AI 2 Flashcards
(23 cards)
cd4 act via
IFN-Y, IL17
t4 hs examples
T1DM , RA, MS (myelin basic protein - brian infiltrated by CD4) , Experimental AI encephalitis (myelin oligodendrocyte glycoprotein)
pemphigus vulgaris t2 disease
epidermal cadherin –> blisters
Familial meditereanean fever protein
Pyrin-Marenostrin (AR disease) expressed in neutrophils, failure to refulaute cryopyrin driven activation of neutrophils
Cryopyrin protein affected in …
monogenic Autoinflammatory diseases AD, NLRP3 gene
monogenic Autoinflammatory diseases affect CK pathways…
TNF or IL-1
Diseases re to pathogensis
Monogenic Autoinflammatory diseases
TNF/il-1
Familial Mediterenean Fever
- Autosomal recessive condition
- Mutation in MEFV gene
- Gene encodes pyrin-marenostrin
- Pyrin-marenostrin expressed mainly in neutrophils
- Failure to regulate cryopyrin driven activation of neutrophils
FMF tx
Colchicine
- Anakinra (Interleukin 1 receptor antagonist)
- Etanercept (TNF alpha inhibitor)
Auto-immune polyendocrine syndrome type 1 (APS1)
Aka auto-immune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome / APECED
Autosomal recessive disorder
Defect in ‘auto-immune regulator’ – AIRE - transcription factor regulates self-antigens and involved in development of T cell tolerance in the thymus à upregulates expression of self-antigens by thymic cells à promotes T cell apoptosis of autoreactive t-cells
failure of central tolerance
- Multiple auto-immune diseases - esp AI hypoPTH (low calcium) + addisons but can also get hypotT, diabetes, vitiligo, enteropathy
- Antibodies vs IL17 and IL22 (immunodeficiency due to anti-ck antibodies) à candidiasis
Immune dysregulation, polyendocrinopathy, enteropathy, X- linked syndrome (IPEX)
Mutations in Foxp3 (Forkhead box p3) which is transcription factor required for development of Treg cells. Failure to negatively regulate T cell responses - autoantibody formation
Autoimmune diseases – enteropathy, DM, hypothyroidism, dermatitis (Exematous type, with high IgE) – can also get psoriasis
Auto-immune lymphoproliferative syndrome (ALPS)
Mutations within FAS pathway leading to defect in apoptosis – many mutations in pathway but similar phenotype e.g. mutations in TNFRSF6 which encodes FAS. Disease is heterogeneous depending on the mutation. Defect in apoptosis of lymphocytes - failure of tolerance (don’t die when recognise self-antigen in thymus), failure of lymphocyte ‘homeostasis’ (don’t die) à lots of AI cells + lots of proliferating cells in response to infections
High lymphocyte numbers with large spleen and lymph nodes - double negative (CD4-CD8-) T cells
Auto-immune disease - commonly auto-immune cytopenias
May be associated with lymphoma – as failure to control T-cell proliferation
Crohns tx
- Corticosteroid – responsive, but don’t want to give it long term so give
- azathioprine
- Anti-TNF alpha antibody
- Ustekinumab (anti-IL12/23)
Crohns histology
Glanulomata
Tissue damage, mucosal ulceration
Focal inflammation in/around crypts
Crohns genetics
IBD-1 locus on chromosome 16 n
- identified as NOD2 (CARD-15, caspase activating recruitment domain -15).
- Three different mutations of this gene have each been shown to be associated with Crohn’s disease.
- NOD2 gene mutations are present in 30% patients (ie not necessary)
- Abnormal allele of NOD2 increases risk of Crohn’s disease by 1.5-3x if one copy and 14-44x if two copies (ie not sufficient on own – common idea in polygenic diseases)
- Mutations also found in patients with Blau syndrome and some forms of sarcoidosis – other inflammatory symptoms
- NOD2 expressed in cytoplasm of myeloid cells - macrophages, neutrophils, dendritic cells
- Acts as a microbial sensor - recognises muramyl dipeptide – and stimulates NFKb and triggers an inflammatory response
AnkSpond x-ray and tx
- Irregular damage, erosive change with sclerosis on x-ray
- Lumbar vertebra – spinal fusion on x-ray
Anti-tnf alpha
Secukinumab (anti-il17a)
ank spond genetics
Type 3 HS
Cryoglobulinaemia
Fc region of IgG
Hepatitis C antigens
Vasculitis, rash
Systemic lupus erythematosus
DNA, histones, RNP
Glomerulonephritis, vasculitis, rash
Rheumatoid arthritis– extent to which it contributes to pathogenesis is unclear
Fc region of IgG
Arthritis
giant cell arteritis tx
high dose cortocosteirods asap
GP HLA
HLA DR15
Genes in polygenic AI disease
