3. HIV 2 Flashcards
(30 cards)
What are the progression of untreated HIV over years?
- Primary infection 0-9 weeks
- Asymptomatic infection/clinical latency = 9 weeks ~ 7 years
- Symptomatic infection and AIDS = 7 years onwards
What happens in acute HIV infection?
- Rapid and massive loss of CD4+ T cells.
- > 60% mucosal T-cells die (resting and activated CD4+ CCR5 memory)
- Massive T-lymphocytes in GALT
- Initial decline in HIV due to CD4 substrate exhaustion
What is the symptoms of primary HIV infection?
Transient CD4 deletion and fever, myalgia, nausea, rash, malaise. pharyngitis, oral thrush, meningitis etc
What is the incubation period of primary HIV infection?
2-4 weeks
Does acute seroconversion occur?
yes in 50-95% cases
When does HIV RNA start to become detectable?
1-18 days of infection?
What is the immune response to HIV?
- after virus dissemination body starts to make free gp41-specific non-neutralizing IgM antibody.
- The virus escapes from CD8 T cells and just keeps escaping virus specific neutralizing antibody.
Why are antibodies ineffective against HIV?
- Because of the high levels of Env glycosylation
- Virus also sheds free monomers of gp120
What are the mechanisms that allow HIV to escape the immune system?
- Sequence variation (high mutation rate and high replication)
- Exposed antigen are highly glycosilated
- Altered antigen presentation (downregulation of MHC1 by Tat, Vpu and Nef
- Loss of effector cells (clonal exhaustion, loss of CD4 help and apoptosis)
- Latency
- Privileged sites (brain)
At what level is the viral load undetectable?
-
What are the causes of T cell depletion?
CD4+ T cell destruction and Chronic immune-activation
How does HIV destroy CD4+ t cells
- Direct destruction of infected cells
- Indirect destruction of uninfected cells
1. Cytolysis by HIV-specific CTL or NK cells
2. Incorporation into synctitia (fused cells)
3. Immune activation of CD4 and CD8 T cells
How does HIV cause chronic immune-activation that deplete T cells?
- Destroy gut mucosal barrier so that microbial products leak into systemic circulation
- Immune system stimulated through TLR receptor
- Elevation of pro-inflam cytokines
- CD4+ T cells enter cell cycle and die
- CD8+ T cells become trapped in lymph nodes
- B cells make auto-Ab
- Also caused impaired T-cell production
What are the effects of HIV on Neutrophil?
Reduced killing of bacteria
What are the effects of HIV on B cell?
- General increase in antibodies
- Autoantibodies
- Poor response to vaccines
- Reduced killing of encapsulated bacteria
What are the effects of HIV on Macrophage?
Reduced phagocytosis, chemotaxis and killing
What are the effects of HIV on NK function?
Reduced function
At what CD4+ level do opportunistic infections occur?
200 CD4+ T lymphocytes/mm3
What are some of the opportunistic infections related to AIDS?
- Pneumocystis jirovecii Pneumonia (PCP)
- Oral infection Candida albicans
- Hairy leukoplakia (EBV reactivation)
- EBV Primary CNS lymphoma
- CMV in retina
- Cachexia
- Kaposi’s sarcoma (HHV-8)
What is the median surival time after
3.7 years
What is the median survival after AIDS?
1.3 years
What is the median CD4 at AIDS?
65 cells/mL
What co-infection actually protects against HIV?
GBV-C (Hep G)
What genetic mutation protects against HIV?
Homozygous for CCR5-D32 mutation, slowed progression if heterozygous
