scholarly journals The Pathogenesis of Tuberculosis–The Koch Phenomenon Reinstated

Pathogens ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 813
Author(s):  
Robert L. Hunter
Keyword(s):  
T Cells ◽  
Animal Models ◽  
Hypersensitivity Reaction ◽  
Alveolar Macrophages ◽  
Adult Type ◽  
New Approaches ◽  
Early Lesion ◽  
Mycobacterial Antigens ◽  
Active Disease

Research on the pathogenesis of tuberculosis (TB) has been hamstrung for half a century by the paradigm that granulomas are the hallmark of active disease. Human TB, in fact, produces two types of granulomas, neither of which is involved in the development of adult type or post-primary TB. This disease begins as the early lesion; a prolonged subclinical stockpiling of secreted mycobacterial antigens in foamy alveolar macrophages and nearby highly sensitized T cells in preparation for a massive necrotizing hypersensitivity reaction, the Koch Phenomenon, that produces caseous pneumonia that is either coughed out to form cavities or retained to become the focus of post-primary granulomas and fibrocaseous disease. Post-primary TB progresses if the antigens are continuously released and regresses when they are depleted. This revised paradigm is supported by nearly 200 years of research and suggests new approaches and animal models to investigate long standing mysteries of human TB and vaccines that inhibit the early lesion to finally end its transmission.

scholarly journals T Cell Immunity against Influenza: The Long Way from Animal Models Towards a Real-Life Universal Flu Vaccine

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 199
Author(s):  
Anna Schmidt ◽  
Dennis Lapuente
Keyword(s):  
T Cells ◽  
T Cell ◽  
Animal Models ◽  
Respiratory Tract ◽  
Memory T Cells ◽  
Real Life ◽  
T Cell Immunity ◽  
Cell Immunity ◽  
Flu Vaccine ◽  
Resident Memory T Cells

Current flu vaccines rely on the induction of strain-specific neutralizing antibodies, which leaves the population vulnerable to drifted seasonal or newly emerged pandemic strains. Therefore, universal flu vaccine approaches that induce broad immunity against conserved parts of influenza have top priority in research. Cross-reactive T cell responses, especially tissue-resident memory T cells in the respiratory tract, provide efficient heterologous immunity, and must therefore be a key component of universal flu vaccines. Here, we review recent findings about T cell-based flu immunity, with an emphasis on tissue-resident memory T cells in the respiratory tract of humans and different animal models. Furthermore, we provide an update on preclinical and clinical studies evaluating T cell-evoking flu vaccines, and discuss the implementation of T cell immunity in real-life vaccine policies.

Cross-recognition by T cells of an epitope shared by two unrelated mycobacterial antigens

1995 ◽  
Vol 25 (11) ◽  
pp. 3173-3179 ◽  
Author(s):  
David P. Harris ◽  
Hans-Martin Vordermeier ◽  
Mahavir Singh ◽  
Carlos Moreno ◽  
Stipo Jurcevic ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterial Antigens

scholarly journals Cooperativity Between CD8+ T Cells, Non-Neutralizing Antibodies, and Alveolar Macrophages Is Important for Heterosubtypic Influenza Virus Immunity

2013 ◽  
Vol 9 (3) ◽  
pp. e1003207 ◽  
Author(s):  
Brian J. Laidlaw ◽  
Vilma Decman ◽  
Mohammed-Alkhatim A. Ali ◽  
Michael C. Abt ◽  
Amaya I. Wolf ◽  
...  
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
Cd8 T Cells ◽  
Alveolar Macrophages ◽  
Neutralizing Antibodies ◽  
Virus Immunity

scholarly journals Effector T cells in rheumatoid arthritis: Lessons from animal models

FEBS Letters ◽  
2011 ◽  
Vol 585 (23) ◽  
pp. 3649-3659 ◽  
Author(s):  
Saba Alzabin ◽  
Richard O. Williams
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Animal Models ◽  
Effector T Cells

scholarly journals S43 Polyfunctional T cells reveal the spectrum of tuberculosis in HIV co-infection through the identification of immunological correlates of latent and active disease

Thorax ◽  
2011 ◽  
Vol 66 (Suppl 4) ◽  
pp. A22-A23
Author(s):  
K. M. Pollock ◽  
D. Montamat-Sicotte ◽  
G. Cooke ◽  
M. Kapembwa ◽  
O. M. Kon ◽  
...  
Keyword(s):  
T Cells ◽  
Polyfunctional T Cells ◽  
Active Disease

scholarly journals New approaches to the representation and analysis of phenotype knowledge in human diseases and their animal models

2011 ◽  
Vol 10 (5) ◽  
pp. 258-265 ◽  
Author(s):  
P. N. Schofield ◽  
J. P. Sundberg ◽  
R. Hoehndorf ◽  
G. V. Gkoutos
Keyword(s):  
Animal Models ◽  
Human Diseases ◽  
New Approaches

