Intestinal lymphoid tissue changes in the cortisone-treated Wistar rat

This paper continues the previous investigation of the Department on the lymphoid tissue of central and peripheral lymphoid organs under different experimental conditions. The morphological reactional modalities of the intestinal lymphoid tissue in the male Wistar rat were followed up under endocrine imbalance conditions following cortisone administration. Seven days after administration cortisone induced a hyperplasia of the intestinal lymphoid tissue in parallel with a depletion of the lymph node parenchyma and a hypercellularity of bone marrow. After a 6-week postcortisone interval, the lymphoid tissue showed changes corresponding to a cellular depletion in parallel with the restoration of the lymph node parenchyma and a normocellular bone marrow.     

Experimental study of late effects of the damaging action of doxorubicin on the lymphoid tissue

It was shown in experiments with CBA/Lac J mice that both a single use of doxorubicin (MID) and its use during a treatment course (1/10 LD50.10) induced impairment of the morphological composition of the central and peripheral lymphoid organs along with changes in the functional activity of separate cell populations of the immune system which persisted over a prolonged period up to 3 months. The course use of the drug resulted in a significant decrease in the proliferative response of the splenocytes to the polyclonal T- and B-cell mitogens in 1 month, which was followed by inhibition of interleukin-2 production. On the contrary, 1 month later, the single administration of the cytostatic induced activation of the LPS-responding cell populations and an increase in production of the growth factor in the culture of T-lymphocytes.     

Effect of cyclosporin on tumor xenotransplantation under the renal capsule in mice

Stimulating effect of cyclosporine on growth and invasiveness of tumor xenographts was studied on a model of rat solid sarcoma M-1 transplanted under the kidney capsule in mice. Cyclosporine was administered subcutaneously in a dose of 25 or 75 mg/kg on days 1-7. The stimulating effect of cyclosporine was directly associated with the immunodepressant dose and accompanied by a decrease in the thymus weight. With using cyclosporine the model of xenographts under the kidney capsule can be of value in screening cytostatics and immunomodulators.     

Theileria parva: Kinetics of infection in the lymphoid system of cattle

The kinetics of infection with Theileria parva in cattle were studied by examining the total cellularity and numbers of parasites in a range of lymphoid organs from animals killed at intervals during the course of the infection. With the dose of T. parva stabilate used, macroschizonts were initially detected in the drainage lymph node about 7 days after inoculation and death of the host resulted on Day 18–19. Associated with the initial detection of parasites, there was a marked increase in cellularity of the drainage lymph node and a more gradual and less pronounced increase in cellularity of the other lymphoid organs. From about Day 12 onward, there was a gradual decrease in the cellularity in all of the lymphoid organs, so that in animals examined in the terminal stages of the infection there was often cellular depletion. The pattern of these cellular changes was similar in groups of Boran and Friesian cattle, although both the increase in cellularity and the terminal depletion were more marked in the Friesians. Blood leukocyte counts in infected Boran started to drop as early as Day 7 of infection and by Day 14 had reached values less than 25% of normal. Quantitation of parasitic schizonts indicated that the numbers of parasites in the lymphoid organs do not increase in a simple exponential manner. Rather, there appears to be an early rapid increase in parasite numbers followed by a phase of less rapid multiplication. Because of the marked changes which occured in total cellularity of the lymphoid organs during the course of the infection, a significant discrepancy was found between the replication rate of the parasite as calculated using total numbers of parasites and that obtained using schizont index (SI). These results indicated that the use of SI, as described in previous studies, is not a reliable method of determining the replication rate of the parasite.     

Morphofunctional changes in the lymphoid tissue of the respiratory organs in gamma-globulin administration

By means of macro-microscopic, histologic, radioautographic and immunomorphologic methods, three forms of the lymphoid tissue structural organization have been revealed in the rat respiratory organs: a lymphoid cluster, a lymphoid follicle and a lymphoepithelial nodule. After gamma-globulin is administered intranasally, the ratio of the lymphoid cells in the organs mentioned changes: the number of small lymphocytes decreases, while that of middle, large lymphocytes and blast cells increase. The lymphoid follicles consist of a central and a marginal zones, in the lymphoepithelial nodules the subepithelial and paranodular zones also exist. The gamma-globulin administration stimulates DNA synthesis by the cells of the lymphoid type and their proliferation; that results in increasing number of the antibody-synthesizing cells and is accompanied with an increasing titre of antibodies in washing from the bronchial tree. At a repeated stimulation, the processes are more intensive and develop more quickly.     

