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Transplant Rejection

Complex process both cellular and humoral immunity plays role T cell mediated rejection
  1. Direct pathway Interstitial dendritic cells in the donor-most important immunogen
    Both CD4+ and CDB+ cells involved     
    CD4+ cells extremely important role
    CD4+ cells release cytokine and CDB cells lyse the grafted tissue
  2. Indirect pathway of lysis of graft is by presentation of antigen by recipients antigen presenting cells.
    1. Antibody mediated rejection Q  
  1. Anti donor antibodies are present in the circulations
  2. Within minutes or hours after transplantation
  3. Initial target - Graft vasculature   
  1. Morphology
    Hyperacute: Gross- cyanotic, mottled, flaccid
    M/E - neutrophils within arterioles, glomeruli and peritubular capillaries
    Fibrin platelets / thrombi in vessels.
  2. Acute
    1. Within days
    2. Both cellular and humoral immunity plays role
    3. Interstitial mononuclear inflammatory infiltrate (CD4, CD6) Acute cellular Rejection
    4. Glomerular and peri tubular capillaries, large number of mononuclear cells
    5. After removal of immunosuppressive drugs
Acute humeral rejection Q
  1. Necrotizing vasculitis
  2. Endothelial necrosis
  3. Deposition of immunoglobulin, fibrin and thrombosis
  4. Arterial lesion (characteristic)
  5. Major alteration occurs in intima - thickened and lumen become marrowQ
Chronic Rejection

Vascular changes –
  1. Seen as obliterative intimal fibrosis especially in cortical arteries.
  2. Interstitial mononuclear infiltrate In form of lymphocytes, plasma cells and eosinophils
  3. Graft versus host disease –
    1. Seen in recipients of bone marrow transplant who are immuno deficient because of primary disease or treatment.
    2. When such recipients receive normal bone marrow cells from allogenic donors, the immuno competent T cells (CD4, CDs, T cells). recognize recipients HLA antigens as foreign and attack the last fossil.  
Mechanism Of Transplant Rejection
Rejection is a complex process in which both cell mediated and humoral immunity (antibody mediated) play a role.
  1. Cell mediated reaction
  1. It is mediated by T cells
  2. T cell recognizes graft by two pathways.
  1. Direct Pathway
  1. Certain cells in the graft express HLA antigen, of these dendritic cells (antigen presenting cells) in the transplant is particularly important.
  2. That means, T cells of the recipient recognize antigen (HLA protein) on the antigen presenting cells of the transplant (donor tissue).
  3. Two types of cells are involved in this pathway.
  • CD-4 T cells = Recognize HLA-II on antigen presenting cells (dendritic cells) and differentiate into TH1 cells that secretes cytokines. These cytokines induce inflammatory reaction with local accumulation of mononuclear cells particularly macrophages which destroy the graft tissue.
  • CD-8 T cells= Recognize HLA -I on APCs and differentiate into cytotoxic- T cells that kill the graft tissue by
  • Perforin - granzyme - dependent killing or    
  • Fas-fas ligand dependent killing.
  1. Indirect pathway
  1. In this pathway HLA molecule of the graft tissue is taken up by antigen presenting cells of the recipient and is presented to CD4 T cells of the recipient. CD-4 T cells become activated and destroy the graft.
  2. In this pathway cytotoxic CD-8 T cells are not involved.
It may present as:
Transplantation of Hematopoietic organs;
Graft versus host disease: immunologically competent cells or precursors are transplanted into immunosuppressed host. Present as –

a. Acute GVH: days to weeks
Acute GVH - Involvement of immune system & epithelia of skin, liver & GITQ by lymphocytic infiltration.

b. Chronic GVH:
  1. May follow acute GVH or occurs insidiously.
  2. Severe damage to skin, immune system and GIT. Q
  3. There is involution of thymus and depletion of lymphocytes from lymph nodes.
  4. Allogenic T cells in the graft lead to GVHD but there are required for engraftment of graft and control of leukemia.
  5. This is known as graft verus leukaemia effect. 
Transplant rejection:
It is mediated by NK cells & T cells of host.Q
Immunosuppression - CMV infection is common Q.

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