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HIV immunolopathology-Grandganett
HIV immunopatholgy
20
Microbiology
Graduate
09/27/2018

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Cards

Term
*What are the groups and subtypes of HIV-1?
Definition
Pandemic form is Group M and there are 8 subtypes (ABCDFGHF).
B is dominant in N. America.
Term
*What is the origin of HIV-1?
Definition
SIVcpz (most closely related to HIV-1). This occurred in Cameroon. Probably occurred well before 1950.
Term
*What are 2 reasons that HIV causes AIDS?
Definition
1. HIV replicates in immune cells, causing dysfunction and direct killing of CD4 cells.
2. Integration of viral DNA results in latency and produces reservoirs of infected cells not susceptible to HIV inhibitors (must be actively replicating to be sensitive to inhibitors).
Term
*Describe the estimated half-lives of different forms of HIV-1 and why this is important for pathogenesis.
Definition
Free virions have very low half lives. Resting CD4+ cells with integrated HIV have essentially infinite half lives.
Term
*What is the innate cellular immune response to HIV-1 with examples?
Definition
1. Aborted viral genomes accumulating in cells infected by cell-cell transmission is recognized by IFI16 and then triggers Caspase-1 activation.

2. APOBEC3 is a cytidine deaminase
Term
How is HAART effective in preventing AIDS?
Definition
Inhibits replication. Results in dramatic decrease in viral titer within 2 weeks, followed by a slower decline.
Term
Limitations of HAART
Definition
1. Long lived memory T cells with latent infections not sensitive to HAART.
2. Privileged organs (i.e. some drugs can't cross bbb)
3. Resurgence of CD4 upon discontinuation of treatment (strict compliance necessary).
4. Only half of the world's infected pop on HAART
5. 99% learn about infection too late to prevent reservoir establishment.
6. 25% of infected population do not know they are infected.
Term
Describe the basic disease progression from infection to AIDS.
Definition
Acute HIV, dramatic rise and fall of HIV titer with minor CD8 response. Years later, replication dramatically increases and simultaneously, CD4 and CD8 T-cells drop dramatically.
Term
4 obstacles to vax development.
Definition
1. Failure to generate high levels of immune effectors (Abs and CTLs)
2. Weak and transient mucosal immunity.
3. Inaccessibility of neutralizing antibody epitopes.
4. Strain variation in pop due to high mutation rate.
Term
Identify the different types of vaccines that have been attempted and their benefits pitfalls.
Definition
1. gp120 with adjuvant (surface glycoprotein). (Ab only)
2. Non-replicating virus vectors (CTL only)
3. Replicating virus vectors (Ab/CTL response)
4. Plasmid encoding HIV proteins (only CTL)
5. Above 4 + HIV peptides (Ab/CTL)
6. Nef- HIV (Ab/CTL)

40 attempts and 40 failures.
Term
AIDS public health data.
Definition
Needle sharing and sex is primary means of spread.

New annual infections on decline. Socioeconomic factors. 20% in US unaware of infection.

~50% of HIV+ on HAART.
Theoretical efficacy of HAART=90%, actual efficacy 25% due to noncompliance.

Coinfection with HCV is problem
Term
Describe the pathologic features of AIDS (2 direct effects and 1 indirect effect).
Definition
1. Dysfunction of immune cells.
2. Direct depletion of CD4 cells
3. Opportunistic infections and cancer.
Term
What's the relationship between HIV replication and AIDS progression?
Definition
Increased replication=faster progression to AIDS.
Term
Define HIV set point, and describe its relationship to AIDS progression.
Definition
Viral load during the latent period (after acute infection and before progression to AIDS). Basically, the viral titer of an individual during this period is a balance between viral replication and immune control. The only way to lower the set point is HAART.

Higher setpoint=faster progression to AIDS. Duh... the more viral particles present which are capable of replication and infection, the quicker the immune system will be exhausted.
Term
Describe the primary entry of HIV into the human body and infection of cells. 6 steps
Definition
1. Mucosal barrier is breached by virus.
2. Local infection of tissue resident immune cells (DCs/Macs).
3. Dissemination to LNs.
4. Immune activation.
5. Establishment of latent reservoir in GALT and other lymphoid tissues.
6. Systemic dissemination of virus and infected cells.
Term
2 ways in which HIV-1 directly causes CD4+ cell death (independent of immune mediated cell killing).
Definition
1. DDR/caspase 3-dependent cell death. Integration produces gaps in cellular DNA which activates the DNA damage response and the DNA-dependent protein kinase. This kinase phosphorylates p53 and Histone 2AX. This activates caspase 3 and causes apoptosis.
2. Caspase 1, IFI16-mediated "Pyroptosis". IFI16 recognizes aborted DNA and induces caspase-1. This is the innate antiviral response and results in release of IL-1B and immune exhaustion. This mode of cell death only occurs upon cell-cell transfer of HIV-1. The cells to which viral particles are transferred accumulate viral DNA and abortive genomes.
Term
Mechanisms of latency (4).
Definition
1. Promoter read-through.
2. RNAP collision (TRXN in both directions.
3. Epigenetic silencing.
4. Chromatin Silencing.
Term
Mechanisms of immune subversion.
Definition
1. Integration creates latent pool.
2. Stealthy entry (target memory cells, hidden epitopes, downregulation of immune molecules)
3. Chronic rep in reservoirs. Immune exhastion and destruction.
4. Genetic variation.
Term
Why is the N-terminal fusion peptide of gp41 (8 AA) a good vaccine target?
Definition
1. It is not glycosylated.
Term
What is passive immunity?
Definition
Administration of broadly neutralizing antibodies. Antibodies were cloned from 2 HIV-1 positive viremic controllers.
Neutralize multiple HIV-1 strains.
Provided protection in rhesus macaques for 30 weeks
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