[Diversity of medical curricula in The Netherlands].
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Biomedical subjects
Publications and source records attributed to H L Langevoort.
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After intratracheal or subcutaneous priming with horseradish peroxidase (HRP), no anti-HRP-forming cells were present in the bronchus-associated lymphoid tissue (BALT) or the lung of the rat. After intratracheal priming and intratracheal boosting with HRP no specific antibody-forming cells were observed either in the BALT or the lung. A few blast cells containing anti-HRP antibody were found in paratracheal lymph nodes, which is possibly the source of anti-HRP-forming cells. After subcutaneous priming in the hind footpad and intratracheal boosting specific antibody-forming cells were present in both the BALT and in the lung. In the BALT these cells were found peripherally, and in the lung perivascularly and peribronchiolarly. The simultaneous appearance of these anti-HRP-forming cells at both sites, their localization and their morphology strongly indicate that they are recruited from the circulation and not formed in situ; the probable source is the popliteal lymph node.
Histological changes in bronchus-associated lymphoid tissue (BALT) following single intratracheal administration of five different antigens were studied in the rat. After administration of T-dependent antigens (i.e., horseradish peroxidase, bovine serum albumin, and Bacillus Calmette Guérin) only minor changes in BALT in the rat occurred. Intratracheal administration of a T-independent antigen (lipopolysaccharide) and a partly T-independent antigen (paratyphoid vaccine) resulted after 1 week in an increase in cytoplasmic IgM-containing (cIgM) blast cells and plasma cells; these appeared to enter via the high endothelial venules (HEV). After 6 weeks, germinal centers were seen.
Mice were primed subcutaneously in the hind footpads with horseradish peroxidase (HRP) and boosted intravenously 10 weeks later. The appearance of cells with cytoplasmic anti-HRP antibody was studied in several lymph nodes. It appeared that following intravenous boosting antibody-forming cells appeared in significant numbers in the popliteal, the lumbar, and (in some animals) the sciatic lymph nodes exclusively. In the other lymph nodes examined specific antibody-forming cells were observed only occasionally. By subcutaneous injection of Evans blue in the hind footpads it was shown that the subcutis of the hind footpads of these animals is drained by the popliteal lymph nodes, the lumbar lymph nodes, and (to a lesser degree) the sciatic lymph nodes. The presence of trapped immune complexes within lymph node germinal centers was confined to these three nodes. Based on these findings, it is concluded that specific antibody-forming cells during the secondary response in these mice are induced exclusively in the lymph nodes draining the site of primary immunization.
Specific antibody-forming cells from spleen, bone marrow and popliteal lymph nodes were studied in mice after subcutaneous priming and intravenous boosting with horseradish peroxidase (HRP). Functional antibody-secreting capacity of these cells was correlated with their morphology at the cell population level. For this purpose, cells synthesizing anti-HRP antibody from the same cell suspensions were studied simultaneously by light and electron microscopy and by a plaque assay. It appeared that the population of cells responsible for antibody synthesis as well as antibody secretion was morphologically heterogeneous: besides plasma cells, considerable numbers of antibody-forming lymphocytes, antibody-forming plasmablasts and antibody-forming immature plasma cells were observed. Immature plasma cells constituted the majority of antibody-forming as well as antibody-secreting cells. Among the immature plasma cells in the popliteal lymph nodes proliferation occurred. Evidence is presented that the light-microscopically identified mature plasma cell is not the main antibody-forming cell. It does not show 3H-Thymidine incorporation and should be considered as a non-dividing end-cell.
The localization of T- and B lymphocytes and interdigitating cells (IDC) was investigated during the regeneration process of splenic implants. For this purpose a two-step immunoperoxidase technique was used to visualize T-cell antigen, immunoglobulins and Ia-antigen on cryostat sections. The specific localization of the repopulating lymphocytes occurred simultaneously with the development of non-lymphoid elements characteristic for the different compartments of the white pulp, i.e., the periarteriolar lymphocyte sheaths (PALS) and follicles. The marginal zone (MZ) developed after the PALS and primary follicles, but before germinal center reactions were found. During ontogeny, however, the development of a broad MZ precedes the formation of follicles. This difference in sequence of events is discussed.
The histology of the specific and non-specific antibody response in mouse and rat bone marrow was studied after subcutaneous priming and intravenous boosting with horseradish peroxidase (HRP). Cells producing specific antibody against HRP were found only occasionally in the bone marrow after subcutaneous priming. After the intravenous boost injection their number gradually increased. These anti-HRP forming cells were found as single cells, randomly dispersed throughout the bone marrow. Such a random distribution was also found for cytoplasmic (non-specific) immunoglobulin containing cells. At no time point after immunization could lymphoid aggregates or trapping of immune complexes be observed in the bone marrow of either species. On the basis of these observations it is concluded that the bone marrow forms a suitable microenvironment for immigrating antibody-forming cells but does not contribute actively to the induction of the immune response.
