Immunology 2 - HIV infection Flashcards
HIV-2 vs HIV-1
Harder to transmit and less virulent
genetic material of HIV-1
RNA, diploid (2 single stranded RNA)
How is HIV RNA incorporated in to human genome?
Uses reverse transcriptase to convert RNA to DNA
Cells which can be infected by HIV
CD4+ T cells, CD4+ monocytes, CD4+ DCs
What is the receptor for the HIV virus?
CD4+ molecules/antigen
HIV co-receptor
CCR5/CXCR4
What does effective immunity to HIV require?
Antibodies to prevent infection and neutralise virus, and sufficient CD8+ T cells to eliminate latently infected cells
Acquired immunity to HIV
Antibodies: anti-gp120 and anti-gp41 (neutralising)
Non-neutralising anti-p24 gag IgG
Where are the CD4+ T cells mainly killed in HIV?
In the gut mucosa
Effects on other cells of infected CD4+ T cells being anergised by the virus
MO/DC are not activated by CD4+ T cells and cannot prime CD8 + T CELLs
CD8+ T nad B cell responses diminished without CD4+ T cell help
CD4+ T cell memory is lost
Infected MO/DC are killed by CTLs or virus
• Replication of the HIV genome is dependent on TWO steps during which errors can occur
- Reverse transcriptase (RNA –> DNA)
- Transcription of DNA in to RNA virus
Both low fidelity
Does antibody coating of HIV virus stop its infectivity?
no
7 main steps of HIV life cycle
- Attachment and entry
- Reverse transcription and DNA synthesis
- Integration
- Viral transcription
- Viral protein synthesis
- Assembly and release of virus
- Maturation
“gravir” which treatment?
integrase inhibitor e.g. raltegravir
“avir” which treatment?
protease inhibitor e.g. ritonavir, indinavir
Example of attachemnt inhibitor and its target
Maraviroc, CCR5 (RANTES)
Median time from HIV infection to AIDS development…
8-10 years
Rapid progressors time from HIV –> AIDS
2-3 years (10%)
Long-term non progressors
<5%, stable CD4+ counts and no symptoms after 10 years
Exposed seronegatives
people who are repeatedly exposed to HIV but do not seroconvert
Elite controllers
Can suppress viral replication
Long term non progressors host genetic factor
Heterozygosity for 32bp deletion in CCR5
LNPs host immune responses factors
Effective cTL and antibody response
Secretion of antibodies that block HIV entry co-receptors
CCR5 –> MIP1a MIP1b, RANTES
CXCR4 –> SDF-1
Screening test for HIV
ELISA
Confirmatory test for HIV
Western blot
How to assess viral load
PCR
How is the CD4+ T cell count monitored?
Flow cytometry
Antigens on T cells
CD3, CD4, CD8, CD19, CD56
2 WAYS to assess HIV ART resistance
Phenotypic (viral replications measured in cell cultures iwth increasing conc of ART)
Genotypic (sequence HIV genome)
General HAART combination
2 NRTIs + NNRTI or PI
When to treat
Treat all immediately if chronic infection confirmed, treat if symptomatic
What is tenofovir an example of?
NucleoTIDE reverse transcriptase inhibitor
What is zidovudine/AZT an example of?
NucleoSIDE reverse transcriptase inhibitor
Example of NNRTI
Efavirenz
Example of a fusion inhibitor
Enfuviritide
Which HIV drug is a P450 inducer?
Efavirenz
Which drugs inhibit P450?
Protease inhibitors e.g. ritonavir, indinavir
Big limitation of HAART
Does not eradicate latent HIV-1
When =is hIV ELISA/western blot positive?
After 10+ weeks infection
