Transplantation of Tissues and Organs Flashcards
Define “histocompatible”
Donor and recipient have compatible tissue types that can coexist without provoking too strong of an immune response
True or false. Autologous transplantation can trigger hypersensitivity reactions.
False. Autologous are your own cells. Allogenic transplantation (i.e. from another person) can trigger hypersensitivity
Why do we produce antibodies against A and/or B antigens?
Cross-reactive with cell-surface carbohydrates of common commensal bacteria
How does cross-match testing before transfusions work?
Agglutination of donor red blood cells if the antibody is present in serum
True or false. After multiple transfusions, it may be difficult to find a compatible donor.
True
Blood group incompatibility can cause type ____ hypersensitivity, leading to fevers, chills, shock, renal failure, or death
Type II (hemolytic reactions)
Where are ABO antigens present aside from erythrocytes?
Endothelial cells of blood vessels
Incompatible donor/recipient transplant causes antibodies to quickly and extensively bind the blood vessels of the graft. Complement is fixed throughout the graft’s vasculature resulting in _______
Hyperacute rejection (can happen on the table)
How does cross-match testing work in regard to HLA I and II?
- Detects antibodies in patients serum that can trigger complement mediated lysis of donor lymphocytes
- anti-HLA I antibodies react with B and T-cells
- anti-HLA II react with B cells
Why is flow cytometry more specific that cross-matching?
It detects ALL antibody binding, not just those that fix complement
Under what circumstances could the body potentially make anti-HLA antibodies?
- Pregnancy → fetus expresses parental HLA; exposed after trauma of birth
- Blood transfusions
- Previous transplant
What is the main source of anti-HLA antibodies used in serological HLA typing?
Multiparous women (have given birth more than once)
What is the difference between transplant rejection and graft-versus host reaction (GVHR)?
- Transplant rejection involves a solid organ transplant
- GVHR involves hematopoietic stemm cell transplantation
_____ occurs when donor T-cells respond to and attack the recipient’s healthy tissue (type IV hypersensitivity).
Graft-versus host disease (GVHD)
____ is when a patient’s tissue is transplanted from one site to another (ex: skin graft, bone graft, ligament repair)
Autograft
_____ involves transplant between two genetically identical individuals
- Isograft
- Syngenic transplant
_____ occurs when a transplant recipient’s naive T-cell population contains clones that recognize HLA allotypes of the transplanted tissue. Takes days to develop
Acute rejection
In acute rejection, CD8 T-cells respond to HLA _____, while CD4 T-cells respond to HLA ____.
- CD8 → HLA I
- CD4 → HLA II
Patients are conditioned with ____ before and after transplantation to hdiminish e risk of acute rejection.
Immunosuppressive drugs
Explain the direct pathoway of allorecognition
Recipient T-cells are stimulated by direct interaction of their receptors with the allogenic HLA molecules expressed by donor dendritic cells
______ rejection is a type III hypersensitivity caused by IgG against HLA I of graft tissue, forming immune complexes that deposit in blood vessels of transplanted organs. Can occur up to 10 years after transplant.
Chronic rejection
In chronic rejection, grafts become infiltrated with _____ expressing B-cells and _____ expressing T-cells
- CD40 expressing B-cells
- CD40-ligand expressing T-cells
What is the function of rituximab?
- Anti-B-cell antibody
- Treats chronic rejection
Explain the indirect pathway of allogenic recognition.
- Activation of helper CD4 T-cells by graft HLA after transplantation
- Induces naive B-cells to become plasma cells
- only occurs if naive B-cells are capable of reacting with graft HLA
______ - regulatory CD4 T-cells suppress alloreactive CD4 and CD8 T-cells. More active in patients with previous blood transfusions with shared HLA-DR allotype of graft.
Transfusion effect
What animal is the most suitable donor species for xenotransplantation? Why?
Pigs
- Organs are similar in size
- Farmed, slaughtered, and consumed by humans in large numbers (less likely to trigger hypersensitivity)
What is the funciton of myeloablative therapy in hematopoietic stem cell transplantation?
- Cripples the recipient’s immune system
- Creates spece for donor cells in bone marrow niche
How long after hematopoietic stem cell transplantation does it take for RBCs to be produced? How long to completely reconstitute the immune system?
- 2-3 weeks RBCs
- ~1 year for full reconstitution
