T1 L15 Intro to transplantation

Question 1

What is transplantation?

Answer 1

Grafting of tissue, usually from one individual to another

Question 2

What is an autograft (autologous) transplant?

Answer 2

To another site on same individual e.g. after burns

Question 3

What is an isograft?

Answer 3

(Iso/syngeneic)

To genetically identical individual (homozygous twins)

Question 4

What is an allograft?

Answer 4

(Allogeneic)

To genetically disparate members of same species

Question 5

What is a xenograft?

Answer 5

To a different species

Question 6

What is the warm ischaemic phase?

Answer 6

Time from interruption of circulation to donor organ until organ is flushed with hypothermic preservation solution

Question 7

What is the cold ischaemic phase?

Answer 7

While organ is preserved in hypothermic state prior to transplantation into recipient

Question 8

What is the mechanism for hyperacute reaction?

Answer 8

Preformed antibodies

Question 9

When does a hyper acute rejection occur?

Answer 9

Minutes to hours

Can be days

Question 10

What is the mechanism for acute rejection?

Answer 10

T cells

Question 11

When does an acute rejection occur?

Answer 11

Days to weeks

can have late acute

Question 12

What is the mechanism for chronic rejection?

Answer 12

Chronic processes including vascular changes in the graft

Question 13

When does chronic rejection occur?

Answer 13

Months to years

can be weeks

Question 14

What are the 4 major blood groups?

Answer 14

A
B
AB
O

Question 15

Who can Rh positive patients receive blood from?

Answer 15

Those who are Rh positive or negative

Question 16

Who can those with group O receive blood from?

Answer 16

Only group O

Question 17

Who can group O donate to?

Answer 17

Everyone

Question 18

Who can group A donate to?

Answer 18

A

AB

Question 19

What happens if someone with group O was given a kidney from a donor with blood group B?

Answer 19

Antibodies would bind to inside of blood vessels in the graft
Complement binds
Triggers complement cascade
Coagulation of blood
Occlude blood vessles
Hyperacute rejection

Question 20

Describe how HLA causes graft injury

Answer 20

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

Question 21

How is hyper acute rejection prevented?

Answer 21

Matching donor and recipient for HLA and ABO blood group antigens using PCR

Question 22

How are HLA antigens cross matched?

Answer 22

Incubation of washed donor cells with recipient serum

Antibody-binding detected by mouse-anti human Ab stain of recipient cells or cytotoxicity

Question 23

Where are class I MHC molecules found?

Answer 23

On all nucleated cells

Question 24

Where are class II MHC molecules found?

Answer 24

On subset of nucleated cells

Question 25

What levels can T-cell activation be interfered with?

Answer 25

Receptor / ligand interaction
Signal transduction
Gene expression
Cell cycle control

Question 26

What types of immunosuppressive drug therapy can interfere with T-cell activation?

Answer 26

Cyclosporin A or tacrolimus
Azathioprine or MMF
Corticosteroids

Question 27

How do cyclosporin A and tacrolimus interfere with T-cell activation?

Answer 27

T-cell inhibition
Calcineurinine inhibitor
Inhibition of cytokine synthesis: IF-2, IFN-gamma

Question 28

How do azathioprine or MMF interfere with T-cell activation?

Answer 28

Antiproliferative - inhibits clonal expansions

Question 29

How do corticosteroids interfere with T-cell activation?

Answer 29

Anti-inflammatory

Inhibit NFkB cytokine synthesis and action

Question 30

Describe the multifactorial components of chronic graft rejection

Answer 30

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

Question 31

What is daclizumab?

Answer 31

IL-2 receptor antagonist that prevents T-lymphocyte proliferation
Used for prophylaxis to acute rejection

Question 32

What is basiliximab?

Answer 32

Monoclonal antibody that acts as IL-2 receptor antagonist and prevents T-lymphocyte proliferation
Used for prophylaxis to acute rejection

Question 33

What is alemtuzumab?

Answer 33

Anti-CD3, anti-CD52

Causes lysis of B lymphocytes

Question 34

Why is greater immunosuppression needed initially?

Answer 34

Passenger leucocytes are present in early phase

Donor cells provide non-self MHC

Question 35

What is the conventional view of transplantation?

Answer 35

Immune system differentiates between self and non-self
Is non-self enough to trigger an immune response?
Why is an embryo not rejected?

Question 36

What is the modern view of transplantation?

Answer 36

Immune system discriminates between dangerous and not dangerous
Self and non-self aren’t important

Question 37

What interactions can be danger signals in the modern view of transplantation?

Answer 37

Tissue injury - hypoxia
Cytokines - TNF, IL-1
Microbial products - LPS, LTA, CpG, DNA
Surgery provides danger signals: trauma, inflammation, ischaemia