Histological and histochemical changes in the peripheral organs of the immune system of dogs in cases of isoniazid poisoning

Most publications on isoniazid poisoning in dogs are devoted to clinical diagnostics, treatment, and prevention of the disease. Histological and histochemical changes are not fully described, though they are important in assessing the toxic effects of isoniazid. Isoniazid is used to treat tuberculosis in humans. Dogs are hypersensitive to this drug. The article highlights the results of macroscopic, histological, and histochemical studies of the dogs’ lymph nodes and spleen in cases of isoniazid poisoning. A pathological examination of 19 corpses of dogs of different ages was performed, during which isoniazid poisoning was posthumously diagnosed, based on anamnesis, clinical signs, pathological autopsy, histological, and histochemical examination. Samples of lymph nodes and spleen were fixed in a 10% aqueous neutral formalin solution, Carnoy’s solution, and Bouin’s fixative. Histoсuts were prepared using a sled microtome and stained with hematoxylin and eosin. Staining was also performed according to the techniques suggested by McManus, Brachet, and Perls. The pathomorphological changes in lymph nodes and spleen were characterized by disorganization of vascular walls and connective tissue fibers of the stroma, dilatation of veins, their overflow with hemolyzed blood, and, in cases of the long clinical course, thrombosis of small vessels. Intravascular hemolysis of erythrocytes resulted in an excessive formation of hemosiderin. Histochemically, the spleen and lymph nodes showed a significant increase in the number of hemosiderophages in the spleen’s red and white pulp and the lymph nodes’ central sinuses and pulp cords. In the spleen, mucoid swelling and necrobiotic changes in the wall structures of the arterioles and arteries progressed with a narrowing of their lumen in dogs suffering from the long clinical course. Increased permeability of the microcirculatory tract vessels of the spleen and lymph nodes, transudate formation, and the destructive changes in the reticular skeleton accompanied hemodynamic violations. A sharp change in blood rheology caused the violation of trophism and metabolism in the immune system. Lymphoid elements of the lymph nodes and white pulp of the spleen were in a state of karyorrhexis and karyolysis. The morphological study of the immune system’s peripheral organs suggests that dogs poisoned by isoniazid demonstrate hemodynamic disorders, changes in the physicochemical properties of blood (hemolysis of erythrocytes and thrombosis). This is the basis of trophic disorders, metabolic malfunctions, and the development of dystrophic processes in all structural elements of the spleen and lymph nodes.

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The histopathology of splenic lymphoma with villous lymphocytes

Blood ◽

10.1182/blood.v84.11.3828.bloodjournal84113828 ◽

1994 ◽

Vol 84 (11) ◽

pp. 3828-3834 ◽

Cited By ~ 157

Author(s):

PG Isaacson ◽

E Matutes ◽

M Burke ◽

D Catovsky

Keyword(s):

Lymph Nodes ◽

Marginal Zone ◽

Molecular Characteristics ◽

White Pulp ◽

Splenic Marginal Zone Lymphoma ◽

Mantle Zone ◽

Marginal Zone B Cells ◽

Splenic Lymphoma ◽

Spleen And Lymph Nodes ◽

Red Pulp

Whereas the hematologic, immunophenotypic, and molecular characteristics of splenic lymphoma with villous lymphocytes (SLVL) have been well documented, the histologic features of the spleen and lymph nodes remain uncharacterized. We have reviewed the histopathology of the spleen in 37 cases of SLVL and of involved splenic hilar lymph nodes in 6 cases. Tissue immunophenotyping was performed in 24 cases, 6 of which had frozen tissue available, and the results were compared with the membrane immunophenotype of the circulating villous lymphocytes and cells extracted from spleen and lymph nodes. In the spleen, SLVL is characterized by involvement of the white pulp follicles, which may be surrounded or replaced by the lymphoma cells. In the red pulp, the cells form small nodules and infiltrate diffusely with sinusoidal invasion. The cytologic appearance of the neoplastic cells varies from a resemblance to small mantle-zone--like lymphocytes to that of marginal-zone cells and there are scattered blast forms. In involved lymph nodes, the infiltrate again centers on the follicles that are usually replaced, but occasionally show preservation of follicle centers; sinuses are often preserved. The tissue immunophenotype is similar to that of marginal-zone B cells. Membrane immunophenotyping may give different results in some cases and may vary depending on the compartment from which the cells are obtained. SLVL in the peripheral blood is a histologically homogeneous entity identical to the condition previously characterised by histopathologists as splenic marginal-zone lymphoma.

