BL Immunology of AIDS Flashcards
Explain the difference between “HIV-seropositive” and “AIDS”
• HIV-seropositive: people who have ANTIBODY to HIV-1
○ Common way that the infection is first detected.
○ About ~20% of people do not yet make the antibody in the blood and go undetected even though they have HIV
• AIDS: when Th (CD4+) cells ˂200/µL blood and/or when they get opportunistic infections or Kaposi’s sarcoma.
virus that causes AIDS, and its classification.
HIV-1, Human Immunodeficiency Virus.
○ HIV-1 is a nontransforming retrovirus (RNA virus that carries no oncogene).
○ Part of the Genus Lentivirus
origin of the AIDS virus and the origins of the current epidemic.
HIV-1 is mostly closely related to Simian Immunodeficiency Virus (SIV) and it probably jumped to humans
HIV: approximate number of cases in the U.S. and in the world
- Number of cases in USA: 1.2 million people living with HIV (20% don’t know it)
- Number of cases worldwide: 33.4 million (31.1-35.8 million)
- incidence has stabilized in recent years
HIV-1 mechanism of entry
a. Virus enters body, adheres to a lectin on DC cell called DC-SIGN
b. Virus uses DC as a Trojan horse to get to lymph nodes, where the Th cells are.
c. HIV binds by its envelope glycoprotein, gp120, to CD4 molecule on surface of Th cells.
d. Binding induces conformational change in gp120 and it can now bind co-receptor, CCR5 or CXCR4 (chemokine receptor).
e. When gp120 binds co-receptor, the gp41 glycoprotein associated with gp120 changes its conformation, exposing hydrophobic region that can melt away the T cell membrane
f. Cell and virus fuse. Virus injects its core into the cell, activates reverse transcriptase and makes dsDNA copy of its RNA.
g. Complex moves to nucleus. With the help of viral integrase, DNA is inserted randomly into a break in the host cell’s DNA as latent virus.
If inidiviuals are missing the CCR5 receptor (∆32 +/+ ), can they get AIDS?
No bc they cant get infected @ the helper T cell level (cant bind HIV antibody)
–> they will not get sick
Distinguish between the roles of Th1, Tfh, and Th2 in the progression of HIV infections.
Scientists think that HIV-infected people have a Th2/Tfh-dominated helper T cell response.
This is not good since the antibody that patient make is NOT protective. If patients made more Th1 they might stimulate more CTL, thus do better with the disease.
possible reasons for which the total number of CD4 cells in AIDS patients decline.
- HIV binds via glycoprotein 120 (gp 120) to the CD4 molecule on the surface of Th cells → Thus, the virus targets CD4 cells.
- In the pre-AIDs stage of the disease, the clearance rate of virus and the replacement rate of CD4 cells are incredible with the entire population of virus being replace daily and CD4 cells being replenished every 3 days.
It seems as though the eventual decline of CD4 cells is a result of simple exhaustion of the body’s ability to make more.
reasons for the apparent ineffectiveness of antibody in HIV infection.
When the HIV virus is replicating, gp120 is produced early and is inserted into the host cell’s plasma membrane.
This insertion allows fusion of an infected CD4 cell with a nearby, uninfected CD4 cell forming a syncytium.
Thus, the virus can be spread from cell to cell without an extracellular phase.
This makes antibodies in the extracellular fluid useless because they never actually have the opportunity to interact with the virus.
The body can produce all of the antibodies it wants, but it is fruitless since they will not be exposed to the virus.
Define and discuss “elite controllers.”
“Elite controllers”: are people who are capable of maintaining normal immune function while harboring HIV virus.
There is a link between HLA genotype and a person’s susceptibility to HIV.
65% of so-called “elite controllers” who harbor HIV, but retain normal immune function for many years are HLA-B57.
The HLA-B57 “elite controllers” produce a more awesome/diverse and more numerous CTL response against HIV peptides than peeps with other HLA alleles.
The most common test for dx of AIDS
+ELISA confirmed with western blot
- viral proteins are fixed to nitrocellulose and the patient’s antibodies must bind to viral proteins gp120 and gp41 for the test to be considered a true positive.
The progression to AIDS takes on average _____ years without treatment.
9
Discuss the prospects and problems of AIDS vaccine development.
- An AIDS vaccine needs to be able to preferentially stimulate Th1 cells and CTLs. The current immunological response to HIV is Th2/Tfh dominated when what is really needed are Th1 cells and CTLs.
- Also, HIV is the most antigenically variable pathogenic virus ever encountered