Role of prostanoids and endothelins in the prevention of cyclosporine-induced nephrotoxicity.

Cyclosporine A nephrotoxicity includes both functional toxicity and histological changes, whose seriousness is dependent upon the dose and the duration of the drug administration. Several vasoactive agents have been found to be implicated in cyclosporine induced nephrotoxicity, among which prostanoids and endothelins are the most important. In previous studies we were able to prevent the early stage (7 days) of cyclosporine (37.4 micromol [45 mg]/kg/day) induced nephrotoxicity in rats either by the administration, i) of OKY-046, a thromboxane A(2)synthase inhibitor, ii) of ketanserine, an antagonist of S(2)serotonergic, a(1)adrenergic, and H(1)histaminergic receptors and iii) of nifedipine, a calcium channel blocker, or by diet supplementation either with evening primrose oil or fish oil. All these protective agents elevated ratios of excreted renal prostanoid vasodilators (prostaglandins E(2), 6ketoF(1 alpha)) to vasoconstrictor (thromboxane B(2)), a ratio which was decreased by the administration of cyclosporine alone. Nifedipine averted the cyclosporine induced increase of urinary endothelin-1 release. All protections were associated with the reinstatement of glomerular filtration rate forwards normal levels whereas renal damage defence, consisting of a decrease of the cyclosporine induced vacuolizations, was variable. Ketanserine and evening primrose oil were the only agents which prevented the animal body weight loss. These data suggest that prostanoids and endothelin-1 may mediate functional toxicity while thromboxane A(2)is involved the morphological changes too, provoked in the early stage of cyclosporine treatment. However, other nephrotoxic factors and additional mechanisms could also be implicated in the cyclosporine induced nephrotoxicity.     

Myelotoxicity of epirubicin]

Epirubicin (pharmorubicin, India), an antitumor antibiotic of the anthracycline group, was studied in regard to its effect on peripheral blood, bone marrow and lymphoid organs (the thymus and spleen) of CBA mice after its intraperitoneal administration in a single dose equal to the MIC (7.8 mg/kg) and in a course dose (1/5 of the MIC 5 times a day). The cytogenetic impairments induced by the cytostatic were estimated on metaphase plates with the bone marrow specimens and by counting the peripheral blood erythrocytes with micronuclei (the micronuclear test). It was shown that epirubicin induced cytogenetic disturbances in the hemopoietic cells within the first 72 hours. The antibiotic had a marked reversible effect on the erythroid population and lymphoid tissues and a moderate toxic action on the granulocyte population. The antibiotic did not affect thrombocytopoiesis. The single administrations had a more pronounced and prolonged myelotoxic and lymphotropic effect.     

Trypanosoma cruzi: early resistance induced by culture-derived trypomastigotes

Previous observations in this laboratory showed that injection of culture-derived trypomastigotes (CT), in CBA/J mice, induced an early increased resistance that was detected 24-72 hr after antigen injection and permitted mice to survive a challenge of 10(5) blood trypomastigotes (BT) corresponding to 2000 LD50%. Present experiments were conducted to determine the optimal conditions for inducing this early resistance and to investigate the early morphological changes which occurred in blood and lymphoid organs of mice infected with either BT or CT. Among nine antigens tested, only living CT showed a protective effect permitting most of mice to survive 30 days after BT challenge, while control mice injected with PBS or other antigens died at 10 +/- 1 days. A dose-response relationship was seen when different doses of CT were tested, higher doses of CT inducing higher survival and lower parasitemia. Injection of CT by either an im or ip route induced similar degrees of resistance but significantly different results were obtained when mice were challenged by using ip or im routes. Higher parasitemia and lower survival were always obtained when animals were challenged by the ip route. Within 72 hr, mice injected with BT presented a lymphopenia which reached a maximum at 48 hr, a depletion of thymic cortical zone, and splenomegaly with hyperplasia of the white pulp and congestion of the red pulp. No gross alterations were observed in animals infected with CT. Overall data suggest that the early resistance is a specifically induced phenomenon and that BT and CT induce different early reactions in the CBA/J lymphoid organs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of selenium and vitamin E dietary deficiencies on chick lymphoid organ development

