PaBi (14): Immunity to malaria Flashcards

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1
Q

Where do sporozoites go after initial injection by mosquito?

A

Into the bloodstream or lymphatics to migrate to the liver but most sporozoites don’t make it out of the skin

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2
Q

How do sporozoites invade the liver cells?

A

Through Kupffer cell, liver macrophages

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3
Q

How do sporozoites avoid an immune response when invading the liver?

A

They kill Kupffer cells with SPECT2 which is a membrane attack complex. This avoids activating the innate immune system.

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4
Q

What is the T cell response to Plasmodium infection?

A

Cytotoxic T cells are activated by sporozoites in the lymph node and kill infected hepatocytes through the classical pathway, by releasing granzymes and perforins.

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5
Q

Give two examples of adhesin proteins that are important for Plasmodium cell invasion?

A

Circumsporozoite protein and TRAP

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6
Q

Why is sterilising immunity to malaria never acquired?

A

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.

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7
Q

What are the pros and cons of the liver stage as the target for vaccine development?

A

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

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8
Q

What is the immune response to blood stage malaria?

A

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.

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9
Q

What causes anaemia in severe malaria?

A

Destruction of infected and uninfected erythrocytes (for every iRBC destroyed, 10 uninfected RBCs are detroyed) and suppression of erythropoiesis by TNFalpha and IFNgamma

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10
Q

What is the antibody response to blood stage malaria?

A

Inhibits merozoite invasion, opsonises merozoites and iRBCs, reduces sequestration and inhibits parasite toxins e.g. GPI anchors to decrease inflammation.

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11
Q

What blood stage surface antigens did people focus on for vaccine development and what are the pros and cons?

A

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.

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