Flashcards in AIDS immunology Deck (21):
Explain the difference between “HIV-seropositive” and “AIDS”.
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
What virus causes AIDS?
What type of virus is HIV?
nontransforming, nononcogenic retrovirus (RNA virus w/ DNA intermediate)
Origins of AIDS virus
Oldest sera+ HIV = 1959
Derived from SIV (infecting chimps)
SIV jumped to humans 3 times to create HIV --> Carribean --> Europe
Origin of Current AIDS Epidemic
Homosexual men vacationining in Haiti (LA, NY, SF)
Approximate # of HIV Cases in US/World
33.4 million people w/ HIV
800,000 in US
Discuss rate of change of HIV incidience
Incidence falling since 1993
but could be rising again
Pathogenesis of AIDS
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
Distinguish between latent vs. productive infection with HIV
Latent = Inserted viral DNA into host cell
Productive = when virus activated and reproducing, and bud from cell, killing host cell
How does HIV spread to othe cells?
During replication, gp120 made and insert into cell membrane
Fusion of infected cells with uninfected CD4+ uninfected cells --> syncytium
No extracellular phase
Distinguish between the roles of Th1 and Th2/Tfh in the progression of HIV infections
What types of infections in AiDS patients?
Why are opportunistic infections dangerous for AIDS patients?
Require T cell mediated immunity to clear
and T cells low by HIV infection
What type of infections are less problematic for AIDS patients?
High grade extracellular pathogens because B cell response still functional
Why do total CD4 counts decline in AIDS patients?
Mass budding or formation of syncytia with uninfected CD4+ cells --> body can't make any more
Why does antibody in HIV infection not effective?
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)
Define "elite controllers"
Do not develop normal AIDS response.
Make more and diverse (more effective) CTL responses to HIV peptides to retain normal immune
Laboratory diagnosis of AIDS
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
Problems with AIDS vaccine development
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
Current possible AIDS vaccine
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