Immuno 5 - Autoinflammatory and Autoimmune disease Flashcards

Question

Type II hypersensitivity reaction Auto-antigens to the following syndromes ``` Goodpasture disease Pemphigus vulgars Graves disease Myasthenia gravis Pernicious anaemia ```

Answer 1

IgG or IgM antibodies Goodpasture disease non-collagenous domain of basement collagen type IV Pemphigus vulgaris Epidermal cadherin ``` Graves disease (IgG antibodies) Thyroid stimulating hormone receptor ``` Myasthenia gravis Anti-cholinesterase receptor Pernicious anaemia Anti - intrinsic factor antibody anti-gastric parietal cell antibody

Answer 2

Inflammation and damage to vessels Immune complex deposition in blood vessels Purpuric skin rash - very characteristic of type III reaction Cutaneous vasculitis Glomerulonephritis Arthritis

Answer 3

Th1 cells activated by APC when the antigen is presented again in the future, the memory Th1 cells will activate macrophages and cause an inflammatory response  HLA class 1 present self-antigens to CD8 T cells → cytolytic granule release from primed CD8 T-cell  cell lysis  HLA class 2 present self-antigen to CD4 T cells* → cytokine production (e.g. IFN-γ) → TNF induction + Lymphotoxin + HLA upregulation (macrophage)  inflammation and tissue damage *CD80/86 receptor on APC interacts with CD28 receptor on CD4

Answer 4

IgG antibodies SLE DNA, Histones, RNP (ribonucleoprotein)

Answer 5

Insulin dependent DM Pancreatic b cell antigen Glutamic acid decarboxylase(GAD65) Islet antigen 2 (IA2) Rheumatoid arthritis Unknown synovial joint antigen anti-ccp anti-RF Multiple sclerosis Myelin basic protein myelin oligodendrocyte protein proteolipid protein Coeliac disease Anti - tissue transglutaminase antibodies Anti-endomyosial antibody

Answer 6

Anti-thyroid peroxidase antibodies Anti-thyroglobulin antibodies o Not useful to measure anti-TG and anti-TPO antibodies as there is a high prevalence in the normal population with no symptoms  just do thyroid biochemistry Both T2 + T4 hypersensitivity reaction

Answer 7

T IV hypersensitivity rxn CD8 T cells infiltrate the pancreas and destroy islet cells Auto antibodies glutamic acid dehydrogenase 65 (GAD65) Islet antigen 2 (IA2) Antibodies that predate the development of the disease Anti-islet cell antibodies Anti-insulin ab Anti-GAD ab Anti-IA2 antibodies

Answer 8

o Ix  Anti-glomerular basement membrane antibody +ve  Crescentic nephritis on biopsy o Detection of auto-antibodies in kidney  Fluorescein conjugated polyclonal anti-human Ig targets auto-antibody which targets the BM  Smooth linear deposition of antibody along the glomerular basement membrane Type II hypersensitivity reaction autoantibody targets non collagenous domain of basement membrane collagen type IV

Answer 9

HLA DR 4 HLA DR 1 PTPN22 polymorphism PADI2, PADI4* polymorphism * peptidyl arginine deiminase • Enzymes involved in deamination of arginine to create citrulline • These polymorphisms are associated with higher levels of citrullination • This creates a high load of citrullinated proteins

Answer 10

• Porphyromonas gingivalis expresses PAD enzyme  promotes citrullination

Answer 11

- Anti cyclic citrullinated peptide (Anti-CCP antibody) best blood test for the dx of Rheumatoid arthritis -Rheumatoid factor rheumatoid factor is an antibody direct against the common Fc region of human IgG (IgM anti-IgG)

Answer 12

Test by staining Hep-2 cells (human epidermoid cancer line)

Answer 13

Type III hypersensitivity reaction Abnormalities in cellular activation --> B cell hyperactivity + loss of tolerance Abnormalities in clearance of apoptotic cells Antibodies directed against intracellular proteins Antibodies bind to antigen to form immune complexes Immune complexes 1) deposit in tissues 2) activate complement 3) stimulate cells expressing Fc and antigen receptors lumpy-bumpy’ pattern of antibodies bound to immune complexes with fluorescein conjugated anti-human Immunoglobulin.

