Plasmodia Immune Evasion

Question 1

What are the methods by which plasmodia evade the immune response?

Answer 1

Intracellular parasitism
Erythrocyte adherance
Antigenic Diversity
'Smokescreen Antigens'
Antigenic Variation
Immune Suppression

Question 2

What do plasmodia evade by being within a cell?

Answer 2

Plasmatoid dendritic cells - found in spleen
Antibodies
MHC epitope hiding

Question 3

What is the role of PfEMP1?

Answer 3

It prevents the erythrocyte moving around the body thus evading the liver and the spleen and preventing it from being detected by immune cells.

Question 4

How do plasmodia vary their essential surface proteins?

Answer 4

They vary the regions that do not need to be conserved.

Question 5

What are two examples of proteins that plasmodia can vary?

Answer 5

Merozoite surface antigen 1 (MSP-1)

Apical membrane antigen 1 (AMA-1)

Question 6

What is the role of AMA-1?

Answer 6

It is secreted at the beggining of the host cell invasion process, which it is essential for.

Question 7

How doe the plasmodia escape immune killing by varying AMA-1?

Answer 7

It has antigenic escape residues that can change to escape the immune response.

Question 8

Give an example of a smokescreen antigen and how does it work?

Answer 8

Circupsporozoite protein (CSP). They are very immunogenic but not immunoprotective. They can divert the immune response away from essential proteins.

Question 9

What is the role of PfEMP-1?

Answer 9

It forms “knob” structures with other parasite proteins on the surface of RBCs that allows the infected RBC to attach to other cells.

Question 10

What is the structure of PfEMP-1?

Answer 10

Exon 1 - highly variable - exposed

Exon 2 - conserved cytoplasmic tail

Question 11

What are var genes and where are they located?

Answer 11

They are the PfEMP-1 genes. Located sub-telomerically and centrally.

Question 12

How many var genes are expressed at a time?

Answer 12

1 per parasite/erythrocyte.

Question 13

What are the mechanisms of var gene control?

Answer 13

Transcriptional control

Epigenetics

Question 14

What is SIR2 and what is its function?

Answer 14

Silent Information Regulator Protein 2. It deacytylates promotor sequences which silences them by causing them to cluster together. Active sequences are seperate from the cluster.

Question 15

Is PfEMP1 a good vaccine target?

Answer 15

It is essential for parasite function and associated with pathology. It also has conserved regions. However, it is also highly polymorphic.

Question 16

How does plasmodia gene transcriptional control differ to that of T. brucei?

Answer 16

Subtelomeric OR central expression site
Monocistronic
RNA Pol 2 rather than pol1

Question 17

Are there other proteins that are variable?

Answer 17

Repetitive interspersed family proteins (RIFINs)

Subtelomeric variant open reading frame (STEVORs)

Question 18

What does variation/non-variation in these protein imply?

Answer 18

Non-variation implies it has a highly conserved function or is not very visible to the immune system.

Question 19

What are the methods by which plasmodia supresses the immune system?

Answer 19

PfEMP1 binding to CD36 can induce APC maturational arrest and therefore poor t cell stimulation

They create a macrophage migration inhibitory factor orthologue (MMIF)

T cell response is biased towards short lived CD4 responses with impaired memory response.

Question 20

What are the candidates for vaccine development and their problems?

Answer 20

Sporozoite/Liver - CSP a promising candidate
Blood - AMA1 MSP1 induce solid immune protection but are allele specific.
Sexual stages - TBVs

Question 21

What is the danger of vaccinating with a subunit vaccine?

Answer 21

Antigenic escape may increase a parasites virulence.