Transplant Immunology

Question 1

autograft

Answer 1

graft from same host

Question 2

syngeneic graft

Answer 2

between two genetically identical individuals

Question 3

allograft

Answer 3

graft from donor of same species but genetically unlike

Question 4

xenograft

Answer 4

between individuals of different species

Question 5

graft vs host disease

Answer 5

when transplanting bone marrow, you run the risk of the immuno-competent cells in the graft attacking the host

Question 6

what antigens in the graft are most commonly the targets of immune mediated rejection and why

Answer 6

MHCs. there appears to be a large number (2-10%) of lymphocytes programmed against foriegn MHC complexes, and this causes rejection

the difficulty in finding donor “matches” is that there is so much MHC polymorphism

Question 7

minor H antigens

Answer 7

many genetic loci code for minor histocompatibility antigens, which can elicit smaller responses over time, but are poorly understood

Question 8

describe priviledged sites w/ respect to graft immunity

Answer 8

some locations are difficult for the immune system to see, and so rejection is not a concern in these places

1. anterior eye
2. brain
3. fetus

Question 9

what cells are most responsible for rejection?

Answer 9

T-cells, specifically CD4

Question 10

describe the difference between direct and indirect allorecognition

Answer 10

direct- TCR binds directly to foreign MHC and elicits
T cell activation regardless of the peptide on the MHC

indirect- TCR recognizes peptide derived from the foreign MHC that is cross presented by normal host APCs on normal host MHCs

Question 11

which MHC is more important when considering matches?

Answer 11

MHC2- b/c response is mediated by CD4

Question 12

hyperacute rejection

Answer 12

occurs w/in minutes or hours, mediated by preexising Ab in the donor. usually the donor has some prior exposure to these antigens via blood transfusions, transplants, etc.

ex. ABO blood types

Question 13

acute rejection

Answer 13

occurs within weeks or months- activated lymphocytes and monocytes. mostly mediated through CTLs, helpterT cells, and monocytes/macrophages

controlled by immunosuppressive drugs

Question 14

chronic rejection

Answer 14

gradual loss of function of graft over months to years. mechanism unclear.

IgM deposits seen in arterial walls and t-cell infiltration also seen

not controlled by immunosuppressive drugs

Question 15

how is host/donor compatability assessed beforehand?

Answer 15

HLA typing to identify MHC sequences

Question 16

bone marrow transplant

Answer 16

grafting of stem cells into host d/t cancers of blood or bone marrow. BMT recipients immune system destroyed prior to transplantation, but infection and GVH disease remain major threats

Question 17

what are the immunosuppresion techniques?

Answer 17

1. drugs
2. radiation
3. ablation
4. biologic agents (anti-CD20, anti-CD3)

Question 18

tolerance vs immunosuprression

Answer 18

tolerance is the depression of an immune response towards a specific antigen

immunosuppression is generalized suppression of the immune system

Question 19

cyclosporin A

Answer 19

fungal antibiotic that inhibit T cell proliferation and differentiation w/o significant B cell effects

Question 20

Tacrolimus

Answer 20

immunosuppressive drug for kidney, heart and liver transplants

Question 21

corticosteroids

Answer 21

inhibit T cell homing, decrease response of macrophages decrease monocyte count, inhibit IL2

in general- major affect on cell mediated immunity

Question 22

azathioprine

Answer 22

blocks nucleic acid synthesis and decreases cell replication. inhibits T and NK cells ADCC

Question 23

cyclophosphamide

Answer 23

prevents S phase in proliferating B cells. highly toxic, carcinogenic, etc

Question 24

irradition

Answer 24

causes lymphocyte death in a dose dependent manner

Question 25

anti-lymphocyte globulin

Answer 25

Abs that bind human lymphocytes and cause C related lysis. major effect is T cells

Question 26

monoclonal Abs

Answer 26

anti-CD3 (against all T cells), anti IL-2 (block t proliferation), etc