Transplant immunology

Question 1

What type of response is responsible for transplant reactions?

Answer 1

adaptive immune response

Question 2

What three major advances have been made thanks to transplantation?

Answer 2

1. technical skills of surgeons
2. transplantation networks that are HLA-typed so that the best matches can be made
3. the availability of immunosuppressive drugs (ex. CYCLOSPORIN A, FRK-506 to inhibit T cell activation or blockade of IL-2 receptor signal with RAPAMYCIN)

Question 3

What are the disadvantages of transplantation?

Answer 3

1. availability of healthy donor organs
2. the disease that killed the patient may destroy the graft
3. immunosuppressive drugs increase the risk of cancer and infection

Question 4

Define autograft

Answer 4

a transplant from one site to another on the same person

Question 5

Define isograft

Answer 5

a transplant between genetically identical individuals (twins). aka syngeneic graft

Question 6

Define allograft

Answer 6

a transpplant between two genetically different individuals

Question 7

Define xenograft

Answer 7

a transplant between individuals of different species

Question 8

In what case are allografts not rejected?

Answer 8

when there are only MHC antigens, like those encoded by the male Y chromosome that are not expressed in females

Question 9

Which cells mediate graft rejection?

Answer 9

T cells

Question 10

What is a second-set rejection?

Answer 10

an MHC-specific second response where the rejection occurs more quickly than the first exposure

Question 11

What happens when a graft is rejected?

Answer 11

When there is revascularization, immune cells infiltrate the area and there is cell necrosis in the graft

Question 12

What are the two functions of MHC molecules?

Answer 12

bind peptide fragments of antigen derived from pathogens to class I or class II MHC to display on APC
genetic gene complex that influences the ability of an organism to accept or reject transplanted tissue from another member of the same species

Question 13

Define MHC haplotype

Answer 13

the particular combination of MHC alleles found on a single chromosome

Question 14

What is the mixed lymphocyte reaction?

Answer 14

T cells from one individual are mixed with lymphocytes from a second individual to test whether or not the T cells divide and proliferate.
This method is used to detect different levels of histocompatibility

Question 15

Which cells are essential for MLR (mixed lymphocyte reaction)?

Answer 15

CD4+ T cells ad macrophages

Question 16

Give an example of acute rejection

Answer 16

kidney graft rejection
donor dendritic cells get into the blood vessels and activate recipient T cells, which travel to the graft and elicit a response

Question 17

Which foreign antigens are present in a fetus?

Answer 17

MHC antigens from father, foreign minor antigens (Y chromosome, RBS antigens, etc)

Question 18

Describe the timeline of a first set skin allograft rejection

Answer 18

1. graft is vascularized in 3-7 days
2. lymphocytes, monocytes, and neutrophils infiltrate and cause inflammation
3. decreasing vascularization at 7-10 days
4. visible necrosis at day 10
5. rejection at 12-14 days post-transplant

Question 19

When does rejection occur in a second set rejection of the same allograft?

Answer 19

after 5-6 days

Question 20

What is a nude mouse?

Answer 20

lacks a thymus gland, also happens to not have any fur

Question 21

What can nude mice be used for?

Answer 21

will not reject human or other species tissues, so tissues can be grown in them and harvested

Question 22

What does irradiation do?

Answer 22

kills the fastest growing cells, ie. immune cells

Question 23

name two experiments that prove that T cells are responsible for graft rejection?

Answer 23

irradiate mice and inject some with serum and some with lymphocytes
OR
inject syngeneic T cells into nude mice and see if they react

Question 24

Which T cells are specifically responsible for graft rejection?

Answer 24

both CD4+ and CD8+, but alone, CD4+ has a greater impact

Question 25

On which cells are ABO antigens found?

Answer 25

erythrocytes, endothelial cells, and epithelial cells

Question 26

Define microcytotoxicity assay

Answer 26

antibodies for the different class I and class II molecules (plus complement) are reacted individually with the donor and recipient WBC in media that contain trypan blue (a vital dye that does not enter and stain live cells)

Question 27

What is the mixed lymphocyte reaction?

Answer 27

1. take the WBC of potential donor and irradiate the cells so they can't proliferate 2. mix them with functional recipient cells 3. incubate for 2-3 days then add 3H-thymidine and measure its incorporation into recipient cells if the cells do not have the same MHC class II, the recipient cells will proliferate and will take up 3H-thymidine

Question 28

What happens if the MHC II loci between a donor and recipient is different?

Answer 28

there is lymphocyte proliferation

Question 29

What happens if the MHC I loci between a donor and recipient is different?

Answer 29

there is killing of target cells

Question 30

If the MHC I and II genes match, can there still be rejection?

Answer 30

yes, due to minor histocompatibility genes of the donor. this creates a weak response and takes a very long time

Question 31

What are the phases of graft rejection?

Answer 31

1. sensitization: alloantigens of the donor the CD4+ and CD8+ T cells of the recipient 2. donor MHC class I molecules present endogenous antigens to the recipient's CD8+ T cells 3. donor class II molecules present alloantigens to the recipient's CD4+ T cells recipient APC can also take donor antigens and present them to CD4+ T cells

Question 32

Is T cell response higher in graft rejection or a regular infection?

Answer 32

in graft rejection

Question 33

Which cells mediate the effector stage of graft rejection?

Answer 33

delayed-type hypersensitivity (DTH) and cytotoxic T lymphocytes (CTL). Ab + complement and Ab-dependent cytotoxicity play a smaller role

Question 34

What role do cytokines play in graft rejection?

Answer 34

1. CTLs and macrophages migrate to the graft, CD4+ T cells produce large amounts of IFN-gamma, IL-2 and TNF-beta, promoting macrophage infiltration 2. IL-2 stimulates proliferation of lymphocytes 3. IFN-gamma induces and maintains DTH & activates macrophages to be more destructive 4. TNF-alpha & -beta with IFN-alpha, -beta, and -gamma upregulate class I molecules & IFN-gamma upregulates class II IFN-beta can be toxic to cells

Question 35

What is a hyperacute reaction?

Answer 35

occurs within the first 24h. If the recipient has pre-existing antibodies, the complement cascades will initiate with infiltration of neutrophils. causes an intense inflammatory response and clots to form, blocking blood flow and inhibiting re-vascularization

Question 36

What could happen if a recipient has had repeated blood transfusions?

Answer 36

WBC in the transfusions could stimulate Abs against MHC antigens, which could react to the graft

Question 37

What could happen if a woman has multiple pregnancies?

Answer 37

she can become sensitized to the father's MHC antigens and develop antibodies to them

Question 38

Define chronic rejection

Answer 38

occurs months or years after transplant & involves Abs and DTH & CTLs. only a new transplant can help the situation

Question 39

immunosuppressive therapies are necessary for ALL allografts. What are the disadvantages?

Answer 39

increases the risk of caner, hypertension, and infections