- New York Medical College
- Microbiology & Immunology
- Microbiology & Immunology 1
Last Modified: 2014-09-04
Transfer of tissues between genetically identical humans
- •Mature T-cells from donor bone marrow graft make their way to 2° lymphoid tissue where they interact with the dendritic cells of the recipient•Almost all BMT recipients suffer from this to some degree•GVHD is a major cause of morbidity and mortality after BMT•Tends to attack primarily the skin, intestines and the liver•Described as a “cytokine storm”
Effector response of the hyper-acute rejection process
PREFORMED antibody (ABO, HLA) + Complement
ABO – food, bacteria
HLA – transfusion (MHC on lymphocytes and platelets ) & pregnancy
The more different peptides are present, the stronger the response
- T cells react w/ donor graft
- low grade chronic inflammatory response (years)
- donor APCs migrate to a local lymph node and stimulate alloreactive recipient T cells
- This direct allorecognition can result in acute rejection of the organ within a few days following the transplantation procedure
Mixed lymphocyte reactions
Take donor cells, irradiate or poison (damage DNA, cant replicate), then add recipient lymphocytes.
If recipient T cells are stimulated, will be measurable via replication through incorporate of radioactive DNA and cytotoxicity.
Typically involve 4 classes of drugs
Treatment of Acute Rejection Rescue Therapy
- Large doses of corticosteroids
- Adjust dosing of the calcineurin inhibitors
- Anti-T-cell antibodies
Steroids up-regulate production of IκBα which prevents NFκB from entering the nucleus
Cytokine production is inhibited
IP3 pathway which activates the Ser/Thr phosphatase Calcineurin
Calcineurin removes a phosphate from the molecule NFAT in the cytoplasm
NFAT then enters the nucleus and binds to the transcription factor AP-1; this complex then activates the transcription of IL-2
MADE FROM FUNGUS
distinct from but has a similar mechanism as CSA
FK506 binds to FK binding protein 12, inhibiting calcineurin, blocking T cell activation
Binds to FK-binding proteins but DOES NOT inhibit calcineurin
Blocks T-cell activation at a later stage - inhibits signal transduction from IL-2 receptors
Is more toxic than CSA and Tacrolimus
-within months to years
- mediated by Th cells that activate delayed-type hypersensitivity reaction that may trigger fibrosis of the graft and/or progressive blood vessel narrowing in the graft
Alloantibodies (primarily to MHC I) react in the vasculature of the transplanted organ and cause thickening of the vessel walls and narrowing of the lumen, activated by T cells
Results in inadequate blood supply and eventually ischemia and graft failure ultimately
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