominant antibody-forming cell in lymph. At the peak of a secondary challenge with horseradish peroxidase, up to 40% of the cells in lymph may be blast cells and, of these, two-thirds may contain specific antibody. It seems probable that most if not all of the blast cells responding to the antigen are involved directly in antibody and DNA synthesis. Cells in all stages of ultrastructural differentiation, and even mature plasma cells, were found to incorporate (3)H-thymidine into their nuclear DNA.

Animals↗