Transplant Immunology - Bailey Flashcards
In regards to transplants, what is the primary reason for morbidity and mortality?
Immune response
________ means transplanting cell or tissue to the same anatomical site.
Orthotopic
_______ means transplanting cell or tissue to a different anatomical site.
Heterotopic
______ means transfer of circulating cells.
transfusion
_____ is graft transplanted from one individual to the same individual.
Autologous graft
______ is graft transplanted between two genetically identical (or very similar) individuals.
Syngeneic graft
______ is graft transplanted between two genetically identical (or very similar) individuals.
Syngeneic graft (Twins or siblings)
_______ is graft between two genetically diverse individuals.
Allogeneic graft
Rejection of Graft is due to ________ mismatch.
MHC mismatch
How are T cells activated?
T cells recognize antigen that is presented to them in the context of MHC.
______ require antigen + MHC2 to be activated.
CD4+
______ require antigen + MHC1 to be activated.
CD8+
If a T cell has high avidity binding to self peptide and MHC, what happens?
Apoptosis of the T cell.
* this is how the body prevents the full development of auto reactive T cells.
Can Alloreactive T cells recognize Allogeneic MHC + Self Peptide?
Some can.
______ T cells will kill the target.
CD8+
____ T cells will produce cytokines to help propagate the immune response.
CD4+
What is direct Alloantigen recognition?
When T cells recognize allogeneic MHC directly
What is indirect Alloantigen recognition?
When APC is used to present antigen to T cell.
What are the 3 ways Allogeneic T cells lead to Graft Rejection?
- Hyperacute rejection
- Acute Rejection
- Chronic Rejection
What is Hyper acute Rejection?
Characterized by thrombosis (Blood clot) formation that begins within minutes to hours and graft dies.
*Antibodies lead to activation of complement cascade.
What is Acute Reaction?
Alloreactive T cells become activated (after about a week) produce cytokines to:
- Activate CD8+ T cells
- Activate B cells to produce antibodies
- Inflammation damages blood endothelial cells.
- Inflammation leads to thrombosis (clot) formation.
- Parenchymal cells can also be affected by CD8+ cells.
What is Chronic Rejection?
Grafts that survive for 6 months or more can eventually develop blood vessel thickening due to intimal smooth muscle formation.
*Growth factors induce intimal thickening
What ultimately leads to the death of a graft?
Loss of vascularization
What is the mechanism of action for Rapamycin?
Blocks lymphocyte proliferation by inhibiting IL-2 signaling.
What is the mechanism of action for Anti-CD3 monoclonal antibody?
depletes T cells by binding to CD3 and promoting phagocytosis or complement mediated lysis.
What is the Mechanism of action for Anti-IL-2 receptor?
Inhibits T cell proliferation by blocking IL-2 binding and depletes activated T cells that express CD25
What is the Mechanism of action for CTLA-4lg?
Inhibits T cell activation by blocking B7 costimulator binding to T cell.
_________ Is a treatment for hematological disease.
Bone marrow transplant.
What is one of the additional risks to bone marrow transplant?
Graft can attack the host. (Graft Versus Host disease)
_____ can produce IFN-gamma.
Natural killer cells
Some cancers can down regulate the expression of ________. Why is this important?
MHC1
*Important because NK cells become activated in the absence of MHC1 and will then kill infected cells.
_____ can produce IFN-gamma (cytokine). Why is this important?
Natural killer cells
* Important b/c helps to activate macrophages that can engulf tumor cells.
Function of tumor macrophages depends upon ___________.
The Microenvironment
______ macrophages can suppress tumors/kill tumor cells.
M1
______ macrophages can enhance tumors.
M2
____ can induce apoptosis in cancer cells.
T cells
Antigen specific T cells are activated where?
In the lymph nodes
______ induces apoptosis in target cell.
Granzyme
_____ helps granzyme enter the target cell.
Perforin
______ may be necessary for CTL activation.
Cross-priming
What is the 2 important roles of Cd4+ cells?
- Help to activate CD8+ cells
2. Produce Th1 cytokines to lead classical (M1) macrophage activation
Can immune system activity lead to the development of cancer? Explain.
Yes,
- Cytokines can lead to hyperplasia (Increased cell proliferation)
- Hyperplaisia can lead to dysplaisa (abnormal cell development)
- Free radicals damage nucleic acids.
* People with chronic inflammation diseases are at increased risk of developing cancer.
