Autoimmune Disorders Flashcards
Diseases in which immune responses target self-antigens, leading to organ and tissue damage.
Autoimmune diseases
The two primary immune mechanisms involved in autoimmune diseases.
T cell-mediated immune responses and autoantibodies
The immune system’s ability to avoid attacking its own tissues.
Self-tolerance
The location where central tolerance occurs.
Primary lymphoid organs (thymus for T cells and bone marrow for B cells)
The elimination of self-reactive T cells during development.
Negative selection
The modification of self-reactive B cell receptors to prevent autoimmunity.
Receptor editing
A state of unresponsiveness in weakly self-reactive B or T cells.
Anergy
The immune cells that suppress immune responses to prevent autoimmunity.
Regulatory T cells
The three key mechanisms involved in peripheral tolerance.
Anergy, inhibition by regulatory T cells, and apoptosis
The main factors that contribute to autoimmune diseases.
Genetics, environmental factors, and immune regulation defects
Certain genes increase susceptibility to this group of diseases.
Autoimmune diseases
Infections, toxins, and dietary components that can trigger autoimmunity.
Environmental factors
The process in which the immune system mistakenly attacks the body’s own tissues.
Immune regulation defects
The theory that suggests autoimmunity arises due to mutations creating altered lymphocyte clones.
Forbidden Clone Theory
The theory that states self-antigens become foreign due to physical, chemical, or biological changes.
Altered Antigen Theory
The theory in which trauma or infection exposes hidden antigens, triggering an immune response.
Sequestered Antigen Theory
The theory that suggests autoimmunity results from defects or deficiencies in immune regulation.
Immunologic Deficiency Theory
The theory that explains how foreign antigens share epitopes with self-antigens, leading to immune cross-reactivity.
Cross-Reactive Antigen Theory
A chronic autoimmune disease of unknown origin that primarily manifests as vasculitis and can affect various organs and tissues.
Systemic Lupus Erythematosus (SLE)
The human leukocyte antigen (HLA) markers associated with SLE.
HLA-A1, HLA-B8, and HLA-DR3
The hallmark autoantibodies of SLE.
Anti-nuclear antibodies (ANA)
The demographic group primarily affected by SLE.
Women, with a strong hereditary tendency
A red rash across the nose and upper cheeks commonly seen in SLE.
Butterfly rash
The most common cause of morbidity and mortality in SLE.
Nephritis (diffuse proliferative glomerulonephritis)
The autoantibodies that target antigens in the nuclei of mammalian cells and are not specific to SLE.
Antinuclear antibodies (ANA)
The autoantibody most specific to SLE and correlates with disease activity.
Anti-double-stranded DNA (Anti-dsDNA)
The autoantibody associated with drug-induced SLE.
Anti-histone
The autoantibody that targets the DNA-histone complex (nucleosomes) and is associated with both SLE and drug-induced SLE.
Anti-deoxyribonucleoprotein (Anti-DNP)
The autoantibody diagnostic of SLE that targets uridine-rich RNA.
Anti-Smith (Anti-Sm)
Common laboratory tests used in the diagnosis of SLE.
CBC
Urinalysis
ESR
C3 measurement
What is the most widely used method for detecting antinuclear antibodies (ANA) due to its high sensitivity?
Indirect immunofluorescence assay (IFA)
What is the standard substrate used in fluorescent ANA testing?
HEp-2 cells
What fluorescent ANA pattern shows uniform staining of the entire nucleus?
Homogeneous (diffuse) pattern
What autoantibodies are associated with the homogeneous ANA pattern?
Anti-double-stranded DNA (Anti-dsDNA)
Anti-histone
Anti-deoxyribonucleoprotein (Anti-DNP)
What fluorescent ANA pattern shows greater staining intensity around the outer circle of the nucleus and is highly specific for SLE?
Peripheral (rim/outline) pattern
What autoantibody is associated with the peripheral ANA pattern?
Anti-double-stranded DNA (Anti-dsDNA)
What fluorescent ANA pattern consists of discrete fluorescent specks throughout the nuclei, without staining the nucleolus or chromatin region?
Speckled pattern
What autoantibodies are associated with the speckled ANA pattern?
