Transplantation of Tissues and Organs

Question 1

Define “histocompatible”

Answer 1

Donor and recipient have compatible tissue types that can coexist without provoking too strong of an immune response

Question 2

True or false. Autologous transplantation can trigger hypersensitivity reactions.

Answer 2

False. Autologous are your own cells. Allogenic transplantation (i.e. from another person) can trigger hypersensitivity

Question 3

Why do we produce antibodies against A and/or B antigens?

Answer 3

Cross-reactive with cell-surface carbohydrates of common commensal bacteria

Question 4

How does cross-match testing before transfusions work?

Answer 4

Agglutination of donor red blood cells if the antibody is present in serum

Question 5

True or false. After multiple transfusions, it may be difficult to find a compatible donor.

Answer 5

True

Question 6

Blood group incompatibility can cause type ____ hypersensitivity, leading to fevers, chills, shock, renal failure, or death

Answer 6

Type II (hemolytic reactions)

Question 7

Where are ABO antigens present aside from erythrocytes?

Answer 7

Endothelial cells of blood vessels

Question 8

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 _______

Answer 8

Hyperacute rejection (can happen on the table)

Question 9

How does cross-match testing work in regard to HLA I and II?

Answer 9

• 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

Question 10

Why is flow cytometry more specific that cross-matching?

Answer 10

It detects ALL antibody binding, not just those that fix complement

Question 11

Under what circumstances could the body potentially make anti-HLA antibodies?

Answer 11

• Pregnancy → fetus expresses parental HLA; exposed after trauma of birth
• Blood transfusions
• Previous transplant

Question 12

What is the main source of anti-HLA antibodies used in serological HLA typing?

Answer 12

Multiparous women (have given birth more than once)

Question 13

What is the difference between transplant rejection and graft-versus host reaction (GVHR)?

Answer 13

• Transplant rejection involves a solid organ transplant
• GVHR involves hematopoietic stemm cell transplantation

Question 14

_____ occurs when donor T-cells respond to and attack the recipient’s healthy tissue (type IV hypersensitivity).

Answer 14

Graft-versus host disease (GVHD)

Question 15

____ is when a patient’s tissue is transplanted from one site to another (ex: skin graft, bone graft, ligament repair)

Answer 15

Autograft

Question 16

_____ involves transplant between two genetically identical individuals

Answer 16

• Isograft
• Syngenic transplant

Question 17

_____ occurs when a transplant recipient’s naive T-cell population contains clones that recognize HLA allotypes of the transplanted tissue. Takes days to develop

Answer 17

Acute rejection

Question 18

In acute rejection, CD8 T-cells respond to HLA _____, while CD4 T-cells respond to HLA ____.

Answer 18

• CD8 → HLA I
• CD4 → HLA II

Question 19

Patients are conditioned with ____ before and after transplantation to hdiminish e risk of acute rejection.

Answer 19

Immunosuppressive drugs

Question 20

Explain the direct pathoway of allorecognition

Answer 20

Recipient T-cells are stimulated by direct interaction of their receptors with the allogenic HLA molecules expressed by donor dendritic cells

Question 21

______ 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.

Answer 21

Chronic rejection

Question 22

In chronic rejection, grafts become infiltrated with _____ expressing B-cells and _____ expressing T-cells

Answer 22

• CD40 expressing B-cells
• CD40-ligand expressing T-cells

Question 23

What is the function of rituximab?

Answer 23

• Anti-B-cell antibody
• Treats chronic rejection

Question 24

Explain the indirect pathway of allogenic recognition.

Answer 24

• 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

Question 25

______ - 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.

Answer 25

Transfusion effect

Question 26

What animal is the most suitable donor species for xenotransplantation? Why?

Answer 26

Pigs

• Organs are similar in size
• Farmed, slaughtered, and consumed by humans in large numbers (less likely to trigger hypersensitivity)

Question 27

What is the funciton of myeloablative therapy in hematopoietic stem cell transplantation?

Answer 27

• Cripples the recipient’s immune system
• Creates spece for donor cells in bone marrow niche

Question 28

How long after hematopoietic stem cell transplantation does it take for RBCs to be produced? How long to completely reconstitute the immune system?

Answer 28

• 2-3 weeks RBCs
• ~1 year for full reconstitution