week 5 malaria life cycle Flashcards
Which form of the parasite is found in the mosquito salivary gland?
sporozoite
this is transmitted to the person
what is the sporozoite?
single cell
What happens to the sporozoites after injection?
after injection into the skin, sporozoites move through dermis until they contact blood vessels.
Sporozoites move into the circulatory system
The sporozoites use the circulatory system to go where?
liver
the parasites require to go through the liver prior to moving to RBC
In liver ____ sporozoites glide over endothelial cells
sinusoids
What interacts with sulfated heparin secreted by stellate cells of the liver?
parasite surface circumsporozoite protein
How does the parasite cross the sinusoid layer?
by invading and transversing across Kupffer cells
what are kupffer cells?
liver macrophages
what happens when the parasite comes into contact with the Kupffer cell?
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.
essentially the Kupffer cell is used as a ___
shuttle
Sporozoite traverses several ___ until it becomes established in one
hepatocytes
where in the hepatocyte is the parasite found?
parasitophorous vacuole
how long does it take the parasite to get to the hepatocyte invasion stage?
30-60mins
once inside the hepatocyte the sporozoite develops into ________
liver schizont
the liver schizont under goes schizonony, what is this?
nucleus divides asynchronously without cytoplasmic division
what is a schizont?
multinucleated parasite
the liver schizont develops into ______
merozoites
Schizont undergoes _____ producing many mononucleated merozoites
budding
what is budding?
migration of nucleus and other organelles to cell membrane, becomes incorporated into merging merozoite
one schizont gives rise to how many merozoites?
thousands
How do the merozoites get into the blood stream?
dying hepatocytes release membrane bound aggregates of merozoites into blood stream
what are the membrane bound aggregates of merozoites known as?
merosomes
merosomes provide what function?
may protect merozoites from phagocytosis by Kuffper cells
after being released into the blood stream the merosomes _________
break up releasing individual merozoites
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
what is the dormant stage also known as?
hypnozoite stage
hypnozoite can reactivate and undergo schizogony resulting in ___
relapse
we do not understand what causes this reactivation
What is the anatomy of merozoites like?
small pear shaped with a pointed apical end that contains the apical complex.
what do the merozoites do?
specifically infect red blood cells - this is rapid in 20 seconds but has 4 distinct stages
what are the 4 distinct stages of RBC invasion?
attachment
reorientation
junction formation
invasion
describe the attachment process.
chance event - random collision - initial interaction
involves reversible interactions between merozoite adhesins and erythrocyte ligand
what are the attachment pathways like?
different attachment pathways operate in different parasite lines / geographical locations
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
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)
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
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
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”)
Now that the parasite is in the RBC what occurs?
asexual cycle
the merozoite differentiates into a ____stage
trophozoite
What are young trophozoites called?
ring stage
because of Giemsa staining pattern
What happens to the ring stage trophozoite as the parasite feeds on haemoglobin?
develops into the mature trophozoite
what is the huge down flaw of the trophozoite?
the feeding stage as this is what the drugs target
How does the trophozoite ring stage feed?
haemoglobin taken up by pinocytosis over whole parasite surface
how does the mature trophozoite stage feed?
haemoglobin taken up by endocytosis via cytosome
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
Proteases digest haemoglobin in semi-ordered, ___ process
sequential
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
when does the trophozoite stage end?
when schizogony (nuclear division) starts
the trophozoites differentiate into __________, this formation takes ___ rounds of nuclear division. Budding occurs producing ____
erythrocytic schizont
3-5
mononucleated merozoites
the erythrocyte bursts and what occurs?
releasing merozoites into bloodstream and invading new erythrocyte. A new asexual cycle is started.
all the process that occur inside a RBC are ____
the asexual cycle
the asexual cycle is usually ______ in a given host
synchronous
What causes the relapsing fever?
the antigens and waste products from the asexual cycle
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
Where does the sexual cycle occur?
insect and partly RBC
some merozoites upon invading erythrocyte develop into _____
gametocyte
why do some merozoites develop into gametocytes?
do not know
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
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
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
the ookinete develops into ____
oocyst
oocyst undergoes meiosis followed by ____
binary fission (sporogony)
oocyst ruptures releasing ___ into ____
sporozoites
haemocoel
the motile sporozoites have specificity to _____, traverse the salivary gland epithelial cells, reside in lumen
salivary gland
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
