scholarly journals Local Lung Immune Response to Mycobacterium bovis Challenge after BCG and M. bovis Heat-Inactivated Vaccination in European Badger (Meles meles)

Pathogens ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 456
Author(s):  
Cristina Blanco Vázquez ◽  
Miguel Prieto ◽  
Marta Barral ◽  
Ramón Antonio Juste ◽  
Sandrine Lesellier ◽  
...  
Keyword(s):  
Immune Response ◽  
B Lymphocytes ◽  
Mycobacterium Bovis ◽  
Plasma Cells ◽  
Protective Efficacy ◽  
Bacterial Load ◽  
Field Conditions ◽  
Local Immune Response ◽  
Analysis Software ◽  
Phagocytic Cells

Tuberculosis (TB) vaccination could be used as a key part of integrated strategies for the disease’s control if an effective and safe vaccine under field conditions is obtained. Recent studies in Spain have evaluated the protective efficacy of two oral vaccines against experimental challenge with live intra-bronchial Mycobacterium bovis in captive badgers: the live-attenuated M. bovis BCG vaccine (Danish strain) and a heat-inactivated M. bovis (HIMB) vaccine. With the objective of increasing the knowledge of the cellular development progress of infection and generating further tools to discriminate between mild and severe TB lesions between and within animals, the immunopathology of tuberculous lesions was studied to characterize the local immune response (cell type profile) within lung granulomas from control (non-vaccinated), BCG vaccinated and HIMB-vaccinated experimentally infected badgers with M. bovis. Four immunohistochemical protocols, for the specific detection of macrophages, T lymphocytes, B lymphocytes and plasma cells within TB granulomas in formalin fixed sections of the right middle lung lobe (lobe targeted for the M. bovis delivery), were performed. Immunolabelled sections were scanned and five randomly selected areas were analyzed with digital image analysis software. The results were expressed as the proportion of the positively immunolabelled area within the total area of the selected site. Data was analyzed using the statistical analysis software (SAS). In the three treatment groups, macrophages were the most abundant inflammatory cells within the granulomas, followed by B lymphocytes and plasma cells. T lymphocyes were absent in those granulomas. This would suggest a predominance of a non-specific innate response mediated by phagocytic cells over an adaptative humoral immune response. The proportion of macrophages and plasma cells was higher in BCG and HIMB-vaccinated badgers, respectively, suggesting the establishment of an adaptative humoral response in HIMB-vaccinated badgers. The lower bacterial load at the lung level, as well as the volume of lesions in lungs using magnetic resonance imaging in badgers with the HIMB vaccine in relation with local immune response presented, must be highlighted, since it would be an advantage in favor of its use under field conditions in terms of reducing TB transmission and environmental contamination.

scholarly journals IFN-α Boosting of Mycobacterium bovis Bacillus Calmette Güerin-Vaccine Promoted Th1 Type Cellular Response and Protection against M. tuberculosis Infection

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
C. E. Rivas-Santiago ◽  
G. G. Guerrero
Keyword(s):  
Immune Response ◽  
Mycobacterium Bovis ◽  
Cellular Immune Response ◽  
Cellular Response ◽  
Bacterial Load ◽  
Bcg Vaccine ◽  
Type I ◽  
Bacillus Calmette Guerin ◽  
Type I Ifns ◽  
Cellular Immune

The role of type I IFNs in the pathogenesis and control of mycobacterial infection is still controversial. It has been reported that type I IFNs exacerbated M. tuberculosis infection through hampering Th1 type cellular immune response. However, under certain conditions they can act as natural immune adjuvants for commercial vaccines. At this point, we have reported recently that successive IFN-alpha boosting of Mycobacterium bovis Bacillus Calmette Güerin (BCG) vaccinated mice protected adult mice from intradermal M. lepraemurium infection and a difference in iNOS was observed. In the present work, we have found that intramuscular IFN-α boosting of Mycobacterium bovis Bacillus Calmette Güerin (BCG) vaccine, either in vitro (human cell line or macrophages derived from PBMC) or in vivo (aerosol mouse model of MTb infection), promoted mostly the development of specific anti-antimycobacterial Th1 type cytokines (IFN-γ; IL-12, TNF-alpha, and IL-17; IL1β) while bacterial load reduction (0.9 logs versus PBS or BCG vaccine) was observed. These findings indicate that, under the experimental settings reported here, interferon alpha can drive or affect the TH cellular immune response in favour of BCG-inducing immunity against M. tuberculosis infection.

