Host genetics and infectious diseases

Question 1

What is required for P vivax to invade an erythrocyte

Answer 1

• P vivax can invade only erythrocytes on which a duffy antigen receptor complex is present(DARC)

Question 2

Which transcription factor activates the DARC gene

Answer 2

GATA-1

• GATA-1 binding site is mutated in duffy negative individuals
• GATA-1 binding is essential for DARC gene activation in erythrocytes but not in leucocytes

Question 3

Genes associated with malaria

Answer 3

• alpha-globin
• beta-globin
• HLA-B

Question 4

Why are some individuals resistant to HIV infection

Answer 4

• Resistant individuals found to be homozygous for 32 bp deletion in the CCR5 gene
• Frameshift mutation and premature stop codon
• Protein is not expressed at cell surface
• CCR5 is a co-receptor for HIV

Question 5

What is maraviroc

Answer 5

• Maraviroc is a chemokine receptor antagonist drug designed to interfere with the interaction between CCR5 and and HIV
• It is an early inhibitor and works by preventing HIV from entering human cells

Question 6

Outcome of mycobacterial infection

Answer 6

• Exposure to infection –> primary infection –90%–> good immune response tuberculin positive wall
  Primary infection –10%–> poor immune response tuberculin negative disease

Question 7

Importance of intact immune response

Answer 7

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

Question 8

Why identify TB susceptibility genes

Answer 8

Prolonged treatment several drugs –> poor compliance MDRTB

• BCG does not protect in endemic regions

Question 9

The five genes within the IL-12/IFN-gamma axis that cause mendelian disease in man

Answer 9

• STAT1
• IFNgammaR2
• IFNgammaR1
• p40
• IL-12Rbeta1

Question 10

What is IFNGR1 deficiency

Answer 10

Interferon-γ receptor 1 (IFNGR1) deficiency is a rare immune deficiency characterized by selective susceptibility to mycobacterial disease caused by genetic mutations in the IFNGR1 gene

Question 11

How does IFNGR1 deficiency increase susceptibility to TB

Answer 11

In the normal host, mycobacteria typically induce IL-12 production by macrophages, which, in turn, trigger IFN-γ production.

In patients with IFNGR1 deficiency, macrophages fail to activate on IFN-γ stimulation from T- and NK-cells, rendering the host susceptible to mycobacteria and intramacrophagic microorganisms

Question 12

Molecular pathology in in IFNGR1 deficiency

Answer 12

Normal - Normal signalling via STAT1

Recessive - No signalling

Dominant - Partial signalling