immunology

Question 1

what are the 4 mechanisms used to induce tolerance

Answer 1

deletion
anergize (switch off)
ignore (ignore the trigger)
regulate (contain the problem)

Question 2

which is more effective, B cell tolerance or T cell tolerance

Answer 2

T cell tolerance (see transient B cell autoantibodies with infections of some kinds all the time)

Question 3

what are the 3 mechanisms for central B cell tolerance and which is the major type

Answer 3

deletion (apoptosis) - major type
anergy
ignorance

Question 4

what causes the ignorance mechanism for B cells

Answer 4

low affinity interactions of the antibodies with self antigens - but there is no cross linking and therefore the cell is not triggered = ignorance

Question 5

what causes the anergy mechanism for B cells

Answer 5

there is some cross linking of the antibodies with self antigen and therefore activation, but because this is a naive B cell the response is to be turned off (unlike mature B cells which would proliferate)

Question 6

what causes the deletion mechanism for B cells

Answer 6

extensive cross linking of the antibodies with self antigen –> induces apoptosis of the B cell

Question 7

What is peripheral B cell tolerance

Answer 7

if an autoreactive B cell gets to the periphery… in the absence of T cell help (CD40L and some cytokines) the B cells life span is short

Question 8

what is a double negative and a double positive thymocyte

Answer 8

double negative - naive T cell that doesnt have CD4 or CD8 yet
double positive - naive T cell that has both CD4 and CD8

Question 9

what are the two main mechanisms for central T cell tolerance

Answer 9

• positive and negative selection –> deletion

- T regs –> regulation

Question 10

what is positive and negative selection of T cells

Answer 10

positive selection - thymocytes that express TCRs capable of recognising self-MHC are selected to survive
negative selection - removal of thymocytes that have too strong a reaction to self MHC

Question 11

what happens if a T cell can not recognise MHC

Answer 11

it dies by neglect

Question 12

how are T cells shown the self antigens it needs to see before leaving the thymus

Answer 12

specific TF = AIRE - turns on some genes to express particular proteins associated with organs other than the thymus –> facilitating negative selection

Question 13

which mechanisms are involved in peripheral T cell tolerance

Answer 13

deletion
anergy
ignorance
reguation

Question 14

explain the ignorance mechanism of tolerance in T cells

Answer 14

the T cell never encounters the antigen (eg. in a place in the body like the eyes that are immunologically privileged)

Question 15

explain the anergy mechanism of tolerance in T cells

Answer 15

there is presentation of the self antigen by MHC cells but there is no costimulation –> failure to proliferate –> inactivation

Question 16

what is the main mechanism by which Tregs help T cell toleance (in general)

Answer 16

expression of Foxp3 –> inhibits a whole bunch of T helper cell responses and CD8 cell responses

Question 17

what are the 2 major types of Tregs

Answer 17

nTreg - derived from the thymus during T cell development (subset of CD4 cells that are committed to Treg)
iTreg - derived following activation of naive CD4 T cell in the presence of TGF-beta

Question 18

how do iTregs promote T cell tolerance

Answer 18

• secrete immunosuppressive cytokines - IL10 and TGF-beta
• express CTLA4 and inhibit co-stimulation
• release molecules that create a ‘suppressive’ environment

Question 19

3 key components that lead to autoimmune disease

Answer 19

• genetic susceptibility
• environmental
• loss of self tolerance

Question 20

autoimmunity results from a

Answer 20

chronic ongoing autoimmune response with ongoing tissue damage

Question 21

2 classes of autoimmune diseases

Answer 21

organ specific

systemic

Question 22

what causes APECED (disease of autoimmunity)

Answer 22

defect in the AIRE gene –> decreased central tolerance –> multi-system autoimmunity

Question 23

what causes IPEX (disease of autoimmunity)

Answer 23

defect in the Foxp3 gene of Treg –> loss of Tregs and peripheral tolerance mechanism

Question 24

what are 3 diseases with B cell mediated autoimmunity

Answer 24

graves disease (stimulatory Ab) - Type 2 HS
myasthenia gravis (inhibitory Ab) - Type 2 HS
SLE (immune complex deposition) - Type 3 HS

Question 25

what are 2 diseases with T cell mediated autoimmunity

Answer 25

insulin dependent diabetes mellitus

multiple sclerosis

Question 26

is MS associated with CD4 or CD8 T cell autoimmunity

Answer 26

CD4

Question 27

what Thelper cells are associated with MS

Answer 27

Th1 and Th17 (IFN-gamma and IL17)–> detrimental

Th2 –> remission

Question 28

what are the two thoughts about the initiation of autoimmune disease

Answer 28

bystander

molecular mimicry

Question 29

what is the bystander thought of autoimmune initiation

Answer 29

infection can activate DCs to provide co-stimulation of T cells with exposure of self Ag due to dying cells

Question 30

in which part of the thymus, and by what cells is AIRE expressed

Answer 30

in the medulla by epithelial cells