Pulmonary response to ozone: Reaction of bronchus-associated lymphoid tissue and lymph node lymphocytes in the rat

1990 ◽  
Vol 51 (2) ◽  
pp. 194-208 ◽  
Author(s):  
Daniel Dziedzic ◽  
Elaine S. Wright ◽  
Nicholas E. Sargent
The Analyst ◽  
2017 ◽  
Vol 142 (4) ◽  
pp. 649-659 ◽  
Author(s):  
Ashley E. Ross ◽  
Maura C. Belanger ◽  
Jacob F. Woodroof ◽  
Rebecca R. Pompano

We present the first microfluidic platform for local stimulation of lymph node tissue slices and demonstrate targeted delivery of a model therapeutic.


2019 ◽  
Vol 23 (2) ◽  
pp. 115-120
Author(s):  
Virginia E Duncan ◽  
Karen M Chisholm ◽  
M Cristina Pacheco

Background Antitumor necrosis alpha (TNFα) therapy is often used in the management of patients with inflammatory bowel disease (IBD) and may have effects on lymphoid tissue architecture and function. The goal of our study was to characterize the effects of TNFα inhibitors on mesenteric lymph node and mucosa-associated lymphoid tissue in patients with IBD. Methods We examined lymphoid tissue morphology in IBD patients treated with TNFα inhibitors compared to untreated controls. Intestinal resections from 19 patients (10 anti-TNFα treated and 9 controls) were reviewed. Immunohistochemistry for CD21, CD20, and CD3 was performed on ileocecal valve lymphoid tissue and mesenteric lymph nodes from the resection specimens to assess follicular architecture. Results Relative to control groups, TNFα-treated groups showed less preserved germinal center architecture, evidenced by lower overall semiquantitative scores for follicular architecture. Likewise, the percentage of secondary follicles to total follicles was decreased in patients treated with TNFα blockade. Conclusions Our results suggest that TNFα inhibitors may play a role in disruption of lymphoid germinal center architecture in patients with IBD. Awareness of this disrupted lymphoid morphology when examining histologic sections from patients with IBD treated with TNFα inhibitors may prevent unnecessary studies to exclude a lymphoproliferative disorder.


Blood ◽  
1999 ◽  
Vol 94 (7) ◽  
pp. 2247-2251 ◽  
Author(s):  
Antonella Aiello ◽  
Ming-Qing Du ◽  
Tim C. Diss ◽  
Huai-Zheng Peng ◽  
Francesco Pezzella ◽  
...  

A 44-year-old woman with a 12-year history of Sjögren’s syndrome (SS) developed a low-grade mucosa-associated lymphoid tissue (MALT) lymphoma in the parotid gland. Two years later, she presented with generalized lymphadenopathy and hepatosplenomegaly and a follicular lymphoma was diagnosed. To investigate the relationship of the two histologically distinct lymphomas, we re-examined their histology and immunophenotype and studied the lymphomatous tissue from the parotid, cervical lymph node, and spleen using molecular genetic methods. Histologic and immunophenotypic studies confirmed the previous diagnoses and also identified a previously unnoticed focus of follicular lymphoma in the second parotid gland biopsy. Polymerase chain reaction (PCR) amplification of the rearranged Ig heavy-chain gene showed the same sized dominant product in the MALT lymphoma and the follicular lymphoma. Similarly, PCR analysis of the t(14:18) translocation yielded an identical sized band from both MALT and follicular lymphoma. Cloning and sequencing of the Ig PCR products showed an identical CDR3 sequence from each lesion, indicating a common clonal lineage. The follicular lymphoma of the parotid gland lymph node and the follicular lymphoma of the spleen showed an identical mutation signature to that of the salivary gland MALT lymphoma. We propose that follicular lymphoma in the parotid gland lymph node may have resulted from colonization of lymphoid follicles by MALT lymphoma cells, following which the tumor cells were induced to express a follicular lymphoma phenotype, due to Bcl-2 overexpression caused by t(14;18), leading to a change in clinical behavior resulting in rapid widespread dissemination of disease. These observations suggest that the distinct phenotypes of low-grade B-cell lymphomas may be the consequence of interplay between genetic and local microenvironmental factors.


