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Parasites and infectious disease > week 5 malaria life cycle > Flashcards

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
Q

In some forms of malaria a dormant stage occurs, what is this?

A

in some p.vivax and p.ovale infections sporozoites do not immediately form schizonts.

infection enters dormant phase

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26
Q

what is the dormant stage also known as?

A

hypnozoite stage

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27
Q

hypnozoite can reactivate and undergo schizogony resulting in ___

A

relapse

we do not understand what causes this reactivation

28
Q

What is the anatomy of merozoites like?

A

small pear shaped with a pointed apical end that contains the apical complex.

29
Q

what do the merozoites do?

A

specifically infect red blood cells - this is rapid in 20 seconds but has 4 distinct stages

30
Q

what are the 4 distinct stages of RBC invasion?

A

attachment
reorientation
junction formation
invasion

31
Q

describe the attachment process.

A

chance event - random collision - initial interaction

involves reversible interactions between merozoite adhesins and erythrocyte ligand

32
Q

what are the attachment pathways like?

A

different attachment pathways operate in different parasite lines / geographical locations

33
Q

describe the reorientation process.

A

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
Q

effectively in a short sentence how does the parasite reorientate itself?

A

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
Q

how does the formation of the junction occur?

A

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
Q

What do the tight junction proteins include?

A

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
Q

Explain the invasion stage

A

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
Q

Now that the parasite is in the RBC what occurs?

A

asexual cycle

39
Q

the merozoite differentiates into a ____stage

A

trophozoite

40
Q

What are young trophozoites called?

A

ring stage

because of Giemsa staining pattern

41
Q

What happens to the ring stage trophozoite as the parasite feeds on haemoglobin?

A

develops into the mature trophozoite

42
Q

what is the huge down flaw of the trophozoite?

A

the feeding stage as this is what the drugs target

43
Q

How does the trophozoite ring stage feed?

A

haemoglobin taken up by pinocytosis over whole parasite surface

44
Q

how does the mature trophozoite stage feed?

A

haemoglobin taken up by endocytosis via cytosome

45
Q

Haemoglobin containing vesicles fuse to form food vacuole, what happens?

A

the food vacuole acidifies and recruits several distinct classes of proteases. these mediate the sequential break down of haemoglobin

46
Q

Proteases digest haemoglobin in semi-ordered, ___ process

A

sequential

47
Q

How is the haemoglobin digested?

A

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
Q

when does the trophozoite stage end?

A

when schizogony (nuclear division) starts

49
Q

the trophozoites differentiate into __________, this formation takes ___ rounds of nuclear division. Budding occurs producing ____

A

erythrocytic schizont
3-5
mononucleated merozoites

50
Q

the erythrocyte bursts and what occurs?

A

releasing merozoites into bloodstream and invading new erythrocyte. A new asexual cycle is started.

51
Q

all the process that occur inside a RBC are ____

A

the asexual cycle

52
Q

the asexual cycle is usually ______ in a given host

A

synchronous

53
Q

What causes the relapsing fever?

A

the antigens and waste products from the asexual cycle

54
Q

which part of the asexual life cycle in p.falciparum leads to severe malarial pathologies?

A

mature trophozoite and schizont infected erythrocytes adhere to capillary endothelial cells leads to severe malaria pathologies

55
Q

Where does the sexual cycle occur?

A

insect and partly RBC

56
Q

some merozoites upon invading erythrocyte develop into _____

A

gametocyte

57
Q

why do some merozoites develop into gametocytes?

A

do not know

58
Q

what happens to the gametocytes?

A

there are 2 types - macro and micro. neither cause pathology and they are cleared from the bloodstream if not taken up by mosquito

59
Q

What happens in the mosquito gut?

A

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
Q

what happens to the micro gamete?

A

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
Q

the ookinete develops into ____

A

oocyst

62
Q

oocyst undergoes meiosis followed by ____

A

binary fission (sporogony)

63
Q

oocyst ruptures releasing ___ into ____

A

sporozoites

haemocoel

64
Q

the motile sporozoites have specificity to _____, traverse the salivary gland epithelial cells, reside in lumen

A

salivary gland

65
Q

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

A

diploid = insect

haploid = human

Parasites and infectious disease (15 decks)

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