L12 - K Okkenhaug - transplantation Flashcards
(39 cards)
2 situations where allogenic cells come into contact are…
Iatrogenic (effects of medical treatment), such as blood transfusion, or
Natural, such as pregnancy in placental mammals.
D: Transplantation
introduction of biological material - organs, tissue, cells or fluids - into an organism.
The main problem with transplanting tissue is that most cells express _____ surface antigens encoded by the ___
The main problem with transplanting tissue is that most cells express polymorphic surface antigens encoded by the MHC
is there such thing as a universal donor?
no
(except in blood transfusiosn)
four possible relationships between transplanted donor material and the recipient,
which scenario of transplantation is the most common clinically?
Allogeneic, the most common type of transplants, display immunological memory.
what is meant by this?
When a recipient that has previously rejected a skin graft is regrafted with skin from the same donor the graft is rejected more rapidly, in a second-set reaction.
describe the role T cells play in tissue rejection
T cell recognition may be through
- direct recognition of the donor MHC or
- indirect recognition, of an antigen presented by self MHC molecules.
3 types of rejection?
1) Hyperacute rejection
2) Acute rejection
3) Chronic rejection
describe hyperacute rejection
Very fast
Hyper acute rejection occurs if there are pre-existing antibodies
eg: rejection of ABO mis-matched red cells (Blood transfusion)➔type II hypersensitivity! Anti-A and anti-B antibodies can also bind other tissues.
T or F:
Hyperacute rejection also takes place in Xenotransplants
T - Natural antibodies recognise differentially glycosylated proteins.
Antibodies can also form against MHC molecules:
give 3 circumstances
- From previous organ transplants (e.g. children who have multiple transplants)
- From pregnancy – at childbirth foetal cells enter maternal circulation and stimulate adaptive response to paternal HLA
- From blood transfusion matched for ABO but not HLA (transplant must include nucleated cells, not just erythrocytes which lack MHC)
why are pig grafts bad news complement wise?
complement does not function well across species. Normally complement is disabled on self tissues by the action of regulatory proteins such as decay accelerating factor (DAF). This does not work on pig tissue and the graft is attacked by the human complement.
does rejection produce a memory response?
yep - cant use the same person again after 1st transplat - rejection second time will be faster
describe acute graft rejection
caused by T cell recognition of the transplanted tissue
involves the response of CD8 T cells to HLA class I differences and CD4 T cells to HLA class II differences.
T cells us direct and indirect recognition modes
Acute rejection can be thought of as a type of Type __ hypersensitivity reaction
Acute rejection can be thought of as a type of Type IV hypersensitivity reaction
This is the main immunological barrier to allotransplantation. It is caused by T cell recognition of the transplanted tissue. Note it is not an issue in blood transfusion – why?
Note it is not an issue in blood transfusion as red blood cells do not carry MHC antigens.
describe the direct recognition of allogenic MHC
allogenic MHc molecules itself is recognised as bad - even if it presents self peptides.
Both CD8+ T cells and CD4+ T cells mediate graft rejection.
why do MHC products cause such reproducible and rapid graft rejection
- individuals inadvertently have a high frequency of T cell receptors reactive with allo-MHC products, irrespective of the loaded peptide
- receptors may not need to bind with a particularly high affinity to result in activation of the T cell
- abundant on cell surface , therefore readily activated
describe indirect recognition
uptake of allogeneic proteins by the
recipient’s own antigen presenting cells
(APC’s) and their presentation to T cells by
self MHC molecules.
male vs female regarding indirect rejction?
Female recipients of a male organs may
generate immune responses against peptides
encoded by genes on the Y chromosome.
can MHc matching be bad sometimes>
for indirect recognition rejection yep
Counter-intuitively, MHC sharing between donor and recipient in indirect recognition may increase reactivity as donor, as well as recipient, dendritic cells can prime recipient T cells for minor peptides
describe chronic rejection
several years
poorly understood
may relate to immune response against blood vessels. The blood supply to the organ is compromised, resulting in ischemia and loss of function.
privileged sites?
Transplants at certain sites may be occur with little or no immune rejection. The most important of these is the cornea.
The absence of lymphatic drainage is probably the critical common factor but some sites also lack vascularisation.
