Vl 8 Plasmodium II

Question 1

How does the Plasmodium merozoite enter an erythrocyte?

Answer 1

1) randomly binds to erythrocyte
2) reorientates⇒ apical complex in proximity to erythrocyte membrane, junction formation
3) parasitous vacuole formation (releasing parasitic proteins from rhoptries and micronemes and shedding of parasite and host cell surface proteins from the membrane)
4) invasion (driven inward by actin-myosin motor)
5) pinching of junction, sheds surface coat

Question 2

Describe the Avexis approach to identify erythrocyte ligands for merozoite invasion

Answer 2

we know: erythrocyte surface ligands bind to parasite surface proteins or other

Avexis: approach with pentamer “antibodies”⇒ strengthened protein interaction can be verified with them⇒ they are tested independently in a screening plate

Question 3

What are problems with anti-merozoite vaccine approaches? Explain.

Answer 3

merozoites invade very fast = only shortly extracellular

merozoite antigens trigger strong antibody responses but do not protect yet

multiple merozoite invasion pathways (e.g. disposable dafi binding proteins)

⇒ have multiple immune evasion strategies: varying sequence while maintaining function, redundancy in multi gene families, reduced antigenicity

Question 4

How do liver stages induce protective immune responses and how are they killed?

Answer 4

Before sporozoite enters hepatocyte: excreted antigens recognized by toll like receptors⇒ can induce NFKB and NO production, killing the exoerythrocytic form (EEF) of plasmodium

sporozoite inside hepatic cell: cell can present antigen to CD8 T-cells via MHC1

at exit of mature EEF from hepatocyte:
-excreted antigens recognized by dendritic cells ⇒ recruit cytotoxic and helper T-cells to kill parasites