Plasmodium AV Flashcards
What are the species of Plasmodium falciparum that infect humans?
malariae vivax falciparum ovale (knowlesi)
The species of Plasmodium tend to have what type of tropism?
They tend to have a limited host tropism
Which species of Plasmodium have shown a wider host tropism?
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
How is infection with Plasmodium similar to infection with Trypanosomes?
Causes relapsing fever
Causes cyclic fever
What is associated with severe malaria?
Sequestration of erythrocytes:
Cytoadherence of erythrocytes
Rosetting of erythrocytes
Platelet mediated clumping
Where can sequestration of erythrocytes occur?
In vital organs including the brain, heart and lungs
What are consequences of erythrocyte sequestration?
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
Why is erythrocyte sequestration beneficial to Plasmodium?
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
What mediates the sequestration of the erythrocytes?
PfEMP1
Plasmodium falciparum erythrocyte membrane protein 1
What type of protein is PfEMP1?
Parasite encoded adhesive protein
Where is PfEMP1 found?
Found on the surface of erythrocytes at electron dense knobs
What forms the electron dense knobs?
KAHRP
PfEMP2
KAHRP stands for?
Knob-Associated Histone Rich Protein
How is it thought KAHRP and PfEMP2 can help to form the knobs?
Through interaction with the submembrane cytoskeleton of the erythrocyte
The C terminus of PfEMP1?
Interacts with KAHRP and PfEMP2
PfEMP1 is encoded by?
var genes
How many var genes are there?
There are around 60 var genes
PfEMP1 is expressed in which fashion?
In a monoallelic fashion
The different PfEMP1 variants recognise and bind different?
Endothelial receptors
PfEMP1 variant involved in placental malaria recognises which receptor?
GAG
Glycosaminoglycan CSA: Chondroitin Sulfate A
What is rosetting and what is beneficial about rosetting?
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
Summarise the immune evasion strategies of P.falciparum?
- Intracellular parasite
- Can switch PfEMP1 variant, antigenic variation
- Rosetting
- Cytoadherence to the endothelial cells
Where are the var genes located the majority of the time?
Located at subtelomeres
Where are some of the var genes located?
Central region of the chromosome
Where can the var genes be located?
Either at the central region of the chromosome
At subtelomeres
What is good about gene location at telomerees?
Telomeres are highly recombinogenic genomic regions
This means they can generate high levels of diversity
In P. falciparum the telomeres are?
Clustered
What is the benefit of clustered telomeres?
Clustering increases the recombination that occurs
Where are the var genes located in the nucleus?
Both the telomeric var genes and those located in the central chromosomal regions are present in the nuclear periphery
Where are the silent var genes located?
In repressive regions of the nuclear periphery where levels of heterochromatin are high. Epigenetic modifications lead to repression of var genes.
How are var genes activated?
Movement in the nuclear periphery
Translocation from the repressive centres to transcriptionally permissive regions of the nucleus
When is the active PfEMP1 variant expressed at high levels, when does high level of var gene transcription occur?
High levels of var gene transcription occurs in the early ring stage of infection
When does PfEMP1 transcription stop?
Towards the later blood-stages of infection
What is the poised state?
It is when a var gene is no longer transcriptionally active but is ready for activation in the next cycle
What does the poised state ensure?
The poised state ensures that the same var gene (and so PfEMP1) is expressed in subsequent rounds of infection
What is a nucleosome made up of?
A nucleosome is made up of DNA wrapped around an octamer of histones
What is euchromatin?
This is the beads-on-a-string model
This is transcriptionally active chromatin
What is heterochromatin?
Transcriptionally inactive
Many histones
Densely and tightly packed
Silenced var genes what type of chromatin?
Heterochromatin
Histones can be modified where?
The histone tails can be modified
What type of epigenetic modifications can be performed on histone tails?
Acetylation
Methylation
Phosphorylation
Which epigenetic histone modification is associated with var gene silencing?
var gene silencing is associated with methylation of a histone
Methylation of which histone in particular?
H3K36
