T1 L15 Intro to transplantation Flashcards

1
Q

What is transplantation?

A

Grafting of tissue, usually from one individual to another

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2
Q

What is an autograft (autologous) transplant?

A

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

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3
Q

What is an isograft?

A

(Iso/syngeneic)

To genetically identical individual (homozygous twins)

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4
Q

What is an allograft?

A

(Allogeneic)

To genetically disparate members of same species

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5
Q

What is a xenograft?

A

To a different species

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6
Q

What is the warm ischaemic phase?

A

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

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7
Q

What is the cold ischaemic phase?

A

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

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8
Q

What is the mechanism for hyperacute reaction?

A

Preformed antibodies

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9
Q

When does a hyper acute rejection occur?

A

Minutes to hours

Can be days

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10
Q

What is the mechanism for acute rejection?

A

T cells

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11
Q

When does an acute rejection occur?

A

Days to weeks

can have late acute

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12
Q

What is the mechanism for chronic rejection?

A

Chronic processes including vascular changes in the graft

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13
Q

When does chronic rejection occur?

A

Months to years

can be weeks

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14
Q

What are the 4 major blood groups?

A

A
B
AB
O

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15
Q

Who can Rh positive patients receive blood from?

A

Those who are Rh positive or negative

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16
Q

Who can those with group O receive blood from?

A

Only group O

17
Q

Who can group O donate to?

18
Q

Who can group A donate to?

19
Q

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

A
Antibodies would bind to inside of blood vessels in the graft
Complement binds
Triggers complement cascade
Coagulation of blood
Occlude blood vessles
Hyperacute rejection
20
Q

Describe how HLA causes graft injury

A
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
21
Q

How is hyper acute rejection prevented?

A

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

22
Q

How are HLA antigens cross matched?

A

Incubation of washed donor cells with recipient serum

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

23
Q

Where are class I MHC molecules found?

A

On all nucleated cells

24
Q

Where are class II MHC molecules found?

A

On subset of nucleated cells

25
What levels can T-cell activation be interfered with?
Receptor / ligand interaction Signal transduction Gene expression Cell cycle control
26
What types of immunosuppressive drug therapy can interfere with T-cell activation?
Cyclosporin A or tacrolimus Azathioprine or MMF Corticosteroids
27
How do cyclosporin A and tacrolimus interfere with T-cell activation?
T-cell inhibition Calcineurinine inhibitor Inhibition of cytokine synthesis: IF-2, IFN-gamma
28
How do azathioprine or MMF interfere with T-cell activation?
Antiproliferative - inhibits clonal expansions
29
How do corticosteroids interfere with T-cell activation?
Anti-inflammatory | Inhibit NFkB cytokine synthesis and action
30
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
31
What is daclizumab?
IL-2 receptor antagonist that prevents T-lymphocyte proliferation Used for prophylaxis to acute rejection
32
What is basiliximab?
Monoclonal antibody that acts as IL-2 receptor antagonist and prevents T-lymphocyte proliferation Used for prophylaxis to acute rejection
33
What is alemtuzumab?
Anti-CD3, anti-CD52 | Causes lysis of B lymphocytes
34
Why is greater immunosuppression needed initially?
Passenger leucocytes are present in early phase | Donor cells provide non-self MHC
35
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?
36
What is the modern view of transplantation?
Immune system discriminates between dangerous and not dangerous Self and non-self aren't important
37
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