W06_03 Pathogenesis of HIV and AIDS

Question 1

how did HIV affect T cells?

Answer 1

causing the T cells to fuse, and then die

Question 2

what’s the typical course of HIV infection?

Answer 2

ADD THE SLIDE!
get infected, HIV titre goes up, T cells come down, but then around 6 weeks, our bodies can fight the infection. T cells recover, but slowly fall, at about 50 cells/mm3 per year. below a count of 200, you start to get really bad symptoms - AIDS.

Question 3

what’s the definition of AIDS?

Answer 3

acquired immunodeficiency syndrome.

1) presence of HIV infection and
2) presence of opportunistic infection or a T cell count of <200 cells/mm3

Question 4

how does an HIV virion bind to a cell?

Answer 4

gp120 on virion binds to CD4 and co-receptor on T cell

Question 5

what aspect of the virus life cycle makes the HIV infection difficult to eradicate?

Answer 5

virus integrates into the DNA of the cell, so you have to kill all the T cells

Question 6

what are the two types of known co-receptors for HIV’s gp120?

Answer 6

CXCR4 and CCR5

Question 7

what’s the natural ligand for CXCR4?

Answer 7

SDF-1

Question 8

what’s the natural ligand for CCR5?

Answer 8

MIP-1alpha, beta; RANTES

Question 9

which mutation gives individuals resistance to certain strains of HIV-1?

Answer 9

CCR5

Question 10

should you give immunization vaccines to HIV patients?

Answer 10

no, it’ll hyperactivate the HIV. things like TNFa, IL-1, IL-6 make HIV crazy

Question 11

how does TNFa increase HIV?

Answer 11

increases NF-kB activation, which goes to bind LTR of HIV-1 and enhances HIV transcription

Question 12

HIV makes 1 billion virions a day!

Answer 12

okay

Question 13

note: there is a direct-killing hypothesis and an indirect-killing hypothesis in HIV/AIDS

Answer 13

CD4 cells not infected with AIDS will also die ex vivo…belief is that HIV releases antigens that activate CD4 cells and force apoptosis

Question 14

what happens in the gut in early HIV infection?

Answer 14

peyer’s patches gone. so lack of immune system there predisposes the bacteria to survive, and even translocate into the blood. high LPS in blood = high T cell activation = early apoptosis

Question 15

note CD4 T cells don’t respond to their normal cytokine stimuli

Answer 15

like IL-2 - fail to proliferate in response to this

Question 16

how is HIV diagnosed?

Answer 16

direct virus directly;

see if antibody response is mounted against HIV antigen - ELISA + western blot

Question 17

which bands do labs look for when western blotting for HIV?

Answer 17

gp120, gp160, gp41

Question 18

what’s the next generation HIV test that we use in Ontario?

Answer 18

HIV-1/HIV-2 antibody AND

gp24 antigen test in ELISA

Question 19

how long does it take to be able to detect these HIV antigens by ELISA and western blot?

Answer 19

4-6 weeks

Question 20

note: the amount of HIV titre in the blood directly influences how quickly the CD4 cells will decrease, and how quickly the person will die

Answer 20

okay

Question 21

why does HIV increase susceptibility to TB?

Answer 21

recall that CD4 cells are there to help the macrophage digest the intracellular TB