Immune response to malaria

Question 1

How many cases of malaria per year?

Answer 1

300-500 million, 1-2 million deaths, 40% of world population exposed to it

Question 2

Which mosquito?

Answer 2

Aneophiles

Question 3

What causes malaria?

Answer 3

Plasmodium falciparum - most severe
Plasmodium vivax - most common
Plasmodium knowlesi - recently discovered in humans

Question 4

Life cycle of malaria

Answer 4

• Injected into blood by mosquito
• Infect the liver RBCs,
• In the RBCs they become merozoites
• Move into the blood stream and become gametocytes
• Sexual stages take place in the mosquito

Question 5

Blood stages in RBCs

Answer 5

Ring stage, trophozoite, schizont and gametocyte

Question 6

Dormant strains

Answer 6

P. vivax and ovale can stay dormant in the liver

Question 7

Pathology of malaria

Answer 7

relapsing fever, observed in peripheral blood smears, enlarged spleen, anemia, TNF induction, glomeronephritis

Question 8

Natural resistance mechanisms against P. vivax

Answer 8

-P-vivax - absent in West Africa due to lack of Duffy antigen so invasion by merozoites can’t take place

Question 9

Natural resistance mechanisms against P. falciparum

Answer 9

• P. falciparum - unfavourable growth of RBCs as a consequence of sickle cell anaemia (A to T, Glutamic acid to Valine). More free haem converting haem to CO
• Carriers have resistance. A or b thalassemias also partial resistance.
• Glucose phosphate dehydrogenase deficiency permits more reactive oxygen.
• Ovalocytosis - cytoskeletal differences

Question 10

Immune responses to malaria

Answer 10

DCs activate IL-12 activating NK cells
NK cells produce IFN-y
Stimulate Naive T cells
Stimulate TH1 cells 
Stimulates B cells to produce IgG
Macrophages produce TNF and O2 and NO leading to cell death

Question 11

Why a lack of immunity to malaria? Preerythrocytic stages

Answer 11

Covered in CSP however very variable (NANP (40)/NVDP) used as decoy due to lots of repeats

Question 12

Immune response to Liver stages

Answer 12

Proteins CSP and LSA-1
CD8 response
IL-1, Il-6, IFNy and TNF produced

Question 13

Merozoites antigens

Answer 13

MSP1 and RAP1 (Rap 1 released by organelles)

MSP1 is a decoy antigen

Question 14

Erythrocytic stages - trophozoite

Answer 14

Intracellular but express PfEMP-1 which are involved in adherence
pfEMP-1 varies a lot with 59 var genes
Antibodies aim to block this adherence
Fever is though to inhibit parasite growth

Question 15

Role of TNF

Answer 15

Regulates parasite growth and is potentiated by IFN-y

Question 16

Celebral malaria

Answer 16

Leads to coma

High levels of TNF in cerebral malaria