Parasitology ◽  
2006 ◽  
Vol 134 (2) ◽  
pp. 281-288 ◽  
Author(s):  
S. M. VENTURIELLO ◽  
M. L. VERZOLETTI ◽  
S. N. COSTANTINO ◽  
M. A. FORASTIERO ◽  
M. E. ROUX

The migratory stage of Trichinella spiralis, the newborn larva, travels along the pulmonary microvascular system on its way to the striated muscle cells. In the present study, an important inflammatory reaction was observed on days 5 and 14 post-infection (p.i.) in the lungs of infected rats. This inflammation was characterized by a Th2 cell phenotype of hyperplastic bronchus-associated lymphoid tissue and by goblet cell hyperplasia. Among the inflammatory cells were eosinophils and mast cells scattered over the pulmonary parenchyma. On day 5 p.i. the number of IgE+, CD4+ and CD5+ cells in the bronchus-associated lymphoid tissue were increased and IgE-secreting lung cells were also detected. At the end of the migratory phase of the infection (day 14 p.i.), only IgE+ cells were detected in high numbers and in the bronchoalveolar lavage fluid, an increment in the total IgE levels as well as the presence of IgE and IgA anti-larvae surface were also detected. In cytotoxicity assays, cells from the bronchoalveolar lavage had considerable biological activity since they were able to kill the larvae even in the absence of specific antibodies. These results show that the lung is an organ involved in the immune response developed early during a T. spiralis infection and suggest its importance in the protection of the host.


2003 ◽  
Vol 47 (1) ◽  
pp. 238-243 ◽  
Author(s):  
Caroline Solas ◽  
Alain Lafeuillade ◽  
Philippe Halfon ◽  
Stéphane Chadapaud ◽  
Gilles Hittinger ◽  
...  

ABSTRACT The variable penetration of antiretroviral drugs into sanctuary sites may contribute to the differential evolution of human immunodeficiency virus (HIV) and the emergence of drug resistance. We evaluated the penetration of indinavir, nelfinavir, and lopinavir-ritonavir (lopinavir/r) in the central nervous system, genital tract, and lymphoid tissue and assessed the correlation with residual viral replication. Plasma, cerebrospinal fluid (CSF), semen, and lymph node biopsy samples were collected from 41 HIV-infected patients on stable highly active antiretroviral therapy regimens to determine drug concentrations and HIV RNA levels. When HIV RNA was detectable, sequencing of the reverse transcriptase and protease genes was performed. Ratios of the concentration in semen/concentration in plasma were 1.9 for indinavir, 0.08 for nelfinavir, and 0.07 for lopinavir. Only indinavir was detectable in CSF, with a concentration in CSF/concentration in plasma ratio of 0.17. Differential penetration into lymphoid tissue was observed, with concentration in lymph node tissue/concentration in plasma ratios of 2.07, 0.58, and 0.21 for indinavir, nelfinavir, and lopinavir, respectively. HIV RNA levels were <50 copies/ml in all CSF samples of patients in whom HIV RNA was not detectable in plasma. HIV RNA was detectable in the semen of three patients (two patients receiving nelfinavir and one patient receiving lopinavir/r), and its detection was associated with multiple resistance mutations, while the viral load in plasma was undetectable. HIV RNA was detectable in all lymph node tissue samples. Differential drug penetration was observed among the three protease inhibitors in the sanctuary sites, but there was no correlation between drug levels and HIV RNA levels, suggesting that multiple factors are involved in the persistence of viral reservoirs. Further studies are required to clarify the role and clinical relevance of drug penetration in sanctuaries in terms of long-term efficacy and drug resistance.


Blood ◽  
2002 ◽  
Vol 99 (7) ◽  
pp. 2483-2489 ◽  
Author(s):  
Rabindra Tirouvanziam ◽  
Ibrahim Khazaal ◽  
Victoire N'Sondé ◽  
Marie-Alix Peyrat ◽  
Annick Lim ◽  
...  

