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MET2 > 36 - Transport Immunology > Flashcards

36 - Transport Immunology Flashcards

1
Q

How long does hyper acute rejection of organ occur

A

Minutes to hours

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2
Q

What causes a hyper acute rejection

A

previous transplant
previous transfusion
previous pregnancy
(individual that has been immunologically primed - pre-existing immune responses mediated by antibodies)

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3
Q

Mechanism of hyperacute rejection

A
  • Antibodies bind to the graft
  • Activate endothelial cells+ complements
  • Activated endothelial cells are pro-coagulant (causes thrombosis, haemorrhage and infarction)
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4
Q

1 hour after hyper acute rejection

A

Neutrophils in peritubular capillaries and glomeruli

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5
Q

12 -24 hours after hyper acute rejection

A

Intravascular coagulation and cortical necrosis

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6
Q

What may you see in vascular and glomerular lesions (hyper acute)

A
  • IgM

- Complement

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7
Q

How long after does acute rejection of transplant occur

A 
1 week - 6 months 
occasionally later (adaptive response)
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8
Q

What can cause acute rejection

A

CD4 T cells
Cell mediated rejection
Antibody mediated rejection

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9
Q

Helper (CD4) T cell acute rejection

A

T cell mediated rejection (CD8 cells) cause direct organ damage
B lymphocytes produce antibody mediated reaction

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10
Q

Cell mediated rejection

A

Aka acute cellular rejection

- Tissue is inflamed with lymphocytes

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11
Q

What is Endarteritis

A

Type 2 rejection
Inflammation of innter lining of artery
(Acute cell mediated rejection)

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12
Q

Antibody mediated rejection

A

Antibodies against any non-self-molecules (ABO, MHC, MICA most common)

  • Endarteritis is v common
  • Much more severe
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13
Q

How can antibody-mediated rejection be detected

A

Complements are activated and this allows to differentiated with cell mediated

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14
Q

What do antibodies activate

A

C1 –> C2 –> C4 and C4 is deposited (C4 is what is detected)

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15
Q

What does CD4 correlate with

A

Donor specific antibodies

Covalently bonds with thio-ester groups on endothelium

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16
Q

Criteria for acute AMR

A

Evidence of acute renal injury on histology
Evidence of antibody activity (CD4 staining in peritubular capillaries)
Circulating anti-donor specific antibodies

17
Q

CMR or AMR more common?

A

CMR is more common than AMR

AMR has higher graft loss than CMR

18
Q

When does chronic transplant rejection occur

A

Months to years

19
Q

What can you do in chronic rejection

A

Impossible to do anything as a lot of pathology

20
Q

Other reasons for graft loss (not rejection issues)

A

Graft was damaged before transplantation
Surgical complications
Recurrence of origin disease

21
Q

How to prevent hyper acute rejection

A

Should not occur in the first place as you could detect beforehand

  • ABO compatibility
  • Screen for presence of pre-formed antibodies (direct cross-match) to see if any binding of antibodies
22
Q

How do you prevent acute rejection?

A

HLA matching

Minimising ischaemia

23
Q

What is HLA matching

A

HLA is the molecule which holds up the antigen on the antigen-presenting cell
Immune system recognises our own and the HLA molecule of others
(Mismatch in HLA causes less chance of survival)

24
Q

Which MHC classes are peptides

A

Class I, II and III

25
Q

Why is MHC so polymorphic

A

To protect from pathogens mutating

Downside is rejection

26
Q

Most common HLA

A

DR4 HLA

27
Q

How does ischaemia make rejection worse

A

Ischaemia up-regulates adhesion molecules – > increases the adhesion of leucocytes in reperfusion –> increases non-specific damage and acute rejection

28
Q

How to prevent chronic rejection

A

Choose the best organ
Minimise surgical damage
Minimise acute rejection
Minimise drug-toxicity

29
Q

Relationship between recipient immune system and graft

A

More aggressive early on but less with time
(loss of bone marrow derived cells of donor)
Development of active regulation

30
Q

Glomerular quota and rejection

A

If the donor is young and healthy it has a better glomerular quota so it can deal with more stresses

31
Q

How can immunosupression prevent rejection

A

Act to prevent T-cell activation

32
Q

Process of T-cell activation

A

T cell recognises an antigen → 2 IC signals → Nucleus activates cytokines → IL2 secreted and bound onto T cells → when nucleus receives signals → replicates

33
Q

Calcineurin inhibitors

A

Cyclospoine and tacrolimus

Inhibit the transduction of signal from recognition of antigen on surface to nucleus

MET2 (28 decks)

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