Solid Organ Transplant Rejection Flashcards
Patients with transplants
-need to take medications to suppress natural immune system response —> prevent rejection
-take medications to prevent infection
Often have some degree of rejection and OI
Transplant organs
Heart, lungs, small intestine, pancreas, liver, kidneys, cornea, cartilage and bone marrow (no considered a solid organ)
Bone marrow transplant rejection
Graft vs host disease
Target of rejection is recipient’s own cells
Any HLA cell is a target
Solid organ transplantation
Target of rejection is only the transplanted organ cells
Rejection is a T-cell mediated immune response
Human leukocyte antigen HLA
HLA systems are made up of HLA antigens the histocompatibility genes aka (MHC) are responsible for coding these proteins located on chromosome 6
Major Histocompatibility complex MHC
HLA of donor and recipients must match to decrease chances of rejection
Class I antigens HLA- A,B,C are responsible for organ rejection
Hyperacute rejection
Occurs immediately when circulation to graft is restored and organ turns white instead of pink
-uncommon due to tissue cross matching
-can occur due to blood transfusion with foreign HLA antibodies (immune system already primed)
Acute rejection
Occurs days to months after transplantation
Cell mediated immune response
Chronic rejection
Occurs months to years
Characterized by slow, weak cell mediated immune response
Steps of organ rejection
Once organ is transplanted the antigen presenting cells (macrophages) present the HLA antigen to both CD4 cells and CD8 cells —> T cell proliferation (TH1 and TH2)
TH1 —cytokines—> activates Cytotoxic T-cells —bind—> with IL2
Cytotoxic T-cells and IL2 create an allogenic cell lysis and further stimulates T-cell proliferation
TH2 —cytokines—>Stimulate B-cell immunity
B cells produce antibodies and bind with allogenic cells —> inflammatory cascade and complement system — > cell lysis
Antibody products cause graft cell cytotoxicity
Calcineurin Inhibitors
Cyclosporine and Tacrolimus
-prevents cytokine production by binding calcineurin —> prevent T cell activation
(Preventative of rejection)
No affect on active T cells
Purine Antagonist anti-metabolite
Azathioprine
Purines and pyrimidines —> building blocks of DNA and RNA
Purine antagonist prevent the growth of DNA and cell division of T cells
Blocks T-cell proliferation and cytotoxicity
(Can only prevent rejection)
Mycophenolate Mofetil
Inosine monophosphate (IMP) molecule used to make DNA and RNA
IMP is a precursor to guanosine
Mycophenolate inhibits enzyme inosine monophosphate dehydrogenase
(Can only prevent rejection)
Corticosteroids
Prednisone and methylprednisolone
Prevents…
RNA and DNA synthesis
Cytokines release
IL2 production and IL2 activation of T-cells
Cytokine induced B cell stimulation
Macrophage activity
Leukocyte chemotaxis
Complement system
Phospholipase A2 from making prostaglandins
This group of medications prevent the immune and inflammatory response
Used to treat rejection
