Transplantation and immunology Flashcards
donor
the individual or specimen donating tissue is the donor
the individual receiving the tissue is the
recipient
the tissue can be described as a transplant but is often called a
graft
tissue may or may no be an organ
what word describes the immune response to the graft, this is separate to graft failure which may occur for other reasons
rejection
autograft
donor is the recipient
isograft
donor is genetically identical to recipient
allograft
donor is same species as recipient
xenograft
donor is of diffenent species
what is a orthotopic graft
donor tissue mobilised into natural anatomical location
heterotopic graft
donor tissue mobilised into unnatural anatomical location e.g. skin, bone, kidney
grafts can be living or cadaveric depending on the state of the donor
England scotland and Wales have an opt-out system for organ donation what do northern ireland do
opt-in
Conditions that typically cause ineligibility for tissue donation Active cancer HIV, hepatitis Ebola virus CJD
DCD- circulatory deceased individuals
DBD - brain dead ones
Living donors
most common living donor organ
kidney
domino transplants
e.g. cystic fibrosis - heart and lungs from deceased donor to CF patient , heart from CF patties to another recipient
what is transplantation immunology
Transplantation immunology - sequence of events that occurs after an allograft or xenograft is removed from donor and then transplanted into a recipient.
A major limitation to the success of transplantation is the immune response of the recipient to the donor tissue
what graft do not provoke an immune reaction
isografts and autografts
the there do
do decullarised transplants carry antigens
no - bioprosthetic valve
vascular transplants are spared
what things mediate the immune reaction
human leukocyte antigens HLA incompatibility
ABO incompatibility
minro histocompatibility complexes
on erythrocytes surface what are the antigens called
agglutinogens
blood groups seperated by presecene of these nations
what are the two glycolipid antigens
A and B
each person has 2 ABO
individuals who lack A or B antigen will have the corresponding antibodies in the serum
anit- A and anti-B antibodies
if some is O blood willl they have no antigens therefore anti-A and aNti-B antibodies will be present
yes
what blood group is universal recipient
AB
what blood group is universal donor
O
HLA know as MHC antigen how many classes
2
MHC -I
MHC II- antigen presenting cells
HLA know as MHC antigen how many classes
2
MHC -I - 3 subtypes
MHC II- antigen presenting cells
matched HLA makes more of a difference
3 patterns of rejection
hyper acute rejection - minutes to hours
acute rejection - weeks to months
chronic rejection - years
what is a hyperacute rejection
this tends to be mediated by pre-formed antibodies (e.g. ABO incompatibility)
where can you find ABO antibodies
line vascular endothelium in addition to RBCs
binding of antibodies mediates immune response
the graft becomes inflamed and organ failure occurs
the graft must be removed immediately to avoid overwhelming the systemic inflammation
acute rejection
humoral or cell mediated ( antibody or T cell mediated)
antibodies are not pre-formed they need to be produced
normall due to HLA incompatibiltity
T cells recognise these cells with the HLA and start an immune response
direct recognition
recognition of an intact MHC molecules displayed by donor APC in graft
T cell recognises the structure of intact allogeneic MHC molecule
involves both CD8 and CD4
indirect recognition
donor MHC is processed and presented by recipient APC by cals II MHC molecules
donor MHC molecule is handled like any other rforign antigen
involves only CD4 and T cells -
once immune process started the rest of acute rejection
cytotoxic T cell kill targets
natural killer trigger apoptosis
t helper cell recruit macohoahse and CD8 TC and type 2 recruit B cells
mononuclear infilatrate occur leading to necrosis of arterial walls
signs may include graft failure and tenderness
can be reversed - if you catch it early enough
chronic rejection
due to long term low grade cell mediated immunity
this may also be related to MHC
endovascular inflammation ( mediated by T cells, alloantibodies, macrophages, cytokines)
smooth muscle hyperplasia - vascular congestion
fibrosis
also know as allograft vasculopathy
new graft will then be required
how do we reduce rejection
donor/recipient matching Cross matching ABO matching ( must) HLA matching ( A,B,C, HLA-D)
immunosuppressive therapy
What is cross matching
test preformed to test for pre-formed antibodies - recipient previously expose to HLAs may be antibodies already present that would increase the chances of rejection
this is tested by cross-matching which involves mixing some of the donors blood cells with the recipients serum. If the cords matching test is negative the transplant is likely to be successful
e.g. lymphocyte sign tests - ANit-HLA antibodies attatahc to HLAs on lymphocyte then complement and trepan blue dye are added - cell damaged bu complement and takes up the dye
when is tissue typing done
before graft takes place and between donor and recipient tissue typed for HLA
HLA myst b matched as closely as poss , but HLA subtype and type of transplant influence importance e.g. HLA DR very important for renal transplant
A 6 antigen match is not always necessary as can use immunosuppressive drugs
3 types of immunosuppressants used
anti-proliferative
glucocorticoid
calcineurin inhibit
what are anti-proliferative
anti-metabolites - methotrexate but the pro drug azathioprine - purine synthesis and impairs DNA replication in cell reducing cell turnover and prolifferatun
glucocorticoids
anti-inflammatory and immunosuppressant
inhibit phophliase As - reduce eicosanoid synthesis, reduce cytosine secretion , reduced adhesion molecules and induces endonuclease that mediate apoptosis within white cells - paradoxically neutrophils frequently raised
calcineurin inhibitors
calcium dependent enzyme
intracellular signallign with T cells - inhibits the enzyme imparts production of Il-2 chichis important for enhancement of cell mediated immunity so no T cell stores e.g. Th2 formation from naive
most important is Tacrolimus
immunosuppression is the balance between
rejection and infections/tumours
what is the major issue of tissue or organ transplant is immune rejection
true
rejection can be 3 processes what are they
hyper acute
acute
chronic - depress of this will always occur in grafts
what is th usual regime for treatment of rejection
triple therapy - steroids, calcineurin inhibitors and antimetabolites
when someone is genetically identical , cellularised and vascular grafts are sued - ABO and HLA matching is performed to reduce what
immune response
