Treatment and results of interstitial lung diseases in video assisted thoracoscopic lung biopsy

In order to establish treatment of interstitial lung diseases in video assisted thoracoscopic lung biopsy, we retrospectively reviewed our experiences. The present study included 7 patients with a mean age of 46.4, range from 24 to 61, who were treated at our department from 1996 through 1999. They were 5 men and 2 women. The pathologic diagnosis was nonspecific interstitial pneumonia in 3 patients who responded to steroid therapy. Three other patients had usual interstitial pneumonia. One patient had lymphocytic interstitial pneumonia. No complications occurred. The results indicate that video assisted thoracoscopic lung biopsy is an effective and safe way to diagnose interstitial lung diseases.     

Enhanced expression of angiotensin II type 1 receptor in usual interstitial pneumonia

BACKGROUND: Angiotensin II, a potent vasoconstrictor, has been considered to be involved in various fibrotic disorders including idiopathic interstitial pneumonias. To clarify whether this agent contributes to the development and progression of usual interstitial pneumonia, a major entity of idiopathic interstitial pneumonias, we immunohistochemically examined expression of its specific receptor, angiotensin II type 1 receptor, in human normal and diseased lung tissues. METHODS: Video-assisted thoracoscopic lung biopsy specimens obtained from patients with usual interstitial pneumonia (n=8) were sectioned and stained using single or double immunostaining techniques with specific antibodies against angiotensin II type 1 receptor and smooth muscle actin. Lung tissues of desquamative interstitial pneumonia (n=2) and normal lung tissues (n=6) were also examined for comparative analyses. RESULTS: Expression of angiotensin II type 1 receptor was limited in vascular and bronchial smooth muscle cells in normal lungs. In contrast, the receptor-positive mesenchymal cells, most of which were also positive for smooth muscle actin and arranged like a bundle, were markedly increased in association with dense collagen deposition in thickened alveolar walls of usual interstitial pneumonia. In desquamative interstitial pneumonia, the fibroproliferative change, including angiotensin II type 1 receptor-positive mesenchymal cell proliferation, was milder than that in usual interstitial pneumonia. CONCLUSIONS: These findings suggest that angiotensin II and its type 1 receptor play a profibrogenic role in idiopathic interstitial pneumonias, particularly in usual interstitial pneumonia. Furthermore, angiotensin II type 1 receptor-positive smooth muscle cells increased in diseased lung tissues may be contractile and may contribute to reduction of airspaces in usual interstitial pneumonia.     

Intravascular lymphoma: a rare but curable cause of interstitial lung disease

A 69-year-old man presented with dyspnoea, cough and diffuse interstitial changes and ground-glass effect on a CT-scan. After 5 months the patient was diagnosed with pulmonary intravascular lymphomatosis. A histologic diagnosis was made by a video-assisted thoracoscopic surgical biopsy. Treatment with combination chemotherapy, i.e. 8 cycles of cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP), resulted in a complete remission and a disease-free survival of 5 years at the last follow-up. Intravascular lymphomatosis is a rare but curable cause of interstitial lung disease. Intravascular lymphomatosis is an uncommon type of non-Hodgkin's lymphoma, characterized by proliferation of neoplastic lymphoid cells within the lumen of small blood vessels, resulting in thrombotic and ischaemic complications in multiple organ systems. Primary pulmonary presentation is even more uncommon. It is important to consider intravascular lymphomatosis in the differential diagnosis of unexplained interstitial lung disease, since early diagnosis and treatment may lead to complete remission and long-term survival.     

Milk IgA responses are augmented by antigen delivery to the mucosal addressin cellular adhesion molecule 1

The mucosal addressin cellular adhesion molecule 1 (MAdCAM) is expressed on the venules of the gut associated lymphoid tissue (GALT); it is also expressed on the venules of the lobules of the mammary gland. We have previously found that MAdCAM-targeting using a rat anti-MAdCAM monoclonal Ab as both antigen and targeting moiety resulted in an enhanced local IgA gut response. We therefore surmised that such targeting may also enhance IgA responses in the mammary gland. We show that our model antigen localizes to the lobules of the mammary glands as well as the GALT, but not to the draining lymph nodes and that targeting MAdCAM results in secretory IgA responses in the milk. We provide evidence that this milk IgA Ab is of a secretory nature and is consistent with derivation from gut plasmablasts that have migrated to the mammary gland. Targeting MAdCAM may be a way for a novel vaccine strategy that affords protection to the mammary gland and the suckling neonate.     

