Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
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?
|
1/5000
|
|
|
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?
|
Days-months-years
|
|
|
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?
|
-Cyclosporine/Tacrolimus
-Corticosteroids -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 -Diarrhea |
|
|
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!!
also.. -Cholestasis -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 |
