Immunology 3: Transplantation Flashcards

1
Q

Why does the cornea fail?

A

degenerative disease, infections, trauma

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2
Q

Why does Skin/Composite fail?

A

burns, trauma, infections, tumours

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3
Q

Why does Kidney fail ?

A

diabetes, hypertension, glomerulonephritis, hereditary conditions

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4
Q

Why does liver fail?

A

cirrhosis, acute liver failure

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5
Q

Why does the heart fail?

A

coronary artery or valve disease, cardiomyopathy, congenital defects

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6
Q

Why does the bone marrow fail?

A

tumours, hereditary diseases

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7
Q

What are the 5 different types of transplantation?

A

-Autografts
within the same individual

-Isografts
between genetically identical individuals of the same species

-Allografts
between different individuals of the same species

-Xenografts
between individuals of different species
e.g pig heart valves

-Prosthetic graft
plastic, metal

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8
Q

Who are the different types of donors?

A

DECEASED DONORS

a) –> donor after brainstem death
- death conformed using neurological criteria

b) –> donor after circulatory death
- death confirmed via cardio-respiratory criteria
- exclude viral infections / malignancy / drug abise
- time limit for kidney = 60 h

LIVING DONORS

  • -> kidney, bone marrow, liver
  • -> may be genetically related / unrelated
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9
Q

How is transplant allocated ?

A
  • transplant selection

- transplant allocation

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10
Q

what are the 2 most relevant protein variations in clinical transplantation ?

A
  1. ABO blood group
    - -> A + B proteins = on RBC / Endothelial cells
    - BUT you can remove antibodies int eh receipients via Plasma exchange
  2. HLA
    - -> cell surface proteins
    - variability of HLA = important against defense against infection + neoplasia
    - recognizes peptides from infectious disease
    - APC take up protein –> present as fragment on cell memb - T cell detects APC on HLA Molecule (HAS TO SEE CHICKEN ON A PLATE - on top of HLA molecule) –> mounts Delayed T cell response
Class I (A/B/C) 
Class II (DR, DQ,DP)  

no. of mismatched in HLA = identified –> used to determine organ allocation

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11
Q

What are the different types of rejection in transplantation ?

A
    1. hyperacute rejection
    1. acute rejection
    1. chronic rejection

-4. T-cell mediated rejection
–> recognizes antigens on endothelial cells
+ also chemokine /
- recruit macrophages / cytotoxic T cells (infiltration)

    1. antibody-mediated rejection
  • -> antibodies against graft HLA + AB Antigen
  • -> antibodies formed against the graft
  • antibodies can arise pre/protrasplantation
  • usually intravascular
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12
Q

How would you diagnose rejection of transplantation?

How would you treat rejection of transplantation?

A

Diagnose = histological examination of graft biopsy

treatment =
immunosuppressive drugs

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13
Q

Post transplantation, how would you monitor for rejection?

A

a) deteriorating graft function
e.g
Kidney transplant: Rise in creatinine, fluid retention, hypertension

Liver transplant: Rise in LFTs, coagulopathy

Lung transplant: breathlessness, pulmonary infiltrate

b) subclinical
- heart –> clinically silent
- kidney

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14
Q

How do immunosuppressive drugs work?

A

By:
- Targeting T cell activation and proliferation

  • Targeting B cell activation and proliferation, and antibody production
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15
Q

Post transplantation infections

A

Increased risk for conventional infections
Bacterial, viral, fungal

Opportunistic infections – normally relatively harmless infectious agents give severe infections because of immune compromise
Cytomegalovirus
BK virus
Pneumocytis carinii (jirovecii)

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16
Q

Post transplantation, what malignancy would patients be susceptible for?

A
  • Skin cancer

- Post transplant lymphoproliferative disorder – Epstein Barr virus driven

17
Q

how would you increase transplantation // donor activity ?

A
  • increase transplant nurse coordinators
  • national exchange program
  • use marginal donors (e.g old / those w comorbidities)
18
Q

HLA A , B, C + HLA DR3 –> most polymorphic expressions

A

-

19
Q

How do you prevent rejection of organ?

A
  • maximise HLA compatibility
  • drugs that terminate complement activation e.g anti - C%
  • splenectomy
  • Bortesomib has anti T cell actions (proteosome inhibitor)
20
Q

Anti CD52 mAB = kills off T cells

Anti - CCD25 MAB =targets

A

-

21
Q

describe the standard immune suppressive regime:

A

Pre transplantation stage: induction agent

from time of transplantation = baseline immunosuppression