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Parasitology > Plasmodium AV > Flashcards

Plasmodium AV Flashcards

1
Q

What are the species of Plasmodium falciparum that infect humans?

A 
malariae
vivax
falciparum
ovale
(knowlesi)
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2
Q

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

A

They tend to have a limited host tropism

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3
Q

Which species of Plasmodium have shown a wider host tropism?

A

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

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4
Q

How is infection with Plasmodium similar to infection with Trypanosomes?

A

Causes relapsing fever

Causes cyclic fever

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5
Q

What is associated with severe malaria?

A

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

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6
Q

Where can sequestration of erythrocytes occur?

A

In vital organs including the brain, heart and lungs

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7
Q

What are consequences of erythrocyte sequestration?

A

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

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8
Q

Why is erythrocyte sequestration beneficial to Plasmodium?

A

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

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9
Q

What mediates the sequestration of the erythrocytes?

A

PfEMP1

Plasmodium falciparum erythrocyte membrane protein 1

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10
Q

What type of protein is PfEMP1?

A

Parasite encoded adhesive protein

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11
Q

Where is PfEMP1 found?

A

Found on the surface of erythrocytes at electron dense knobs

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12
Q

What forms the electron dense knobs?

A

KAHRP

PfEMP2

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13
Q

KAHRP stands for?

A

Knob-Associated Histone Rich Protein

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14
Q

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

A

Through interaction with the submembrane cytoskeleton of the erythrocyte

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15
Q

The C terminus of PfEMP1?

A

Interacts with KAHRP and PfEMP2

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16
Q

PfEMP1 is encoded by?

A

var genes

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17
Q

How many var genes are there?

A

There are around 60 var genes

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18
Q

PfEMP1 is expressed in which fashion?

A

In a monoallelic fashion

19
Q

The different PfEMP1 variants recognise and bind different?

A

Endothelial receptors

20
Q

PfEMP1 variant involved in placental malaria recognises which receptor?

A

GAG

Glycosaminoglycan CSA: Chondroitin Sulfate A

21
Q

What is rosetting and what is beneficial about rosetting?

A

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

22
Q

Summarise the immune evasion strategies of P.falciparum?

A
  • Intracellular parasite
  • Can switch PfEMP1 variant, antigenic variation
  • Rosetting
  • Cytoadherence to the endothelial cells
23
Q

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

A

Located at subtelomeres

24
Q

Where are some of the var genes located?

A

Central region of the chromosome

25
Q

Where can the var genes be located?

A

Either at the central region of the chromosome

At subtelomeres

26
Q

What is good about gene location at telomerees?

A

Telomeres are highly recombinogenic genomic regions

This means they can generate high levels of diversity

27
Q

In P. falciparum the telomeres are?

A

Clustered

28
Q

What is the benefit of clustered telomeres?

A

Clustering increases the recombination that occurs

29
Q

Where are the var genes located in the nucleus?

A

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

30
Q

Where are the silent var genes located?

A

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

31
Q

How are var genes activated?

A

Movement in the nuclear periphery

Translocation from the repressive centres to transcriptionally permissive regions of the nucleus

32
Q

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

A

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

33
Q

When does PfEMP1 transcription stop?

A

Towards the later blood-stages of infection

34
Q

What is the poised state?

A

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

35
Q

What does the poised state ensure?

A

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

36
Q

What is a nucleosome made up of?

A

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

37
Q

What is euchromatin?

A

This is the beads-on-a-string model

This is transcriptionally active chromatin

38
Q

What is heterochromatin?

A

Transcriptionally inactive
Many histones
Densely and tightly packed

39
Q

Silenced var genes what type of chromatin?

A

Heterochromatin

40
Q

Histones can be modified where?

A

The histone tails can be modified

41
Q

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

A

Acetylation
Methylation
Phosphorylation

42
Q

Which epigenetic histone modification is associated with var gene silencing?

A

var gene silencing is associated with methylation of a histone

43
Q

Methylation of which histone in particular?

A

H3K36

Parasitology (17 decks)

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