AutoInflam & Autimmune Flashcards
(20 cards)
What are the three essential criteria for a disease to be classified as autoimmune?
1) Presence of autoantibodies or autoreactive T cells, 2) Evidence that these immune components are pathogenic, and 3) Reproduction of the disease in experimental models.
How does central tolerance prevent autoimmunity?
Central tolerance eliminates self-reactive T and B cells during development in the thymus and bone marrow, respectively, via negative selection.
What is the role of HLA (MHC) genes in autoimmune disease susceptibility?
Certain HLA alleles present self-antigens more effectively, predisposing individuals to autoimmune responses (e.g., HLA-B27 with ankylosing spondylitis).
How does molecular mimicry contribute to autoimmunity?
Pathogens contain antigens similar to self-antigens, leading the immune system to mistakenly attack self-tissues (e.g., rheumatic fever after strep infection).
Differentiate systemic vs. organ-specific autoimmune diseases.
Systemic diseases (e.g., SLE) affect multiple organs due to circulating immune complexes, while organ-specific diseases (e.g., Hashimoto’s) target a single tissue.
What lab findings support a diagnosis of systemic lupus erythematosus (SLE)?
Positive ANA, anti-dsDNA, anti-Sm antibodies, low complement levels (C3/C4), and presence of immune complexes.
Describe the immunopathology behind rheumatoid arthritis (RA).
Synovial inflammation due to autoreactive T cells and autoantibodies (RF, anti-CCP), leading to pannus formation and joint destruction.
What is the hallmark autoantibody in Sjögren’s syndrome?
Anti-Ro (SSA) and anti-La (SSB) antibodies, associated with dry eyes, dry mouth, and glandular lymphocytic infiltration.
Attacks secretory glands
What clinical features distinguish systemic sclerosis (scleroderma)?
Skin thickening, Raynaud’s phenomenon, esophageal dysmotility, and fibrosis of internal organs. ANA with anti-Scl-70 (diffuse type) or anti-centromere (limited type).
What is epitope spreading and how does it worsen autoimmune disease?
An initial immune response to one self-epitope leads to reactivity against other self-epitopes over time, broadening tissue damage.
What is the pathophysiologic role of type III hypersensitivity in autoimmune disease?
It involves immune complex deposition in tissues, leading to inflammation and damage—seen in conditions like lupus and vasculitis.
What is the significance of anti-cyclic citrullinated peptide (anti-CCP) antibodies?
Highly specific marker for rheumatoid arthritis, often detected early and predictive of disease severity.
Which cytokines play a key role in autoimmune inflammation?
TNF-α, IL-1, IL-6, and IL-17 are major pro-inflammatory mediators driving tissue damage in diseases like RA and psoriasis.
What are regulatory T cells (Tregs), and how do they prevent autoimmunity?
Tregs suppress autoreactive T cells and maintain immune tolerance through cytokines like IL-10 and TGF-β.
How does epigenetics influence autoimmunity risk?
Modifications like DNA methylation and histone acetylation can alter gene expression of immune-regulatory genes without changing DNA sequence.
Name a disease where complement deficiency increases autoimmune risk.
C1q deficiency increases risk for systemic lupus erythematosus due to impaired clearance of apoptotic cells.
What distinguishes limited from diffuse systemic sclerosis (scleroderma)?
Limited: CREST symptoms and anti-centromere Abs. Diffuse: widespread skin involvement, organ fibrosis, anti-Scl-70 Abs.
Endothelial cell damage and fibroblast overproduction of ecm
What features are seen in mixed connective tissue disease (MCTD)?
Overlapping features of SLE, scleroderma, and polymyositis, with positive anti-U1 RNP antibodies.
How do environmental triggers contribute to autoimmunity?
Infections, smoking, drugs, and UV light can modify self-antigens or stimulate immune responses, triggering disease in genetically susceptible individuals.
What is the mechanism of biologics like TNF inhibitors in autoimmune diseases?
They block pro-inflammatory cytokines (e.g., TNF-α) to reduce immune-mediated inflammation and tissue destruction in diseases like RA and IBD.
