HIV Part 2 Flashcards
Histological examination of lymph nodes show?
Influx of CD8 T cells
How does HIV exploit dentritic surveillance network?
- Hitches ride to lymph nodes, before trasfer to CD4 T cell
- Via Sialyllactose head on GM3 ganglioside (glycosphingolipid)
- On HIV membrane
- Recognised by dentritic cell
- Taken in
Sialylactose head on GM3 ganglioside
- Sialyated head
- On lactose (galactose+Glucose)
Consequence of loss of Th activity
mount a delayed-type hypersensitivity reaction
HIV infected dendritic schematic diagram
- HIV entering vagina -> unprotected sex
- Crossing epithelial layer
- Submucosal epithelium =encounter immature dentric cell
- Lectin (dentric cell) attachment to GM3 ganglioside on HIV virus
- Movement to lymph node
- Dentric cell mature in lymph node, enter germinal centre and pass HIV -> CD4+ T cells
- How? filopodia (actin rearrangement)
Antibody abnormalities in HIV positive patients
- High increase of antibodies (Ig)
- Production of autoantibodies
- Affecting RBC, sperm cells and myelin sheeth in neurons
Define viraemia
High levels of viral particles in bloodstream after infection due to rapid phase of viral replication
What is the initial immune response to HIV?
- Recognise gp120,p24 (nucleocapsid) and pO1(reverse transcriptase proteins)
- Mount a resonse: Increase number of CD8+ cytotoxic T cells and antibody
- Combined-> 99% clearance
- Virus enters latent/dormant stage
- Persist -> chronic infections
- Challenge: manage and treatment against HIV
Immune response
Lower viraemia suggests?
Slower progression to AIDs compared to higher viraemia
Immune response
What did advanced methods of viral RNA detection in latent phase indicate?
- Active replication present even in latent phase
- > Persistent level of active viral replication
- > Viraemia
- Concentrated in lymph nodes
- Physically- structural abnormalities
- Worsening as disease progressed
Immune response
Whats the importance of treatment?
- Drug -> block new infections
- clears 30% viral load/day
- Without drug
- > Rapid rate of viral replication, easily replace the cleared viral load
- 2 billion CD4 T cell eliminated and replaced by immune system
- > gradual decline of CD4 T cells
The traditional concept of the latent stage of HIV infection as a period of relative quiescence is now being redefined to what?
- Dynamic phase
- Intense viral replication and destruction
- Continueous of cycle of CD4 T cells being lost and replenishes
What is latent phase indicative of?
- Immune activity
- Viral acitivity
- Even if infection seems less active on surface
Why does the immune system not completely clear the virus?
- High replication rate- overwhems immune system
- Proviral Latency- unable to detect and recognise by immune system
- Mutation rate- changes its antigen to not match CD8+ t cells and antibodies
Whats the dual mechanism that results in the loss of CD4 T cells?
- Direct killing by the virus
- Immune system-mediated destruction
- Vulnerable to recognition and attack by immune system
Explain direct killing by the virus
- HIV replicated
- > damage to cell
- Reduce CD4 overtime
Explain Immune system-mediated destruction?
- Infected CD4 display viral antigens
Viral Antigens
* Viral peptides presented by MHC I molecules
* soluble gp120 bound to CD4 T cell
- Viral antigens recognised by CD8+ cytotoxic killer T cells
- Killing infected CD4+
What is present in the blood and lymph of HIV positive patients?
Soluble gp120
Binds to CD4 T cell
Potential exam diagram question
Killing Mechanism of CD4 T cells diagram
Killing of CD4 T cells.
(a) HIV may directly causelysis of CD4 T cells.
(b), (c) Infected cells bearing HIV antigens may be killed by antibody and complement (b) or killed by **antibody-dependent cell-mediated cytoxicity **(ADCC) (c).
(d) HIV-infected cells presenting HIV peptides on their class I MHC molecules may be killed by CD8 T cells.
Which drug targets caspase 1 and pyroptosis of lymphoid CD4 T-cells
Drug- VX-765 in lymphoid tissues
* Inhibits activation of caspase-1 enzyme
* main enzyme thay mediates pyroptosis
Benefits
* Preserve CD4 cells
* Reduce inflammation
Diagram of Pyroptosis CD4 T cell location
HIV Vif degrades Inteferon-a JAK/STAT1 and 3 pathway
- Vif = HIV protein
- Interfers the IFN-alpha signalling pathway
- > activated by STAT 1 andn STAT 3 proteins
- > enter nucleus and regulate gene expression->antiviral defense
- Vif intefer via targeting degredation of cellular protein
- > dampen ability to respond to inteferon
- > initiating antiviral response
indirectly suppresses the interferon-alpha (IFN-α) signaling pathway by targeting the antiviral protein APOBEC3G for degradation.
New Antiviral Strategy
compound= PA-457
* Normal capsid protein is assembled cone -shaped assemble ssRNA and other components
* PA-457 - intefers with normal processing of capsid protein
* How: prevent cleavage of capsid protein from gag protein
* No longer cone-shaped “leaky sphere”
* >doesn’t fully enclose viral RNA
*»_space;inability to replicated and infect new cells
Potential target antiviral therapy
HIV-1 Epitopes Targeted by Broadly Neutralizing Human Monoclonal Antibodies
- Epitopes are specific regions-surface of the envelope proteins
- > recognized by the immune system
- > targets for antibodies
- neutralize a wide range of HIV strains
- due to their recognition of conserved epitopes
Vaccine strategy
* antibodies that can effectively target these specific epitopes on the virus.
The arrows indicate four areas, or epitopes, of the envelope that are the targets of human monoclonal antibodies that, in laboratory assays,have proved capable of neutralizing a wide array of virus strains.