Extractable nuclear antigens (ENA)
What fluorescent ANA pattern shows prominent staining of the nucleoli within the nucleus?
Nucleolar pattern
What autoantibodies are associated with the nucleolar ANA pattern?
Anti-ribonucleoprotein (Anti-RNP)
Anti-RNA
What fluorescent ANA pattern shows discrete speckles in the nuclei during interphase and chromatin of dividing cells?
Centromere pattern
What autoantibody is associated with the centromere ANA pattern?
Anti-centromere
What are two immunoassay techniques used for detecting antinuclear antibodies (ANA)?
Enzyme immunoassay (EIA)
Chemiluminescent immunoassay (ChLIA)
What is the microsphere-based method used for ANA detection?
Microsphere multiplex immunoassay (MIA)
What fluorescence-based test uses Crithidia species for ANA detection?
Crithidia luciliae Immunofluorescence
What outdated method was historically used for ANA detection?
Ouchterlony double diffusion
What is a chronic inflammatory disease that primarily affects joints and periarticular tissues but can also involve the heart, blood vessels, and lungs?
Rheumatoid arthritis (RA)
What happens to the articular cartilage in rheumatoid arthritis?
It becomes replaced by fibroid granulation tissue.
What are the key autoantibodies associated with rheumatoid arthritis?
Rheumatoid factor (RF)
Anti-cyclic citrullinated peptide (Anti-CCP)
An IgM autoantibody that reacts with the Fc portion of IgG.
Rheumatoid factor (RF)
What tests are used to detect rheumatoid factor (RF)?
Manual agglutination using charcoal or latex particles
Enzyme-linked immunosorbent assay (ELISA)
Chemiluminescent immunoassay (ChLIA)
Nephelometry
An atypical amino acid formed from arginine by peptidyl arginine deiminase.
Citrulline
Where is citrulline found?
Granulocytes
Monocytes
Macrophages
What laboratory test is used to detect anti-cyclic citrullinated peptide (Anti-CCP) antibodies?
Enzyme-linked immunosorbent assay (ELISA)
What diseases are associated with anti-neutrophil cytoplasmic antibodies (ANCA)?
Wegener’s granulomatosis
Microscopic polyangiitis (MPA)
Churg-Strauss Syndrome
What method is used to screen for anti-neutrophil cytoplasmic antibodies (ANCA)?
Indirect immunofluorescence (IIF) using ethanol-fixed leukocytes
What are the two fluorescence patterns observed in ANCA testing?
Cytoplasmic (c-ANCA)
Perinuclear (p-ANCA)
What ANCA pattern is characterized by diffuse, granular staining in the neutrophil cytoplasm?
Cytoplasmic (c-ANCA)
What autoantibody causes the cytoplasmic ANCA (c-ANCA) pattern?
Proteinase 3 (PR3) ANCA
What disease is associated with cytoplasmic ANCA (c-ANCA)?
Granulomatosis with polyangiitis (GPA/Wegener’s granulomatosis)
What ANCA pattern shows fluorescence surrounding the lobes of the neutrophil nucleus?
Perinuclear (p-ANCA)
What causes perinuclear ANCA (p-ANCA)?
Antibodies against positively charged antigens
What diseases are associated with perinuclear ANCA (p-ANCA)?
Microscopic polyangiitis (MPA)
EGPA/Churg-Strauss Syndrome
What type of autoimmune hemolytic anemia is IgG-mediated and may be idiopathic or secondary?
Warm autoimmune hemolytic anemia (Warm AIHA)
What type of autoimmune hemolytic anemia is IgM-mediated and associated with primary atypical pneumonia?
Cold autoimmune hemolytic anemia (Cold AIHA)
What percentage of warm autoimmune hemolytic anemia cases are idiopathic?
1/2 of the cases
What condition is cold autoimmune hemolytic anemia linked to?
Cold agglutinin disease
What autoimmune hemolytic anemia is mediated by cold-reacting IgG?
Paroxysmal Cold Hemoglobinuria (PCH)
What antigen is targeted in Paroxysmal Cold Hemoglobinuria (PCH)?
P antigen
What is the temperature-dependent behavior of the biphasic antibody in PCH?
