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
what is insulitis and how it might play a role in beta cell destruction?
- insulitis is the inflammation of islet cells
- the presence of auto reactive immune cells with insulitis infiltrates like B cells, T cells, macrophages and dendritic cells result in increased inflammation which lead to beta cell death
what are enteroviruses and how do they replicate?
enteroviruses are any group of RNA viruses (including those causing polio and hepatitis A) which typically occur in the gastrointestinal tract, sometimes spreading to the central nervous system or other parts of the body
how is viral infection sensed by cells and what anti-viral responses are mounted?
viral infection is sensed by:
1. dsRNA
2. interferons (proteins expressed by viruses)
2. presence of VP1 (viral capsid)
anti-viral responses include activation CD8, APC and B cells to neutralise the viral antigen
how can you say that enteroviruses may be causing T1D?
- enhanced expression of Mda-5 (viral sensor/interferon expresser) in beta cells + expression in alpha cells
- enhanced PKR activity in VP1 immunopositive islet (beta cells) cells
- reduced Mcl-1 in islets expressing VP1
- presence of VP1 (viral capsid) in islets of children with T1D
- dsRNA present in beta cells in T1D
