Renal Transplant: T-Cell mediated Hypersensitivity

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