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Introduction: Respiratory infections have an enormous, worldwide epidemiologic impact on humans and animals. Among the prophylactic measures, vaccination has the potential to neutralize this impact. New technologies for vaccine production and delivery are of importance in this field since they offer the potential to develop new immunization approaches overriding the current limitations that comprise high cost, safety issues, and limited efficacy.Areas covered: In the present review, the state of the art in developing plant-based vaccines against respiratory diseases is presented. The review was based on the analysis of current biomedical literature.Expert commentary: Preclinical and clinical evaluations of several vaccine candidates against influenza, tuberculosis, respiratory syncytial virus, pneumonia, anthrax and asthma are discussed and placed in perspective.

Introduction: Marginal zone B-cell lymphoma is a rare disease which can be considerably difficult to recognize and diagnose when signs of systemic involvement are absent. Case Presentation: We report the case of a 57-year-old woman with initial olfactory disturbance, followed by psychosis, diabetes insipidus and hypothalamic eating disorder as an uncommon clinical presentation of marginal zone B-cell lymphoma. Conclusion: Marginal zone B-cell lymphoma should be considered as a potential differential diagnosis in patients with hypothalamic disturbances.

Primary Bronchus-Associated Lymphoid Tissue (BALT) Lymphoma Bronchus-associated lymphoid tissue (BALT) lymphoma is a rare extra-nodal marginal zone lymphoma representing 0.5% of lung tumours. In order to share experience in the management of BALT lymphoma, we report a well-investigated case with unusual features as complex familial oncologic history and synchronous benign thyroid disease. The patient was a 44-year-old woman with prolonged unspecific respiratory complaints. By computed tomography (CT), bilateral atelectasis-like pulmonary lesions were found in the 3rd, 5th, 6th and 8th segments of the right lung and in the 3rd segment of the left lung. We performed diagnostic video-assisted wedge resection of the 5th segment of right lung. Pathologic and immunohistochemical examination yielded the diagnosis of BALT lymphoma. After staging by bone marrow biopsy and abdominal CT, chemotherapy was recommended by the oncologic council.

Background: The functions of the bronchus-associated lymphoid tissue (BALT) are under the control of the autonomic nervous system (sympathetic and parasympathetic nerve fibers). Objectives: The relationships between the adrenergic nerve fibers and β-adrenergic receptors were studied in the human BALT with the aim to demonstrate a probable neuromodulation. Methods: Morphological observations (staining with hematoxylin-eosin and scanning electron microscopy images) were carried out on samples of human BALT harvested during autopsies. Moreover, histochemical staining for norepinephrine (adrenaline = adrenergic nerve fibers) as well as for other catecholamines was performed. Finally, β-adrenergic receptors were stained by means of a β-blocking, radiolabeled drug (pindolol 125I). All our data were submitted to morphometric analysis (quantitative analysis of images and statistical analysis of data). Results: Our results provide direct evidence of the presence and distribution of catecholaminergic nerve fibers and related β-adrenergic receptors in BALT. β-Adrenergic receptors are present above all in the most richly innervated part of the BALT, and are, therefore, in close relationship with their related adrenergic nerve fibers. Conclusions: Studies on the distribution of adrenergicneurotransmitters and related β-adrenergic receptors in the human BALT are the first step for the demonstration of a probable neuromodulation of BALT.

Rationale: Lymphoid interstitial pneumonia (LIP) is a rare disease with lymphocytic infiltration of the alveolar interstitial and air spaces, sometimes classified as a clonal lymphoproliferative disease (LPD) with high prevalence in patients with immunodysregulation. Although association of mucosa-associated lymphoid tissue (MALT) lymphoma development with infectious agents has been well described, it is not so in the case of LIP. Attempts to demonstrate an infective cause by direct microbe detection have failed, but association with atypical specific immune response to opportunistic infectious agent has not been studied. Patient concerns and Diagnoses: We performed clinical, biochemical, and immunologic analysis of patients LIP that arises primarily from the common variable immune deficiency (CVID) with normal immunoglobulin class M (IgM) level and mild infectious course as a result of immunodysregulation. At the age of 13 multiple nodules, areas of consolidation were observed and LIP was confirmed by histological examination. The progression of the disease with massive splenomegaly (17→27 cm), lymphadenopathy soft tissue infiltration coincides with high standardized uptake value (SUV was 3.1–5.2), regulatory T cells decrease (CD4+25highFoxP3+ level −0.02%, i.e., 8 cells per 100 μL), oligoclonal gammapathy: very high IgM (3340 mg/dL) and β2-microglobulin (18.8 mg/L) level observed 10 years later. Immune response polarization was observed in humoral and cellular compartment -Th and Tc-dependent: 10.8% of lymphocytes are CD8high+CMV pp65-pentamer positive cells (Epstein–Barr virus-specific not observed). Specific immune response polarization correlates with negative immunofixation, light chains κ/λ = 2.84 and narrow, but non-monoclonal T cell receptor (TCR)/ B cell receptor (BCR) repertoire. Lessons: Taking everything into account, this case report shows that LIP is a consequence of immune-dysregulation in CVID, that is, Treg deficiency, narrow lymphocyte repertoire, and abnormal ability to respond to cytomegalovirus (CMV) antigens. It may be visualized by positron emission tomography (PET) and monitored by CMV-specific immune response, β2-microglobulin level, and IgM paraproteinaemia, but not by immunofixation and κ/λ ratio.

