Transplantation Flashcards

1
Q

What situation leads to a transplant?

A

“Tissue/organ undergone an Irreversible Pathological Process which either Threatens Patient’s Life or Significantly Hampers QoL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the 4 major types of graft?

A

Xenograft - From an animal
Allograft - From another person
Isograft - From someone genetically identical
Autograft - From yourself

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Define Histocompatibility?

A

State in which the donor and recipient share the same (or sufficiently similar) alleles of HLA genes that they express the same MHC proteins and so would not attack the graft

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Where are HLA alleles found?

A

on chromosome 6

Each person has 2 sets of alleles and they are co-dominantly expressed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How are HLA alleles inherited

A

As Haplotypes (meaning 2 half sets, one from each parent)

Hence each person is 1/2 identical to each parent and so has a 1/4 chance of being identical to a sibling

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the major requirements for tissue typing?

A

HLA match, particularly:

  • HLA-A
  • HLA-B
  • HLA-DR

And ABO blood group

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What do HLA-A & HLA-B code for?

A

MHC 1

Found on all nucleated cells, present intracellular antigens and recognised by CD8+ T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What does HLA-DR code for?

A

MHC 2

Found on APCs, presents extracellular antigens and recognised by CD4+ T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are privileged sites?

A

Places with little to no blood flow and so no immunity. They don’t require tissue matching or immunosuppression

E.g. Cornea

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the major causes of rejection?

A

HLA/ABO incompatible
Pre-formed immunity (sensitized to donor antigen)
Failed Immunosuppression (incl non-compliance)
Infections or environmental triggers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How do we categorize rejection?

A

Immediate
Acute
Chronic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What causes an immediate rejection?

A

HLA/ABO antibodies
They activate complement leading to inflammation and thrombosis

Happens in minutes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Acute rejection occurs within 6 months. What happens?

A

Cell & Ab mediated

The graft is infiltrated by cells (T, B, NK & macrophages ) –> Endothelial damage and parenchymal cell damage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What happens in chronic rejection?

A

Ab mediated & innate immunity

This is the most common kind

Chronic inflammation in blood vessels- -> smooth muscle proliferation –> Vessel occlusion and eventually organ failure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How can you treat someone who’s rejecting their organ?

A

Corticosteroids
Anti-thymocyte Globulin
Plasmapharesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

how do you prevent someone rejecting an organ?

A

ABO matching
Tissue Typing (HLA)
Prophylactic Immunosuppresants

17
Q

Other than rejection what else can go wrong in a transplant?

A
Infection
Neoplasia
Drug SEs
Recurrence of disease
Surgical complications
18
Q

What are the types of immunosuppresants used in organ transplant?

A

Corticosteroids
Cyclosporinfor solid organ graft transplantation (by interferring with T cell signalling)
Calcineurin inhibitors (Tacrolimus) - inhibits IL-2 gene transcription
RIpamycin - interacts with signalling downstream of the IL-2 receptor
Anti-proliferatives (Azathioprine) - inhibit lymphocyte proliferation

19
Q

What’s the difference between graft rejection and Graftvshost disease?

A

In rejection the host attacks the graft

In GvH, white cells in the donated tissue attack the host’s body

20
Q

So what is required for GvH disease?

A

Graft must contain immunocompetent cells

Recipient must have defective immunity (pretty likely since you’re smacking them with immunosuppresants)

HLA mismatch

21
Q

What can we do to prevent GvH?

A

Tissue Typing (HLA)

Can do Donor Marrow T cell Depletion

22
Q

What kind of donors are associated with the longest life, least rejection and best health?

A

1) Living Donors (Related or unrelated)
2) Living donors altruistic
3) Brain Death Donors (DBD)
4) Cadaveric Death Donors (DCD)

So 4 are the least healthy transplants and 1 the most

23
Q

What causes hyperacute rejection in unmodified xenografts?

A

Natural IgM Human Anti-Swine Abs

24
Q

Define Autologous transplant

A

Tissue returning to same individual after period outside the body, usually frozen, stem cells, skin graft, ovaries etc

25
Q

Synergeneic transplant definition

A

Transplant between identical twins (isograft)

26
Q

Allogenic transplant definition

A

transplant between genetically nonidentical members of the same species providing a risk of rejection

27
Q

Cadaveric transplant definition

A

Uses organs from a dead donor

28
Q

Xenogenic transplant

A

Transplant between species, thus carrying a high risk of rejection

29
Q

How do we chose a recipient for an organ?

A

ABO compatibility
Negative serum cross match with Donor’s T-lymphocytes
HLA match

30
Q

What happens in autologous SCT?

A

Marrow is removed, frozen and reinfused after potent chemotherapy has been given

31
Q

What is wrong with allogenic SCT?

A

MUCH RISKIER

Mortality is as high as 20%

32
Q

When is allogenic SCT carried out?

A

SCID

Aplastic aneamia

33
Q

Stem cells sources

A

Bone marrow
Peripheral blood
Cord blood

34
Q

How do we condition the patient before stem cell therapy?

A

High dose Chemo
High dose radio
To destroy diseased/damaged stem cells already present

35
Q

What is GVHD and when does it occur?

A
Graft versus Host disease occurs when donor T cells from allogenic graft react to recipient antigens due to a mismatch in either minor or major histocompatibility antigens.
Can occur up to 4 weeks later
Multisystemic
Acute = 70% mortality
Minimise T cells in donation