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50 Cards in this Set

  • Front
  • Back
What are the 2 types of transplants done?
-HSCT (bone marrow)
-SOT (solid organ)
What are the 2 pathways of Tcell recognition for transplant rejection?
1. Direct
2. Indirect
What is the direct pathway?
The MHC molecules on APC's in the graft are recognized by the recipient's own Tcells and induce a cell-mediated reaction.
What is the indirect pathway?
APCs from the recipient present foreign peptides from the graft to the recipient's own Tcells which respond and react.
What is acute humoral rejection?
The development of antibodies to a graft
What is hyperacute rejection caused by?
Preformed antibodies to the graft
Is hyperacute rejection very common or clinically significant? Why?
No; because crossmatching is now done prior to transplant.
What is the direct pathway of Tcell-mediated rejection associated with?
Acute cellular rejection
What is the indirect pathway of Tcell-mediated rejection associated with?
Chronic cellular rejection
What is the usual manifestation of acute humoral rejection? Why?
Vasculitis - because the initial target of the antibodies is the graft vasculature.
How do we describe the genetics of MHC?
As polygenic and polymorphic
What does polygenic mean?
There are several MHC genes
What does polymorphic mean?
There are many alleles of each of the several genes!
What are the odds of being a perfect HLA match with an unrelated person?
Does being a perfect HLA match with a graft donor help much?
No not a lot
What is more important that being a complete HLA match?
Crossmatching donor WBC's to the recipient's serum, to see if they are recognized as foreign and rejected.
Why is crossmatching essential?
To prevent hyperacute rejection and graft loss within hours.
When the direct pathway of allorecognition occurs, what are the resulting effector mechanisms?
-CD8 cell becomes a CTL which directly attacks the graft
-CD4 cell becomes a Th1 cell and stimulates inflammation
When the indirect pathway of allorecognition occurs, what are the resulting effector mechanisms?
CD4 cells damage the graft by local delayed type hypersensitivity, but there is no direct lysis of the graft.
What are the 3 forms of rejection?
1. Hyperacute
2. Acute
3. Chronic
How soon does hyperacute rejection occur?
Within minutes to hours after transplant
What is the basis of hyperacute rejection?
Preformed antibodies present in the recipient's circulation
What is the main pathology of hyperacute rejection?
Vascular thrombosis
What is the timeframe for acute rejection?
What is the main pathology of acute rejection?
Interstitial inflammation and vasculitis
How is acute rejection treated?
With immunosuppressive medications
What is the main pathology of chronic rejection? Timeframe?
Vascular fibrosis
-occurs over months to years
What is the classic example of hyperacute graft rejection?
ABO mismatch
What is the principal cause of early graft failure?
Acute rejection
What is acute rejection mainly mediated by?
Tcells reacting against alloantigens in the graft.
What are 3 types of medications used to suppress immune reactions?
-Anti-CD3 monoclonal antibody
How do Cyclosporine and Tacrolimus work?
By inhibiting calcineurin which blocks Tcell cytokine secretion
How do the corticosteroids suppress the immune system?
By inhibiting macrophage cytokine secretion to reduce inflammation
How does Anti-CD3 monoclonal Ab work as an immunosuppressant?
By binding CD3 and promoting phagocytosis and C'mediated lysis - depletes Tcells.
What are the complications of taking immunosuppressants?
-Increased susceptibility to infections
-Increase in certain malignancies
What does chronic graft rejection lead to?
Loss of graft function
What is the basic mechanism of chronic graft rejection?
-Tcell secreted cytokines stimulating fibroblast proliferation and vascular smooth muscle proliferation in the graft
What is the ultimate result of chronic graft rejection?
Graft vessel occlusion
What are 3 histologic findings in chronic kidney rejection?
1. Graft arteriosclerosis
2. Tubular atrophy
3. Interstitial fibrosis
Why is the incidence of chronic rejection and graft arteriosclerosis rising?
Because treatments for acute rejection have gotten much better.
In what patients is GVHD mostly observed?
HSCT recipients
What is hematopoietic stem cell transplant usually given to treat?
Hematologic malignancy
What is the basis of GVHD?
-DONOR Tcells mount immune response to RECIPIENT tissues
Why is GVHD a reaction of donor against recipient?
Because the recipient's own immune system has been depleted or even ablated.
What are the 3 manifesting symptoms of GVHD?
-Skin rashes
-Liver damage - increased bilirubinemia
What is the skin reaction that is caused by GVHD called?
Interface dermatitis
What is the cause of the skin lesions in GVHD?
Apoptosis of keratinocytes
What are the causes of the increased bilirubin in GVHD?
-Bile duct damage!!
-Lobular hepatitis
What is the cause of diarrhea in GVHD?
Apoptotic bodies in crypts
What are the microscopic findings in GVHD?
-Skin keratinocytes are pink and pyknotic
-Apoptotic bodies on GI biopsy