Graft Rejection

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

      Graft rejection
0bjectives:
1.Introduction.
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):

                         CD4

      + CD8 cells              cytokine

                                 inflammation
   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
  immunogenic.(why?)
 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
    complex
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)
 Time:
     occurs within minutes to hours.
 Complication:
     Rapid thrombosis, no vascularization.
     Infarcts.
     Acute systemic inflammation .
 Prognosis:
     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:
Reaction:
    cellular: Primary activation of T cells.
    &humoral.
Time:
   weeks after transplantation..
Complication:
   organ failure (mainly in vascularized organs)
   recurrent episodes          chronic rejection.
Prognosis:
    treatable.
Acute rejection
Diagnosis:
     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)
Time:
    along years.
Complication:
    loss of function gradually.
Prognosis:
    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
Treatment:
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

       2.repeated.
               Not enough


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

2.Irradiation:
4.Induce tolerence:
      by multiple blood transfusion.

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