autoinflammatory and autoimmune disease Flashcards
what is familiarl mediterranean fever
autosomal recessive mutation in MEFV gene leading to increased procaspase and more neutrophils.
how does familial mediterranean fever present
abdo pain, chest pain (pleurisy and pericarditis), arthritis, rash, associated with AA amyloidosis
how is familial mediteranean fever treated
colchicine - binds tubulin in neutrophils, anakinra (IL1 antagonist), etanercept - tnf alpha inhibitor
what is autoimmune polyendocrinopathy candidiasis ectodermal dystrophy syndrome (apeced)
recessive, defect in autoimmune regulator AIRE, upregulates experession of self antigens
how does apeced present
hypoparathyroidism, addisons, candidiasis, diabetes
what is immune dysregulation, polyendocrinopathy, enteropathy, x linked syndrome (IPEX)
- Mutations in FOXP3 which is required for development of T-reg cells
- Failure to negatively regulate T-cell responses → auto-reactive B-cells autoantibody formation
how does IPEX present
• Autoimmune diseases ‘diarrhoea, dermatitis and diabetes’ o Enteropathy o Diabetes mellitus o Dermatitis o Hypothyroidism
what is autoimmune lymphoproliferative syndrome (ALPS)
• Mutations in FAS pathway → e.g. mutations in TNFRSF6 to encode FAS (disease heterogenous depending on mutation) • Defect in apoptosis of lymphocytes o Failure of tolerance o Failure of lymphocyte homeostasis •
what are the signs and symptoms of autoimmune lymphoproliferative syndrome
• S/S: lymphocyte (lots), large spleen, lymph nodes, lymphoma (‘double negative cells’ T-cells CD4-ve, CD8 -ve)
o Lymphocytosis + large spleen + lymph nodes
o Autoimmune diseases (i.e. autoimmune cytopenias)
o Lymphoma
what are the genes involved in crohns
• IBD1 gene on Chr16 identified as NOD2 (CARD-15, caspase activating recruitment domain 15)
o 3 different mutations of this gene have been shown to be associated with Crohn’s disease
o NOD2 gene mutations are present in 30% of patients (so, it isn’t necessary)
o Abnormal allele of NOD2 increases risk of Crohn’s by 1.5-3x if 1 copy present, 14-44x if 2 copies
Mutations found in patients with Blau syndrome and some forms of sarcoidosis
• NOD2 expressed in cytoplasm of myeloid cells – macrophages, neutrophils, dendritic cells
o NOD2 = a cytoplasmic microbial sensor – recognises muramyl dipeptide stimulates NFK-beta ( TNFa)
o Activation induces autophagy in dendritic cells
what is type 1 gel and coombs
• Rapid allergic reaction
• Pre-existing IgE antibodies to allergen IgE bound to Fc receptors on mast cells and basophils cell degranulation
• Release of inflammatory mediators
o Preformed → histamine, serotonin, proteases
o Synthesised → leukotrienes, prostaglandins, bradykinin, cytokines
• Increased vascular permeability, leukocyte chemotaxis and SM contraction
• Usually foreign antigen → pollens, drugs, food, insect, animal hair
• Possible involvement of self-antigens in some cases of eczema
what is type 2 gel and coombes
antibody reacting with cellular antigen, Goodpasture, pemphigus vulgaris, graves disease, myasthenia gravis
what is type 3 gel and coombs
Type 3: antibody reacting with soluble antigen to form immune complex
• Antibodies bind to soluble antigen to form circulating immune complex
• Immune complexes deposit in blood vessels
o Complement activation, infiltration of macrophages and neutrophil
o Cytokine and chemokine expression
o Granule release from neutrophils
o Increased vascular permeability
• Inflammation and damage to vessels
o Cutaneous vasculitis
o Glomerulonephritis
o Arthritis
what is type 4 gel and coombs
Type 4: delayed type hypersensitivity - T cell mediated response
• Tissue destruction by… o HLA class 1 present SELF-antigens to CD8 T cells → cell lysis o HLA class 2 present SELF-antigen to CD4 T cells → cytokine production → inflammation and tissue damage e.g. insulin dependent diabetes mellitis, rheumatoid arthritis, multiple scleross
what type of gel coombs reaction is diabetes
t4
