Tolerance and Autoimmunity

Question 1

Central tolerance occurs in

Answer 1

the generative lymphoid organs

recognition of self Ag will lead to apoptosis, b cell receptor editing or development of regulatory T cells

Question 2

Peripheral tolerance occurs in

Answer 2

peripheral tissues

recognition of self Ag in the peripheral tissue results in Anergy, apoptosis, or suppression (by T regs)

Question 3

AIRE protein

Answer 3

Autoimmune regulator protein
stimulates expression of peripheral “tissue-restricted” self Ag in the thymus
involved in the negative selection T cells undergo

Question 4

FoxP3 upregulates

Answer 4

CD25 in regulatory T cells

Question 5

Peripheral T cell tolerance is mediated by this receptor

Answer 5

CTLA-4 - preferentially binds B7 (from APCs) in the absence of infection/inflammation
Its activation leads to T cell anergy

Question 6

Fates of a B cell that recognizes self (3)

Answer 6

1) receptor editing
2) deletion
3) Anergy

Question 7

Autoimmunity is chronic due to

Answer 7

amplification loops - small numbers of self-Ag lymphocytes increase in number after response, gets worse in subsequent bouts with autoimmunity

Question 8

Autoimmunity is persistent due to

Answer 8

epitope spreading - response against one self-Ag causes damage that releases other Ag - T lymphocytes may be reactive to these Ag

Question 9

SLE

Answer 9

defective apoptosis leads to increase nucleic acid Ag

ends up producing auto-Ab

Question 10

RA

Answer 10

inflammation of the synovium
Th17/Th1 cytokine release sustains the inflammatory response
Auto Ab production against Rheumatoid factor (Fc protion of IgG)
leads to the destruction of cartilage and bone

Question 11

Inhibit TNF-alpha

Answer 11

Infliximab (remicade) 
adalimumab (Humira) 
Golimumab (Simponi) 
Etanercept (Enbrel) 
Certolizumab pegol (cimzia)

Question 12

Blocking CD25 with monoclonal Ab would serve to

Answer 12

decrease T cell autocrine response to IL-2

Question 13

Blocking CTLA-4 with monoclonal Ab would serve to

Answer 13

prevent B7 binding CD28, promote anergy

Question 14

Blocking adhesion molecules/chemokine receptors with monoclonal Ab would serve to

Answer 14

prevent infiltration of T cells into the periphery

Question 15

Monoclonal Ab specific for anti- CD20 would

Answer 15

target mature naive B cells for deletion

Question 16

IPEX means

Answer 16

no Treg cells in periphery

due to FoxP3 mutations