PaBi (14): Immunity to malaria Flashcards
Where do sporozoites go after initial injection by mosquito?
Into the bloodstream or lymphatics to migrate to the liver but most sporozoites don’t make it out of the skin
How do sporozoites invade the liver cells?
Through Kupffer cell, liver macrophages
How do sporozoites avoid an immune response when invading the liver?
They kill Kupffer cells with SPECT2 which is a membrane attack complex. This avoids activating the innate immune system.
What is the T cell response to Plasmodium infection?
Cytotoxic T cells are activated by sporozoites in the lymph node and kill infected hepatocytes through the classical pathway, by releasing granzymes and perforins.
Give two examples of adhesin proteins that are important for Plasmodium cell invasion?
Circumsporozoite protein and TRAP
Why is sterilising immunity to malaria never acquired?
Because a very small number of sporozoites infect the liver so it is very hard to find them all- would need a huge number of CD8+ T cells to search the entire liver for infected cells. Tregs may suppress the immune response and promote tolerance to sporozoites.
What are the pros and cons of the liver stage as the target for vaccine development?
There are very few parasites to get rid of but if you miss even one infected cell you have no immunity to the blood stage
What is the immune response to blood stage malaria?
APCs can recognise the GPI anchor, haemozoin and A-T rich DNA. Macrophages are activated and can phagocytose and produce NO and TNFalpha to kill infected cells but this also causes the malaria fever spike. NK cells and helper T cells produce IFNgamma to stimulate macrophages and Th cells also produce IL-10 to prevent the immune system getting out of control.
What causes anaemia in severe malaria?
Destruction of infected and uninfected erythrocytes (for every iRBC destroyed, 10 uninfected RBCs are detroyed) and suppression of erythropoiesis by TNFalpha and IFNgamma
What is the antibody response to blood stage malaria?
Inhibits merozoite invasion, opsonises merozoites and iRBCs, reduces sequestration and inhibits parasite toxins e.g. GPI anchors to decrease inflammation.
What blood stage surface antigens did people focus on for vaccine development and what are the pros and cons?
Merozoite surface protein 1 (MSP1), apical membrane antigen 1 (AMA) and PfEMP1- these are all highly immunogenic but very polymorphic. Reticulocyte-binding protein homologue 5 (RH5) is very conserved but not particularly immunogenic.