scholarly journals Relationship between lymph concentration of cytokines and structural transformations in mesenteric lymph nodes in chemotherapy, surgical treatment, and chemotherapy of experimental breast cancer

2020 ◽  
pp. 37-45
Author(s):  
О.В. Казаков ◽  
А.Ф. Повещенко ◽  
Н.Б. Орлов ◽  
Т.В. Райтер ◽  
О.В. Повещенко ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Surgical Treatment ◽  
Lymph Nodes ◽  
Thoracic Duct ◽  
Plasma Cells ◽  
Local Immune Response ◽  
Mesenteric Lymph Nodes ◽  
Mesenteric Lymph ◽  
Medullary Cords

Цель исследования - анализ корреляции морфометрии брыжеечных лимфатических узлов и концентрации цитокинов в лимфе грудного протока при химиотерапии рака молочной железы, хирургическом лечении и последующей химиотерапии. Методика. Рак молочной железы индуцировали введением N-метил-N-нитрозомочевины 5 раз с интервалом 7 сут подкожно в область 2-й молочной железы справа. Курс химиотерапии проходил по схеме CMF. Корреляцию между концентрациями 24 цитокинов лимфы и числом клеток структурных зон лимфатических узлов оценивали по коэффициенту ранговой корреляции Спирмена. Результаты. После химиотерапии РМЖ, по сравнению с РМЖ без лечения, морфологические преобразования в лимфатических узлах свидетельствуют о снижении активности местного иммунного ответа. Исследование корреляции концентрации цитокинов в лимфе со структурными изменениями в лимфатических узлах выявило зависимости направленные на повышение иммуномодулирующего и противоопухолевого действия цитокинов. После оперативного лечения РМЖ и последующей химиотерапии, по сравнению только с химиотерапией РМЖ, выявлены положительные связи иммунобластов с цитокином GRO/KC в герминативных центрах, цитокина IL-6 - с митотически делящимися клетками в герминативных центрах и мозговых тяжах, IL-5 - с иммунобластами в мозговых тяжах, хемокина MIP-1a - со зрелыми плазматическими клетками в мозговых синусах. Увеличено количество иммунобластов, средних и малых лимфоцитов в герминативных центрах, возросло количество малых лимфоцитов, незрелых и зрелых плазматических клеток в мозговых синусах. Увеличены площади мозговых тяжей и паракортикальной зоны. Выявлена корреляция: цитокина IL-1α с малыми лимфоцитами, IL-6 с иммунобластами, IL-7 и IL-18 - со средними лимфоцитами, GRO/KC - с иммунобластами, IL-17 - с макрофагами в Т-зависимой зоне; IL-7 и IL-18 - с иммунобластами, IL-12 - с макрофагами, MIP-1a и MCP-1 со зрелыми плазматическими клетками в мозговых синусах. Заключение. После оперативного лечения РМЖ c последующей химиотерапией, по сравнению только с химиотерапией РМЖ, выявлены взаимозависимости концентрации цитокинов в лимфе грудного протока с морфологическими изменениями в брыжеечных лимфатических узлах, которые могут указывать на повышение активности местного звена иммунного ответа. The aim of this study was to analyze correlations of the morphometry of mesenteric lymph nodes with cytokine concentrations in thoracic duct lymph in chemotherapy and surgical treatment with subsequent chemotherapy of breast cancer. Methods. Breast cancer was induced by subcutaneous injection of N-methyl-N-nitrosourea 5 times with 7-day intervals, into the region of the 2nd breast on the right. The course of chemotherapy was performed according to the CMF scheme. Correlations between concentrations of 24 cytokines of the lymph and cells of lymph node structural regions were estimated by the Spearman rank correlation coefficient. Results. After chemotherapy for breast cancer compared to untreated breast cancer, morphological transformations in lymph nodes indicated decreased activity of the local immune response. Analysis of correlations between lymph concentrations of cytokines and structural changes in lymph nodes identified relationships aimed at increasing the immunomodulatory and antitumor effects of cytokines. After surgical treatment of breast cancer and subsequent chemotherapy compared to chemotherapy alone, positive correlations were found for immunoblasts with cytokine GRO/KC in germinative centers, for cytokine IL-6 with mitotically dividing cells in germinative centers and medullary cords, for IL-5 with immunoblasts in medullary cords, and for chemokine MIP-1a with mature plasma cells in medullary sinuses. Numbers of immunoblasts and medium and small lymphocytes were increased in germinative centers whereas numbers of small lymphocytes and immature and mature plasma cells were increased in medullary sinuses. Areas of medullary cords and the paracortical zone were increased. Correlations were found for cytokine IL-1α with small lymphocytes, for IL-6 with immunoblasts, for IL-7 and IL-18 with medium lymphocytes, for GRO/KC with immunoblasts, for IL-17 with macrophages in the T-dependent zone, for IL-7 and IL-18 with immunoblasts, for IL-12 with macrophages, and for MIP-1a and MCP-1 with mature plasma cells in medullary sinuses. Conclusion. After surgical treatment of breast cancer and subsequent chemotherapy compared to chemotherapy alone, cytokine concentrations in lymph of the thoracic duct were observed to correlate with morphological changes in mesenteric lymph nodes, which may indicate increased activity of the local immune response.

