Alteration of the construction and cellular composition of ileo-colonic lymph nodes of rhesus macaques after administration of salmonella vaccine]

In stained histological sections, percentage ratio of areas to different cellular elements in structural components of the ileocolonic lymph nodes was studied in mature Macaca rhesus, normal and after injection of salmonella vaccine. A rather considerable reaction in all structural components and cell composition of the lymph nodes was demonstrated as a response to immunization of the animals. These changes were demonstrated in decreased area occupied by the cortical substance and in increased area occupied by the medullar substance of the lymph node. In the cortical substance, together with decrease in the cortical plateau, total number of folliculi rises with formation of light centers in them. Calculation of cellular elements revealed that in the cortical substance cytopoietic function was inhibited; that was expressed in decreasing mitoses and blast forms in the cells. Most drastic alterations occur in myelin cords of the lymph nodes. Together with increasing area, a considerable reaction of acidophilic leucocytes, premature plasma cells and macrophages is observed. Their number increases notably.     

Cellular composition of the lymph nodes of monkeys (rhesus macaque) under normal and experimental conditions]

By means of mathematical methods, quantitative and qualitative changes were studied in different structural components of the mesenteric (ileocecal) lymph nodes in normal monkeys (Macaca rhesus) and under per os administration of Salmonella typhi murium, streptomycin-dependent. Cellular composition was calculated in the cortical plateau, cortical (lymphoid) cords and in follicules. Average percent of every cell type was determined. Vaccine administration, was stated to inhibit cytopoiesis in the cortical plateau and in the follicules with light centers. An inverse correlation was noted between the content of small and medium size lymphocytes. Different reactivity of certain structural components in the lymph nodes was demonstrated. As a response to the vaccine administration, plasmocellular acidophilic and macrophagal reactions were most pronounced in the cortical (lymphoid) cords.     

Peritoneal macrophages introduced into mouse foot pads enter the germinal center of regional lymph nodes nonspecifically.

Male mice were injected into their foot pads with sheep erythrocytes (SRBC) to form lymph follicles in the germinal centers in the popliteal lymph nodes. 4 weeks later, peritoneal macrophages labeled with carbon from syngeneic donors sensitized with SRBC or typhoid-paratyphoid bacilli (TAB) were separately injected into the foot pads as well. The popliteal lymph nodes were histologically examined at 6 h to 5 days after injection. Labeled macrophages appeared in the marginal sinus, migrated straight across the cortex from the marginal sinus to the lymph follicles and then entered the germinal centers. There was no difference in the mode of appearance, migration and localization of labeled macrophages in the regional lymph nodes between the mice given labeled macrophages from SRBC-sensitized donors and those given macrophages from TAB-sensitized donors. The entrance of lymph macrophages into the germinal centers of the regional lymph nodes would be immunologically nonspecific. After the injection of Pelikan ink into the foot pads, the macrophages which have taken up carbon in the peripheral tissue reached the regional lymph nodes via the afferent lymphatics and then entered the germinal centers, mainly through the medullary pole of the lymph follicles, after migrating along their immediate exterior from their marginal sinus to their medullary pole.     

Function of the follicular dendritic cell in the germinal center of lymphoid follicles

The authors made an immunocytochemical examination of the germinal centers (GCs) of (1) lymph follicles in physiological lymph nodes and (2) extra-nodal tissues of divergent diseases including thyroid disorders, rheumatoid arthritis, Warthin's tumor and Kimura's disease (Eosinophilic lymphfolliculoid granuloma). In these germinal centers, the presence of immunoglobulins (IgG and IgM), early acting complement components (C1q, C4, C3c, C3d), receptors for C3b and C3d and dendritic reticulum cell-1 was demonstrated in lace-like network patterns which were proven electron-microscopically to coincide with the surface of follicular dendritic cells. IgE was distributed in a lace-like pattern in the GCs of proliferating follicles of Kimura's disease, in which the lysis of follicles was frequently observed. This lysis appeared to be related to the presence of complement components. In the germinal centers of extra-nodal tissues, including the thyroid tissues accompanying the lymph follicles, rheumatoid arthritis synovial tissues as well as Warthin's tumors, thyroglobulin, rheumatoid factor and salivary amylase were detected as specific antigens, occurring in lace-like patterns. It is possible that follicular dendritic cells may play a role in the genesis of GCs and be responsible for the immune response through C3 receptors.     

