Autoimmunity

Question 1

Autoimmunity

Answer 1

Immune reaction against self-antigen

Question 2

Central Tolerance

Answer 2

Central tolerance - clonal deletion of self-reactive T and B lymphocytes

thymus - T cells
bone marrow - B cells

Question 3

Peripheral Tolerance

Answer 3

Peripheral tolerance - removal of self-reactive T cells that escape intrathymic negative selection

Question 4

AIRE

Answer 4

• transcription factor
• promotes the expression of self proteins by thymic
epithelial cells
• thymic expression of these proteins permits the clonal elimination of tissue-specific T cells

Question 5

Autoimmune Poly-Endocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED)

Answer 5

• organ-specific autoimmune disease caused by a defect in a single gene
• all persons who lack a functional autoimmune regulator gene (AIRE) gene develop the disease and one functional gene prevents the disease

Question 6

What are symptoms of APECED?

Answer 6

pernicious anemia
autoimmune hepatitis
alopecia
vitiligo

Question 7

What is the role of infection in autoimmunity?

Answer 7

Molecular mimicry can lead to the generation of auto-Ab

Question 8

What is the main population affected by Systemic Lupus Erythematosus?

Answer 8

Women - African American women have high frequency

Question 9

What is the genetic component of SLE?

Answer 9

• HLA-DQ locus linked to production of anti-double-stranded DNA, anti-Sm, and antiphospholipid antibodies
• Inherited deficiencies of complement components, such as C2, C4, or C1q

Question 10

What are some triggers for SLE?

Answer 10

• Ultraviolet B light
• Sex hormones
• Dietary factors
• Infectious agents
• Smoking

Question 11

What sex hormones are related to SLE?

Answer 11

Abnormal estrogen metabolism in both male and female patients with SLE as well as low levels of testosterone

Question 12

What are some drugs that can trigger SLE?

Answer 12

– Procainamide
– Hydralazine
– D-penicillamine
– Isoniazid
– Minocycline
– Phenytoin
– Ethosuximide

Question 13

What are the 3 mechanisms that can underlie SLE?

Answer 13

Hyperactive T cells
Hyperactive B cells
Inadequate regulatory mechanisms

Question 14

What antigen is specific for SLE diagnosis?

Answer 14

Smith (Sm) antigen

Question 15

What are some of the common identifiers for SLE?

Answer 15

Patients with depressed complement levels, dsDNA and two criteria most likely have SLE.

Question 16

SLE Treatment

Answer 16

• Nonsteroidal anti-inflammatories - helpful with fever arthralgia or arthritis but systems should be assessed immunologically and followed for renal and hepatic dysfunction
• Antimalarials - useful for skin and arthritis symptoms
• Corticosteroids - used in high doses 1-2mg/kg for life-
threatening SLE

Question 17

What is scleroderma (systemic sclerosis)?

Answer 17

It is a multisystem disorder characterized by inflammatory, vascular, and fibrotic changes of skin and various internal organ systems

Question 18

Diffuse cutaneous scleroderma

Answer 18

– rapid development of symmetric skin thickening

– high risk of visceral disease early in the course

Question 19

CREST Syndrome

Answer 19

Calcinosis, Raynaud’s, esophageal dysmotility, sclerodactyly, telangiectasias

Question 20

What correlates with the severity of systemic sclerosis?

Answer 20

Thickness of the skin - hence the level of fibrosis

Question 21

Scleroderma Treatment

Answer 21

• Corticosteroids for inflammation

- CCBs for Raynaud’s phenomenon (nifedipine)