Bronchus-associated lymphoid tissue (BALT) was first described in the lungs of rabbits and differs greatly between species. It is part of the integrated mucosal immune system. This review clarifies its morphological definition and focuses on the situation in humans. The frequency of BALT at different ages, after chronic stimulation and in different diseases is described. In healthy humans, BALT can only be found in the lungs of children and adolescents. The role of BALT in lung transplantation and in the development of low-grade malignant lymphomas in the airways is also discussed. Furthermore, questions concerning the inducibility of BALT as an entry site for vaccines, and the regulation of its activity for future therapeutic interventions in pulmonary immune reactions are addressed.

A trial was conducted to observe the immediate and chronic effects in goats of dexamethasone administration on the bronchus-associated lymphoid tissue (BALT) response to intranasal administration of formalin-killed Pasteurella haemolytica A2. Twenty-four goats were divided into four groups. Those in group 1 were injected intramuscularly with 1 mg/kg dexamethasone on three consecutive days, followed by intranasal exposure to formalin-killed P. haemolytica A2 one day after the last dexamethasone treatment. The goats in group 2 were similarly injected with dexamethasone followed by intranasal exposure to formalin-killed P. haemolytica A2 21 days after the last dexamethasone treatment. The animals in group 3 were exposed intranasally to formalin-killed P. haemolytica A2 without prior dexamethasone treatment. The animals in group 4 were untreated controls. The intranasal exposures to formalin-killed P. haemolytica A2 were repeated 2 weeks later. Intranasal exposure to formalin-killed P. haemolytica 1 day after dexamethasone treatment further reduced the number and size of BALT compared to the untreated control. Significantly (p

Rheumatoid arthritis–related interstitial lung disease (RA-ILD) is associated with significant morbidity and mortality. Studies in humans have found that the incidence of bronchus-associated lymphoid tissue (BALT) correlates with the severity of lung injury. However, the mechanisms underlying the development of BALT during systemic autoimmunity remain unknown. We have determined whether systemic autoimmunity in a murine model of autoimmune arthritis can promote the development of BALT by generating a novel murine model derived from K/BxN mice. Transgenic mice with the KRN T-cell receptor specific for the autoantigen, glucose-6–phosphate isomerase (GPI), were crossed with GPI-specific immunoglobulin heavy and light chain knock-in mice, producing mice with a majority of T and B cells specific for the same autoantigen. We found that 67% of these mice demonstrated lymphocytic infiltration in the lungs, localized to either the perivascular or peribronchial regions. Fifty percent of the mice with lymphocytic infiltration manifested lymphoid-like lesions resembling BALT, with distinct T and B cell follicles. The lungs from mice with lymphoid infiltrates had increased numbers of cytokine-producing T cells, including IL-17A+ T cells and increased major histocompatibility complex Class II expression on B cells. Interestingly, challenge with bleomycin failed to elicit a significant fibrotic response, compared with wild-type control mice. Our data suggest that systemic autoreactivity promotes ectopic lymphoid tissue development in the lung through the cooperation of autoreactive T and B cells. However, these BALT-like lesions may not be sufficient to promote fibrotic lung disease at steady state or after inflammatory challenge.

症例は集検で胸部異常陰影を指摘された75歳女性で, 胸部単純X線像で右中肺野に不整形の淡い腫瘤影を認め, 空気気管支像を伴っていた.経気管支鏡的肺生検で, 小型リパ球の集籏を認めたため偽リンパ腫が疑われ, 右上葉切除郭清を施行した.病理所見で, 増殖した中型リンパ球はcentrocyte-like cellと考えられ, lymphoeithelial lesionの形成や, 2次ろ胞への浸潤がみられ, 形質細胞への分化も認められたため, 気管支粘膜由来のびまん性中細胞型悪性リンパ腫と診断した.さらに, 細胞内免疫グロブリンの検出で, Ig Gとλへのmonoclonalityが認められ確診した.本邦での気管支粘膜由来の悪性リンパ腫の報部1は, 自験例を含め4例と極めて稀なことから報告した.

