AUTOIMMUNITY Flashcards
familiarization
A result of breakdown in self-tolerance that leads to the immune system responding to self-molecules as if they were foreign
Autoimmunity
Selective destruction of the insulin-producing B cells of the islets of Langerhans in the pancreas
Type I Diabetes
Antibodies present in Type I Diabetes
- Anti-glutamic acid decarboxylase (GAD) antibodies
other antibodies:
- Anti-insulin antibodies
- Anti-Insulinoma antigen 2 abs
- IA-2BA (phogrin)
- ICA (Islet cell Abs)
HLA present in Type I Diabetes
HLA-DR3
HLA-DR4
Chronic systemic inflammatory disorder in which joint cartilage, ligaments, and tendons are destroyed
Rheumatoid Arthritis
Antibodies present in Rheumatoid arthritis:
Rheumatoid factor:
IgM or IgG antibodies specific for Fc region of IgG
HLA present in Rheumatoid arthritis
HLA-DR4
Immune complexes are formed and lodge in the basement membrane of the kidney, skin, and joints
Systemic Lupus Erythematosus
Antibodies present in SLE
- Anti-nuclear antibodies
- Anti-extractable nuclear antibodies
- Anti-ds DNA antibodies
- Anti-phospholipid antibody
HLA present in SLE
HLA-DR2
HLA-DR3
Unregulated secretion of T3 and T4 due to the stimulation of TSH receptor by antibody; most common cause of hyperthyroidism.
Elevated T3 and T4 are first tested
Low TSH levels
Increased radioactive iodine uptake
Grave’s Disease
Antibody present in Grave’s disease:
Anti-TSH receptor antibodies
note:
Elevated T3 and T4 are first testes
Low TSH levels
Increased radioactive iodine uptake
HLA present in Grave’s Disease
HLA-DR3
Destruction of the thyroid gland; hypothyroidism
Hashimoto’s Thyroiditis
Antibodies present in Hashimoto’s Thyroiditis:
- Anti-thyroid peroxidase antibodies (anti-microsomal antibodies)
- Anti-thyroglobulin antibodies
Destruction of parietal cells of the stomach mucosa leads to intrinsic factor deficiency
Pernicious Anemia
Antibodies present in Pernicious Anemia
- Anti-parietal cell antibodies
- Anti-intrinsic factor antibodies
Neuromuscular transmission disorder due to antibodies that inhibit and block acetylcholine binding
Myasthenia Gravis
Antibodies present in Myasthenia Gravis:
Antibodies specific for acetylcholine receptor
HLA present in myasthenia Gravis
HLA-B8
HLA-A1
HLA-DR3
Skin fibroblasts reproduce faster and secrete more collagen deposition leading to thickened, hardened skin
Scleroderma
HLA present in Scleroderma
HLA-DR3 (weak)
Clinically present as dry eyes and mouth; the presence of rheumatoid factor and anti-nuclear antibodies are indicative of a systemic disease with many tissues involved
Sjogren’s Syndrome
HLA present in Sjogren’s Syndrome
HLA-DR3
Characterized by the presence of autoantibody to glomerular, renal tubular, and alveolar basement membranes, resulting primarily in injury to the glomerulus that can rapidly progress to renal failure
Goodpasture’s Syndrome
Antibodies present in Goodpasture’s Syndrome
Antiglomerular basement membrane antibodies
HLA present in Goodpasture’s syndrome
HLA-DR15 or DR4
Antibodies present in Wegener’s granulomatosus
Antineutrophilic cytoplasmic antibodies (ANCA)
Antibodies present in Primary biliary cirrhosis
Antimitochondrial antibodies
Antibodies present in Chronic active hepatitis
Antismooth muscle antibodies
HLA present in Chronic active hepatitis
HLA-B8
All of the following may contribute to autoimmunity except
a. clonal deletion of self-reactive T cells
b. molecular mimicry
c. increased expression of class II MHC antigens
d. polyclonal activation of B cells
a. Clonal deletion of self-reactive T cells
Clonal deletion eliminates self-reactive T cells, preventing autoimmunity.
Factors contributing to autoimmunity:
b. Molecular mimicry: Similarity between self and foreign antigens triggers immune response.
c. Increased expression of class II MHC antigens: Enhances antigen presentation.
d. Polyclonal activation of B cells: Stimulates antibody production.
