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immunology > Transplantation > Flashcards

Transplantation Flashcards

1
Q

What criteria must be met for a transplant?

A
  • Tissue/organ undergone an Irreversible Pathological Process which either Threatens Patient’s Life or Significantly Hampers QoL
  • Alternative treatment is not available
  • Disease must not recurre
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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

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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

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4
Q

Where are HLA alleles found?

A

on chromosome 6

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

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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

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6
Q

What are the major requirements for tissue typing?

A

HLA match, particularly:

  • HLA-A
  • HLA-B
  • HLA-DR

And ABO blood group

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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

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8
Q

What does HLA-DR code for?

A

MHC 2

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

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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

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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
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11
Q

How do we categorize rejection?

A

Immediate
Acute
Chronic

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12
Q

how do you prevent someone rejecting an organ?

A

ABO matching
Tissue Typing (HLA)
Prophylactic Immunosuppresants

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13
Q

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

A 
Infection
Neoplasia
Drug SEs
Recurrence of disease
Surgical/ ethical complications
Graft vs host disease
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14
Q

What are the types of immunosuppresants used in organ transplant?

A
  • CCS
  • T-cell blockade: cyclosporin and tacrolimus
  • IL-2 blockade: monoclonal antibodies and rapamycin
  • Antiproliferatives
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15
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

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16
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

17
Q

What can we do to prevent GvH?

A

Tissue Typing (HLA)

Can do Donor Marrow T cell Depletion

18
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

19
Q

what are privileged transplantation sites?

A

Tissues which do not receive much blood supply and therefore require less mismatching

20
Q

What are the types of graft rejection

A
  • Hyperacute : within minutes
  • Accelerated: 2-5 days
  • Acute : 7-21 days
  • Chronic: months to years
21
Q

What are hyper acute graft rejection due to?

A

Hyperacute:

  • Preformed antibodies binding to ABO or HLA antigens on graft.
  • Triggers a type 2 hypersensitivity
22
Q

what is accelerate graft rejection due to?

A

presence of T-cells which are presensitised to the donor

23
Q

what is acute graft rejection due to?

A

newly sensitised T cells to donor

24
Q

what is chronic rejectoion due to?

A

Multifactorial

usually related to T cells

25
Q

Classification of GVHD?

A

Acute: can last up to 4 weeks post transplant
- affects skin, gut, liver and lungs
Chronic: occurs later and can affect skin and liver

26
Q

Immunopathology of graft rejection?

A

1- Afferent phase: donor MHC molecules on “passenger leucocytes” within the graft are recognized by recipients CD4+ T Cells (ALLORECOGNITION)
2- Efferent phase : CD4+ cells recruit effector cells responsible for tissue damage of rejection e.g. macrophages, CD8+ cells, NK cells, B lymphocytes

27
Q

What are the two mechanisms of graft rejection?

A

Direct: T cell recognises unprocessed allogenic MHC on graft APC

Indirect: presentation of a processed peptide of allogenic MHC bound to self MHC

28
Q

Types of stem cell presentation?

A

Autologous: self stem cells which have been frozen, conditioned and rein fused

Allogenic: much riskier

29
Q

when are allogenic stem cells preferred?

A
  • Hamatological malignancy
  • Aplastic anaemia
  • primary immunodeficiency
30
Q

Sources of stem cells?

A
  • Bone marrow
  • Peripheral blood
  • Cord blood
31
Q

How can stem cells be conditioned?

A
  • high dose chemo
  • high dose RT
  • Destroy recipients stem cells and allow engraftment of donor cells
32
Q

How does CCS work?

A
  • At low doses they predominantly act on antigen-presenting cells, preventing some of the early stages of graft rejection.
  • Higher doses of corticosteroids have direct effects on T cells and are used to treat episodes of rejection.
33
Q

What are the two types of IL-2 blockade?

A

1- Monoclonal antibodies against IL-2 receptor :
•used to treat ACUTE episodes of graft rejection
• completely blocks IL-2
•vey potent immunosuppressive drug
•e.g. basiliximab, daclizumab..

2- Rapamycin
•Less potent than monoclonal antibodies and easier to take
•Used to prevet graft rejection
•Blocks pathway further down

34
Q

Main problem with xenotransplantation?

A
  • Primates assemble different sugar side chains from other species.
  • Galactose-α1,3-galactose (gal-α1,3-gal) is a sugar present on the cells of most non-primate species.
  • The immune system can recognize gal-α1,3-gal, and all humans possess antibodies against it following exposure to gut bacteria.
  • Antibodies against gal-α1,3-gal bind onto xenotransplanted organs, activate complement, and trigger hyperacute rejection.

immunology (8 decks)

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