Malaria Flashcards
what is the pathology of malaria
recurrent fever, parasites in peripheral blood smears, enlarged spleen, TNF induction, glomerulonephritis, cerebral malaria
which antigen confers resistance to P.virax malaria
Duffy antigen
what confers resistance to Plasmodium falciparum
unfavourable conditions eg sickle cell anaemia, glucose-6-phosphate dehydrogenase deficiency and ovalocytis
how is the infection acquired
through mosquito vectors derived through the bite and into the blood
what does the parasite first enter as
sporozoite
what cells do sporozoites infect
liver cells
for how long do sporozoites replicate in liver cells
10-16 days
when are sporozoites released
after differentiation
what is the new form of sporozoite which is released from liver cells
merozoite
what cells do merozoites infect
red blood cells
what form has the highest pathogenicity
merozoites
why does host develop cyclic fevers when merozoites infect RBCs
due to RBC bursting peridically so merozoit can infect more cells
how does the parasite replicate in liver cells and RBCs
asexually
how soon do symptoms appear after being bitten
10-15 days
which species of malaria parasite causes the most deaths
p. falciparum
what is the liver phase called
the exoerythrocytic phase
what is the RBC phase called
erythrocitic phase
how does the parasite escape undetected from liver cells
by wrapping itself in cell membrane of infected liver cell
what do some of the merozoites a sexually divide into
schizonts
what do merozoites which do not divide asexually into schizonts do
differentiate into sexual forms called gametocytes
what form is taken up by the mosquito when it feeds on blood
gametocytes
what is produced when the male gametocyte undergoes rapid nuclear division
8 flagellated daughter cells called microgametes
where do gametocytes mature
in the mosquito gut
what is produced when female and male gametocytes fuse
ookinete
after the ookinete develops to form a oocyst what happens
the oocyst ruptures, releasing 100s of sporozoites into mosquito body which migrate to salivary glads
how does a lack of the duffy antigen confer resistance to p. vivax
the duffy antigen is the receptor used by p. vivax merozoites to enter RBC
what are the reasons for lack of adaptive immuniy to malaria
antigenic diversiy between species, strains and stages
‘hiding’ in RBCs
little T cell memory
misdirection or supression of immune response
what is the immune response to sporozoites in the pre erythrocytic stage (stage 1)
sporozoites are in blood so vulnerable to sera antibodies which prevent invasion and motility and all of anti-sera reacts to circumsporoite protein
what is the repeat found in the highly antigeneic repeat sequence of the circumsporoite protein
NANP or NVDP
what is thought to be th reason for variation in the repeats of the repeat region in csp
decoy antigen
what is the immune response to pre-erythrocytic stage in the liver (stage 2)
parasite Ags expressed on hepatocyte surface causing specific CD8+ response as well as induction of IL-1 IL-6 IFNg and TNF and ntrogen oxide
what is the immune response to erythrocytic stages
initially TH1 response, releaseing cytokines incl IFNg to induce cell mediated response
later TH2 induce Ab dependant response
what is the immune respose to the merozoites stage 1 of erythrocytic stage (extracellular stage)
elicits antibody responce blocking invasion into RBCs
antibodies respond to antigens on surface eg MSP-1 and Ags released by organelles
which protein aside from CSP has highly variable regions which potentially serve as a decoy
MSP-1
what is the immune response to trophozoites, stage 2 of erythrocytic pathway (in RBCs)
infected cells express proteins on RBC surface eg PfEMP-1 so Ig response to these block cytoadherance
what are the 2 ways fevers are induced in malaria
contents of burst RBC may be phagocytosed activating release of cytokines IL-1 and TNF.
GPI anchored proteins on parasite surface activate macrophage release of cytokines
how does periodic fever benefit the person suffering from malaria
inhibits parasite growth however aids parasite synchronisation and survival so fever switches off when levels fall below threshold as safeguard mechanism causing it to be periodic
how might TNF regulate parasite growth
negative feedback mechanism
what is the effect of IFNg on TNF
TNF is potentiated
what percentage of infections lead to cerebral malaria
1%
what is the clinical patholog of cerebral malaria
coma
what causes coma in cerebral malaria
accumulation of parasitised RBCs in capillaries of the brain, blocking normal blood flow
which receptor is found to be upregulated in cerebral malaria
TNFR
at what level does antigen diversity occur
population level
at what level does antigen variation occur
individual level
