HIV Immunology Flashcards
4 risk profiles for HIV testing
- Gay MSM accounts 80% HIV cases nsw
- IDUs
- Pregnant woman - antenatal care
- Girls 14-24 South Africa
What are the 3 broad complications of AIDS
- Infection by opportunistic pathogens
- Certain malignancies - lymphoma, kaposis sarcoma, cervical cancer
- Depletion of CD4 cells in number and function
Typical timeline of HIV infection untreated
- Window period 2-3 weeks undetectable
- Primary infection 5-21 days similar to glandular fever
- Clinical latency - asymptomatic 7-8 years
- AIDS 200 CD4 threshold OR aids-defining illness
- Death 1-2 years after diagnosis
What type of virus is HIV and 2 features of these…
Retrovirus of 10,000 base pairs
- Reverse transcribed by viral transcriptase
- Integration into genome for replication
Mechanism of HIV entry into cell
- Envelop gp120 binds CD4
- Sequentially, gp120 binds chemokine receptors (CCR5/CXCR4) on CD4 cells
- BOTH conform changes, expose fusogenic domain of gp41 - allows fusion into cell
- Reverse transcription - dsDNA
- Integration
Two tests run for HIV and what do they tell
- CD4 T cell count - indicates immune reserve
2. Viral load - estimate of how fast immune reserve is being destroyed, and also infectivity of patient
Correlation of CD4 count with disease
500 - normal 400 - TB, kaposis sarcoma 200 - PCP 100 - CMV 50 - non hodgkins lymphoma, MAISONETTES
2 features that contribute towards HIVs high mutation rate
- High turnover
T1/2 viral particle 6hrs
T1/2 inf cell 2.5days - Mistake ridden
1 mistake/copied genome
Viral load values (copies/mL) at…
- Average viral load
- Seroconversion
- Late in disease
- Clinically undetectable
- Av viral load asymp 10^4 - 10^5
- Seroconversion 10^7 copies/ml serum
- Late in disease 10^6
- <20 copies/mL
What tests are performed to confirm HIV diagnosis
ELISA test for HIV antibodies. If positive, run western blot - very sensitive blood test
5 features of seroconversion illness in HIV
- Fever, rash, sore throat, enlarged LNs
- Reversal in CD4:CD8 ratio - CD8 activated to kill CD4 infected cells
- Rise in CD8 T cell number
- Detectable antibodies
- Reduced viral load in peripheral blood
Location of epitopes for neutralising antibodies (3) and difficulties faced
- V3 hyper-variable loop of gp120. Block initial binding to CD4
- Chemokine receptor binding face gp120. Block interaction to CCR5. Ig too big but other molecules synthetically possible
- Gp41 fusogenic domain. Looks like self antigens
Describe the alterations in CD4 T cell function in HIV (4)
- Reduction in IL-2 production. Less stimulus for CD8 cells
- Loss of proliferation
- Memory to HIV cells lost (or never generated)
- Loss of CD4 response to other pathogens. TB earlier than CMV
Dendritic cells are _________ with virus and are effective amplifiers of virus by interacting with CD4 T cells
DECORATED
Sit at end of DC filopodia - where CD4 T cells communicate
What 3 drugs are involved in anti-retroviral therapy. Why is combination essential
Minimum 3 drugs
2 nucleoside reverse transcriptase inhibitors plus 1 integrase inhibitor
Virus has to become resistant at multiple sites simultaneously.
More drugs = more mutations required
Less viral load = Less viral turnover = less mutations