Mice were given subcutaneous priming injections of horse radish peroxidase (HRP) in the hind leg foot pads, and ten weeks later intravenous booster injections. Cell suspensions of popliteal lymph nodes, spleen and bone marrow were obtained at various time intervals after boosting and incubated in vitro for 1 h in the presence of 3H-thymidine (3H-TdR). In each suspension the number of cells showing simultaneously anti-HRP antibody and incorporation of 3H-TdR was determined. Whereas in spleen and bone marrow only very few 3H-TdR labelled antibody-forming cells were observed, a clear proliferative response was noticed in the popliteal lymph nodes. Already on the first day after booster injection proliferation of cells showing incipient antibody synthesis was demonstrable in lymph nodes. It is strongly suggested that most - if not all - antibody-forming cells in these animals are derived from proliferating cells in the local draining lymph nodes. A relationship between the route of primary immunization and nature and location of the secondary proliferative response is discussed.
Regeneration of splenic tissue after autologous subcutaneous implantation provides a useful model for studying the development of splenic tissue. The development of the various non-lymphoid cells of the white pulp in the rat is described. It appears that regeneration of the implants is initiated by ingrowing vessels and a newly formed reticulum, which forms the microenvironment for the homing lymphocytes. Marginal metallophils are found at their characteristic location at the inner border of the marginal sinus five weeks after implantation. Trapping of antigen-antibody complexes reappears when the first primary follicles can be recognized.
The histogenesis of the popliteal lymph node in the rat and the popliteal and inguinal lymph nodes in the rabbit was examined by light microscopy. Special emphasis has been laid on the initial lymphocyte population in the lymph node anlage. In the rat on the seventeenth day of gestation lymphoid cells populate a limited mesenchymal area along the vein wall. The next day the mesenchyme shows a bulb-shaped outgrowth causing an indentation in the wall of a lymph vessel, running parallel to the vein and having a saccular widening at this place. The bulb-shaped lymphoid outgrowth fills up the widened lymph vessel; the subcapsular sinus originates from the remaining parts of the lymph vessel. At birth the lymph node can be divided into a primitive cortex consisting of an area with evenly scattered lymphocytes among the basic network of reticular cells and a medulla. About three days after birth an ovoid area containing a dense concentration of lymphocytes is observed in the inner cortex. In the next days it expands in both lateral and medullary direction but not into the outer cortex. Primary follicles appear in the outer cortex 18 days after birth. The development of the inguinal and popliteal lymph nodes in the rabbit shows the same characteristics as the histogenesis of the popliteal lymph node in the rat. The morphogenesis of the lymph node is summarized in a schematic diagram.
The effect of linoleic acid on the electrophoretic mobility of red blood cells from both MS patients and normal subjects was studied. An extensive statistical evaluation of the data clearly demonstrated that there was no difference in behaviour of red blood cells from patients and normal subjects in the presence of linoleic acid. Even a tendency for the mobility of erythrocytes to be decreased in patients and increased in normal subjects after addition of linoleic acid was not observable.
Since the central area is an integral part of the guinea pig thymus, the cells in this area were compared with those in the thymic cortex and medulla in cryostat-sections by using methods for demonstration of E-, EA-, EAC-adherence and surface membrane immunoglobulins. In the extra cortical central area (ECCA) 15 to 25% of the lymphocytes showed EAC-adherence and 5 to 10% appeared to bear surface membrane immunoglobulins (SIg). In the lymph sinuses up to 70% of the lymphocytes were EAC- and SIg-positive. A small amount of EAC-adhering cells was present in the medulla of the central area. Cortical lymphocytes were EAC- and SIg-negative. From these results we conclude that in the guinea pig thymus B lymphocytes are specifically localized in the central area.
There have been many attempts in the past to classify phagocytic mononuclear cells and to define the cell system they are considered to form-among these being the "macrophage system" of Metchnikoff, the "reticulo-endothelial system" of Aschoff, and the "reticulo-histiocyte system" proposed by Volterra and reintroduced by Thomas. None of these is entirely adequate in the light of present knowledge. In 1969, therefore, a group of workers proposed a new classification of all highly phagocytic mononuclear cells and their precursors in what they termed the "mononuclear phagocyte system". This system includes the promonocytes and their precursors in the bone marrow, the monocytes in the peripheral blood, and the macrophages in the tissues. Subsequent consultation with numerous other specialists throughout the world led to a certain number of changes in this classification, which is now proposed in revised form.Inclusion of cells in the "mononuclear phagocyte system" is based on similarities in the morphology, function, origin, and kinetics of the phagocytes. By these criteria reticular cells, dendritic cells, endothelial cells, and fibroblasts (fibrocytes) are excluded. The proponents point out that as new knowledge is acquired modifications may have to be made, certain cells being added to or removed from the new classification.
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