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Lymphocytosis Induced in Mice by Supernatant Fluids of Bordetella pertussis Cultures: A Histopathological Study

Blood ◽

10.1182/blood.v42.4.611.611 ◽

1973 ◽

Vol 42 (4) ◽

pp. 611-621 ◽

Cited By ~ 4

Author(s):

Thomas J. Athanassiades ◽

Stephen I. Morse

Keyword(s):

Lymph Nodes ◽

Bordetella Pertussis ◽

Marked Decrease ◽

Histopathological Study ◽

White Pulp ◽

Circulating Lymphocytes ◽

Spleen And Lymph Nodes ◽

Culture Supernatants ◽

Lymphocyte Populations ◽

Later Phase

Abstract Intravenous injection into mice of phase I Bordetella pertussis culture supernatants produces a marked lymphocytosis. The evolution of lymphocytosis was correlated with histopathological alterations in the lymphoid organs. The early phase, 17 hr to day 3, was associated with massive depletion of both lymphocytes from the white pulp of the spleen and of cortical thymocytes. There was a corresponding profound decrease of splenic and thymic weights. The later phase was associated with a marked decrease in lymphocytes of lymph nodes while concomitantly the spleen and thymus appeared to be repopulating. Both thymic-dependent and thymic-independent lymphocyte populations were mobilized from spleen and lymph nodes. There was a striking diminution in the number of lymphocytes contained within the walls of postcapillary venules (PCVS) of all lymph nodes between 2 and 7 days. The data suggest that initially the lymphocytosis is due predominantly to release of splenic lymphocytes and to a lesser extent of thymocytes into the circulation. Subsequently, the lymphocytosis is sustained by the depopulation of the lymph nodes. Lymph node depopulation is maintained by the failure of circulating lymphocytes to emigrate from the blood through the PCVS.

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Incidence of Apoptosis in the Lymphoid Organs of Normal or Malaria Infected Mice is Decreased in CD18 and Urokinase - Receptor (UPAR, CD87) Deficient Mice

Developmental Immunology ◽

10.1155/2001/75259 ◽

2001 ◽

Vol 8 (3-4) ◽

pp. 183-191 ◽

Cited By ~ 5

Author(s):

Pierre Francois Piguet ◽

Chen da Laperrousaz ◽

Christian Vesin ◽

Yves Donati

Keyword(s):

Lymph Nodes ◽

Annexin V ◽

Urokinase Receptor ◽

Lymphoid Organs ◽

White Pulp ◽

Facs Analysis ◽

Surface Molecules ◽

Spleen And Lymph Nodes ◽

Serum Igg Levels ◽

Deficient Mice

Incidence of apoptosis was investigated in the spleen and lymph nodes of +/+, CD18 -/- and urokinase receptor (uPAR, CD87) -/- mice, untreated orPlasmodium Berghei Anka(PbA) infected. In non infected mice, incidence of apoptosis was lower in the lymph nodes of CD18 -/- and uPAR -/- than in +/+ mice, as seen by FACS analysis to count the number of hypodiploid and Annexin-V binding cells. Infection of mice with PbA resulted in a marked increase in the size of spleen and lymph nodes 7–8 days after infection, which was slightly higher in uPAR -/- and CD18 -/- than in +/+ mice. PbA infection increased about 7 fold the incidence of apoptosis in the lymphoid organs of +/+, especially in the white pulp and germinal centers of the spleen and lymph nodes, while in contrast it was unchanged in PbA infected CD18 -/- or uPAR -/- mice. Serum IgG levels, and number of circulating leukocytes were significantly higher in both uPAR and CD18 -/- than in +/+ mice. These results indicate that the CD18 and uPAR surface molecules, which are known to be associated in the cell membrane, have an important influence upon the incidence of cell survival in both normal or stimulated lymphoid organs.

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Response of the immune system of mammary tumor-bearing rats to cyclophosphamide and soluble low-molecular mass tumor-associated antigens: The spleen and lymph nodes

International Journal of Molecular Medicine ◽

10.3892/ijmm.9.3.311 ◽

2002 ◽

Author(s):

H. Ben-Hur ◽

G. Kossoy ◽

D. Schneider ◽

J. Zandbank ◽

I. Zusman

Keyword(s):

Immune System ◽

Lymph Nodes ◽

Molecular Mass ◽

Mammary Tumor ◽

Tumor Associated Antigens ◽

Tumor Bearing ◽

Spleen And Lymph Nodes

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ROLE OF THE THYMUS IN IMMUNE REACTIONS IN RATS

Journal of Experimental Medicine ◽

10.1084/jem.116.2.187 ◽

1962 ◽

Vol 116 (2) ◽

pp. 187-206 ◽

Cited By ~ 143

Author(s):

Byron H. Waksman ◽

Barry G. Arnason ◽

Branislav D. Janković

Keyword(s):