Induction of lymph follicle formation with several mitogens and adjuvants in the mouse popliteal lymph node

The formation of lymph follicles in draining popliteal nodes was investigated in young adult male mice which had been injected in the rear footpad with several mitogens and adjuvants, and killed after 3-21 days. PPD (100 micrograms-1 mg) and PHA (25-500 micrograms) induced germinal centers in association with existing follicles and mild plasmacytosis, but failed to produce new follicles in draining nodes. Endotoxin LPS (50-200 micrograms), Con A (50 micrograms-1 mg) and PWM (50 micrograms-1 mg) induced germinal centers within existing follicles and plasmacytosis, and also produced new follicles which soon developed germinal centers. Both Freund's complete and incomplete adjuvants (FCA and FICA, 25 microliters) induced virtually no germinal centers and plasmacytosis, but produced a significant number of new primary follicles. Poly (A, U) (600 micrograms) produced neither germinal centers nor plasmacytosis, and did not induce new follicles. Analysis of the distribution of lymphoid cells which had incorporated 3H-thymidine in the draining nodes at 3 days after the injection of test substances indicated that PPD, PHA, LPS, Con A and PWM preferentially stimulated in vivo the same types of lymphocytes as they do in vitro. FCA triggered lymphocyte activation in the deep cortex, whereas Poly (A, U) appeared not to stimulate lymphocytes in vivo. In further experiments, induction of lymph follicles with artificially precipitated PPD and PHA was studied. The draining nodes treated with alum-precipitated PPD or PHA were found to produce a significant number of new follicles.(ABSTRACT TRUNCATED AT 250 WORDS)     

The early postnatal development of the primary immune response in TNP-KLH-stimulated popliteal lymph node in the rat

Summary The popliteal lymph nodes were removed from young rats of various ages five days after a single immunization with TNP-KLH in the hind footpads. Cryostat sections of the lymph nodes were investigated by means of enzyme and immunohistochemical techniques at the light-microscopical level.The presence and localization of anti-TNP antibody-containing cells were examined using a new technique to visualize specific antibodies. Moreover, the development of the lymph nodes following exogenous antigenic stimulation was compared with that of unstimulated lymph nodes.Specific antibody-containing cells could not be found before day 15 after birth, in rats immunized at day 10. From that time these lymphoid cells were located primarily at the border between cortex and medulla. Younger popliteal lymph nodes showed only aspecific immunoglobulin-containing lymphoid cells. With age, the number of specific antibody-containing cells tended to increase. These cells were more mature, according to morphological criteria and were located nearer the medulla.The first primary follicles were seen at day 19, as was the case in unstimulated animals. The first secondary follicles, containing germinal centers, were detected at day 23, whereas in unstimulated popliteal lymph nodes they were never found.Trapping of immune complexes could not be demonstrated before day 33 after birth. The later appearance of this phenomenon might be a consequence of the techniques applied to demonstrate specific antibody-containing cells.Abbreviations PLN popliteal lymph node - FDC follicular dendritic cell - IDC interdigitating cell - HEV high endothelial venule - TNP trinitrophenyl - KLH keyhole limpet hemocyanin - PBS phosphate-buffered saline - GCPC germinal center precursor cell - sIg surface immunoglobulin - cIg cytoplasmic immunoglobulin     

Ontogeny of the antigen-reactive lymph follicle-forming capacity of the popliteal lymph node in neonatal mice

