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week 5 malaria life cycle Flashcards

1
Q

Which form of the parasite is found in the mosquito salivary gland?

A

sporozoite

this is transmitted to the person

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2
Q

what is the sporozoite?

A

single cell

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3
Q

What happens to the sporozoites after injection?

A

after injection into the skin, sporozoites move through dermis until they contact blood vessels.

Sporozoites move into the circulatory system

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4
Q

The sporozoites use the circulatory system to go where?

A

liver

the parasites require to go through the liver prior to moving to RBC

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5
Q

In liver ____ sporozoites glide over endothelial cells

A

sinusoids

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6
Q

What interacts with sulfated heparin secreted by stellate cells of the liver?

A

parasite surface circumsporozoite protein

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7
Q

How does the parasite cross the sinusoid layer?

A

by invading and transversing across Kupffer cells

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8
Q

what are kupffer cells?

A

liver macrophages

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9
Q

what happens when the parasite comes into contact with the Kupffer cell?

A

When the sporozoite comes into contact with the Kupffer cell, the sporozoite invades the kupffer cell. It is taken up by phagocytosis into the Kupffer cells (macrophages) and uses this to cross the epithelial layer to be delivered into the cells that lie below the epithelial layer and below the patocytes.

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10
Q

essentially the Kupffer cell is used as a ___

A

shuttle

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11
Q

Sporozoite traverses several ___ until it becomes established in one

A

hepatocytes

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12
Q

where in the hepatocyte is the parasite found?

A

parasitophorous vacuole

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13
Q

how long does it take the parasite to get to the hepatocyte invasion stage?

A

30-60mins

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14
Q

once inside the hepatocyte the sporozoite develops into ________

A

liver schizont

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15
Q

the liver schizont under goes schizonony, what is this?

A

nucleus divides asynchronously without cytoplasmic division

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16
Q

what is a schizont?

A

multinucleated parasite

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17
Q

the liver schizont develops into ______

A

merozoites

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18
Q

Schizont undergoes _____ producing many mononucleated merozoites

A

budding

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19
Q

what is budding?

A

migration of nucleus and other organelles to cell membrane, becomes incorporated into merging merozoite

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20
Q

one schizont gives rise to how many merozoites?

A

thousands

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21
Q

How do the merozoites get into the blood stream?

A

dying hepatocytes release membrane bound aggregates of merozoites into blood stream

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22
Q

what are the membrane bound aggregates of merozoites known as?

A

merosomes

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23
Q

merosomes provide what function?