Conjugated linoleic acid ameliorates viral infectivity in a pig model of virally induced immunosuppression

We investigated the cellular and molecular immunoregulatory actions of conjugated linoleic acid (CLA) of relevance to viral disease pathogenesis and antiviral responses. To test the hypothesis that CLA ameliorates viral disease, we developed a viral challenge model by infecting pigs with type-2 porcine circovirus (PCV2). After 42 d of dietary supplementation with either soybean oil (n = 16) or CLA (n = 16), half of the pigs in each group were challenged with PCV2. We examined the effect of CLA on the development of lesions (i.e., lymphoid depletion and pneumonia) and observed the kinetics of the immune responses against PCV2. The viral infection depleted immature B cells (IgM+SWC3+) and favored proapoptotic mRNA expression profiles [i.e., suppressed B-cell leukemia/lymphoma-xl (Bcl-xl) and stimulated Bcl-2 homologous antagonist/killer (Bak)] in the external inguinal lymph nodes. B-cell depletion was more accentuated in pigs fed the control diet, whereas interleukin (IL)-2 mRNA expression was downregulated. Histopathological examination of the lungs revealed that the interstitial pneumonia tended to be more severe in infected pigs fed the control diet, which were also affected by growth retardation. CD8+ T cells were the primary cellular targets of CLA action in peripheral blood (CD8+CD29low and CD8+CD45RC+) and thymus (CD8+ and CD4+CD8+). CLA interacted with PCV2 to increase the proliferation of CD8+ T cells and to suppress PCV2-specific interferon (IFN)-gamma production in CD4+ T cells. At the molecular level, these cellular immunoregulatory properties were associated with differential patterns of peroxisome proliferator-activated receptor (alpha and gamma) mRNA expression between diets in virally infected pigs.     

Respiratory manifestations of AIDS

Respiratory disorders are present in at least 40% of patients with the acquired immunodeficiency syndrome (AIDS) and are the commonest mode of presentation. Lung pathology ranges from infections, both opportunistic and non-opportunistic, to Kaposi's sarcoma and lymphoid interstitial pneumonia. AIDS-related lung problems must increasingly be considered in the differential diagnosis of the breathless patient.     

Unusual pneumoconiosis in two patients with heavy print toner,and paper dust exposure

Workers in a print shop are exposed to photocopier toner dust and paper dust over a prolonged period of time. However, there are only rare case reports of toner and paper dust induced lung damage in humans. We reviewed our consultation files for a period of 30 years from 1987 to 2018 to look for cases with a diagnosis of giant cell interstitial pneumonia (GIP), printer toner exposure and paper dust exposure resulting in lung disease. There were two cases which met our inclusion criteria. Slides, clinical histories and imaging were reviewed. Both the patients had worked in print shops, and had no history of exposure to hard metals. Patient 1 presented with shortness of breath and cough over several months, while patient 2 was asymptomatic at presentation. Both the patients underwent surgical lung biopsies. Histopathologic examination from both the cases showed a spectrum of pathology, including features of GIP, desquamative interstitial pneumonia, chronic bronchiolitis with lymphoid hyperplasia, and particulate matter consistent with toner. Energy dispersive spectroscopy was performed on one case, and it revealed no cobalt or tungsten particles. The unusual combination of findings is very suggestive that toner particles with or without paper dust exposure were responsible for the pathologic changes in the lungs of these patients. This possibility should be explored further with additional patients who work in print shops where they are exposed to paper dust and paper toner and have signs or symptoms of diffuse lung disease.     

Quantitative analysis of influenza virus-specific B cell memory generated by different routes of inactivated virus vaccination

We consider both Ab-secreting cell (ASC) and memory B cell (B_Mem) populations in a quantitative analysis of virus-specific B cell memory generated by intramuscular or intranasal vaccination of mice with inactivated influenza virus. After both forms of vaccination, the memory phase was characterized by localization of ASCs in the bone marrow and dispersion of B_Mem to organized lymphoid tissues. The stronger IgG response to intramuscular vaccination correlated with larger numbers of IgG ASCs in the bone marrow and IgG B_Mem. IgA production was only prominent in the response to intranasal vaccination and was associated with IgA ASC localization in the lung and IgA B_Mem formation. Notably, few IgG ASCs or B_Mem localized in the lung after intramuscular vaccination, in contrast to the situation following influenza pneumonia. Our analysis links the nature of immunization to characteristics of the state of B cell memory that may relate to protective immunity.     

