Lecture 17

Question 1

Why isn’t there communal immunity to the 60 variants of the PfEMP1 protein?

Answer 1

There is variation within the 60 copies

This is due to ectopic recombination

Question 2

Recombination between heterologous chromosomes is Malaria’s way of

Answer 2

generating rapid diveristy in var genes

Question 3

Chromosomes are usually found in _ clusters with Malaria cells

Answer 3

4

Question 4

The alignment of genes in groups of 4-5 allows for…..

Answer 4

ectopic recombination

Question 5

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

Answer 5

True

Question 6

Plasmodium parasites export 100’s of proteins into RBC cytosol, What is their main role?

Answer 6

Crucial virulence and nutrient uptake roles

Question 7

An example of plasmodium protein is KAHRP, when knocked out…

Answer 7

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

Question 8

The PEXEL motif (a string of AAs) is a…

Answer 8

cleavage site that is recognised in the ER by an enzyme known as Plasmepsin V

Question 9

___% of exported genes are essential to growth (can’t be knocked out)

Answer 9

25%

Question 10

If the cleavage occurred in the ER, by PEXEL, proteins follow a very particular _____ pathway and dumped their proteins into a specific place

Answer 10

If the cleavage occured in the ER, by PEXEL, proteins follow a very particular vesicular pathway and dumped their proteins into a specific place

Question 11

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)

Answer 11

Plasmodium specific and in the correct location

Essential to blood-stages

Energy source, an un-folding mechanism

Binds transiting cargo PEXEL proteins

Question 12

EXP2 forms the ___ of PTEX

Answer 12

pore

Question 13

Anti-malarial drugs can target >..

Answer 13

PTEX

Question 14

What are the 3 types of Malarial vaccines in development?

Answer 14

1. Pre-erythocytic (prevent infecting the liver). RTS,S is on phase 3 clinical trial
2. Transmission blocking - to protect mosquito, gives antibodies to mosquito when it bites
3. Blood- - Anti-meroziote antibodies

Question 15

True or False

Different Plasmodium species prefer different RBCs

Answer 15

True

Question 16

Plasmodium _______ recognises all RBCs, old and young - not all like all other species of Malaraia

Answer 16

Plasmodium falciparum recognises all RBCs, old and young - not all like all other species of Malaraia

Question 17

parasite Cells are outside of other cells for about ____ during invasion

Answer 17

1.5 minutes

Question 18

Looking at Blood-stage vaccine

Antigens have been idnetified but _____ is not well known for each

Answer 18

function

Question 19

The RBC surface us highly _______

Answer 19

polymorphic - very hereogenous

e.g none of west africe expresses the Duffy glycoprotein, the rest of the world does

Question 20

Duffy glycoprotein, essential for plasmodium vivax to…

Answer 20

enter RBCs

Question 21

Instead of just one or two secondary ligands bein responsible for binding RBCs there are at least _

Answer 21

8

Question 22

Plasmodium falciparum however has a lot of different _____ that can bind to different receptors

Answer 22

Ligands

Question 23

True or False

Parasites can switch their invasion henotype, can alter receptor/ligand usage

Answer 23

True

Question 24

What happens if you delete the ligand EBA175 used by W2mef?

Answer 24

You get a transcriptional switch, no longer expresses EBA175, it expresses another evasion ligand called Rh4

Question 25

True or False

A single parasite, genetically identical, can switch the ligand it expresses to enter RBCs

Answer 25

True

Question 26

The different ligands ecode for different receptor binding characteristics - this is a problem for…

Answer 26

vaccine development

Question 27

Alternate invasion pathways allow parasites to invade via a diverse range of RBC receptors and to avoid ________

Answer 27

immunity

Question 28

EBA and Rh proteins are important targets of inhibitory ________

Answer 28

antibodies

Question 29

At least _ pathways for invasion need to be covered for a vaccine to work

Answer 29

3