Transplantation

Question 1

What is an autologus graft (isograft)?

Answer 1

a graft transplanted from an individual to the same individual

Question 2

What is a syngeneic graft?

Answer 2

a transplant between two genetically identical individuals

Question 3

What is an allogeneic graft?

Answer 3

a transplant between two genetically dissimilar individuals of the same species

Question 4

What is a xenogeneic graft?

Answer 4

a transplant between members of two different species

Question 5

What are orthotopic grafts?

Answer 5

is a graft that is placed in its normal anatomic location

Question 6

What is a heterotropic graft?

Answer 6

A transplant placed in an anatomically different site

Question 7

What are first and second set rejections?

Answer 7

Basically first and second immune responses to grafts

Question 8

What are immunologicall privileged sites?

Answer 8

locations in the body where an allogeneic transplant can be placed without risk of rejection

Question 9

What are the three reasons for immunologically privileged sites?

Answer 9

1. Extracellular fluid does not leave through lymph system
2. TGF-beta released at these sites
3. Fas ligand expressed on cells to induce T cell apoptosis

Question 10

What is Sympathetic ophthalmia?

Answer 10

an eye disease that occurs when one eye is damaged by trauma and an autoimmune response to eye proteins ensues to threaten the undamaged eye

Question 11

Are transplants between identical twins ever rejected?

Answer 11

Rarely

Question 12

Are transplants between genetically dissimilar individuals rejected?

Answer 12

Almost always

Question 13

Can children give grafts to parents or vice versa?

Answer 13

No

Question 14

What are the molecules that are being rejected in grafts?

Answer 14

MHC class I and II

Question 15

How fast do hyperacute rejections take place? What is the mechanism behind this?

Answer 15

within minutes, due to complement being activated by memory antibodies, and causing thrombosis

Question 16

What are examples of hyperacute rejections?

Answer 16

Incorrect blood transfusions

Question 17

How long do acute rejections take to develop?

Answer 17

1 month

Question 18

What are the two mechanisms behind acute rejection?

Answer 18

1. Acute humoral rejection d/t antibody and complement mediated lysis of graft tissue
2. Acute cellular rejection caused by cell mediated lysis by CTLs

Question 19

What is the treatment for acute rejections?

Answer 19

increased immunosuppression such as high dose steroid therapy or anti-T cell antibodies

Question 20

How long does chronic rejection take place?

Answer 20

Over months / years

Question 21

What is the pathogenesis of chronic rejection?

Answer 21

Not totally known, but there are fibrotic changes in the graft

Question 22

What is the pathogenesis of graft rejection?

Answer 22

Host APCs present MHC proteins of graft as foreign molecules via the class II pathway.

Question 23

How are CTLs activated against grafts, if the grafts do not have self MHC cells?

Answer 23

T cells recognize self peptide with foreign MHC. Basically fools T cells.

Question 24

True or false: either dendritic cells from the donor (direct) or recipient (indirect) can be used to activate graft rejection

Answer 24

True

Question 25

What are the three means through which grafts are destroyed in the acute rejection?

Answer 25

1. CD8+ CTLs lyse graft cells 2. CD4+ T cells recruit macrophages 3. Alloantibodies activate complement

Question 26

What are minor histocompatability antigens?

Answer 26

none MHC factors that may generate an immune response

Question 27

What happens after dendritic cells present MHC molecules to host T cells?

Answer 27

CD4+ Th cells prodive IL-2 and IFN-gamma to activate CD8 T cells to produce CTLs

Question 28

What are the three strategies used to reduce graft rejection?

Answer 28

1. Select compatible graft 2. Immunosuppression 3. Deplete passenger leukocytes from graft

Question 29

What is the effect of corticosteroids?

Answer 29

Lyse immature thymocytes, block release of cytokines from macrophages, inhibit leukocyte migration

Question 30

What is the mech of action of cyclosporine?

Answer 30

Inhibits IL-2 and IFN-gamma

Question 31

What is the major drawbacks of cyclosporin?

Answer 31

It's nephrotoxic

Question 32

What is anti-lymphocyte globulin and how does it work?

Answer 32

Horse immunogloin against human lymphocytes. Kills all human lymphocytes to prolong graft

Question 33

What is graft-versus-host disease?

Answer 33

When bone marrow cells attack the rest of the body

Question 34

What causes acute GVHD?

Answer 34

mature T cells responding to host alloantigens.

Question 35

How can you remove the T cells from bone marrow transplants?

Answer 35

in vitro treatment with anti-CD3 monoclonal antibodies (along with Complement)

Question 36

Why would you want to have some variation in HLA type for leukemia pts?

Answer 36

To kill CA

Question 37

What is the chemical given to bone marrow donors to increase stem cells/ spill into blood?

Answer 37

Granulocyte colony-stimulating factor (G-CSF)

Question 38

What are the three major mechanisms that prevent a mother's body from killing a fetus?

Answer 38

1. Trophoblasts cells do not express paternal MHC proteins 2. Trophoblast cells secrete TGF-beta 3. Y is broken down at fetal-materal interface, diabling T lymphocytes

Question 39

Why does the liver carry an increased risk of GVHD?

Answer 39

Has a lot of donor lymphocytes

Question 40

What is the function of HLA-G expressed by fetal trophoblast cells?

Answer 40

Inhibits NK cells

Question 41

What are the three steps involved in the activation of CTLs against a graft?

Answer 41

1. Dendritic cells present antigen to CD4+ T cells 2. CD4+ T cells release IL-2 and IFN-gamma to stimulate CTLs. 3. CTLs kill via CD8+/MHC I graft cells

Question 42

What is the difference between direct and indirect stimulation of T cells in graft rejection?

Answer 42

Direct = using donor's dendritic cells Indirect = using recipients dendritic cells

Question 43

What is the mechanism of action for cyclosporine?

Answer 43

Inhibits the expression of IL-2 and IFN-gamma, preventing CTL formation.

Question 44

Cyclosporine is not good at inhibiting secondary immune responses. What is the effect of this?

Answer 44

Pts retains ability to fight off infections that he/she has already been exposed to.