We introduce a novel in vivo model of human mucosal immunity, based on the implantation of human fetal bronchial mucosa and autologous peribronchial lymph node (PLN) in the severe combined immunodeficiency (SCID) mouse. In the SCID host, human fetal bronchi implanted alone retain macrophages and mast cells but lose T cells. In contrast, fetal bronchi co-implanted with PLN contain, in addition to macrophages and mast cells, numerous T cells and B cells, often clustered in intramucosal bronchus-associated lymphoid tissue (BALT). Functionally, bronchus–PLN cografts are able to mount robust αβ and γδ T-cell–mediated immune responses to Pseudomonas aeruginosa and 3,4-epoxy-3-methyl-1-butyl-diphosphate challenges. No other autologous lymphoid organ (bone marrow, thymus, liver) allows for BALT development in co-implanted bronchi, which suggests special ontogenetic and functional relations between extramucosal PLN and intramucosal BALT. Overall, the bronchus–PLN cograft appears as a promising model for human bronchial immune development and function. Our study is the first to document long-term ex vivo maintenance of functional human lymph nodes as native appendices to mucosal tissue. Our results, therefore, suggest a simple strategy for developing similar experimental models of human immune function in other mucosae.


1922 ◽  
Vol 35 (1) ◽  
pp. 39-62 ◽  
Author(s):  
Louise Pearce ◽  
Wade H. Brown

A widespread dissemination of Treponema pallidum from a local focus of inoculation in the rabbit constantly occurs by way of the lymphatics. Spirochetes were regularly recovered from the satellite lymph nodes by animal inoculation after scrotal inoculation; they were present as early as 2 days, when no specific primary reaction was detected, and at later periods of from 5 to 61 days after inoculation. Other superficial nodes at remote sites such as the popliteals and with no syphilitic lesions in the drainage area have also been shown to harbor active organisms. Although spirochetes were found in relatively few of the lymph node emulsions, the orchitis resulting from their injection was of a rapidly progressive type with an incubation period but slightly longer than that produced by a testicular or skin nodule emulsion rich in spirochetes. It has further been shown that a syphilitic infection is sufficiently established in the rabbit body within 48 hours after scrotal inoculation so that the primary lesion is no longer essential for its maintenance. Active treponemata survive in the popliteal lymph nodes for long periods of time and have been regularly recovered from them in cases of true latency. The lymph nodes, therefore, function as reservoirs of the organisms. The ability to recover the spirochetes from lymphoid tissue through successive generations is seen in the serial passage of lymph node emulsion to testicle during an 18 months period. The persistence of spirochetes in lymphoid tissue irrespective of the presence or absence of syphilitic lesions is a characteristic and fundamental feature of syphilis of the rabbit. The existence of infection, therefore, may be demonstrated at any time by the recovery of spirochetes from the popliteal lymph nodes by animal inoculation. This fact is of great practical importance in the therapy of the infection and may be profitably utilized in determining the ultimate effect of a therapeutic agent. These experiments demonstrate that the disease is not confined to the site of local inoculation but that lymphogenous dissemination of treponemata regularly takes place, and that during the course of this process organisms become localized in the lymph nodes and exist there indefinitely irrespective of the occurrence of manifestations of disease. The intimate relation of Treponema pallidum to lymphoid tissue is an essential concept of syphilis of the rabbit, and from this point of view, the infection is primarily one of lymphoid tissue.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4564-4564
Author(s):  
Kathryn P. Beal ◽  
Carol Portlock ◽  
Joachim Yahalom

