L: 21 Transplantation 1 and 2

Question 1

Autograft

Answer 1

grafts exchanged from one part to another of the same individual

Question 2

isograft

Answer 2

grafts exchanged between different individuals of identical genetics (identical twins)

Question 3

Allografts

Answer 3

Grafts exchanged between nonidentical members of same species

Question 4

Xenografts

Answer 4

grafts exchanged between members of different species

Question 5

Problems with Xenografts

Answer 5

particularly susceptible to rapid attack by natural occurring Abs and complement. Increased chance of success if human genes are inserted into genome

Question 6

Explain Direct Allorecognition

Answer 6

T cell recognizes unprocessed allogenic MHC molecules on graft APCs

Question 7

Explain Indirect Allorecognition

Answer 7

T cell recognizes processed peptide of allogenic MHC molecule bound to self MHC molecule on host APC

Question 8

In the direct pathway the T cell receptor on recipient T cells directly recognize?

Answer 8

The donor MHC molecules

Question 9

In the indirect response the recipient T cell recognize donor MHC molecules that have been processed by?

Answer 9

Recipient APCs

Question 10

What pathway is most important during chronic rejection

Answer 10

Indirect Pathway

Question 11

Phases of Host vs. Graft

Answer 11

Hyperacute- immediate
Acute- week-months
Chronic- months-years
*In all cases the host has immune response to graft
**Most important thing to remember is onset time frame.

Question 12

Graft vs. host

Answer 12

Onset varies

Donor cells proliferate and attack the recipient tissue T cells in graft

Question 13

Hyperacute graft rejection

Answer 13

Caused by pre-existing ABs that are reactive to donor tissue AND HAPPENS WITHIN MINUTES. Abs bind to endothelial cells which activate Classical pathway of complement activation—-leads to cell death
(ABO blood group incompatibility)
ABs b

Question 14

Acute graft rejection

Answer 14

Occurs in days to weeks and is initiated by alloreactive T cells. Donor DC’s migrate to the lymph nodes draining the organ and stimulate a primary recipient response

Question 15

Chronic Graft Rejection

Answer 15

Occurs in months to years occurs d/t occlusion of blood vessels and subsequent ischemia of the organs.
MAIN PATHOGENIC MECHANISM is the indirect pathway.
**Chronic rejection does not respond to immunosuppressive therapy

Question 16

Non-immunologic factors in chronic graft rejection

Answer 16

• Ischemia-reperfusion
• Recurrence of disease
• Effects of nephrotoxic drugs

Question 17

What 4 variable determine transplant outcome

Answer 17

1. Condition of the allograft
2. Donor-host antigenic disparity
3. Strength of host anti-donor response
4. Immunosuppressive regimen

Question 18

During the Donor - Recipient work-up what is established first?

Answer 18

ABO blood group compatibility

Question 19

ABO is a barrier to transplantation of what?

Answer 19

Solid organs

• *Not a barrier to corneal, heart valve, and bone/tendon graft transplantations
• *ABO incompatibility is not important to stem cel, transplant

Question 20

Group A Abs and Ags

Answer 20

ABs- anti-B

Ag- A

Question 21

Group B Abs and Ags

Answer 21

ABs- anti A

Ag - B

Question 22

Group AB Abs and Ags

Answer 22

Abs - None

Ags - A/B

Question 23

Group O Abs and Ags

Answer 23

Abs Anti- A/B

Ags - none

Question 24

What is the universal donor and recipient?

Answer 24

Universal donor- O

Universal recipient- AB

Question 25

The success of transplantation is dependent on matching of what Ags?

Answer 25

``` MCH Ags Which are encoded by MHC class I and class II ```

Question 26

HLA compatibility between donor and recipient is required due to?

Answer 26

Extreme polymorphism of HLA

Question 27

In humans, the MCH is termed?

Answer 27

Human leukocyte antigen complex (HLA complex)

Question 28

Where is HLA antisera mostly obtained

Answer 28

Multiparous women or planned immunization of volunteers

Question 29

What is cross-matching used for?

Answer 29

used to test the recipient serum for preformed Abs against donor HLAss

Question 30

Why is cross-matching needed?

Answer 30

To prevent hyperactive Ab-dependent rejection of graft

Question 31

What test is used to screen for preformed Abs?

Answer 31

Microcytotoxicity test | Recipient's serum is mixed with donors, if no cell damage, then potential donor identified. No stain=no antibodies

Question 32

What test may be used for class II HLA typing?

Answer 32

Mixed lymphocyte reaction (MLR). If class II antigens the same, no proliferation will occur. Used to determine if donor cells stimulate proliferation of recipients lymphocytes*****Ags need to be the same for transplantation****Stained=same

Question 33

What is Host vs Graft response?

Answer 33

Host Immune system attacks the donor tissue

Question 34

What type of immune response occurs with Host vs Graft

Answer 34

Adaptive immune response | Rxn is much more vigorous and strong vs rxn seen against pathogen

Question 35

Effector mechanism of graft rejection- Humoral

Answer 35

Th2 (IL-4, IL-5, and IL-10)

Question 36

Effector mechanism of graft rejection-Cellular

Answer 36

Th2 (IL-2, IFN-gamma)

Question 37

Graft-Versus-Host Disease

Answer 37

occurs when transplants are small bowel, lung, or liver because of natural higher number of T cells ***Occurs in immunocompromised recipients

Question 38

A new era of transplantation and immunosuppression opened up with the discovery of what drug?

Answer 38

Cyclosporine A (CsA)

Question 39

Steroid mechanism

Answer 39

Anti-inflammatory

Question 40

Cyclosporin A mechanism

Answer 40

Inhibits IL-2 gene transcription

Question 41

Anti-CD3 monoclonal antibody mechanism (OKT 3)

Answer 41

T-cell activation, opsonization and depletion

Question 42

Tacrolimus mechanism

Answer 42

Inhibits IL-2 gene transcription

Question 43

Anti-CD25 monoclonal antibodies (IL-2R alpha chain) Sirolimus

Answer 43

Inhibits IL-2 function Inhibits cytokine-mediated signal

Question 44

What tests are done prior to transplant

Answer 44

1. ABO blood grouping 2. Tissue typing (identify HLAs) 3. Cross-matching (check for pre-formed antibodies) 4. Mixed lymphocyte reaction (check to see if donor stimulates recipient lymphocytes)

Question 45

What does the Ag-Ab complex activate?

Answer 45

Classical complement cascade which results in lymphocyte lysis