Pathogenesis of T1DM Flashcards
Descent from which continent has the highest rates of T1DM
Europe
What cells in the body are destroyed in T1DM and how are they destroyed
Immune destruction of beta cells of the islets of the pancreas via infilitrating cytotoxic (CD8+) T cells
Describe the pathogenesis “model” of T1DM
1) After birth an immune balance is established in which autoreactive T-cells are kept in check by immune regulation
2) Unknown trigger changes the immune tolerance to an unbalanced state
3) This imbalance is between autoreactive T cells and T-regulatory cells
4) This unbalanced state results in activation of B cells (to produce islet autoantibodies) and effector T cells
Which chromosome contains all HLA genes
6
What are the two main types of HLA genes that are linked to diabetes
HLA-DQ and HLA-DQ
What immune cells do class II MHC antigens present to
CD4 lymphocytes
What important genetic concept is present between DR and DQ genes
Linkage disequilibrium
What HLA gene is protective against T1DM
DQ-6
When do islet autoantibodies typically develop
Between 9 months and 2 years
Describe the two main theories behind environmental causes of T1DM
Viral infections and the north/south hypothesis
What virus is thought to be the most strongly linked to T1DM and why
Enterovirus (coxsackie B) because development of autoimmunity follows seasonal enterovirus infection (associated with DAISY cohort)
Describe the molecular mimicry hypothesis
Molecular mimicry is defined as the theoretical possibility that sequence similarities between foreign and self-peptides are sufficient to result in the cross-activation of autoreactive T or B cells by pathogen-derived peptides.
Describe the north south hypothesis
T1DM is much higher in the northern hemisphere and this is suspected to be due to vitamin d deficiency during pregnancy
What antibodies are markers for T1DM pathogenesis
Islet autoantibodies
What are the 4 beta-cell protein autoantibodies produced in diabetes
Insulin, GAD65, IA-2 and ZnT8 transporter (93% of T1DM patients have at least one of these)
What percentage of the islet cells are destroyed when T1DM becomes present
90%
Describe the ideal therapeutic goals in T1DM (4)
1) Prevention of immune destruction
2) Preservation of beta cell mass
3) Replacement or regeneration of beta cells
4) Automated insulin delivery
Describe primary prevention of type 1 diabetes
Targeting high risk individuals prior to developing islet autoimmunity
Describe secondary prevention of type 1 diabetes
Aimed at targeting individuals once autoantibodies have developed (non-autoantigen approach and auto-antigen approach)
Describe intervention of type 1 diabetes
Targeting individuals newly diagnosed with T1DM
Describe teplizumab
It is an anti-CD3 antibody that can prevent the development of type 1 diabetes
