【正文】 gs therapeutic cloning Xenografts HLA and disease There is a relationship between certain HLA antigens and specific diseases Ankylosing spondylitis Inflammatory condition in which the vertebrae are inflamed and deformed, leading to fusion of the joints in the spine. Those with HLAB27 are 100 times more likely to have this disease. 90% of those afflicted carry HLAB27 (versus 5% of general pop) maybe triggered by a bacterial infection Klebsiella However, 10% of cases do NOT have B27. Not all with B27 allele get disease. ?= HLAB27 is a significant factor but not the sole factor in ankylosing spondylitis. Why do we have a plicated HLA system? Need to be able to recognize self from nonself During development immune system learns who is “self” a large group of diseases is related to the inability to differentiate “self” immune system has decided that a cell of our body is not of our body Autoimmune Diseases When the immune system attacks the tissues of an individual’s own body it is called autoimmunity. Autoantibodies recognize “self” proteins. Some mechanisms include: Viruses use host proteins on the viral cell surface. These host proteins bee the target of the immune system which responds as if they are viral proteins. Thymocytes which recognize “self” antigens survive instead of apoptosing. Nonself antigen may coincidentally resemble “self” antigens. Autoimmune disorder Symptoms Target of Antibodies Glomerulonephritis Lower back pain Kidney cell antigen that resembles Streptococcus antigen Graves disease Restlessness, weight loss, irritability, increased heart rate and blood pressure Thyroid gland antigen Myasthenia gravis Muscle weakness Nerve message receptors on skeletal muscle cells Pernicious anemia Fatigue and weakness Binding site for vitamin B on cells lining stomach Rheumatoid arthritis Joint pain and deformity Cells lining joints Systemic lupus erythematosus Red rash on face, fever, weakness and kidney damage DNA, neurons, blood cells Type I diabetes Thirst, hunger, weakness, emaciation Pancreatic beta cells Ulcerative colitis Lower abdominal pain Colon cells Inherited immune deficiencies Mutations in genes encoding proteins used in immunity result in impaired immune response. 20 types of inherited immune deficiency Chronic granulomatous disease: mutation of oxidase enzyme results in neutrophils that cannot kill bacteria. Severe bined immune deficiency (SCID) impacts both humoral and cellular immunity due to lack of mature B cells and/or T cells. Xlinked agammaglobulinemia (XLA) usually boys characterized by having multiple serious bacterial infection during childhood (20 or more in 5 years). have normal T cells patients don’t have any mature B cell can39。t make antibodies protected for the first 6 months by maternal antibodies rest of life always having severe infections pneumonia and strep SCID severe bined immunodeficiency Both antibodymediated and cellmediated immune responses are nonfunctional usually die at a young age from a minor bacterial threat “boy in the bubble” David – died at age 12 lacked of a thymus gland Some SCID cases are due to ADA deficiency (adenos