Other autoimmunity contributors:
1. Genetic predisposition
2. Environmental triggers (infections, toxins)
3. Immune dysregulation
4. Epitope spreading
5. Cytokine imbalance
Autoimmune diseases:
1. Rheumatoid arthritis
2. Lupus
3. Multiple sclerosis
4. Type 1 diabetes
5. Hashimoto’s thyroiditis
Which of the following would be considered an organ-specific autoimmune disease?
a. SLE
b. RA
c. GPA
d. Hashimoto’s thyroiditis
d. Hashimoto’s thyroiditis
Hashimoto’s thyroiditis is an organ-specific autoimmune disease, targeting the thyroid gland.
Characteristics:
1. Autoantibodies against thyroid antigens (thyroglobulin, TPO)
2. Thyroid inflammation and damage
3. Hypothyroidism
Other options:
a. SLE (Systemic Lupus Erythematosus): Non-organ-specific, affecting multiple organs.
b. RA (Rheumatoid Arthritis): Non-organ-specific, primarily affecting joints.
c. GPA (Granulomatosis with Polyangiitis): Non-organ-specific, affecting blood vessels.
Examples of organ-specific autoimmune diseases:
1. Hashimoto’s thyroiditis (thyroid)
2. Type 1 diabetes (pancreas)
3. Multiple sclerosis (central nervous system)
4. Myasthenia gravis (neuromuscular junction)
5. Pernicious anemia (stomach)
SLE can be distinguished from RA on the basis of which of the following?
a. Joint pain
b. Presence of antinuclear antibodies
c. Immune complex formation with activation of complement
d. Presence of anti-dsDNA antibodies
d. Presence of anti-dsDNA antibodies
Anti-double-stranded DNA (anti-dsDNA) antibodies are highly specific for Systemic Lupus Erythematosus (SLE), distinguishing it from Rheumatoid Arthritis (RA).
SLE characteristics:
1. Anti-dsDNA antibodies
2. Antinuclear antibodies (ANA)
3. Immune complex formation
4. Complement activation
5. Multi-organ involvement (skin, kidneys, joints, brain)
RA characteristics:
1. Rheumatoid factor (RF)
2. Anti-citrullinated protein antibodies (anti-CCP)
3. Joint inflammation and destruction
4. Limited organ involvement
Joint pain (a) and immune complex formation with complement activation (c) occur in both SLE and RA.
The presence of antinuclear antibodies (b) is common in SLE but can also occur in RA and other autoimmune diseases.
Which of the following would support a diagnosis of drug-induced lupus?
a. Antihistone antibodies
b. Antibodies to Smith antigen
c. Presence of RF
d. Antibodies to SS-A and SS-B antigens
a. Antihistone antibodies
Drug-induced lupus (DIL) characteristics:
Laboratory Findings
1. Antihistone antibodies (80-90% sensitivity)
2. Anti-nuclear antibodies (ANA)
3. Mild elevation of ESR and CRP
Clinical Features
1. Arthritis/arthralgia
2. Myalgias
3. Fever
4. Serositis (pleurisy, pericarditis)
5. Skin rash (less common)
Drugs associated with DIL
1. Hydralazine
2. Procainamide
3. Isoniazid
4. Minocycline
5. Carbamazepine
Other options:
b. Antibodies to Smith antigen: Specific to systemic lupus erythematosus (SLE).
c. Presence of RF: Common in SLE and rheumatoid arthritis.
d. Antibodies to SS-A and SS-B antigens: Associated with Sjögren’s syndrome.
A peripheral pattern of staining of the nucleus on IIF is caused by which of the following antibodies?
a. Anti-Sm antibody
b. Anti-SSA/Ro antibody
c. Centromere antibody
d. Anti-dsDNA
d. Anti-dsDNA antibody
The peripheral (rim) staining pattern on indirect immunofluorescence (IIF) is typically associated with Anti-dsDNA antibody. This pattern is characteristic of systemic lupus erythematosus (SLE).
a. Anti-Sm antibody: Produces a speckled nuclear staining pattern.
b. Anti-SSA/Ro typically shows a speckled or homogeneous pattern.
c. Centromere antibody: Displays a characteristic centromere staining pattern.