Immune Response of the Endolymphatic Sac to Horseradish Peroxidase: Immunologic Route from the Middle Ear to the Inner Ear

1989 ◽  
Vol 98 (12) ◽  
pp. 975-979 ◽  
Author(s):  
Minoru Ikeda ◽  
Claus Morgenstern
Keyword(s):  
Immune Response ◽  
Horseradish Peroxidase ◽  
Inner Ear ◽  
Middle Ear ◽  
Plasma Cells ◽  
Endolymphatic Sac ◽  
Local Immune Response ◽  
Frozen Sections ◽  
Response Region

Twenty guinea pigs were immunized with horseradish peroxidase (HRP) intradermally and challenged with 5 mg of the same antigen in the tympanic bulla. The appearance of immunoglobulin-producing cells (plasma cells) in the inner ear structure was examined immunohistochemically in frozen sections. Four to 10 days following antigen challenge, 5 of the 20 animals showed significantly increased plasma cells in the subepithelial connective tissue of the endolymphatic sac (ES). Those cells showed positive reactions, mainly with IgG followed by IgM. The cells that reacted positively with IgA were few. Some of these plasma cells were considered to contain the specific antibody against HRP. The results indicate the role of the ES as a local immune response region for the inner ear complex, as well as the existence of an immunologic route from the middle ear cavity to the inner ear, particularly to the ES.

scholarly journals Immunohistochemical Assessment of Immune Response in the Dermis of Sarcoptes scabiei—Infested Wild Carnivores (Wolf and Fox) and Ruminants (Chamois and Red Deer)

Animals ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1146
Author(s):  
Ileana Z. Martínez ◽  
Álvaro Oleaga ◽  
Irene Sojo ◽  
María José García-Iglesias ◽  
Claudia Pérez-Martínez ◽  
...  
Keyword(s):  
Immune Response ◽  
T Lymphocytes ◽  
B Lymphocytes ◽  
Red Deer ◽  
Plasma Cells ◽  
Inflammatory Cells ◽  
Sarcoptes Scabiei ◽  
Type I ◽  
Effective Response ◽  
Wild Mammals

