AIDS Flashcards
Explain the difference between “HIV-seropositive” and “AIDS”.
Seropositive = Ab to HIV AIDS = symptoms of opportunistic infections or Kaposi’s sarcoma, or their Th (CD4+) cells fall below 200/uL of blood, it’s AIDS
Name the virus that causes AIDS, and its classification.
HIV-1: a non transforming retrovirus (RNA virus that carries no oncogene)
Discuss the origin of the AIDS virus and the origins of the current epidemic.
HIV-1 evolved recently from SIVcpz ~1940s in Zaire (now the Democratic Republic of Congo).
Determined by checking blood banks (found in 59 in DRC)
Mid-60s: HIV moved to the Caribbean, then Europe a little later
Epidemic in the USA started in NY, LA, SF, was probably brought in by men who had vacationed in Haiti (very high incidence of AIDS among recent Haitian immigrants and refugees)
Identify the approximate number of cases in the U.S. and in the world, and discuss the rate of change in incidence.
USA: 1.16 million
World: 33.4 million
Incidence is falling in CO
Discuss the pathogenesis of AIDS, including target cell types, mode of entry of the virus into a cell, mode of exit, latency versus productive infection.
Virus enters body and hitches a ride on DC to LN
gp120 binds CD4, inducing a conf change in gp120
gp120 binds CCR5 (CXCR4), inducing conf change in gp41
gp41 “melts away the Th membrane, fusion occurs
Virus is injected into cell
RT uses RNA to make dsDNA
DNA moves to nucleus, inserts into genome via integrase
It’s latent, gets activated somehow, makes virus, BUDS OFF
Distinguish between the roles of Th1, Tfh, and Th2 in the progression of HIV infections.
Response to HIV is tilted towards Tfh and Th2 rather than Th1, so the helping of CTL activation via IL-2 from Th1 is diminished. If patients made more Th1 they might stimulate more CTL, and do better.
Discuss the types of infections seen in AIDS patients, and provide an immunological basis for this spectrum.
The infections seen in AIDS are primarily of types that require T cell-mediated immunity.
We see viral infection, including CMV, hepatitis and especially HSV and VZV.
We see fungi, especially Candida albicans and Pneumocystis jirovecii.
Protozoan infections, such as Toxoplasma, Cryptosporidium, and Isospora are very serious.
Infections with opportunistic intracellular bacteria – usually Mycobacterium avium complex or MAC, and more and more commonly, M. tuberculosis
Discuss possible reasons for which the total number of CD4 cells in AIDS patients decline.
With time, CD4 cells are gradually lost; it looks like simple exhaustion of the ability to make more of them
Discuss reasons for the apparent ineffectiveness of antibody in HIV infection.
When the virus is replicating, gp120/gp41 is made early, and it becomes inserted into the cell’s plasma membrane.
This allows fusion of the infected cell to nearby uninfected CD4 cells, and a syncytium forms.
In this way the virus can spread without an extracellular phase.
Also, the key epitope on HIV seems to be well-concealed within the gp120/gp41 complex and almost invisible to B cells
Define and discuss “elite controllers.”
They harbor HIV but retain normal immune function for many years
Most have HLA-B57.
They make more, and more diverse, CTL against HIV peptides than people with other HLA alleles.
Theory: HIV peptides fit elegantly in B57 pocket = better presentation to T cells
Describe the laboratory diagnosis of AIDS.
First do ELISA, but it gets false positives so confirm with Western (or PCR if it’s available)
Discuss the prospects and problems of AIDS vaccine development.
We need a vaccine that can preferentially stimulate Th1 cells and CTL, current vaccines seem to be best at inducing antibody responses, and antibody doesn’t protect very well (key epitope is buried. Some people do make this Ab tho (called broadly neutralizing Antibody, or bnAb).
- HIV exhibits tremendous global genetic diversity.
- Its immense mutational capacity allows evasion of both T and B cell immunity.
- HIV goes latent in the host genome, from which it cannot be eliminated by conventional antiretroviral drugs.
- There has been no known example of spontaneous immune clearance, to use as the basis for data-driven vaccine design.
- Although bnAbs have been found, they are rare, only found in a subgroup, take years to develop, and are extensively hypermutated; no method exists now for induction of these Abs by immunization.
