Plasmodium AV

Question 1

What are the species of Plasmodium falciparum that infect humans?

Answer 1

malariae
vivax
falciparum
ovale
(knowlesi)

Question 2

The species of Plasmodium tend to have what type of tropism?

Answer 2

They tend to have a limited host tropism

Question 3

Which species of Plasmodium have shown a wider host tropism?

Answer 3

Knowlesi and falciparum
Knowlesi is a simian malaria in Asia, has been seen to infect humans in Malaysia and Thailand
Falciparum has been seen to infect gorillas in Africa

Question 4

How is infection with Plasmodium similar to infection with Trypanosomes?

Answer 4

Causes relapsing fever

Causes cyclic fever

Question 5

What is associated with severe malaria?

Answer 5

Sequestration of erythrocytes:
Cytoadherence of erythrocytes
Rosetting of erythrocytes
Platelet mediated clumping

Question 6

Where can sequestration of erythrocytes occur?

Answer 6

In vital organs including the brain, heart and lungs

Question 7

What are consequences of erythrocyte sequestration?

Answer 7

Can lead to microvascular occlusion
Capillaries and other blood vessels can become blocked which can lead to hypoxia (lack of oxygen reaching tissues) and anaerobic glycolysis (build up of lactic acid). This may make it difficult for individuals to breathe

Question 8

Why is erythrocyte sequestration beneficial to Plasmodium?

Answer 8

It is beneficial as when Plasmodium infects erythrocytes it can cause them to become rigid. These altered parasitised erythrocytes can be recognised and removed by the spleen. Sequestration prevents the transport of the infected erythrocytes to the spleen

Question 9

What mediates the sequestration of the erythrocytes?

Answer 9

PfEMP1

Plasmodium falciparum erythrocyte membrane protein 1

Question 10

What type of protein is PfEMP1?

Answer 10

Parasite encoded adhesive protein

Question 11

Where is PfEMP1 found?

Answer 11

Found on the surface of erythrocytes at electron dense knobs

Question 12

What forms the electron dense knobs?

Answer 12

KAHRP

PfEMP2

Question 13

KAHRP stands for?

Answer 13

Knob-Associated Histone Rich Protein

Question 14

How is it thought KAHRP and PfEMP2 can help to form the knobs?

Answer 14

Through interaction with the submembrane cytoskeleton of the erythrocyte

Question 15

The C terminus of PfEMP1?

Answer 15

Interacts with KAHRP and PfEMP2

Question 16

PfEMP1 is encoded by?

Answer 16

var genes

Question 17

How many var genes are there?

Answer 17

There are around 60 var genes

Question 18

PfEMP1 is expressed in which fashion?

Answer 18

In a monoallelic fashion

Question 19

The different PfEMP1 variants recognise and bind different?

Answer 19

Endothelial receptors

Question 20

PfEMP1 variant involved in placental malaria recognises which receptor?

Answer 20

GAG

Glycosaminoglycan CSA: Chondroitin Sulfate A

Question 21

What is rosetting and what is beneficial about rosetting?

Answer 21

Rosetting is when uninfected erythrocytes surround parasitised erythrocytes. This is beneficial as it may protect the parasitised erythrocytes from immune responses such as innate immune responses

Question 22

Summarise the immune evasion strategies of P.falciparum?

Answer 22

• Intracellular parasite
• Can switch PfEMP1 variant, antigenic variation
• Rosetting
• Cytoadherence to the endothelial cells

Question 23

Where are the var genes located the majority of the time?

Answer 23

Located at subtelomeres

Question 24

Where are some of the var genes located?

Answer 24

Central region of the chromosome

Question 25

Where can the var genes be located?

Answer 25

Either at the central region of the chromosome | At subtelomeres

Question 26

What is good about gene location at telomerees?

Answer 26

Telomeres are highly recombinogenic genomic regions | This means they can generate high levels of diversity

Question 27

In P. falciparum the telomeres are?

Answer 27

Clustered

Question 28

What is the benefit of clustered telomeres?

Answer 28

Clustering increases the recombination that occurs

Question 29

Where are the var genes located in the nucleus?

Answer 29

Both the telomeric var genes and those located in the central chromosomal regions are present in the nuclear periphery

Question 30

Where are the silent var genes located?

Answer 30

In repressive regions of the nuclear periphery where levels of heterochromatin are high. Epigenetic modifications lead to repression of var genes.

Question 31

How are var genes activated?

Answer 31

Movement in the nuclear periphery | Translocation from the repressive centres to transcriptionally permissive regions of the nucleus

Question 32

When is the active PfEMP1 variant expressed at high levels, when does high level of var gene transcription occur?

Answer 32

High levels of var gene transcription occurs in the early ring stage of infection

Question 33

When does PfEMP1 transcription stop?

Answer 33

Towards the later blood-stages of infection

Question 34

What is the poised state?

Answer 34

It is when a var gene is no longer transcriptionally active but is ready for activation in the next cycle

Question 35

What does the poised state ensure?

Answer 35

The poised state ensures that the same var gene (and so PfEMP1) is expressed in subsequent rounds of infection

Question 36

What is a nucleosome made up of?

Answer 36

A nucleosome is made up of DNA wrapped around an octamer of histones

Question 37

What is euchromatin?

Answer 37

This is the beads-on-a-string model | This is transcriptionally active chromatin

Question 38

What is heterochromatin?

Answer 38

Transcriptionally inactive Many histones Densely and tightly packed

Question 39

Silenced var genes what type of chromatin?

Answer 39

Heterochromatin

Question 40

Histones can be modified where?

Answer 40

The histone tails can be modified

Question 41

What type of epigenetic modifications can be performed on histone tails?

Answer 41

Acetylation Methylation Phosphorylation

Question 42

Which epigenetic histone modification is associated with var gene silencing?

Answer 42

var gene silencing is associated with methylation of a histone

Question 43

Methylation of which histone in particular?

Answer 43

H3K36