The ontogenetic development of the reactive lymph follicle-forming capacity of the popliteal lymph node was investigated immunohistochemically in young mice which had received a single injection of hemocyanin (KLH) in a rear footpad at a predetermined age (between 1 and 21 days). The mice were sacrificed at various intervals after injection. In non-stimulated young mice, primary lymph follicles first appeared in the popliteal node at 11 days of age. When KLH was given to 7-day-old or older mice, each draining popliteal node showed a marked increase in B lymphocytes in the extrafollicular zone 3 days after injection and produced a number of "new" lymph follicles outside the pre-existing follicles over the next few days. In mice injected at 2-4 days of age, these nodes showed an increase in B lymphocytes in the outer cortex and had produced several lymph follicles by 8 days of age. The number of lymph follicles produced by each node tended to increase in line with age at injection. These results indicate that neonatal popliteal nodes become able to produce lymph follicles in response to exogenous antigens some time before ontogenetically developing follicles appear. The formation of new lymph follicles observed in draining popliteal nodes after KLH injection at an early postnatal age is discussed in relation to the ontogenetic development of stromal cells (precursors of follicular dendritic cells) that are capable of interacting with B lymphocytes and the extent of B lymphocyte influx into the node induced by KLH stimulation.     

Sites of lymph follicle formation in the draining popliteal lymph nodes of mice locally injected with antigenic and mitogenic substances

Our previous studies showed that some antigenic and mitogenic substances, when locally injected into mice, efficiently produced new lymph follicles outside pre-existing follicles in draining lymph nodes, whereas others had virtually no effect. In the present experiments, young adult male mice were injected with several antigens and mitogens in the rear footpad, and the number and development sites of newly produced lymph follicles in the draining popliteal nodes were studied using serial sections of the nodes obtained between 5 and 21 days after injection. In the unstimulated state, each popliteal node contained a limited number of lymph follicles which mostly lay in a portion of the peripheral cortex overlaying the deep cortex (this portion is referred to as the PCOU), whereas a portion of the peripheral cortex extending beyond the deep cortex (referred to as the PCBU) was underdeveloped with only occasional follicles. Mice treated with soluble PHA or fluid tetanus toxoid developed germinal centers in association with existing follicles but failed to produce new follicles. The PCBU of the draining nodes remained underdeveloped, and the number and distribution pattern of lymph follicles within a draining node were comparable to those in the control node. Animals treated with LPS (50 micrograms), Con A, alum-precipitated PHA or alum-precipitated tetanus toxoid produced significantly large numbers of new follicles outside pre-existing follicles in the draining nodes, the new follicles produced in the PCBU being generally more numerous than those in the PCOU. In these draining nodes, the peripheral cortex, comprising a number of follicles, was found to overlie the deep cortex and extend beyond the deep cortex towards the hilar region. In animals given a less effective stimulant, such as ferritin or a smaller dose of LPS (10 micrograms), the draining nodes produced a relatively small number of new follicles, most of which were formed in the PCBU. The present results indicate that in the mouse popliteal node, the PCBU is morphologically underdeveloped under normal conditions, but develops lymph follicles in response to exogenous stimuli more readily than the PCOU, and that substances efficient in inducing follicle formation can be regarded as capable of stimulating the development of the peripheral cortex.     

Development and cell phenotypes in primary follicles of foetal sheep lymph nodes

Lymph nodes from sheep foetuses and postnatal lambs were examined to determine the participation of different leucocyte populations in primary follicle formation, with special emphasis on the emergence and subsequent development of follicular dendritic cells during late gestation and early postnatal life. A series of immune and enzyme histochemical markers was used. The first 5′-nucleotidase-positive primary follicles were found at 80 days gestational age (gestation in sheep is 150 days) in superficial cervical lymph nodes. In the last month of gestation the primary follicles possessed follicular dendritic cells, macrophages, dendritic cells, and CD5-positive lymphocytes, in addition to IgM-positive cells. Follicular dendritic cells in primary follicles were found to be ultrastructurally immature. These follicular dendritic cells were characterised by a few, coarse surface projections and many ribosomes attached to the endoplasmic reticulum. A final differentiation to mature follicular dendritic cells was coincident with the postnatal germinal centre reaction. Computer-assisted morphometric analysis demonstrated that the size of 5′-nucleotidase-positive primary follicles in the distal jejunal lymph node, but not in the superficial cervical lymph node, increased significantly during late gestation. It was concluded that stromal cells in primary follicles of foetal sheep lymph nodes were a continuously developing population but that ultrastructural maturity was only achieved in the germinal centres of postnatal lambs.     