Sarcoptic mange is caused by the mite Sarcoptes scabiei and has been described in several species of domestic and wild mammals. Macroscopic lesions are predominantly hyperkeratotic (type I hypersensitivity) in fox, chamois and deer, but alopecic (type IV hypersensitivity) in wolf and some fox populations. To begin to understand the immune processes underlying these species differences in lesions, we examined skin biopsies from wolves (Canis lupus), foxes (Vulpes vulpes), chamois (Rupicapra rupicapra) and red deer (Cervus elaphus) naturally infested with S. scabiei. Twenty skin samples from five animals per species were used. Sections were immuno-stained with primary antibodies against Iba1 to detect macrophages, lambda chain to detect plasma cells, CD3 to detect T lymphocytes and CD20 to detect B lymphocytes. Skin lesions contained significantly more inflammatory cells in the fox than in the wolf and chamois. Macrophages were the most abundant inflammatory cells in the lesions of all the species studied, suggesting a predominantly innate, non-specific immune response. Lesions from the wolf contained higher proportions of macrophages than the other species, which may reflect a more effective response, leading to alopecic lesions. In red deer, macrophages were significantly more abundant than plasma cells, T lymphocytes and B lymphocytes, which were similarly abundant. The fox proportion of plasma cells was significantly higher than those of T and B lymphocytes. In chamois, T lymphocytes were more abundant than B lymphocytes and plasma cells, although the differences were significant only in the case of macrophages. These results suggest that all the species examined mount a predominantly innate immune response against S. scabiei infestation, while fox and chamois may also mount substantial humoral and cellular immune responses, respectively, with apparently scarce effectiveness that lead to hyperkeratotic lesions.

scholarly journals PM2.5 Mediated Alterations In The In Vitro Human Granuloma Resulting In Reactivation Of Mycobacteria

2021 ◽  
Author(s):  
Athisankaran Punniyamurthy ◽  
Sumedha Sharma ◽  
Khushpreet Kaur ◽  
Uma Nahar Saikia ◽  
Ravindra Khaiwal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Particulate Matter ◽  
Mycobacterium Bovis ◽  
Bacterial Load ◽  
Granuloma Formation ◽  
Human Pbmcs ◽  
Cytokine Levels ◽  
Mycobacterial Antigens

Abstract Exposure to pollutants diminishes the immune response to mycobacterial antigens relevant to contain the infection in the granuloma, thus leading to reactivation of latent bacilli. Present study was therefore designed based on the hypothesis that exposure to particulate matter pollutant PM2.5 affects the granuloma formation and reactivation of latent mycobacterial bacilli contained in the granuloma. For the extraction of PM2.5, based on initial standardizations, teflon filter was selected over the quartz filter. Two different approaches were used to study the effect of PM2.5 on the human PBMCs granuloma formed by Mycobacterium bovis BCG at MOI 0.1. In the first approach, granuloma formed in the presence of PM2.5 was loosely packed and ill-defined with significant downregulation of dormancy associated mycobacterial genes, upregulation of reactivation associated rpfB gene along with a significant increase in TNFα level without any change in the bacterial load in terms of CFUs. In the second approach, PM2.5 treatment of already established human PBMCs granuloma formed with M. bovis BCG also led to its disruption. Although, in these conditions, downregulation of dormancy associated genes was observed but there was also a decrease in the expression of reactivation associated rpfB gene without any change in the cytokine levels. Therefore, it can be inferred that in the presence of PM2.5, there is poor granuloma formation along with a change in mycobacterial gene expression characteristics of active bacilli and alteration in host immune response without any significant changes following treatment of already established granuloma with the pollutant.

scholarly journals Assessment of the Immune Response Induced in Neonatal Calves by Vaccination with Mycobacterium bovis BCG Phipps Under Field Conditions

