T1D summary

Question 1

mediators of B cell death

Answer 1

CD8
CD4- Th1 and Th2
Macrophages
B cells

Question 2

if B cells are infected with an enterovirus they will express

Answer 2

VP1

Question 3

VP1 expression is also correlated with increased..

Answer 3

PKR and Mda5

Question 4

PKR mediates

Answer 4

translational arrest

Question 5

Mda5

Answer 5

unregulated IFN-1- stimulates other cells around to stop protein synthesis- apoptosis

Question 6

both PKR and Mda5 stop labile proteins being produced e.g.

Answer 6

Mlc-2

Question 7

Mlc-2

Answer 7

usually prevents apoptosis

Question 8

concept of insulitiis

Answer 8

• autoantibodies
• B cell and antibody response
• destruction of cells which overexposes HLA-1 (binding region on MHC-1)

Question 9

HLA-1

Answer 9

binding region on MHC I

Question 10

autoantibodies in T1 diabetes do not themselves

Answer 10

cause β-cell destruction, but rather reflect autoimmune activity; the β-cell destruction is mediated through T-cell

Question 11

enterovirus implicated

Answer 11

cocksackie virus B

Question 12

how do virus’ infect B cells

Answer 12

hijack CAR receptors and enter the B cell (alpha cells have better immune response), because of insulin granules

Question 13

CAR found on

Answer 13

insulin granules

Question 14

virus convert RNA into

Answer 14

sdRNA

Question 15

persistent infection

Answer 15

virus evades immune system- staying the B cell surviving

- doesn’t cause cell to die or evoke an immune response

Question 16

how does persistent infection occur

Answer 16

viral replication complex

Question 17

the viral replication complex

Answer 17

stops recognition of virus and avoids cellular response by stopping production of sdRNA

Question 18

viral replication complex means that virus’ can

Answer 18

permits within B cell without triggering acute immune response

Question 19

persistent infection is a reason for

Answer 19

late onset- something trigger virus to start replicating dsRNA, meaning it is recognised by the immune system

Question 20

acute infection

Answer 20

virus starts producing dsRNA rapidly (no viral replication complex), meaning immune system destroys straight away

Question 21

acute infections are characterised by

Answer 21

sudden onset

Question 22

biology of +ve single stranded viruses

Answer 22

ssRNA uses reverse transcriptase to convert ssRNA to dsRNA

Question 23

dsRNA

Answer 23

evokes a strong immune response- not human (unless within viral replication complex)

Question 24

ssRNA has a specific surface protein which

Answer 24

binds to CAR receptor - increasing uptake

Question 25

vaccine development

Answer 25

difficult to identify an immunogenic antigen produced by the virus
- may evoke an autoimmune repsonse

Question 26

why is diabetes not an infectious disease

Answer 26

• won’t get the disease unless have the genetics for it

Question 27

genetics variation which increases susceptibility to T1D

Answer 27

if you have polygenic mutations (PKR and Mda5)- may have increased susceptibility to B cell destruction by virus’

Question 28

most diabetes is

Answer 28

polygeneic

Question 29

name two non polygenic T2D

Answer 29

• neonatal (ABCC8, KCNJ11)

- mody (HNF1a, HNF1b, HNF4b and glucokinase)

Question 30

GAD

Answer 30

glutamic acid decarboxylase- antigen found on surface or B-cells

Question 31

anti-GAD antibodies found in how many patients

Answer 31

50-70%- usually later stage