Which of the following would be considered a significant finding in Graves disease?
a. Increased TSH levels
b. Antibody to TSHR
c. Decreased T3 and T4
d. Antithyroglobulin antibody
b. Antibody to TSHR (Thyroid-Stimulating Hormone Receptor)
Graves’ disease characteristics:
1. Hyperthyroidism
2. Antibodies to TSHR (stimulating receptors)
3. Increased T3 and T4 levels
4. Low TSH levels
Significant findings:
1. TSHR antibodies (TRAb)
2. Thyroid-stimulating immunoglobulins (TSI)
3. Diffuse thyroid enlargement
Other options:
a. Increased TSH: Hypothyroidism, not Graves.
c. Decreased T3/T4: Hypothyroidism.
d. Antithyroglobulin antibody: Present in Hashimoto’s thyroiditis and other autoimmune thyroid diseases.
Destruction of the myelin sheath of axons caused by the presence of antibody is characteristic of which disease?
a. MS
b. MG
c. Graves disease
d. Goodpasture’s syndrome
a. MS (Multiple Sclerosis)
Multiple Sclerosis (MS) characteristics:
Pathophysiology
1. Autoantibody-mediated demyelination
2. Myelin sheath destruction
3. Axonal damage
4. Inflammation
Clinical Features
1. Vision problems (optical neuritis)
2. Muscle weakness/numbness
3. Coordination/balance issues
4. Cognitive difficulties
5. Fatigue
Diagnostic Criteria
1. McDonald criteria (clinical, imaging, laboratory)
2. Presence of oligoclonal bands (IgG)
3. Anti-myelin basic protein antibodies
Other options:
b. MG (Myasthenia Gravis): Antibodies target acetylcholine receptors.
c. Graves’ disease: Autoantibodies stimulate thyroid-stimulating hormone receptors.
d. Goodpasture’s syndrome: Antibodies target collagen in basement membranes (kidneys/lungs).
Blood was drawn from a 25-year-old woman with suspected SLE. A FANA screen was performed and a speckled pattern resulted. Which of the following actions should taken next?
a. Report out a diagnostic for SLE
b. Report out as drug-induced lupus
c. Perform an assay for specific ANAs
d. Repeat the test
c. Perform an assay for specific ANAs
FANA (Fluorescent Antinuclear Antibody) screen results:
1. Speckled pattern: Indicates presence of antinuclear antibodies (ANAs)
2. Requires further testing to identify specific antibodies
Next steps:
1. Perform specific ANA assays (e.g., ELISA, Western blot)
2. Test for antibodies against:
- dsDNA
- Sm
- SSA/Ro
- SSB/La
- RNP
1. Evaluate clinical symptoms and medical history
Reporting options:
a. Premature, as FANA alone doesn’t confirm SLE.
b. Unlikely, as drug-induced lupus typically shows antihistone antibodies.
d. Unnecessary, unless laboratory error is suspected.
Which of the following is a mechanism used to achieve peripheral tolerance?
a. Negative selection of autoreactive T cells in the thymus
b. Apoptosis of autoreactive B cells in the bone marrow
c. Editing of B-cell receptors that weakly recognize self-antigens in the bone marrow
d. Lack of a costimulatory signal to autoreactive T cells in the lymph nodes
d. Lack of a costimulatory signal to autoreactive T cells in the lymph nodes
Peripheral tolerance mechanisms:
1. Lack of costimulation (d): Inhibits autoreactive T-cell activation.
2. T-regulatory cells (Tregs): Suppress immune responses.
3. Clonal anergy: Inactivated autoreactive T cells.
4. Suppressive cytokines (IL-10, TGF-β): Modulate immune responses.
Central tolerance mechanisms:
a. Negative selection of autoreactive T cells in the thymus.
b. Apoptosis of autoreactive B cells in the bone marrow.
c. Editing of B-cell receptors in the bone marrow.
Epitope spreading refers to
a. post-translational modifications to self-antigens.
b. modifications in gene expression that are not caused by changes in DNA sequence
c. expansion of the immune response to unrelated antigens
d. cross-reaction of the immune response to a pathogen with a similar self-antigen
c. expansion of the immune response to unrelated antigens
Epitope spreading:
Definition
1. Expansion of autoimmune response from initial epitope to adjacent or unrelated epitopes.
2. Intramolecular (within the same molecule) or intermolecular (across different molecules).
Mechanisms
1. Molecular mimicry
2. Cross-reactivity
3. Cryptic epitope exposure
4. Dendritic cell activation
Examples
1. Multiple sclerosis (MS)
2. Systemic lupus erythematosus (SLE)
3. Rheumatoid arthritis (RA)
Other options:
a. Post-translational modifications: Alter self-antigen structure/function.
b. Epigenetic modifications: Influence gene expression without DNA sequence changes.
d. Molecular mimicry: Immune response to pathogens cross-reacts with self-antigens.