Entamoeba histolytica: lymphoreticular changes in gerbils (Meriones unguiculatus) with experimentally induced cecal amebiasis

Antibody responses and changes in the lymphoreticular tissues of gerbils with experimental cecal amebiasis were studied from 5 to 60 days PI. Changes in the cecum consisted of lymphoid follicle hyperplasia and depletion of lymphocytes, followed by follicle atrophy and histiocytosis. Mesenteric lymphadenopathy, and histologic alterations in the lymph nodes paralleled the progressive development of amebic cecal lesions. Early in the infection (5 to 10 days PI) mesenteric lymph nodes showed cortical follicle hyperplasia, blastogenesis in the paracortical areas (PCA) and intense lymphoblast and plasma cell activity in the medullary cords. At 20 to 30 days PI, the cortical follicles, the PCA and the medulla were depleted of lymphocytes and there was histiocytosis throughout the organ. At 60 days PI, lymphocyte repopulation took place in the PCA, and cortical follicles had active germinal centers. Spleen follicles did not increase in number as the infection progressed, but became hyperplastic. Antibody titers to ameba were low throughout the cecal infection but rose whenever amebic metastasis to the liver occurred. The results of this study indicate that lymphocytes from the submucosal lymphoid follicles and the draining lymph nodes may control the pathogenesis of the infection. Lymphoreticular tissue alterations could result from antigenic stimulation and migration of cells to the sites of infection.     

Features of the structure of the regional lymph nodes of the duodenum in monkeys

By means of morphometric methods, duodenal regional lymph nodes were studied in rhesus and lapunder macaques. It was demonstrated that in monkeys the connective tissue framework, cortical plateau, medullary substance, cortical substance, sinuses and follicles are expressed differently. Cellular elements in the lymph nodes analysed in the monkeys subjected to a comparative investigation demonstrated their uneven distribution in the same structural components. Small lymphocytes were predominate cellular elements. There were rather essential differences in the number of plasmic cells, mitotically dividing cells, acidophilic granulocytes, mast cells and macrophages. Certain species differences were demonstrated to exist both in structure and cell composition of the lymph nodes that seemed to depend on some local peculiarities of immunogenic reactions.     

Development and cell phenotypes in primary follicles of foetal sheep lymph nodes

Lymph nodes from sheep foetuses and postnatal lambs were examined to determine the participation of different leucocyte populations in primary follicle formation, with special emphasis on the emergence and subsequent development of follicular dendritic cells during late gestation and early postnatal life. A series of immune and enzyme histochemical markers was used. The first 5-nucleotidase-positive primary follicles were found at 80 days gestational age (gestation in sheep is 150 days) in superficial cervical lymph nodes. In the last month of gestation the primary follicles possessed follicular dendritic cells, macrophages, dendritic cells, and CD5-positive lymphocytes, in addition to IgM-positive cells. Follicular dendritic cells in primary follicles were found to be ultrastructurally immature. These follicular dendritic cells were characterised by a few, coarse surface projections and many ribosomes attached to the endoplasmic reticulum. A final differentiation to mature follicular dendritic cells was coincident with the postnatal germinal centre reaction. Computer-assisted morphometric analysis demonstrated that the size of 5-nucleotidase-positive primary follicles in the distal jejunal lymph node, but not in the superficial cervical lymph node, increased significantly during late gestation. It was concluded that stromal cells in primary follicles of foetal sheep lymph nodes were a continuously developing population but that ultrastructural maturity was only achieved in the germinal centres of postnatal lambs.     

