Infectious Disease -- HIV Packet Additions #1 Flashcards
p24
Role in pathogenesis and monitoring
Core protein
Screening antibodies are made to this protein
gp120
Role in pathogenesis and monitoring
Coat protein which binds to CD4
Binds with CCR5 or CXCR4 to fuse with the cell
Identify and describe the three major stages of HIV
Primary Infection -Acute HIV, virus dissemination and seeding, rapid blood CD4 drop
Clinical Latency - Slowly dropping Blood CD4s
AIDS - Constitutional Symptoms, Opportunistic Disease, Death
Can HIV be transmitted by insect bite?
Nope
What are SEVI?
Semen derived enhancers of viral infection
Prostatic acid phosphates that assemble into amyloid like fibers
Effect of Circumcision on HIV transmission…
Increased transmission with uncircumsized.
Caused by increased presence of dendritic cells in the foreskin or retention of infected vaginal/rectal fluids under the foreskin
Seroconversion following HIV needle stick is ___%
0.3%
List CD4+ cells that HIV can bind to
T cells, NK cells, Monocytes, Macrophages, dendritic cells, glial cells
CCR5 is expressed primarily on…
HIV specific for CCR5 is called….
Monocytes and Lymphocytes
Monocytotrophic (M-Trophic)
CXCR4 is expressed primarily on…
HIV specific for CXCR4 is called…
Only T lymphocytes
Lymphotropic (T-Trophic)
Why does the switch to CXCR4 so rapidly escalate T cell destruction?
It binds a wider range of T cell types, including naive T cells and thymocytes. Also, lose some of the CD8 cell blocking
How do activated CD8 cells partly block viral uptake of HIV?
Production of RANTES, MIP-1a, MIP1b
These bind CCR5 and block the virus uptake
Once CXCR4, nothing it can do.
Explain HIV viral uptake into a cell
Gp120 binds CD4, then the coreceptor
gp41 binds, then undergoes conformational change
Fusion peptide generated that fuses virus+cell membrane
Describe the process of Lymph Node burn out
Loss of CD4 T cells in the gut leads to progressive, systemic inflammatory infection. Initially, this will cause lymphadenopathy and hypergammaglobulinemia, corresponding to germinal center hyperplasia. Later, all of the inflamm. cytokines will cause architectural and fxnal disruption of LN with cell loss and fibrosis.
Describe initial CD4 T cell loss
Initially large numbers are lost from LN, modest drop in blood levels
Usually mostly lost from Peyer’s patches
Reasons other than CD8 lysis and viral proliferation for CD4 loss in infection?
- Apop. of uninfected CD4 in LN from TLR induced entry to S phase
- Blocked fxn by gp120 binding (no antigen presenting)
- Fusion into syncytia, where they die
What type of cells are never recovered by HAART? Significance of this?
HIV-specific CD4 cells
HIV specific CD4s are probably the first to die
Progression of Immune Cell Loss
- Loss of fxnal CD4, no new cell/Ab mediated responses
- Loss of memory Bs and T cell precursors
- Loss of CD8
- Polyclonal B cell activation with no new responses
- Autoimmune Destruction
Viral load of an HIV patient should be assessed at least every..
3 months
Early in infections, HIV viral particles can be seen…
Follicular mantle cells
Dendritic Processes
Describe acute retroviral syndrome
- High levels of viral replication, viremia, and widespread N seeding
- Controlled by host anti-viral immune response
- Develops within 3-6 weeks and lasts 2-4 weeks
Describe prolonged latent infection
Patient may remain well
Slow immune deterioration
Progression indicated by steady state viremia
Describe Accelerated Progressive Immunodeficiency
Opportunistic Infections, Dementia, Neoplasms
Three latent infections that tend to be reactivated in AIDS
Toxoplasmosis
TB
Herpes Zoster
Explain kaposi’s sarcoma
HHV8 associated
Masses of proliferative spindle-shaped cells form blood channels (make endo, smooth musc, perictes)
Three forms of Non-Hodgkin’s Lymphoma
Systemic (80%)
Primary CNS Lymphomas
Body Cavity Based Lymphomas
Ways considered to boost anti-viral response without destruction of HIV specific CD4 cells
HAART + Interleukins
Passive Transfer of HIV-specific T cells
RANTES+MIP
Abs against cell debris or rapidly mutating epitopes