2.9 immuno Flashcards
(13 cards)
Kidney allograft rejection steps
Kidney’s dendritic cells migrate to spleen where they activate effector T cells
Effector T cells migrate to graft via blood
Effector T cells destroy kidney graft
Skin graft - what happens in rejection
Skin graft has langerhans cells
Langerhans cells migrate to lymph node where they activate host effector cells
Effector cells migrate to graft via blood
Effector cells destroy graft
Characteristics of acute organ rejection
Swelling
Hemorrhage
Necrotic tissue
What drugs are used to prevent graft rejection
Prednisone (corticosteroid)
Cyclosporin
FK506 / tacrolimus
Rapamycin (prevents IL2 signaling)
Mechanism of steroid action
Steroid goes thru plasma membrane and binds receptor in cytosol
Binding displaces hsp90 dimer from receptor, so now DNA binding site exposed
Receptor+steroid enters nucleus and binds specific DNA sequences in promoter region
Increase in IkBa which decreases NFkB immune activation
Mechanism of CsA and tacrolimus
CsA binds cyclophilin, tacrolimus binds FKBP
These bind to calcineurin and prevent it from activating NFAT
Now NFAT can’t go to nucleus and activate AP1, which forms a transc factor of IL2 gene for T cell clonal expansion
Graft vs host disease steps
Bone marrow transplant has donor T cells
Donor T cells blood to second lymphoid tissues
Donor T cells interact with host dendritic cells and proliferate
Differentiated CD4 and 8 T cells enter tissues and cause damage
Acute rejection uses
Direct recognition
Chronic rejection uses
Indirect recognition
Hyper acute graft rejection
When recipient already has antibodies against donor antigens, a rapid Ab mediated rejection occurs
Prevent by cross matching blood to detect Ab against donor Ag
Fetus might be well tolerated by mother because of
Trophoblast cells of placenta lack MHC expression
Secrete Th2 inducing cytokines (TGFb, IL4, IL10) favors T cell tolerance
Mixed lymphocyte reaction
Donor APC
Host T cell
3H-T
If T cells proliferate (can see through 3H-T), not compatible
Depends on MHC class II
51Cr-release assay
Cytotoxic T cell from host
Donor cells labeled with 51Cr
Detect increase in 51Cr from T cell killing donor cell
Depends in MHC I