Transplantation 1 Flashcards
what is transplantation
the act of transferring cells, tissues, or organs from one
site to another
when did joseph Murray perform his first successful kidney
transplant from living donor
1954
what did Dr Christian Barnard carry out in 1967
the 1st human heart
transplant
Autograft
Tissue is derived from ‘self’, and can be transplanted back
to the same place or another site (same one body)
isograft e.g. first human kidney transplant in 1954
tissue transplanted between genetically identical twins
whats the most common transplant type
Allograft e.g kidney, heart, pancreas, lung, liver, bowel, bone, skin
whats an allograft
Tissue transferred from one individual to another
Xenograft e.g.
Tissue transferred from one species to another (eg.
Heart valves)
why is whole organ xenografting limited
due to the potential for hyperacute rejection
what are immunologically privileged sites e.g.
sites where grafts aren’t rejected e.g cornea, brain, testis, uterus (fetus)
what do corneal allograft transplants not require as they are immunologically privileged sites
no assessment of HLA type and no administration of immunosuppressive drugs
what is the major barrier to overcome in transplantation
Human Leucocyte Antigens (HLA)
how many classical HLA loci are there, each encoded by seperate genes
name them
6
Class I (A,B,C)
Class II (DR, DQ,DP)
Why do HLA’s determine histocompatibility
as they allow tissue to be recognised as ‘self’ or ‘non-self’ by the host IS
what is the primary function of HLA’s, making them very polymorphic
to serve as
recognition molecules in the initiation of an immune
response
what do HLA’s present to effector cells of IS (T cells)
peptides from foreign substances
What cells are HLA class I expressed on
what pathogens do they recognise
on nearly all cells (nucleated)
pathogens that reside inside cells e.g. viruses
What cells are HLA class II expressed on
what pathogens do they recognise
immune cells - antigen presenting
pathogens that reside outside the cells e.g. bacteria
what do HLA-A define
the locus
what does HLA-A24 show
the serologically defined antigen
what does asterisk mean in HLA-A*24
that the allele has been defined by molecular methods (low resolution)
what resolution does HLA-A*24:01 show
where is this required
higher resolution, specific allele
required for haematopoietic stem cell transplant
what do father and mother produce when looking at HLA inheritance
4 haplotypes (sets of DNA variants along single chm)
what must be determined for all organ recipients and donors to minimise chance of rejection
major HLA loci
what are used to determine HLA loci
how
terasaki trays
plates with serum containing anti-HLA
antibodies. patient cells and complement get added and death occurs in
wells where antibody reacts with patient sample
Dyes show live (green) and dead (red) cells
although can get DNA from buccal swabs/saliva, what does the system in NHS labs do for HLA typing
extracts genomic DNA from whole blood
whats the first step in determining HLA type by a molecular method
Sequence-specific primer (SSP) PCR
what do SSP tests consist of
multiple different PCR primers specific for
known HLA polymorphisms in a kit format
what are produced in SSP PCR if primers are complementary to DNA sample
Specific amplicons
what do Individuals who are HLA-B27 (around 8%) have an increased risk for and get screened
ankylosing
spondylitis and other inflammatory disorders
what disorder is HLA-B57 associated with
drug-induced inflammatory disorder
what patients in the UK are screened for HLA-B57 before beginning
Abacavir (reverse transcriptase inhibitor) treatment
all HIV positive patients
what major risk factor for hyperacute rejection was recognised over 40 years ago
recipients having
antibodies to antigens expressed on donor cells
what may the antibodies on donor cells causing hyperacute rejection be due to
pregnancy
blood transfusion
previous transplantation
what assays seek to identify donor-specific HLA antibody-mediated responses for given recipient
CDC crossmatch assays
2 main reasons for kidney transplant
diabetes
High blood pressure
3 main reasons for heart transplant
ischaemic heart disease
idiopathic dilated cardiomyopathy
congenital HD
2 types of transplant donors
living
cadaveric
what are kidney transplants subject to
ABO/HLA compatibility
what are cadaveric donors
Those which are deemed to be ‘brain stem dead’ following
appropriate testing
whats transplant allocation based on for kidney and pancreas
blood group match and
HLA-A, B and DR
what is performed for all transplants, prior to surgery
a crossmatch
For heart and lung, logistics may prevent the crossmatch, so a virtual crossmatch is
performed instead
what type of graft rejection should never happen
hyperacute
what graft rejection always happens to some degree with
solid organ
chronic
what response mediates hyperacute rejection
humoral response
what are 2 causes hyperacute rejection which is usually seen within minutes of transplantation
pre-existing donor-specific
antibodies in the recipient
accidental
ABO mismatch
what cascade is initiated when ab’s activate the complement pathway in hyperacute rejection
the blood clotting cascade
what timeframe does acute rejection occur over
several days
what is acute rejection caused by
activation of t lymphocytes
what attack happens to endothelial cells in acute rejection due to mismatched HLA
cytotoxic t cell attack
end result of chronic rejection
vascular disease
what bind to endothelial cells and recruit Fc-receptor
bearing monocytes/MQ in chronic rejection
alloantibodies
what do Inflammatory components in the vessel wall in chronic rejection lead to
damage,
thickening of the vessel wall and narrowing of lumen, inadequate
blood supply and damage
what does allogeneic transplantation require if the transplant is to survive
immunosuppression by drugs
