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Immunology Final - Transplantation
Transplantation.
53
Immunology
Undergraduate 3
05/09/2012

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Term
Autograft:
Definition
Grafts from yourself.
Term
Isograft:
Definition
Grafts from an identical twin.
Term
Allograft:
Definition
Grafts from the human species.
Term
Xenograft:
Definition
Grafts from a different species.
Term
Cornea transplant comes from -
Definition
A cadaver.
Term
Lung transplant comes from -
Definition
A brain-dead donor.
Term
Heart transplant comes from -
Definition
A brain-dead donor.
Term
Liver transplant comes from -
Definition
A cadaver.
Term
Bone marrow transplant comes from -
Definition
Needle aspiration from a living donor.
Term
Kidney transplant comes from -
Definition
Living donor, or cadaver.
Term
Pancreas transplant comes from -
Definition
A cadaver.
Term
Blood transplant comes from -
Definition
Transfusion from a living donor.
Term
Skin transplant comes from -
Definition
Usually yourself (autologous) - typically burn victims.
Term
Limiting factors of transplantation:
Definition
Not enough supply/donors.
ABO incompatibility.
HLA incompatibility.
Term
Why is it important to match HLA and MHC antigens for transplantation?
Definition
To avoid cell-mediated and/or humoral responses to foreign HLA or MHC antigens.
Term
How many rejections for allografts?
Definition
Two sets.
Term
Allograft first-set rejection is what type of response?
Definition
Primary immune response.
Revascularization: leukocytes arrive by 3-7 days.
Full rejection by 10-14 days.
Term
Allograft second-set rejection is what type of response?
Definition
Secondary immune response: immunologic memory.
Rejection begins by 3-4 days.
Full rejection by 5-6 days.
Term
Revascularization occurs with what rejection set of an allograft?
Definition
First-set rejection.
Term
First-set rejection process:
Definition
Day 1: Graft.
Days 3-7: Revascularization.
Days 7-10: Cellular infiltration.
Days 10-14: Thrombosis and necrosis (damages blood vessels, blood clots, necrotic tissue)
Term
Second-set rejection process:
Definition
Day 1: Graft.
Days 3-4: Cellular infiltration.
Days 5-6: Thrombosis and necrosis (Necrotic tissue and blood clots)
Term
Cells involved in allograft rejection:
Definition
CD4+ and CD8+ populations are involved.
Increased levels of INF-Gamma.
Dendritic cells (involved in rejection and tolerance)

Pretreatment with donor cells can promote tolerance.
Term
Histocompatible:
Definition
Tissues that are genetically similar.
Generally indicating allograft acceptance.
Term
Haplotype:
Definition
Genes closely linked, such that they are inherited as a group (MHC)
Term
Most vigorous rejection is due to:
Definition
MHC locus/HLA locus.
Term
HLA stands for:
Definition
Human Leukocyte Antigen.
Term
HLA consists of how many alleles from each loci?
Definition
Two.
Term
Loci of MHC Class I genes:
Definition
A, B and C.
Term
Loci of MHC Class II genes:
Definition
DR, DQ and DP.
Term
Everybody has how many haplotypes? Where do they come from?
Definition
Two. One from mother, one from father.
Term
Stage 1 of allograft rejection is:
Definition
Sensitization stage.
Term
What happens in the sensitization stage of allograft rejection?
Definition
T cells of the recipient proliferate in response to antigens on the graft.
- Both CD4+ and CD8+ cells react.
- Donor APC's migrate to lymph nodes and stimulate host T cells there.
- Host APC's (dendritic cells) can migrate into graft and endocytose foreign antigens -- dendritic cells can cross-present endocytic antigens in the context of MHC I.
Term
What is direct allorecognition?
Definition
When donor APC's (allogenic APC) migrate to lymph nodes and stimulate host T cells (alloreactive T cell) there.
-T cell recognizes unprocessed allogenic MHC molecule on graft APC's.
Term
What is indirect allorecognition?
Definition
When host APC's (dendritic cells) migrate into graft and endocytose foreign antigens.
- T cell recognizes processed peptide of allogenic MHC molecule bound to self MHC molecule on host APC.
Term
Stage 2 of allograft rejection is:
Definition
Effector Stage.
Term
What is involved in the effector stage of allograft rejection?
Definition
Host immune system attacks the graft (Type IV - delayed hypersensitivity)
- CTL-mediated cytotoxicity.
- Compliment mediated antibody response.
- ADCC.

TH cells play a key role:
- IL-2: T cell proliferation and CTL response
- IFN-Gamma: DTH response, increased MHC II expression
- TNF-Beta: Increased cytotoxicity.
Term
What are the clinical types of graft rejection?
Definition
Hyperacture rejection.
Acute rejection.
Chronic rejection.
Term
When does hyperacure rejection take place?
Definition
Less than 24 hours after graft - can happen in minutes.
Term
When does acute rejection take place?
Definition
Weeks after graft.
Usually begins about 10 days post-transplant, with full rejection after 10-14 days.
Term
When does chronic rejection take place?
Definition
Months to years after graft.
Term
What triggers hyperacture rejection occur?
Definition
Pre-existing antibody.
Term
What cells make acute rejection occur?
Definition
T cell and cytokines.
Term
What type of immune response is chronic rejection?
Definition
Humoral and cell-mediated.
Term
What happens when chronic rejection is cell-mediated?
Definition
Lymphocyte infiltration of graft.
Term
What happens when chronic rejection is humoral?
Definition
Rejection vasculitis; associated with development of donor specific HLA antibodies.
Term
What is histocompatibility testing for?
Definition
- To determine ABO and HLA type of patients and donors.
- Selection of donor tissues with minimal difference between donor and recipient.
- Look for evidence of prior sensitization.
- Identify incompatible transplants by in vitro crossmatching.
Term
Does the patient need immunosupprives therapy of the donor is a perfect HLA match?
Definition
Yes because other minor histocompatibility antigens will likely differ and can eventually cause transplant rejection.
Term
To avoid hyperacute rejection:
Definition
Use ABO compatible blood.
Term
Where are blood group antigens expressed?
Definition
RBC's, epithelial cells, and endothelial cells.
Term
To avoid acute or chronic rejection:
Definition
Use donor tissue with similar or identical HLA antigens as recipient.

If patient has evidence of prior sensitization, avoid using organs/tissues with those HLA antigens.
Term
Matching solid organs - what is priority?
Definition
ABO incompatibility - HLA matching is secondary priority.

Solid organ transplants almost always have to be ABO identical.
Term
Matching stem cell/bone marrow transplants - what is priority?
Definition
HLA matching - ABO is secondary priority (ABO antigens are not found on stem cells - therefore, no hyperacture rejection)

If HLA is not matched there can be graft rejection, as well as rejection of patient by graft.
Term
What happens in Graft vs. Host Disease (GVHD)?
Definition
Lymphocytes from the donated graft attack allogenic antigens of the recipient.

50-70% of bone marrow transplants are affected by GVHD.

Symptoms:
- Skin reactions.
- GI hemorrhaging.
- Liver failure.
- Splenomegaly.
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