Abstract Background: Bronchial-associated lymphoid tissue (BALT) lymphoma, an indolent marginal zone lymphoma, is a rare clinical entity with only few published reports on its optimal management and treatment outcome. In the absence of a well established standard of care, different treatment options are available including surgery, radiation, chemotherapy, immunotherapy or merely observation. We analyzed a large cancer center’s experience with the management of BALT lymphoma patients during the last 12 years. Patients and Methods: Nineteen cases of BALT lymphoma were identified from a database of 175 cases of MALT lymphoma pathologically confirmed at our center. We retrospectively reviewed the clinical data and treatment results. Results: There were 12 (63%) men and 7 (37%) women with a median age of 68 years (range 37–81 years). Seven (37%) patients were asymptomatic at diagnosis and were diagnosed after radiologic studies ordered either for routine evaluation or for pre-operative clearance showed unexpected abnormalities. The 12 (63%) symptomatic patients had non-specific pulmonary complaints such as cough, shortness of breath, or dyspnea on exertion. One patient had B symptoms (significant unintentional weight loss). Twelve patients (63%) had unilateral lung involvement and 7 (37%) had bilateral involvement on chest CT. Twelve patients had FDG-PET scans at the time of diagnosis and all had FDG uptake in pathologically confirmed sites of disease with a median SUV of 3.2 (range 1.3–26). Five patients (26%) had radiographically enlarged hilar or mediastinal lymph nodes including 1 with pathologically confirmed transformation to diffuse large B-cell lymphoma in a mediastinal lymph node and 1 with progression to a supraclavicular lymph node. Fifteen patients (79%) had stage I or II disease limited to their thorax. One patient had previously treated MALT of the bilateral orbits, 1 patient was also found to have MALT involving her small bowel, 1 patient also had bone marrow involvement, and 1 patient had extensive disease involving not only lung parenchyma but also mediastinal lymph nodes, and bilateral axillary, supraclavicular, and cervical lymph nodes. Ten patients were treated with surgery alone (8 had wedge resections, 2 had lobectomies). Six received chemotherapy alone and 2 had rituximab alone. One received radiation (RT) alone. With a median follow-up of 28 months (range 11–146 months), no patients were lost to follow-up. At 5 years, overall survival was 91% and disease free survival was 42%. At latest follow-up all patients were alive with the exception of one patient who died of his disease (the patient who had extensive lung parenchymal disease and lymphadenopathy) and 8 patients (42%) were without evidence of any disease after RT(1), chemotherapy(2), or surgery(5). Conclusion: In one of the largest series of BALT lymphoma patients with complete follow-up, we document good response to local treatment and overall excellent prognosis. Of interest, BALT lymphoma lesions are PET-positive and thus are similar to lung cancer lesions. Limited lesions may be safely resected and patients remain disease-free, but even some patients with unresectable disease respond to chemotherapy and are rendered disease-free or stable.


2003 ◽  
Vol 71 (1) ◽  
pp. 401-410 ◽  
Author(s):  
Saeed Ahmed ◽  
M. Colmenares ◽  
L. Soong ◽  
K. Goldsmith-Pestana ◽  
L. Munstermann ◽  
...  

ABSTRACT The levels of protection found in vaccine studies of murine visceral leishmaniasis are significantly lower than for cutaneous leishmaniasis; whether this is due to the high-challenge murine model employed and/or is a consequence of differences required in tissue-specific local immune responses is not understood. Consequently, an intradermal murine model of visceral leishmaniasis has been explored. Intradermal inoculation established a chronic infection in susceptible mice which was associated with a pattern of parasite clearance with time postinfection in the liver and skin; in contrast, parasite persistence and expansion was observed in lymphoid tissue (spleen and draining lymph node). The course of disease found appears to be similar to those reported for subclinical canine and human visceral leishmaniasis. Clearance of parasites from the skin was correlated with an inflammatory response and the infiltration and activation of CD4+ and CD8+ T cells. In contrast, in lymphoid tissue (lymph node or spleen), the production of Th1/Th2 cytokines (interleukin-4 [IL-4], IL-10, and gamma interferon) appeared to correlate with parasite burden and pathogenesis. In vaccination experiments employing the Leishmania infantum D-13 (p80) antigen, significantly higher levels of protection were found with the intradermal murine model (29 to 7,500-fold more than naive controls) than were found with a low-dose intravenous infection model (9 to 173-fold). Thus, this model should prove useful for further investigation of disease pathogenesis as well as vaccine studies of visceral leishmaniasis.


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