Immuno 8: HIV Infection Flashcards
Which cells does HIV mainly infect ?
CD4+ T helper cells
Name 2 co-receptors of T cells that HIV-1 needs to bind to in order to cause infection ?
CCR5 or CXCR4
List 3 routes of transmission of HIV ?
Sexual- especially anal sex
Infected blood- Needle sharing, transfusions, blood products
Vertical transmission- Mother to child during birth or breast feeding
At which 2 parts of HIVs lifecycle do mutations occur that create variation in its genome ?
1- When reverse transcriptase converts viral RNA into DNA
2- When viral DNA is transcribed in the host’s nucleus into viral RNA
List 4 possible mechanisms that can could cause long term non-progression in HIV infected patients ?
CCR5 mutation
Effective CTL & HTL response
Infection with attenuated strain of HIV
Secretion of chemokines that block HIV entry into cells - MIP-1a
Which tests are done for HIV screening, diagnosis, severity ?
HIV antibodies on ELISA (screening test)
HIV antibodies on Western blot (Confirms diagnosis)
Viral RNA on PCR (viral load)
CD4+ count on flow cytometry
Why does HAART not eliminate HIV infection ?
There is a reservoir of HIV in resting CD4+ cells
List 3 classes of anti retroviral drugs and an example of a drug in each ?
Nucleoside reverse transcriptase inhibitors (NRTI)- Zidovudine
Nucleotide RTI- Tenofovir
Non-NRTI- efavirenz
Protease inhibitor- ritonavir
what are the receptors and coreceptors for HIV
CD4 molecule = receptor for HIV-1
most infecting strains also need co-receptors CCR5/CXCR4 to enter cells
what are the features of natural HIV immunity
mobilised within hours of infection + involves:
- inflammation
- non-specific activation of macrophages
- non-specific activation of NK cells and complement
- release of cytokines and chemokines
- stimulation plasmacytoid dendritic cells by toll-like receptors
what are the features of acquired HIV immunity
anti-gp120
anti-gp41
non-neutralising anti-p24 gag IgG
what are the effects of HIV-1 on CD8+ T cells
CD4+ T cells are disabled (anergised) by the virus
so monocytes and dendritic cells are not activated by CD4+ T cells and cannot prime naive CD8+ T cells
CD8+ T cell and B cell responses are diminished without help from CD4+
CD4+ memory cells lost
infected monocytes and dendritic cells will be killed by the virus or by CD8+ T cells
what is the life cycle of HIV
attachment and entry reverse transcription and DNA synthesis integration viral transcription viral protein synthesis assembly and release of the virus maturation
what is the clinical course of HIV
median time from HIV infection to development of AIDS = 8-10 years
viral burden predicts disease progression
rapid progressors take 2-3 years
long-term non-progressors have stable CD4+ counts and no symptoms after 10 years
exposed-seronegatives (ESN) = people who are repeatedly exposed to HIV but do not seroconvert
list some possible mechanisms for long term non-progression in HIV
host genetics:
- slow progressor of HLA profile
- mannose binding lectin alleles
heterozygosity for 32-bp deletion in chemokine receptor CCR5
host immune respone factors:
- effective CTL + HTL responses
- secretion of CD8 antiviral factor
- secretion of chemokines that block HIV co-entry receptors CCR5 + CXCR4
virologic factors:
- infection with attenuated strains of HIV