Immunosuppression in experimental trypanosomiasis: effects of Trypanosoma equiperdum on the pathogenesis of influenza virus infection in deer mice (Peromyscus maniculatus).

The effects of Trypanosoma equiperdum infections on the immunological and pathological responses of deer mice (Peromyscus maniculatus) to influenza virus exposure were investigated. Mice carrying a 5 week trypanosome infection along with an age- and sex-matched trypanosome-free control group were simultaneously exposed to influenza Ao (WSN) virus. T. equiperdum infection significantly (P less than 0.01) converted a sub-lethal virus attack into a fatal pneumonic process in a small proportion of animals. In addition, the trypanosome caused a reduction (p less than 0.1) in virus replication on PID 1 and 2, accompanied later by a tendency towards virus persistence in the lungs of affected mice. This tendency was manifested by a log reduction in virus titres between PID 2 and 4 and PID 4 and 6 in the lungs of trypanosome-infected mice, compared to 2 log drops over the same periods in the lungs of control mice. T. equiperdum infection also significantly (p less than 0.001) depressed serum and pulmonary neutralizing antibody titres to influenza virus.

Monocyte function in rhesus monkeys with simian acquired immune deficiency syndrome.

Monocyte function in rhesus monkeys with simian acquired immune deficiency syndrome (SAIDS) was compared with that in age-matched normal juvenile rhesus monkeys. The functional tests were 1) chemotaxis, 2) phagocytosis of opsonized Candida albicans, 3) killing and/or growth inhibition of Candida albicans, 4) generation of respiratory burst, and 5) monocyte-derived macrophage response (morphology and/or respiratory burst) to stimulating agents such as lymphokines, gamma interferon, endotoxin, and phorbol myristate acetate. The monkeys tested had either clinical SAIDS (alive with lymphadenopathy, splenomegaly, and lymphopenia or neutropenia) or had terminal SAIDS (moribund due to the disease). Responses of monocytes from 14 monkeys with clinical SAIDS were indistinguishable from those of 9 normal juvenile rhesus monkeys, whereas monocytes from 3 monkeys with terminal SAIDS had enhanced phagocytosis and respiratory burst capacity. Chemotaxis, candidacidal/stasis activity, and response to stimulating agents were normal in these terminal cases. Plasma from the SAIDS monkeys was as capable of opsonizing yeasts and of being able to generate chemotactic factors by endotoxin as was control plasma. SAIDS retrovirus (SRV) was detected by co-cultivation of pure monocyte-derived macrophage cultures with Raji cells, an indicator cell line which forms syncytia in the presence of SRV. Four terminal SAIDS cases and one late-stage clinical SAIDS case were virus-positive when the number of macrophages in the cultures ranged from less than 50 to about 500. Terminal SAIDS monocyte-derived macrophages in culture as long as 17 days produced SRV. These data show that in monkeys with SAIDS the major effector functions of monocytes and macrophages involved in host defense are intact (even up until death). Additionally, some of the monocytes are productively infected, and these infected monocytes are viable and adherent in culture.

Preparation of primary cultures of tick cells.

Primary cell cultures were prepared from preimaginal bodies from the nymphal ticks, Rhipicephalus sanguineus, Dermacentor andersoni, and Amblyomma maculatum, and from the hemocytes of late-stage nymphal and adult ticks, Ornithodoros coriaceus. The dissection methods for obtaining preimaginal bodies and hemocytes for culture are described. A culture mediu, designated RML 375, was used for both culture methods. Primary cultures were established with minimal contamination. Preimaginal body cultures may be maintained for 2 to 8 months or longer and hemocyte cultures for 1 to 9 months. Cultured cells form incomplete monolayers and tend to grow in clusters. Subculturing these cells is difficult, although A maculatum have been sucessfully subcultured several times. A brief review of arthropod tissue culturing is presented and potential applications of the method are discussed.

Immunosuppression in deer mice with experimentally induced trypanosomiasis.

Light and electron microscopic examinations of deer mice (Peromyscus maniculatus) chronically infected with Trypanosoma equiperdum revealed hyperplasia of germinal center lymphocytes (germanocytes) in the lymph follicles of spleen and lymph nodes and infiltration of the splenic red pulp cords and nodal medullary cords with plasma cells. Proliferation and infiltration of plasma cells caused disruption of the B- and T-lymphocyte areas in these organs. Stimulation of splenic lymphocytes in vitro by phytohemagglutinin and concanavalin A revealed marked depression in T-lymphocyte response; stimulation with lipopolysaccharide and pokeweed mitogens showed depression of B-cell response. Deer mice infected with virulent trypanosomes had decreased immunologic response to injection of sheep red blood cells, whereas deer mice given radioattenuated trypanosomes had normal to enhanced immunologic response to injection of sheep red blood cells.

Clinical, serologic, and pathologic changes in calves with experimentally induced Trypanosoma brucei infection.

In 7 calves inoculated with Trypanosoma brucei and observed for 105 days, the minimal clinical signs were occasional lethargic periods associated with parasitemia. Rectal temperatures increased by postinoculation day (pid), 10, remained moderately high until PID 50 to 60, and then returned to base line. Moderate anemia occurred between PID 15 and 25. Slightly increased lymphocyte count with relative decrease in neutrophil count was found in 3 calves. Monocytosis of minimal degree occurred 14 days after parasitemia. Trypanosome counts of low level and irregular frequency were found throughout the infection. The average number of trypanosomes in blood was approximately 1,000/ml. Antibody titers, as determined by the indirect immunofluorescent antibody method, appeared on PID 22 and stayed at moderate levels. The immunoglobulin M first increased at PID 5 and remained high (av 216% of base line value) throughout infection, but immunoglobulin G was never increased. Histopathologic study revealed proliferative changes in the lymph nodes and spleen characteristic of humoral antibody (B-cell) response. Mononuclear cell infiltration (lymphocytes and plasma cells), eosinophols, and edema were common in the lymph nodes, spleen, liver, heart, brain, hypophysis, testes, kidney, skeletal muscle, adrenal gland, pancreas, and uterus.

