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Biomedical subjects

D E Bice

Publications and source records attributed to D E Bice.

At least 73 records · Page 4Linked to original sources

Regional immunologic responses following localized deposition of antigen in the lung.

This study evaluates the immune response in individual lung-associated lymph nodes of beagle dogs after immunization in specific lung lobes. A particulate antigen, sheep red blood cells (SRBC), was used for immunization. The numbers of anti-SRBC antibody-forming cells (AFC) in the tracheobronchial and in the mediastinal lymph nodes were determined 5 days after deposition of SRBC in the left or right apical or left or right diaphragmatic lung lobes. Results indicated that translocation of the SRBC antigen to these lymph nodes was basically ipsilateral because larger numbers of antigen-specific AFC were consistently found in lymph nodes from the same side of the lung that received SRBC immunization. Of 16 dogs immunized, only two did not show ipsilateral antigen stimulation of the lung-associated lymph nodes. This variance occurred only in a single lymph node in each dog. Although the SRBC antigen induced AFC predominantly in the ipsilateral lymph nodes, some AFC were also found in the contralateral lymph nodes. The largest numbers of AFC in the contralateral tracheobronchial lymph nodes were found after immunization in the right apical or right diaphragmatic lung lobes.

Animals↗

Immunology of the lower respiratory tract. Serial morphologic changes in the lungs and tracheobronchial lymph nodes of dogs after intrapulmonary immunization with sheep erythrocytes.

Sequential histologic changes in immunized and contralateral lung lobes, and ipsilateral and contralateral tracheobronchial lymph nodes were evaluated from dogs after intra-pulmonary immunization with sheep erythrocytes. In addition, changes in the relative numbers of unstimulated lymphocytes, activated lymphocytes, and plasma cells were determined for immunized and contralateral lung lobes by the use of bronchopulmonary lavage. Histologic evidence of an immune response occurred 2 days after immunization in ipsilateral tracheobronchial lymph nodes and on Day 5 in immunized lung lobes. Pulmonary lymphoid infiltrates appeared initially around pulmonary venules and veins. There was expansion of these infiltrates into alveolar spaces, where mixed mononuclear aggregates were formed in association with alveolar macrophages 7 days after immunization. A similar but attenuated and delayed response occurred within contralateral control lung lobes, although mononuclear aggregates were not found. Activated lymphocytes in lavage samples increased prior to histologic evidence of pulmonary lymphoid infiltrates. These results suggest that after intrapulmonary immunization the lung recruits circulating immunocytes produced in ipsilateral lung-associated lymph nodes as the source of specific antibody-forming cells in bronchoalveolar air spaces.

Animals↗

Methods to evaluate the effects of toxic materials deposited in the lung on immunity in lung-associated lymph nodes.

Intratracheal instillation of sheep red blood cells (SRBC) induced a primary immune response in lung-associated lymph nodes of Chinese hamsters and Fischer-344 rats. Few or no anti-SRBC antibody forming cells (AFC) were found in the spleen or cervical lymph nodes after intratracheal immunization. The number of AFC was significantly suppressed in the lung-associated lymph nodes from hamsters exposed by inhalation of 239PuO2 and in rats exposed by intratracheal instillation of benzo(a)pyrene (BaP). Although the immunologic function of the lung-associated lymph nodes was suppressed by 239PuO2 and BaP exposure, there was no observable increase in the number of AFC in distant lymphoid tissues. These data indicate that damage to lung cells and/or cells in lung-associated lymph nodes can suppress immunity induced by deposition of antigen in the lung. Even though lung-associated lymph nodes in exposed animals contained lower numbers of AFC, antigen instilled into the lungs of exposed animals did not significatnly translocate to distant lymphoid tissues. This indicates that the antigen filtering capacity of the lung-associated lymph nodes was not altered.

Aerosols↗

Adjuvant properties of Micropolyspora faeni.

