Wednesday, February 17, 2010

How TB challenges the host (Try answering)



I was attending a Colloquim on Innate Immunity in Johannesburg on Monday and Tueday 15-16 Feb and here is a scenario that you will find interesting. The figure above shows how TB is attacked by the cells of the immune system in an attempt to kill it. TLR4 is a protein on cells and it binds TB bacteria using the extracellular component and once this is achieved, Protein A binds the intracellular domain of TLR-4, leading to internalization and killing of TB.

Try these Questions:
1. Which of the two strains of TB is likely to be killed in this way. Study the amino acid composition of the structures to make your argument.
2. TLR4 has 3 components: the extracellular domain, transmembrane domain, and intracellular domain. Each of the domains has different amino acid composition. Can you comment on the relevance of these differences in structure.
3. TB is ultimately supposed to be killed by an enzyme called Lysozyme at pH2. If lysozyme is rich in Tryptophan, why would a pH of 2 be required?
4. What type of amino acids would you expect to find dominating Protein A.
5. If you were to design a drug that could directly kill TB, what kind of drug would you design (look at the amino acid composition of TB to guide you).

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