Chapter 7 : Human Tuberculosis

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The study of human mycobacterial granuloma is rendered difficult by the limitations of tissue availability and because direct study of protective immune response to is impossible. Bronchoalveolar lavage (BAL) can be used to assess localized lung immune responses during tuberculosis (TB), provides insights into immunologicc ompartmentalization, and may reflect processes in the granulomatous tissue adjacent to the bronchoalveolar spaces. The study of bronchoalveolar cells (BAC) from the bronchoalveolar spaces also allows assessment of alveolar MΦ and lymphocyte functions at the site of disease in the lungs from TB patients. Researchers have recently studied BAC from tuberculin skin test (TST)-positive healthy household contact (HHC) of sputum culture-positive, untreated TB index cases with three-plus-positive sputum smears, i.e., highly infectious cases. Ex vivo studies of cells from the bronchoalveolar spaces have been performed to feasibly obtain cells from the site of infection (reactivation disease) during TB. The most prominent finding of BAL studies in TB patients is a compartmentalized pulmonary immune response. Characterization of alveolar lymphocytes in human pulmonary tuberculosis are provided in this chapter. Understanding of the role of dendritic cells (DC) during mycobacterial infection is emerging. In vitro data indicate that DC are potent antigen-presenting cells as well as activators of T cells. Resolution of granuloma formation after successful TB chemotherapy is evidence for the importance of metabolically active in triggering granulomatous tissue reactions.

Citation: Schwander S, Ellner J. 2003. Human Tuberculosis, p 173-206. In Boros D (ed), Granulomatous Infections and Inflammations. ASM Press, Washington, DC. doi: 10.1128/9781555817879.ch7

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Figure 1

Frequencies of IFN-γ-producing cells in PBMC and BAC of tuberculin skin testpositive healthy household contacts of patients with active tuberculosis (HHC) and healthy tuberculin skin test-positive control individuals from the community (CC) by ELISPOT assay. Frequencies of IFN-γ-producing cells in PBMC and BAC from HHC ( = 10) (A) and CC ( = 15) (B) were determined by ELISPOT assay and are expressed as IFN-γ spots per 10 PBMC and BAC. PBMC and BAC were stimulated with PPD and Ag 85 complex from H37Rv culture filtrate (Ag 85co). Control cultures (background) were stimulated with medium alone (Medium). Results are presented as pairs of autologous PBMC and BAC data for each study individual. Visibility of overlapping data points was improved by separating the data points through minor horizontal shifting. •, HHC and CC individuals in whom frequencies of IFN-γ-producing cells in BAC were ≥ 3-fold higher than those in PBMC (for HHC, = 4 for PPD and = 5 for Ag 85co; for CC, = 1 for PPD and = 1 for Ag 85co). Frequencies of IFN-γ-producing BAC in response to Ag 85co were significantly higher in BAC from HHC (A) than in BAC from CC (B) ( = 0.022). Reprinted from reference 116 with permission. © 2000 The American Association of Immunologists, Inc.

Citation: Schwander S, Ellner J. 2003. Human Tuberculosis, p 173-206. In Boros D (ed), Granulomatous Infections and Inflammations. ASM Press, Washington, DC. doi: 10.1128/9781555817879.ch7
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Figure 2

Cytospin preparations of BAC (original magnification, ×160). Wright's stain of BAC from unaffected (A) and affected (B) lung of pulmonary tuberculosis patient shows increase in alveolar lymphocytes in affected lung (arrow); an occasional neutrophil also can be seen. Reprinted from reference 115 with permission of the University of Chicago Press. © 1996 by The University of Chicago. All rights reserved.

Citation: Schwander S, Ellner J. 2003. Human Tuberculosis, p 173-206. In Boros D (ed), Granulomatous Infections and Inflammations. ASM Press, Washington, DC. doi: 10.1128/9781555817879.ch7
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Figure 3

DNA synthesis by BAC (A) and PBMC (B) to mycobacterial and nonmycobacterial antigens from patients with pulmonary tuberculosis and healthy subjects. BAC and PBMC were stimulated with tetanus toxoid (TT), antigen, 30/32-kDa antigen 85-protein complex from H37Rv culture filtrate (Ag 85), or PPD, and incorporation of [3H]thymidine was determined after 5 days in culture. Responses of unstimulated cells (culture medium) were <1,000 cpm (data not shown). Horizontal lines represent medians. For PPD, = 16 tuberculosis patients and = 23 healthy subjects; for other stimuli, > 5 (both study groups). Reprinted from reference 117 with permission of the University of Chicago Press. © 1998 by the Infectious Diseases Society of America. All rights reserved.

Citation: Schwander S, Ellner J. 2003. Human Tuberculosis, p 173-206. In Boros D (ed), Granulomatous Infections and Inflammations. ASM Press, Washington, DC. doi: 10.1128/9781555817879.ch7
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Figure 4

Frequencies of IFN-γ-producing BAC by ELISPOT from patients with pulmonary tuberculosis and healthy subjects, determined in cells stimulated with medium alone (both healthy subjects and tuberculosis patients) or with PPD (healthy subjects [=4], radiographically unaffected lungs from tuberculosis patients [ = 3; two symbols overlap], and radiographically affected lungs from tuberculosis patients [ = 6]). Horizontal lines represent medians. Reprinted from reference 117 with permission of the University of Chicago Press. © 1998 by the Infectious Diseases Society of America. All rights reserved.

Citation: Schwander S, Ellner J. 2003. Human Tuberculosis, p 173-206. In Boros D (ed), Granulomatous Infections and Inflammations. ASM Press, Washington, DC. doi: 10.1128/9781555817879.ch7
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Table 1

Characterization of alveolar lymphocytes in human pulmonary tuberculosis

Citation: Schwander S, Ellner J. 2003. Human Tuberculosis, p 173-206. In Boros D (ed), Granulomatous Infections and Inflammations. ASM Press, Washington, DC. doi: 10.1128/9781555817879.ch7

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