Anti-CCP (cyclic citrullinated proteins) is specifically associated with which autoimmune disease?
a. RA
b. MG
c. Autoimmune hepatitis
d. Goodpasture’s syndrome
a. RA (Rheumatoid Arthritis)
Anti-CCP (Anti-Cyclic Citrullinated Peptide) antibodies:
1. Highly specific (~95-98%) for RA diagnosis.
2. Detectable years before symptoms appear.
3. Associated with aggressive disease course.
4. Predictive of joint damage and erosions.
RA characteristics
1. Joint inflammation
2. Synovial hyperplasia
3. Cartilage/bone destruction
4. Autoantibodies (RF, anti-CCP)
Other options:
b. MG (Myasthenia Gravis): Associated with anti-acetylcholine receptor antibodies.
c. Autoimmune hepatitis: Associated with anti-nuclear and anti-smooth muscle antibodies.
d. Goodpasture’s syndrome: Associated with anti-GBM (glomerular basement membrane) antibodies.
Which autoantibodies are strongly associated with granulomatosis with polyangiitis (Wegener’s granulomatosis)
a. ANA
b. ANCA
c. AMA
d. SMA
b. ANCA (Anti-Neutrophil Cytoplasmic Antibodies)
Specifically:
1. c-ANCA (cytoplasmic): Targeting proteinase 3 (PR3).
2. p-ANCA (perinuclear): Targeting myeloperoxidase (MPO).
Granulomatosis with Polyangiitis (GPA) characteristics:
1. Vasculitis
2. Granulomatous inflammation
3. Necrotizing lesions
4. Respiratory and renal involvement
Diagnostic criteria:
1. Clinical symptoms
2. ANCA positivity
3. Biopsy findings
4. Imaging studies
Other options:
a. ANA: Associated with systemic lupus erythematosus.
c. AMA: Associated with primary biliary cholangitis.
d. SMA: Associated with autoimmune hepatitis.
A technologist performs an IIF test for ANCA and observes that there is an intense fluorescent staining of the nuclear lobes of the neutrophils. How can this type of staining be differentiated from a peripheral ANA pattern?
a. perform the test on formalin-fixed leukocytes
b. Perform IIF with HEp-2 cells
c. Perform an ELISA for ANCAs
d. All of the above
d. All of the above
Differentiating c-ANCA from peripheral ANA:
1. Formalin-fixed leukocytes (a): Inhibits ANCA staining.
2. HEp-2 cells (b): Helps distinguish ANA patterns.
3. ELISA for ANCA (c): Confirms specific antibodies (PR3/MPO).
Combining these methods ensures an accurate distinction between c-ANCA and peripheral ANA.
A 20-year old woman made an appointment to see her physician because she was experiencing intermittent diarrhea. laboratory testing revealed that she also had an iron deficiency anemia. To determine if the patient has celiac disease, her doctor should order which of the following laboratory tests?
a. Anti-tTG
b. Antigliadin
c. antigluten
d. All of the above
a. Anti-tTG (Anti-tissue transglutaminase)
This test is:
1. Highly sensitive (~90-100%)
2. Specific (~95-100%)
3. Recommended as initial screening by the American College of Gastroenterology and National Institutes of Health.
Other options:
b. Antigliadin antibodies: Less sensitive/specific.
c. Antigliadin: Similar limitations.
d. Combination testing: Not necessary for initial screening
Antimitochondrial antibodies are strongly associated with which disease?
a. Autoimmune hepatitis
b. Celiac disease
c. primary biliary cirrhosis
d. Goodpasture’s syndrome
c. Primary biliary cirrhosis (PBC)
Antimitochondrial antibodies (AMAs:
1. Present in 90-95% of PBC patients.
2. Target mitochondrial antigens (e.g., E2 component of pyruvate dehydrogenase).
3. Diagnostic criterion for PBC.
Primary Biliary Cirrhosis characteristics:
1. Chronic liver disease.
2. Autoimmune destruction of bile ducts.
3. Cholestasis.
4. Cirrhosis.
Other options:
a. Autoimmune hepatitis: Associated with ANA and anti-smooth muscle antibodies.
b. Celiac disease: Associated with anti-tTG and antigliadin antibodies.
d. Goodpasture’s syndrome: Associated with anti-GBM antibodies.
