Transplant Immunology Flashcards
what is the primary reason for mortality after a transplant ?
immune response to graft leads to rejection
difference b/w orthotopic and heterotopic
orthotopic is transplanting cell/tissue to the same anatomical site
heterotopic is transplanting to a different site
what is the difference b/w and autologous graft, synergeneic graft, and allogenic graft ?
autologous is graft to and from same individual
synergeneic is a graft from genetically identical ind. (twin)
allogenic is from genetically different individual
what complications in transplants are the result of what type of graft ?
allogenic graft
A MHC (a) graft will _______ by an MHC (a) host, whereas a MHC (a) graft will _________ by an MHC (b) host
- Not be rejected
- will be rejected
What is the difference b/w CD8 and CD4 T cells ?
CD8 - cytotoxic t cells, MHC I restricted
CD4 - helper t cells, MHC II restricted
what 3 things do T cells NEED to become effector T cells
- recognize Ag
- MHC activation
- Costimulatory molecule activation
T cells can recognize an alloantigen 2 ways, what are they and how do they differ ?
1 - Direct - T cell receptor engages naked alloantigen
2 - Indirect - APC engulfs an alloantigen, processes it then presents it to T cells
Indirect alloantigen recognition is an example of ?
Cross presentation or cross priming
once a T cell recognizes an alloantigen either directly or indirectly, what occurs ?
T cell becomes activated
What are the 3 ways an allogeneic T cell can lead to graft rejection
1 - hyperacute rejection (w/in minutes to hours)
2 - acute rejection (about 1-2 weeks)
3 - chronic rejection (6 months)
what happens during hyperacute rejection ?
Pre-existing alloreactive Ab are present in recipient
-leads to activation of complement cascade = inflammation = thrombosis formation
what occurs during acute rejection ?
CD8 and CD4 (T cells) become activated leading to
- Cytotoxic t cells lyse target
- helper t cells activate B cells to produce Ab (and same thing happens as hyperacute rejection)
What happens in chronic graft rejection
survive for about 6 months, but eventually blood vessels thicken from increased growth factor production = occlusion of vessels = graft rejecetion
In order from best to least, which types of grafts are least likely to cause rejection
1 - autologous
2 - synergeneic
3 - allogenic
Besides prevention, what is another strategy that can be used to reduce the probablitlity of graft rejection
immunosupression via drugs
There are 4 immunosupression drugs we need to know that prevent graft rejection, what are they ?
Rapamycin
Anti-CD3 monoclonal Ab
Anti-IL-2 receptor Ab
CTLA-4 Ig
How does immunosupression drug rapamycin work
inhibits IL-2 signaling = No T cell proliferation
how does immunosupression drug Anti CD3 monoclonal Ab work ?
depletes T cells by binding to CD3 = phagocytosis
how does immunosupression drug Anti IL-2 receptor Ab work
inhibits IL-2 binding = No T cell proliferation
how does immunosupression drug CTLA-4 Ig work ?
CTLA blocks co-stimulatory activation = no T cell activation (CTLA-4 doesnt allow CD28 to bind to B7)
What are the 2 uses/ reasons for a bone marrow transplant
1 - treatment of hematological disesase
2 - restore an immune system destroyed by chemo/radiation
what is the name of the disease, when the graft attacks the host in a bone marrow transplant ?
graft versus host disease
-hapens b/c trying to introduce a completely new immune system
cells of what part of the immune system are Ag specific
adaptive immune system
Some cancers downregulate MHC I, if this occurs what cells would become activated
NK cells, respond when no MHC is present
Activated NK cells produce what important cytokine related to cancer immunology, what is the main function of this cytokine
IFN-gamma
-activates macrophages
What are the 2 types of macrophages that affect cancer development
M1 macs - supress tumors
M2 macs - enhance tumors
What distinguishes the function of what type of macrophage will be produced (M1 or M2) ?
cytokine microenvironment
What cytokines lead to M1 macrophages
IFN-gamma
Good for fighting cancer
what cytokines lead to M2 macrophages
IL-1, IL-4, IL-13
BAD for fighting off cancer
Why are M2 macrophages bad for fighting off tumors ?
B/C they are healing/regenerative macs
-produce growth factors which inevitably enhance tumors
what is the principal mechanism in tumor immunity, and how do these cells work ?
CD8 cytotoxic T cells
-once bind to Ag and become activated = they degranulate releasing perforin and granzyme B
-
what is the diff. in function of perforin vs. granzyme B
perforin forms pore for granzme to enter target then granzyme induces apoptosis of target cell
What are CD4 T cells potential roles in fighting off cancer ?
1 - Help activate CD8 T cells
2 - Prod. Th1 cytokines which lead to M1 macrophages (tumor supressors)
What are B cells/Ab role in fighting off cancer ?
Some Ab can bind cancer cells = activates NK cells = degranulation = apoptosis
Is there any way that an overexpression of the immune response can actually cause cancer ?
Yes, if to much inflammation you increase risk of cancer
how does cancer increase the risk of cancer development
1 - Increase inflammation —-> increased cytokines
——> hyperplasia (increase cell proliferation) —–> dysplasia (abnormal cell dev.)
2 - Increase inflammation —-> increase free radicals damaging nucleic acids
