TB Case Study Flashcards
What structural features of M. tuberculosis act to protect it when inside macrophages?
M. tuberculosis has an unusual waxy coating to its cell wall, consisting of mycolic acid and glycolipids, bound to a phosphorylated polysaccharide (arabinogalactan).
What is the causative agent of TB?
Mycobacterium tuberculosis
Rod shaped
Infects macrophages of the immune system
How do macrophages infected with M. tuberculosis signal their infection status to T cells?
Infected macrophages release the cytokine IL-12 that stimulates T cell proliferation. Macrophages also present mycobacterial antigens to T helper cells via MHC class I and class II molecules, and via a class I-like molecule called CD1. (Note: macrophages, T helper cells and cytokines are all described in detail in Block 2 Unit 1.)
What factors are used by macrophages in an attempt to destroy M. tuberculosis?
The unstable, reactive species used by macrophages against pathogens include: reactive oxygen intermediates (sometimes also called reactive oxygen species), hydrogen peroxide (H2O2), hypohalites, and nitric oxide (NO). Interferon gamma, released by activated T cells, activates macrophages and strongly induces the synthesis of NO in macrophages. However, because of its protective cell wall, M. tuberculosis has partial resistance to these cytotoxic molecules and is not always killed.
Although not mentioned in this mini-lecture, recent experiments have shown that lipid components of the M. tuberculosis cell wall disrupt the fusion of phagosomes to lysosomes within macrophages, preventing the mycobacteria from being delivered to the acidic, digestive enzyme-rich lysosome. This greatly increases the survival chances of the mycobacterium within macrophages.
Describe the diagnostic techniques used for tuberculosis?
Sputum sample analysis
Sample is place onto a slide and undergoes a ZiehlNeelson acid-fast stain. If identified then antibiotic resistance is investigated to establish he next course of treatment
Chest x rays to establish if lesions are present
PCR (polymerase chain reaction) which amplifies the DNA which can be analysed to see if there is mycobacterium DNA
Blood test for anti mycobacterium antibodies
Most common test is the mantoux skin test which involves mycobacterial antigens being injected under the skin provoking an immune response
The size of the area of inflammation (called an induration) is a measure of the exposure to the TB
What is the vaccine used to protect against TB?
BCG
This is an attenuated bovine TB strain which does not cause disease
What is DOTS?
Directly observed treatment short course
Aimed at ensuring patients complete their treatment
Lack of completion causes drug resistance
