Lecture 7 - Transplant Immunology (Bailey) Flashcards
Orthotopic
Transplanting a cell or tissue to the SAME anatomical site
Heterotopic
Transplanting a cell or tissue to a DIFFERENT anatomical site
Autologous graft
graft transplanted from one individual to the same individual
Syngeneic graft
transplanted between 2 genetically identical (or very similar) people
allogeneic graft
b/t two genetically different people
What is DIRECT alloantigen recognition?
When T-cells recognize allogeneic MHC (or allogenic MHC + self peptide)
What is an allogeneic MHC?
A non-self MHC
What is INDIRECT alloantigen recognition?
When an APC engulfs an allogenic MHC (or entire allogeneic cell), processes the MHC like a foreign protein, and presents the allogeneic MHC in the context of self MHC.
What are the 3 different types of graft rejection that can occur?
- Hyperacute rejection
- Acute rejection
- Chronic rejection
What is HYPERACUTE graft rejection?
- happens in a couple of days
- graft dies
- pre-existing alloreactive antibodies bound to the graft
What is ACUTE rejection?
- happens in a week
- cytotoxic T cells develop against graft
- B cells produce alloreactive antibodies
What is CHRONIC graft rejection?
- grafts survive for 6+ months
- alloreactive T cells produce cytokines
- macrophages activated
- inflammation
- growth factor production
- thickening of vascular smooth muscle (intimal smooth muscle)
What do hyperacute, acute, and chronic graft rejection have in common?
vascular damage leads to organ failure
Why is IL-2 important?
T-cell clonal expansion
What happens if you block CD3?
blocks activation of the T cell receptor (TCR)
What happens if you block B7?
blocks the costimulation needed for activation of T cells
What is graft versus host disease?
Graft begins to fight against the host cells
What happens when tumors down-regulate MHC I?
NK cell activation & tumor protection
What does activated NK cells produce?
IFN-(gamma)
What does IFN-(gamma) do?
lead to activation of macrophages
Macrophages are sensitive to…
cytokin microenvironment
If IFN-(gamma) is present, a macrophage will become…
an M1 Macrophage
classical activation
If any TH2-assocated cytokines (such as IL-4, IL-13, or IL-10) are present, a macrophage will become…
an M2 Macrophage
alternative activation
What do M1 macrophages do?
engulf & kill tumor cells
What do M2 macrophages do?
promote tumors
involved in wound healing and tissue remodeling
Principal cells involved in anti-tumor immunity
cytotoxic T lymphocytes (CTL)
What cells can induce apoptosis in cancer cells?
T cells
What does a T cell release from its granules to induce apoptosis in a target cell?
perforin
granzyme
What is CROSS-PRIMING?
APC engulfs tumor cell, processes antigen, and presents it w/ MHC I to CTL
What do CD4+ T cells use to fight tumors?
their cytokines help activate CTL and macrophages (which can kill tumor cells)
What do B cells do to fight tumors?
Antibody-mediated NK cell cytotoxicity
they bind to tumor cells so NK cells can recognize them and become activated. Then NK cells kill tumor cell.
Is the immune system always protective against cancer?
No
How does chronic inflammation lead to cancer?
cytokines lead to increased cell proliferation (hyperplasia), causing abnormal cell morphology, and the development of free radicals that can damage DNA
