Malaria - pathogenesis and host immune response

Question 1

Key aspect(s) of complicated malaria that cause pathology

Answer 1

Cytoadherence

Question 2

What mediates cytoadherence of malaria infected RBCs to vessel walls in brain? (inc. REF)

Answer 2

ICAM-1

Cunningham et al. (2017)

Question 3

What causes the distinct pathologies associated with cerebral malaria?

Answer 3

CNS blockage

Question 4

How does the ingestion of an infected RBC by a macrophage lead to an increase in the expression of adhesion molecules in vessels?
(inc. REF(s))

Answer 4

(Lawrence, 2009; Liu, 2017)

Pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs) and Glycosyl-Phosphatidly-Inositol (GPI) detected by toll-like receptors (TLR)

-> cascades of pro-inflammatory cytokines (e.g. Interleukin-1B and TNF-alpha)
(through direct activation, (major histocompatability complex) MHC1 and MHC2 or the caspase-1 pathway)

Question 5

Symptoms of uncomplicated malaria

Answer 5

Fever paroxysms
Chills/rigour/headache
Normochromic normocytic anaemia
Low platelet count

Question 6

Complicated Malaria (examples and cause)

Answer 6

Vessel blockage ->
placental malaria
bilious malaria (liver)
liver+spleen+kidneys -> sepsis-like symptoms

Question 7

What does the lysis of infected red blood cells cause?

Answer 7

release of cytokines

e.g.) TNF-alpha, Interleukin-1B

Question 8

What pathologies dow the lysis of red blood cells cause?

Answer 8

Fever paroxysms
Chills/rigour/headache
Normochromic normocytic anaemia
Low platelet count

Question 9

What initial “normal” immune response can lead to pathologies associated with complicated malaria?

Answer 9

A macrophage ingesting an infected red blood cell.