A soluble immunosuppressor substance in spleen in deer mice infected with Trypanosoma brucei.

A soluble substance that blocks B-cell response was extracted from spleen of deer mice (Peromyscus maniculatus) chronically infected with Trypanosoma brucei. Immunosuppressor activity of this substance was demonstrated by plaque-forming cell assays of spleen cells from Swiss/Webster mice inoculated with sheep red blood cells and simultaneously given the suppressor substance, and of spleen cell cultures treated with sheep red blood cells and suppressor substance. Studies by light and electron microscopy of spleen of immunosuppressed Swiss/Webster mice showed that the suppressor substance blocks germinal center formation and prevents plasma cell differentiation in the red pulp cords.

Pathogenesis of Trypanosoma equiperdum in rabbits.

Seventeen rabbits experimentally infected with Trypanosoma equiperdum were examined for lesions at different times during a 5-month period. A chancroid developed at the inoculation site in the skin, and later, similar lesions appeared in skin of the ears, eyelids, and nose. The inflammatory reaction was primarily granulomatous, and viable trypanosomes were present in all skin lesions. The rabbits had reticuloendothelial hyperplasia of spleen and lymph nodes. In 3 rabbits, there was amyloid deposition in splenic lymph nodules and renal glomeruli. Amyloid had typical fibrillar appearance by electron microscopy (EM) and was reactive for immunoglobulin M (IgM) and immunoglobulin G (IgG) with fluorescent antibody (FA). With time, there was lessening capability of T equiperdum to agglutinate in antiserums of infected rabbits, suggesting that antigenic variation occurred during infection. The serum concentrations of IgM and IgG increased significantly in the infected rabbits and then remained elevated or they decreased, though fluctuating widely. Three of 5 infected rabbits demonstrated depressed antibody response to injected ovine erythrocytes.

Immunofluorescent studies on chronic pneumonia in swine with experimentally induced African swine fever.

Chronic pneumonia experimentally produced in 14 pigs with African swine fever (ASF) virus was studied by immunofluorescene (IF) and histopathologic techniques. Frozen sections prepared from pulmonary tissues of the infected pigs were stained with fluorescein-conjugated antiserums against ASF viral antigen, porcine immunoglobulin G (IgG), procine complement (C), and porcine fibrinogen. The viral antigen(s) was mainly seen in macrophages and cell debris in alveolar walls and lumens. This finding indicates that the virus replicated in the cytoplasm of alveolar macrophages that subsequently degenerated and released the viral antigen. Diffuse immunoglobulin (Ig) deposition was found in necrotic cells and debris. Immunoglobulin also was seen bound to intracytoplasmic inclusion bodies in some degenerating alveolar macrophages. This finding indicates that antibody against ASF viral antigen(s) excluded from blood circulation or produced by local immunocytes (or both) reacted with viral antigen at intramacrophage and extramacrophage levels and resulted in the formation of insoluble antigen-antibody (Ag-Ab) complexes. The participation of C in the immune complex was evident in the early stage of the pneumonia, but was less evident in the subsequent extensive, progressive necrotic processes. Fibrin deposits were visible only in the early necrotic area of alveolar walls and lumens. Possible mechanisms inducing extensive necrosis are discussed.

Pathologic features of chronic pneumonia in pigs with experimentally induced African swine fever.

Chronic pneumonia developed in 14 pigs inoculated with an attenuated strain of African swine fever (ASF) virus. The pathogenesis of the pneumonia was as follows: (1) Interalveolar septums became thickened by accumulation of lymphocytes and monocytes; (2) lung developed focal areas of lymphocytes and macrophages; (3) necrosis began abruptly in these foci, beginning with the cells in the alveolar lumens, developing in centrifugal direction, and eventually affecting all structures in its path; (4) necrotic tissue became calcified; and (5) a mantle of mononuclear cells (including plasma cells) and fibrous tissue formed around the necrotic area. Viremia occurred in the 14 pigs at postinoculation day (PID) 14, and precipitating antibody was increased significantly at PID 58.

Prognostic factors associated with radiotherapy of squamous cell carcinoma of the nasal plane in cats.

Ninety cats were irradiated for treatment of squamous cell carcinoma of the nasal plane. The 1- and 5-year progression-free survival rates were 60.1 +/- 5.5% and 10.3 +/- 6.2%, respectively. Analysis of progression-free survival times revealed that clinical stage and tumor proliferative fraction (estimated by the use of a proliferating cell nuclear-antigen immunohistochemical method) had significant prognostic value. Conversely, coat color, presence of multiple facial carcinomas, histologic grade, and feline immunodeficiency virus infection status were not found to have prognostic value. Acute radiation reactions were mild and self-limiting. Severe chronic radiation reactions were more frequent in cats infected with feline immunodeficiency virus. Results of the study indicated that cats with squamous cell carcinoma of the nasal plane benefit from radiotherapy and that treatment might be improved by increasing the radiation dose as well as altering the dose-fractionation scheme.

Exophthalmos in a horse resulting from an adenocarcinoma of the frontal sinus.

A fifteen-year-old thoroughbred gelding with exophthalmos of the left eye, was found at necropsy to have an adenocarcinoma of the left frontal sinus. The tumour extended caudally through the cribriform plate into the orbit, displacing the eyeball anteriorly.