Immunology of AIDS

Question 1

What is the difference between HIV-seropositive and AIDS?

Answer 1

HIV-seropositive: people who have ANTIBODY to HIV-1 sera (specifically the glycoproteins gp120 and gp41)

• 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.

Question 2

AIDS

1. What is the name of the virus that causes it?
2. What is the classification of the virus?

Answer 2

1. AIDS is caused by HIV-1, Human Immunodeficiency Virus
   
   • HIV-1 is a nontransforming retrovirus (RNA virus that carries no oncogene and reproduces by copying its RNA to DNA by using reverse transcriptase).
2. Part of the Genus Lentivirus

Question 3

1. What are the origins of the HIV-1 virus?
2. Where did the HIV epidemic begin in the US?

Answer 3

1. HIV-1 is mostly closely related to Simian Immunodeficiency Virus (SIV) and it probably evolved as recently as the 1940’s - (Simian’s are a form of Primate FYI)
2. Disease probably moved to Caribbean in mid-60’s (Cuban soldiers coming from Angola, i.e. Africa) and to Europe later. US epidemic started in NY, LA and SanFran, brought by men who had vacationed in Haiti

Question 4

AIDS

1. What is the approx number of cases in the USA?
2. What is the approx number of cases in the world?
3. Generally describe the change in rate of incidence of AIDS

Answer 4

1. Number of cases in USA: 1.2 million people living with HIV (20% don’t know it)
2. Number of cases worldwide: 33.4 million (31.1-35.8 million)
3. Incidence in Colorado has been falling since 1993, because there was a lot of money for educational programs, but there is speculation that incidence will rise because education programs have stopped (no funding). Worldwide, the incidence of HIV has stabilized in recent years.

Question 5

What is the latent period of AIDS versus when it becomes a productive infection?

Answer 5

Exposure occurs → high blood virus levels peak at 6 weeks → antibodies to HIV peak at 9 weeks, while viral levels fall (but not to zero). Mean incubation time: 9.5 years without treatment.

Question 6

What is the mechanism of progression of the AIDS virus?

Answer 6

1. Virus enters body, adheres to a lectin on DC cell called DC-SIGN
2. Virus uses DC as a Trojan horse to get to lymph nodes, where the Th cells are.
3. HIV binds by its envelope glycoprotein, gp120, to CD4 molecule on surface of Th cells.
4. Binding induces conformational change in gp120 and it can now bind co-receptor, CCR5 or CXCR4 (chemokine receptor).
5. 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.
6. Now HIV is inside the nucleus and is able to use its reverse transcriptase to incorporate itself into the host genome → cell becomes an active producer of HIV

Question 7

What is the role of Th1, Th2, and Tfh as it relates to the progression of HIV?

Answer 7

Scientists think that HIV-infected people have a Th2/Tfh-dominated helper T cell response. Perhaps the way HIV loads into the DC has something to do with this, polarizing the DC so that it favors Th2/Tfh over Th1.

This is not good since the antibody that patients make is NOT protective. If patients made more Th1 they might stimulate more CTL, thus do better with the disease.

Question 8

What is Synctitia, and how does it relate to HIV/AIDS progression?

Answer 8

Synctitia: Inducing Th cells to bind together and allow viral material to be shared between the two of them.

Consequence: Virus can pass from cell to cell (via syncytia) without ever exposing to antibody. Therefore, Ab that people make is not effective

Question 9

What type of infections would be expected in a person with AIDS?

Answer 9

• Infections seen in AIDS patients are primarily of types that require T cell-mediated immunity.

1. Viral infections:
2. Fungal infections:
3. Protozoan infections:
4. Bacteria:
   
   • Extracellular bacterial pathogens not much of a problem because a person still retains the ability to make T-independent antibody response to capsular polysaccharides.

Question 10

Why do CD4 levels eventually decline in patients with AIDS?

Answer 10

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.

• Eventual decline of CD4 cells is a result of exhaustion of the body’s ability to make more. This is usually seen by a declining CD4/CD8 ratio (normally 1.5-3)

Question 11

ELITE CONTROLLERS

1. What are they?
2. What is the most common HLA allele they carry?

Answer 11

1. “Elite controllers”: are people who are capable of maintaining normal immune function while harboring HIV virus
2. The HLA-B57 “elite controllers” produce a more diverse and more numerous CTL response against HIV peptides than peeps with other HLA alleles.

Question 12

What is the most common lab test used to diagnose HIV?

Answer 12

Most common test is measuring antibody to HIV by way of an ELISA

• Positive ELISA must be confirmed using Western Blot– patient’s antibodies must bind to viral proteins gp120 and gp41 for the test to be considered a true positive.

Full-blown AIDS enters the picture when a patient’s CD4 count drops below 200. The progression to AIDS takes on average 9 years without treatment.

Question 13

What is the biggest barrier to creating a vaccine against HIV?

Answer 13

1. Current vaccines are best at inducing an antibody response, but antibodies are very ineffective against HIV because key epitopes are well-concealed within the gp120/gp41 complex - via synctitia
2. Developing a vaccine against AIDS is also challenging because HIV is the most antigenically variable pathogenic virus ever encountered