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Kidneys and Hormones > Immune aspects of kidney transplant > Flashcards

Immune aspects of kidney transplant Flashcards

1
Q

Do transplantations between non-identical twins show rejection?

A

No - share bone marrow in utero

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2
Q

What does HLA stand for?

A

Human leukocyte antigen

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3
Q

What does HLA do?

A

Responsible for the activation of the immune response

Stimulate T and B cell responses

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4
Q

What class of HLA are expressed on all nucleated somatic cells?

A

Class I HLA-B

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5
Q

What happens in organ rejection?

A

HLA recognises proteins on the transplanted organ as non-self and attacks it by mounting an immune response

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6
Q

What are 3 types of HLA molecules?

A

HLA-A, -B and -DR

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7
Q

What do -A, -B and -DR represent on HLA molecules?

A

Important alleles

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8
Q

Where are HLA-DR found?

A

On immune cells

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9
Q

How many alleles code for each HLA subtype (-A, -B, -DR)?

A

2 alleles

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10
Q

How do we use the HLA molecule to determine the compatibility between potential donor and recipient?

A

Compare the alleles that make up the HLA subtypes between the recipient and donor

For example, for the HLA-A

Donor = two alleles that code for this molecule are HLA-A1 and HLA-A1

Recipient = two alleles that code for this molecule are HLA-A1 and HLA-A2

Matching = 1

Do the same for HLA-B and HLA-DR

Complete match = 0, 0, 0
Complete mismatch= 2, 2, 2

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11
Q

What is the relationship between HLA and MHC?

A

HLA = MHC in humans

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12
Q

What determines the alleles that code for the HLA subtypes?

A

Alleles are inherited from your parents

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13
Q

What is the role of HLA-DR?

A

Binds to specialised antigen presenting cells

Stimulates activation and proliferation of T cells

Releases cytokines which stimulate the immune response

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14
Q

What effect does HLA mismatching have on success of transplantation?

A

The more different the HLA - the greater the immune response - the more immunosuppression is needed - the higher the probability of rejection of the graft

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15
Q

What is transplant rejection?

A

Process by which the immune response attacks the donor organs

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16
Q

What are the three types of transplant rejection?

A
  1. Hyperacute
  2. Acute
  3. Chronic
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17
Q

What is the timeline of hyperacute transplant rejection?

A

Minutes - hours

18
Q

Why does hyperacute transplant rejection occur?

A

Pre formed antibodies are present in the body

Due to the antibodies being exposed to ANY foreign HLA in the past

Exposure to foreign HLA happens in

Pregnancy
Blood transfusion
Previous transplantation

19
Q

Describe a method to test for preformed antibodies in a host

A
  1. Take serum from the recipient in which there would be preformed antibodies
  2. Mix serum with donor cells
  3. Add complement to lyse the antibodies stuck to the donor cells
  4. Detect whether these are preformed antibodies
20
Q

What do preformed antibodies attack?

A

Donor HLA antigens

Blood group antigens

21
Q

How do preformed antibodies lead to transplant rejection?

A

Preformed antigens stick to endothelial cells

Trigger complement and clot formation

Form inflammation within the vessel

Occlude the transplanted organ blood supply = ischaemia

22
Q

What is the timeline of acute transplant rejection?

A

Days - weeks

23
Q

What leads to acute transplant rejection?

A

Can be

Cell-mediated -> T cells, macrophages and monocytes

Antibody mediated -> bind to HLA molecules or other antigens present in the blood vessels

24
Q

What leads to organ rejection in acute transplant rejection?

A

Triggering of the complement cascade acts as an amplification signal of inflammation and coagulation

Eventually leads to organ rejection

25
Q

What is the timeline of chronic transplant rejection?

A

Months - years

26
Q

What mechanisms leads to chronic transplant rejection?

A

Cellular and humoral rejection

T cell mediated response to donor cells

Complement activation

27
Q

Very little can be done to slow down chronic transplant rejection

TRUE or FALSE

A

True

28
Q

What percentage of grafts are lost due to chronic transplant rejection?

A

50%

29
Q

What are methods by which we have managed to increase transplant donations?

A

Paired donation

Desensitisation crossmatch positive

Plasmapheresis

30
Q

What is paired donation?

A

If living donors are not suitable for the recipient - check to see if they are suitable for another recipient

Non compatible donors can ve switched between the two recipients

31
Q

How does desensitisation crossmatch positive work?

A

Remove the antibodies after observed HLA mismatch

32
Q

How does plasmapheresis work?

A

Perform before transplantation

Removal, treatment and return of plasma from the blood circulation

Decrease the antibodies that might attack the transplanted to negligible levels

33
Q

How can ABO-blood group mismatch lead to organ rejection?

A

If the donor and recipient are blood group mismatched then they suffer hyperacute rejection

Preformed antibodies against these antigens

34
Q

What are blood group antigens?

A

Big antigen system expressed on the blood vessel wall

35
Q

What is accommodation?

A

Endothelial cells lining blood vessels become down regulated to the effect of autoantibodies

36
Q

What is the consequence of accommodation?

A

Number of antobodies increases to before plasmapheresis

But there are no adverse effects since antibodies do not instigate inflammation

37
Q

What is the definition of tolerance in context to transplantation?

A

When the recipient becomes tolerant to the antigens presented by the donor organ

So no autoantibodies are produced against the transplanted organ

38
Q

What would be the consequences of tolerance in context to transplantation?

A

Indefinite graft survival

No need for:

  • Immunosuppression - no drug related side effects, infections or nephrotoxicity
  • No chronic rejection - no need for re-transplantation
  • Impact organ shortage
39
Q

What was Peter Medawar’s experiment?

A

Cells from brown-haired mouse where injected into white-haired embryo

Skin from the brown donor animal grafted onto the white recipient

Mouse grew both white and brown hair due to tolerance

White mouse became tolerant to the antigens from the brown mouse as cells were injected into the embryo

40
Q

How can injection of CD4+CD25+ regulatory T cells increase organ survival.

A

The regulatory cells regulate the immune response

To prevent rejection

Minimise withdrawal of immunosuppressive drugs

41
Q

What is the future of reducing organ rejection?

A

In vitro expansion and reinfusion of autologous CD4+CD25+ REGULATORY cells in patients with increased autoimmune reactivity

Kidneys and Hormones (39 decks)

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