Trypanosomiasis Flashcards
What is the causative agent of trypanosomiasis?
Trypanosoma brucei (a kinetoplast)
What is the vector of trypanosomiasis?
Tsetse fly (Glossina spp.), lives in the heart of Africa
Why is trypanosomiasis difficult to immunise against?
Ultimately, all those infected die unless treated, so there is no natural immunity to try to mimic. Additionally, pharmaceutical companies are less prone to engage/invest in drug discovery/development against diseases that affect the poorest people
Describe the selection pressure that drives the immune evasion strategy of African trypanosomes
Since T. brucei is an extra-cellular parasite, it is continuously exposed to cellular and humoral immune system therefore, driving their immune evasion strategy
How does T. brucei evade the immune system?
By using antigenic variation of their variant surface glycoproteins (VSG). VSG molecules are expressed on the cell surface which creates a dense coat that prevents adaptive immunity from detecting or accessing invariant antigens
What is the host’s immune response to T. brucei infection?
B-cell mediated antibody response develops to the parasites’ VSG coat, eliminating most of the parasites from the bloodstream by complement-mediated lysis and opsonisation/phagocytosis.
1% of trypanosomes display an antigenically different VSG, thereby escaping the initial antibody response. Proliferation occurs and a new wave of parasitaemia is observed. Antigenic shift in VSG continues to occur. causing several subsequent waves of parasitaemia (characteristic of HAT)
In what way does antigenic variation succeed?
It prolongs the time that the parasite resides in the host, thereby enhancing transmission to a new host (via tsetse fly). It also allows trypanosomes to infect previously infected hosts
What is a GPI anchor?
A glycolipid that anchors the C-terminus of VSGs to the membrane bilayer
What is meant by antigenic variation?
Describes the existence of several forms of the same gene (var genes) within one organism [same lady, lots o dresses)
What is meant by allelic polymorphism
The existence of genetically stable alternative forms of antigen-coding genes but in different strains
What are both antigenic variation and allelic polymorphism used for?
Both are used to evade the immune system and can be generated by sexual recombination, or mutation and imperfect DNA repair mechanisms
What are VSG genes, and how many of these does the T. brucei genome contain?
A family of genes encoding antigenically distinct surface antigens. T. brucei genome contains 100s, sometimes >1000s of these
What are pseudogenes?
Silent (VSG) genes, organised in tandem arrays
Why must the cell express one variant antigen gene at a time?
To avoid exhausting the surface antigen repertoire
Where are VSG gene arrays located in the chromosome, and what is the significance of this?
VSG gene arrays are located in sub-telomeric regions. Telomeres are particularly recombinogenic areas so this makes them a good place to put genes where diversity needs to be generated (i.e. antigenic variation)