Breakdown of mucosal immunity in gut by 2,3,7,8-tetraclorodibenzo-p-dioxin (TCDD)

Objectives Mucosal immunity plays a pivotal role for body defense against infection and allergy. The aim of this study was to clarify the effects of 2,3,7,8-tetraclorodibenzo-p-dioxin (TCDD) on mucosal immunity in the gut. Methods Fecal IgA level and oral tolerance induction were examined in TCDD-treated mice. Flow cytometric and histological analyses were also performed. Results Single oral administration of low dose 2,3,7,8-TCDD resulted in a marked decrease in IgA secretion in the gut without any effects on the cellular components of gut-associated lymphoid tissues (GALT) including Peyer’s patches (PPs) and mesenteric lymph nodes (LNs). Decressed IgA secretion by TCDD was not observed in aryl hydrocarbon receptor (AhR)-deficient mice. Flow cytometric analysis revealed that IgA B cells in PPs and the mesenteric LNs remained unchanged in the TCDD-treated mice. An immunofluorescence study also demonstrated that a significant number of cytoplasmic IgA cells were present in the lamina propria of the gut in the TCDD-treated mice. Furthermore, oral tolerance induction by ovalbumin (OVA) was impaired in the TCDD-treated mice and OVA-specific T cell proliferation occurred in the peripheral lymphoid tissues including the spleen and LNs. Conclusions These results suggest that a relatively low dose of TCDD impairs mucosal immunity in the gut and induces systemic sensitization by oral antigens.     

Mucosal and systemic immune responses induced after oral delivery of vaccinia virus recombinants

The immune responses elicited after oral delivery of vaccinia virus (VV) recombinants are not well defined. In this study we show with mice, that after oral administration of a VV recombinant expressing the luciferase reporter gene, VV gene expression takes place for several days in gut-associated lymphoid (GALT) tissues as well as in the spleen. After 14 days, a significant mucosal IgA response against VV was detected in vaginal and intestinal washings, as well as a systemic specific IgG response, which was principally of the IgG2a subclass. Furthermore, orally immunized mice developed cellular immune responses to VV (CD8+ T cells and T helper activities) in mesenteric lymph nodes (MLN) and spleen. Oral immunization with a VV recombinant expressing, either the envelope protein of HIV or beta-galactosidase, induced a specific immune response, locally and systemically, against gp120 and beta-gal. The cytokine pattern found in supernatants of spleen and MLN cells after stimulation with VV antigens or gp120 was clearly of type 1 cytokines. These studies demonstrate that VV recombinants administered by the oral route generate mucosal and systemic immune responses against antigens of the virus vector and to the recombinant products. These observations are of significance in the use of poxvirus vectors as vaccines.     

Thymus and pulmonary lymph node response to acute and subchronic ozone inhalation in the mouse

Ozone is an oxidant gas which primarily injures the centroacinar portion of the lung. While the classical lesion of oxidant-mediated lung damage is relatively well described, the effect of this form of injury on the lymphocytic arm of the pulmonary defense system is less clear. In the present experiments we exposed CD-1 female mice to ozone at a level of 0.7 ppm for 20 hr per day for 1-28 days and observed the lymphocyte response in the pulmonary lymph nodes and the thymus. In the mediastinal lymph nodes we observed a marked hyperplastic response that was prominent in the paracortex and was characterized by the presence of blastic forms. In contrast, the thymus underwent an atrophic response characterized by cellular loss in the cortical region. Prior surgical adrenalectomy of ozone-exposed animals eliminated part, but not all of the thymic atrophy response, indicating that adrenal-mediated stress alone did not account for all of the observed effect. Thymectomy of animals prior to ozone exposure produced a 40% reduction in the mediastinal lymph node response, suggesting that a part of the node hyperplasia is thymus dependent. The results of these experiments indicate that lymphoid organs are altered following oxidant-mediated lung damage in the mouse. The changes are observed in the absence of exogenous antigenic stimulation and suggest that lymphoid cells are an integral aspect of the host response to high-level ozone inhalation.     