Diets specifically deficient in selenium (Se) and/or vitamin E or adequate in both nutrients were fed to chicks from the time of hatching. Lymphoid organs (bursa, thymus, and in some instances, spleen) were collected from chicks 7-35 days of age. Growth of the chicks fed these diets was monitored over the experimental period as was lymphoid organ growth. The development of the primary lymphoid organs was further assessed by histological techniques and the organ contents of vitamin E (alpha-tocopherol) and Se were determined. Specific deficiencies of either Se or vitamin E were found to significantly impair bursal growth as did a combined deficiency. Thymic growth was impaired only by the combined deficiency diet. Severe histopathological changes in the bursa resulted from the combined deficiency and these were detectable by 10-14 days after hatching. These changes were characterized by a gradual degeneration of the epithelium and an accompanying depletion of lymphocytes. Similar changes, although slower to develop and less severe, were observed in the thymus as a result of the combined deficiency. When both serum and tissue levels of vitamin E and Se were monitored, it was observed that these were rapidly and independently depleted by the specific deficiency diets. These data suggest that the primary lymphoid organs are major targets of Se and vitamin E dietary deficiencies and provide a possible mechanism by which immune function may be impaired.     

Morphology of lymphoid organs in a cichlid teleost, Tilapia mossambica (Peters).

In Tilapia mossambica organized lymphoid tissues are present in the thymus, head-kidney and spleen, whereas they are lacking in pericardial tissue, liver, mesonephros, intestine and rectum. No lymphoid tissue was observed in the chondrocranium and cartilaginous viscerocranium of young adults. The thymus in Tilapia is encapsulated by thin strands of collagen fibers and consists of outer, middle and inner zones. While middle and inner zones are comparable to the thymic cortex and medulla of higher vertebrates, the homology of the outer zone is not clear. At the anterior end of the thymus, a loose aggregation of lymphocytes without a definite boundary has been observed. The head-kidney is characterized by the presence of lymphoid follicles, a subcapsular sinus, a hilus-like area and lymphatic vessels. The spleen is grossly divisible into white pulp and red pulp; the white pulp contains only a reticular area without definite lymphoid centers and the latter contains predominantly erythrocytes. Morphological changes in the lymphoid organs associated with immune response have been discussed.     

Ultrastructural studies of C1300 neuroblastoma cell interaction with syngeneic spleen lymphoid cells.

Sensitized and unsensitized spleen lymphoid cells from A/J mice were induced to form rosettes with cells of clone NB6R of syngeneic C1300 neuroblastoma cells. Light and transmission electron microscopy were applied in combination with ⁵¹Cr release experiments to follow the time course of reaction after rosette formation. With unsensitized lymphoid cells, rosettes formed but target cell morphology in general remained unchanged. With sensitized lymphoid cells a progressive series of morphological changes in the target cells was seen, initially in the mitochondria and, later, when specific ⁵¹Cr release became significant, in the formation of large surface blebs and protrusions. Our data also show another phenomenon occasionally following rosette formation. Lymphocytes were seen within the target cell; these either apparently transformed to lymphoblasts and killed the target cell from the inside or alternatively were destroyed by the host cell and their material was reutilized.     

Thymus, peripheral lymphoid tissues and immunological responsiveness of the pituitary dward mouse (author's transl)]

Snell's pituitary dwarf mice (dw) were used for studies on the relationship between hypophysis and lymphoid organs. The age-dependent changes of thymus or spleen weights of dwarf mice were compared with those of normal littermates. The suppression of growth of the thymus or spleen in dwarf mice was recognized at 5th day of age. Although involution of the thymus varied among animals, a strong positive correlation was demonstrated between relative thymus weight and body weight in 30 approximately 40 days old dwarf mice. Lymphoid organs of dwarf mice were reconstituted by injection of growth hormone and or thyroxin. Relative thymus weight significantly increased in dwarf mice when the treatment with growth hormone started at 7 days of age, but the same treatment at 3 months of age did not show any effect on the increment of relative thymus weight. On the other hand, the antibody-forming capacitiy against sheep erythrocytes of dwarf mice was significantly increased even when the treatment with growth hormone was started at 3 months of age. A marked increase in the number of lymphoid cells in dwarf mice was observed by treatment with thyroxin, even if treatment was started either at 7 days or 3 months of age. Similar changes were also obtained in the antibody-forming capacity.     

