Infection 1) Host genetics and ID

Question 1

Why is it important to identify genes that predispose / protect from disease?

Answer 1

Understand pathogenesis

Identify pathways important in immunity for new treatments and vaccines

Question 2

What methods can be used to identify human ID susceptibility genes?

Answer 2

Animal models
Mendelian disease in humans
Family based linkage studies
Population based association studies
Quantitative trait analysis

Question 3

Describe how P.vivax invades in those who are Duffy positive

Answer 3

P.vivax invades erythrocytes which express DARC.
Transcription factor GATA-1 activates DARC.
GATA-1 binding is essential for DARC gene activation in erythrocytes

Question 4

What genes are associated with malaria?

Answer 4

Cell wall and receptors:
 - alpha-globin
 - beta-globin
 - glucose-6-phosphate dehydrogenase
 - spectrin
 - erythrocyte band 3
 - glycophorin A
 - glycophorin B
 - duffy chemokine receptor
 - CD36
Immune response:
 - HLA-B
- HLA - DRB1
 - TNF 
 - iNOS
 - ABO blood group
 - ICAM-1
 - complement receptor
 - CD40L
 - IFN-gamma receptor 1

Question 5

Why are some individuals resistant to HIV infection?

Answer 5

Homozygous for 32bp deletion in CCR5 gene

Frameshift mutation and premature stop codon so protein isn’t expressed at cell surface

Question 6

What is maraviroc?

Answer 6

Chemokine receptor antagonist

Acts against HIV by interfering with interaction between HIV and CCR5

Question 7

What 5 mutations in IL-12/IFN-gamma axis cause mendelian disease?

Answer 7

STAT1
IFN-gamma-R2
IFN-gamma-R1
IL-12R-beta-1
p40

Question 8

What groups don’t have an intact immune response?

Answer 8

Extremes of age
Co-infection with HIV
Post-measles
Diabetes
Renal disease
Steroid therapy
Anti-TNF treatment

Question 9

Why is it important to identify TB susceptibility genes?

Answer 9

Prolonged treatment with several drugs
Poor compliance causes MDRTB
BCG doesn’t protect in endemic regions