Intro to transplantation

Question 1

Question

Answer 1

Answer

Question 2

syngenic

Answer 2

transplantation between genetically identical individuals

Question 3

allogenic

Answer 3

transplantation between genetically dissimilar individuals of same species

Question 4

xenogeneic

Answer 4

transplantation between different species

Question 5

minor histocompatability antigen

Answer 5

normal proteins on cell surface that are polymorphic in nature

Question 6

evidence that graft rejection is caused by lymphocytes

Answer 6

occurs 7-14 days after first transplant-role of lymphocytes

rejection occurs more rapidly second time-role of memory (3-7 days later)

rejection of distinct graft 7-14 days-specific response (the ability to reject a graft rapidly can be transferred to a naive individual by lymphocytes from a sensitized individual)

Question 7

evidence for role of MHC in grafts?

Answer 7

transplant between genetically identical individuals not rejected

transplant between genetically non-identical individuals is rejected

EXCEPT–> graft from inbred parental strain (MHCb) is not rejected by MHCa/b
BUT graft from MHCa/b is rejected by a mouse with strain MHCa

Question 8

direct alloantigen recognition

Answer 8

allogenic APC presents allogenic MHC**activates CTLs

Question 9

indirect alloantigen recognition

Answer 9

self APCs present allogenic MHC proteins**activates CD4 T cellscan also have allo-antibodies produced by alloreactive B cells in indirect pathway

Question 10

high probability that T cells recognize allogenic MHC due to?

Answer 10

T cells are selected to have low affinity -allogenic MHC not negatively selected - may be high affinityself MHC restricted T cells are able to recognize foreign MHCallogenic MHC with bound peptide may mimic self MHC and peptide complex

Question 11

what triggers costimulation expression in transplantation patients?

Answer 11

induces inflammation, taking a tissue and placing into recipient
Treatments aimed at blocking costimulation for less inflammation?

Question 12

hyperacute rejections

Answer 12

within minutes

thrombosis of graft vessels followed by ischemic necrosis

host circulating antibodies are specific for antigens on graft endothelial cells (IgG usually, and are present prior to transplantation due to previous transplantations, blood transfusions or multiple pregnancies)

complement activation leads to endothelial cell injury, thrombosis and vascular occlusion occur

Question 13

how to prevent hyperacute?

Answer 13

cross-match with antibodies

every donor and recipient are matched for blood type and potential recipients are tested for antibodies against the cells of the prospective donor

Question 14

acute rejection

Answer 14

within days to weeks

rejection stimulated by alloantigens in the graft

mechanism:-acute cellular rejection (CTL and CD4)-microvascular endothelialitis (inflammation within the endothelial cells)

acute antibody-mediated rejection characterized by transmural necrosis of graft vessel walls

Question 15

acute rejection treatable?

Answer 15

YES!

Question 16

chronic rejection

Answer 16

months to years after transplant
refractory**

T cells and antibodies against alloantigens

immune response results in fibrosis of graft tissue and gradual narrowing of vessels-

graft arteriosclerosis

Question 17

immunosuppressive drugs for T cells used in transplantation

Answer 17

azathioprine, rapamycin, cyclosporine, anti-IL-2R, anti-TCR (OKT3, thymoglobulin)

Question 18

rapamycin

Answer 18

targets mTORC1

Interfers with signaling from
IL-2 receptor

Question 19

azathioprine

Answer 19

no proliferation

Question 20

cyclosporine

Answer 20

Interfers with signal transduction from TCR

Question 21

CTLA4-Ig

Answer 21

inhibits CD28 B7 interaction

Question 22

thymoglobulin, OKT3

Answer 22

no TCR activation

Question 23

side effects of immunosuppression

Answer 23

malignancy- T cells have the ability to survey the body and eliminate tumor cells (transformed cells) that have formed, so if we suppress T cells then have resulting malignancy in some cases

infections

drug toxicity= side effects of immunosuppressive drugs

Question 24

non T cell targets for immunosuppression

Answer 24

alloantibodies and alloreactive B cells

anti-inflammatory drugs

inhibitors of leukocyte migration

Question 25

strategy to minimize alloantigenic effects?

Answer 25

cross-matching-testing for preformed antibodies against donor HLA

Question 26

why do people develop anti-A and anti-B antibodies for blood group antigens?

Answer 26

normal gut flora has similar epitopes

Question 27

lewis antigen

Answer 27

fucosylation at additional terminal sites of blood group antigen

Question 28

rhesus antigen

Answer 28

Rh15% of population has deletion or other alteration in RHd allele

Question 29

Can ABO-incompatible transplant be done?

Answer 29

yes, more likely to be successful in children

mechanisms that can take up the antibodies against antigen A and B or reduce B cell population that is producing antibodies

Question 30

GVHD

Answer 30

graft versus host disease

reaction of mature grafted T cells to alloantigens of the host

usually against minor histocompatability antigens

acute less than 100 days (epithelial cell death in the skin, liver and GI tract)

chronic greater than 100 days (fibrosis and atrophy without acute cell death)

treated by immunosuppression

Question 31

hematopoietic stem cell transplant

Answer 31

transfer allogenic pluripotent hematopoietic stem cells from bone marrow to a recipient

patient treated with radiation beforehand to deplete bone marrow to make room for the transferred cells

can cause GVHD

Question 32

example of immunologic cross reaction

Answer 32

allogeneic MHC molecules containing peptides derived from the allogeneic cells of the donor may look like self MHC molecules plus bound foreign particles

Question 33

how do you distinguish between acute and chronic rejection in transplantation? and what is the next step in treatment for both?

Answer 33

Get biopsy of tissue
acute–> endotheliallitis
chronic –> fibrosis

if it is acute–> back of immunosuppressive drugs

if chronic–> increase immunosuppressive agents

Question 34

how is GVHD different from acute rejection?

Answer 34

in acute rejection the recipient is attacking the donor graft tissue

whereas in GVHD donor is affecting recipient

Question 35

why are the skin and intestinal tract targeted in acute GVHD?

Answer 35

T cells recognize MHC/antigen

Skin in intestinal tract may have more MHC on their suface and makes them targets

Inflammation can also propagate GVHD b/c it upregulates MHC expression

Question 36

methods employed to maintain graft tolerance

Answer 36

immunosuppressive agents

reduction of immunogenicity

tolerance induciton- (co-stimulatory blockage, hematopoietic chimerism, transfer of T-regs)