Morphologic changes in the thymus and lymphoid nodules of the appendix of the white rat subjected to increasing physical loads

By means of histological and morphometrical methods the thymus and appendage have been studied in male white rats subjected to a dosed physical loading (swimming). The physical loading is accompanied with essential changes in structure and cell composition of the immunogenic organs. The rate and character of the changes depend on the adaptability level of the animal's organism to the physical loading. At adaptation to the loading, the process of age involution of the thymus decelerates, amount of lymphoid nodules in the appendage increases, comparing the control parameters, contents of lymphocytes noticeably increase in all zones of the lymphoid nodules. When adaptation to the physical loading is not sufficient, the rate of the thymus involution sharply increases, while in the appendage the number of the lymphoid nodules decreases. However, in some animals at a sharp involution of the thymus, the changes in the appendage do not differ from the control ones.     

Histopathological observations of spontaneous regression of Rous sarcomas in Japanese quails.

Turmors induced in Japanese quails by the Schmidt-Ruppin strain of Rous sarcoma virus were examined histopathologically. The following three phases were recognized in the quails whose tumors regressed finally (regressor). Phase I was between days 4 and 7 of virus inoculation, when growth of tumor cells was seen with predominant infiltration of heterophils. Phase II, from days 10 to 14, was characterized by necrosis of tumor cells and focal accumulation of lymphoid cells which frequently formed follicle-like nodules. In phase III from days 18 to 24, tumor cells and heterophils disappeared, whereas diffuse infilitration of lymphoid cells, plasma cells and histiocytes were demonstrated. In the quails whose tumors progressed (progressor), growth of tumor cells and infiltration of heterophils at phase I seemed to follow a pattern similar to that of regressors, but subsequent infiltration and focal accumulation of lymphoid cells were rare. These morphological findings suggested an immunological reaction against tumor cells by lymphoid cells.     

Distribution and morphologic characteristics of lymphoid cells in the canine popliteal lymph nodes in their normal state and under antigen effect

By means of morphometry, light and electron microscopy methods peculiarities in distribution of small, middle and large lymphocytes, as well as plasmocytes in various zones of the popliteal lymph nodes have been studied in normal and in dynamics up to one year after subcutaneous injection of BCG vaccine into the left hind paw. The antigen produces certain changes in density and morphological parameters of lymphoid cells both in the regional and in the contralateral lymph nodes. For them 3 periods are specific. During the first 3 days they are not antigen-dependent (stipulated by the stress reaction), during 7-24 days antigen-dependent processes of proliferation and differentiation of lymphocytes get into action. In 3 months a new wave of the immune response is observed.     

Morphological changes after large-field irradiation of dogs and autologous bone marrow transplantation

The effect of an automyelotransplant taken from a nonirradiated area of bone marrow has been studied after large fields irradiation in dogs. Certain changes occurring in the hemopoietic organs and in some other vitally important organs have been revealed. The automyelotransplantation contributes to a quicker repopulation of the bone marrow and stimulates lymphoid hemopoiesis in the spleen; that plays a positive role in overcoming the bone marrow syndrome at radiation illness. In other organs (gastrointestinal tract, kidneys, lungs, heart) given various doses of irradiation, in the control and test (with automyelotransplantation) groups similar morphological changes have been revealed.     

