Tolerance and Autoimmunity

Question 1

What is the definition of immunologic tolerance?

Answer 1

A cells unresponsiveness to a specific antigen

Question 2

What is self-tolerance?

Answer 2

All individuals are tolerant to self-antigens

Question 3

When does autoimmunity occur?

Answer 3

From the breakdown of self-tolerance

Question 4

Differentiate between central and peripheral tolerance.

Answer 4

Central Tolerance- induced in immature self-reactie lymphocytes in the primary lymphoid organs

Peripheral Tolerance- induced in mature self-reactive lymphocytes in the lymph nodes or in submucosal sites

Question 5

What 3 things does central tolerance lead to?

Answer 5

Deletion by apoptosis
Change of BCR specificity
Development of Treg cells

Question 6

What 3 things does peripheral tolerance lead to?

Answer 6

Deletion by apoptosis
Inactivated (anergy)
Suppressed by Treg cells

Question 7

What organ does central tolerance take place?

Answer 7

Thymus

Question 8

Describe the binding affinity that lead to central tolerance.

Answer 8

If the antigen binds too tightly and too weakly the T cell will undergo apoptosis

The antigen binding affinity must be just right to stimulate positive selection and allow migration into the blood as mature T cells

Question 9

What happens to a thymocyte f FoxP3 is not present?

What happens when a thymocyte contains FoxP3?

Answer 9

If the TCR becomes self-reactive then without FoxP3 the cell will die

If FoxP3 is present when the TCR becomes self-reactive then the cell will survive and become a Treg cell

Question 10

What organ do Treg cells mature in?

Answer 10

Thymus

Question 11

What are the 2 pathways for apoptosis of self-reactive T cells?

Answer 11

Mitochondrial (intrinsic)
Death Receptor (extrinsic)

Question 12

How do B cells undergo peripheral tolerance?

What are the 3 possible outcomes?

Answer 12

When mature B cells recognize antigen in the peripheral tissues in the absence of specific Th cells.

This causes them to become unresponsive or die by apoptosis. They also can be inhibited by inhibitory receptors.

Question 13

What are the 3 possibilities of B cells that undergo central tolerance?

Answer 13

If there is strong self antigen recognition:

• Apoptosis
• BCR editing -> Non-self reactive B cell

If there is weak self antigen recognition:
B cell becomes Anergic

Question 14

Treg cells are key mediators of ______ tolerance

Answer 14

Peripheral Tolerance for both T cells and B cells

Question 15

Mutations in what gene leads to the failure of central tolerance and causes Autoimmune Polyendocrine Syndrome?

Answer 15

AIRE

In the absence of AIRE, self reactive T cells are not eliminated and lead to the deletion of self reactive T cells. They enter tissues and cause injury where the antigens are produced.

*Note that this is the only gene associated with Central Tolerance

Question 16

Mutation in what gene causes SLE?

Answer 16

C4- defective in the clearance of immune complexes

Question 17

Mutation in what gene causes the failure of anergy of CD4+ T cells?

Answer 17

CTLA-4

Question 18

Mutation in what gene causes Autoimmune Lymphoproliferative Syndrome?

Answer 18

Fas/FasL- cannot delete anergic self reactive B cells

Question 19

Mutation in what gene causes IPEX?

Answer 19

FoxP3- leads to a deficiency of regulatory T cells

Question 20

If you knockout CTLA-4, what physical features would you see on a patient? Hint: you can palpate this.

Answer 20

They would have enlarged lymph nodes because T cells would be really active and swell within the lymph node

Question 21

Autoimmune dieases are ____, ____, and ________

Answer 21

Chronic, Progressive, and Self-Perpetuating

Question 22

Failure of _____ or ____ cells self tolerance is the cause of all autoimmune diseases

Answer 22

B or T cells

Question 23

Most autoimmune diseases are associated with _______. What are the 3 types?

Answer 23

MHC Class II

HLA- DR/DP/DQ

• This is because MHC Class II control the action of CD4+ T cells
• Note that the HLA allele itself does not cause autoimmunity

Question 24

What kind of hypersensitivity is Inflammatory Bowel Disease?

Answer 24

Type IV Hypersensitivity

Question 25

What kind of hypersensitivity is SLE?

What is the diagnostic test for this disease?

Answer 25

Type III Hypersensitivity

Anti-nuclear Abs

Question 26

What kind of hypersensitivity is RA?

Answer 26

Type IV Hypersensitivity