Flashcards in Transplant Immunology Deck (46):
Transfer of one's own tissue from one site to another.
Transfer of tissue between identical twins.
Transfer of tissue between genetically different species.
Transplant into an anatomical normal recipient site.
Transplant into anatomically abnormal site.
Are transplants ever rejection-free?
No - always have some degree of rejection.
What is rejection?
An immune-mediated response; immune cells are attacking a foreign body. This is particularly problematic for organs and tissues that are highly vascularized.
What causes rejection?
Recognition of foreign MHC antigens by T cell activation.
What does not express MHC? How is matching done for this?
RBC - recipients must be matched for ABO and Rh blood types.
Explain the mouse experiment.
Mouse B got some Mouse A bits transplanted onto it. Acute rejection occurred 10-14 days out. Another Mouse B got some Mouse A bits transplanted onto it, as well as first Mouse B's bits. Acute rejection occurred 3-7 days out. 3rd Mouse B got Mouse A bits and an injection of 2nd Mouse B's lymphocytes. Hyperacute rejection occurred 3-7 days out - added leukocytes to presensitized donor tissue and response is quicker.
Do we have antibodies for our own antigens?
What do we make antibodies to in terms of blood?
The antigen we lack in the ABO blood group system
Explain the antibodies and antigens of blood.
2 antigens (agglutinogens A & B) on surface of RBC that allow immune system to recognize cell as self. 2 antibodies (agglutins - anti-A & anti-B) in the plasma. H antigen is foundation upon which A & B antigens are built. A gene codes for a transferase that adds N-acetylgalactosamine to terminal sugar of H-antigen. B gene codes for enzyme that adds D-galactose to terminal sugar of H antigen.
What is Rh factor?
Rhesus factor - protein that 85% of the population contains in their blood (RhD+).
ABO blood typing that determines antigens on patient's or donor's blood. Cells are tested with the antisera reagents anti-A, anti-B.
ABO blood typing that determines antibodies in patient's or donor's serum of plasma. Serum is tested with reagent A1 and B cells.
Why is it a problem for an Rh(-) mother to be pregnant with an Rh(+) baby?
Blood mixing happens during birthing. The mother's blood will be exposed to fetal blood, causing a Type II hypersensitivity response. Antibody binding to antigen activates the classical complement pathway, leading to MAC, which causes blood lysis and hemolysis in the mother's next pregnancy, as during this one she will have antibodies against her baby's Rh(+) blood.
Matching MHC Class I (especially HLA-_) and Class II HLA-__ alleles is more important for ________ _______ than matching other MHC antigens.
Transplants must always be matched for what type of antigens?
What types of molecules are MHC Class I?
Almost all nucleated cells
What types of molecules are MHC Class II?
What is the name of the following phenomenon involving MHC: multiple variants of each gene within the population as a whole?
What are the 2 mechanisms of allogenic transplant rejection?
This mechanism of allogenic transplant rejection involves replication of an intact MHC molecule displayed by donor APC in the graft. Self MHC molecules recognize the structure of an intact allogenic MHC molecule. It is most common in acute rejection and involves both CD8 & CD4 T cells.
What are the HLA loci for MHC Ia?
A, B, C
What are the HLA loci for MHC Ib?
E, F, G, H
This mechanism of allogenic transplant rejection involves donor MHC that is processed and presented by recipient APC (basically handled like any other antigen). It is more common in chronic infection and involves only CD4+ T cells (MHC Class II antigen presentation).
What can you do to detect tissue incompatibility, i.e. decrease likelihood of rejection?
Blood typing & mixed leukocyte reaction
What are you doing when you take leukocytes from both donor and recipient, irradiate them to stop proliferation, then mix them all together? Why do this?
Mixed leukocyte reaction (MLR) - low responses = better tissue match for transplant
Which type of rejection is extremely rare?
Which type of rejection occurs hours to days after transplantation, targets the vascular endothelium (immediate thrombosis), within 24-48 hours causes antibody-mediated and complement-dependent graft destruction by coagulative necrosis, and has preformed antibodies specific to MHC?
Which types of cells are mediators of hyperacute rejection?
B cells & preformed antibodies
Which type of rejection is most commonly seen (45-70% of patients)?
Which type of rejection occurs days to months after transplant (usually 3 months), is T cell mediated (predominantly CD4 & CD8 T cells, directed against donor MHC antigens), and is the target of current immunosuppression?
Which types of cells are mediators of acute rejection?
T cells, predominantly CD4 & CD8
Which type of rejection occurs in 2-5% of patients?
Which type of rejection is a slow, indolent process occurring months to years after transplantation; has immune and non-immune components; causes ischemic injury; is characterized by arteriole thickening and interstitial fibrosis; and is untreatable?
How would you manage chronic rejection?
What types of hypersensitivities are involved with chronic rejection?
Type II & Type IV (unclear, but Type III may play a role)
An immunologically competent graft is transplanted into an immunologically suppressed recipient. Patient presents with fever, pancytopenia, weight loss, rash, and diarrhea. Patient may present with hepatosplenomegaly. What does this patient have? Explain what's happening.
Graft vs. host disease - grafted cells survive and react against the host cells
What type of tissue is more likely to succumb to graft vs. host disease? Why?
immunocompetent tissue - bone marrow, skin; continued immunocompetent cell production, which may trigger an immune response against the host
What are some prevention and treatment options for allograft rejection?
Reduction of allograft immunogenicity
Induction of donor specific tolerance
What are methods of immunosuppression for the prevention and treatment of allograft rejection?
Drugs that inhibit/kill T lymphocytes
Toxins that kill proliferating T cells
Antibodies that deplete/ihibit T cells
What are methods for reducing immunogenicity of allografts in the prevention and treatment of allograft rejection?
ABO blood typing
HLA typing and matching
How can you induce donor specific tolerance for the prevention and treatment of allograft rejection?