7 Tolerance and Autoimmunity (1 Hour)

Question 1

What causes peripheral tissue self antigens to be presented in the thymus?

Answer 1

AIRE (autoimmune regulator)

Question 2

What does a defect in AIRE cause?

Answer 2

Autoimmune polyendocrinopathy

Question 3

Loss of FoxP3 in mice causes

Answer 3

Widespread autoimmunity

Question 4

Tregs make up what percentage of circulating CD4 cells

Answer 4

5-10

Question 5

What two signals do T cells need to become active?

Answer 5

TCR binding to HLA

CD80 binding to CD28

Question 6

What keeps T cells inactive in the absence of infection

Answer 6

CTLA4 preferentially binds CD80

Question 7

What makes a professional APC?

Answer 7

Constitutive expression of CD80

Question 8

What 3 fates can a self recognizing B cell undergo?

Answer 8

Receptor editing of the Ig V region

Deleted

Reduced receptor expression resulting in an anergic B Cell

Question 9

What are the principal factors in autoimmunity?

Answer 9

Susceptibility genes and environmental triggers

Question 10

What are the effector mechanisms of autoimmunity?

Answer 10

Immune complexes, circulating autoantibodies, and autoreactive T cells

Question 11

What causes issues understanding autoimmune diseases?

Answer 11

They are heterogenous and multifactorial

Self antigens are often not identified

Clinical manifestation is prolonged and variable after initiation

Question 12

Why are autoimmune diseases chronic?

Answer 12

There are many amplification loops

Question 13

What causes persistence and progression of autoimmune??

Answer 13

Epitope spreading

Self-reactivity causes other Ag to be released and react

Question 14

What autoimmune do we know the most about? What HLA allele is responsible?

Answer 14

Akylosing spondylitis

HLA B27

Question 15

What is needed for manifestation of SLE?

Answer 15

Defective genes and an environmental trigger

Question 16

What defective mechanism causes SLE?

Answer 16

Defective apoptotic process leading to increased nucleic Ags

Question 17

An antibody against what causes RA?

Answer 17

Rheumatoid factor (Fc portion of IgG)

Question 18

Anti CD25 Ab what?

Answer 18

T cell autocrine function to IL2

Question 19

Anti-CTLA4 Ab promote what?

Answer 19

Anergy, blocks B7(CD80) from binding to CD28

Question 20

What does a mutation of FoxP3 cause?

Answer 20

IPEX, leads to loss of function of T cells and thus uninhibited T cell activation

Question 21

What are the symptoms of IPEX

Answer 21

Intractable diarrhea leading to failure to thrive, dermatitis, and IDDM

Question 22

What clinical signs do we see in IPEX?

Answer 22

Normal serum Ab but elevated IgE

This results in dermatitis