Similarity and difference of the response of Peyer's patches and mesenteric lymph nodes of rats to polychemotherapy]

The structure of the Peyer's patches and mesenteric lymph nodes of rats at different periods after polychemotherapy was investigated by light microscopy. After the use of antitumor drugs the number of the blasts and mytoses in the lymphoid follicles with the mesenteric lymph node bright centres and in the Peyer's patch follicles lowered, that along with the decrease of the size of the mantle zone in the lymph node follicles and the decrease of the area of the bright centres in the follicles of the lympoid formations in the intestinal wall was evident of the proliferation inhibition and B cells differentiation in the lymphoid organs. After the polychemotherapy the size of the germinative centres of the Payer's patch follicles decreased while the size of the mantle zone remained unchanged. The size of the mantle zone in the follicles of the mesenteric lymph nodes decreased while the size of the germinative centres did not change. The different responses of the lymphoid organs could be associated with some remote location of the lymph nodes with respect to the antigen source (damaged epithelium and intestinal lumen contents).     

Microscopic structure of the mesenteric lymph nodes of monkeys]

The structure and cytoarchitectonics of mesenterial lymph nodes were studied in thin histological sections by different methods. Under study were 5 rhesus monkeys and 3 hamadryas baboons. The square surface of different structural elements of the nodes (the cortical and medullary substances, follicles, the connective tissue framework, sinuses) occupied by them in sections was calculated and the amount of cellular elements was determined (%). Comparison of the data obtained in rhesus monkeys and baboons speaks of certain species-specific features of the organs under study. The morphological picture of lymph node sections in baboons (as compared with rhesus monkeys) might suggest earlier ageing of nodes in baboons.     

Age and features of the construction and cellular composition of superior tracheobronchial lymph nodes in adult humans]

Age peculiarities in composition of the upper tracheobronchial lymph nodes have been studied in 60 corpses at the age of 16-70 years. Cause of death has not been connected with diseases of blood, lymphatic system or thoracic origins. Routine histological and morphometric methods have been applied. Certain age-dependent rearrangement in the connective tissue stroma, trabecular vegetations and differences in correlations of structural components have been noted. A rather essential volumetric increase of the medullary substance takes place at the level of hilus of the lymph node. Cellular composition of the lymph nodes is greatly polymorphous but is more or less constant for each age group. The number of macrophages containing carbon pigment is increasing with age.     

Germinal centers and the B-cell system

Summary Germinal centers of the rabbit appendix were studied for the presence of complement receptors, immunoglobulin and alkaline phosphatase. In popliteal lymph nodes, de novo-developing germinal centers were studied with respect to these markers up to 21 days after sheep red blood cell (SRBC)-stimulation. In addition, the possible presence of antigen (SRBC) receptor-bearing cells in these germinal centers was investigated.The results may be summarized as follows: 1) Germinal centers in the appendix as well as those in popliteal lymph nodes were rich in complement receptor-bearing cells. Complement-receptor density did not significantly change during a germinal-center reaction. 2) Immunoglobulins were present only at very low densities on the surface of lymphoid cells in the densely populated area of germinal centers. In germinal centers of popliteal lymph nodes lymphoid cells in the thinly populated area again showed higher densities. Immunoglobulins possibly complexed with antigen on the surface of follicular dendritic cells were not observed in the initial phase of a germinal center reaction. In contrast, in germinal centers of the appendix, immunoglobulin was present in excessive amounts throughout the thinly populated area, possibly complexed with antigen, which is also abundantly present. 3) Reticular staining patterns of alkaline phosphatase were present in the densely populated area, but absent in the thinly populated area of germinal centers in both appendix and popliteal lymph nodes. Primary follicles and young germinal centers were alkaline phosphatase-negative. 4) Antigen receptor-bearing cells were detected in germinal centers of popliteal lymph nodes as early as 5 days after SRBC-stimulation, reaching a maximum at day 10.In conclusion, with the present experimental approach, microenvironmental differences were shown between the densely populated area and the thinly populated area of germinal centers. However, no indication was obtained for a postulated maturation event of the lymphocytes within germinal centers, or for functional differences that may exist between germinal centers in the appendix and popliteal lymph nodes.     

