Transplant Immuno Flashcards
T/F. The primary reason for morbidity and mortality involves the immune response.
True.
What reasons lead to morbidity and mortality?
immune response to the graft = rejection
infection due to immunosuppression
graft attacks the host (graft vs host disease/bone marrow transplant)
Define graft.
Cells or tissues that is being transplanted
Orthotopic means transplanting a cell or tissue to the ___ (same/different) anatomical site. Heterotopic means transplanting cells or tissue to the ___ (same/different) site.
same; different
What is the process of the transfer of circulating cells from one individual to another?
transfusion
What type of graft is transplanted from one individual to the same individual?
Autologous graft
A ___ graft is transplanted between two genetically identical (or very similar) individuals.
syngeneic graft
Define allogeneic graft.
graft between two genetically different individuals
Explain the Sir Peter Medawar experiment?
skin graft from one mouse to another. 7-10 days later inflammation at graft site lead to rejection.
What is the second set rejection?
Mice sensitized with rejected skin graft prior to new graft showed rejection after 3 days. This showed immunological memory
What happened after mice B were given lymphocytes from another mouse B that has already rejected a graft from mouse A?
mice B will reject graft A after 3 days. This showed that lymphocytes mediate rejection and memory
How are T cells acitvated?
T cells recognize antigen that is present to them in the context of MHC.
CD4+ T cells require antigen + MHC ___ to be activated. CD8+ T cells require antigen + MHC ___ to be activated. What else is also needed?
II; I; co-stimulation
How does the body prevent the development of autoreactive T cells? When does this work?
Immature thymocytes with low avidity binding to self peptide and MHC allow T cells to mature into antigen specific cells. However, high avidity binding to self peptide and MHC leads to apoptosis.
This only works for self peptide and self MHC.
What percentage of T cells can recognize self peptide and non-self MHC?
2%
Explain allorecognition.
The self MHC-restricted T cell recognizes the allogeneic MHC molecule whose structure resembles a self MHC-foreign peptide complex.
T/F. Most of the peptides are likely to be self peptides that are the same in the donor and the recipient, but the donor peptides are displayed by allogeneic MHC molecules and therefore appear different from self peptide-self MHC complexes.
True.
What is it called when T cells recognize allogeneic MHC (or allogeneic MHC + self peptide) directly?
Direct alloantigen recognition
How does indirect alloantigen recognition occur?
- recipient APC can engulf allogeneic MHC
2. recipient APC can process the MHC
How does indirect alloantigen recognition or cross presentation or cross priming occur?
- recipient APC can engulf allogeneic MHC
- recipient APC can process the MHC molecule and express it with self MHC.
- Alloreactive T cell recognizes self MHC presenting peptide from allogeneic MHC
How do allogeneic T cells lead to graft rejection?
hyperacute, acute and chronic rejection
Which type of rejection is characterized by thrombosis formation and eventually occlusion of the graft blood vessel that beings within minutes to hours?
hyperacute rejection
In hyperacute rejection, ___-___ alloreactive antibodies lead to activation of the ___ cascade. This leads to inflammation withing the blood vessel causing ___ ___, recruitment of leukocytes and thrombosis formation.
pre-existing; complement; reactive endothelial
What becomes activated in acute rejection?
Alloreactive T cells become activated (after about a week) and produce cytokines.
In acute rejection, cytokines produce activated CD___+ T cells, B cells to produce antibodies, cause damage to blood endothelial cells leading to thrombosis and ___ cells are also affected.
8; parenchymal
What happens in chronic graft rejection?
grafts survive for 6 months or more but eventually develop blood vessel thickening due to intimal smooth muscle formation.
In chronic graft rejection, alloreactive ___ cells produce cytokines that activate parenchymal ___. The inflammation can induce ___ factor production and this induces intimal thickening which cuts off the blood supply.
T; macrophages; growth
transplant autologous > ___?
syngeneic
transplant syngeneic > ___?
allogeneic
___ blocks lymphocyte proliferation by inhibiting IL-2 signaling.
Rapamycin
Anti-___monoclonal antibody depletes T cells by binding to CD3 and promoting phagocytosis or complement mediated lysis. This is used to treat ___ rejection.
CD3; acute
Anti-IL-2 receptor (CD25) antibody inhibits T cell proliferation by blocking ___ binding and depletes activated T cells that express CD25.
IL-2
CTLA-4 inhibits T cell activation by blocking ___ constimulator binding to T cell CD28.
B7
What disease can result from bone marrow transplantation?
graft-versus host disease
What is the evidence that the immune system is involved?
if you transplant tumor cells into a mouse the tumor grows. Then add CD8 T cells and the tumor is eradicated
What is the antigen that antigen specific T cells are specific for?
- mutated self protein
- production of oncogenes or mutated tumor suppressor genes
- abnormally expressed self protein
- oncogenic virus
Why is it important that some cancers down-regulate the expression of MHC I?
because this activates NK cells
What do NK cells produce and why is it important?
IFN-gamma activates macrophages which can engulf tumor cells
What does the function of tumor macrophages depend upon?
the cytokine environment
INF-gamma leads to ___ (M1/M2) macrophage activation.
M1
___, ___, and ___ lead to M2 macrophage activation.
M2
T/F. M1 macrophages can suppress tumors/kill tumor cells. M2 macrophages can enhance tumors.
True.
The principal mechanism of tumor immunity is killing of tumor cells by ___ T lymphoctes. They are most effective against ___ virus-induced tumors.
CD8+; DNA
Antigen specific T cells are activated in ___ ___ and migrate into tissue to find the antigen that caused activation. There ___ and MHC I + peptide as well as costimulation leads to ___. This releases ___ that induces apoptosis and ___ that helps granzyme enter the cell.
lymph nodes; TCR; degranulaiton; granzyme; perforin
In ___-___, APC engulf a tumor cell (that contains tumor antigen) then it process the tumor antigen and expresses the antigen along with MHC I for CD8+ T cells to recognize.
cross-priming
What are the two potentially important factors for CD4+ T cells?
- help activate CD8 + T cells
2. produce Th1 cytokines to lead to classical M1 macrophage activation.
___ cells produce antibodies that are recognized by NK cells and lead to antibody-dependent cellular cytotoxicity.
B
How can the immune systems activity lead to the development of cancer?
- cytokines can lead to hyperplasia (increased cell proliferation)
- Hyperplasia can lead to dysplasia (abnormal cell development)
- Free radicals damage nucleic acids.