Adjuvant Action of Capsular Polysaccharide of Klebsiella pneumoniae on Antibody Response

Changes in the number of cells and the weight of various lymphoid organs of mice, such as the regional lymph node (right inguinal node), spleen, thymus, bone marrow, and peripheral blood, were followed after the subcutaneous injection of the capsular polysaccharide of Klebsiella pneumoniae (CPS-K). For comparison, the changes after injection of various polyclonal lymphocyte activators (PLA) including various preparations of bacterial lipopolysaccharide (LPS) were concurrently studied. The number of cells of all of the lymphoid organs tested and that of nucleated cells in the peripheral blood decreased significantly within a few days after injection of CPS-K, and increased later. Above all, the increase in the number of cells and in the weight of the regional lymph node was most prominent (about 10 times larger than that of the normal control). Such a marked increase in the number of cells of the regional lymph node was not induced by the injection of any preparation of LPS or any other PLA tested. The initial decrease in the number of cells after CPS-K injection was most marked and long lasting in the thymus. Although LPS prepared by Westphal's method from Escherichia coli O55 or Salmonella enteritidis exhibited a stronger decreasing effect on the number of cells of the thymus, the effect of LPS prepared by Westphal's method from E. coli O111 or that by Boivin's method from E. coli O55 was similar to that of CPS-K. It is concluded therefore that CPS-K has the ability to decrease the number of cells of various lymphoid organs, especially that of the thymus, initially after injection, which is a property in common with LPS, and CPS-K has a unique ability to increase markedly the cells of various lymphoid organs, especially those of the regional lymph node, at later stages after injection. Considering that CPS-K exhibits a much stronger adjuvant effect on the antibody response than does LPS or other polyclonal lymphocyte activators, it is suggested that this extraordinarily potent activity of CPS-K in increasing the number of cells of the regional lymph node is closely related to its strong adjuvant action.     

Comparative pathomorphologic study of the toxic properties of a corpuscular pertussis vaccine and of a cell-free pertussis preparation

The comparative study of morphological changes in the body of outbred mice under the action of corpuscular pertussis vaccine and acellular pertussis preparation has been made. The corpuscular vaccine has been shown to produce a pronounced, dynamically increasing toxic effect, thus causing the damage of lymphoid thymic and spleen cells, prolonged interstitial reaction in the lungs, destructive inflammatory process at the site of injection. The acellular pertussis preparation is less toxic, induces less pronounced changes in these organs at the early period of the experiment, stimulates the proliferation of lymphoid cells and lymphoblast transformation. As noted in this study, the damaging action of pertussis vaccine is mainly indicated by pathological phenomena appearing in the organs of the immune system, pulmonary parenchyma and muscular tissue (in the inoculation zone).     

The immune system and age

Basing on numerous facts, obtained during last years at investigation of the immune system organs, a definite idea has been formed on peculiarities of their structure during certain stages of human ontogenesis. The immune organs appear early in embryogenesis and by birth they have reached their morphological maturation. This is evident as formation of diffuse lymphoid tissue in lymphoid noduli, that can have germinative centers, where young cells of the lymphoid line are formed. The immune system organs develop especially quickly after birth during first years of the postnatal ontogenesis. The peak in development of the organs of immunogenesis, amount and size of the lymphoid noduli occurs during the childhood and adolescent age. Each immune organ has its peculiarities that are determined by their place in the organism, value and intensity of antigenic effect. Beginning from the adolescence and youth amount of the lymphoid tissue and lymphoid noduli in the organs decreases, in their place connective and adipose tissue grows out.     

Rat thymus reconstitution after thymocyte destruction by glucocorticoid treatment--from the view of endogenous DNA synthesis and soybean lectin responsiveness in thymocytes

The dynamic process in rat thymocyte restoration after their destruction by glucocorticoid (GC) administration was examined. Thymus weight and thymocyte count became minimal 4-5 days after the administration. Then the thymus took a course of recovery. Endogenous DNA synthesis in thymocytes, reflecting their proliferation within thymus, decreased for 4 days but began to increase 6-8 days after GC treatment. Thymocyte responsiveness to soybean lectin (SBL), a possible stimulator for T-cell-precursors, showed elevation 4-5 days after the treatment. A marked decrease of lymphocytes in the cortex and unclearness of cortico-medullary junction were observed 2-3 days after GC treatment. Clusters of small lymphoid cells, which possibly contained SBL-responding cells, were found in the subcapsular area 4 days after the treatment and successively, large lymphocytes became visible in the same area. Thereafter, small lymphocytes in the cortical mid and deep zones increased, and cortico-medullary junction was restored. These histological features are discussed from the view of correspondence with the dynamic changes of endogenous DNA synthesis and SBL responsiveness in the thymocytes after GC administration.