Immunology - Autoinflammatory and autoimmune disorders Flashcards by Yasmin Kamara

What is the difference between auto-immune and auto-inflammatory diseases?

Auto-inflammatory involves innate immune system
Auto-immune involves adaptive immune system

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Which type of cell can produce IL1 and NFkappaB?

Neutrophil

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What is the role of cryopyrin in inflammation?

Induces IL1/NFkB secretion by neutrophils

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What is the role of pyrin-marenostin in inflammation?

Inhibits IL1/NFkB secretion by neutrophils

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What is the inheritance pattern of Familial Mediterannean Fever?

Autosomal recessive

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What is the mutation that causes Familial Mediterannean Fever?

MEFV mutation -causing inactivated pyrin-marenostrin (inhibitory of inflammation)
Cryopyrin therefore not opposed

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What are 5 symptoms of Familial Mediterannean Fever?

Periodic fevers of about 2-4 days duration
chest pain (Pleurisy & pericarditis)
abdo pain (peitonitis)
Arthritis
Rash

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What is the long-term risk of Familial Mediterannean Fever why by what mechanism?

AA amyloidosis
(specifically kidney deposition as leads to nephrotic syndrome)
because liver produces serum amyloid A as acute phase protein

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What is the treatment for Familial Mediterannean Fever?

Colchicine 500 micrograms BD
This binds tubulin in neutrophils

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What is the defect that causes APS-1? give 2 consequences

AIRE (autoimmune rgeulator)

-> autoreactive B cells
-> autoreactive T cells

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give 2 roles of AIRE?

Upregulates expression of self antigen by T cells
promotes T cell apoptosis

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Give 3 associated conditions of APS-1

Auto-immune diseases
Hypoparathyroidism
Addisons
Candidiasis - most common -

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What is the pathophysiology of candida susceptibility in APECED?

Auto-antibodies vs IL17 and IL22 are produced, which are interleukins that are important in candida immunity

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What does IPEX stand for?

Immune polyendocrinopathy enteropathy X-linked syndrome

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What is the mutation that causes IPEX?

FOXP3

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What is the usual role of FOXP3?

Required for regulatory T cell development and function

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What is the pathophysiology of IPEX?

FOXP3 mutation –> failure to negatively regulate T cell responses –> lots of autoreactive *B* cells - form autoantibodies

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What are the 3 symptoms of IPEX?

3Ds - Diarrhoea, Diabetes, Dermatitis

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What does ALPS stand for?

Autoimmune Lympho Proliferative Syndrome

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What mutation causes ALPS?

Fas pathway mutation

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What are 4 the symptoms of ALPS?

Defect in lymphocyte apoptosis –>
splenomegaly and lymphadenopathy
lymphocytosis
double negative T cells (CD 4 AND C8 -ve)

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Recall 2 mutations associated with Crohn’s disease

IBD1 on chromosome 16
NOD2 (stimulates TNFa)

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What is the HLA association of ankylosing spondylitis?

HLA-B27

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Where in the body is most affected by ankylosing spondylitis?

Areas where there are high tensile forces

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Recall 2 genetic associations of Grave's disease

HLA-DR3 CTLA4

Recall 3 genetic associations of SLE

HLA-DR3 CTLA4 PTPN22

What are 2 HLA association of Rheumatoid Arthritis?

HLA-DR4 HLA DR1

What is the HLA association of Goodpasture's disease?

HLA-DR15

Recall the Gel and Coombs classification of hypersensitivity

Type 1: immediate and IgE mediated Type 2: Antibody to cellular antigen mediated Type 3: Immune complex mediated Type 4: Delayed type - T cell mediated

Recall four type 2 hypersensitivity diseases

Grave's Goodpasture's Pemphigus vulgaris Myasthaenia

Against what is the auto-antibody directed in Goodpasture's disease?

Non-collagenous domain of type 4 collagen in the basement membrane autoantibody = anti GBM (glomerular basement membrane)

Against what is the auto-antibody directed in pemphigus vulgaris?

Cadherin

Against what is the auto-antibody directed in Grave's?

