Immuno - Autoinflammation/Autoimmunity, Hypersensitivity Disorders and Transplantation Flashcards
Familial Mediterranean Fever
- MEFV mutation (monogenic auto inflammatory condition)
- Periodic fevers and serositis
- Abnormal TNFa/IL1 signalling
- Affects pyrin-mamrenostrin complex which controls activation of neutrophils
Rx:
oColchicine - disrupts tubules in neurophils
oAnakinra- IL1-R antagonist
oEntanercept- TNFa inhibitor
Crohn’s
- NOD2/CARD15 mutations (polygenic auto inflammatory disease)
- Affects ability of innate immune system to recognise bacteria = abnormal inflammatory response to microbes
- Risk also affected by: other genes, environment
HLA-B27 Mutations
Ank spon, psoriatic arthritis, behcets. HLA-B27 affects CD8 T cells, Th17 cells, NK cells etc.
RA, Myasthenia Gravis, pernicious anaemia, SLE
Polygenic autoimmune diseases
Risk affected by: HLA associations Mutations in: - PTPN22 -ve T cell regulator - CTLA4 -ve T cell regulator - Dysregulation of T cells → autoimmunity
Goodpastures HLA
DR15
Graves HLA
DR3
SLE HLA
DR3
T1DM HLA
DR3/DR4
Rheumatoid arthritis HLA
DR4
APECED
Central tolerance breakdown - mutation of TF AIRE – usually causes expression of self-antigens in thymus to enable -ve selection of autoreactive T cells
- Autoimmune
- PolyEndocrinopathy - hypoparathyroidism
- Candidiasis
- Ectodermal - skin/nails
- Dystrophy
IPEX
Mutation in FoxP3 – required for T reg cell development
CD25+ FoxP3+ = T reg cell
- Immune dysregulation
- Polyendocrinopathy
- Enteropathy
- X-linked
ALPS
Mutation of Fas pathway (apoptosis)
T cells not killed in thymus → enter periphery untolerised
- Autoimmune
- Lymphoproliferative
- Syndrome
Splenomegaly, lymphadenopathy, autoimmune cytopenia, lymphoma
T1 Hypersensitivity Reactions
IgE and mast cell mediated –> vasodilation, increased permeability and smooth muscle spasm
Sx: angioedema, urticaria, rhino conjunctivitis, wheeze, D&V
Conditions: atopic dermatitis, food allergy, oral allergy syndrome, latex food syndrome (certain foods associated with latex allergy), allergic rhinitis, acute urticaria (50% idiopathic, 50% food/drugs/febile illnesses etc - wheals completely resolve within 6 weeks), anaphylaxis
Anaphylaxis
IgE-mediated mast cell degranulation - peanut, penicillin, stings, latex
Non-IgE-mediated mast cell degranulation: NSAIDs, IV contrast, opioids, exercise.
Rx: elevate legs, adrenaline, chlorphenamine, hydrocortisone
Ix:
Skin prick testing
RAST –> measure levels of IgE in serum against specific antigen. Less sensitive than skin prick.
Component-resolved diagnostics - tests for specific allergen proteins
Challenge test - do in hosp
During an acute ep -mast cell tryptase
Type 2 Hypersensitivity Disorders
Ab mediated
- Haemolytic disease of the newborn
- Autoimmune haemolytic anaemia (+ITP = Evan’s syndrome)
- ITP - abs to glycoprotein IIb/IIIa on platelets
- Goodpastures
- Pemphigus vulgaris
- Graves
- Myasthenia gravis (ACh receptor)
- Acute thematic fever
- Pernicious anaemia
- Wegner’s
- Churg Strauss
- Microscopic polyangitis
- Chronic urticaria (wheals lasting >6 weeks, associated with angioedema in most cases. IgG against FceR1 or IgE)