Graft Rejection

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Graft Rejection Powered By Docstoc
					Faculty of medicine.
Alexandria university.
Department of pathology.

      Graft rejection
2.Types of transplantation.
3.Graft rejection.
4.Causes of graft rejection.
5.Mechanism of graft rejection.
6. Types of graft rejection.
7.Treatment of graft rejection.
Transplantation :
  Transferring cells, tissues, or organs
from one site to another
Types of transplantation:
Autologous graft = auto graft.
Synegenic graft = syngraft.
Allogeneic graft = allograft.
Xenogenic graft = xenogaft.
Graft rejection:
    Occurs when a transplanted organ or tissue
fails to be accepted by the body of the
transplant recipient.
    Causes of graft rejection:
      Pleomorphism of MHC genes

Different MHC Ags within species& individuals

T Lymphocytes recognize transplanted organ as
foreign& release cytokines that lyse cells.

               Graft failure
Mechanism of graft rejection:

 2.Antibody Mediated Reactions
    (Humoral rejection)
 Mechanism of graft rejection:
1.T Cell Mediated (Cellular rejection):


      + CD8 cells              cytokine

   Lysis of grafted tissue.
                               mononuclear cells
Types of T cell mediated reaction:
1. Direct Pathway:
 T cells of recipient recognize allogenic MHC molecule
  on the surface of an APC in donor.
 interstitial dendritic cells of donor organs are the best
 CD4+ and CD8+ T cells of recipient encounter antigens
  in lymph nodes
 CD4+ proliferate, release cytokines& trigger delayed
  hypersensitivity reaction.
 Cytokines       vascularity &induceinflammation.
 mature CTLs are generated and lyse grafted tissue .
2. Indirect pathway:
recipient T lymphocytes recognize antigens
after being presented by own antigen-
presenting cells.
same as presentation of microbial antigens.
2.Antibody Mediated Reactions :
(Humoral rejection)
1. In Hyperacute reaction:
   previous exposure to the donor antigens.
   As in:
        previous rejected kidney transplant.
        Multiparous women.
        Previous blood transfusion.
2. In chronic rejection:
   not previously exposed to the donor antigen.
   Abs cause damage by complement, ADCC &Ag Ab
Types of graft rejection:
a) Hyper acute = immediate.
b) Acute      = cellular.
c) Chronic    = fibrosis.
Hyper acute rejection:
 Reaction due to:
     complement + preexisting antibodies as
     (ABO)       (humoral)
     occurs within minutes to hours.
     Rapid thrombosis, no vascularization.
     Acute systemic inflammation .
     Organ is removed.
Steps involved:
     Morphology of hyper acute
In hyper acutely rejecting kidney
 Grossly:

   cyanotic, mottled, flaccid and may excrete few
  drops of bloody urine
 Microscopically:

   Acute necrotizing vasculitis.
   Neutrophil accumulation.
   Platelet aggregation.
   Complements activation &endothelial damage.
   Acute inflammation &vascular thrombosis.
Hyper acute rejection:
Acute rejection:
    cellular: Primary activation of T cells.
   weeks after transplantation..
   organ failure (mainly in vascularized organs)
   recurrent episodes          chronic rejection.
Acute rejection
     signs& symptoms.
     Lab diagnosis& tissue biopsy.
Morphology of acute rejection:
There is acute cellular rejection
 1. T lymphocyte infiltration.
 2. injury of the tissue.
 3. injury of organ bood vessels
Chronic rejection:
 Reaction: cellular
    chronic immune response.
    fibrosis of internal blood vessels.
    (allograft vasculopathy)
    along years.
    loss of function gradually.
    need anew transplant usually after a decade
    Morphology of chronic rejection:
   Loss of function in transplanted organs
   termed chronic allograft vasculopathy
   Grossly
    vascular changes: of dense intimal fibrosis in
    the cortical arteries& renal ischemia
     glomerular loss and tubular atrophy
    shrinkage of renal parenchyma.
   Microscopically:
    vascular lesions
    mononuclear cell infiltrates
Chronic kidney rejection
a) Hyperacute rejection:
    only by removal of the organ immediately

b) Chronic rejection:
    irreversible & cannot be prevented.
    only treatment is a new transplant after
    10 years.
c) Acute rejection:
       1.high dose corticosteroids.

               Not enough

               Not enough

       3.tripple therapy.
Triple therapy:
1.Corticosteroids e.g Cyclosporin A.
2.Calcineurin inhibitor.
3.Antiproliferative agent .
    antibodies against blood vessels.
    &blood transfusion        remove antibodies
    against the transplant.
Graft associated immune suppression:
     lyse mature T cells.
     + Dnase
       cytokine synthesis
       IL1, IL6& TNF
1.Metabolic toxins:
       lymphocyte growth.

4.Induce tolerence:
      by multiple blood transfusion.

      against T cell surface proteins.
      monoclonal Ab against CD3.
      antibodies against b cells.
      Can also remove Ab by plasmapheresis
Thank you…..