Ch. 10 Immune response to tumor and transplants Flashcards
1
Q
Immune surveillance
A
- adaptive immune system detects and kills cells that are outgrowth of transformed cells
- obviously doesn’t always work though
2
Q
Types of Tumor antigens
A
- body sees these as foreign
- normal proteins just over-expressed or expressed in the wrong place
- mutated proteins
- products of oncogenes or mutated tumor suppressor genes
- products of oncogenic viruses
3
Q
which cell is used to fight tumors?
A
CD8+ CTL’s
4
Q
how do tumors activate CTL’s?
A
- all cells have MHC-I so they can present antigens, BUT no co-stims (or most cells don’t have MHC-II) so they can’t activate the CD8+ cells
- so response to tumor cells requires cross-presentation or cross priming - DC cells eat the tumor cells and present antigens to both CD4 and CD8 T-cells
- cross- priming - one cell types presents antigens from another cell and activates T- lymphocytes for the tumor cell
- then the CTL is activated for that and it can go kill tumor cells that present with MHC-I even without co-stimulation
5
Q
tumor cell evasion strategies
A
- Antigen loss variants - they stop expressing that antigen that is immunogenic
- don’t express MHC-I so can’t be killed by T-cells
- produce natural immune suppressing cytokines - TGF-Beta
6
Q
Tumor Immuno therapy
A
- give anti-tumor effectors
- monoclonal antibodies to stimulate complement or immune
- Antibodies against CD20 on B-cells in b-cell tumor
- VEGF in colon cancer
- stimulae own immune response
- inject IL-2
- Adoptive cellular immuno therapy
- Vaccinations
- vaccinate with own tumor cells
- take out DC cells, and expose them to tumor then put them back in body hoping they present tumor antigens
- plasmids with tumor DNA hope that DC’s pick up
- inject tumor cells that also express IL-2 or co-stimulators to activate immune system to their antigesn
7
Q
Types of transplants
A
- syngeneic - btw two identical animals (or same) - grafts accepted
- Allogeneic - btw different individuals of same species - rejected
- xenogeneic - btw individuals of different species - rejected
8
Q
main rejection in transplants?
A
- MHC molecules
9
Q
Direct alloreognition
A
- Donor MHC on donor APC’s are recognized by host (self) t-cells
- requires that donation included APC cells
- ## probably more important in acute rejection and a CTL response
10
Q
Indirect allorecognition
A
- Self (host) APC cells ingest the graft and then present alloatnigens (foreign) to host T-cells
- usually involved in chronic rejection
- probably invove CD4+ and delayed hypersensitivity
11
Q
Mixed lymphocyte reaction (MLR)
A
- Mix host T-cells with donor leukocytes and measure reaction to determine how compatible they are.
12
Q
Hyperacute graft rejection
A
- mediated by antibodies
- they were already present in host - maybe previous transfusions
- antibodies bind to antigen in donor blood vessel
- occurs in minutes
- antibodies activate clotting and complement system
- leads to thrombosis in graft vessel - main characteristic
- leads to
13
Q
Acute graft rejection
A
- mediated by T-cell attack of graft - mainly CTLs but also T-cells may damage vessels
- antibodies also involved in vessel damage
- ## days to weeks
14
Q
Chronic Graft rejection
A
- Mediator is again T-cells
- slow loss of graft function over months to years either from fibrosis or narrowing of graft vessels
- T-cells react to alloantigens
- T-cells also secrete cytokines that increase fibrosis and intima growth (smooth muscle)
15
Q
Cyclosporin
A
- Blocks Calcineurin - signal transduction pathway for T-cells (important cuz they control graft rejection) that leads to NFAT transcription factor production
- broad immuno suppressor
- allows many organ transplantations
- don’t have to worry much about HLA matching anymore b/c can just suppress immune system with this - when ppl are dying and can’t wait for transplant