Transplant Immunology Flashcards
What is transplant rejection?
Destruction of grafted tissues by immune responses caused by genetic differences between the donor and the recipient
Define allogenic
Individuals of the same species who are genetically different
What gives rise to most allotypic antigens?
Polymorphic genes (MHC class I and II molecules; blood group antigens)
Define autograft
Graft of tissue from one site to another on the same patient
Define syngeneic graft
Graft between genetically identical patients (isograft)
Define zenograft
Graft between two different species
Attack by what type of cell leads to transplant rejections (tissues) or graft-versus-host disease (bone borrow)?
T-Cells
What is the most common type of tissue transplant?
Blood transfusions
Do erythrocytes express MHC class I or II molecules?
Neither
What are the primary targets of alloreactivity for blood transfusions?
The A, B, and O antigens (also think about Rh factor)
What blood type is the universal donor? Why? Universal acceptor?
Blood type O, because it is the basis for both A and B.
Blood type AB, because it has no specific antibodies against A or B
Which Rh factor is of largest concern?
Rh D Antigen
When does hyperacute rejection occur?
When donor tissue comes from a person whose blood-type is not compatible with the recipient. (ex A donating to B)
What mediates hyperacute rejection?
It is mediated by preformed antibodies of the recipient that is specified for alloantigens of the grafted tissue
What happens in a hyperacute rejection?
Vascular endothelium expressing the same blood group antigens that are expressed on erythrocytes bind to each other and initiate the complement and clotting cascades
What is the effector mechanism of hyperacute reaction?
IgG and IgM directed against A, B, and O antigens
What mediates an acute rejection?
Effector CTL’s responding to allotypic differences between blood and donor; MHC class I and II are most polymorphic genes in genome
Why does an acute rejection take longer than a hyperacute rejection?
About 11-15 days after transplantation because there are no preformed effector cells (must prime and generate new CD8+ T cells)
What is a nude mouse?
A mouse with an athymic phenotype (cannot produce mature T cells so cant reject a zenograft)
What is second set rejection?
An accelerated acute response because an immune response is already primed from first graft
Can a rejection occur from identical HLA haplotypes?
Yes, and it is mediated by minor histocompatibility complexes
How long does a rejection from identical HLA haplotypes take?
Much longer, 30-60 days
If we improve HLA matching between donor and recipient, does this help the transplant?
Yes, the closer the match the better (done by serological and DNA techniques)
Which HLA types are of the most concern?
HLA-A, HLA-B, HLA-DR
What needs to be matched for a liver transplant?
Blood antigen; Liver transplant doesn’t depend on HLA matching, liver is refractory to acute rejection
What needs to be matched for a corneal transplant?
Nothing! Cornea is not vascularized
What are Rh antigens?
A complex set of protein alloantigens expressed on RBC’s
When do we worry about Rh antigens during pregnancy?
The pregnancy of an Rh- woman carrying an Rh+ baby; dont want the mother to make antigens against the Rh antigens, more concerned in second pregnancy than first
When do immune responses form when an Rh- mother is carrying an Rh+ baby?
Not until after birth when the mother is exposed to a large amount of the baby’s blood
Subsequent pregnancies of an Rh+ baby to an Rh- mother lead to what?
Hemolytic disease of the newborn
What is Rhogam? When is it administered?
It is an anti-RhD antibody administered after birth that will precent the mother from mounting an Rh- specific immunity
T/F, Rhogam is administered to mothers that have different blood types than the baby.
False, give to mothers with the same blood type
Are blood group antigens expressed more on vascular endothelium or RBCs?
Vascular endothelium
What is graft-versus-host disease (GVHD)?
A mature T-cell attack on the recipient’s tissue occurring after bone marrow transplant. More widespread than transplant rejection.
What are the principle tissues effected by GVHD?
Skin, intestines, and liver (inflammation of bile duct)
What are the grades of GVHD?
I-IV on the basis of skin, liver, and GI tract involvement
How can we prevent GVHD from occurring?
Deplete all of the mature T cells from the bone marrow of the donor; immunosuppressive drugs
Why am I not including any information about drugs from Miller?
He is not testing us on them, learn drugs for the other professors.