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Addis Ababa University Libraries Electronic Thesis and Dissertations: AAU-ETD! >
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Thesis - Medical Microbiology >
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http://hdl.handle.net/123456789/1224
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| Title: | ROLE OF DENDRITIC CELLS IN THE INITIATION OF IMMUNITY TO MYCOBACTERIUM TUBERCULOSIS INFECTION |
| Authors: | ADANE, MIHRET |
| Advisors: | Dr. Shreemanta K. Parida
Professor Asrat Hailu |
| Copyright: | 2005 |
| Date Added: | 24-May-2008 |
| Publisher: | Addis Ababa University |
| Abstract: | M. tuberculosis is one of the most ubiquitous and extraordinary effective human pathogens,
with one-third of the world’s population being infected and is second to HIV in the number
of deaths per year from a single infectious agent. These high numbers of deaths occur
despite effective therapy available through the WHO DOTS (Directly Observed Therapy,
short course) program, widespread vaccination with BCG, and the host’s ability to mount a
protective immune response.
Numerous studies in humans and animal models over the years have shown that cellmediated
immunity is necessary for protection against M. tuberculosis infection. In cellmediated
immunity, antigens should be presented by Antigen Presenting Cells (APCs) in
the context of MHC I or MHC II molecules to T cells. Dendritic cells (DC) are unique
among all APCs in the adult immune system in many critical ways and play an essential
role in the initiation and maintenance of immune response to pathogens, moreover DCbased
immunization protocols have been shown to mediate protection against a wide
spectrum of infectious diseases caused by viral, bacterial, parasitic and fungal pathogens as
well as cancer. However, whether the interaction between the human DC and M.
tuberculosis represents a defence mechanism by the invaded host, or a smoke screen,
masking the presence of an invader is still not clearly understood.
To analyze the interactions between M. tuberculosis and immune cells, human peripheral
blood monocyte derived immature DC were infected with M. tuberculosis H37Rv wild type
strain. DC were found to internalize the mycobacteria and show dose dependent infection
and necrosis with different multiplicity of infection. In this study we investigated whether
M. tuberculosis induced maturation of DC. Fluorescence activated cell analysis of mean
fluorescence intensity of cell surface expression markers CD40, CD54, CD80, CD83,
CD86 and HLA DR in infected DC revealed significant (p<0.05) upregulation following
infection with M. tuberculosis in comparison to immature DC with no stimulation.
Lipopolysaccharide (LPS) from Salmonella abortus equi, a known DC maturation agent,
was used as a positive control and showed a comparable upregulation of cell surface
markers as observed with M. tuberculosis infected DC. We have also investigated the
ability of the M. tuberculosis infected DC to induce T cell proliferation. Fluorescence
activated cell analysis of mixed leukocyte reaction using 5 and 6-carboxyfluorescein
diacetate succinimidyl ester (CFSE) dilution technique revealed that the M. tuberculosis
infected DC induced T cell proliferation. These data clearly demonstrate that M.
tuberculosis induces activation and maturation of human monocyte derived immature DC
in vitro. |
| Description: | A THESIS SUBMITTED TO THE SCHOOL OF GRADUATE PROGRAMME OF ADDIS
ABABA UNIVERSITY IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE
DEGREE OF MASTER OF SCIENCE IN MEDICAL MICROBIOLOGY |
| URI: | http://hdl.handle.net/123456789/1224 |
| Appears in: | Thesis - Medical Microbiology
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