Vaccine for T1D Flashcards
what are the immune cells present in insulitis infiltrate?
- CD8+ T cells
- CD20+ B cells
- CD45+ cells
- CD68+ macrophages
- CD4+ T cells - absent
in what order of prevalence are immune cells present in islet infiltration as beta cell are destroyed?
CD8>CD20>CD68>CD4
which virus is associated with T1D?
enterovirus
which viral capsid is prevalent in T1D?
- VP1
- VP2
- VP3
- VP4
VP1
name the viral sensors that could be activated in infected islet cells and what function do they mediate?
- protein kinase R - translational arrest (switcher of protein synthesis and stops the virus from replicating)
- Mda5 - viral sensor/interferon expresser (can sense sRNA)
- RIG-1 interferon expression
- TLRs - interferon expression
enhanced PKR is found in which cells?
- islets cells
- VP1 immuno positive islet cells
- Both
Both
how does Pkr mediate its effect?
Pkr works by phosphorylating eukaryotic initiation factor (elF2alpha) -> inhibits its activity and prevents protein translation
what is Mcl-1 and where is it found in T1D?
Mcl-1 is an anti-apoptic protein and is found in islet cells
what is the impact of PKR on Mcl-1
- PKR mediates translational arrest in islet cells
- Mcl-1 are present in islets therefore, its inhibits the production of Mcl-1 as well
- since mcl-1 is an anti-apoptic protein inhibiting its formation will also terminate the anti-apoptotic property therefore, resulting in increased apoptosis
Mcl-1 is selectively depleted from islets?
A. True
B. False
why?
A. True, they are depleted from islets cells because PKR mediates its effect of translational arrest of cells resulting in decreased new Mcl-1 formation
what is DNA characteristics of
- acute infection
- persistent infection
- acute infection - presence of excess single positive strands over negative strands + VP1 expressed in infected cells
- persistent infection - equal number of positive and negative RNA strands -> dsRNA + VP1 less demonstrable
dsRNA is detected in islet cells in T1D?
- True
- False
- True, detected in beta cells of T1D and absent in alpha cells
what is Mda5 and where is it found in islet cells?
Mda5 is viral sensor
- it is found in endocrine cells of non-diabetic patients
- it is expressed in alpha cells of T1D but higher expression in beta cells
- dsRNA detected in beta cells of elevated Mda5
what is the evidence that T1D is an autoimmune disease?
- immune infiltrates like enhanced CD8+ T Cells , CD20+ B cells, CD45+, CD68+ macrophages and reduced CD4+ cells are detected in islet cells of T1D
- islet auto antibodies are detected
how are islet auto-antibodies involved in T1D?
the presence of auto antibodies and auto reactive T-cells are directed against islets cells or their antigenic constituents e.g. GAD-65, IA-2 and insulin