transplant rejection
TRANSCRIPT
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TRANSPLANT REJECTION
BALAJI.RALTHEANZ 09’
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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
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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
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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
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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.
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Rejection reactions 1. Hyperacute 2. Acute a. cellular b. humoral 3. Chronic
MORPHOLOGY
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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
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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
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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
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CHRONIC REJECTION
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GRAFT ATERIOSCLEROSIS
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Immunosuppressive agents 1. Cyclosporin 2. Azathioprine 3. Steroids 4. Rapamycin 5. Monoclonal antibodies.
METHODS OF INCREASING GRAFT SURVIVAL
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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
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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
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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
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Days to weeks after allogenic bonemarrow transplantation.
Clinical features 1. Generalised rash 2. Jaundice 3. Ulceration of gut 4. Bloody diarrhea
ACUTE GVH
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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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