The authors present a case of histologically proven bronchus-associated lymphoid tissue (BALT) lymphoma of the lung in a patient with primary Sjogren's syndrome that manifested on thin-section CT scan as a mosaic pattern of inhomogeneous attenuation due to mixed small airway and infiltrative abnormalities

Age-related changes of the catecholaminergic nerve fibers of the trachea, bronchial smooth muscle, lung capillaries and bronchus-associated lymphoid tissue (BALT) were studied in male Wistar rats aged 3 months (young), 12 months (adult) and 24 months (old/aged). Catecholamine histo- and immuno-fluorescence techniques were used, associated with image analysis and high pressure liquid chromatography with electrochemical detection of nor-epinephrine (nor-adrenaline). In young rats, blue-green fluorescent nerve fibers supply the trachea-bronchial smooth muscle and tracheal and bronchial glands. These structures are innervated by a delicate network of nerve fibers, being rich in varicosities. Pulmonary capillaries are sparsely innervated. The highest nor-epinephrine concentration was found in the trachea and bronchi, followed by BALT. The density and the pattern of noradrenergic nerve fibers of the trachea-bronchial tree or of the pulmonary vessels were similar in young and adult rats. In aged rats, a loss of noradrenergic nerve fibers, involving primarily the supply to the smooth muscle of the trachea-bronchial tree, was observed. Fluorescence microscopic techniques demonstrated a higher sensitivity than nor-epinephrine assay in detecting changes of the sympathetic nerve supply of the trachea-bronchial tree, pulmonary vessels and BALT. The possible significance of reduced noradrenergic nerve supply of the trachea-bronchial-pulmonary tree in aged rats is discussed.

Interstitial lung disease, although of prognostic impact for patients with cystic fibrosis (CF), remains difficult to assess without histopathologic investigations. As changes of peripheral blood lymphocyte subsets (LS) may accompany severe systemic lymphocyte immune responses, we compared peripheral LS of 44 patients with CF, 23 non-CF patients with recurrent pulmonary infections and 83 healthy controls (flow cytometry; CD3, CD19, CD16, CD56, CD4, CD8, CD11b, CD45RA, CD45RO, HLA-DR and CD25 antigens). Additional immunohistochemistry was performed on lung tissue of four CF patients aged 0·5, 12, 17 and 20 years, respectively. Patients with CF showed low absolute counts of CD4+CD45RO+ memory helper T cells, CD16+CD56+ NK cells, CD8+ and interleukin-2 receptor-positive T cells in peripheral blood (P

T HE BRONCHUS-associated lymphoid tissue (BALT) is a conspicuous part of the local immune system of the lung. In acute rejection, the BALT is the first target due to its high immunogenicity.’ Previously, we reported reduction of BALT in long-term-surviving rat lung allografts2,3 which are indefinitely accepted with a short course of treatment with cyclosporine A (CyA). These lung allografts are not maintained by classic tolerance because recipient lymphocytes could respond to donor antigens4 We hypothesized that the BALT might be damaged by immunologic events because of its high immunogenicity. Therefore, we investigated the serial histologic changes of the BALT of these lung allografts at different timepoints after transplantation.

OBJECTIVE To investigate CT and (18)F-flurodeoxyglucose ((18)F-FDG) positron-emission tomography/CT findings of primary endobronchial marginal zone B-cell lymphoma of the bronchus-associated lymphoid tissue (BALT). MATERIALS AND METHODS From June 2006 through April 2012, seven patients (six female, one male; age range, 21-61 years; mean age, 49 years) were examined who were pathologically diagnosed with the primary endobronchial marginal zone B-cell lymphoma of BALT. We evaluated the locations and characteristics of the lesions on CT and (18)F-FDG-PET/CT scans. The lesions were classified into the following three patterns: 1) solitary intraluminal nodule; 2) several tiny nodular protrusions; and 3) diffuse wall thickening. RESULTS A solitary intraluminal nodule was observed in four patients (57.1%), several tiny nodular protrusion in two patients (28.6%), and diffuse wall thickening in one patient (14.3%). The lesions were categorized into 3 major locations: confined to the trachea (n = 3), confined to the lobar bronchus (n = 2), and diffuse involvement of the trachea and both main bronchi (n = 2). All lesions demonstrated homogeneous iso-attenuation as compared with muscle on pre- and post-enhancement scans. Secondary findings in the lungs (n = 3; 42.9%) included postobstructive lobar atelectasis (n = 1), air trapping (n = 1), and pneumonia (n = 1). On (18)F-FDG-PET/CT (n = 5), 4 lesions showed homogeneous uptake with maximum standardized uptake values (mSUV), ranging 2.3-5.7 (mean mSUV: 3.3). One lesion showed little FDG uptake. CONCLUSION Primary endobronchial marginal zone B-cell lymphoma of the BALT manifests as three distinct patterns on CT, with the solitary intraluminal nodule presenting as the main pattern. Most lesions demonstrate homogeneous but weak FDG uptake on (18)F-FDG-PET/CT.

