T.bruci AV Flashcards
What is the name of the African trypanosome?
T.brucei
What are the two forms of T.brucei?
T.brucei rhodesiense
T.brucei gambiense
Which form of T.brucei is the West African form?
T.brucei gambiense
Which form of T.brucei is the East African form?
T.brucei rhodesiense
Which form of T.brucei has an extensive reservoir in ungulates?
Rhodesiense
East African?
Rhodesiense
West African?
Gambiense
Which form of T.brucei primarily infects humans?
Gambiense
Are the East and West African forms morphologically distinguishable?
No
Lifecycle stages?
1) Metacyclic trypomastigotes are injected
2) Form blood stream trypomastigotes
3) Binary fission
4) Taken up by tsetse fly and become procyclic trypomastigotes in the midgut
5) Binary fission
6) Become epimastigotes as they leave the midgut, move to the salivary gland
7) Binary fission
8) Becomes metacyclic trypomastigotes
How many stages of infection are there?
Two
What occurs in the first stage of infection?
There is cyclic/relapsing fever
What occurs in the second stage of infection?
There is penetration of the blood-brain barrier, they infect the CNS
What are the symptoms of the second stage of infection?
Confusion
Loss of coordination
Interruption of sleep cycle
What disease does T.brucei cause?
Sleeping sickness
What is the antigenic variant present?
VSG
VSG stands for?
Variant Surface Glycoprotein
VSG is attached via a?
Lipid GPI anchor
Which form is VSG coat not present in?
The procylic form
What does the procyclic form have?
A procyclin invariant coat
VSGs all share a?
Conserved tertiary structure
VSG coat is internalised every?
12 minutes
Where does endocytosis occur?
Flagellar pocket
The movement of T.brucei generates?
Hydrodynamic forces
What do the hydrodynamic forces do?
They cause the rearward translocation of VSG
VSG antibody complexes move towards the flagellar pocket faster as?
The antibody acts as a sail
What is the flagellar pocket?
It is where the flagellum emerges
It is where endocytosis takes place
It is a membrane invagination
What is located posterior to the flagellar pocket, flagellum and basal bodies?
Kinetoplast DNA
VSG expression sites are located where?
At telomeres
What are VSG bloodstream expression sites?
Polycistronic transcriptional units
VSG bloodstream ES are located where?
Telomeres
VSG bloodstream ES encode?
VSG gene
ESAGs
ESAGs?
Expression Site Associated Genes
Expression sites are transcribed by?
RNA Pol I
How can VSG expression be switched?
- Expression site switch
- Telomere exchange
- Duplicative gene conversion
- Segmental gene conversion
What does duplicative gene conversion require?
5’ homology = 70bp repears
3’ homology= part of VSG, conserved 3’ region of VSG genes
How many VSG genes and pseudogenes are there?
> 1500
What produces chimaeric/mosaic VSG?
Segmental gene conversion
What are telomeres?
Highly recombinogenic regions of the genome
Where can VSG genes be located?
ES sites
Telomeres
Subtelomeres
What is always located at the telomeres?
VSG expression sites (ES)
Switching from one variant is not random as there is a?
Preferential hierarchy of VSG activation, switch is not a random process
What are the mechanisms of T.brucei immune evasion?
- Dense VSG coat
- Sheltering invariant surface receptors
- Invariant surface receptors in the flagellar pocket
- Coat cleaning
- Antigenic variation
Metacyclic trypomastigotes express what and why?
VSG in preparation for entry into humans
How many MC-ES?
~25
Similarities between B-ES and M-ES?
Both telomeric
Both transcribed by RNA Pol I
Main difference between M-ES and B-ES?
M-ES has ~25 ES Promoter directly upstream of VSG gene No ESAGs, only VSG is expressed Inefficient/no gene conversion due to the lack of 70bp repeats Monocistronic
B-ES is?
A polycistronic transcriptional unit
M-ES is?
A monocistronic transcriptional unit