T1 L15 Intro to transplantation Flashcards
What is transplantation?
Grafting of tissue, usually from one individual to another
What is an autograft (autologous) transplant?
To another site on same individual e.g. after burns
What is an isograft?
(Iso/syngeneic)
To genetically identical individual (homozygous twins)
What is an allograft?
(Allogeneic)
To genetically disparate members of same species
What is a xenograft?
To a different species
What is the warm ischaemic phase?
Time from interruption of circulation to donor organ until organ is flushed with hypothermic preservation solution
What is the cold ischaemic phase?
While organ is preserved in hypothermic state prior to transplantation into recipient
What is the mechanism for hyperacute reaction?
Preformed antibodies
When does a hyper acute rejection occur?
Minutes to hours
Can be days
What is the mechanism for acute rejection?
T cells
When does an acute rejection occur?
Days to weeks
can have late acute
What is the mechanism for chronic rejection?
Chronic processes including vascular changes in the graft
When does chronic rejection occur?
Months to years
can be weeks
What are the 4 major blood groups?
A
B
AB
O
Who can Rh positive patients receive blood from?
Those who are Rh positive or negative
Who can those with group O receive blood from?
Only group O
Who can group O donate to?
Everyone
Who can group A donate to?
A
AB
What happens if someone with group O was given a kidney from a donor with blood group B?
Antibodies would bind to inside of blood vessels in the graft Complement binds Triggers complement cascade Coagulation of blood Occlude blood vessles Hyperacute rejection
Describe how HLA causes graft injury
Induce phenotypic changes in donor vasculature Causes endothelial cell (EC) activation --> promotes recruitment of leucocytes & CD4 T-cell proliferation in response to alloantigen HLA class II on endothelial cell Complement-activating antibodies trigger classical pathway through binding of C1q --> production of anaphylatoxins C3a & C5a --> potential to directly augment leucocyte recruitment & T-cell alloresponses Monocytes, neutrophils & natural killer cells express Fc receptors (FcyRs) which can interact with heavy chain of HLA antibodies bound to donor ECs
How is hyper acute rejection prevented?
Matching donor and recipient for HLA and ABO blood group antigens using PCR
How are HLA antigens cross matched?
Incubation of washed donor cells with recipient serum
Antibody-binding detected by mouse-anti human Ab stain of recipient cells or cytotoxicity
Where are class I MHC molecules found?
On all nucleated cells
Where are class II MHC molecules found?
On subset of nucleated cells
What levels can T-cell activation be interfered with?
Receptor / ligand interaction
Signal transduction
Gene expression
Cell cycle control
What types of immunosuppressive drug therapy can interfere with T-cell activation?
Cyclosporin A or tacrolimus
Azathioprine or MMF
Corticosteroids
How do cyclosporin A and tacrolimus interfere with T-cell activation?
T-cell inhibition
Calcineurinine inhibitor
Inhibition of cytokine synthesis: IF-2, IFN-gamma
How do azathioprine or MMF interfere with T-cell activation?
Antiproliferative - inhibits clonal expansions
How do corticosteroids interfere with T-cell activation?
Anti-inflammatory
Inhibit NFkB cytokine synthesis and action
Describe the multifactorial components of chronic graft rejection
Large extent depends on damage done to graft between removal from donor and being re-perfused in recipient
Major histocompatibility antigens may contribute
Factors such as infection or atherosclerosis
What is daclizumab?
IL-2 receptor antagonist that prevents T-lymphocyte proliferation
Used for prophylaxis to acute rejection
What is basiliximab?
Monoclonal antibody that acts as IL-2 receptor antagonist and prevents T-lymphocyte proliferation
Used for prophylaxis to acute rejection
What is alemtuzumab?
Anti-CD3, anti-CD52
Causes lysis of B lymphocytes
Why is greater immunosuppression needed initially?
Passenger leucocytes are present in early phase
Donor cells provide non-self MHC
What is the conventional view of transplantation?
Immune system differentiates between self and non-self
Is non-self enough to trigger an immune response?
Why is an embryo not rejected?
What is the modern view of transplantation?
Immune system discriminates between dangerous and not dangerous
Self and non-self aren’t important
What interactions can be danger signals in the modern view of transplantation?
Tissue injury - hypoxia
Cytokines - TNF, IL-1
Microbial products - LPS, LTA, CpG, DNA
Surgery provides danger signals: trauma, inflammation, ischaemia