Objectifs pedagogiques Describe the normal lymphoid constituents in the chest. Understand the role of bronchus associated lymphoid tissue (BALT). Describe the diseases that are derived from the BALT.

A primary pulmonary malignant lymphoma is a rare disease. It is thought to be a category of non-Hodgkin's lymphoma arising from the bronchous-associated lymphoid tissue (BALT). The majority of primary pulmonary lymphomas are low-grade, small B-cell lymphomas, which are associated with Sjogren's syndrome and similar autoimmune disorders. A case of primary pulmonary low-grade B-cell lymphoma arising from the BALT was encountered in a patient with systemic lupus erythematosus. A 54-year-old man was admitted to the hospital for the evaluation of left pleuritic chest pain and multiple joint pain in both hands. Serologic tests for collagen vascular disease were performed. The results of ANA and anti-ds-DNA were all positive. The computed tomography of the chest showed patchy consolidations in the left lower lobe with a pleural effusion and a video-assisted thoracoscopic biopsy was performed. Here we report a case of a low-grade B-cell lymphoma of BALT in a patient with systemic lupus erythematosus with a review of the relevant literatures.

The primary pulmonary lymphomas are uncommon, accounting for 0.5% of primary lung tumor and 0.4% of all malignant lymphomas. The majority of primary pulmonary lymphomas are of B-cell originating from bronchus associated lymphoid tissue(BALT). Angiocentric lymphoma is a rare type of primary pulmonary lymphomas characterized by polymorphic lymphoid infiltrates, which make it even more difficult to differentiate from benign infiltration. The radiographic findings are variable, depending on the stage of evolution of the disease. The prognosis of angiocentric lymphoma is poor, nearly two-thirds of the patients with grade 2 or 3 angiocentric lymphomas were died within a year of diagnosis. We report a case of primary pulmonary angiocentric lymphoma manifested as a mass of right lower lobe.

A study of a random series of 503 lungs from children of all ages and comprising a cross-section of almost all deaths in children in Sheffield shows that ‘mural bronchitis’ is not seen at birth but increases progessively with post-natal age. These lesions bear no relationship to unexpected death in infancy. They are probably a normal component of children's lungs, and an indication of bronchus associated lymphoid tissue. There is a positive correlation between the presence of prominent lesions and long-standing history of respiratory symptoms.

Nine patients with chronic or recurrent pneumonia had as a principal abnormality the presence of lymphoid masses around the bronchi and bronchioles. Many small airways were obstructed or destroyed. We found that the lymphoid tissues had characteristics of bronchus-associated lymphoid tissue (BALT). While BALT performs an essential immunologic function in airways, hyperplasia of this structure may contribute to bronchial pathology.

Summary Background Primary Sjogren's syndrome (pSs) is an autoimmune rheumatic disease that may express in a small number of patients a spectrum of lymphoproliferative diseases. The aim of this study was to describe clinical, imaging and pathology features of the extranodal marginal zone B-cell lymphoma (MZCL) of the lung of mucosa-associated lymphoid tissue (MALT) type in patients with pSs. Methods All patients ( N = 10 ) with biopsy proven MZCL of the lung of MALT type diagnosed in a tertiary teaching hospital during the last 7 years were studied. Results Seven patients had pSs. Almost all patients presented an indolent clinical course, contrasting strongly with the spectacular radiological findings in both chest roentgenograms and computed tomography. Pathology infiltration patterns observed were either nodular, peribronchial–perivascular, alveolar, or interstitial. Immunohistochemical study in all cases showed B cell phenotypes. Immunoglobulin light chain restriction was demonstrated in all patients. Monoclonal IgM( κ ) was evident in 5/7, IgM( λ ) in 1/7 and IgG ( κ ) in 1/7 of patients. Conclusions Lung MZCL associated with pSs are characterized by an important dissociation between clinical expression and radiological pattern. Clinical presentation and imaging features are not specific. Therefore, histologic documentation is mandatory to ensure diagnosis. Various chemotherapeutic agents in combination with rituximab lead to partial or complete remission in the majority of patients.