Organ-Specific Immunity

Question 1

Recall the two HLA classes.

Answer 1

Question 2

Recall alleles for genes encoding MHC molecules that confer the highest risk of type 1 diabetes

Answer 2

• Serotype
  
  • HLA-DQ2: DQA1*0501 & DQB1*0201
  • HLA-DQ8: DQA1*0301 & DQB1*0302

Question 3

______________ confer the highest risk of T1D.

Answer 3

Question 4

High-risk MHC alleles can present ____________ to T cells.

Recall why is the HLA class II region associated so closely with T1D (and other autoimmune diseases)?

Answer 4

Question 5

Recall how alleles for insulin are associated with thymic expression & T1D risk

Answer 5

Question 6

Recall how an allele for PTPN22 is associated with T1D risk.

Answer 6

Increased phosphatase activity is predicted to:

• alter TCR signalling and diminish apoptosis induction during the negative selection of beta cell-specific thymocytes allowing autoreactive T cells to escape into the periphery
• alter BCR signalling that results in defective B cell tolerance and allows autoreactive B cells to escape into the periphery

Question 7

Recall identified islet self-antigens.

Answer 7

Question 8

Recall the association of islet autoantibodies and T1D clinical presentation.

Answer 8

Question 9

Are beta-cell antigen-specific autoantibodies directly pathogenic?

Answer 9

Question 10

Recall the phenotype of circulating beta-cell specific T cells in T1D patients

Answer 10

Question 11

How to detect beta-cell specific T cells?

Answer 11

Question 12

What are T-cell antigen targets associated with T1D?

Answer 12

Question 13

___________________ is the pathologic hallmark of type I diabetes.

Answer 13

Question 14

Recall characteristics of insulitis in pancreatic tissue from T1D patients

Answer 14

Both CD4+ and CD8+ T cells are detected in the islets that recognize beta-cell-derived antigens

• These autoreactive T cells secreted IFNgamma and other inflammatory cytokines = effector T cells

Question 15

Recall the immunohistological staining of an islet showing early stages of T1D destruction.

Answer 15

Question 16

Recall method in ‘capturing’ the islet-infiltrating T cells.

Answer 16

Question 17

Upregulation of HLA class I correlates with ___________________________.

Answer 17

Upregulation of HLA class I correlates with the number of CD8+ T cells in the islets

Question 18

Recall the correlation of viral infection with T1D.

Answer 18

Hyperexpression of HLA class I molecules are observed in tissues from patients with recently diagnosed type 1 diabetes

HLA class I and class II molecules can be upregulated in vitro by culturing human beta cells in vitro with IFNg

Question 19

___________________ recognize and kill beta cells.

Answer 19

Question 20

Recall the suspected path of an autoreactive T cell.

Answer 20