Answer 14

Patient A’s result is 1:640 titre = the minimal dilution at which the antibody can be detected  Measured by titre (minimal dilution at which antibody can be detected)  I.E. 1: 640 means it has taken 640 dilutions to get to minimal concentration – this means that the antibody is very strong as at 640 dilutions it is still present (very strong antibody)  I.E. 1: 60 means it has only taken 60 dilutions to get minimal concentration (very weak antibody)

Answer 15

dsDNA Anti-ENA ab (extractable nuclear antigens) - ab associated with ribonucleoproteins Ro, La, Sm, U1RNP Anti-topoisomerase AB (Anti-SCL70 AB) Centromere

Answer 16

dsDNA - homogenous staining ENA - speckled antibody

Answer 17

Homogenous staining on ELISA Highly specific for SLE Very high titres often associated with more severe disease incl. renal + CNS involvement Titres useful in disease monitoring (vs anti-ENA ab where titres are not helpful in disease monitoring)

Answer 18

 Quantitation of C3 + C4 acts as a surrogate marker of disease activity  Depletion of C4 occurs first [FOUR = FIRST] and then depletion of C3  We measure inactivated complement proteins, not activated forms  (formation of antibody-antigen immune complexes – activate complement cascade via classical pathway – complement components become depleted if constantly consumed-can act as a marker of disease activity)

Answer 19

Lupus anti-coagulant Anti-cardiolipin Anti-B2 glycoprotein 1

Answer 20

limited (does not progress beyond forearms) - anti-centromere ab Diffuse (progresses beyond forearms) - anti-topoisomerase ab (anti-scl70) ``` (CREST=) Calcinosis Raynaud's Oesophageal dysmotility Sclerodactyly Telangiectasia Pulmonary HTN ```

Answer 21

o Dermatomyositis (skin involvement – periorbital rash + Gottron’s papules)  Within muscle – perivascular CD4 T cells and B cells  Immune complex mediated vasculitis – T3 response o Polymyositis (no skin involvement – no rash)  Within muscle – CD8 T cells surround HLA Class I expressing myofibres  CD8 T cells kill myofibres via perforin/granzymes – T4 response o Investigations  Positive ANA (in some patients) – Extended myositis panel o Anti-aminoacyl transfer RNA synthetase antibody  Anti-Jo-1 (cytoplasmic) o Anti-SRP (Anti-signal recognition peptide antibody) (nuclear + cytoplasmic) (PM) o Anti-Mi2 (nuclear) (DM>PM)

Answer 22

anti-dsDNA SLE anti-ENA - Ro, La, Sm, RNP - SLE (all), Sjogrens (Ro, La) - scl70 (diffuse cutaneous systemic sclerosis (CREST)) - centromere (limited cutaneous systemic sclerosis (CREST) Cytoplasmic aminoacyl transfer RNA synthetase ab Jo-1 (Myositis)

Answer 23

o Microscopic polyangiitis / Microscopic polyarteritis / MPA o Granulomatosis with polyangiitis / Wegener’s granulomatosis / GPA o Eosinophilic granulomatosis with polyangiitis / Churg-Strauss syndrome / eGP

Answer 24

Anti neutrophil cytoplasmic antibody o Antibodies specific for antigens located in primary granules within the cytoplasm of neutrophils o Inflammation may lead to expression of these antigens on cell surface of neutrophils  antibody engagement with cell surface antigens may lead to neutrophil activation (type II hypersensitivity)  activated neutrophils interact with endothelial cells causing damage to vessels  vasculitis o Help in diagnosis and monitoring of disease activity

Answer 25

cANCA Cytoplasmic fluorescence Associated with antibodies to enzyme proteinase 3 granulomatous polyangiitis with renal involvement pANCA Perinuclear staining pattern Associated with antibodies to myeloperoxidase Less sensitive and specific than cANCA microscopic polyangiitis and eosinophilic granulomatous polyangiitis

Immuno 5 - Autoinflammatory and Autoimmune disease Flashcards

(50 cards)