AIDS immunology

Question 1

Explain the difference between “HIV-seropositive” and “AIDS”.

Answer 1

HIV Seropositive = people with the antibody to HIV are infected with the virus

AIDS = when CD4 < 200/uL or opportunistic infections (pneumocystis pneumonia)/Kaposi’s sarcoma

Question 2

What virus causes AIDS?

Answer 2

HIV-1/HIV

Question 3

What type of virus is HIV?

Answer 3

nontransforming, nononcogenic retrovirus (RNA virus w/ DNA intermediate)

Question 4

Origins of AIDS virus

Answer 4

Oldest sera+ HIV = 1959

Derived from SIV (infecting chimps)

SIV jumped to humans 3 times to create HIV –> Carribean –> Europe

Question 5

Origin of Current AIDS Epidemic

Answer 5

Homosexual men vacationining in Haiti (LA, NY, SF)

Question 6

Approximate # of HIV Cases in US/World

Answer 6

33.4 million people w/ HIV

800,000 in US

Question 7

Discuss rate of change of HIV incidience

Answer 7

Incidence falling since 1993

but could be rising again

Question 8

Pathogenesis of AIDS

Answer 8

1) HIV enters body and bind to lectin (DC-SIGN) on dendritic cells
2) Infect Th cells in lymph node
3) viral gp120 binds CD4 on Th cell
4) Induces conformational change in gp120 to bind to co-receptor CCR5
5) gp41 changes conformation exposing highly hydrophobic region
6) region inserts into T cell, causing fusion of viral envelope with T cell membrane
7) Reverse transcripts activated, make viral DNA
8) DNA enters nucleus and insert randomly into host DNA using viral integrate

Question 9

Distinguish between latent vs. productive infection with HIV

Answer 9

Latent = Inserted viral DNA into host cell

Productive = when virus activated and reproducing, and bud from cell, killing host cell

Question 10

How does HIV spread to othe cells?

Answer 10

During replication, gp120 made and insert into cell membrane

Fusion of infected cells with uninfected CD4+ uninfected cells –> syncytium

No extracellular phase

Question 11

Distinguish between the roles of Th1 and Th2/Tfh in the progression of HIV infections

Answer 11

a

Question 12

What types of infections in AiDS patients?

Answer 12

Opportunistic
virus
fungi
protozoa
intracellular bacteria

Question 13

Why are opportunistic infections dangerous for AIDS patients?

Answer 13

Require T cell mediated immunity to clear

and T cells low by HIV infection

Question 14

What type of infections are less problematic for AIDS patients?

Answer 14

High grade extracellular pathogens because B cell response still functional

Question 15

Why do total CD4 counts decline in AIDS patients?

Answer 15

Mass budding or formation of syncytia with uninfected CD4+ cells –> body can’t make any more

Question 16

Why does antibody in HIV infection not effective?

Answer 16

HIV infects CD4+ cells without an extracellular phase
(infected cells fuse with uninfected cells to form syncytium so HIV never exposed to a antibody in cytoplasm)

HIV induces Th2/Tfh dominated T response (Th1 response more effective at stim more CTL for better outcome)

Question 17

Define “elite controllers”

Answer 17

Have HLA-B57.

Do not develop normal AIDS response.

Make more and diverse (more effective) CTL responses to HIV peptides to retain normal immune

Question 18

Laboratory diagnosis of AIDS

Answer 18

1) First run ELISA
2) If positive, confirm with Western Blot using viral protein preps stained with patient’s antibodies

Pt’s antibodies must bind gp120/gp41

Question 19

Problems with AIDS vaccine development

Answer 19

Antibody mediated immunity via vaccines not effective against HIV
(We need to stimulate Th1/CTL)

Epitopes for HIV infection folded into proteins requiring multiple conformational changes to expose

Question 20

Current possible AIDS vaccine

Answer 20

Finding other HIV epitomes (some people make antibody to) and neutralize them

We need a vaccine that can preferentially stimulate Th1 cells and CTL; the current vaccines seem to be best at inducing antibody responses

Key epitopes on HIV seem to be well-concealed within the gp120/gp41 complex
broadly neutralizing antibody- rare

Question 21

Long term survivors

Answer 21

homozygous for a 32 base pair deletion in the gene for chemokine receptor, CCR5