transplantation

Question 1

allogenic tissue

Answer 1

unrelated individual of the same species donates tissue

Question 2

autograft

Answer 2

tissue from same individual moved from one site to another e.g burn wounds

Question 3

acute rejection

Answer 3

occurs after a allograft transplant without immunosuppression
10-14 days

Question 4

chronic rejection

Answer 4

with effective immunosuppression
over many years/decades
organ begins to be degraded
transplant wont last forever

Question 5

hyper acute rejection

Answer 5

xenograft rejected within hours

Question 6

alloantigen

Answer 6

antigen that differs between members of the same species

Question 7

MHC

Answer 7

major source of alloantigen
most polymorphic protein in human population
3 alleles are co dominant, so a cell can express up to 6 different MHCs - difficult to match

Question 8

ABO system

Answer 8

for blood grouping
determined by a single gene
encodes for a enzyme that modified cell surface antigen H into A or B or H (non functional)
human produce IgM antibodies against wrong antigen (e.g anti-B) due to cross reaction with bacteria antigen

Question 9

allele O

Answer 9

encodes a non functional enzyme
antigen is H
has both anti A and anti B antibodies, only accepts blood from another O

Question 10

Rejection is T cell mediated

Answer 10

nude mice lack a thymus and show no rejection

Question 11

minorhistocompatability proteins

Answer 11

male specific antigens encoded on Y chromosome

another source of alloantigen

Question 12

direct rejection

Answer 12

APC from graft tissue migrate out of graft into recipient lymph nodes
present donor antigen to recipient T cells
activated CD8 migrate to graft and attack as they recognise alloMHC directly

Question 13

indirect rejection

Answer 13

allogenic cells from the graft are processed by recipient APC and presented to CD4 and CD8 cells via MHC
CD8 cells cant attack graft directly, due to differing MHC on the graft
CD4 activate macrophages and B cell killing

Question 14

tissue damage

Answer 14

CD8 directly target cells with MHC
CD4 cells help T cells make anti-graft antibodies, destroy graft via ADCC and complement activation
CD4 cells from indirect recognition activate macrophages, ROS killing and phagocytosis

Question 15

T cells react with allo-MHC

Answer 15

tissue presents new MHC to T cells before they have undergone thymus education - they bind strongly as they have not undergone negative/positive selection

Question 16

improving outcomes of transplantaiton

Answer 16

target T cell activation:
belatecept blocks co stimulation 
sirolimus blocks MHC presentation 
cyclosporin blocks signalling pathwats 
target: depleting graft of APC 
Alemtuzimab

Question 17

xenograft

Answer 17

hyper acute rejection
a-Gal on pig cells is added by UDP-galactosyl transferase
pseudogene in humans - dont have enzyme, dont have a gal.
a-gal epitope is also on bacteria –> humans have high titre of anti a -gal antibodies
pig organ rapidly coated in antibody leading to complement mediated destruction.
v fast due to pre existing immunity.

Question 18

modifying pig organs

Answer 18

inactivate UDP-Galactosyl transferase so no a-gal on surface
express complement inactivating proteins on cells

Question 19

fetus

Answer 19

half allograft
no expression of MHCII at trophoblast - no T cell activation
only a special class of MHCI expressed, HLA-G which inhibits NK cells