2.4 Autoimmune Disorders Part 1

Question 1

What is central and peripheral tolerance?

Answer 1

Central = occurring in the bone / thymus

Peripheral = Occurring in the periphery

Question 2

What is the general progression of T cell maturation?

Answer 2

Double positive to single positive

Question 3

What type of selection is occurring when T cells are double and single positive respectively?

Answer 3

Double = Positive selection (recognize MHC?)

Single = negative selection (bind self antigen?)

Question 4

What is autoimmune polyendocrine syndrome?

Answer 4

Mutation in the AIRE gene, that inhibits the thymus medullary epithelial cells from expressing self antigens for T cell negative selection, allowing self reactive T cells to escape into the periphery

Question 5

Where do positive and negative selection occur in the thymus respectively?

Answer 5

Positive = cortex
Negative = medulla

Question 6

What are the cells in the medulla of the thymus that hold self antigen to test maturing T cells?

Answer 6

• Dendritic cells

- Medullary epithelial cell

Question 7

What is the classic triad of s/sx in Autoimmune polyendocrine syndrome?

Answer 7

1. Hypoparathyroidism
2. Adrenal gland failure
3. Chronic candida infections or oral mucosa

Question 8

What are the two processes that B cells can undergo if they bind to self MHC molecules presented by bone marrow Dendritic cells?

Answer 8

• Receptor editing (reexpression of RAG genes)

- Apoptosis through the mito pathway

Question 9

What are the genes that are responsible for the rearrangement of B cell Ig?

Answer 9

RAG

Question 10

What are the two outcomes of peripheral tolerance?

Answer 10

-anergy or apoptosis

Question 11

Which is on which cells: CD28 and B7

Answer 11

CD28 = CD4 cells
B7 = APCs

Question 12

What is the mechanism by which T cells undergo anergy in the periphery?

Answer 12

If not costimulatory molecules (e.g. CD28 / B7 interaction), then cell shuts down

Question 13

What is the mechanism by which B cells undergo apoptosis in the periphery?

Answer 13

B cell continuously binds antigen without receiving costimulatory signal induces apoptosis via the Death receptor (CD95) and FasL

Question 14

What is autoimmune lymphoproliferative syndrome (ALPS)?

Answer 14

Mutations in the Fas apoptosis pathway, allowing for the survival of self reactive lymphocytes

Question 15

What are the s/sx of ALPS? (3)

Answer 15

• Autoimmune hemolytic anemia / thrombocytopenia
• LAD / HSM
• Lymphoma

Question 16

What are Tregs? How do they work?

Answer 16

T cells that suppress immune cell responses via expression of CTLA4, which binds B7 on APCs, and inhibits the costimulatory molecules

Question 17

What are the cytokines that Tregs can secrete to reduce the immune response? (2)

Answer 17

IL-10

TGF-beta

Question 18

What is the function of IL-10 in the reduction of immune response?

Answer 18

Lowers the expression of MHC class II

Question 19

What are the three proteins that identify a T reg?

Answer 19

CD4
CD25
FOXP3

Question 20

What is the other name for CD25?

Answer 20

IL-2 Receptor

Question 21

What is FOXP3?

Answer 21

Transcription factor for Tregs that is needed for their development

Question 22

Why is there an association between CD25 polymorphisms and DM I / MS?

Answer 22

If CD25 (=IL-2 receptor) is defective, then Tregs are not produced properly, and thus cannot calm immune system

Question 23

What is IPEX syndrome? Defect in this?

Answer 23

Immune dysfunction
Polyendocrinopathy
Enteropathy
X-linked

Defect in FOXP3, leading to defective Tregs

Question 24

Who is classically affected by autoimmune diseases?

Answer 24

Women of childbearing age

Question 25

What are the diseases that HLA-B27 are associated with? (4)

Answer 25

Psoriatic arthritis
Ankylosing spondylitis
IBDs
Reactive arthritis

Question 26

What is the PTPN22 gene mutation?

Answer 26

Y phosphatase mutation that results in cell signalling defect for apoptosis of autoimmune cells

Question 27

What is the cause of the overlapping features of autoimmune diseases?

Answer 27

Epitope spreading–new antigens exposed as autoimmune cells destroy cells