Transplant Immunology Flashcards
________ to a graft can lead to rejection.
Immune response
What is a graft?
cells or tissues that are being transplanted
What is an orthotopic transplant?
Transplanting of a cell or tissue to the same anatomical site (i.e. treatment of recession)
A ________ transplant involves cells/tissues that are transplanted in a different anatomical site.
Heterotopic
What is a transfusion?
Transfer of circulating cells from one individual to another
What is an autologous graft?
Graft transplanted from one individual to the same individual
What is a syngeneic graft?
Graft transplanted between two genetically identical (or very similar) individuals
What is an allogeneic graft?
Graft between two genetically different individuals (i.e. donor lists)
If the ______ molecule does not match, T cells will recognize the graft as foreign.
MHC
In order for T cells to be activated, they must recognize antigen presented in the context of _____ and with the presence of ________.
MHC
Costimulatory molecules
CD4+ T Cells require antigen and MHC class____.
II
CD8+T Cells require antigen and MHC class_____.
I
CD8+T Cells require antigen and MHC class_____.
I
Some Alloreactive T cells will recognize Allogeneic MHC + Self Peptide through ______ recognition.
Direct
What is “direct alloantigen recognition”?
When T cells recognize allogeneic MHC (or allogeneic MHC + self peptide) directly
the antigen presenting cell in the graft expresses its own MHC. The self T cell recognizes this unprocessed allogeneic MHC molecule through its graft APC directly
What is “indirect alloantigen recognition”?
The allogeneic APC (graft cell) will present its MHC and the host’s APC will take the MHC from the allogeneic APC and engulf it. The host APC will then process the MHC and express the allogeneic peptide within its own MHC. The alloreactive (host) t cells recognize self MHC because of the allogeneic peptide that it presents.
What are the three types of graft rejections that result from allogeneic T cells?
- Hyperacute
- Acute
- Chronic
Which type of rejection occurs within minutes or hours and is characterized by thrombosis formation and eventual occlusion of the graft blood vessel?
Hyperacute rejection
Which type of rejection occurs within minutes or hours and is characterized by inflammation, thrombosis formation and eventual occlusion of the graft blood vessel?
Hyperacute rejection
_______ rejection is now less common due to the pre-screening for alloreactive antibodies.
Hyperacute
Which type of rejection occurs when alloreactive T cells become activated and produce cytokines? How long does this usually take?
Acute Rejection
about a week
During acute rejection, cytokines activate ______ and activate _______.
CD8+ T cells = lyse host
B cells = produce antibodies
Which type of graft rejection is characterized by intimal smooth muscle formation and blood vessel thickening?
Chronic Graft Rejection
In what time frame does Chronic Graft Rejection typically occur?
6 months or more
In chronic rejection, inflammation induces production of _____ _______ that induce intimal thickening.
Growth Factors
In chronic rejection, inflammation induces production of _____ _______ that induce intimal thickening.
Growth Factors
In what two ways can graft rejection be prevented?
- Prevention by using compatible grafts:
- autologous(self) instead of syngeneic(twin)
- syngeneic(twin) instead of allogeneic(no relation)
- Immunosuppression
What is the mechanism of action for the drug, Rapamycin?
Blocks lymphocyte proliferation by inhibiting IL-2 signalling
Why is the drug “Anti-CD3 monoclonal antibody” used?
It depletes T cells by binding to CD3 and promoting phagocytosis or complement-mediated lysis
What is “Anti-IL-2 receptor (CD25) Antibody”?
A drug used to inhibit T cell proliferation by blocking IL-2 binding and depleting activated T cells that express CD25
What is “CTLA-4-Ig”?
Drug that inhibits T cell activation by blocking B7 costimulator binding to T cell CD28
What is “CTLA-4-Ig”?
Drug that inhibits T cell activation by blocking B7 costimulator binding to T cell CD28
_______ transplants are used for treatment of hematological diseases and to restore an immune system destroyed by radiation and chemotherapy.
Bone Marrow
What is the leading cause of morbidity and mortality in children and adults?
Cancer
What evidence suggests that the immune system is involved in cancer?
As tumors increase in age, macrophages and other immune cells also increase in numbers. Also, the transfer of T cells into a tumor recipient mouse showed eradication of the tumor.
In a normal situation, the ________ receptor on the NK cell recognizes MHC Class I and there is no cell killing.
Inhibitory
In a virally infected cell, the expression of ______ is inhibited and the ‘inhibitory receptor on the NK cell’ is not engaged, resulting in NK cell activity and killing of the cell.
MHC Class I
What results from the down-regulation of MHC Class I by cancer cells?
MHC Class I is not produced NK cells are not able to bind their inhibitory receptor NK cells remain ON Additionally, NK cells produce IFN-gamma IFN-gamma activates Macrophages
The function of tumor macrophages will depend on the _____ _______.
cytokine microenvironment
What are the types of macrophages?
M1 Macrophages = classical (activated by IFN-gamma)
M2 Macrophages = Alternative (activated by IL-4, IL-13, IL-1)
What is the biological function of M1 Macrophages?
Suppress or Kill Tumor Cells
What is the biological function of M2 Macrophages?
Enhance Tumors by promoting growth
also play a part in angiogenesis and tissue repair
What is the principle mechanism of tumor immunity?
CD8+ Cytotoxic T Lymphocytes
After the TCR on the T cell binds MHC1 + Peptide, costimulation results in degranulation: release of _____ and _______.
Perforin
Granzyme
Perforin helps ______ to enter the target cell where it will then induce apoptosis.
Granzyme
What is “cross priming”?
- An APC engulfs a tumor cell and its tumor antigen
- CD4+ T cells secrete cytokines that stimulate CTL differentiation
- the APC processes the antigen and expresses the tumor antigen on its MHC 1
- CD8 cells recognize the MHC1 and the tumor antigen
What is the importance of CD4+ T cells in tumor eradication?
- Help to activate CD8+ T cells via cytokine production
2. Produce Th1 cells that lead to M1 Macrophages (IFN-gamma –> tumor suppression)
What is the principle way in which B cells assist in tumor suppression?
Antibodies activate NK cells and lead to “antibody-dependent cellular cytotoxicity”….apoptosis
How does immune system activity lead to the development of cancer?
INFLAMMATION
- cytokines lead to hyperplasia (inc. cell proliferation)
- hyperplasia leads to dysplasia (abnormal cell develp)
- Free radicals damage nucleic acids
