Chapter 6- Rejection of Tissue Transplant

Question 1

Process of Rejection

Answer 1

T cells and antibodies produced against graft antigens react against and destroy tissue graft

Question 2

Where are major antigenic differences between the donor and the recipient?

Answer 2

HLA alleles

Question 3

Characteristics of HLA genes

Answer 3

highly polymorphic

always some differences between individuals

Question 4

Allografts

Answer 4

same species

Question 5

Xenografts

Answer 5

grafts from one species to another

Question 6

2 types of T-Cell Mediated Reactions

Answer 6

Acute cellular rejection, chronic rejection

Question 7

When does Acute Cellular Rejection occur?

Answer 7

initial months after transplantation

Question 8

Clinical signs of acute cellular rejection

Answer 8

organ failure

increased vascular permeability and local accumulation of mononuclear cells

Question 9

What cells secrete cytokines during acute cellular rejection

Answer 9

activated CD4+ T cells

Question 10

What occurs during chronic rejection

Answer 10

lymphocytes react against alloantigens in vessel wall

cytokines released to induce local inflammation

Question 11

3 types of Antibody-Mediated Reactions

Answer 11

hyperacute, acute antibody-mediated, chronic antibody-mediated rejection

Question 12

How does hyperacute antibody-mediated rejection occur?

Answer 12

preformed antidonor antibodies are present in circulation of recipient

Question 13

Why would a recipient have preformed antidonor antibodies?

Answer 13

From previous transplant, prior blood transfusions, and multiparous women

Question 14

How does acute antibody-mediated rejection occur?

Answer 14

Antidonor antibodies produced after transplantation

Question 15

What is the initial target of antidonor antibodies in acute antibody-mediated rejection?

Answer 15

graft vasculature

Question 16

How does chronic antibody-mediated rejection occur?

Answer 16

gradual development

affects vascular components

Question 17

Methods of Increasing Graft Survival (5)

Answer 17

HLA matching
Immunosuppressive therapy
T cell and B cell depleting antibodies
Pooled intravenous IgG
Plasmapheresis

Question 18

How does HLA matching increase graft survival in kidney transplants?

Answer 18

benefit if all polymorphic HLA alleles are matched

Question 19

What organs is HLA matching not done?

Answer 19

liver, heart, lungs

Question 20

What immunosuppressive therapies are used to increase graft survival?

Answer 20

steroids to reduce inflammation
mycophenolate mofetil to inhibit lymphocyte proliferation
Tacrolimus to inhibit T cell function

Question 21

Risk of using immunosuppressive therapy

Answer 21

increased risk of infections

Question 22

How does pooled intravenous IgG increase graft survival?

Answer 22

suppresses inflammation

Question 23

When is plasmapheresis used?

Answer 23

severe antibody-mediated rejection

Question 24

Polyoma virus

Answer 24

reactivates when a person is too immunosuppressed

infects renal tubules

Question 25

Immunosuppression and Increased Latent Viruses

Answer 25

increased risk for re-activation of latent viruses EBV-induced lymphomas HPV Kaposi sarcoma

Question 26

What is a bone marrow transplant?

Answer 26

transplantation of hematopoietic stem cells

Question 27

What is a HSC transplant used for? (3)

Answer 27

hematologic malignancies bone marrow failure syndromes inherited stem cell defects

Question 28

Bone marrow failure syndrome

Answer 28

aplastic anemia

Question 29

Inherited Stem Cell defects

Answer 29

sickle cell anemia thalassemia immunodeficiency states

Question 30

Where do transplanted HSC cells come from? (2)

Answer 30

Peripheral blood after they are mobilized from bone marrow after given hematopoietic growth factors Umbilical cord form newborn

Question 31

How does the recipient allow transplanted stem cells to engraft?

Answer 31

recipient treated with high doses of chemotherapy to destroy immune system

Question 32

When does Graft-vs-Host Disease occur?

Answer 32

transferred cells from donor recognize alloantigens in recipient and attack the host cells

Question 33

When is GVHD most seen?

Answer 33

in HSC transplantation

Question 34

When is GVHD rarely seen?

Answer 34

in transplantation of solid organs rich in lymphoid cells or transfusion of unirradiated blood ex. liver

Question 35

How to minimize GVHD

Answer 35

HLA-matching

Question 36

When does acute GVHD occur?

Answer 36

within days/weeks/couple months after bone marrow transplantation

Question 37

What clinical manifestations occur with GVHD? (4)

Answer 37

immune system, skin (rash), liver (jaundice), intestine (diarrhea)

Question 38

What occurs during chronic GVHD? (4)

Answer 38

cutaneous injury, chronic liver disease, damage to GI tract, immune system devastated

Question 39

Immune system in chronic GVHD

Answer 39

shrinking of thymus, depletion of lymphocytes in lymph nodes | recurrent and life-threatening infections

Question 40

What mediates GVHD?

Answer 40

T lymphocytes in the transplanted donor cells | *depletion of T cells may eliminate GVHD

Question 41

Risks for depleting T cells to help GVHD (3)

Answer 41

recurrent tumors in leukemic patients increased graft failures increased risk of EBV related B cell lymphoma