11:9: Autoimmunity Flashcards
What is autoimmunity?
- Immune rxn against self antigen
- Can be directed against single tissue/organ or against many
What is self tolerance?
- Lack of responsiveness to self antigens
What is immunologic tolerance?
- Making lymphocytes unresponsive to self antigen
- “Self tolerance”
- Result of central tolerance
What is central tolerance?
- Clonal deletion of self reactive T and B cells
- Occurs in thymus for T cells
- Occurs in marrow for B cells
What is peripheral tolerance?
- Removal of self reactive T cells that escape intrathymic negative selection
What happens to T cells that to not recognize self antigen?
Allowed to undergo clonal proliferation
What is AIRE?
“Autoimmune regulator”
- Transcription factor promoting expression of self antigen by thymic epithelial cells
- Allows for elimination of self directed T cells
What is APECED?
- Occurs when you lack AIRE
- Develop organ specific autoimmune disease
- Often shows problems with eyes, teeth and fingers
What is receptor editing?
- Rearrangements altering specificity of B cell receptor to avoid autoreactivity
- Occurs in bone marrow
4 mechanisms of peripheral tolerance?
- Anergy
- Suppression by Tregs
- Clonal deletion by induced cell death
- Antigen sequestration
What is anergy?
- A reaction between self reactive T cell and its antigen that leads to expression of proapoptotic proteins and silencing of those T cells
- Most self antigens do not possess stimulatory molecules necessary to mount T cells response
How to Tregs impact T cells?
- Release cytokines to suppress function of autoreactive T cells
What is Fas-FasL ligand?
Leads to apoptosis of self reactive T cells in periphery
What is antigen sequestration?
- Certain areas such as brain eyes and testis have limited exposure to T cells so the celf antigens here are protected
- Can lead to prolonged inflammation / infection because of this as well
What is molecular mimicry?
- Virus or bacteria shares epitopes with self proteins expressed on human
- Leads to immune response against human as well
- Rheumatic fever is example of this
What is exposure of cryptic self?
- Infection in area usually not exposed to immune system allows self antigen to spread to areas it is not normally present
- Can lead to autoimmune rxn
What is SLE?
“Systemic lupus erythematosus”
- Multisystem autoimmune disease caused by variety of antibodies
What is necessary for SLE?
- Ptn. must have multiple susceptibility genes
- Triggering factor
- Abnormal immune response: hyperactive B/T cells with inadequate regulation
What are some triggering factors for lupus?
- UVB light
- Sex hormones
- Dietary factors
- Infections agents
- Drugs
- Smoking
Why does UVB exposure exacerbate SLE?
- Sun kills skin cells releasing self antigen leading to development of autoantibodies
Who is more at risk for LUPUS?
Females: due to sex hormones
African Americans
What drugs can trigger lupus?
"For example (IE), private message (PM) the PHD Isoniazid Ethosuximide Phenytoin Minocycline Procainamide Hydralazine D-penicillamine
How can you identify drug induced lupus?
Presence of antihistone antibodies
What is necessary to diagnose lupus?
4 of 11 symptoms
What are the symptoms of lupus
- Butterfly rash: face
- Discoid rash: anywhere on body
- Photosensitivity
- Oral or nasal ulcers
- Arthritis: non deforming
- Serositis: fluid around lungs or heart
- Kidney disease
- Brain disease: seizures or psych
- Low RBC, WBC, or Platelet count
- Antinuclear antibodies
- Specific autoantibodies
What is SSA associated with?
Neonatal SLE
Role of IC in SLE?
- Low levels can be seen
- C1/2/4 deficiencies can be associated with SLE
- Immuno fluorescence can show deposition of IC
What are antiphospholipid antibodies?
- Found to be circulating in SLE
- Lead to prolonged PTT and false pos VDRL
- Lead to thrombocytopenia
- Ptn with these is more prone to thrombotic episodes than bleeding and spontaneous abortion
What can antiphospholipid antibodies lead to?
Anemia
Neutropenia
Thrombocytopenia
What is neutropenia?
Low WBCs
What is thrombocytopenia?
Low platelets
What is systemic sclerosis?
- Multisystem disorder
- Characterized by inflammatory, vascular and fibrotic changes of skin and organ systems
- Pathogenesis is not known
Two type of scleroderma?
- Diffuse cutaneous
2. Limited cutaneous: CREST syndrome
What does presence of anticentromere antibody indicated?
CREST syndrome
What does CREST stand for?
Calcinosis- Ca deposits on skin
Raynaud’s - Low blood flow to hands
Esophageal dysmotility - problems w/ contraction
Sclerodactyly - thickness of skin on fingers / toes
Telangiectasias - spider veins / small dilated vessels
What is calcinosis?
Ca deposits on skin
- Seen in CREST
What is Raynaud’s syndrome?
- Low blood flow to hands
- Seen in CREST
What is Esophageal dysmotility?
- Problems w/ contraction of esophagus
- Seen in CREST
What is Sclerodactyly?
- Thickness of skin on fingers / toes
- Seen in CREST
What is Telangiectasias?
- Spider veins / small dilated vessels
- Seen in CREST
What is anticentromere antibody associated with?
Systemic sclerosis
Clinical presentation of systemic sclerosis?
- Raynaud’s phenomenon
- fibrosis of the skin (scleroderma)
- telangiectasia, calcinosis
- esophageal hypomotility
- arthralgias and /or arthritis
- intestinal hypofunction
- pulmonary fibrosis - from fibrosis
- hypertension - from fibrosis
- renal failure (leading cause of death) - from fibrosis
What is skin fibrosis indicative of in sclerosis?
- The more skin fibrosis the more underlying organ fibrosis
How to test Scleroderma?
- CXR
- ESR
- Antibody testing
- Urinalysis for renal involvement
