19: Transplant Immunology Flashcards
Alloantigens
Antigen which varies between members of the same species
Alloreactions
Immune responses directed against alloantigens
Immunogenetics
A subfield of immunology devoted to the genetics of alloantigens
Autograft
Graft of tissue from one site to another site on the same individual
Syngeneic graft (isograft)
Graft of tissue from one person to another person that is genetically identical
Allogeneic transplant (allograft)
Graft of tissue from one person to another person that is genetically different
Transplant rejection
Alloreactions developed by a recipient’s immune system that are specific for grafted tissue
Graft vs. host reaction
Reaction mounted by mature T cells contained in grafted tissue against tissues of the recipient
Zenograft
Graft between two individuals of different species
Transplantation of tissues requires solutions to what 3 basic problems?
- Transplant must be able to perform its basic function
- Health of the donor/recipient must be maintained during surgery
- Immune system must be prevented from mounting adaptive immune responses that destroy the grafted tissue
Immune responses mounted by a recipient that are directed at transplanted tissues are caused by ___________.
Genetic differences between the donor and the recipient (i.e differential expression of HLA)
What is the easiest and most commonly used transplantation procedure?
Blood transfusion
Why are the alloantigens that cause most transplant rejections not a problem for blood transfusions?
RBCs don’t express MHC class I or MHC class II molecules
What would happen if a person who has type O blood receives a transfusion of type A or type B blood?
- The person’s anti-A or anti-B antibodies will bind to the transfused RBCs
- This results in complement activation and rapid clearance of the transfused RBCs
- Results in fever, chills, shock, renal failure, and sometimes death
Why is everyone tolerant to O antigen?
Structurally, A and B antigens are just O antigen with something added on, so there’s nothing for people to be intolerant to on O.
T or F: People that do not express RhD will not have antibodies specific for RhD in their circulation
T
What are 2 theories for why a fetus isn’t treated like an allograft and rejected during pregnancy?
- Placenta may serve as a partial barrier to the mother’s T cells. It’s a fetal tissue and it lacks expression of MHC class I molecules
- Placenta and uterine epithelium produce TH2 cytokines, which tend to promote antibody responses while suppressing T cell-mediated responsiveness
What solves the problem of Rh incompatibility in pregnancy?
Immunization with RhoGam (a preparation of Ab specific for RhD+ erythrocytes). Mothers treated with RhoGam will destroy all of the fetal RBCs that enter the mother’s circulation, preventing an Rh-specific immune response.
What is hyperacute organ rejection mediated by?
Pre-formed antibodies of the recipient that are specific for the HLA alloantigens of the grafted tissue
In what situation would hyperacute transplant rejection occur?
When donor tissue comes from a person whose blood-type is not compatible with the recipient
What happens in hyperacute transplant rejection?
- Antibodies of the recipient bind to the donor antigens along the vascular endothelium of the grafted tissue
- Complement activation occurs through the vasculature of the graft, and very rapid graft rejection occurs
How do you test to see the degree to which a patient seeking transplant has been sensitized to potential donors?
Panel-reactive antibody (PRA): Test their sera against a panel of individuals from the populations
What cells mediate acute graft rejection?
Effector CTLs that respond to HLA differences between the donor and recipient
What is acute graft rejection?
Newly formed immune response initiated against alloantigens following the graft procedure (no preformed responses to alloantigens because there hasn’t been any previous exposure)
When does acute graft rejection usually take place?
11-15 days after transplantation in the absence of an anti-inflammatory drug treatment. This is the time it takes to prime a CD8 T cell response
T or F: Rejection of tissue from an identical HLA haplotype match can occur.
True dat
Transplant rejection mediated by responses to major histocompatibility antigens is (slower/faster) than rejection mediated by responses to minor histocompatibility antigens.
Faster
What are the pathways by which HLA molecules can stimulate acquired immune responses?
- Direct pathway
2. Indirect pathway
What is the direct pathway for HLA molecules?
Naive T cells of the recipient recognize self peptides of the donor loaded onto donor HLA molecules on donor APCs
What is the indirect pathway for HLA molecules?
- Peptides from donor HLA molecules are presented by recipient APCs to naive T cells of the recipient
- The donor APCs that provided the peptides migrate to secondary lymphoid tissue of the recipient and undergo apoptosis
- Components of the dead cells are phagocytosed by resident APCs
- Antigens are processed by MHC Class II and CD4 effector cells participate in the acute graft rejection
Don’t really know if this is all the steps… I’m kinda confused.
Chronic rejection typically correlates with __________.
The presence of antibodies specific for MHC class I molecules of the grafted tissue
T or F: Success rates of transplantation can be greatly improved by HLA matching.
T
Which HLA loci appear to be the most important for matching?
HLA-A, HLA-B, and HLA-DR
What characterizes chronic rejection?
Reactions in the vasculature of the graft that result in thickening of vessel walls and narrowing of their lumina. Gradually blood supply is reduced to the point that the function of the grafted tissue is lost
What mediates chronic rejection?
Alloreactive, MHC class I-specific antibodies that bind to vascular epithelia of the grafted tissue and attract Fc receptor bearing cells
What is the major cause of morbidity and mortality following bone marrow transplantation?
Acute graft vs. host disease
What are the primary targets for GVHD?
Skin, intestines, and liver
What is GVHD mediated by?
Mature T cells in the donor tissue that react to antigens of the recipient tissues
How can you prevent GVHD?
- Deplete T cells from the bone marrow before grafting
- Drug treatment can help control the incidence and severity of GVHD
What’s the big difference between GVHD and rejection of a solid organ transplant?
GVHD is systemic whereas solid organ transplant alloreactions are limited to the transplanted organ
GVHD presents similarly to ______ deficiency?
AIRE
T or F: Success of liver transplantation does not depend on HLA-crossmatching.
T: A,B,O type is the only genetic factor that must be considered before liver transplantation
T or F: Corneal transplants do not require HLA matching, just immunosuppressive drugs.
F: They don’t require HLA matching or immunosuppressive drugs because the cornea is not vascularized
