Transplantation Immunology Flashcards
What are the most widely used agents for immunosuppression in transplant patients?
Cyclosporin A and Tacrolimus
Minor H antigens
Polygeneic proteins other than MHC that can cause rejection
What is the difference between the term allogeneic and xenogeneic?
Allogeneic refers to genetic difference between two individuals of SAME species, xenogeneic refers to differences between individuals in DIFFERENT species
Which tends to lead to a larger immune response, an alloantigen or a xenoantigen?
An alloantigen
What is a bigger problem in xenografts, cell-mediated problems or antibody problems?
Natural antibodies
What antibody makes up up to 1 percent of circulating human IgG and why is this antibody relevant in xenografting?
ant-Gal (antibody for mamallian carbohydrate alpha-galactosyl). Humans lack this epitope but most other species have it
Define each of the following terms and say whether each is accepted or rejected: autografts (autologous grafts), isografts (syngeneic grafts), allografts (allogeneic grafts)
Autografts are from self, isografts are from identical twins, allografts are from others. First two accepted, allografts rejected with speed dependent on level of genetic difference
Second-set rejection
The development of T-cell memory towards an alloantigen leads to rapid rejection of a graft from the some allogeneic donor
Direct pathway of allorecognition
Host T cells respond to donor MHC molecules expressed on donor derived dendritic cells
Indirect pathway of allorecognition
Host T cells respond to peptide fragments of donor MHC molecules expressed on host dendritic cells by host MHC (donor cell was ingested by host DC)
Four types of HLA typing used for donor-recipient matching
Serological (antibodies), Mixed Lymphocyte Reaction (mix their blood and see what happens), DNA analysis (PCR or sequencing), Cross matching (looking for preformed antibodies to prevent hyperacute rejection)
Hyperacute rejection
Minutes to hours. Anti-donor antibodies and complement deposition
Accelerated rejection
Days. Reactivation of sensitized T and B cells
Acute rejection
Days to weeks. Primary activation of T cells, with or without alloantibodies
Chronic rejection
Months to years. Loss of tolerance, slow cellular or humoral reaction, recurrence of disease. Mechanism not totally known
What typically begins the recipient immune response after an allograft?
Passenger leukocytes or APCs from donor presenting to recipient T cells (ie Direct Pathway)
What determines immunogenicity of different tissues and list some examples from most immunogenic to lowest
Level of residing APCs. Bone marrow (highest), skin, islets of Langerhans, heart, kidney, liver (lowest)
What immunological reagents are used for immunosuppression of allograft recipients?
Monoclonal antibodies aimed at T cells (anti-CD3, anti-CD4, anti-CD8), can be coupled with toxins. Also, mAb for IL-2 targets only activated T-cells. Also, polyclonal antibodies such as ATG
What two drugs are hallmarks of post allograft immunosuppression and how do they work?
Cyclosporin A and tacrolimus. Block NFAT transcription factors, which activate IL-2 production
Why is rapamycin given to organ recipients?
It blocks signaling through the IL-2 receptor, helping achieve T-cell immunosuppression
What drugs are given to organ recipients to achieve immunosuppression?
Steroids, immunlogic reagents (eg mAbs), cyclosporin A, tacrolimus, rapamycin, and MMF
Mycophenolate Mofetil (MMF)
Given to organ recipients to achieve immunosuppression, inhibits IMPDH, which is necessary for de novo synthesis of purines (T and B cells need this pathway, other cells can use salvage pathways)
What is Graft-versus-Host Disease (GVHD), what organs does it primarily effect, and what can be done to prevent it?
T-cells in donated marrow recognize recipient allogantigens. Targets skin, liver, gut in particular. Can be due to MHC or minor H antigens. Prevented by elimination of donor T cells from the inoculum
In what leukemias is relapse after BMT most common and what is the relationship between relapse and GVHD?
CML and AML pts. Relapse shows inverse relationship with GVHD occurrence.
