malarial lifecycel

Question 1

What are the 5 main plasmodium species causing malaria (in order of severity)?

Answer 1

P. falciparum (causes most death)
P. vivax (causes significant mortality)
P. ovale
P. malariae
P. knowlesi

Question 2

What other animals can plasmodium infect?

Answer 2

Lizards and birds.

Question 3

Where are p. falciaprum infections concetrated to? How does spread compare to P. vivax?

Answer 3

desnely concentrated in africa where in some cases you get extremely high rates of transmission.
p.vivax has a much broader distribution.

Question 4

What aspect of the blood phase is most responsible for disease? And what are the 3 characteristic symptoms?

Answer 4

in blood phase, infected erythrocytes become sticky, sticking to blood vessels.
In brain, this can cause cerebromalaria (major cause of death)
Also cause metabolic lactic acidosis or placental malaria (intrauterine growth retardation)
And direct and indirect haemolysis causes severe anaemia.

Question 5

Why might malaria infection increase susceptibility to bacteraemia?

Answer 5

Because haemolysis increases iron availability and impairs macrophage function.

Question 6

What is a protozoan?

Answer 6

a single cell eukaryotic organism.

Question 7

What are the different intracellular and extracellular stages of Plasmodium that differ in their cellular and sub cellular architecture.

Answer 7

worm like sporozoite (injected by the mosquito)
merozoite (blood phase)
hepatyocyte and erythrocyte stages.

Question 8

What are the 6 basic stages of plasmodium life cycle?

Answer 8

mosquito (injectino of sporozoite)
sporozoite travels to the liver to infect the hepatocytes
multiplies in liver and burst out into blood.
asexual stage in blood
sexual blood
mosquito (takes up gametes)

Question 9

What are shared characteristics of the extracellular sporozoite and merozoite?

Answer 9

They are solitary, mobile and polar. Have orgaenelles at their apex which are specialised for invasion.

Can’t be targeted by T cells.

Question 10

Shared features of intracellular plasmodium stages

Answer 10

many organisms wthin a host cell that undergo multiple round of mitosis.
exist in parasitophorou vacuole- allows feeding on host prtoeins and lipids.

Question 11

Which of the intracellular stages can be targeted by T cells?

Answer 11

Intracellular hepactoye stages can be T cell targets (not erythrocytes).

Question 12

Describe the series of steps leading to sporozoite infeciton of the hepatocytes.

Answer 12

sporozoites injected thorugh mosquito proboscis, and traverse thruogh the human dermis and across dermal endothelium into the blood.

Exits from the blood at the liver across the liver sinusoids.
Traverses across hepatocytes before prouctively infecting a chose hepatocyte.

Question 13

Why are sporzoites difficult to study vs blood stage?

Answer 13

Because they can’t be cultured they have to be grown in mosquitos.

Question 14

What drives sporozoite mobility?

Answer 14

actin myosin motor via attachments to the ctyoskelton and host substrates.

Question 15

where does traversal occur and what enables non specific wounding and punching in this process?

Answer 15

occurs in the dermis and the liver.

Phospholipases and perforin like proteins help wounding and punching.

Question 16

What buds off after extensivite mitotic replciation in the hapatocytes?

Answer 16

merosomes full of merzoites.

Question 17

How quick are the sporozoite, liver and blood stages?

Answer 17

Very brief- 30 mins.
7 days for liver.
blood stage can be indefinite.

Question 18

Which species can and can’t form domant liver stages?

Answer 18

p. flaciparum can’t.

P. vivax and ovale can form dormant hypnozites (enables spread via reactivation)

Question 19

What can be the issue with hypnozoites?

Answer 19

Eradicatino requires primaquine, as normal drugs only target blood stage.
However some people have a RBC deficiency of the enzyme G6PD making them sensitive to primaquine.

Question 20

Desribe the 5 asexual blood stage cycle

Answer 20

ring stage, early trophozoite, trophozoite, late schizont and merozoites.

Question 21

Which stage of the asexual blood-stage cycle can be targeted by vaccination?

Answer 21

When large biomasses of merozoites are released, although they can invade RBCs within seconds.

Question 22

Which stage of the asexual blood-stage cycle can be targeted by metabolism drugs?

Answer 22

the early trophozoite and trophozoite stages- to inhibt growth of plasmodium inside RBCs.

Question 23

Which stage is responsible for cytoadherence and pathogenesis?

Answer 23

after the trophozoite stage (and through late schizont)

Question 24

What brief processes are part of merozoite invasion of RBCs?

Answer 24

low affinity interactions with RBC.
Then reorientation towards apical end and junctoin formation.
actin mysoin motor drives invagination and establsiment of parisitophourous vacuole.

Question 25

which and how can antibiotics help prevent plasmodium growth?

Answer 25

by inhibiting protein translation of parasites (tetracyclin and doxycycline.

Question 26

What are two examples of artemisinins and how are they supposed to work?

Answer 26

artemether and artesunate.

activated by parasitic haem iron and will then release free radicals that alkylate or modify parasitic proteins.

Question 27

How do quinines work?

Answer 27

Interfere with parasitic ability to digest haemoglobin.

Question 28

What group of genes and proteins are mostly responsible for cytoadherence to enodthelium receptors?

Answer 28

var genes that encode ~60 PfEMP1 proteins which are presented on the RBC membrane.

Question 29

What effect does cytoadherence have on dtectio of malria?

Answer 29

When they are sequestration in periodic cycles, they wont’ show up in blood test.

Question 30

Why is cytoadherence beneficial for parasties?

Answer 30

because otherwise due to their mechanical properties, less deformable infected RBCs would be removed by spleen.

Question 31

What receptors do PfEMP1 proteins bnid in the placenta, brain and microvasculature?

Answer 31

CSA (placenta)
ICAM1 (CD54) (brain)
CD35/6 (CR1) (microvasculature)

Question 32

How do PfEMP1 proteins avoid antibody responses?

Answer 32

encoded by 60 var genes with polymorphism.
epigenetically regulated so only one var gene expressed by a parasite.
epigenetic patterning is clonally inherited.
But there is slow swtiching that creates reserved PfEMP1s that evade then predominate immune responses.

Question 33

What causes long term waves of parasitemia?

Answer 33

swtiching of PfEMP1 expression/

Question 34

Why are some adults immune to clincial symptoms?

Answer 34

Due to repeated exposure and acquisition of broad immunity to repsond to infections asymptomatically.

Question 35

What responses are mounted against malaria?

Answer 35

CD8 T cell response found against hapactocytes, but not thought to be protective.
Ab response to blood stage (mostly PfEMP1) antigens thoguht to be most protective.

Question 36

What happens to parasites that have committed to gametocyte differenittin in erythrocytes?

Answer 36

Taken up into mosquito mid gut in blood meal/

Sensing of this causes male gametophytes to exfalggelate and mate via axonemes processes.

Question 37

What happens after zygote differentition into ookinete?

Answer 37

traverses through midgut epithelium, to form oocyst with dividing parasitic syncitium.
sporozoites mature and release in haemocoel and invade salivary gland.

Question 38

How could you target antigen in midgut?

Answer 38

Via immunising against midgut antigens which will mix with Ab in blood meal.