Introduction to Transplantation Immunology

Question 1

syngenic

Answer 1

transplantation between genetically identical individuals

Question 2

allogenic

Answer 2

transplantation between genetically dissimilar individuals of same species

Question 3

xenogeneic

Answer 3

transplantation between different species

Question 4

minor histocompatability antigen

Answer 4

normal proteins on cell surface that are polymorphic in nature

Question 5

evidence that graft rejection is caused by lymphocytes

Answer 5

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

rejection occurs more rapidly second time
-role of memory

rejection of distinct graft 7-14 days
-specific response

Question 6

evidence for role of MHC in grafts?

Answer 6

transplant between genetically identical individuals not rejected

transplant between genetically non-identical individuals is rejected

Question 7

direct alloantigen recognition

Answer 7

allogenic APC presents allogenic MHC

**activates CTLs

Question 8

indirect alloantigen recognition

Answer 8

self APCs present allogenic MHC proteins

**activates CD4 T cells

can also have allo-antibodies produced by alloreactive B cells in indirect pathway

Question 9

high probability that T cells recognize allogenic MHC due to?

Answer 9

T cells are selected to have low affinity
-allogenic MHC not negatively selected - may be high affinity

self MHC restricted T cells are able to recognize foreign MHC

allogenic MHC with bound peptide may mimic self MHC and peptide complex

Question 10

what trigger costimulation expression in transplantation patients?

Answer 10

fuck

Question 11

hyperacute rejections

Answer 11

within minutes
thrombosis of graft vessels followed by ischemic necrosis

host circulating antibodies are specific for antigens on graft endothelial cells

complement activation leads to endothelial cell injury

thrombosis and vascular occlusion occur

Question 12

how to prevent hyperacute?

Answer 12

cross-match with antibodies

Question 13

acute rejection

Answer 13

within days to weeks
rejection timulated by alloantigens in the graft

mechanism:

• acute cellular rejection (CTL and CD4)
• microvascular endothelialitis
• acute antibody-mediated rejection characterized by transmural necrosis of graft vessel walls

Question 14

acute rejection treatable?

Answer 14

YES!

Question 15

chronic rejection

Answer 15

months to years after transplant

T cells and antibodies against alloantigens

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

Question 16

immunosuppressive drugs for T cells used in transplantation

Answer 16

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

Question 17

rapamycin

Answer 17

targets mTORC1

Question 18

azathioprine

Answer 18

no proliferation

Question 19

cyclosporine

Answer 19

inhibits calcineurin

important one**

Question 20

CTLA4-Ig

Answer 20

inhibits CD28 B7 interaction

Question 21

thymoglobulin, OKT3

Answer 21

no TCR activation

Question 22

side effects of immunosuppression

Answer 22

malignancy
infections
drug toxicity

Question 23

non T cell targets for immunosuppression

Answer 23

alloantibodies and alloreactive B cells

anti-inflammatory drugs

inhibitors of leukocyte migration

Question 24

strategy to minimize alloantigenic effects?

Answer 24

cross-matching

-testing for preformed antibodies against donor HLA

Question 25

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

Answer 25

normal gut flora has similar epitopes

Question 26

lewis antigen

Answer 26

fucosylation at additional terminal sites of blood group antigen

Question 27

rhesus antigen

Answer 27

Rh

15% of population has deletion or other alteration in RHd allele

Question 28

Can ABO-incompatible transplant be done?

Answer 28

???/

Question 29

GVHD

Answer 29

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
chronic greater than 100 days

treated by immunosuppression

Question 30

hematopoietic stem cell transplant

Answer 30

transfer allogenic pluripotent hematopoietic stem cells

patient treated with radiation to deplete bone marrow