Phuah, Jiayao
(2013)
Elucidating the Role of the Humoral Response in Mycobacterium tuberculosis infected Cynomolgus Macaques.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Mycobacterium tuberculosis remains as a global burden today with an estimated one-third of the global population being infected and at risk of developing active infection. Most studies in the immunology and pathogenesis of tuberculosis have revealed the importance of cellular immunity in controlling the infection. However, the role of the humoral immune response is poorly understood, particularly in the primate models of M. tuberculosis infection. The primary goal of this thesis was to understand how B cells and antibody contribute towards containment of M. tuberculosis within the cynomolgus macaque model of infection. The thesis starts off by characterizing B cells and antibody profiles within the granulomas of M. tuberculosis infected cynomolgus macaques. B cells were noted organize themselves into clusters that resemble germinal centers found in lymphoid organs or in chronic autoimmune conditions, within the granuloma. The effect of B cell depletion on the outcome of M. tuberculosis infection in cynomolgus macaques was also performed. The study findings suggest that B cells and antibody contribute very little in terms of disease control in the early stages of natural M. tuberculosis infection. However, subtle differences such as a slight increase in bacterial burden within individual granulomas and altered cytokine correlations within individual granulomas were noted. Macrophage behavior in the absence of B cells and antibody was also studied using
granuloma tissue derived from the B cell depletion study. No differences were found within the macrophages in the absence of B cells at least at the acute stage of infection. The experiments detailed in this thesis suggest that the humoral response is not crucial towards M. tuberculosis control in the early stages of natural infection. However, the findings in this thesis suggest that B cells and antibody may play a role in long term chronic control of tuberculosis infection.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
18 October 2013 |
| Date Type: |
Publication |
| Defense Date: |
30 September 2013 |
| Approval Date: |
18 October 2013 |
| Submission Date: |
17 October 2013 |
| Access Restriction: |
2 year -- Restrict access to University of Pittsburgh for a period of 2 years. |
| Number of Pages: |
182 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Immunology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
B cells; Tuberculosis; Non human primate |
| Date Deposited: |
18 Oct 2013 13:06 |
| Last Modified: |
15 Nov 2016 14:15 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/19898 |
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