summary with malaria L27 Flashcards
brief about the plasmodium life cycle
malaria = disease
plasmodium spp. = parasite
need two hosts, human and mosquito
in humans… intermediate host
11-14 days
skin - sporozoites enter and travel to the liver
liver - invasion and replication
blood - erythrocytic cycle = fever
in mosquitos … definitive host
7-14 days
gametocytes ingested and matura - sexual stages
fertilisation —> ookinete —> oocyst gut wall
release of sporozoites —> salivary gland
what are sporozoites
these are motile, elongated, slender forms of malaria parasite that can enter the human body when mosquitoes bite
infectious form of plasmodium
trigger immune responses like CTL priming
sporozoites when injected
must exit skin quickly to reach blood stream
migration - sporozoites are motile and migrate through the dermis to seek for a blood vessel
destruction - immune system reacts to destroy invading sporozoites via macrophages
lymph node entry - Travel to draining lymph node where taken up by APC
antigen processing and presentation of sporozoites
exogenous antigens are presented via MHC 2 to CD4+
endogenous antigens are presented via MHC 1 to CD8+
cross presentation mediated by perforin 2 can export antigen from an endosome to cytoplasm
sporozoite journey after mosquito bite - from skin to liver
- enter skin in bite and migrate to find blood vessels and enter blood streams reach liver in <30mins
sporozoite journey after mosquito bite - liver targeting
liver targeting
- actively target liver and cross sinusoidal barrier and enter hepatocytes
- suffer cells (liver macrophages) may try to destroy
sporozoite journey after mosquito bite - inside hepatocytes
only 100 are infected
each infected hepatocyte produces up to 90,000 meroziotes
these will burst out and begin blood stage of infection
immune response in liver
infected hepatocytes recognise sporozoites and release type 1 interferons IFNA/B
these signal to neighbouring heptacoytes to enhance MHC 1 expression and makes cell better targets for CTLS
CTLs recognising and killing infected cells
patrol for antigen and MHC 1 and bind with TCR AND CD8
FAS/Fasl PATHWAY to kill - death receptor activation —> caspases —> apoptosis
or
perforin and granzyme B - perforin makes pores —> granzyme B enters —> apoptosis
organ changes in malaria
hepatomegaly - enlarged liver caused by infection and inflammation form filtering debris of dead cells and parasites
splenomegaly - enlarged spleen
- filters parasitised RBC
- activates immune cells
- can do extracemedullary haematopoiesisi - RBC production outside bone marrow in severe cases
clinical malaria driven by blood stage infection
parasite infecting RBC - this is asexual reproduction stage and is repeated over and over again to increase parasite load
merozoites are released into blood from burst hepatocytes and invade RBCs, asexually replicate and burst
this causes symptoms like fever, chills, headache, anaemia as RBC destruction
malaria pigments - Hz
haemozoin Hz
brown crystalline pigments produced by plasmodium parasites during blood stage infection , a by product of Haemoglobin digestion
is an immunostimulant and activates macrophages and DC to trigger cytokine production - IL-10, IL-12 TNF-A, activating TLR9 to enhance innate immune response
bone marrow dysfunction
Dyserythropoiesis = Suppression of red cell production, seen in acute/severe malaria
decrease in erythroid progenitors
caused by cytokine IFNY TNFA to inhibit erythropoiesis and caused by haemozion that triggers apoptosis of progenitor cells
Red Cell Deformability
RBCs must squeeze through splenic slits – shape and flexibility are key!
Malaria reduces deformability of both:
Infected RBCs
Some uninfected RBCs
↓ Deformability → spleen traps → worsens anaemia
Inflammation & Cytokine Storm
Rupture of RBCs releases:
PAMPs (parasite antigens)
DAMPs (host cell debris)
This induces massive cytokine release → systemic inflammation.
Sporozoite to Blood Stage: Lifecycle Overview
Stage Description
Sporogony In mosquito → sporozoite formation
Liver Stage Hepatic schizogony (sporozoite → merozoites)
Blood Stage Asexual replication in RBCs → symptoms
Gametocytes Taken up by mosquito → sexual cycle begins again
Humoral (Antibody) Responses
Antibodies target cell-free parasite stages:
Sporozoites – block liver entry.
Merozoites & iRBCs – limit blood stage replication.
Gametocytes – block mosquito transmission.
PfEMP1 – Immune Evasion Molecule
~60 variants; only 1 expressed at a time
Major mechanism of antigenic variation
Binds host receptors:
EPCR, ICAM1, CD36
Upregulated during inflammation
CD36 low in brain vessels → explains cerebral malaria tropism