A

may protect merozoites from phagocytosis by Kuffper cells

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24
Q

after being released into the blood stream the merosomes _________

A

break up releasing individual merozoites

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25
In some forms of malaria a dormant stage occurs, what is this?
in some p.vivax and p.ovale infections sporozoites do not immediately form schizonts. infection enters dormant phase
26
what is the dormant stage also known as?
hypnozoite stage
27
hypnozoite can reactivate and undergo schizogony resulting in ___
relapse | we do not understand what causes this reactivation
28
What is the anatomy of merozoites like?
small pear shaped with a pointed apical end that contains the apical complex.
29
what do the merozoites do?
specifically infect red blood cells - this is rapid in 20 seconds but has 4 distinct stages
30
what are the 4 distinct stages of RBC invasion?
attachment reorientation junction formation invasion
31
describe the attachment process.
chance event - random collision - initial interaction involves reversible interactions between merozoite adhesins and erythrocyte ligand
32
what are the attachment pathways like?
different attachment pathways operate in different parasite lines / geographical locations
33
describe the reorientation process.
Parasite adhesins undergo proteolysis. at that point the link between the parasite and RBC is broken parasite shifts slightly and the adjacent parasite adhesins interact with adjacent RBC ligands apical end makes contact with erythrocyte membrane
34
effectively in a short sentence how does the parasite reorientate itself?
so effectively by proteases snapping and breaking apart the parasite can rotate itself such that the apical end can come into contact with the RBC membrane (erythrocyte)
35
how does the formation of the junction occur?
secretory bodies release contents parasite protein complexes insert into erythrocyte membrane while components of complex remaining bound to the parasite bridge between host and pathogen cells called tight junction appears as electron dense zone at parasite/erythrocyte boundary
36
What do the tight junction proteins include?
rhoptry neck proteins (RON2, 4 and 5). RONs inserted in erythrocyte membrane to form RON complex apical membrane antigen-1 (AMA-1). AMA-1 transmembrane protein (crosses parasite membrane) ‘extracellular’ region binds to RON complex ‘inner cellular’ region interacts with aldolase in parasite cytoplasm aldolase binds to F-actin. actin interacts with myosin located in inner membrane complex
37
Explain the invasion stage
tight junction formation causes invagination of erythrocyte membrane parasite forcibly enters through invagination tight junction functions as biological (myosin) motor as invasion progresses, tight junction forms a ‘ring of contact’ with erythrocytes eventually parasitophorous vacuole formed within which the parasite lives as invasion progresses, components of tight junction are degraded by serine protease, PfSUB2 (“sheddase”)
38
Now that the parasite is in the RBC what occurs?
asexual cycle
39
the merozoite differentiates into a ____stage
trophozoite
40
What are young trophozoites called?
ring stage | because of Giemsa staining pattern
41
What happens to the ring stage trophozoite as the parasite feeds on haemoglobin?
develops into the mature trophozoite
42
what is the huge down flaw of the trophozoite?
the feeding stage as this is what the drugs target
43
How does the trophozoite ring stage feed?
haemoglobin taken up by pinocytosis over whole parasite surface
44
how does the mature trophozoite stage feed?
haemoglobin taken up by endocytosis via cytosome
45
Haemoglobin containing vesicles fuse to form food vacuole, what happens?
the food vacuole acidifies and recruits several distinct classes of proteases. these mediate the sequential break down of haemoglobin
46
Proteases digest haemoglobin in semi-ordered, ___ process
sequential
47
How is the haemoglobin digested?
Plasmepsins make initial cleavage. Releases haem and globin Proteases digest globin to peptides then to amino acids. Peptides and amino acids transported from food vacuole to parasite cytoplasm. Used to make new proteins / energy source
48
when does the trophozoite stage end?
when schizogony (nuclear division) starts
49
the trophozoites differentiate into __________, this formation takes ___ rounds of nuclear division. Budding occurs producing ____
erythrocytic schizont 3-5 mononucleated merozoites
50
the erythrocyte bursts and what occurs?
releasing merozoites into bloodstream and invading new erythrocyte. A new asexual cycle is started.
51
all the process that occur inside a RBC are ____
the asexual cycle
52
the asexual cycle is usually ______ in a given host
synchronous
53
What causes the relapsing fever?
the antigens and waste products from the asexual cycle
54
which part of the asexual life cycle in p.falciparum leads to severe malarial pathologies?
mature trophozoite and schizont infected erythrocytes adhere to capillary endothelial cells leads to severe malaria pathologies
55
Where does the sexual cycle occur?
insect and partly RBC
56
some merozoites upon invading erythrocyte develop into _____
gametocyte
57
why do some merozoites develop into gametocytes?
do not know
58
what happens to the gametocytes?
there are 2 types - macro and micro. neither cause pathology and they are cleared from the bloodstream if not taken up by mosquito
59
What happens in the mosquito gut?
RBC breaks down gametocytes released, differentiate into gametes (gametocytogenesis) micro-gametocytes  micro-gametes macro-gametocytes  macro-gametes micro-gametocytes undergoes a. 3 x nuclear division b. flagella formation (exflagellation) macro-gametocytes no morphological changes
60
what happens to the micro gamete?
micro-gamete (nucleated flagella) separate fuse with macro-gamete  diploid zygote zygote develops into motile ookinete ookinete crosses mosquito gut lining/wall, emerging on basal side of epithelium
61
the ookinete develops into ____
oocyst
62
oocyst undergoes meiosis followed by ____
binary fission (sporogony)
63
oocyst ruptures releasing ___ into ____
sporozoites | haemocoel
64
the motile sporozoites have specificity to _____, traverse the salivary gland epithelial cells, reside in lumen
salivary gland
65
Mosquito is PRIMARY or DEFINITIVE HOST host where parasite reaches maturity & sexually reproduces Mammals (humans) are INTERMEDIATE HOSTS - Used to get from insect to insect
diploid = insect haploid = human

Parasites and infectious disease (15 decks)

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