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Principles to understand
immediate graft rejection is mediated by ABO or preformed HLA antibodies. they attack vascular endothelium and provoke clotting
acute rejection (2 weeks) is mediated by T cells
late rejection (months to years) is due to both T cells and antibodies
recurrence of the original disease occurs after years
survival of grafts is best in identical twins, followed by HLA-matched siblings, HLA-matched living related donors, HLA-matched cadaveric donors, HLA-mismatched donors
bone marrow ablation before the graft, followed by hematopoietic stem cell transplantation, seems to produce permanent graft survival in NOD (non-obese diabetic) mouse model
this works best when you are young and your thymus is still working
T-cell-mediated autoimmune disease
insulin-dependent diabetes mellitus: autoantigen is against pancreatic β-cell. β-cell transplantation would be futile if autoimmune disease persists
rheumatoid arthritis: autoantigen is unknown synovial joint antigen leading to joint inflammation and destruction
experimental autoimmune encephalomyelitis (EAE), multiple sclerosis: autoantigen is antigen against myelin; leads to brain invasion by CD4 T cells and weakness
DR3/4in healthy controls and diabetics
DR3/4 phenotype is not directly related to diabetes
however, DR3/4 are linked to a DQ antigen that does present a particular pancreatic β cell peptide differently
Category: Pathology Notes
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