Transplantation Lecture Flashcards
list the 3 problems with organ transplantation
- transplant must be able to maintain normal function
- health of recipient and transplant must be maintained during surgery
- the recipient’s immune system must be prevented from responding to the transplant causing rejection
What is autologous transplantation
when stem cells are from the patients own body
What is allogeneic transplantation
When stem cells are taken from donor to recipient
In order for allogenic transplantation to be successful both donor and recipient must be
histocompatible
What does it mean to be histocompatible
the donor and recipient have compatible tissue types and can coexist without provoking a strong immune response
Serum of blood group O people have which class of antibodies against A and B antigens
IgG
ABO antigens are present on A. Kidneys B. Erythrocytes C. Endothelial Cells of blood vessels D. All of the above
D: all of the above
Describe how hyperacute rejection occurs
Incompatible tissue between donor and recipient results recipient antibodies that bind the blood vessels of the graft(donor antigen), complement if fixated throughout the vasculature
What procedures can avoid hyperacute rejection
- typing
- cross matching for ABO
Antibodies against donor blood group antigens bind vascular endothelium of graft initiating an inflammatory response that occludes blood vessels describes which process?
A. Acute Rejection
B. Hyperacute Rejection
C. Histocompatibility
D. Graft Versus Host Disease
B
Hyperacute rejection is
A. Slow
B. Rapid
B
Blood antigen Incompatibility can cause type __ hypersensitivity
II
what type of rejection is the most devastating rejection of organs
hyperacute
Where and when is HLA I expressed
vascular endothelium, constitutively
Where and when is HLA II expressed
vascular endothelium when there is infection, inflammation and trauma
What are alloantigens
self antigen that vary between members of the same species
Alloreactions are
immune responses induced by alloantigens
What is immunogenetics
the study of genetics of alloantigens and the impact on the immune system
What are the two types of alloreactions
- transplant rejection
2. graft versus host disease
What is an autograft
when tissue is transplanted from donor to recipient
When tissue or organ is grafted and transferred from one person to another who is genetically identical that is called.
A. Allograft
B. Xenograft
C. Isograft
D. Autograft
C
When donor and recipient are of different species, this type of transplant is called
A. Allograft
B. Xenograft
C. Isograft
D. Autograft
B
What are the effects of hemolytic reactions
- fever
- chills
- shock
- renal failure
- death
HLA class I antibodies react with
B cells and T cells
HLA class II antibodies react with ____ cells
B
What are the 3 general steps of hematopoietic stem cells transplantatoin
- irradiation and chemotherapy to clear recipient stem cells making space for donor cells
- hematopoietic cell infusion
- patient is healthy
What cells are responding in graft vs host disease?
T cells
Describe what generally happens in Graft Versus Host Disease
The donor T cells in the graft attack the recipients healthy tissue
What is an autograft?
when a patients tissue is transplanted from one area to another
What is an isograft?
an syngeneic transplant: a transplant between two genetically identical individuals
Acute rejection is a type __ hypersensitivity
4
____ T cells respond to HLA class _
CD8, 1
_____ T cells respond to HLA class ___
CD4, 2
Inflamed state of transplanted organ induces
A. Recipient T cells to migrate to secondary lymphoid tissue
B. Donor derived T cells to migrate to secondary lymphoid tissue
C. Donor Derived Dendritic cells to migrate to secondary lymphoid tissue
D. Recipient dendritic cells to migrate to secondary lymphoid tissue
C
Donor derived dendritic cells present
A. Donor derived antigen to recipient T cells
B. Donor Derived antigen to recipient macrophages
C. Recipient antigen to other donor dendritic cells
D. Recipient antigen to donor B cells
A
*slide 16
Describe what happens in the direct pathway of allorecognition
Recipient T cells are stimulated by a direct interaction between their receptors with allogenic HLA molecules expressed by DONOR cells
In the direct path of allorecognition, _____ T cells are stimulated by _____ dendritic cells
recipient, donor
Describe the direct pathway of allorecognition
Donor dendritic cells from transplant activate recipient T cells that go back to the transplant and damage the epithelial cells of the transplant
What is used to treat chronic rejection
Anti B cell antibody (rituximab)
____ antibodies against HLA I form immune complexes that deposit in blood vessels of transplanted organ occurs in _____ rejection
IgG, Chronic
What is the function of Anti CD52
it binds leukocytes and activates complement on the cell to destroy it in preparation for organ transplant to prevent it from initiating an immune response
Calcium influx during T cell activation results in the activation of
A. cyclosporin
B. NFAT
C. Tacrolimus
D. Calcineurin
D
What is calcineurin
a phosphatase that activates NFAT
What is the role of NFAT in T cell activation
it binds AP-1 to form an active transcription factor
How does cyclosporin act?
it binds calcineurin preventing the binding of NFAT to AP-1 thus inhibiting IL-2 transcription
Belatacept binds_____ and prevents engagement of CD28
B7
Antibodies that bind to pig endothelial cells
Xenoantibodies
What is the function of belatacept?
A drug that binds B7 and prevents B7:CD28 engagement thus preventing the co-stimulatory signal
T/F: Anti CD25 engages the low affinity IL-2 receptor ON naive alloreactive T cells
False, binds the HIGH affinity IL-2 receptor on ACTIVATED T cells
What is the function of Anti CD25
to bind high affinity IL-2 receptor on active T cells and prevent the generation of signal 3 of activation of cyclin D
Where are the targets for immunosuppressive drugs
- MHC and TCR binding
- B7 and CD28 costimulatory signal
- Anti-CD52 to initiate complement on T cell
- Calcineurin via Cyclosporin to prevent NFAT activation and blocking IL-2 Transcription
- Anti-CD25 to block the IL-2 receptor
What is myeloblative therapy?
a procedure that cripples the patients immune system and creates space for donor cells
The allogenic difference in minor histocompatibility H-Y antigens is due to
the bound peptide NOT the MHC molecule
What gives rise to minor histocompatibility antigen differences between donor and recipient?
polymorphic self proteins that differ sin amino acid sequence between people
