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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