Sensitizes red blood cells at 4°C
Causes hemolysis at 37°C
What laboratory test is used to demonstrate Paroxysmal Cold Hemoglobinuria (PCH)?
Donath-Landsteiner test
What autoimmune disease causes thyroid destruction and hypothyroidism?
Hashimoto’s Thyroiditis
What histological changes occur in Hashimoto’s Thyroiditis?
Lymphocytic and plasma cell infiltration
Germinal centers replace thyroid tissue
What autoantibodies are present in Hashimoto’s Thyroiditis?
Anti-thyroglobulin (Tg)
Anti-thyroid peroxidase (TPO)
How does Hashimoto’s differ from Graves’ Disease?
Hashimoto’s: Hypothyroidism
Graves’: Hyperthyroidism
What autoimmune disease causes hyperthyroidism?
Graves’ Disease
What autoantibody overstimulates the thyroid?
TSH receptor antibodies (TRAbs)
What are the treatments for Graves’ Disease?
Surgery
Radioactive iodine
What is another name for Type I Diabetes Mellitus?
Insulin-dependent diabetes mellitus (IDDM)
Juvenile-onset diabetes mellitus
What causes Type I Diabetes Mellitus?
Autoimmune destruction of pancreatic beta cells.
What autoantibodies are linked to Type I Diabetes Mellitus?
Anti-ICA512
Anti-IAA
Anti-GAD65
Anti-IA-2β
When does hyperglycemia occur in T1DM?
After most beta cells are destroyed.
What protein triggers celiac disease?
Gluten (in wheat, barley, rye)
Why is gliadin significant in celiac disease?
It becomes more immunogenic after modification by tissue transglutaminase.
What genetic markers are linked to celiac disease?
HLA-DQ2
HLA-DQ8
What does celiac disease damage?
Intestinal mucosa
What antibodies are found in celiac disease?
Anti-deamidated gliadin peptides
Anti-tissue transglutaminase
Anti-endomysium
What was Autoimmune Hepatitis (AIH) formerly called?
Chronic active hepatitis
What HLA markers are associated with AIH?
HLA-DRB1
HLA-DQB1
What autoantibodies are present in AIH?
Anti-smooth muscle (SMA)
Anti-liver kidney microsomal (anti-LKM-1)
Anti-liver cytosol type 1 (anti-LC-1)
Anti-mitochondrial (AMA)
What is the most common autoimmune liver disease?
Primary Biliary Cirrhosis (PBC)
What is the pathology of PBC?
Progressive destruction of intrahepatic bile ducts
What HLA markers are linked to PBC?
HLA-DRB1
HLA-DQA1
HLA-DPB1
HLA-DQB1
What autoantibody is characteristic of PBC?
Anti-mitochondrial antibody (AMA)
What neuromuscular disorder causes muscle weakness and fatigue?
Myasthenia Gravis
What autoantibody is found in Myasthenia Gravis?
Anti-acetylcholine receptor (Anti-AChR)
Where are AChRs located?
Skeletal muscles
What is the function of AChRs?
Bind acetylcholine to trigger muscle contractions
Why does Myasthenia Gravis cause muscle weakness?
Block or destroy acetylcholine receptors
What percentage of Myasthenia Gravis patients have Anti-AChR?
90%
What autoimmune disease affects the brain and spinal cord white matter?
Multiple Sclerosis
Why is Multiple Sclerosis considered an autoimmune disease?
T-cell attack CNS
What immunoglobulin is abnormally produced?
IgG
What test detects oligoclonal bands?
CSF electrophoresis
How do oligoclonal bands appear in normal vs. abnormal conditions?
Normal: Absent in CSF & plasma
Abnormal: Present in CSF, absent in plasma
What autoantibody is present in Goodpasture’s Syndrome?
Anti-GBM
Why does Goodpasture’s Syndrome cause kidney & lung damage?
Anti-GBM attacks basement membranes
What are the renal & pulmonary symptoms?
Renal: Hematuria, proteinuria, low creatinine clearance, uremia
Pulmonary: Cough, SOB, hemoptysis
What HLA marker is linked to Goodpasture’s Syndrome?
HLA-DRB1-15
