Transplant (Leitenberg)

Question 1

Isograft or syngraf, or syngeneic transplant

Answer 1

donor and recipient genetically identical

Question 2

Allograft

Answer 2

within species

Question 3

First set rejection

Answer 3

7-14 days; causes development of memory T and B cells

Question 4

Second set rejection

Answer 4

accelerated rejection associated with characteristics of immunological memory

Question 5

What is transplant rejection mediated by?

Answer 5

HLA molecules

Question 6

Precursor frequency of reactive T cells specific for non-self HLAs is high because…

Answer 6

there is no negative selection for T cells that recognize non-self HLA

Question 7

Primary exposure to tissue with non-self MHC molecules results in…

Answer 7

rapid rejection

Question 8

Because of allorecognition, recipient T cells respond to…

Answer 8

foreign MHC ag on graft

Question 9

Direct allorecognition

Answer 9

-donor APC presents donor MHC/peptide to T cell

Question 10

In GVHD for bone marrow transplant, direct allorecognition occurs when… And what are CD4 and CD8 responding to?

Answer 10

donor T cells recognize MHC/peptide complexes expressed by recipient cells

• CD4 T cells respond to allogenic MHC II expressed by donor cells
• CD8 T cells respond to MHC I molecules

Question 11

Indirect Allorecognition and CD4 vs CD8

Answer 11

Recipient APC presents donor MHC peptides

• CD4: exogenous processing pathway
• CD8: cross-presentation pathway

Question 12

Isohemagglutinins

Answer 12

pre-formed ab against non-self ABO RBC markers

Question 13

Why must you blood type match for transfusions?

Answer 13

ABO glycoprotein markers on RBC

Question 14

What causes an immune response due to fetal-associated RBC ag?

Answer 14

-Rh antigens

Question 15

Platelets and granulocytes can trigger an immune response do to…

Answer 15

HLA allorecognition

Question 16

Autologous bone marrow transplant

Answer 16

• done in patients with high doses of chemo

- HSC are collected prior to chemo and re-infused after

Question 17

Allogenic bone marrow transplant is done in these pts

Answer 17

-done in pt w/ certain leukemias or bone marrow failure

Question 18

Hyperacute graft rejection time frame

Answer 18

minutes to hours

Question 19

Hyperacute graft rejection due to…

Answer 19

preformed ab against and activation of complement, indicating prior exposure (pregnancy, transfusions, transplants)

Question 20

What role does complement play in hyperacute graft rejection?

Answer 20

rapid ab-ag interaction w/ tissue ag –> leads to inflammation and damage to transplanted organ, organ vessels, ischemic tissue damage

Question 21

Acute graft rejection time frame

Answer 21

1-2 weeks (due to T cell priming, clonal expansion, differentiation)

Question 22

Acute graft rejection mechaim

Answer 22

T cell mediated response to non-self MHC alleles

Question 23

In acute graft rejection, transplanted tissue has predominant ____ infiltrate but may include some ____

Answer 23

T cell infiltrate; B cells and ab activated by T cells

Question 24

Acute graft rejection - controlled via

Answer 24

immunosuppressants

Question 25

Chronic graft rejection time

Answer 25

months to years after transplant

Question 26

Chronic graft rejection mediated by…

Answer 26

cell-mediated AND ab-mediated

Question 27

Chronic graft rejection causes

Answer 27

fibrosis/scarring of transplanted tissue and associated BV

Question 28

What is GVHD?

Answer 28

occurs when transplanted (donor) tissue contains foreign lymphocytes that are anti-recipient

Question 29

What kind of transplant is GVHD common in?

Answer 29

bone marrow transplants (recipient is often immunosuppressed due to chemo, etc.)

Question 30

What mediates GVHD?

Answer 30

allogenic HSC transplants contain mature and memory T cells that circulate in blood to secondary lymphoid organs and interact w/ dendritic cells

Question 31

Acute GVHD

Answer 31

activation of innate inflam response

Question 32

Chronic GVHD is analogous to ____ but is more___

Answer 32

chronic rejection in solid organ transplant; more systemic

Question 33

GVL: GVHD can be HELPFUL in ____ treatment because ______.

So would you do identical twin transplants in leukemic pt?

Answer 33

leukemia; donor T cells target recipient leukemic cells

no because it would eliminate GVL effect

Question 34

Serologic (cross-match test)

Answer 34

screens for preformed Ab in recipient to known HLA ag

• mix donor lymphocytes w/ recipient serum
• determine if recipient has preformed ab to donor HLA ag (if yes - contraindication)
• complement-mediated cytotoxicity or fluorescent labeling used to read interaction

Question 35

Mixed lymphocyte rxn (MLR) does this ____ and measures ___

Answer 35

-mix cells from recipient and donor to measure T cell proliferation and effector fn

Question 36

MLR one way rx

Answer 36

donor cells are irradiated so only recipient cells are able to proliferate (if recipient has alloreactive cells, then those will prolif)

Question 37

MLR two way rxn

Answer 37

no irradiation; proliferation of both donor and recipient measured

Question 38

DNA testing for HLA genes

Answer 38

PCR

Question 39

Name 4 drugs used as immunosuppressive therapy

Answer 39

• corticosteroids
• calcineurin phosphatase inhibitors
• anti-lymphocyte ab
• blocking anti-CD28 AB OR CTLA-4 Ig fusion protein

Question 40

What do corticosteroids do?

Answer 40

inhibits production of pro-inflamm cytokines/inhibits lymphocyte activation

Question 41

Calcineurin inhibitors

Answer 41

inhibits NFAT-dependent IL-2 gene transcription