Immune Defence against Malaria Flashcards
(36 cards)
What is the global burden of malaria?
- 600,000 deaths annually (CDC)
- 300 million clinical cases p/year
What are the causative agents of malaria?
Plasmodium falciparum (most deadly)
Also:
- P. vivax
- P. malariae
and others
What are some innate immune defenses to malaria?
- Skin; blocks sporozoite entry into blood
- Kupffer cells
- DCs & macrophages
- Natural killer cells
- Spleen
What are kupffer cells and how do they defend against Plasmodium attack?
Kupffer cells are liver macrophages, and they can phagocytose sporozoites
How do DCs and macrophages defend against Plasmodium attack?
Detect plasmodium via PRR-PAMP recognition; release of inflammatory cytokines like IL-12 and IFN-a
How do natural killer cells defend against Plasmodium attack?
May kill early infected cells. Also promotes IFN-y
What is the role of the spleen in defending against Plasmodium attack?
Filters out red blood cells with decreased deformability (i.e infected and aged RBCs)
What is evidence of the role of the spleen in Plasmodium immune defence?
Individuals without a spleen have a greater than 5x higher risk of severe mortality and death
What is the adaptive immune response to the initial infection/liver stage?
- IgG antibodies block sporozoite motility to prevent liver cell invasion
- Cytotoxic CD8+ T cells kill infected liver cells that are presenting parasite peptides on MHC I
What is the adaptive immune response to the blood stage?
- IgG and IgM opsonise merozoites, blocking the invasion of RBCs
- Neutrophils phagocytose opsonised merozoites
What is the overall role of CD8+ T cells?
They are crucial at the liver stage, but become ineffective once the parasite is in RBCs (as RBCs lack MHC I)
What is most important in the blood stage (merozoites) in immune defence?
Antibodies, in particular IgG. They do not prevent infection, but reduce severity
What is the role of Tfh cells in Plasmodium immune defence?
Enable class switching and affinity maturation- crucial for long term protection
How would you describe the adaptive immunity provided by the host against plasmodium?
Mostly non-sterilising (particularly once the parasite reaches the blood stage).
This allows for a chronic, low-level infection
What are 3 immune evasion mechanisms implemented by Plasmodium?
- Sequestration
- Antigenic variation
- Immunosuppression
What is sequestration?
An immune evasion technique that involves hiding Plasmodium infected RBCs in tissues away from the spleen, to avoid being filtered out
How does sequestration work?
After P. falciparum infects a RBC, it exports proteins to the RBC surface which bind to endothelial receptors on blood vessel walls in deep tissue.
This causes infected RBCs to adhere (sequester) to blood vessel walls, instead of circulating in the blood
What is the primary protein exported to the RBC surface during sequestration?
PfEMP1
What are the main tissues at which RBCs sequest?
- Brain
- Lung
- Adipose tissue
What is the clinical implication of sequestration?
Not only promotes parasite survival, but also underlies pathogenesis of severe malaria syndromes, through microvascular obstruction and local inflammation (e.g. in brain)
What is cerebral malaria?
Severe neurological complication of malaria which is caused by sequestration in the brain blood vessels. Sequestration results in local inflammation and swelling; brain damage
What is the gene family involved in Plasmodium antigenic variation?
var gene family- 60 var genes
What do different var genes encode?
Each var gene encodes a different variant of PfEMP1.
Only one var gene is expressed in an individual parasite at one time
What does PfEMP1 stand for?
Plasmodium falciparum erythrocyte membrane protein 1