Lymph Nodes ◽

Plasma Cells ◽

Germinal Centers ◽

White Pulp ◽

Size Number ◽

Splenic White Pulp ◽

Spleen And Lymph Nodes ◽

Lymphoid Nodules ◽

Lymphatic Organs

In rats thymectomized at birth, there was a profound depletion of small lymphocytes in various lymphatic organs. In the spleen, these cells were completely lacking from the Malpighian bodies and splenic white pulp. Empty reticular structures remained surrounding the white pulp arterioles. In the lymph nodes, large masses and nodules of small lymphocytes (primary lymphoid nodules) were either markedly depleted or absent, as were the zones of these cells normally surrounding germinal centers. In both spleen and nodes, germinal centers appeared normal in size, number, and cellular make-up; and plasma cells were found in normal or even increased number in their customary position. Rats which in spite of thymectomy developed intense Arthus or delayed reactivity showed incomplete depletion of the lymphoid tissue. It is concluded that small lymphocytes of the spleen and lymph nodes may come, in large part, directly from the thymus and are not derived from medium and large lymphocytes of the germinal centers. It is suggested that there may be a second population of small lymphocytes whose function is unrelated to the thymus lymphocytes.

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Pathomorphological characteristic of immune organs for circovirus infection of piglets

Scientific Messenger of LNU of Veterinary Medicine and Biotechnology ◽

10.15421/nvlvet8329 ◽

2018 ◽

Vol 20 (83) ◽

pp. 150-155

Author(s):

G. Kotsyumbas ◽

M. Shkil

Keyword(s):

Lymph Nodes ◽

Sharp Decrease ◽

Giant Cells ◽

White Pulp ◽

Mesenteric Lymph Nodes ◽

Immune Organs ◽

Vascular Walls ◽

Mesenteric Lymph ◽

Pulp Cells ◽

Hematoxylin And Eosin

The article elucidates the results of pathoanatomical and histological searches of peripheral immune organs for circovirus infection of piglets. In one of the farms of Transcarpathian region among the pigs of 3–4 months of age were found clinically ill animals, blood was taken, serum test was performed and circiiros was diagnosed. The pathoanatomical autopsy of 12 corpses of piglets was done. During the autopsy of corpses macroscopic changes were studied and samples of mesenteric lymph nodes and spleen were taken, which were fixed in 10% neutral formalin, dehydrated in alcohols of increasing concentration, followed by sealing and filling with paraffin. From paraffin blocks, histological cuts were made, stained with hematoxylin and eosin, using the Van Gizon method. Light microscopy and photographing were performed using a Leica DM-2500 (Switzerland) microscope and Leica DFC450C cameras and the Leica Application Suite Version 4.4 software. For macroscopic examination, in all cases, hyperplasia of the spleen and serous-hemorrhagic lymphadenitis have been established. For histological examination of mesenteric lymph nodes in sick piglets with cirrhosis against a background of severe congestive hyperemia, diapedeous hemorrhages, exudation, there was a sharp decrease in the number of lymphocytes in the lymph nodes, activation of reticuloendothelial cells, transformation of them into epithelioid and formation of giant cells. The detection of polycarocytes in the lymph nodes of sick piglets on the circus is a morphological confirmation of the cytopathic effect of the virus. The histological search of the spleen of pigs for circovirus infection on the background of blood filling, edema of trabeculae, plasma permeation of vascular walls was marked by an intensive decrease in the number of white pulp cells, as evidenced by a sharp decrease in the lymph nodes themselves. The revealed histostructural changes indicated a depletion of the spleen, suppression of its generative function, and an immunosuppressive state of one of the organs of immunogenesis.

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Soufeng sanjie formula alleviates collagen-induced arthritis in mice by inhibiting Th17 cell differentiation

Chinese Medicine ◽

10.1186/s13020-021-00448-9 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Di Hua ◽

Jie Yang ◽

Qinghai Meng ◽

Yuanyuan Ling ◽

Qin Wei ◽

...

Keyword(s):