探讨临床检验白细胞计数、C-反应蛋白与红细胞沉降量在儿童肺炎中的诊断意义

目的 通过临床对儿童肺炎患儿检验白细胞计数、C-反应蛋白与红细胞沉降量,分析该检测在儿童肺炎中的诊断价值.方法 选取某院2010年1月～2011年1月所收治的儿童肺炎患儿100例进行血清检测.C-反应蛋白的检测采用免疫比浊法,红细胞沉降量的检测采用韦斯特伦法,白细胞计数的检测采用全自动三分类血球计数仪,观察患者检测后的数据结果,并进行分析评价以上指标检测在儿童肺炎中的诊断价值.结果 经过临床检查所有患者均为浸润类型肺炎患儿,其中32例患儿为肺泡型,68例患儿为间质型,而肺泡型患儿血清中的C-反应蛋白与红细胞沉降量水平要明显高于间质型肺炎(P/0.05),但是白细胞计数之间差异无统计学意义(P＞0.05).结论 白细胞计数与红细胞沉降量水平在儿童肺炎患儿中的检测中受到一定的限制,而C-反应蛋白可以作为首选诊断标准,在临床中具有非常重要的意义.     

Comparative lung immunotoxicity of inhaled quartz and coal combustion fly ash

Some inhaled particles that are deposited in the terminal airways and alveoli clear to the lung-associated lymph nodes, and insoluble particles have a long half-life in these tissues. Because the lung-associated lymph nodes are essential in the induction of immunity after lung immunization, the accumulation of inhaled particles in these tissues could alter immune responses that develop after lung immunization. This study evaluated the effects of inhaled insoluble fly ash particles or alpha quartz on the immune functions of lung-associated lymph nodes. F344 rats were exposed for 20 days by inhalation of fly ash from a fluidized bed combustor (FBC) or a pulverized coal combustor (PCC). Rats were similarly exposed to quartz particles (Min-U-Sil). Control rats were exposed to filtered air. Groups of ten exposed and ten control rats from each group were immunized by intratracheal instillation of 10(8) sheep red blood cells at 4, 6, 40, and 52 weeks after the start of exposures. The cellularity of the lung-associated lymph nodes and antibody-mediated immunity were evaluated at 7 days after immunization. Tissues from lung and lung-associated lymph nodes were taken for histopathology. The inhalation of FBC fly ash, PCC fly ash, and quartz particles all significantly increased the number of lymphoid cells in the lung-associated lymph nodes at each of the sacrifice times. However, FBC fly ash had no significant effect on antibody immunity, while both PCC fly ash and quartz caused suppression of antibody responses at 52 weeks after the start of exposure. Histopathology data showed that exposure to quartz and PCC fly ash caused significant cellular changes in lungs and lung-associated lymph nodes, while FBC fly ash had less effect. These data indicate that an acute exposure (20 days) to relatively insoluble particles significantly increased the cellularity of the lung-associated lymph nodes for up to 52 weeks after the start of the exposure, but the pulmonary toxicity of the particles inhaled appeared to influence the effects of the exposure on antibody immune responses.     

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

The purpose of this work is to assess the effect of ozone, a reactive product of environmental photochemical oxidation, on lymphocytes of the lung. We exposed male Fischer rats to ozone at a concentration of 0.5 ppm for 20 hr/day for 1-14 days. Animals were treated with radioactive thymidine and were sacrificed at Day 1, 2, 3, 7, or 14 of exposure. Lungs and mediastinal lymph nodes were removed and prepared for histologic examination, evaluation of labeling indexes, and morphometric measurement. We examined two components of the lymphocyte response of the lung: the airway-related response, represented by the reaction of the bronchus-associated lymphoid tissue (BALT), and the deep lung-related response, represented by reaction of the mediastinal lymph node. Lymphocytes of both the BALT and the mediastinal lymph node showed elevated radioactive thymidine uptake; however, no evidence of cell death was observed at either site. The cells of the specialized epithelium covering the BALT (lymphoepithelium) showed increased vacuolization, indicating altered cellular function. The average size of BALTs was unchanged by ozone exposure. Under experimental conditions ozone can affect a variety of cells in the lung including bronchial epithelial cells, macrophages, and Type 1 cells. We have shown for the first time that in addition to these cells, the rat BALT also proliferates in response to ozone. In addition we confirm previous work in the mouse which shows that the mediastinal lymph node reacts as well. The airways can be affected by inflammation, can be targets of infection, and can respond to chemical irritants with bronchoconstrictive responses. They are an important target organ for hypersensitivity responses and are a primary site for pulmonary cancer formation. A role for lymphocytes has been implicated in each of these processes. Therefore, the clinical significance of ozone on BALT and mediastinal lymph node responses could be appreciable in terms of potentiation of, or protection against, such responses.     

The importance of combining xylene clearance and immunohistochemistry in the accurate staging of colorectal carcinoma.

