Plasmodia and Disease Flashcards
What are the common symptoms of malarial infection?
Fever
Anaemia
Cerebral Syndrome
What causes fever?
Host cell immune response to merozoite release. Things like TNF and IL-6. Mainly from macrophage origin.
What is the role of fever?
It increases T and B cell proliferation and kills immature parasite stages (which is why infections become synchronous). It stops the parasite populaiton becoming too large and overwhelming the host.
How does aneamia relate to parasitaemia in plasmodial infection?
It doesnt seem too. Often parasitaemia is quite low.
What factors contribute to anaemia?
Anti-erythrocyte IgM production
Bone marrow depression and subsequent supression of reticulocytosis.
Rosetting - healthy blood cells bind to infected which are then cleared by immune system.
What is thought to cause cerebral malaria?
Why is this?
Macrophage activation leading to a cytokine storm (TNF IL1 and IL6)
TNF used to treat cancer patients produces similar syndrome.
How do cytokines interfere with the brain?
Disrupts the HPA axis
Affects neurons and neurotransmitters
What is the older theory of cerebral malaria?
Binding of infected RBCs to endothelial cells in the brain causes obstruction to cerebral blood flow.
Why is the vascular obstruction theory unlikely to be completely true?
There are no stroke like symptoms and cerebral malaria sufferers often recover.
Why might the two theories of cerebral malaria be linked?
Endothelium can be activated by cytokines that up regulate adhesion molecules.
Why is CSP not a great vaccine candidate?
It is only found on sporozoites and not on any of the later blood stages.
How could a vaccine against the liver stage of the parasite be useful?
CTLs could ‘buy the immune system so time’ to develop resistance to the blood stages by preventing merozoite release.
What are the problems with vaccinating against MSP?
Monoclonal antibodies can protect against it but dont seem to be produced in human disease.
The antibody levels would have to be very high as the invasion of erythrocytes is very quick.
What are the advantages of invading erythrocytes?
Steady supply of new cells.
They contain haemoglobin (food)
No nucleus so no stress response to invasion.
No MHC so cant be targetted by CTLs
Why is anti toxin therapy not a long term solution?
Toxins are phospholipids so do not interact with MHC complexes so do not stimulate T cells. Therefore the response is short lived (only stimulates B cells) and will not stimulate memory responses.