2017 ◽  
Vol 1 (1) ◽  
pp. 47-61
Author(s):  
Fernando Díaz Otero  ◽  
Laura Jaramillo Meza  ◽  
José Ángel Gutiérrez Pabello  ◽  
Felipe Ángel Castañeda Cuevas ◽  
Camila Arriaga Díaz  ◽  
...  
Keyword(s):  
Immune Response ◽  
Mycobacterium Bovis ◽  
Field Conditions ◽  
Mycobacterium Bovis Bcg ◽  
Neonatal Calves

scholarly journals Virulence, Immunogenicity, and Protective Efficacy of Two Recombinant Mycobacterium bovis Bacillus Calmette-Guérin Strains Expressing the Antigen ESAT-6 from Mycobacterium tuberculosis

2003 ◽  
Vol 71 (4) ◽  
pp. 1656-1661 ◽  
Author(s):  
Lang Bao ◽  
Wei Chen ◽  
Huidong Zhang ◽  
Xiaoying Wang
Keyword(s):  
Immune Response ◽  
Mycobacterium Tuberculosis ◽  
Fusion Protein ◽  
Mycobacterium Bovis ◽  
Specific Antibody ◽  
Culture Medium ◽  
Protective Efficacy ◽  
Lung Histology ◽  
Antibody Titers ◽  
Cellular Immune

ABSTRACT We constructed two recombinant Mycobacterium bovis BCG (rBCG) strains expressing ESAT-6 of Mycobacterium tuberculosis, named rBCG-1 and rBCG-2. rBCG-1 contained the ESAT-6 gene linked to BCG hsp60 and expressed a fusion protein, while rBCG-2, with a secretory sequence, could secret ESAT-6 into the culture medium. There was no evidence for increased virulence of the two rBCG strains when we made a comparison between them and BCG with regard to organ bacterial loads, lung histology, and survival time. rBCG-1 induced significantly higher specific antibody titers and stronger cellular immune response than BCG, whereas rBCG-2 had immunogenicity similar to that of the parental BCG strain. Both rBCG-1 and rBCG-2 conferred marked protection against M. tuberculosis infection, yet in terms of protective efficacy, they showed no significant improvements upon conventional BCG vaccine.

scholarly journals Lymphocyte Recruitment and Protective Efficacy against Pulmonary Mycobacterial Infection Are Independent of the Route of Prior Mycobacterium bovis BCG Immunization

2002 ◽  
Vol 70 (3) ◽  
pp. 1410-1416 ◽  
Author(s):  
Umaimainthan Palendira ◽  
Andrew G. D. Bean ◽  
Carl G. Feng ◽  
Warwick J. Britton
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Mycobacterium Bovis ◽  
Protective Efficacy ◽  
Bacterial Load ◽  
Mycobacterial Infection ◽  
Rapid Expansion ◽  
Pulmonary Endothelium ◽  
Subsequent Exposure ◽  
Cell Adhesion Molecule 1

ABSTRACT Mycobacterium tuberculosis infects humans through the lung, and immunity to this chronic infection is mediated primarily by CD4+ T lymphocytes. Recently we have demonstrated that the recruitment of lymphocytes to the lung during primary aerosol M. tuberculosis infection in mice occurs predominantly through the interaction of α4β1 integrin on CD4+ T cells and vascular cell adhesion molecule-1 on the pulmonary endothelium. To investigate the effect of route of immunization with Mycobacterium bovis BCG on the pattern of T-cell recruitment to the lung, we have analyzed the differences in expression of integrins on activated memory CD4+ T cells infiltrating the lung following primary BCG immunization by aerosol, intravenous, and subcutaneous routes and after subsequent aerosol challenge with M. tuberculosis. There were marked differences in the patterns of recruitment of activated CD4+ T cells to the lung following primary immunization by the three routes. Expansion of CD44hi CD62Llow CD4+ T cells in the lung occurred following aerosol and intravenous BCG immunizations, and the lymphocyte recruitment was proportional to the pulmonary bacterial load. The majority of infiltrating CD4+ T cells expressed α4β1 integrin. On subsequent exposure to aerosol BCG rapid expansion of gamma interferon-secreting α4β1 + CD4+ T cells occurred to the same extent in all immunized mice, regardless of the route of immunization. Similar expansion of α4β1 + CD4+ memory T cells occurred following M. tuberculosis challenge. The three routes of BCG immunization resulted in the same level of protection against aerosol M. tuberculosis or BCG challenge in both the lungs and spleen. Therefore, recruitment of effector T lymphocytes and protective efficacy against pulmonary mycobacterial infection are independent of the route of prior BCG immunization.

