Immuno 11: Autoimmune And Auto-inflammatory Disorders 2 Flashcards
Patient presents with nervousness, diarrhoea, heat intolerance and on examination has exophthalmos. What is the most likely auto-immune disease causing this ?
Grave’s disease
What causes hyperthyroidism in Grave’s disease ?
IgG antibodies that stimulate TSH receptors
What type of hypersensitivity reaction is grave’s disease ?
Type 2
What is a goitre ?
Enlarged thyroid due to T and B cell infiltration
What causes hypothyroidism in Hashimoto’s Thyroiditis ?
Anti-thyroid peroxidase antibodies and anti-thyroglobulin antibodies
(most common cause of hypothyroidism in iodine-replete areas)
What type of hypersensitivity reaction is hashimoto’s thyroiditis ? (2 option)
Type 2 and type 4
List 2 of the auto-antigens presented by MHC class 1 molecules to cytotoxic CD8+ T cells that causes destruction of the Beta cells of the pancreas in Type 1 diabetes mellitus
islet antigen 2 (IA2)
Glutamic acid dehydrogenase (GAD)
List the 4 antibodies associated with T1DM ?
Anti-islet cell antibodies
Anti-GAD antibodies
Anti-insulin antibodies
Anti-IA2 antibodies
Which auto- antibodies are associated with pernicious anaemia ?
Anti-IF antibodies (Intrinsic factor)
Pernicious anaemia is an example of a …………. anaemia
Macrocytic
Anti-IF antibodies in pernicious anaemia causes failure of …….. absorption
Vitamin B12
Pernicious anaemia can cause subacute …………
Subacute degeneration of the spinal cord
Apart from anti IF antibodies which other auto-antibodies are seen in pernicious anaemia ?
Anti-parietal cell antibodies
Patient presents with drooping eyelids and weakness which is worse at the end of the day. What is the likely diagnosis ?
Myasthenia gravis
Deficiency of which vitamin causes subacute degeneration of the spinal cord ?
Vitamin B12
Seen in pernicious anaemia
Which Autoantibodies cause Myasthenia gravis ?
Nicotinic acetylcholine receptor antibodies
failure of depolarisation
Which test is used to diagnose Myasthenia Gravis ?
Tensilon test - give very short-acting acetylcholinesterase - causes rapid improvement in symptoms
*type II hypersensitivity reaction
Which autoimmune disease causes haematuria, proteinuria and pulmonary haemorrhage ?
Goodpasture’s syndrome
What Histological finding on renal biopsy suggests Goodpasture’s syndrome ?
Crescentric nephritis
Which auto-antibodies are associated with Goodpasture’s syndrome ?
Anti-basement membrane antibodies
Patient presents with Pain and stiffness of multiple joints in the hands. He also has a normocytic anaemia and elevated ESR and CRP. What is the most likely diagnosis ?
Rheumatoid arthritis
Which HLA polymorphisms are associated with Rheumatoid arthritis ?
HLA DR4
HLA DR1
(others = PTPN22, those affecting TNF, IL1, IL6, IL10, PA2 + PD4)
Which bacterial gum infection is associated with Rheumatoid arthritis ?
Porphyromonas gingivalis (expresses PDA)
Is smoking associated with increased or decreased risk of rheumatoid arthritis ?
Increased
Which antibodies are characteristically seen in rheumatoid arthritis ?
Anti-CCP antibodies (95% specific)
Anti-Rheumatoid factor (IgM anti IgG variant)
Which 3 types of hypersensitivity reactions occur in Rheumatoid arthritis ?
Hypersensitivity 2- antibody binds to CCP (peptides) causing complement activation (classical pathway), Macrophage and NK cell activation
Hypersensitivity 3- Immune complexes deposit
Hypersensitivity 4- APCs present peptides (citrulinated, self) to CD4+ T cells causing release of IFN gamma and IL-17 which activate macrophages and fibroblasts. MMPs and TNF-alpha are then released
What is a ‘Pannus’ in Rheumatoid arthritis ?\
Inflammed synovial cartilage which invades the articular cartilage and adjacent bone structures
Increase in synovial fluid volume
Which auto-antibodies are characteristic of connective tissue diseases ?
ANA
How do you test for ANA ?
Flourescently label anti human antibodies which will bind to ANA. Mix with patients serum and Hep 2 cells.
List 6 pathologies seen in SLE ?
SOAP BRAIN MD
Serositis
Oral or nasal ulcers
Arthritis in > 2 joints
Photosensitivity
Blood disorders Renal ANA Immunologic Neurologic symptoms
Malar rash
Discoid rash
(abnormalities in clearing apoptotic cells. Antibodies bind to antigens forming immune complexes, deposit in tissues eg skin, joints, kidneys)
Histology of the kidney shows “Lumpy bumpy” pattern of immunoflourescence.
Which disease is more likely:
A) SLE
B) Goodpasture’s disease
A- SLE
causes lumpy bumpy pattern due to immune complex deposition (type 3 hypersensitivity reaction)
Which Auto-antibody is useful for monitoring disease severity in SLE ?
