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MBD/MI (Wothaya) > Transplantation And Immunosupressive Drugs > Flashcards

Transplantation And Immunosupressive Drugs Flashcards

1
Q

What is transplantation?

A

Introduction of biological material into an organism

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2
Q

What are the types of donor?

A

Autologous
Syngeneic
Allogenic
Xenogenic

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3
Q

What is an autologous donor/patient relationship?

A

Transplant from one part of a patient to another

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4
Q

What is an syngeneic donor/patient relationship?

A

Transplant from a donor to a recipient that are genetically identical and therefore do not create immunogenic problems (identical twins)

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5
Q

What is an allogenic donor/patient relationship?

A

Donor and recipient are the same species but genetically different

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6
Q

What is an xenogenic donor/patient relationship?

A

Donor and recipient are different species

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7
Q

What are immune responses to transplant caused by?

A

MHC differences between donor and recipient

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8
Q

What is NGS used for?

A

To see differences between donor and recipient HLAs

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9
Q

What is another word for T-cell activation?

A

Allorecognition

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10
Q

What are the examples of indirect allorecognition?

A

Self HLA + self peptide

Self HLA + non-self peptide

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11
Q

What are the examples of direct allorecognition?

A

Matched HLA + peptide

Unmatched HLA + peptide

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12
Q

Which allorecognition will lead to no T cell activation?

A

Self HLA + self peptide

Matched HLA + peptide

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13
Q

Which allorecognition will lead to T cell activation?

A

Self HLA + non-self peptide

Unmatched HLA + peptide

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14
Q

What is increased with more HLA mismatches?

A

Chance of rejection

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15
Q

Why are dead donors bad?

A

Likely to be inflamed due to ischaemia, so more likely to be rejected as the inflammation will flag it up to the immune system

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16
Q

What are the types of rejection?

A

Hyperacute
Acute
Chronic

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17
Q

How quickly does hyperacute rejection happen?

A

Within a few hours of transplant

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18
Q

What is the method of hyperacute rejection?

A

Antibodies fix to endothelial cells
Complement fixation
Accumulation of innate immune cells
Endothelial damage, platelets accumulate and thrombi develop

19
Q

What does hyperacute rejection require?

A

Pre-existing antibodies

20
Q

What generally happens in acute rejection?

A

Inflammation results in activation of organ resident dendritic cells

21
Q

What happens in acute rejection?

A

Inflammation results in activation of organ resident dendritic cells
Dendritic cells move to secondary lymphoid tissue where they encounter circulating effector T cells
Macrophages and CTL increase inflammation and destroy transplant

22
Q

When does chronic rejection occur?

A

Months or years after transplant

23
Q

What is the method of chronic rejection?

A

Alloantibodies recruit inflammatory cells to the blood vessel wall of the transplanted organ
Increased damage enables immune effectors to enter and damage tissue of the blood vessel wall
Blood vessel wall thickened and lumen narrowed -> loss of blood supply
-> donor derived cells die
Membrane fragments containing donor MHC are taken up by host DC
Donor MHC is processed into peptides which are presented by host MHC

24
Q

How do antibodies cause damage to transplanted tissue?

A

Recognition of Fc region leading to:

  • complement activation
  • Antibody dependant cellular cytotoxicity (Fc receptors on NK cells)
  • Phagocytosis (Fc receptors on macrophages)
25
Q

What happens in haematopoietic stem cell transfer?

A

Transplanted HSCs can find their way to bone marrow after infusion and regenerate

26
Q

What is graft versus host disease?

A

When transplanted tissue is immune cells themselves, there is risk of the donor immune cells attacking the host

27
Q

What is the best approach to graft vs host disease treatment?

A

Prevention

28
Q

What reduces the chance of GVHD?

A

Removing T cells from transplant or suppressing their function

29
Q

When can GVHD be beneficial?

A

Removing original leukaemia may prevent disease relapse

30
Q

What are the phases of immunosupression?

A

Induction, maintenance and rescue phases of treatment

31
Q

What are the types of immunosuppressants?

A

General immune inhibitors
Cytotoxic
Inhibit T cell activation

32
Q

What are examples of general immune inhibitors?

A

Corticosteroids

33
Q

What are examples of cytotoxic immunosuppressants?

A

Methotrexate

34
Q

What are examples of immunosuppressants that inhibit T cell activation?

A

Cyclosporine

35
Q

How does cyclosporin work?

A

Blocks T cell proliferation and differentiation

36
Q

What are the two types of immunosuppressive induction?

A

Antibody induction therapy

Triple drug regimen

37
Q

What antibodies are used in antibody induction therapy?

A

Lymphocyte depleting rabbit anti-thymocyte globulins

38
Q

What are the types of drugs used in the triple drug regimen?

A

Calcineurin inhibitor
Antiproliferative agent
Corticosteroid

39
Q

What is the maintenance bit of the immunosuppressive regime?

A

Triple drug regimen at lower doses

40
Q

What is T cell mediated rejection treated with?

A

Anti-thymocyte globulin (ATG) and steroids

41
Q

What is B-cell mediated rejection treated with?

A

IVIg or anti-CD20 antibody and steroids

42
Q

What can immunosuppressive drug toxicity lead to?

A

Organ failure

43
Q

What are transplant patients more susceptible to?

A

Infection and malignancy

MBD/MI (Wothaya) (57 decks)

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