Plasmodia Immune Evasion Flashcards
What are the methods by which plasmodia evade the immune response?
Intracellular parasitism Erythrocyte adherance Antigenic Diversity 'Smokescreen Antigens' Antigenic Variation Immune Suppression
What do plasmodia evade by being within a cell?
Plasmatoid dendritic cells - found in spleen
Antibodies
MHC epitope hiding
What is the role of PfEMP1?
It prevents the erythrocyte moving around the body thus evading the liver and the spleen and preventing it from being detected by immune cells.
How do plasmodia vary their essential surface proteins?
They vary the regions that do not need to be conserved.
What are two examples of proteins that plasmodia can vary?
Merozoite surface antigen 1 (MSP-1)
Apical membrane antigen 1 (AMA-1)
What is the role of AMA-1?
It is secreted at the beggining of the host cell invasion process, which it is essential for.
How doe the plasmodia escape immune killing by varying AMA-1?
It has antigenic escape residues that can change to escape the immune response.
Give an example of a smokescreen antigen and how does it work?
Circupsporozoite protein (CSP). They are very immunogenic but not immunoprotective. They can divert the immune response away from essential proteins.
What is the role of PfEMP-1?
It forms “knob” structures with other parasite proteins on the surface of RBCs that allows the infected RBC to attach to other cells.
What is the structure of PfEMP-1?
Exon 1 - highly variable - exposed
Exon 2 - conserved cytoplasmic tail
What are var genes and where are they located?
They are the PfEMP-1 genes. Located sub-telomerically and centrally.
How many var genes are expressed at a time?
1 per parasite/erythrocyte.
What are the mechanisms of var gene control?
Transcriptional control
Epigenetics
What is SIR2 and what is its function?
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.
Is PfEMP1 a good vaccine target?
It is essential for parasite function and associated with pathology. It also has conserved regions. However, it is also highly polymorphic.
How does plasmodia gene transcriptional control differ to that of T. brucei?
Subtelomeric OR central expression site
Monocistronic
RNA Pol 2 rather than pol1
Are there other proteins that are variable?
Repetitive interspersed family proteins (RIFINs)
Subtelomeric variant open reading frame (STEVORs)
What does variation/non-variation in these protein imply?
Non-variation implies it has a highly conserved function or is not very visible to the immune system.
What are the methods by which plasmodia supresses the immune system?
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.
What are the candidates for vaccine development and their problems?
Sporozoite/Liver - CSP a promising candidate
Blood - AMA1 MSP1 induce solid immune protection but are allele specific.
Sexual stages - TBVs
What is the danger of vaccinating with a subunit vaccine?
Antigenic escape may increase a parasites virulence.