TSH receptor (stimulating)

Against what is the auto-antibody directed in myasthaenia gravis?

Acetylcholine receptor

Recall two examples of type 3 hypersensitivity disorders

SLE Rheumatoid arthritis

What is rheumatoid factor?

Antibody directed against the Fc portion of IgG

Mutations in which enzymes are associated with rheumatoid arthritis and why?

PAD enzymes - these are involved in citrullinisation

How can you test for anti-nuclear antibody (ANA)?

Stain Hep-2 cells with indirect immunofluorescence. get homogenous pattern

Which antibody is most specific for SLE?

Anti-dsDNA

Recall the expected C3 and C4 levels in active vs severe SLE

inactive: both normal Active: low C4 Severe: both low

Which 2 antibody tests should be done to investigate anti-phospholipid syndrome?

1. Lupus anti-coagulant 2. Anti-cardiolipin

What are the 2 types of systemic sclerosis?

CREST (limited cutaneous systemic sclerosis) Diffused cutaneous systemic sclerosis

What is the autoantibody involved in CREST?

Anti-centromere

What is the autoantibody involved in diffuse cutaneous systemic sclerosis?

Anti-topoisomerase (Scl70)

What are the 6 symptoms of CREST?

Calcinosis Raynaud's Esophageal dysmotility Sclerodactyly Telangiectasia PLUS PRIMARY PULMONARY HTN (important)

What are the symptoms of diffuse cutaneous systemic sclerosis?

Same as CREST, but additionally: - More GI disease - Interstitial lung disease - Renal crisis

What are the 2 forms of idiopathic inflammatory myopathy?

Dermatomyositis Polymyositis

What is the phrase "helicopter rash" pathognemonic for?

Dermatomyositis

Recall 2 symptoms of dermatoyositis

periorbital Rash gottron's papules

What is the main symptom of polymyositis?

Proximal myopathy NO rash

What is the main autoantibody association of small vessel systemic vasculitides?

ANCA

Recall 3 examples of small vessel systemic vasculitides

1. Microscopic polyangiitis 2. Granulomatosis with polyangiitis 3. Eosinophilic granulomatosis with poly-angiitis

Which of the small vessel vasculitides is associated with cANCA?

Granulomatosis with polyangiitis (previously Wegener's)

Which of the small vessel vasculitides is associated with pANCA?

Microscopic polyangiitis Eosinophillic granulomatosis with polyangiitis (previously Churg Strauss)- EGPA - Patients affected typically have severe allergies or sinus problems, which progress to severe asthma prior to the systemic vasculitis. It is treated with corticosteroids.

What is cANCA?

Antibody to proteinase 3

What is pANCA?

Antibody to myeloperoxidase

in addition to colchicine, give 2 drugs that can be used in FMF

anakira - IL 1 receptor antagonist etanercept - TNFalpha inhibitor

what 4 things increase in FMF

lots of neutrophils so increased IL 1 NFKappaB to TNFa apoptosis

state 4 monogenic auto immune diseases

1. Familial med fever 2. Autoimmune polyglandular syndrome type I (APS1) aka APECED 3. IPEX - Immune dysregulation, polyendocrinopathy, enteropathy, X linked syndrome 4. ALPS - autoimune lymphoprolifertaive syndrome

give the abnormalities of IPEX, APS-1 and ALPS

IPEX = abnormal Regulation of T cells APS -1 = abnormality in tolerance ALPS = abnormality of lymphocyte apoptosis

2 drugs for crohns disease

corticosteroid (pred) anti TNFA antibody - infliximab

management of crohns

diet induced remission (whole protein modular diet) maintain remission w mesalazine (an aminosalicylate)

give an example of a polygenic auto inflammatory disease

crohns

give an example of a mixed pattern disease

ankylosing spondy typically NO autoantibodies mixed = innate AND adapative

3 symptoms of AS

low back pain and stiffness enthesisits large joint arthritis

define a polygenic autoimmune disease

mutationS in genes condoning proteins in pathwayS of ADAPTIVE immune

is hashimotos thyroiditis hyper or hypo? what 2 antibodies

HYPOthyroidism anti TPO antibodies (thyroid peroxidase antibodies) anti thyroglobulin antibodies

