Lecture 18: Transplant Immunology Flashcards
In general, what is the 1 reason why grafted tissue is rejected?
genetic differences between the donor and recipient
What type of graft is this:
graft of the same tissue from one site to another on the same pt
autograft
What type of graft is this:
graft between genetically identical pts
syngenic graft
What type of graft is this:
graft between 2 genetically different pts (but are of the same species)
allograft
What type of graft is this:
Is always accepted (pretty much always)
autograft
What type of graft is this:
graft between 2 individuals of different species
zenograft
What type of graft is this:
graft between identical twins
syngenic graft
_______ genes gives rise to most allogenic antigens.
polymorphic
What are examples of allogenic Ags?
MHC class I and II molecules blood group Ags
What is the difference between transplant rejection and GVHD?
in transplant rejection the recipient’s CD8 T cells attack the donor tissue (localized) and in GVHD the CD8 T cells in the grafted tissue attack the hosts cell (systemic)
T or F: erythrocytes express MHC class I but not MHC class II molecules.
False: they express NEITHER I or II
What are the primary targets of alloreactivity in blood transfusions? Why?
A, B, and O Ags bc the normal gut flora produces molecules that are almost identical to the A, B, and O Ag –> cross reaction
Why is O blood type considered the universal donor?
bc it is the main component of the A and B Ags
A person with type A blood can receive blood from blood types ________
A and O
A person with AB blood type can receive blood from _____
A, B, and O
A person with type O blood type CANNOT receive blood from ________
A, B, or AB
If a person is RhD- can they receive RhD+ blood?
No, they will see the RhD as a foreign substance and attack the blood that has been admin to them
Can a person with A RhD+ receive blood from an O RhD- ?
yes
Can a person with A RhD+ receive blood from an O RhD+ ?
yes
Can a person with A RhD- receive blood from an O RhD+ ?
no
Describe a hyperacute rejection reaction
recipient has PRE-FORMED Abs against grafted tissue endothelium. These Abs get deposited in the graft’s vasculature and initiate the complement cascade –> opsonization –> phagocytosis and inflammation –> rapid death of graft
Describe an acute rejection rection
Immune system recognizes MHC on graft as a foreign substance –> CD8 T cell response generated –> CTLs start killing the graft 11-15 days after transplantation
T or F: there is inflammation associated with an acute transplant rejection
false: no inflammation
What cells mediate acute graft rejection?
dendritic cells present Ag to naive T cells to make CD8 T cells. CD8 T cells cause the tissue damage
An A blood type pt receives a transplant from an AB donor. WIthin 48 hrs will there be rejection?
Yes
An A blood type pt with hyper IgM syndrome receives a transplant from an AB donor. WIthin 48 hrs will there be rejection?
Yes, IgM and IgG opsonize and participate in acute organ rejection
What Ab isotypes mediate hyperacute transplant rejection?
IgM and IgG
What is second set rejection?
when you give a pt a second allograft and they reject it much faster than the first time the rejected it. This is bc they already have CD8 T cells primed
What hypersensitivity reaction is acute rejection similar to? How are they different?
similar to type IV HS bc both are CD8 mediated. they are different bc the immune system does not need to be primed to have an acute rejection reaction (it will happen with the first exposure to the Ag)
What is the difference between a graft with an incompatible minor histocompatibility vs an major histocompatibility
Minor HCs reactions take a much longer time to reach rejection of the graft
What can greatly improve the success rate of transplants?
HLA matching
What techniques are used to determine HLA haplotypes?
combo of serological and DNA
What HLA loci are the most important for matching?
A, B and DR
T or F: individuals with similar or identical MHC class I and MHC class II haplotypes are best suited as recipient:donor pairs.
T
T or F: A higher degree of HLA matching does not correlate to the long term health of the patient.
F: it does correlate
T or F: A high degree of HLA matching is necessary for a successful liver transplant.
False: liver transplants do not depend on HLA matching. they are one of the exceptions
What types of transplants are the exceptions to HLA matching?
liver and cornea
T or F: Corneal transplants do not require pt to be on immunosuppresive drugs after the transplant
true
Why do corneal transplants not need HLA matching or immunosuppressive drugs to ensure successful transplantation?
bc they cornea is not vascularized. Therefore, CD8 T cells do not have access to the donor tissue
What are the genetic factors that need to be considered before a liver transplant?
A, B, or O blood types
What type of graft are fetuses considered? (auto, allo, syngenic, zenogenic)
allograft
What are 2 proposed explanations for why the mother’s immune system does not reject a fetus?
- the placent lacks MHC I or II and is able to serve as a barrier to the mom’s T cells
- placenta and uterine epithelia produce Th2 cytokines that promote Ab response but down regulate cell mediated response
But really, no one knows whats going on. Just like me.
What are a complex set of protein alloantigens that are expressed on RBCs?
Rh Ags
If you are Rh __ you are not tolerate to RhD blood (= you will make anti-RhD Abs)
negative (-)
What can be a complication of an RhD- mother carrying an RhD+ child?
If the fetal blood gets into the maternal circulation (after birth or from trauma…aka the same thing) then the mother’s immune system will make Abs against the RhD. These IgG anti-RhD Abs will enter into fetal circulation and cause destruction of fetal RBCs = hemolytic disease
What is the preventative treatment used for RhD- mothers?
they are given an injection of anti-RhD Abs (rhogam)
*“This is done so that the fetal RhD positive erythrocytes are destroyed before her immune system can discover them.” -wikipedia
When should rhogam be administered?
- Right after birth (to protect future pregnancies)
2. ?????? and i dont understand this slide, plz ezplain :(
What is the major cause of morbidity and mortality after bone marrow transplantation?
GVHD
During GVHD, what are the 3 principle tissues affected?
- skin
- intestines
- liver (inflamm of bile duct)
GHVD has a similar presentation to what immunodeficiency?
AIRE deficiency (i.e. self reactive T cells escape tolerance mechanisms and can attack host cells)
How can graft tissue be prepared to prevent GVHD?
deplete all T cells from done marrow graft
