HIV Flashcards
What are the hallmarks of HIV?
immunosuppression
immune activation
chronic inflammation
When does HIV become AIDs?
when CD4 T cell levels <200 cycles/mm3
- are more susceptible to opportunistic infections
What is the mechanism of action of HIV? What cells does it target?
infects CD4 T helper cells preferentially
- lymph node is the main site of infection as it is the location of B and T cells
other cells travelling to the lymph node are also infected
- antigen presenting cells like dendritic cells, macrophages
What cell types does HIV target? The absence of what feature makes it harder for cells to be infected?
cells with CD4 cell surface receptor molecules
- the absence of co-receptor CCR5 and CXCR4 makes it harder to contract HIV
cells with Fc receptor sites or complement receptor site
- monocytes, macrophages, B lymphocytes, natural killer cells, dendritic cells, microglial cells
What is the latent period during HIV infection?
period of clinical latency in which they have few or no symptoms
- can last between months and years (minimum 3 months)
- HIV replicates but at a slow rate
- CD4 T cell levels are maintained
Where are T cells made? Where are T cells developed/educated?
T cells are made in the bone marrow
T cells are educated in the thymus
Where are CCR5 and CXCR4 receptors found?
CCR5
- memory T lymphocytes
- macrophages
- dendritic cells
CXCR4
- memory T lymphocytes
- naive T lymphocytes
What is the initial site of HIV replication? Where does HIV replication move to (major site)?
initial site is within inflammatory cells at the site of infection or within peripheral blood mononuclear cells
- all leukocytes
= neutrophils, monocytes, macrophages
major site of replication
- lymph nodes, spleen, liver, bone marrow
- the gut associated lymphoid tissue
= reservoir for HIV
Where does the majority of CD4 T cell death occur?
gut associated lymphoid tissue
- due to the high levels of replication occurring here causing severe T cell depletion
Where is the HIV reservoir?
HIV establishes latent infection within memory CD4 T cells
- cells are maintained indefinitely even if HIV is eradicated
- are dormant until reinfection
HIV can also establish lung term infection of the naive CD4 T cells, monocytes and macrophages
How is HIV integrated into cells?
HIV infects resting T cells
- these cells carry partially transcribed, unintegrated viral double stranded cDNA
- can be degraded in the absence of activation
HIV infects resting cells
- upon activation via stimulation by antigens, they begin clonal proliferation which allows the integration of viral dscDNA into the host cell genome and activates HIV replication
- induces post integration latent state and a continuous low level replication even in the absence of activation
How does HIV evade the immune system?
hide in microglial cells on the central nervous system
hide in resting T cells
decrease the expression of MHC 1 molecules
- allows HIV to escape detection by cytotoxic T cells
decreases the expression HLA
- avoids activation of natural killer cells
have a high mutation rate
induces apoptosis in by standing cells
How is HIV monitored?
CD4 T cell count
viral load
full blood count
renal function
liver function
bone profile
What are the types of therapeutic strategies?
immunosuppressants + HAART
- decrease activation of CD4 T cells and reduce their susceptibility to viral infection and replication
reactivation of latent reservoirs
- to eradicate latent HIV
What is U=U? How is it achieved?
U=U means that people with HIV who achieve and maintain an undetectable viral load
- the amount of HIV in the blood, <50 copies/mL