The prognosis of colorectal carcinoma relies heavily on pathological staging which includes the metastatic state of lymph nodes. Colorectal resectates from 47 patients (41 with colorectal carcinoma and six with non-malignant disease) were entered into a study to assess the best method for detecting metastases in lymph nodes. The maximum number of lymph nodes was harvested at an initial careful examination of the specimen. Subsequently, the pericolic and perirectal fat was dissected out, dehydrated in alcohol, cleared in xylene and further lymph nodes were recovered. Both sets of lymph nodes were examined by the standard histological method and subsequently stained immunohistochemically for cytokeratins (CK). The mean number of lymph nodes recovered at the initial dissection from all 47 cases was 6.7, this was raised to 58.2 after xylene clearance, ie an average of 51.5 lymph nodes were not recovered by traditional methods. At the initial dissection no epithelial cells were detected in any of the lymph nodes from the nonmalignant cases or 25 of the malignant cases. In the other 16 cases, epithelial cells were detected by H&E in 38 lymph nodes. Thus the initial staging was 3 Dukes A, 22 Dukes B and 16 Dukes C. After immunohistochemistry, eight additional cases (originally staged Dukes B) showed epithelial cells in the lymph nodes, these were chiefly occult invasion, raising the involved lymph nodes number to 70. After xylene clearance and applying the CK staining, an additional 135 lymph nodes were found to be involved, thus the overall number of involved lymph nodes was increased to 205. The combined technique changed the Dukes staging in 12 out of 41 cases of colorectal carcinoma, resulting finally in 3 Dukes A, 10 Dukes B and 28 Dukes C, ie 55% of Dukes B become Dukes C.     

Microanalyses of lesions and lymph nodes from coalminers' lungs

The dust content and composition of lesions and hilar lymph nodes from the lungs of British coalworkers have been examined. Samples of macules, fibrotic nodules, and massive fibrosis (both peripheral and central sites) were dissected from 49 lungs. The highest mean dust concentrations (about 20%) were found in nodules and massive fibrosis. Overall there were no significant differences between the selected lesion types and their respective whole lung dust composition, although the central sites of massive fibrosis were found to contain on average a higher proportion of coal and a lower proportion of ash and its measured constituents, quartz and kaolin plus mica, than the edge of the lesion (p less than 0.001 for each component). There were striking differences between recovered lung and lymph node dusts. An examination of 180 specimens showed a mean quartz in lymph node dust of 20.3% compared with 6.1% in lung dust. As expected the proportion of quartz was greater in lymph nodes and lungs from men who had worked "low" rank (high ash) coal. By contrast with the corresponding figures for lung dusts, however, the mean proportion of quartz in nodes did not increase over the pathological range of pneumoconiotic lung disease. On average the proportions of kaolin and mica in lymph nodes reflect those found in lungs. The lymphotrophic nature of quartz was clearly shown although it was not possible to show an association between this clearance pathway and any particular type of lesion.     

Interstitial Lung Disease and Profound Hypoxaemia in a Severely-malnourished Child with Very Severe Pneumonia and Potential Lymph-node Tuberculosis: An Uncommon but Serious Co-morbidity

A nine-month old boy was initially admitted at the Acute Respiratory Infection Unit of Dhaka Hospital of icddr,b and soon after transferred to the Intensive Care Unit of the same hospital. The boy had problems of very severe pneumonia (confirmed by radiology), severe hypoxaemia, severe malnutrition, and Down''s syndrome. The patient was treated according to the hospital protocol for the management of pneumonia and malnutrition. During the hospital stay, hypoxaemia was persistent with very little improvement of pneumonia; a number of differentials, such as pneumocystis jirovecii pneumonia, lymph-node tuberculosis, were added to the problems. Subsequently, the patient''s hypoxaemia improved with the empirical use of antitubercular drugs. However, the patient again developed persistent hypoxaemia and, after unsuccessful treatment for a hospital-acquired pneumonia, the problems further expanded to include interstitial lung disease (ILD). This was confirmed by high-resolution computed tomography, and the patient was treated with prednisolone for 6 months, along with antitubercular drugs. He fully recovered from ILD, hypoxaemia, and pneumonia both clinically and radiologically. Therefore, severely-malnourished children having wet cough and pneumonia with persistent hypoxaemia should be assessed for the possible existence of interstitial lung disease. This may help provide a prompt and appropriate management to reduce morbidity and deaths in such patients.Key words: Hypoxaemia, Infant, Interstitial lung disease, Lymph-node tuberculosis, Severe malnutrition, Very severe pneumonia     

Microanalyses of lesions and lymph nodes from coalminers'' lungs.

