Lecture 17 Flashcards
Why isn’t there communal immunity to the 60 variants of the PfEMP1 protein?
There is variation within the 60 copies
This is due to ectopic recombination
Recombination between heterologous chromosomes is Malaria’s way of
generating rapid diveristy in var genes
Chromosomes are usually found in _ clusters with Malaria cells
4
The alignment of genes in groups of 4-5 allows for…..
ectopic recombination
True or False
Every time there is a blood life cycle of Malaria there is more recombination going on that normal amounts.
Leads to different looking var genes
True
Plasmodium parasites export 100’s of proteins into RBC cytosol, What is their main role?
Crucial virulence and nutrient uptake roles
An example of plasmodium protein is KAHRP, when knocked out…
cells were smooth
parasites don’t adhere to vascular endothelium
can’t hold on in physiological flow pressure
An example of the importance of exporter proteins, one of hundreds
The PEXEL motif (a string of AAs) is a…
cleavage site that is recognised in the ER by an enzyme known as Plasmepsin V
___% of exported genes are essential to growth (can’t be knocked out)
25%
If the cleavage occurred in the ER, by PEXEL, proteins follow a very particular _____ pathway and dumped their proteins into a specific place
If the cleavage occured in the ER, by PEXEL, proteins follow a very particular vesicular pathway and dumped their proteins into a specific place
What are the essential things of a putative Plasmodium translocon of PEXEL proteins = PTEX?
(PTEX is the machinery PEXEL proteins recognise on the parasite membrane)
Plasmodium specific and in the correct location
Essential to blood-stages
Energy source, an un-folding mechanism
Binds transiting cargo PEXEL proteins
EXP2 forms the ___ of PTEX
pore
Anti-malarial drugs can target >..
PTEX
What are the 3 types of Malarial vaccines in development?
- Pre-erythocytic (prevent infecting the liver). RTS,S is on phase 3 clinical trial
- Transmission blocking - to protect mosquito, gives antibodies to mosquito when it bites
- Blood- - Anti-meroziote antibodies
True or False
Different Plasmodium species prefer different RBCs
True
Plasmodium _______ recognises all RBCs, old and young - not all like all other species of Malaraia
Plasmodium falciparum recognises all RBCs, old and young - not all like all other species of Malaraia
parasite Cells are outside of other cells for about ____ during invasion
1.5 minutes
Looking at Blood-stage vaccine
Antigens have been idnetified but _____ is not well known for each
function
The RBC surface us highly _______
polymorphic - very hereogenous
e.g none of west africe expresses the Duffy glycoprotein, the rest of the world does
Duffy glycoprotein, essential for plasmodium vivax to…
enter RBCs
Instead of just one or two secondary ligands bein responsible for binding RBCs there are at least _
8
Plasmodium falciparum however has a lot of different _____ that can bind to different receptors
Ligands
True or False
Parasites can switch their invasion henotype, can alter receptor/ligand usage
True
What happens if you delete the ligand EBA175 used by W2mef?
You get a transcriptional switch, no longer expresses EBA175, it expresses another evasion ligand called Rh4
True or False
A single parasite, genetically identical, can switch the ligand it expresses to enter RBCs
True
The different ligands ecode for different receptor binding characteristics - this is a problem for…
vaccine development
Alternate invasion pathways allow parasites to invade via a diverse range of RBC receptors and to avoid ________
immunity
EBA and Rh proteins are important targets of inhibitory ________
antibodies
At least _ pathways for invasion need to be covered for a vaccine to work
3
