How does HIV cause AIDS?

Question 1

Define pathogenesis in the context of HIV

Answer 1

The interplay between HIV and the immune system that ultimately leads to the loss of immune control of multiple pathogens and cancers

Question 2

What causes CD4 depletion?

Answer 2

• destruction of CD4 T cells

- lack of regeneratioin of CD4 T cells

Question 3

What is meant by immune activation?

Answer 3

• activated cells express activation markers (CD38)
• activated cells make more stuff (Igs, cytokines)
• activated cells may enter the cell cycle (can result in apoptosis)

Question 4

Difference in responses between Vervet +SM and Macaques + humans

Answer 4

Vervet and SM

• high VL
• little CD4 depletion
• no AIDS

Macaques and humans

• high VL
• CD4 depletion
• OIs, AIDS and death

Question 5

Describe the human data that supports the immune activation hypothesis

Answer 5

• immune activation is a strong independent predictor of clinical progression to AIDS
• reduction of immune activation may predict CD4 T cell increase after ART better that virus suppression

Question 6

What is the immune activation hypothesis?

Answer 6

• immune activation leads to increased cell turnover, activation-induced apoptosis, more targets for HIV infection, immune senescence/ premature aging of IS

Question 7

What is microbial translocation?

Answer 7

• translocation of gut-derived microbes/microbial products to systemic circulation without overt bacteremia

Question 8

How can microbial translocation be measured?

Answer 8

• by bacterial components (LPS and bacterail DNA)

Question 9

Two types of pathogen-induced programmed cell death

Answer 9

• apoptosis

- pyroptosis

Question 10

Describe apoptosis

Answer 10

• shrinkage of cell
• intact membrane
• blebbing of membrane-enclosed apoptotic bodies for phagocytosis
• no inflammation

Question 11

Describe pyroptosis

Answer 11

• cytosolic swelling
• rupture of cell membrane
• release of cell contents
• proinflammatory cytokines

Question 12

Describe the vicious pathogenic cycle of HIV

Answer 12

• HIV infection
• release of pro-inflammatory cytokines and cellular contents (pyroptosis)
• inflammation
• recruitment of healthy CD4 T cells

Question 13

How is there a lack of regeneration of CD4 T cells in HIV?

Answer 13

• destruction of immune precursor cells/naive cells

- destruction of lymphoid tissue

Question 14

Marker for progenitor cells in thymus

Answer 14

• CD34

Question 15

How can we measure thymic output?

Answer 15

• measure TRECs (TCR excision circles) in naive cells

Question 16

Changes in lymph node architecture in HIV

Answer 16

• collagen deposition disrupts fibre network
• thickened capsule
• fewer cells