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Autoimmune disease Viral disease Neurologic disorders Allergic reactions

MHC and disease association. Autoimmune disease Viral disease Neurologic disorders Allergic reactions. MHC genes and Pathogen defence. Significant associations of HLA Alleles with increased risk for various diseases.

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Autoimmune disease Viral disease Neurologic disorders Allergic reactions

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  1. MHC and disease association • Autoimmune disease • Viral disease • Neurologic disorders • Allergic reactions

  2. MHC genes and Pathogen defence

  3. Significant associations of HLA Alleles with increased risk for various diseases

  4. Population studies show association of susceptibility to IDDM with HLA genotype Affected siblings share 2 HLA haplotypes much more frequently than expected Certain HLA genotype are frequently found in diabetic patients DR3/4 tight linkage to DQb,

  5. Position of the DQb chain affects susceptibility to insulin-dependent diabetes mellitus AA 57 forms a salt bridge Across the peptide binding cleft of DQ Possible explanation: 1.) Allelic variants of MHC molecules differ in ability to present the autoantigenic peptides to autoreactive T cells 2.) Shaping of the T cell repertoire

  6. Hereditary hemochromatosis • Defective regulation of iron absorption • Disease associated with mutation in the nonclassical MHC class I gene HLA-H • Onset with 40 or 50 years, nonspecific symptoms • Iron overload and accumulation eg in the liver, leads to severe illness and cancer • HLA-H carries mutation at position 283 (no association with b2-microglobulin possible)

  7. Significant associations of HLA Alleles with increased risk for various diseases • Both inherited and environmental factors play a role in the induction of autoimmune disease • Inbred mice show uniform susceptibility to autoimmune disease • But also other independly segregating disease susceptibility loci have been defined • Also amount of self antigen transcribed in the thymus plays a role

  8. In the fight against viruses and tumors: high MHC I expression on target cells:good or bad ?? NK cell NK cell Lysis No lysis CD8 cell CD8 cell No Lysis Lysis Tumor cell: little MHC I Tumor cell: lots of MHC I

  9. “Innate Immunity”, D080

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