Vl 8 Plasmodium II Flashcards
How does the Plasmodium merozoite enter an erythrocyte?
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
Describe the Avexis approach to identify erythrocyte ligands for merozoite invasion
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
What are problems with anti-merozoite vaccine approaches? Explain.
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
How do liver stages induce protective immune responses and how are they killed?
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