Cellular composition of the deep cervical and apical axillary lymph nodes in mature and aged humans]

Quantitative investigation of the cellular composition of follicles, cortical plato and myelinated strands of the regional lymphatic nodes in man has shown the lymphocytes (small, medium-size and large) to be prevailing cellular elements in all structural components of the node. Among them there are many small lymphocytes. In myelinated strands there are more reticular, plasma, mast cells and macrophages than in the cortical plato of the lymphatic node. The follicles of the lymphatic nodes are more homogeneous structural components. They consist mainly of lymphocytes. The cellular composition of profound cervical and apical axillary lymphatic nodes is different in the quantitative contact of cellular elements. It also changes depending on age and symmetry.     

抗原物质引起滤泡的形成:一次投入与多次投入的比较

实验以不同方式投入抗原物质,即一次投入与分次投入,并观察了新产生滤泡数,维持的滤泡数,实验用小鼠２４ 只, 于足底注入铝和钥孔　血蓝素附合物（ＡＫＬＨ）, 分一次注入与三次注入组; 三次注入组又分间隔５ 日及间隔二周注入。注入后第３ 周与第１２ 周分别取出腘淋巴结,应用免疫组化法,第三周末观察可见一次投入产生的滤泡多, 而第十二周发现分次投入维持的滤泡数多。可见反应性滤泡的形成, 不仅与刺激物的性状和投入量有关, 而且与投入的方法有关     

Changes in the lymph nodes of rabbits following application of the breakdown products of fluoroplast]

Tracheobronchial, mesenterial and inguinal lymph nodes of 15 mature rabbits which were subjected to inhalation of valatile products of fluoroplast destruction were studied. The action of this drug for 1-40 days activated the reactive centers of follicles. The amount of blasts, plasmic cells, eosinophils, macrophages, lymphocytes increased in regional tracheobronchial and distant mesenterial lymph nodes. The prolonged action during 120 days resulted in decreased blasto- and lymphopoesis in the regional tracheobroncheal lymph nodes, depression of the reticular epithelium, suppression of the phagocytic and plasm cell reactions, decreased nucleic metabolism in the cells. Mesenterial lymph nodes retained their functions. The lymphopoesis in them and nucleic metabolism in the cells were intensified. The blastic, plasmic cell, eosinophilic and mast cell reactions were well pronounced.     

Histopathological study on six cases of calf leukosis.

A pathological study was carried out on six calves 4 to 10 months of age affected with lymphoid tumors. Most of the lymph nodes enlarged in consequence of leukotic changes in all the calves. These changes occurred also in other various organs. When the leukotic lesions were investigated to clarify the distribution and histological manifestation, three pathological patterns were discriminated among them. One of the patterns was seen in four cases, in which leukotic lesions were present constantly in bone marrow, thymus, liver and kidney. In the lymph nodes, tonsils, and intestinal lymphatic apparatus, neoplastic cellular proliferation took place in paracortical or interfollicular areas and medullary cords obliterating the lymph follicles. Leukotic involvement was observed in the interstitial and the vascular connective tissue in the thymus, as well as in liver and kidney. A second pattern of lesion was revealed in one of the other two cases. Besides lymph nodes in which neoplastic proliferation was seen in the paracortical area, only the thymus manifested intralobular neoplastic involvement in this case. In the remaining case, the leukotic lesion was characterized by the presence of neoplastic cellular masses resembling large lymph follicles in appearance in the lymphatic tissues. It was manifested distinctly in the spleen. Severe thymic atrophy and granulocytic hyperplasia in bone marrow were present in this case.