Trigger 4 - Vaccination for Type 1 Diabetes Flashcards
Infection of beta cells with enterovirus leads to ____________, which causes autoimmune attack against beta cells.
Insulitis
The overriding immune cell population involved in Type 1 Diabetes is __________.
Cytotoxic CD8+ T cells
What is the mechanism by which Fas receptor induces apoptosis in beta cells?
A. Caspase-3 activation
B. Perforin release
C. Jak-STAT signaling
D. NF-kB translocation
A. Caspase-3 activation
Which cytokines are involved in the immune response against beta cells?
A. IL-6 and IL-8
B. IL-1B, TNF-a, and IFN-y
C. IL-2 and IL-4
D. IL-10 and TGF-beta
B. IL-1B, TNF-a, and IFN-y
True or False: Fas expression on CD8+ T cells is influenced by IFN-y and IL-1B stimulation.
True
True or False: NO production, induced by IL-1B, IFN-y, and TNF-a synergy, leads to ATP depletion and cell death.
True
Define “Insulitis” in the context of Type 1 Diabetes.
Insulitis refers to the autoimmune attack against beta cells, involving the infiltration of immune cells, such as T and B lymphocytes, macrophages, and dendritic cells, into the pancreatic islets.
Define “FasL/Fas” and its role in the apoptosis pathway.
FasL/Fas refers to the interaction between Fas ligand (FasL) on CD8+ T lymphocytes and Fas receptor on beta cells. This interaction activates the apoptotic pathway through the recruitment of Fas-associated death domain (FADD) and subsequent activation of caspase-8.
Describe the role of perforin and granzyme in CD8+ T cell-mediated apoptosis of beta cells.
Perforin and granzyme released from CD8+ T cells play a crucial role in beta cell apoptosis. Perforin induces pore formation in the beta cell membrane, allowing the entry of granzyme. Granzyme activation leads to the activation of Bid, initiating the mitochondrial death pathway and ultimately causing apoptosis.
Describe the mechanisms by which cytokines IL-1B and IFN-y contribute to beta cell death in Type 1 Diabetes.
IL-1B binds to its receptor, leading to the activation of NF-kB and MAPK pathways. IFN-y, on the other hand, induces the dimerization of Jak1 and Jak2, leading to the recruitment of STAT1. These pathways converge to regulate the expression of pro-apoptotic elements, including caspases, Fas, and iNOS.
Perforin and granzyme, released from CD8+ T cells, mediate beta cell apoptosis through the formation of pores in the membrane via a __________ mechanism.
Ca2+
The synergy of IL-1B, IFN-y, and TNF-a leads to the production of __________, which elicits DNA damage and activates PARP, ultimately inducing cell death.
NO (Nitric Oxide)
Which immune cell population is the predominant one in insulitis during Type 1 Diabetes?
A. B lymphocytes
B. Macrophages
C. Cytotoxic CD8+ T cells
D. Dendritic cells
C. Cytotoxic CD8+ T cells
What is the role of FADD in the FasL/Fas-mediated apoptosis pathway?
A. Cleavage of caspase-3
B. Recruitment of perforin
C. Activation of Bid
D. Formation of pores in the membrane
A. Cleavage of caspase-3
True or False: Insulitis involves the infiltration of immune cells, including only T lymphocytes and macrophages.
False
True or False: Fas expression is influenced by IL-2 and IL-4 stimulation.
False
Define “Cytotoxic CD8+ T cells” and explain their role in Type 1 Diabetes.
Cytotoxic CD8+ T cells are a subset of T lymphocytes that play a crucial role in Type 1 Diabetes by mediating the autoimmune attack on beta cells. They release perforin and granzyme, leading to beta cell apoptosis.
Define “Nitric Oxide (NO)” and describe its role in beta cell death.
Nitric Oxide (NO) is a signaling molecule produced during the synergy of IL-1B, IFN-y, and TNF-a. NO induces DNA damage and activates PARP, contributing to beta cell death through ATP depletion.
Describe the steps involved in Fas receptor activation and its downstream effects on beta cells.
Fas receptor activation involves trimerization and recruitment of Fas-associated death domain (FADD), followed by caspase-8 activation. Caspase-8 then cleaves caspase-3, initiating the mitochondrial death pathway by cleaving Bid, leading to beta cell apoptosis.
Describe the role of cytokines IL-1B, TNF-a, and IFN-y in the immune response against beta cells during early insulitis.
These cytokines, secreted by immune cells like CD8+ cytotoxic T cells and CD4+ helper T cells, contribute to the progression of insulitis. IL-1B activates NF-kB and MAPK pathways, while IFN-y regulates the expression of pro-apoptotic elements, leading to beta cell death. TNF-a also plays a role in this synergistic process.
Insulitis is defined as the presence of at least __________ CD45+ cells/islets in a minimum of 3 islets.
15
Peri-insulitis involves infiltrates of immune cells at the __________ of the islets.
Periphery
What is the main role of CD45+ cells in insulitis?
A. Beta cell destruction
B. Insulin production
C. Immune cell infiltration
D. Islet regeneration
C. Immune cell infiltration
What percentage of islets typically show insulitis in a T1D pancreas?
A. 5-10%
B. 10-30%
C. 30-50%
D. 50-70%
B. 10-30%