hashimotos is a combo of what 2 hypersensitivity reaction types

type 2 and 4

give a type 4 hypersensitivity condition

type 1 diabetes

1st presentation of T1DM, what 3 things to screen for

TFTs LFTs coeliac

what 2 antibodies in pernicious anaemia? what type of hypersensitivity reaction

type 2 hypersen autoantibodies against intrinsic factor (so can't absorb B12 - causing pernicious, megalomaniac anaemia & SCDC) Gastric parietal cell antibodies

tensilon test is positive in what type 2 hypersensitivity condition

myasthenia gravis | (drooping eyelids, weakness worse on repetition at end of day)

what 4 autoantibodies in T1DM

they pre date development of disease anti - glutamic acid decarboxylase (anti GAD) anti-insulin antibodies anti islet cell anti IA 2

what polymorphism in RA

PTPN22

What antibody is most specific for RA

anti CCP (cyclic citrullinated peptide)

butterfly rash in what condition

SLE

what other antibody may be found in SLE. give 4 ribonucleoproteins

anti ENA (extractable nuclear antigen) Ro La Sm U1RNP do NOT need these for diagnosis

recurrent miscarriage or VTE seen in what condition?

anti phospholipid

what skin is involved in CREST

hands peri oral skin

what skin is involved in diffuse cutaneous systemic sclerosis

hands AND proximal past forearms

what type hypersensitivity is dermatomyositis

type 3

what type of hypersensitivity is polymyositis

type 4

what ribonuclear proteins in sjogren's

Ro La

give an antibodiy in the myopathies

Anti-Jo1 Anti-Mi2 DM\>PM anti SRP -PM

state 2 large vessel vasculitis

takayasu's GCA/polymyalgia rheumatica

state 2 medium vessel vasculitis

kawasaki polyarteritis nodosa

what is ANA used to screen for vs ANCA

ANA - connective tissue diseases ANCA- small subset of the vasculitides

what autoantibody in ITP

anti-glycoprotein IIb antibodies

what 2 autoantibodies in autoimmune hepatitis

anti-liver kidney microsomal-1 antibody and anti-smooth muscle antibody.

what autoantibody in Primary Biliary Cirrhosis

Anti-Mitochondrial antibody (AMA Middle aged women are predominantly affected in a ratio of 9:1 F:M.

what HLA in coeliac

HLA dq2

whats Jaccoud's arthropathy and in what condition

condition characterised clinically by 'reversible'joint deformities such as swan neck, thumb subluxation, ulnar deviation, 'boutonniere' and hallux valgus, along with an absence of articular erosions on a plain radiograph. SLE

antibodies against Myelin Basic Protein?

multiple sclerosis

arteritis reveals a "rosary bead" appearance of small aneurysms = which vasculitis

PAN There may be other signs present, such as livedo reticularis. If a biopsy is required, a typical site is the Sural nerve (a superficial nerve in the calf of the leg).

in addition to anti TTG and anti endomysial, what else should be checked in coeliac

Hence, in IgA deficiency (1 in 600 people), they may be falsely negative. IgA levels should always be assessed at the same time when assessing for coeliac disease.

classic presentation of wegeners

A rapidly progressive glomerulonephritis in addition to nosebleeds or coughing blood suggests Wegener's granulomatosis. Nosebleeds suggest Wegner's - as this is a site classically affected. As a small-to-medium vessel vasculitis, it may also cause peripheral neuropathy and the elevated CRP is due to the high levels of inflammation. Wegener's is associated with C-ANCA.

electrophoresis shows oligoclonal IgG, what condition

multiple sclerosis

What specific malignancy are people with Sjogren's syndrome at greater risk of?

malt lymphoma

What virus is polyarteritis nodosa associated with?

hep b

what 3 antibodies in PBC

ANA AMA p ANCA

is pANCA more common in CD or UC

Which cytokine is important in the pathogenesis of rheumatoid arthritis, anyklosing spondylitis and inflammatory bowel disease?

TNFa

what susbset of T cells are associated w the transcription of FOXP3

T regulatory cels