Autoimmune disease Viral disease Neurologic disorders Allergic reactions
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Transcript of Autoimmune disease Viral disease Neurologic disorders Allergic reactions
• Autoimmune disease
• Viral disease
• Neurologic disorders
• Allergic reactions
MHC and disease association
Population studies show association of susceptibility to IDDM with HLA genotype
Certain HLA genotype are frequently found in diabetic patientsDR3/4 tight linkage to DQ
Affected siblings share 2 HLA haplotypes much more frequently than expected
Position of the DQ 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 cells2.) Shaping of the T cell repertoire
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)
• 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
Significant associations of HLA Alleles with increased risk for various diseases
In the fight against viruses and tumors: high MHC I expression on target cells:
good or bad ??
NK cell
CD8 cell
Tumor cell: lots of MHC I
No lysis
Lysis
NK cell
CD8 cell
Tumor cell: little MHC I
Lysis
No Lysis