Retinoic Acid Is Elevated in the Mucosa of Patients With Active Ulcerative Colitis and Displays a Proinflammatory Role by Augmenting IL-17 and IFNγ Production

2020 ◽  
Vol 27 (1) ◽  
pp. 74-83 ◽  
Author(s):  
Ritika Rampal ◽  
Nahidul Wari ◽  
Amit Kumar Singh ◽  
Ujjwalkumar Das ◽  
Sawan Bopanna ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
T Cells ◽  
Retinoic Acid ◽  
Crucial Role ◽  
Intestinal Inflammation ◽  
Γδ T Cells ◽  
Inflammatory Conditions ◽  
Invariant T Cells ◽  
Active Disease

Abstract Background All-trans retinoic acid (RA) plays a crucial role in promoting Foxp3+ Treg generation while reciprocally inhibiting Th1/Th17 generation. Our previous research highlighted that in the face of inflammatory conditions, RA plays a contrary role where it aggravates intestinal inflammation by promoting interferon (IFN) γ and interleukin (IL)-17 differentiation in vitro. Methods In this study we translated our in vitro results into a clinical setting where we estimated mucosal and serum RA levels along with the immunophenotypic profile (IL-17, IFNγ, Foxp3, IL-10) in adaptive (CD4, CD8) and innate-like T cells (mucosal associated invariant T cells and γδ T cells) in patients with ulcerative colitis in remission or with active inflammation. Results This is the first study to estimate RA levels in the human gut and shows that patients with active disease had increased mucosal RA levels as compared with patients in remission (4.0 vs 2.5 ng/mL; P < 0.01) and control patients (3.4 vs 0.8 ng/mL; P < 0.0001). This effect was accompanied by significantly elevated IL-17 and IFNγ in tissue CD4+, CD8+, mucosal associated invariant T+ cells, and γδ + T cells. Moreover, the raised RA levels in patients with active disease showed a positive correlation with proinflammatory cytokines (IL-17, IFNγ) and a negative correlation with IL-10. We also found that RA negatively correlated with IL-9, thereby reinstating our previous finding that RA inhibits Th9 differentiation. Conclusions These data confirm our previous in vitro results that in the presence of inflammation, RA plays a crucial role in maintaining gut inflammation by upregulating proinflammatory markers.

scholarly journals Ex Vivo Characterization of Early Secretory Antigenic Target 6-Specific T Cells at Sites of Active Disease in Pleural Tuberculosis

2005 ◽  
Vol 40 (1) ◽  
pp. 184-187 ◽  
Author(s):  
K. A. Wilkinson ◽  
R. J. Wilkinson ◽  
A. Pathan ◽  
K. Ewer ◽  
M. Prakash ◽  
...  
Keyword(s):  
T Cells ◽  
Ex Vivo ◽  
Pleural Tuberculosis ◽  
Early Secretory Antigenic Target ◽  
Active Disease

scholarly journals Dendritic cell progenitors phagocytose particulates, including bacillus Calmette-Guerin organisms, and sensitize mice to mycobacterial antigens in vivo.

1993 ◽  
Vol 178 (2) ◽  
pp. 479-488 ◽  
Author(s):  
K Inaba ◽  
M Inaba ◽  
M Naito ◽  
R M Steinman
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Antigen Processing ◽  
Blood Stream ◽  
Active Immunization ◽  
Bacillus Calmette Guerin ◽  
Antigen Uptake ◽  
Gm Csf ◽  
Mycobacterial Antigens

Dendritic cells, while effective in sensitizing T cells to several different antigens, show little or no phagocytic activity. To the extent that endocytosis is required for antigen processing and presentation, it is not evident how dendritic cells would present particle-associated peptides. Evidence has now been obtained showing that progenitors to dendritic cells can internalize particles, including Bacillus Calmette-Guerin (BCG) mycobacteria. The particulates are applied for 20 h to bone marrow cultures that have been stimulated with granulocyte/macrophage colony-stimulating factor (GM-CSF) to induce aggregates of growing dendritic cells. Cells within these aggregates are clearly phagocytic. If the developing cultures are exposed to particles, washed, and "chased" for 2 d, the number of major histocompatibility complex class II-rich dendritic cells increases substantially and at least 50% contain internalized mycobacteria or latex particles. The mycobacteria-laden, newly developed dendritic cells are much more potent in presenting antigens to primed T cells than corresponding cultures of mature dendritic cells that are exposed to a pulse of organisms. A similar situation exists when the BCG-charged dendritic cells are injected into the footpad or blood stream of naive mice. Those dendritic cells that have phagocytosed organisms induce the strongest T cell responses to mycobacterial antigens in draining lymph node and spleen. The administration of antigens to GM-CSF-induced, developing dendritic cells (by increasing both antigen uptake and cell numbers) will facilitate the use of these antigen-presenting cells for active immunization in situ.

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