Autoimmunity Flashcards
Autoimmunity
Immune reaction against self-antigen
Central Tolerance
Central tolerance - clonal deletion of self-reactive T and B lymphocytes
thymus - T cells
bone marrow - B cells
Peripheral Tolerance
Peripheral tolerance - removal of self-reactive T cells that escape intrathymic negative selection
AIRE
• 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
Autoimmune Poly-Endocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED)
- 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
What are symptoms of APECED?
pernicious anemia
autoimmune hepatitis
alopecia
vitiligo
What is the role of infection in autoimmunity?
Molecular mimicry can lead to the generation of auto-Ab
What is the main population affected by Systemic Lupus Erythematosus?
Women - African American women have high frequency
What is the genetic component of SLE?
- 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
What are some triggers for SLE?
- Ultraviolet B light
- Sex hormones
- Dietary factors
- Infectious agents
- Smoking
What sex hormones are related to SLE?
Abnormal estrogen metabolism in both male and female patients with SLE as well as low levels of testosterone
What are some drugs that can trigger SLE?
– Procainamide – Hydralazine – D-penicillamine – Isoniazid – Minocycline – Phenytoin – Ethosuximide
What are the 3 mechanisms that can underlie SLE?
Hyperactive T cells
Hyperactive B cells
Inadequate regulatory mechanisms
What antigen is specific for SLE diagnosis?
Smith (Sm) antigen
What are some of the common identifiers for SLE?
Patients with depressed complement levels, dsDNA and two criteria most likely have SLE.
SLE Treatment
• 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
What is scleroderma (systemic sclerosis)?
It is a multisystem disorder characterized by inflammatory, vascular, and fibrotic changes of skin and various internal organ systems
Diffuse cutaneous scleroderma
– rapid development of symmetric skin thickening
– high risk of visceral disease early in the course
CREST Syndrome
Calcinosis, Raynaud’s, esophageal dysmotility, sclerodactyly, telangiectasias
What correlates with the severity of systemic sclerosis?
Thickness of the skin - hence the level of fibrosis
Scleroderma Treatment
- Corticosteroids for inflammation
- CCBs for Raynaud’s phenomenon (nifedipine)
