transplantation immunology Flashcards
autografts
grafts exchanged from one part to another part of the same individual
isografts
grafts exchanged between different individuals of identical genetic constitutions (e.g. identical twins)
allografts (allogeneic)
grafts exchanged between nonidentical members of the same species
xenografts (zenogeneic)
grafts exchanged between members of different species
what type of grafts are especially susceptible to rapid attack by naturally occuring Abs and completment
xenografts
HLA Ags are ____ expressed
co-dominantly
polymorphisms in class ____ HLA Ags are particularly strong barriers to transplantation
1
because every nucleated cell expresses class I
class 2 HLA- three most important for transplantation pairs are
HLA-DR
HLA-DP
HLA-DQ
allograft recognition: direct vs indirect:
- direct
- ____ APC → ____ T cell
- recipient T cell recognizes the ____ foreign MHC found on the donor APC
- ____ APC → ____ T cell
- indirect
- ____ APC (with processed MHC from donor tissue) → ____ T cell cell
- the key part of this pathway is the ____ of Ag by MHC
- ____ rejection
- donor recipient
- unprocessed
- recipient recipient
- processing
- chronic
host vs graft:
- non-immune injury to graft → generation of ____
- host T-cells enter the allograft and recognize ____ ____
- cytokine field amplifies entire process
- two types of rejection
- humoral: ____
- cellular: ____
- DAMPS
- foreign MHC
- TH2
- TH1
non-immunological factors (condition of allograft) that impact transplant outcomes:
- damaged grafts ( ____ trauma and ischemia-reperfusion injury)
- ____ ____ ____ : time an organ is without blood circulation and is kept cold from the time the organ is removed from the donor to the time it is transplanted into the recipient
- when transplanted, damaged graft tissues release ____ which trigger several biochemical cascades leading to immediate tissue damage
- release clotting factors ( ____ )
- fibrinopeptides actviates ____ cells and ____ cells (chemoattractant)
- ____ results in vasodilation
- can lead to ____
- when transplanted, damaged graft tissues release ____ which trigger several biochemical cascades leading to immediate tissue damage
- ____ ____ ____ : time an organ is without blood circulation and is kept cold from the time the organ is removed from the donor to the time it is transplanted into the recipient
- mechanical
- cold ischemia time
- mediators
- fibrinopeptides
- endothelial mast
- bradykinin
- rejection
- cold ischemia time
ABO matching is not important for
corneal transplantation
heart valve transplantation
bone and tendon grafts
ABO incompatibility is not a contraindication to ____ ____ transplantation
stem cell
testing for ABO blood group:
- fresh blood
- anti-A serum
- ____ occurs (due to complement )
- type ____ blood
- ____ occurs (due to complement )
- anti-B serum
- ____ does not occur
- not type ____ blood
- ____ does not occur
- anti-A serum
- fresh blood
- anti-A serum
- agglutination
- A
- anti-B serum
- agglutination
- B
- agglutination
- agglutination
- anti-A serum
ABO compatibility chart:
- type A
- compatible washed RBCs:
- compatible plamsa:
- type B
- compatible washed RBCs:
- compatible plamsa:
- type AB
- compatible washed RBCs:
- compatible plamsa:
- type O
- compatible washed RBCs:
- compatible plamsa:
- type A
- A and O
- A and AB
- type B
- B and O
- B and AB
- type AB
- A, B, AB, and O
- AB
- type O
- O
- A, B, AB, and O
MHC is termed the ____ ____ ____ , HLA complex
human leukocyte antigen
HLA compatibiity between donor and recipient it required due to the extreme ____ of HLA
polymorphism
MHC I Microtoxicity Test:
- ____ cells + ____ serum
- complement will form and ____ accumulates in cells ( ____ present
- no dye accumulation (Abs are not present) → potential ____
- donor recipient
- dye Abs
- donor
preformed Ab testing: Microtoxicity test:
- tests for ____ Ab against ____ HLA
- donor cells are isolated and ____ serum (containing Ab) is added
- ____ is added (if recipient Ab is specific for donor cells, classical complement pathway is activated)
- ____ is added (if complement is ativated, dye enter cells via pore created by MAC)
- if cell cytoplasm is stained, that means the recipient Abs will ____ donor cells
- recipient donor
- recipient
- complement
- dye
- attack
HLA Class II typing - mixed lymphocyte response:
- isolated ____ cells (presumably APCs since they have MHC II) are ____ so they are incapable of proliferated)
- ____ cells (that are capable of proliferating) are added in addition to radiolabeled thymidine
- (usually lymphocytes that are strongly reactive to self MHC are eliminated during development) if non-recipient MHC class II is introduced, recipient lymphocytes can react to it since they were never tested ____ it
- this is detected as the ____ recipient cells will incoporate the radiolabeled thymidine into their ____
- donor irradiated
- recipient