Anti- dsDNA - disease monitoring
ANA used in diagnosis
Which of these Auto-antibodies is not often seen in SLE ?
A) ANA B) dsDNA C) topoisomerase (Scl70) D)smith E)Ro D)La
C- Anti- topoisomerase (Scl70) is seen in Diffuse Cutaneous Systemic Sclerosis and not in SLE
All the other antibodies can be seen in SLE
Ro and La are more present in Sjögren’s syndrome
What is the Triad for Antiphospholipid syndrome ?
Recurrent venous or arterial thrombosis
Recurrent miscarriage
Thrombocytopenia
List the 2 main antibody tests in APLS ?
Anti-Cardiolipin antibody
Lupus anticoagulant test- coagulation dependent on phospholipids is prolonged
List the 6 pathologies seen in Limited Cutaneous Systemic Sclerosis (CREST) ?
Calcinosis Raynauds Esophageal dysmotility Sclerodactyly Telangectasia Primary pulmonary hypertension
Which features of cutaneous Systemic Sclerosis are different to CREST ?
Skin involvement goes beyond forearm Renal involvement: scleroderma kidney/renal cysts more extensive GI disease Interstitial pulmonary disease Also has all the other features of CREST
ANA staining is an important prognostic indicator in SS
Which 2 antibodies allows differentiation of CREST from Diffuse cutaneous Systemic Sclerosis ?
CREST- Anti-centromere antibodies
Diffuse cutaneous systemic sclerosis- Anti-Topoisomerase antibodies (Scl70)
Which disease causes weakness, malaise, peri-orbital heliotrope rash and gottron’s papules ?
Dermatomyositis
How is polymyositis different to dermatomyositis ?
There is no rash in Polymyositis
Name 1 autoantibody seen in dermatomyositis ?
Anti-aminoacyl tRNA synthetase antibody (anti-Jo1)
Anti- Mi2 is more common in DM than PM
Name 1 autoantibody seen in Polymyositis ?
anti-signal recognition peptide antibody
Patient presents with recurrent nosebleeds and breathlessness. Examination reveals collapse of the nose bridge. X ray shows cavitation get lesions. What is the likely cause ?
ANCA associated vasculitis (small vessel)
List 3 types of small vessel vasculitis (ANCA associated vasculitis) ?
Microscopic polyangitis (MPA)
Granulomatosis with polyangitis (GPA) (aka wegener’s)
Eosinophilic granulomatosis with polyangitis (eGPA) (Churg-Strauss syndrome)
Which type of ANCA is associated with granulomatosis with polyangitis ?
A) cANCA
B) pANCA
A- suggests Granulomatosis with polyangitis with renal involvement
(pANCA suggests MPA or eGPA)
Which auto-antibodies can be seen in Primary sclerosis cholangitis / Autoimmune hepatitis ?
Anti- SMA
Autoimmune hepatitis can also have anti-LMK-1
Which type of ANCA is associated with eosinophilic granulomatosis with polyangitis (Churg-strauss syndrome) ?
P-ANCA
Which antibodies are associated with Primary billiard cirrhosis ?
Anti-mitochondrial antibodies
Patient presents with blurry vision and weakness in her legs. CSF shows Oligoclonal bands of IgG on electrophoresis.
Most likely diagnosis ?
What type of hypersensitivity reaction is this ?
Multiple sclerosis (MS)
Optic neuritis and demyelination.
Type 4 hypersensitivity reaction targeting oligodendrocyte and myelin proteins.
Which antibody is characteristic of Pemphigus vulgaris ?
Anti- Demoglein 3
Which disease is suggested by a +ve Nikolsky’s sign ?
Pemphigus vulgaris
Bullae rupture easily
Skin histology shows acantholytic cells (separation of keratinocytes caused by loss of intercellular cadherin connections). Leading to blistering.
Most likely diagnosis ?
Pemphigus vulgaris
Immunofluorescence shows A linear pattern of IgG and C3 at the basement membrane. Causes blistering.
Most likely diagnosis ?
Bullous pemphigoid.
List 2 diseases for which interferon Beta is a treatment ?
- Relapsing MS
- Bechets
for which disease is inteferon gamma used as a treatment ?
Chronic granulomatous disease
Describe complement profiles in SLE
formation of antibody-antigen immune complexes will activate the classical pathway
complement becomes depleted
active disease - low C4
severe active disease - low C3 + C4
features of systemic sclerosis
inflammation with Th2 and Th17 cells
cytokines lead to activation of fibroblasts and the development of fibrosis
loss of B cell tolerance to nuclear antigens
list 3 idiopathic inflammatory myopathies
dermatomyositis - within muscle, immune complex mediated vasculitis (type III response)
polymyositis - within muscle, type IV response
list 2 large vessel vascilituses
Takayasu’s arteritis
Giant cell arteritis/ polymyalgia rheumatica
list 2 medium vessel vasculituses
anti-GBM disease
IgA disease
Cryoglobulinaemia
