2-Transplantation

Question 1

autologous graft

Answer 1

from indiv to same indiv
-no chance of rejection

i.e. bone marrow or blood harvested and saved for future like cancer treatment

Question 2

syngeneic graft

Answer 2

or syngraft

b/t two genetically identical indivs like twins
-not expect rejection (low/none)

Question 3

allogeneic graft

Answer 3

b/t genetically dissimilar indivs
-most common form of transplant
-anticipate some episode of rejection

Question 4

xenogeneic graft

Answer 4

or xenograft

b/t members of two diff species like pigs bc organ size similar
-usually to inc longevity for human transplant later

Question 5

orthotopic vs heterotopic transplants

Answer 5

ortho = normal anatomic location

hetero = placed in anatomically diff site
i.e. heart bypass surgery with saphenous V > coronary A

Question 6

first set rejection

Answer 6

7-10 days after graft transplanted b/t non identical indivs

aka primary immune resp

Question 7

second set rejection

Answer 7

graft transplanted AGAIN then rejected in 2-3 days (faster than first set rejection)

aka secondary immune resp

Question 8

immunologically privileged sites

Answer 8

where allogenic transplant placed w/o risk of rejection
@anterior chamber eye, cornea, testes, brain

via TGF-beta and Fas ligand

Question 9

sympathetic ophthalmia

immuno privileged sites

Answer 9

one eye damaged by trauma and autoimmune resp to eye proteins threatens the undamaged eye
-removal of damaged eye and immunosuppressive therapy

Question 10

transplantation laws

Answer 10

1. transplants b/t identical twins never rejected
2. b/t genetically dissimilar indivs almost always rejected
3. grafts from children rejected by either parent bc express antigens seen as foreign

Question 11

why foreign?

Answer 11

class I and II MHC proteins foreign bc
1. expression is polymorphic- specific set of MHC
2. edu of thymocytes so other MHC foreign
3. prob that two random indivs express same MHC very small

Question 12

hyperacute rejection

Answer 12

within MINUTES of attaching graft to recipients blood supply
-mediated by pre-existing antibodies > complement
-untreatable but uncommon bc tech now can detect antibodies pre surgery

Question 13

acute rejection

Answer 13

within ONE MONTH

two types
1. humoral- antibody + complement mediated lysis of graft = necrosis of blood vessel
2. cellular-cell mediated lysis by CTLs, NK, or macros

Question 14

chronic rejection

Answer 14

MONTHS OR YEARS after

unknown mech but fibrosis and collagen + accelerated atherosclerosis
-unresponsive to immunosuppression

Question 15

alloreactivity

indirect

Answer 15

indirect alloantigen presentation = recipient APC + allogenic/foreign MHC to activate T cells

but CTLs not lyse foreign class I bearing bc can’t recognize non self class I MHC

Question 16

alloreactivity

direct

Answer 16

donor/allogenic MHC + donor APC

polymorphic amino acids of foreign MHC mimick conformation of both self MHC and foreign peptide so TCR can recognize

Question 17

alloreactivity activation

Answer 17

1. direct donor dendritic cells and indirect recipient dendritic cells present alloantigens to stim CD4
2. alloreactive CD4 T helper cells syn IL-2 and IFN-gamma for CD8 to syn CTLs to lyse graft cells
3. alloreactive B cells prod antigraft antibodies

Question 18

strategies to prevent rejection

Answer 18

1. select most compatible graft to reduce graft immunogenicity
2. immunosuppression
3. deplete passenger leukocytes from graft, get rid of donor APC cells/dendritic cells

Question 19

how to select most compatible

Answer 19

class I/II MHC proteins by serological and molecular techniques
-siblings may have some rejection from minor histocompatibility antigen diffs

Question 20

immunosuppression strategy

Answer 20

1. corticosteroids
2. cyclosporine- best drug to inhibit cell mediated immunity but not as effective at inhibiting 2 immune resp compared to 1
3. anti-lymphocyte globulin- common to get serum sickness (type III hypersensitivity)

Question 21

graft vs host disease

Answer 21

1. acute GVHD- quickly following marrow transplant, epi cells necrosis of skin/liver/GI
2. chronic GVHD- fibrosis in organs

anti-CD3 antibodies + complement = dec incidence GVHD but dec chance of engraftment

Question 22

graft vs leukemia effect

Answer 22

help prevent cancer bc GVHD rxn removes minimal residual disease/tumor cells but fine line

Question 23

bone marrow donation

Answer 23

siblings best for HLA match
-relatively safe from pelvis

also do leukapheresis + sorting by flow cytometry for less invasive

Question 24

fetal immunology

Answer 24

to prevent immune resp vs fetal antigens
-trophoblasts not xpr paternal MHC
-may secrete inhibitory cytokines
-tryptophan is broken down at fetal maternal interface so T lymphs react poorly to antigen