HLA Human leukocyte antigen
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HLAHuman leukocyte antigen
Katrín Jónsdóttir
2. okt. 2008
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Yfirlit
• Sérhæft ónæmissvar
• MHC vs. HLA
• Uppbygging HLA
• Fjölbreytni HLA
• Samanburður á HLA class I og II
• Sjúkdómar tengdir skorti á HLA
• Fylgni HLA genasamsæta við sjúkdóma
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Sérhæft ónæmissvar
• B-frumur Vessabundið ónæmissvar
• T-frumur Frumubundið ónæmissvar
APC
T-fruma
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MHC vs. HLA
• Major Histocompatibility Complex, MHC
• Human Leucocyte Antigen, HLA
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Uppbygging HLA
MHC class I MHC class IIHLA class I HLA class II
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Fjölbreytni
• HLA class I
– A
– B
– C
• HLA class II
– DR
– DP
– DQ
– DR-α + auka β
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Fjölbreytni
• Langflestir arfblendnir
• Genasamsæturnar jafnráðandi og því bæði genin tjáð
• Mikil fjölbreytni milli einstaklinga
>400 genasamsætur af sumum HLA class I/II genum
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Samanburður á HLA class I og II
• Umfrymi HLA class I – Cytotoxic T-frumur með co-receptor CD8
• Intracellular vesicles HLA class II – Hjálpar T-frumur með co-receptor CD4
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Vefur HLA class I HLA class II
Eitilvefur
T-frumur +++ +
B-frumur +++ +++
Macrophagar +++ ++
Aðrar APC +++ +++
Aðrar kyrndar frumur
Neutrophilar +++ -
Hepatocytar + -
Kjarnalausar frumur
Rauð blóðkorn - -
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HLA class I skortur Bare lymphocyte syndrome type I
• Stökkbreyting í TAP sem tengir peptíðbrotin við HLA class I sameindina
• Sjaldgæft, erfist autosomal víkjandi
• Getur verið frá því að vera einkennalaust í það að vera lífshættulegt
• Krónískar bakteríusýkingar í efri/neðri loftvegum og húðsýkingar
• Meðferð symptomatisk
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HLA class II skortur Bare lymphocyte syndrome type II
• Skortur á tjáningu HLA class II
• Fáar CD4 T-frumur og hypogammaglobulinemia
• Sjaldgæft, erfist autosomal víkjandi
• Endurteknar veiru, bakteríu og sveppasýkingar
• Meðferð: Beinmergsskipti eða IVIG og profylaxisk sýklalyf
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Áhrif genasamsæta HLA
Auknar líkur á höfnun transplants ef missamræmi í DR, B eða í minna mæli A
Betri horfur í HIV: B57 og B27Verri horfur í HIV: B35
Betri lifun í malaríusýkingum: B53
Auknar líkur á gigtsjúkdómum:• Hryggikt: B27• Akút anterior uveitis: B27• Goodpasture’s syndrome: DR2• Multiple sclerosis: DR2• Graves´ sjúkd.: DR3• Myastheina gravis: DR3• Lupus: DR3• DM1: DR3/DR4 • Rheumatoid arthritis: DR4• Hashimoto’s thyroiditis: DR5
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