2.4 Autoimmune Disorders Flashcards
Was is the underlying cause of autoimmune disorders?
Loss of self-tolerance
Positive Selection
Double positive cells are checked for binding of MHC and Ag - cells that progress become single positive cells
Negative Selection
Single positive cells are checked for binding to self-Ag - those that do are killed so that they are not allowed to attack self tissues
What happens with AIRE mutation?
Autoimmune Polyendocrine Syndrome - loss of the presentation of some self Ag on the dendritic cells and the medullary cells in the thymus leading to autoimmune lymphocytes
What is the triad of autoimmune polyendocrine syndrome?
- Hypoparathyroidism
- Adrenal Failure
- Candida Infections
How is central tolerance in B cells generated?
Negative Selection of the immature Ig
What are the mechanisms that occur with failure of negative selection for B cells?
- Receptor Editing
- Apoptosis
Peripheral Tolerance
T cell that binds self-Ag with the T-cell receptor on the MHC II without the secondary CD28-B7 signal can lead to:
- Anergy
- Apoptosis
Autoimmune Lymphoproliferative Syndrome (ALPS)
Fas apoptosis pathway mutation - allows for the survival of self reactive lymphocytes in the periphery - IgG generated against cells in the blood
What are some signs of ALPS?
- Cytopenia
- Lymphadenopathy
- Hepatosplenomegaly
What does FOXP3 mutation cause?
IPEX Syndrome
What are the markers of T regulatory cells?
- CD25
- FOXP3
What are some of the triggers for the self-reactive lymphocytes?
- Bystander Activation
- Molecular Mimicry
Bystander Activation
Infection or inflammation leads to the activation of the self-reactive lymphocyte as a side effect of the triggering condition - but it is not direct
Systemic Lupus Erythematous
Chronic and systemic with flares and remissions
What populations are SLE more common in?
African Americans and Hispanics - more seen in females
What is the pathogenesis of SLE?
Type III reaction due to Ag-Ab complex deposition in multiple tissues as Ab are directed against the hosts nuclear material leading to the activation of complement
How is SLE developed?
- UV light causes cell apoptosis releasing DNA
- Self-reactive B cells are activated
- DCs amplify the signal leading to the priming of B cells to the next exposure event
What is early complement deficiency associated with (C1q, C4, C2)?
Lupus
What are some clinical findings of lupus?
- Fever
- Weight Loss
- Fatigue
- LAD
- Raynaud’s Sign
- Butterfly Rash on Face
- Discoid Rash
- Nasopharyngeal Ulcers
- Arthritis
- Sensitivity to Sunlight
- Renal Damae
- Libman-Sacks Endocarditis
What hypersensitivity reaction is responsible for the anemia, thrombocytopenia and leukopenia seen in lupus?
Type II - direct Ab
What is a lab sign for lupus?
ANA Ab
- anti-dsDNA or anti-Sm are the specific Ab
- antiphospholipid Ab also indicative of SLE
What are the 3 antiphospholipid Ab?
- Anticardiolipin
- Lupus Anticoagulant
- Anti-B2 Glycoprotein I
What can anticardiolipin cause a false positive for?
Syphilis - VDRL and RPR
What labs does lupus anticoagulant interfere with?
It will cause an elevated PTT
What is the coagulation state caused by lupus anticoagulant - APA Syndrome?
Hypercoagulable which is PARADOXICAL
Antihistone Ab
Characteristic of drug induced lupus
What drugs can induce lupus?
- Hydralazine
- Procainamide
- Isoniazid
What are some treatments for SLE?
- Avoid sun
- Glucocorticoids
- Immunosuppressants
Sjogren Syndrome
Autoimmune destruction of the lacrimal and salivary glands - Type IV lymphocyte mediated damage with fibrosis
What are the clinical findings o f Sjogren Syndrome?
Dry eyes and mouth
Who is a common patient of Sjogren syndrome?
Older woman
What is a common associated disorder with Sjogren syndrome?
Rheumatoid Arthritis - rheumatoid factor will often be present
What are the autoimmune Ab in Sjogren syndrome?
Anti-ribonucleoprotein - two of this class are the anti-SSA and anti-SSB
What can anti-SSA cause?
Neonatal lupus and congenital heart block
What cancer does Sjogren’s syndrome increase risk of?
B-cell Lymphoma
Scleroderma
Hardening of tissue due to fibroblast activation and deposition of collagen
What is the limited type of scleroderma?
CREST Syndrome
What are the features of CREST syndrome?
Calcinosis/Anti-Centromere Ab Raynaud's Sign Esophageal Dysmotility Sclerodactyly Telangiectasis
What is the diffuse type of scleroderma?
Skin with visceral involvement often int eh GI tract and lungs (most common cause of death). Can also affect the kidneys (second most common cause of death)
What are the Ab found in diffuse scleroderma?
DNA Topoisomerase I Ab
Mixed Connective Tissue Disease
Mixed features of SLE, sclerosis and polymyositis
What Ab will be seen in mixed connective tissue disease?
ANA with serum Ab against U1 ribonucleoprotein