Cell Differentiation ◽

Lymph Nodes ◽

Inflammatory Cytokines ◽

Th17 Cell ◽

Collagen Induced Arthritis ◽

Expression Levels ◽

Th17 Cell Differentiation ◽

Spleen And Lymph Nodes ◽

Seed Coats

Abstract Background Rheumatoid arthritis (RA) is a chronic autoimmune disease. Soufeng sanjie formula (SF), which is composed of scolopendra (dried body of Scolopendra subspinipes mutilans L. Koch), scorpion (dried body of Buthus martensii Karsch), astragali radix (dried root of Astragalus membranaceus (Fisch.) Bge), and black soybean seed coats (seed coats of Glycine max (L.) Merr), is a traditional Chinese prescription for treating RA. However, the mechanism of SF in treating RA remains unclear. This study was aim to investigate the anti-arthritic effects of SF in a collagen-induced arthritis (CIA) mouse model and explore the mechanism by which SF alleviates arthritis in CIA mice. Methods For in vivo studies, female DBA/1J mice were used to establish the CIA model, and either SF (183 or 550 mg/kg/day) or methotrexate (MTX, 920 mg/kg, twice/week) was orally administered to the mice from the day of arthritis onset. After administration for 30 days, degree of ankle joint destruction and serum levels of IgG and inflammatory cytokines were determined. The balance of Th17/Treg cells in the spleen and lymph nodes was analyzed using flow cytometry. Moreover, the expression levels of retinoic acid receptor-related orphan nuclear receptor (ROR) γt and phosphorylated STAT3 (pSTAT3, Tyr705) in the spleen were detected by immunohistochemistry. Furthermore, the effect of SF on Th17 cells differentiation in vitro was investigated in CD4+ T cells under Th17 polarization conditions. Results SF decreased the arthritis score, ameliorated paw swelling, and reduced cartilage loss in the joint of CIA mice. In addition, SF decreased the levels of bovine collagen-specific IgG in sera of CIA mice. SF decreased the levels of inflammatory cytokines (TNF-α, IL-6, and IL-17A) and increased the level of IL-10 both in the sera and the joint of CIA mice. Moreover, SF treatment rebalanced the Th17/Treg ratio in the spleen and lymph nodes of CIA mice. SF also reduced the expression levels of ROR γt and pSTAT3 (Tyr705) in the spleen of CIA mice. In vitro, SF treatment reduced Th17 cell generation and IL-17A production and inhibited the expression of RORγt, IRF4, IL-17A, and pSTAT3 (Tyr705) under Th17 polarization conditions. Conclusions Our results suggest that SF exhibits anti-arthritic effects and restores Th17/Treg homeostasis in CIA mice by inhibiting Th17 cell differentiation.

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EXTH-14. A NOVEL LONG-ACTING INTERLEUKIN-7 AGONIST, NT-I7, INCREASES CYTOTOXIC CD8 CELLS AND ENHANCES SURVIVAL IN MOUSE GLIOMA MODELS

Neuro-Oncology ◽

10.1093/neuonc/noaa215.368 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii89-ii89

Author(s):

Subhajit Ghosh ◽

Ran Yan ◽

Sukrutha Thotala ◽

Arijita Jash ◽

Anita Mahadevan ◽

...

Keyword(s):

T Cells ◽

Lymph Nodes ◽

Cd8 T Cells ◽

Peripheral Blood ◽

Cervical Lymph Nodes ◽

Cd8 Cells ◽

Interleukin 7 ◽

Long Acting ◽

Spleen And Lymph Nodes ◽

Mouse Glioma

Abstract BACKGROUND Patients with glioblastoma (GBM) are treated with radiation (RT) and temozolomide (TMZ). These treatments can cause prolonged severe lymphopenia, which is associated with shorter survival. NT-I7 (efineptakin alfa) is a long-acting recombinant human IL-7 that supports the proliferation and survival CD4+ and CD8+ cells in both human and mice. We tested whether NT-I7 would protect T cells from treatment-induced lymphopenia and improve survival. METHODS C57BL/6 mice bearing intracranial tumors (GL261 or CT2A) were treated with RT (1.8 Gy/day x 5 days), TMZ (33 mg/kg/day x 5 days) and/or NT-17 (10 mg/kg on the final day of RT completion). We followed for survival and profiled CD3, CD8, CD4, FOXP3 in peripheral blood over time. In parallel, we assessed cervical lymph nodes, bone marrow, thymus, spleen, and the tumor 6 days after NT-I7 treatment. RESULTS Median survival in mice treated with NT-I7 combined with RT was significantly better than RT alone (GL261: 40d vs 34d, p< 0.0021; CT2A: 90d vs 40d, p< 0.0499) or NT-I7 alone (GL261: 40d vs 24d, p< 0.008; CT2A: 90d vs 32d, p< 0.0154). NT-17 with RT was just as effective as NT-I7 combined with RT and TMZ in both GL261 (40d vs 47d) and CT2A (90d vs 90d). NT-I7 treatment significantly increased the amount of CD8+ cells in the peripheral blood and tumor. NT- I7 rescued CD8+ T cells from RT induced lymphopenia in peripheral blood, spleen, and lymph nodes. NT-I7 alone or NT-I7 in combination with RT increased the CD8+ T cells in peripheral blood and tumor while reducing the FOXP3+ T-reg cells in the tumor microenvironment. CONCLUSIONS NT-I7 protects T-cells from RT induced lymphopenia, improves cytotoxic CD8+ T lymphocytes systemically and in the tumor, and improves survival. Presently, a phase I/II trial to evaluate NT-I7 in patients with high-grade gliomas is ongoing (NCT03687957).

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