Immunology: HIV Infection

Question 1

Outline the mechanisms of immune deficiency associated with HIV-1 infection

Answer 1

• HIV targets CD4+ T cells (and monocyte lineage cells)
• Uses CD4 to enter cells
• Induces a selective loss of CD4+ T Helper cells
• Loss of T helper cells lead to Reduced B cell activation and reduced CD8+ T cell activation
• Immunological memory is also lost

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• HIV can also be taken up by follicular dendritic cells in the lymph nodes
• Most HIV strains us the CD4 molecule to enter cells (Aswell as co-receptor molecules CCR5 and CXCR5)
• Infected monocyte derived dendritic cells (MO/DC) are killed by virus or CTL.

Question 2

What are the viral and host factors that affect the outcome of HIV-1 infection?

Answer 2

-Viral burden predicts disease progression (Essentially how much of the virus is present in the blood). -Host factors that lead to long term non-progression -Slow progressor HLA profile -Heterozygosity for 32-bp deletion in chemokine receptor CCR5 -Secretion of CD8 antiviral factor -Effective CTL and HTL responses

Question 3

Outline the life cycle of HIV-1

Answer 3

1. Attachment/Entry
2. Reverse Transcription & DNA Synthesis
3. Integration
4. Viral Transcription
5. Viral Protein Synthesis
6. Assembly of Virus & Release of Virus
7. Maturation

Question 4

Describe the targets for current treatment of HIV-1

Answer 4

-Fusion Inhibitors (FIs) -Prevents Virus from entering cells -Eg Enfuvirtide -Attachment Inhibitors (AIs) -Prevents virus from entering cells -Not currently used clinically -RNA transcription inhibitors -Nucleoside or non-nucleoside (NRTIs or NNRTIs). The difference between NNRTIs and NRTIs is how they stop reverse transcriptase from working. -NRTI (Eg Abacavir) -NNRTI (Eg efavirenz) -Prevent reverse transcription of viral RNA into DNA -Integrase Inhibitors (INIs) -Prevents viral DNA form joining the host DNA -Eg Raltegravir -Protease inhibitors (PIs) -Prevents cleavage of newly formed viral proteins -Eg Atazanavir

Question 5

Explain the use of laboratory tests in the diagnosis and monitoring of patients with HIV-1 infection

Answer 5

• HIV is screened for using anti-HIV antibodies detected by ELISA blood test
• Anti-HIV antibody western blot confirms diagnosis of HIV
• Viral load is measured and determines prognosis/ progression
• Patients are monitored by measuring their CD4+ T cell count (Flow cytometry)

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-PCR for viral RNA can also diagnose (Very sensitive and can detect trace amounts)

Question 6

Describe the role of antiretroviral drugs in treatment of HIV-1

Answer 6

-To reduce the viral load in the host -To increase CD4 T cell counts -To improve the hosts immune system (reduce opportunistic infections)

Question 7

What is HAART?

Answer 7

-Highly Active Anti-Retroviral Therapy -HAART = 2NRTIs + PI (or NNRTI)

Question 8

Limitations of HAART?

Answer 8

-Doesn’t fully eradicate latent HIV in the host -Significant toxicities -Fails to restore specific HIV T cell responses