- against
- proliferating DNA
Host vs Graft:
- ____ immune system recognizes and attacks ____ tissue
- three types:
- recipient donor
- hyperacute
- acute
- chronic
- hyperacute
graft vs host:
- ____ immune cells that “piggy back” in with the transplant recognize, proliferate, and attack the ____
- mostly occurs in transplantation of ____ ____ as it will produce donor immune cells in the recipient
- donor recipient
- bone marrow
acute graft rejection (HvG):
- ____ T cells recognize and attack ____ tissue (primarily foreign MHC - ____ rejection)
- occurs within ____ to ____) (T cells need to be exposed to donor Ag and have time to activate
- ____ DCs (via MHC class II mismatch) found in the transplanted tissue can also stimulate recipient immune system (direct rejection)
- primarily ____ rejection, although indirect mechanism can occur as well
- recipient donor direct
- days to weeks
- donor
- direct
hyperacute graft rejection (HvG):
- ____ Abs recognize and attack transplanted Ags (humoral rejection)
- mechanism of ____ rejection (mechaism for other reactions)
- reaction is ____ (minutes to hours) and can even occur during the transplant)
- presents with ____ and ____ of graft vessels
- preformed
- ABO
- immediate
- thrombosis and occlusion
chronic graft rejection (HvG):
- occurs within ____ to ____ following transplantation
- immune mediated:
- caused by fibrosis/thickening of ____ muscle in vessels supplying donated tissue resulting in ____
- ____ play a large role
- primarily ____ rejection
- non-immune mediated:
- ischemia-____ damage
- recurrence of the ____ that caused failure of organ
- the effects of ____ drugs
- transplanted tissue was ____ during transplantation and that damage progreses over time
- months to years
- smooth ischemia
- macrophages
- indirect
- smooth ischemia
- reperfusion
- disease
- nephrootoxic (cyclosporine A)
- damaged
- reperfusion
the immune response against a graft is more or less vigorous than the response seen against a pathogen?
more
(due to higher frequency of T cells that recognize the graft as foreign)
graft vs host rejection:
- ____ immune cells recognize and attack ____ Ag (combination or donor APCs and T cells involved)
- ____ T cells are mostly responsible for tissue damage via Fas/FasL interaction
- this is more likely in tissues that have more resident immune cells such as ____ , ____ , and ____
- most commonly seen with ____ ____ transplants
- presents with ____ , ____ , and ____
- reaction is directed against ____ ___ ____ of the recipient (HLA Ags are usually match)
- donor recipient
- CD8+
- lungs, liver, and intestine
- bone marrow
- diarreha, rash, and jaundice
- minor histocompatibility Ags
primary goals of immunosupression:
- to prevent immune rejection of transplanted tissue by ____ immune response
- to minimize ____ side effects and toxicities
- downregulating
- drugs
steriods (specifically glucocorticoids) generally suppress immune response as part of their function by
blocking NFkB
cylcosporine A and tacrolimuns prevent T cell activation by blocking ____ pathway (production of IL-2 included in this); this toxic to ____ and can lead to kidney transplatnation rejection
NFAT
kidneys
OKT3 (anti-CD3 mAb) blocks CD3, a component of the TCR complex, preventing
T cell activation
CTLA-4-Ig fusion protein binds to ____ blocking CD28 co-stimulation of T cells
CD80/86
Anti-CD-25 mAB blocks ____ signaling inhibiting T cell proliferation and survival
IL-2
corticoids:
- are ____ glucocorticoids
- mechanism of action:
- blocks ____
- inhibition of ____ proliferation
- induction of lymphocyte ____
- used clinically for treatment of transplant ____
- anti-inflammatory
- NFkB
- T-cell
- apoptosis
- NFkB
- rejection
anti-CD3 mAB (OKT 3):
- blocks ____ signaling in T-cells
- used for ____ theapy (therapy administered at the time of organ transplantation) and treatment of acute or steriod-resistant rejection
- CD3 signaling
- induction
cyclosporine A (CsA):
- is a peptide isolated from the ____ species
- inhibits ____ dependent pathway of T-cell activation
- inhibits translocation of ____ into the nucleus which inhibits transcription of ____
- used for immunoprophylaxis as a basic component of most immunosuppressive protocols in all types of ____ transplants
- fungus
- calcium (calmodulin/calcineurin)
- NFAT IL-2
- organ
tacrolimus:
- is a macrolide lactone islated from ____ ____ bacteria
- inhibits the ____ dependent pathway of T-cell activation
- inhibits the translocation of ____ to the nucleus which inhibits transcription of ____
- used in all type of organ transplants for induction and maintenance immunoprophylaxis and treatment of ____ rejection
- streptomyces spp
- calcium (calmodulin/calcineurin)
- NFAT IL-2
- acute
calcineurin inhibitors are associated with ____ toxicity leading to graft loss
kidney
CTLA4-Ig fusion protein:
- binds ____ blocking ____ co-stimulation of T cells
- CD80/86 CD28