scholarly journals Enhanced immune response and protection efficacy of a DNA vaccine constructed by linkage of the Mycobacterium tuberculosis Ag85B-encoding gene with the BVP22-encoding gene

2009 ◽  
Vol 58 (4) ◽  
pp. 462-468 ◽  
Author(s):  
Wanhong Yao ◽  
Shengwu Liu ◽  
Xueju Qu ◽  
Shaobo Xiao ◽  
Yan Liu ◽  
...  
Keyword(s):  
Immune Response ◽  
Mycobacterium Tuberculosis ◽  
Dna Vaccine ◽  
Plasmid Dna ◽  
Histopathological Examination ◽  
Protective Efficacy ◽  
Bacterial Load ◽  
Dna Encoding ◽  
Promising Tool ◽  
Encoding Gene

Plasmid DNA vaccines have been widely explored for use in tuberculosis immunization but their immunogenicity needs improvement. In the present study, we incorporated the bovine herpesvirus 1 VP22 (BVP22)-encoding gene, which encodes a protein that demonstrates a capability for disseminating the expressed antigen to neighbouring cells, into a DNA vector in which it was fused to the Ag85B-encoding gene of Mycobacterium tuberculosis (Mtb), and investigated whether this linkage could enhance immune response and protective efficacy in C57BL/6 mice compared to plasmid DNA encoding Ag85B alone. After immunization in mice, Ag85B-specific ELISA antibodies and spleen lymphocyte proliferative responses induced by DNA co-expressing BVP22 and Ag85B were significantly higher than those obtained in mice immunized with Ag85B-encoding DNA alone, except for the number of gamma interferon secreting cells. In addition, based on histopathological examination and bacterial-load determination in lung and spleen, protection against intravenous Mtb H37Rv challenge evoked by the BVP22–Ag85B DNA immunization exceeded the response elicited by Ag85B DNA alone, which was not significantly different from that provided by Bacillus Calmette–Guérin (BCG). These results suggested that DNA vaccine consisting of BVP22 and Ag85B-encoding DNA enhanced immune response and protection against intravenous Mtb H37Rv challenge in mice, indicating that BVP22-encoding DNA might be a promising tool to enhance TB DNA vaccine efficacy.

Altered Fine Structure of B Lymphocytes Correlated with Defective Terminal Differentiation

1973 ◽  
Vol 31 ◽  
pp. 386-387
Author(s):  
Dale E. Bockman ◽  
L. Y. Frank Wu ◽  
Alexander R. Lawton ◽  
Max D. Cooper
Keyword(s):  
Immune Deficiency ◽  
B Lymphocytes ◽  
Plasma Cells ◽  
Present Report ◽  
Specific Antigen ◽  
Terminal Differentiation ◽  
Second Stage ◽  
Two Stages ◽  
Deficiency Diseases ◽  
Cell Line Generation

B-lymphocytes normally synthesize small amounts of immunoglobulin, some of which is incorporated into the cell membrane where it serves as receptor of antigen. These cells, on contact with specific antigen, proliferate and differentiate to plasma cells which synthesize and secrete large quantities of immunoglobulin. The two stages of differentiation of this cell line (generation of B-lymphocytes and antigen-driven maturation to plasma cells) are clearly separable during ontogeny and in some immune deficiency diseases. The present report describes morphologic aberrations of B-lymphocytes in two diseases in which second stage differentiation is defective.

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