The adjuvant properties of Micropolyspora faeni, an important source of antigenic material in the production of farmer's lung, were evaluated by comparing antibody- and cell-mediated immune responses of rabbits to bovine serum albumin (BSA) incorporated in complete Freund's adjuvant (CFA), incomplete Freund's adjuvant (IFA) and incomplete Freund's adjuvant with 5-10 mg/ml homogenized M. faeni (MFA). Rabbits immunized with BSA in CFA or MFA developed significantly increased antigen-induced macrophage migration inhibition, lymphocyte stimulation, and delayed skin reactivity when compared to those immunized with BSA in IFA. No similar adjuvant effect on specific antibody production was observed in rabbits immunized using BSA in MFA. These data suggest that M. faeni can act as a selective immunologic adjuvant for delayed hypersensitivity. This adjuvant property might be important in the induction of mononuclear cell infiltrates seen in human hypersensitivity pneumonitis.

Adjuvants, Immunologic↗

Passive transfer of experimental hypersensitivity pneumonitis with lymphoid cells in the rabbit.

Although precipitating antibody is associated with human hypersensitivity pneumonitis, there is evidence that cell-mediated hypersensitivity may be involved in disease pathogenesis. In this study, interstitial, and peribronchial lesions were produced by respiratory challenge of rabbits passively sensitized with ovalbumin-sensitive lymph node cells. Ovalbumin sensitivity of donor rabbits and lymph node cells was demonstrated by skin testing, migration inhibition factor (MIF) production using alveolar wash cells as migrating cells, and lymphocyte stimulation. Passive cell transfer was accomplished by intraperitoneal injection with all lymph node cells obtained from one donor transferred to one recipient. Recipients were challenged by aerosol or intratracheal injection of antigen immediately or 24 hr after passive sensitization and were killed 48 hr after challenge. Lesions in rabbits passively sensitized by lymph node cells and challenged with antigen by intratracheal inoculation consisted of focal pneumonitis with intra-alveolar edema and infiltrates of mononuclear cells in alveoli and alveoli septa. Aerosol challenge of passively sensitized animals produced similar changes, but peribronchial tissue containing macrophages and germinal centers was prominent in this group. Antiovalbumin serum recipients challenged by intratracheal injection demonstrated only mild peribronchial mononuclear cell infiltrates, without pneumonitis. Control animals receiving lymph node cells only or challenge only demonstrated no changes in lung histology.

Animals↗

Lymphocyte stimulation and plasma inhibition in patients with malignant neoplasms. A comparative study with three mitogens.

The blastogenic response of lymphocytes from patients with malignant neoplasms was evaluated by stimulation with three phytomitogens (PHA, PWM, and Con A). The response of patient lymphocytes to all three mitogens was significantly lower than that of control lymphocytes, and most patients with abnormal PHA responses also responded abnormally to PWM and Con A. However, a few patients with normal PHA responses were abnormal to Con A, suggesting the suppression of a Con A-sensitive population. The observation that PWM responses were abnormal in patients with lowered PHA lymphocyte stimulation indicates that both T and B lymphocyte mitogen responses were suppressed in these patients. Plasma from patients was capable of either inhibiting or enhancing lymphocyte mitogen stimulation. However, inhibitory plasmas were generally from patients with abnormal mitogen responses.

Concanavalin A↗

Effects on rat lung immunity by acute lung exposure to benzo(a)pyrene.

This study describes the effect of intratracheal instillation of benzo(a)pyrene (BaP) on immunological responses in the lung-associated lymph nodes, cervical lymph nodes, and spleen after deposition of 10(8) sheep red blood cells (SRBC) in the lung or peritoneal cavity of rats. An increased number of anti-SRBC antibody-forming cells was observed in the lung-associated lymph nodes when rats were immunized simultaneously with BaP installation. A suppression in the number of anti-SRBC antibody-forming cells occurred when SRBC were given intratracheally 4 or 7 days after BaP. The effects of the BaP appeared to be on the function of the cells in the lung-associated lymph nodes rather than due to changes in the exposed lung. BaP-induced changes in antigen handling or in regulatory populations of immune cells in the lung-associated lymph nodes may be responsible for the immune alterations observed.

