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Path - Immunology > Transplant > Flashcards

Transplant Flashcards

1
Q

What are the three phases of the immune response transplanted graft?

A
  • Phase 1: recognition of foreign antigens
  • Phase 2: activation of antigen-specific lymphocytes
  • Phase 3: effector phase of graft rejection
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2
Q

What are the most relevant protein variations in transplants?

A

ABO blood. group

HLA

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3
Q

Where is HLA coded fo?

A

Chromosome 6 on MHC

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4
Q

What are the two main immune components for rejection?

A

T cell mediated rejection

antibody (B cell) mediated rejection

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5
Q

What are the three types of HLA class I?

A

A, B, C

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6
Q

What are the three types of HLA class II?

A

DR, DQ, DP

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7
Q

What cells is HLA I presented on?

A

ALL cells

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8
Q

What cells in HLA II presented on?

A

APCs

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9
Q

Why has the high variability (polymorphism) evolved in HLA?

A

So that HLA molecules can present a wide variety off antigens

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10
Q

What are the three most polymorphic/immunogenetics class subtypes for HLA?

A

A, B, DR

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11
Q

Explain T cell mediated rejection broadly

A
  1. APC presents donor HLA to recepient HLA
  2. T cell activates > inflammatory cell recruitment
  3. Effector phase > organ damage
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12
Q

What are the 3 key signals required for T cell activation?

A
  1. APC - T cell receptor interaction
  2. Co-stimulatory signal
  3. Amplification > activation via cytokine production
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13
Q

What are the actions. of activated T cells?

A 
Proliferation 
Produce cytokines 
Provide help to CD8 cells 
Provide help to antibody production 
Recruit phagocytic cells
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14
Q

Whose APCs work in rejection, the recipient or the donor’s?

A

BOTH

Because if you transplant in an organ, that organ will contain APCs from the donor

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15
Q

Where does APC- T cell interaction occur?

A

In the lymph nodes

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16
Q

Which two cell types are activated in the effector phase ?

A

Cytotoxic T cells > granzyme, perforin, Fas ligand

Macrophages > phagocytosis, release of proteolytic enzymes, cytokine and free radical production

17
Q

What do T cells do / how do they interact with endothelium in the effector phase?

A

They tether, roll and arrest on endothelial surface

They then crawl through interstitial and start attacking the tubular epithelium

18
Q

What are typical histological features of T cell mediated rejection?

A

Lymphocytic interstitial infiltration
ruptured tubular basement membrane
Tubulitis (inflame cells within the tubular endothelium)

19
Q

What can a fail in kidney transplant function be due to?

A 
Rejection
Nephrotoxic drugs
Viral infection (from immunosuppressioN) 
vascular disease 
lymphoma (viral)
20
Q

Explain the two types of antibodies you need to be weary of in transplants?

A

Anti-A and Anti-B antibodies (naturally occurring)

Anti-HLA antibodies (form following exposure)

21
Q

How do antibodies act in a transplant?

A
  • Antibodies bind to HLA antigens on endothelium of blood vessel in transplanted organ
    Antibodies then fix complement which assembles to form MAC > ENDOTHELIAL CELL LYSIS
  • Binding of complement also recruits monophages, NK, neutrophils
  • Inflammatory cells within kidney capillaries (CAPILLARITIS) also cause endothelial injury
22
Q

What is the end product of antibodies acting against a transplant?

A

GRAFT FIBROSIS

23
Q

What are the two key ways we prevent graft rejection?

A 
Tissue typing (AB/HLA typing)
Immunosuppression
24
Q

When do we screen for anti-HLA antibodies=?

A 
BEFORE transplant 
AT time of transplant (once organ assigned )
AFTER transplant (repeat measurement to check for new antibody formation)
25
Q

What three techniques can be used for anti-HLA antibody screening?

A

Cytotoxicity assay
Flow cytometry
Solid phase assay

26
Q

What are key drug types given for immunosuppression in T cell mediated rejection?

A 
Steroids
Calcineurin inhibitors 
Cell cycle inhibitors 
TCR inhibitors 
Monoclonal antibodies
27
Q

What are key drug types given for immunosuppression in B cell mediated rejection?

A 
anti CD20 (rituximab)
BAFF inhibitors (target cytokines that promote B cell activation and growth) 
Proteasome inhibitors (block antibody production by plasma cells)
Complement inhibitors
28
Q

What categories is the general immunosuppression treatment made up of?

A

Induction agent
Baseline immune suppression
treatment of episodes of acute rejection

29
Q

What is given for baseline immune suppression

A

TRIAD:

  • Calcineurin inhibitor
  • cell cycle inhib ( mycofenolat mofetil OR azathioprine)
  • steroids
30
Q

How do you treat episodes of acute rejection?

A

Cellular: steroids, OKT3/ATG

Antibody-mediated: IVIG, plasma exchange, antiC5, antiCD20

31
Q

Name some calcineurin inhibitors

A

tacrolismus

Ciclosporin

32
Q

Name some cell cycle inhibitors

A

mycofenolate mofetil

azathioprine

33
Q

Name some TCR inhibitors

A

OKT3

ATG (Anti-Thymocyte globulin)

34
Q

What can you give for GvHD prophylaxis?

A

methotrexate/cyclosporin

35
Q

How do you treat GvHD’

36
Q

What are common viral associated malignancies?

Path - Immunology (11 decks)

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