EXAM 4 Organ Transplantation and Rejection Flashcards
what are the 3 fundamental problems with organ transplantations?
- transplant must perform its functions
- transplant and recipient health must be maintained
- recipient immune system must not reject the transplant
what are the two transplant types?
- solid organ
- blood
- bone marrow/hematoepoitic stem cell
- transfusion
transplantations are a solution for ___, but they are not a permanent ___
- organ failure
- solution
transplant type: donor and recipient are the same individual
autologous
transplant type: donor and recipient are genetically identical
syngeneic
transplant type: donor and recipient are genetically different but of the same species
allogeneic
most common
transplant type: donor and recipient are of different species
xenogeneic
___ limits allogeneic transplant survival
organ rejection
what are the 3 types of organ rejection?
- hyperacute
- acute
- chronic
hyperacute organ rejection is a type ___ hypersensitivity, occurs in ___ to ___ (timing), and involves blood type ___
- II
- minutes to hours
- alloantibodies
acute organ rejection is a type ___ hypersensitivity, involves ___ and ___ cells, and involves ___ mismatches
- IV
- CD4 and CD8 T cells
- HLA
chronic organ rejection is a type ___ hypersensitivity and involves chronic transplant ___
- III
- inflammation
most transplants are ___
allogeneic
___ and ___ improve transplant organ survival rates
donor matching and immunosuppressants
___ between donors and recipients are the biggest predictors of transplant success.
histocompatibility
- blood type
- major HLA genes
- minor HLA genes
as donor and recipient histocompatibility mismatches increase, transplant success ___
decreases
the number of mismatches increases with time
___ are the most common transplantations
blood transfusions
erythrocytes do not express MHC I or II. how is this helpful for histocompatibility?
no HLA matching (and therefore, no mismatching)
for blood transfusions, what is matched between donor and recipient?
- blood type
- rhesus D antigens
are leukocyte transfusions common?
no, they are rarely performed
what is removed from blood fractions before blood transfusions?
leukocytes
how often can blood be donated?
- whole blood - every 56 days
- plasma - every 28 days
- platelets - every 15 days
what are the blood fractions that are commonly transfused?
- erythrocytes
- plasma - water, protein (albumin and Ig), organic compounds, inorganic salts
- platelets - clotting factors
___ antigens dictate blood type and transfusion success
ABO
gut bacteria express antigens similar to ___ and ___
A and B
antibodies created against antigens are not expressed on ___
erythrocytes
what antigens will a type O recipient reject?
A, B, and AB
which antigen recipient can accept all donations?
AB
(can accept O, A, B, or AB)
what type of hypersensitivity reaction occurs when blood types do not match?
II
___ is the universal blood donor
O RhD-
___ is the universal blood recipient
AB RhD+
can transplants come from cadavers?
yes
which transplants can be done from live, healthy donors?
kidney and liver (parts of the liver - not the whole thing, obv)
in solid organ transplants, the transplant and recipient are in a state of ___
inflammation
what rejection types are graft rejections?
hyperacute, acute, and chronic
how does degree of match vary with the cornea, liver, and kidney?
- cornea - no matching or immunosuppression
- liver - only blood type match
- kidney - HLA and blood type match
how can HLA and blood type matching be determined using mixed lymphocyte reactions?
- mixed lymphocyte reaction - measure T cell proliferation and T cell cytotoxicity to determine if it is a match
HLA and blood type matching can be determined in what two ways?
- genetically
- mixed lymphocyte reaction
why do pre-existing blood type antibodies cause hyperacute rejection
- ABO and rhesus incompatibility
- pre-existing anti-HLA class I antibodies
- type II hypersensitivity
- occurs within minutes
- irreversible organ loss
- prevented by compatibility assessment
direct and indirect ___ leads to graft rejection
allorecognition
which pathway of allorecognition that leads to graft rejection describes acute rejection?
- direct pathway
- CD4/CD8 mediated
- type IV
which pathway of allorecognition that leads to graft rejection describes chronic rejection?
- indirect pathway
- antibody mediated
- type III
direct and indirect allorecognition is carried out by ___ antigens
HLA class I and II, and also minor HLA antigens
how does direct allorecognition cause acute rejection?
- transplant dendritic cells activate recipient T cells
- direct MHC interaciton, independent of peptide
- days to weeks
- type IV hypersensitivity
allogeneic MHC activates ___ cells directly
T
- direct recognition of foreign MHC
- MHC is structurally different
- peptide largely irrelevant
- activated transplant dendritic cells express B7
- CD8 and Cd4 Th1 response
antibodies against transplant MHC I cause ___ rejection. what type of hypersensitivity? what else happens?
- chronic
- type III hypersensitivity
- chronic inflammation
- progressive loss of blood and nutrient supply
- years
bone marrow/hematopoietic stem cells transplantations result in a destruction of the ___
- endogenous blood system
- replacement with transplanted stem cells
what are some reasons for bone marrow/hematopoietic stem cell transplantations?
- blood diseases
- myeloid and lymphoid cancers
bone marrow/hematopoietic stem cell transplantations can be ___ or ___ transplant types
autogeneic and allogeneic
what are two possible negative outcomes of bone marrow/hematopoietic stem cell transplantations?
rejection and graft vs host disease (GVHD)
bone marrow/hematopoietic stem cell transplant donor and recipient must share some ___ and ___ haplotypes
HLA class I and II
if a donor doesn’t have the same HLA haplotypes, those new blood cells being produced will not respond to infection because the MHC will not interact with the T cells, so there will be no adaptive immune response. There needs to be some degree of similarity between donor and recipient.
what is describe as transplant adaptive immune cells that target and kill recipient tissues?
graft vs host disease
what can happen in GVHD caused by hematopoietic transplants?
- GI, liver, and skin problems are most pronounced
- can be beneficial in fighting cancers
donor T cells cause ___ GVHD
acute
alloreactive ___ cells can kill recipient leukemia
- NK cells
___ suppress NF-kappa B transcriptional activity
corticosteroids
describe corticosteroids
- immunosuppressants
- prednisolone is the active compound
- increase IκBα production to block NF-κB function
- broad activity
- non-specific
- many adverse side-effects
what are the signals needed for immunosuppression to target T cell activation?
- signal 1 - activation
- signal 2 - survival
- signal 3 - proliferation
which two drugs inhibit T cell activation?
cyclosporin and tacrolimus
___ and ___ prevent T cell survival and proliferation
belatacept and anti-CD25