Animals↗

Pulmonary immunity to ragweed in a Beagle dog model of allergic asthma.

To create an allergy model in the dog, allergic Beagles with high levels of serum immunoglobulin E (IgE) and eosinophilia were bred; resulting puppies were sensitized to ragweed by intraperitoneal (IP) injection within 24 hours of birth through 22 weeks of age. At least 50% of the puppies developed high levels of serum IgE and eosinophilia. As young adults, 6 of these dogs, and 6 control age-matched, nonallergic, nonimmunized dogs were exposed by inhalation to ragweed twice at 13-day intervals, and a third time 45 days later. Total and ragweed-specific serum IgE and ragweed-specific serum IgG were increased significantly in allergic dogs relative to baseline. Allergic dogs had significantly greater levels of antibody specific for ragweed, as well as higher eosinophil counts in the bronchoalveolar lavage fluid, compared to nonallergic dogs. Airway reactivity to histamine in allergic, but not nonallergic dogs, increased significantly after aerosol exposure to ragweed. After a third exposure to ragweed, airway responses to histamine were elevated in the allergic dogs and remained high for at least 5 months. These results demonstrate the potential of the allergic dog model for investigating the underlying pulmonary immune mechanisms and therapeutic treatment of allergic asthma.

Allergens↗

Translocation of particles from lung lobes or the peritoneal cavity to regional lymph nodes in beagle dogs.

Knowing the clearance pathways from the lung for inhaled materials is important to our understanding of the kinetics of particle clearance from the lung and other defense mechanisms, such as development of immune reaction to inhaled antigens. To determine the pathways and amounts of particles translocated to regional lymph nodes, radiolabeled fused aluminosilicate particles were instilled into specific lung lobes or injected into the peritoneal cavity of beagle dogs and the dogs were necropsied 34, 182, or 365 d later. Individual lung lobes cleared particles to one or two lymph nodes, and specific lymph nodes accumulated particles from one to three lung lobes. Lymph nodes that collected particles from the lung included the left mediastinal node, left tracheobronchial lymph node (TBLN), right TBLN, left middle TBLN, and right middle TBLN. The destinations for translocated particles were primarily the nodes proximate to the tracheal bifurcation. Particles injected into the peritoneal cavity were translocated mainly to mesenteric lymph nodes and left sternal and right sternal lymph nodes, with a small percentage of the particles going also to the left TBLN.

Animals↗

Nedocromil sodium inhibits canine adenovirus bronchiolitis in beagle puppies.

Nedocromil sodium is a nonsteroidal anti-inflammatory drug used to control asthmatic attacks. Our hypothesis is that nedocromil sodium inhibits virus-induced airway inflammation, a common trigger of asthma. We nebulized nedocromil sodium into beagle dogs (n = 10, mean +/- SEM ages: 149 +/- 13 days) before and after inoculation with canine adenovirus type 2 (CAV2). Control dogs (n = 10) received saline aerosols and were either infected with CAV2 (Sal/CAV2, n = 7, mean +/- SEM ages: 140 +/- 11 days) or were not infected (Sal/Sal, n = 3, ages: 143 +/- 0 days). All dogs were anesthetized with choralose (80 mg/kg i.v.), intubated, and mechanically ventilated. Pulmonary function tests and bronchoalveolar lavage (BAL) were performed using standard techniques. Pulmonary function tests revealed no significant change between the nedocromil sodium and non-nedocromil-treated groups. The percentage of infected bronchioles was quantitated as the number of inflamed airways of 40 bronchioles examined times 100 for each dog. Nedocromil-treated dogs had significantly (p < 0.05) less mucosal inflammation (mean +/- SEM, 39% +/- 5%), epithelial denudation (36% +/- 5%), and BAL neutrophilia (11 +/- 3) than did Sal/CAV2 dogs (51% +/- 6%, 57% +/- 4%, and 33% +/- 8%, respectively). We concluded that pretreatment with nedocromil sodium aerosols attenuated CAV2-induced airway inflammation in these beagle puppies.

Adenoviridae Infections↗