Transplantation Immunology

Question 1

What are the most widely used agents for immunosuppression in transplant patients?

Answer 1

Cyclosporin A and Tacrolimus

Question 2

Minor H antigens

Answer 2

Polygeneic proteins other than MHC that can cause rejection

Question 3

What is the difference between the term allogeneic and xenogeneic?

Answer 3

Allogeneic refers to genetic difference between two individuals of SAME species, xenogeneic refers to differences between individuals in DIFFERENT species

Question 4

Which tends to lead to a larger immune response, an alloantigen or a xenoantigen?

Answer 4

An alloantigen

Question 5

What is a bigger problem in xenografts, cell-mediated problems or antibody problems?

Answer 5

Natural antibodies

Question 6

What antibody makes up up to 1 percent of circulating human IgG and why is this antibody relevant in xenografting?

Answer 6

ant-Gal (antibody for mamallian carbohydrate alpha-galactosyl). Humans lack this epitope but most other species have it

Question 7

Define each of the following terms and say whether each is accepted or rejected: autografts (autologous grafts), isografts (syngeneic grafts), allografts (allogeneic grafts)

Answer 7

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

Question 8

Second-set rejection

Answer 8

The development of T-cell memory towards an alloantigen leads to rapid rejection of a graft from the some allogeneic donor

Question 9

Direct pathway of allorecognition

Answer 9

Host T cells respond to donor MHC molecules expressed on donor derived dendritic cells

Question 10

Indirect pathway of allorecognition

Answer 10

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)

Question 11

Four types of HLA typing used for donor-recipient matching

Answer 11

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)

Question 12

Hyperacute rejection

Answer 12

Minutes to hours. Anti-donor antibodies and complement deposition

Question 13

Accelerated rejection

Answer 13

Days. Reactivation of sensitized T and B cells

Question 14

Acute rejection

Answer 14

Days to weeks. Primary activation of T cells, with or without alloantibodies

Question 15

Chronic rejection

Answer 15

Months to years. Loss of tolerance, slow cellular or humoral reaction, recurrence of disease. Mechanism not totally known

Question 16

What typically begins the recipient immune response after an allograft?

Answer 16

Passenger leukocytes or APCs from donor presenting to recipient T cells (ie Direct Pathway)

Question 17

What determines immunogenicity of different tissues and list some examples from most immunogenic to lowest

Answer 17

Level of residing APCs. Bone marrow (highest), skin, islets of Langerhans, heart, kidney, liver (lowest)

Question 18

What immunological reagents are used for immunosuppression of allograft recipients?

Answer 18

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

Question 19

What two drugs are hallmarks of post allograft immunosuppression and how do they work?

Answer 19

Cyclosporin A and tacrolimus. Block NFAT transcription factors, which activate IL-2 production

Question 20

Why is rapamycin given to organ recipients?

Answer 20

It blocks signaling through the IL-2 receptor, helping achieve T-cell immunosuppression

Question 21

What drugs are given to organ recipients to achieve immunosuppression?

Answer 21

Steroids, immunlogic reagents (eg mAbs), cyclosporin A, tacrolimus, rapamycin, and MMF

Question 22

Mycophenolate Mofetil (MMF)

Answer 22

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)

Question 23

What is Graft-versus-Host Disease (GVHD), what organs does it primarily effect, and what can be done to prevent it?

Answer 23

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

Question 24

In what leukemias is relapse after BMT most common and what is the relationship between relapse and GVHD?

Answer 24

CML and AML pts. Relapse shows inverse relationship with GVHD occurrence.

Question 25

After BMT what cells can target leukemia cells and prevent leukemia relapse?

Answer 25

NK cells and donated alloreactive T cells