18. Tissue Transplants (Rejection)

Question 1

Graft rejection occurs based on

Answer 1

immunological principles

Question 2

How is the degree and type of immune response varied?

Answer 2

with type and source of grafted tissue

Question 3

Name four types of graft possible:

Answer 3

1. Autograft
2. Isograft
3. Allograft
4. Xenograft

Question 4

What two types of graft are usually accepted?

Answer 4

Autograft and isograft

Question 5

Autograft

Answer 5

self-tissue grafted to another self area (skin, blood vessels)

Question 6

Isograft

Answer 6

transplant between two genetically identical individuals (inbred strains of mice, identical twins)

Question 7

Allograft

Answer 7

tissue transferred between genetically different members of the same species (majority of transplants)

Question 8

Xenograft

Answer 8

tissue transferred between different species (baboon heart into a human)

Question 9

First set rejection

Answer 9

complete 12-14 days after the first graft; memory of the anti-graft response is generated

Question 10

Second set rejection

Answer 10

complete much faster, within 5-6 days; due to memory response generated after first set rejection

Question 11

What is the role of T cells in graft rejection?

Answer 11

T cells mediate graft rejection; primarily CD4+ T cells, but CD8+ also play a small role

Question 12

Explain what happens when splenic T cells from a first set rejection mouse (necrosis of tissue) are placed into a first skin graft mouse.

Answer 12

second set rejection induced

Question 13

Histo-compatible

Answer 13

tissues which are antigenically similar

Question 14

Histo-incompatible

Answer 14

tissues which are antigenically dissimilar

Question 15

Which loci are most likely to lead to rejection in transplantation scenarios?

Answer 15

MHC genes

Question 16

What percent chance do siblings have of MHC match?

Answer 16

25%

Question 17

What percent chance do parent to offspring transplants have of MHC match? Why?

Answer 17

50% due to always having one MHC haplotype in common

Question 18

Blood group and AG differences have what effect on transplants:

Answer 18

They produce the most intense graft rejections

Question 19

What compatibility is first checked in donor/recipient matching?

Answer 19

Blood group Ag found on RBCs, epithelial and endothelial cells

Question 20

What compatibility is checked second in donor/recipient matching?

Answer 20

MHC compatibility

Question 21

What would allow organ transplant between mismatched people?

Answer 21

Anti-rejection drugs

Question 22

List the four steps of the Sensitization Stage.

Answer 22

1. CD4+ and CD8+ T cells recognize alloantigens expressed on foreign graft cells
2. The T cells proliferate in response
3. Recognize the donor MHC molecules directly
4. Memory T cells generated

Question 23

List the three components of the Effector Stage.

Answer 23

1. Variety of mechanisms participate in effector stage of graft rejection
2. Heavy infiltration of recipient cells into graft tissue, similar to a DTH reaction
3. Production of antibodies against donor HLA molecules or endothelial Ag

Question 24

Acute Rejection is mediated by what type of response?

Answer 24

T cell response

Question 25

Which type of rejection occurs through mechanisms described for effector stage?

Answer 25

acute rejection

Question 26

Which type of rejection induces a massive infiltration of lymphocytes and macrophages, which leads to proliferation of T cells?

Answer 26

acute rejection

Question 27

One year kidney graft survival rates were what percentage in US in 2008?

Answer 27

97%

Question 28

Ten year kidney graft survival rates were what percentage in US in 2008?

Answer 28

60%

Question 29

Chronic rejection mechanisms include both humoral and cell-mediated recipient responses. T or F?

Answer 29

TRUE

Question 30

When does Chronic Rejection occur?

Answer 30

months or years after acute rejection reactions have subsided

Question 31

Immunosuppressive therapy can be either ___________ or _____________.

Answer 31

general or target specific

Question 32

Monoclonal antibodies achieve what desired effect?

Answer 32

immunosuppressive

Question 33

How might T cells be depleted prior to transplant? Why?

Answer 33

monoclonal antibodies to CD3; to suppress immune response and increase chances for graft acceptance

Question 34

Soluble CTLA-4 fusion proteins can induce what in T cells?

Answer 34

anergy

Question 35

Ideal Specific Immunosuppressive Therapy would be:

Answer 35

specific

Question 36

Some "immunologically privileged sites" are characterized by what components?

Answer 36

Allografts in such areas are less likely to experience rejection, while some organs are more amenable to clinical transplantation than others or easier to obtain surgically. In some cases, harvest cells may be transferred.

Question 37

What are some examples of "immunologically privileged sites"?

Answer 37

* Corneal transplants are highly successful (no lymphatics) * Cartilage, heart valves

Question 38

Is immune tolerance to allografts favored in certain instances?

Answer 38

Yes; Tregs -Presence and activities of TREG cells found in clinical operational tolerance cases -Situations where grafts are tolerated after complete removal of anti-rejection drugs -Involvement of TREG cells and their cytokines in prevention of rejection is an area of active research