The dust content and composition of lesions and hilar lymph nodes from the lungs of British coalworkers have been examined. Samples of macules, fibrotic nodules, and massive fibrosis (both peripheral and central sites) were dissected from 49 lungs. The highest mean dust concentrations (about 20%) were found in nodules and massive fibrosis. Overall there were no significant differences between the selected lesion types and their respective whole lung dust composition, although the central sites of massive fibrosis were found to contain on average a higher proportion of coal and a lower proportion of ash and its measured constituents, quartz and kaolin plus mica, than the edge of the lesion (p less than 0.001 for each component). There were striking differences between recovered lung and lymph node dusts. An examination of 180 specimens showed a mean quartz in lymph node dust of 20.3% compared with 6.1% in lung dust. As expected the proportion of quartz was greater in lymph nodes and lungs from men who had worked "low" rank (high ash) coal. By contrast with the corresponding figures for lung dusts, however, the mean proportion of quartz in nodes did not increase over the pathological range of pneumoconiotic lung disease. On average the proportions of kaolin and mica in lymph nodes reflect those found in lungs. The lymphotrophic nature of quartz was clearly shown although it was not possible to show an association between this clearance pathway and any particular type of lesion.     

Comparison of intranasal and transcutaneous immunization for induction of protective immunity against Chlamydia muridarum respiratory tract infection

Chlamydia pneumoniae causes a range of respiratory infections including bronchitis, pharyngitis and pneumonia. Infection has also been implicated in exacerbation/initiation of asthma and chronic obstructive pulmonary disease (COPD) and may play a role in atherosclerosis and Alzheimer's disease. We have used a mouse model of Chlamydia respiratory infection to determine the effectiveness of intranasal (IN) and transcutaneous immunization (TCI) to prevent Chlamydia lung infection. Female BALB/c mice were immunized with chlamydial major outer membrane protein (MOMP) mixed with cholera toxin and CpG oligodeoxynucleotide adjuvants by either the IN or TCI routes. Serum and bronchoalveolar lavage (BAL) were collected for antibody analysis. Mononuclear cells from lung-draining lymph nodes were stimulated in vitro with MOMP and cytokine mRNA production determined by real time PCR. Animals were challenged with live Chlamydia and weighed daily following challenge. At day 10 (the peak of infection) animals were sacrificed and the numbers of recoverable Chlamydia in lungs determined by real time PCR. MOMP-specific antibody-secreting cells in lung tissues were also determined at day 10 post-infection. Both IN and TCI protected animals against weight loss compared to non-immunized controls with both immunized groups gaining weight by day 10-post challenge while controls had lost 6% of body weight. Both immunization protocols induced MOMP-specific IgG in serum and BAL while only IN immunization induced MOMP-specific IgA in BAL. Both immunization routes resulted in high numbers of MOMP-specific antibody-secreting cells in lung tissues (IN>TCI). Following in vitro re-stimulation of lung-draining lymph node cells with MOMP; IFNgamma mRNA increased 20-fold in cells from IN immunized animals (compared to non-immunized controls) while IFNgamma levels increased 6- to 7-fold in TCI animals. Ten days post challenge non-immunized animals had >7,000 IFU in their lungs, IN immunized animals <50 IFU and TCI immunized animals <1,500 IFU. Thus, both intranasal and transcutaneous immunization protected mice against respiratory challenge with Chlamydia. The best protection was obtained following IN immunization and correlated with IFNgamma production by mononuclear cells in lung-draining LN and MOMP-specific IgA in BAL.     

Antigen targeted to secondary lymphoid organs via vascular cell adhesion molecule (VCAM) enhances an immune response

The localisation of antigen within secondary lymphoid organs can significantly increase the immune response. Using the monoclonal antibody M/K 2.7, which recognises murine vascular cell adhesion molecule (VCAM), we have shown antigen accumulation within organs of the secondary lymph such as the draining lymph nodes and spleen. Similar accumulation was not apparent in other, non-lymphatic organs. We then compared the immune response to antigen targeted to secondary lymphoid organs, via VCAM recognition, with untargeted antigen. The model antigen used, rat IgG1, was shown to be a weak murine immunogen, not eliciting any measurable antibody or cellular response. However, the same antigen targeted to VCAM, was shown to elicit an IgG1 antibody response and T cell proliferation, also marked by IFNgamma expression. These results confirm the effectiveness of targeting antigen to secondary lymphoid organs in enhancing an immune response and identify VCAM as a useful target.