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TRANSPLANT REJECTION
BALAJI.RALTHEANZ 09’
Rejection is a complex process in which “recepient immune system recognize the graft as foreign and attacks it”.
It involves 1. Cell mediated immunity 2. Circulating antibodies
REJECTION
It is caused by T-cell mediated reactions. Destruction of grafts occurs by 1. CD8+ CTLs 2. CD4+ helper cells Delayed hypersensitivity is triggered by
CD4+ helper cells. 2 pathways 1. Direct pathway 2. Indirect pathway
CELLULAR REJECTION
It is called humoral rejections. 2 types 1. Hyperacute
2. Acute
HYPERACUTE: Presence of preformed antidonor
antibodies. Transplant rejection has already occurred.
ANTIBODY MEDIATED REACTIONS
ACUTE: Initial exposure to class I&II HLA
antigens. Antibodies causes injury by 1. Complement dependent
cytotoxicity 2. Inflammation 3. Antibody dependent cell
mediated cytotoxicity.
Rejection reactions 1. Hyperacute 2. Acute a. cellular b. humoral 3. Chronic
MORPHOLOGY
Occurs within minutes or hours after transplantation.
Kidney becomes 1. Cyanotic 2. Mottled 3. Flaccid Immunoglobulin and complement
deposition occurs. Neutrophils accumulate leading to occlusion
of capillaries & fibrinoid necrosis.
HYPERACUTE
Cellular – mononuclear cell infiltrate Humoral – vasculitis ACUTE CELLULAR: Seen within initial months after
transplantation. Mononuclear cells accumulates in
glomerular and peritubular capillaries leading to FOCAL TUBULAR NECROSIS.
Treatment – cyclosporin.
ACUTE
Also known as rejection vasculitis. Necrotizing vasculitis characterised by
intimal thickening. Presence of complement breakdown
product C4d – indicator of humoral rejection.
Treatment – B cell depleting agents.
ACUTE HUMORAL REJECTION
CHRONIC REJECTION
GRAFT ATERIOSCLEROSIS
Immunosuppressive agents 1. Cyclosporin 2. Azathioprine 3. Steroids 4. Rapamycin 5. Monoclonal antibodies.
METHODS OF INCREASING GRAFT SURVIVAL
ANOTHER METHOD: Prevention of host T cells from
receiving co-stimulatory signals (B7-1&2) from dendritic cells.
DISADVANTAGES: EBV induced lymphoma HPV induced squamous cell carcinoma Kaposi sarcoma
Hematopoietic stem cell transplants are used for
1. Hematological malignancy 2. Aplastic anemia 3. Thalassemia 4. Non hematological cancersPROBLEMS: 1. Immunodeficiency 2. GVH disease
HEMATOPOIETIC STEMCELLS
Occurs in any situation in which “immunologically competent cells or their precursors are transplanted to immunologically crippled recipients and the transferred cells recognize allo-antigens in the host”.
It may be 1. Acute 2. Chronic
GRAFT VS HOST DISEASE
Days to weeks after allogenic bonemarrow transplantation.
Clinical features 1. Generalised rash 2. Jaundice 3. Ulceration of gut 4. Bloody diarrhea
ACUTE GVH
Follow acute syndrome or occur insidiously.
Clinical features 1. Cutaneous injury 2. Cholestatic jaundice 3. Esophageal strictures 4. Depletion of lymphocytes It is a life threatning condition. Treatment – bonemarrow transplants.
CHRONIC GVH
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