transplantation immunology Flashcards
Type of transplantation
- Auto
- Allo
- Xeno
- Isograft
Autograft
- Transplant tissue is the same as tissue of recipient.
- Does not require immunosuppresant
Allograft
- Transplant of an organ or tissue between two genetically non-identical members of the same species
Xenograft
- A transplant of organs or tissue from one species to another
- Only works when material is inert (tissue antigens have been removed)
Isograft
- Transplant is to genetically identical recipient
Ischaemic phases
Warm
- The time between interrupt of circulation to donor organ, and time when organ is flushed with hypothermic preservation solution.
Cold:
- The period of time when the organ is preserved in a hypothermic state, before transplanted into recipient
Main types of graft rejection (3)
Hyperacute
- Minutes/ hours/ days
Acute
- Days-weeks
Chronic
- Months, years
Difference between abc transfusion and solid organ graft
Blood contains antibodies against ABO antigens, not just antigens on cells.
- Solid organ grafts just contain antigens
- ABO antigens are expressed on all stroll cells
HLA antigens are expressed by what type of cells?
All nucleated cells
HLA graft injury mechanism
Microvascular inflammation
= Ab mediated rejection
- HLA induces phenotypic changes in donor vasculature
- Endothelial cell are activation= leucocytes recruitment, CD4 proliferation - Complement activating antibodies activate classical pathway- C1q
- Produces C3a, C5a= leucocytes recruitment, T cell responses - Fc receptors on monocytes, NK and neutrophils interact with HLA ab on donor EC
- WBC recruitment
- Phagocytosis
- Ab cellular cytotoxicity
Matching HLA
Done via PCR
1 or 2 field code:
- HLA-A:02 or HLA-A02:01
Chance of siblings being HLA identical
1:4
Cross matching HLA
Ensures that there are no ab against graft tissue in the donor.
- Recipient serum is taken, may contain anti-HLA ab against donor tissue.
- Cell based: Recipient serum is incubated with donor lymphocytes
- Mouse anti-human Ab is conjugated with flourescent
- If Anti-HLA Ab present= binds and detection
Hyperacute rejection
Occurs minutes/ hours/ days after donor tissue has been grafted.
Due to preformed HLA ab against donor tissue, attack the donor organ/tissue.
T cells and MHC
Can recognise non-self MHC or self-MHC with foreign peptide.
- 10% of T cell recognise non-self MHC
MHC 1
- On all cells
MHC 2
- Certain cells (APC)
Recognition of self versus non self foreign MHC
Non self APC, T cell either
- Binds mainly on presented peptide (peptide-dominant binding)
- Binds mainly on presenting MHC (MHC dominant binding)
- Or both
Self APC
- TCR binds to both the foreign peptide and the presenting self MHC
Acute rejection
Occurs days/ weeks
- Due to mechanism of T cells recognising foreign MHC or foreign peptides
Chronic rejection
Occurs months/ years after grafting
Involves a complex process
- Dependent on the damage done when graft is removed from donor, before repercussion into recipient (especially warm ischaemic time)
Immunosuppression with transplants
Cyclosporin A, Tacrolimus
Azathiprine, MMF
Drugs can be reduced after a few months
- Early stage= passenger leucocytes provided non self MHC so strong immunosuppression required
- Later stage, recipient leucocytes recognised self MHC w/ foreign peptide
