Transplant Immunology

Question 1

define:

syngeneic, allogeneic, xenogeneic

Answer 1

syngeneic - transplantation between genetically identical individuals

allogeneic - transplantation between genetically dissimilar individuals of the same species

xenogeneic - transplantation between different species

Question 2

minor histocompatibility antigen

Answer 2

normal proteins on the cells surface that are polymorphic in nature and have been found to be involved in transplant rejection or acceptance

• H-Y has been found to be involved in rejection of male graft in female host)

Question 3

describe direct alloantigen recognition

Answer 3

occurs when graft APC presents antigen to host T cells. usually T cells are negatively selected to prevent high affinity binding to MHC but when there is graft involved there is no way to present graft MHC to T cells in the thymus.

mechanism 1: T cell interacts with graft MHC and, although doesnt interact with the peptide presented, binds in a way that it sees the graft MHC as self-MHC+peptide causing activation.

mechanism 2: T cells interacts with graft MHC and binds the peptide and graft MHC in peptide binding region. Causes the T cell to see the graft MHC as foreign and reaction

Question 4

Describe hyperacute rejection

Answer 4

transplant rejection that occurs within minutes to hours after operation.

• characterized by thrombosis and vascular occlusion of graft vessels and followed by ischemic necrosis
• caused by presence of already existing antibodies in host against donor tissue.
• completely preventable through cross-matching test

Question 5

Describe acute rejection

Answer 5

transplant rejection response that occurs within days to weeks after operation

• characterized by transmural necrosis of graft vessels walls
• CTL and CD4 mediated that have been stimulated by alloantigens in graft
• treatable w/ immunosuppressant medications

Question 6

Describe chronic rejection

Answer 6

response occuring months to years after transplant

• characterized by fibrosis of graft tissue and gradual narrowing of vessels (graft arteriosclerosis
• mediated by T cells and antibody reaction against alloantigens
• refractory (no real way to prevent)

Question 7

Describe how immunosuppressive medications work.

Answer 7

prevent IL-2 production (cyclosporine), prevent proliferation (rapamycin, azathioprine, anti-IL2R), prevent activation (AntiTCR), prevent costimulatory signals (CTLA4-Ig)

Question 8

What are the side effects of immuno suppression?

Answer 8

malignancy, increased infections because of dampened immune system, and drug toxicity and effects on the kidneys, liver and more (limited use).

Question 9

what are strategies to minimize alloantigenic differences?

Answer 9

(1) blood group matching
(2) HLA allele matching
(3) cross-matching test

Question 10

Graft-vs-Host Disease (GVHD)

Answer 10

reaction of mature grafted T cells to alloantigens of the host (bone marrow transplants) - often directed against minor histocompatibility antigens. can be treated by immunosuppression.

• acute: epithelial cell death in skin, liver, and GI
• chronic: characterized by fibrosis and atrophy w/o acute cell death