Transplantation Flashcards
What is transplantation
When one body part damaged it can be replaced with one taken from elsewhere- also called graft
Donor who gives, recipient/host who receives graft
Types of transplants
Depends on relationship between donor and recipient
Autograft: Within same organism, one body part to another
Isograft: Between genetically identical individuals (indentical twins)
Allograft: Most common way, Between organisms of same species w diff genotypes
Xenograft: Between diff species , rapidly rejected (except cell free porcine heart valves)
Allografts are generally rejected, why is it rejected faster when a second allograft is made from the same donor
This is called second-set rejection and is an example of secondary immune response.
How are allografts accepted and how are they rejected
Experiment using mice:
Allograft accepted if any parent gives graft to offspring- this is bc offspring immune system knows the antigens from each parent
Allograft rejected if offspring gives graft to either parent- bc the hybrid carries anigens from the other parent
ALLOGRAFT FATE IS NOT JUST DETERMINED BY RELATIONSHIP BUT THE PRESCENCE OF NEW ANTIGENS IN THE GRAFT
Mechanisms of rejection
HYPER ACUTE: Minutes to hours- Complement system
ACCELERATED: Days- Reactivation of sensitized T cells
ACUTE: days to weeks- primary activation of T cells
CHRONIC: monthsto years- slow loss of graft function, antobodies slow cell mediated response,
How does T cell recognize an antigen again
Their TCR binds MHC together with an antigenic peptide
which is endogenous (for MHC-I) or phagocytosed (for
MHC-II). TCR senses MHC + peptide as a whole.
Positive selection in the thymus results in T cells
binding weakly or moderately self-MHC + peptide.
What is the role of cell mediated immunity/ MHC in allograft transplantation
Allograft has different MHC antogens ( not self) so T cells will bind them STRONGLY
If MHC-II is different, T helpers will be activated.
If MHC-I is different, graft cells will be perceived and treated as
own cells infected by a virus, and T killers will target
them.
Which genes are the most important for graft fate
MHC
Skin allograft rejection
Grafted skin triggers cell mediated immunity more than any other tranpant
So allografts only used temporarily to cover wounds then autografts used
What are the cases when humoral response takes part in
When donor cells hv carbohydrate surface epitopes that receipient doesnt have: Baso ABO blood groups
- hyper acute
- Igm activates complenent
-Producton T independent so uncontrollable
When graft has well developed blood vessels:
- T dependent antobodies so IgG
- immune complexes damage blood vessel walls
- chronic rejection
How can you manage transplantation rejection
Immunosuppressent drugs- to down regulate immune resposne
HLA matching of donor and recipient- (HLA genes help reconise self and foreign cells)
The fetus carries paternal antigens and therefore is a semi-allograft. How does the maternal immune
system tolerate it?
marsupials have not solved this problem in their evolution. They have short pregnancies and
the young are born very immature in order to be saved in time from the maternal “host-vs-graft”
reaction.
How does trophoblast protect fetus from maternal immune response
- Even tho its nucleated, it lacks MHC 1 antogens
- It has special MHC antogens which are ignored by T killers
- It induces specific tolerance to fetal antigens and local non specific immunosupression
- Maternal T lymphocytes cannot migrate between its
cells because its outer layer is syncytial
(syncytiotrophoblast).
What is the normal imcompatibilty reaction after transplant
host vs graft
What happens in a graft vs host reaction
If mature allogenic T cells are transplanmted into host but the host is unable to reject them, then a GVH reaction occurs
The grafted t cells reject the host tissue
