transplantation

Question 1

most relevant protein variations in clinical transplantation

Answer 1

ABO blood group, HLA coded on chromosome 6 by MHC (most significant)

Question 2

location of A and B proteins with carbohydrate chains in ABO blood group

Answer 2

on red blood cells, in endothelial lining of blood vessels in transplanted organ

Question 3

what antibodies are naturally occuring concerning ABO blood group

Answer 3

anti-AB antibodies

Question 4

group A: antibodies in plasma and antigens in red blood cell

Answer 4

anti-B antibodies in plasma, A antigen in red blood cell

Question 5

group B: antibodies in plasma and antigens in red blood cell

Answer 5

anti-A antibodies in plasma, B antigen in red blood cell

Question 6

group AB: antibodies in plasma and antigens in red blood cell

Answer 6

no antibodies in plasma, A and B antigens in red blood cell

Question 7

group O: antibodies in plasma and antigens in red blood cell

Answer 7

anti-A and anti-B antibodies in plasma, no antigens in red blood cell

Question 8

how to overcome ABO-incompatible transplantation due to antibody-mediated rejection

Answer 8

remove antibodies in recipient by plasma exchange (good outcomes even if antibody comes back); used in kidney, heart and liver

Question 9

what are HLA

Answer 9

cell surface antigens with highly variable portion (polymorphic with lots of alleles for each locus; each individual has most often 2 types for each HLA molecule)

Question 10

why are HLA highly variable

Answer 10

for defence against infections and neoplasia, as proteins presented to immune cells in context of HLA

Question 11

what to T cells see with regard to peptide and HLA

Answer 11

peptide in context of HLA framework

Question 12

describe presentation and response of donor graft antigens in mis-matched HLA transplant

Answer 12

recipient HLA molecule on APC, with donor HLA fragment (transplanted organ) associated with it; recognised by T cells to activate immune system

Question 13

class I of HLA, and cells expressed on

Answer 13

A,B,C; expressed on all cells

Question 14

class II of HLA, and cells expressed on

Answer 14

DR, DQ, DP; expressed on APC and upregulated on other cells

Question 15

MHC class I molecule

Answer 15

a1, a2, a3, B2

Question 16

MHC class II molecule

Answer 16

a1, a2, B1, B2

Question 17

human MHC class I isotypes

Answer 17

HLA-: A/B/C/E/F/G

Question 18

human MHC class II isotypes

Answer 18

HLA-:DM/DO/DP/DQ/DR

Question 19

most important HLA isotypes which are associated with transplantation due to being highly polymorphic

Answer 19

HLA: -A,-B,-DR (6 possible mismatches between recipient and donor as 2 HLA alleles (1 from each parent) per isotype)

Question 20

what does minimising HLA differences between donor and recipient achieve

Answer 20

improved transplant outcome

Question 21

sibling to sibling % chance of mismatch

Answer 21

25% chance 6 mismatches, 50% chance 3 mismatches, 25% chance 0 mismatches

Question 22

what does exposure to foreign HLA molecules in transplantation result in, and what can this cause

Answer 22

immune reaction to foreign epitopes, causing immune graft damage and failure (rejection - most common cause of graft failure)

Question 23

how is rejection diagnosed

Answer 23

histological examination of graft biopsy

Question 24

how to treat organ rejection

Answer 24

immunosuppresive drugs

Question 25

what cells mediate hyperacute and acute rejection

Answer 25

T cells

Question 26

what mediates chronic rejection

Answer 26

antibodies

Question 27

T cell mediated rejection process

Answer 27

donated cells shed HLA antigens -> presented by APC to T cells within local lymph nodes -> T cells activate and mount immune response -> T cells recirculate through blood to reach donor organ (tether, roll, arrest, diapedesis); see interstitial inflammation (not intravascular), ruptured basement membrane and tubulitis (invasion of tubular epithelium)

Question 28

T cell mediated rejection: what cells infiltrate graft first

Answer 28

alloreactive CD4+ cells

Question 29

T cell mediated rejection: what 3 things do cytotoxic T cells do

Answer 29

release toxins to kill target, punch holes in target cells (perforin), cause apoptotic cell death (Fas-ligand)

Question 30

T cell mediated rejection: what 4 things do macrophages, recruited by T cells, do

Answer 30

phagocytosis, release proteolytic enzymes, produce cytokines, produce oxygen and nitrogen radicals

Question 31

antibody-mediated rejection: what do antibodies target

Answer 31

graft HLA and AB antigen

Question 32

antibody-mediated rejection: when can antibodies arise

Answer 32

pre-transplantation (sensitised) or post-transplantation (de novo)

Question 33

antibody-mediated rejection: what do antibodies activate

Answer 33

complement and macrophages (also recruit pro-inflammatory cells and cause coagulation intravascular)

Question 34

2 methods of monitoring for rejection post-transplant

Answer 34

deteriorating graft function, subclinical (kidney, heart with regular biopsies)

Question 35

what is measured for deteriorating graft function in kidney transplant

Answer 35

rise in creatinine, fluid retention, hypertension

Question 36

what is measured for deteriorating graft function in liver transplant

Answer 36

rise in liver function tests, coagulopathy

Question 37

what is measured for deteriorating graft function in lung transplant

Answer 37

breathlessness, pulmonary infiltrate

Question 38

what is measured for deteriorating graft function in heart transplant

Answer 38

can’t, so conduct regular biopsies