Immunology of AIDS & Drugs Flashcards
What does it mean to be HIV-seropositive?
People are ‘seropositive’ if they have antibody to HIV, which is the most common way in which infection is first detected
When is someone considered to have AIDS?
HIV-seropositive individuals once they get symptoms of opportunistic infections or Kaposi’s sarcoma, or their Th (CD4+) cells fall below 200/uL of blood. (normal range: 500-1000/
What virus causes AIDS?
HIV-1, for Human Immunodeficiency Virus. HIV is a nontransforming retrovirus (carries no oncogene), and reproduces by its RNA into DNA by means of reverse transcriptase.
T or F: HIV evolved from SIV (simian immunodeficiency virus)
True
Where/when did HIV originate from?
as recently as the 1940s and possibly in Zaire
What is the approximate number of cases in the U.S. and in the world?
- US: 1,144,500 people (16% don’t know it)
- World: 35.3 Million
How many new cases of HIV infection per year in the US?
50,000
When do blood virus level peak?
6 weeks
When do blood anti-HIV Abs peak?
9 weeks
What is the mean incubation period of HIV without treatment?
9.5 years
T or F: HIV is taken up by dendritic cells but not harmed
True. They bind to DC-SIGN on DC and use it as a mean to get to T cells.
Where does HIV bind on the CD4 T cell?
on the CD4 molecule……
What on HIV surface binds to CD4? What does that lead to?
gp120 binds to CD4, changes conformation and is now allowed to bind to CCR5 (gp120 co-receptor, known chemokine receptor)
How is gp41 activated?
by the binding of gp120 to CCR5
How does gp41 allow entry of virus into cell?
By exposing a very hydrophobic region that literally melts away the T cell’s membrane, so the cell and virus fuse.
How does HIV show diversity in proteins with a small genome?
- Uses 3 different reading frames to encode 9 genes: pol, env, and gag which are common to all RT viruses. Additionally, has 6 more genes regulating latency and virulence
- alternative RNA splicing, and
- protease-mediated cleavage of 3 large precursor proteins making a total of 16 polypeptides.
How is latency regulated?
It may be that HIV goes latent in resting cells and replicates productively in activated ones (that’s the proposed idea, no evidence).
T or F: the response to HIV is tilted towards Tfh and Th2 rather than Th1
True. the helping of CTL activation via IL-2 from Th1 is diminished
What change in the immune system promote a better response against HIV?
If patients made more Th1 they might stimulate more CTL, and do better.
What kind of immunity is affected in AIDS?
Cell-mediated immunity
What types of infections seen in AIDS patients?
primarily of types that require T cell-mediated immunity.
- viral infection, including cytomegalovirus, hepatitis and especially herpes simplex and zoster
- fungi, especially Candida albicans and Pneumocystis jirovecii
- opportunistic intracellular bacteria usually Mycobacterium avium complex or MAC and M. tuberculosis (leading cause of death in AIDS pts)
Why does the total number of CD4 cells decline?
looks like simple exhaustion of the ability to make more of them. it has been estimated that the entire population of virus is replaced daily, and CD4 cells every 3 days
How does HIV infect near by cells without an extracellular phase?
Early expression of gp120 & 41, relocation to plasma membrane, binding to near by cells resulting in fusion of the two cells and formation of a syncytium.
Are Abs effective against HIV?
No, Though they bind to the virus, they do not block infection of Th cells. There are neutralizing epitopes on the virus, but they are shielded by carbohydrate (gp120/41) and not readily available to B cells.
What are elite controllers?
They make more, and more diverse, CTL against HIV peptides. They are HLA-B57. harbor HIV but retain normal immune function for many years
What is the laboratory diagnosis process of AIDS?
Most common: Anti-HIV antibody via ELISA, HOWEVER, must be confirmed with a western blot due to false positives.
Virus RNA PCR, available in wealthy areas.
Discuss the prospects and problems of AIDS vaccine development
we need a vaccine that can preferentially stimulate Th1 cells and CTL; the current vaccines seem to be best at inducing antibody responses, and antibody doesn’t protect very well. The key epitope on HIV seems to be well-concealed within the gp120/gp41 complex and almost invisible to B cells
-some people make is broadly neutralizing (bnAb)
What is the standard Antiretroviral Therapy (ART)?
combines a protease inhibitor and two reverse transcriptase inhibitors
What HIV drugs are targeted at RT?
RT inhibitors:
- nucleosides, which are competitive inhibitors and chain-terminator
- non-nucleoside inhibitors, bind a hydrophobic pocket on enzyme, changes the conformation and activity of the catalytic site.
What kind of drugs inhibit cleavages of the pol-gag-env polyprotein?
protease inhibitors.
What is Enfuvirtide (Fuzeon®)?
binds to part of gp41, prevents fusion b/t virus and cell. Fusion inhibitor.
Maraviroc (Selzentry®)?
CCR5 antagonist that blocks viral entry into CD4+ cells. Binds transmembrane portion of CCR5
Raltegravir, what it do?
integrase inhibitor, inhibits insertion of virus genome in host DNA.
