Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

MIIM30003 - Medical & Applied Immunology > Lecture 12 - Transplant Immunology I > Flashcards

Lecture 12 - Transplant Immunology I Flashcards

You may prefer our related Brainscape-certified flashcards:
USMLE® Step 1 flashcards
1
Q

Which organs are commonly transplanted?

A
  • Corneas
  • Lungs
  • Liver
  • Heart
  • Kidneys
  • Pancreas
  • Intestines
  • Femoral and saphenous veins
  • Bone
  • Skin
  • Tendons
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the various types of transplant?

Give examples of tissues / organs that are commonly transplanted for each

A
  1. Autograft
    • Transplant of tissue from one location to another within an individual
    • Skin grafts
  2. Isograft
    • Transplant between genetically identical individuals
    • Kidneys
  3. Allograft
    • Transplant between two different individuals of the same species
    • Solid organs transplant
  4. Xenograft
    • Transplant between to individuals of different species
    • Porcine valves
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

List some of the highlights of transplantation over the past centuries

A

1668 - van Meeneren

1869 - Reverdin

1906 - Zirm

1954 - Joseph Murray
• First kidney transplant

1963 - James Hardy
• First lung transplant

1963 - Thomas Starzl
• First liver transplant

1964 - Christiaan Barnard
• First heart transplant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

List the immunoprivileged sites in the body

A
  • Eye
  • Brain
  • Testis
  • Uterus
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Describe the ABO blood groups

A

Four groups:
1. A
• Natural Abs against B in circulation

  1. B
    • Natural Abs against A
  2. AB
    • No natural Abs
    • Universal recipient
  3. O
    • Abs against A and B
    • Universal donor

The A and B refer to terminal residues on carbohydrates on the surface of our RBCs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Who discovered the ABO blood groups

A

Landsteiner

1901

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Describe Medawar’s experiments with skin grafts

A

Demonstrated that graft rejection was immune mediated

Observations:
• Skin grafts between genetically identical (identical MHC) individuals (mice) were accepted

  • Skin grafts to allogeneic recipients resulted in rapid rejection: ‘First set rejection’
  • Repeated this results in accelerated rejection of graft: ‘Second set rejection’
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Which hallmarks of the immunological response are seen in transplant rejection?

A

Memory

Specificity

Increasing magnitude with subsequent exposure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Which cells mediate transplant rejection?

A

T cells
• CD4+
• CD8+

B cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

When were HLA molecules discovered?

A

1959

Dausset and van Rood

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Where are MHC molecules encoded?

A

p arm of Ch. 6

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

List the various HLA loci

A

Class I:
• B
• C
• A

Class II:
• DP
• DQ
• DR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

HLA genes are highly…

A

polymorphic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Describe the pros and cons of HLA polymorphism

A

Pros:
• Means that individuals wan present a wide range of peptides

Cons:
• Challenging to match for transplantation between individuals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Where is most of the ‘variation’ in HLA molecules?

A

CDRs
Within the peptide binding cleft

Class I: α1 domain
Class II: β1 domain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Which are the major molecules responsible for transplant rejection?

A

MHC

17
Q

Characterise the correlation between HLA matching and transplant rejection

A

With increasing HLA mismatches, transplant rejection is more likely

18
Q

Is is possible for HLA matched transplants to be rejected?

A

Yes
There are other Ags that can mediate rejection:

Minor histocompatability Ags

19
Q

Compare importance of HLA matching in renal and lung transplant

A

Renal transplant:
• HLA matching is important
• Hence, there is a national registry

Lung tx:
• Matching is not as important
• No national registry
• Lungs are routinely transplanted across HLA mismatch

20
Q

Describe minor histocompatability Ags

A

Allopeptides presented by MHC molecules on the graft cells

Peptides derived from:
• Proteins only present in the donor (e.g. H-Y male Ags)
• Polymorphic proteins

21
Q

Describe how H-Y Ags can cause rejection

A

Ags encoded on the Y chromosome will be absent in females, and thus the immune system will not be tolerant of them

When organs are transplanted from males into females, there is de novo generation of Abs against these H-Y Ags

Detection of H-Y Ab in recipient correlates with acute transplant rejection

22
Q

Describe how polymorphic proteins can lead to transplant rejection

Give examples

A

There are many proteins that can be polymorphic

The recipient’s immune system will not be tolerised against these slightly different Ags

Examples of minor H Ags:
 • HA-1
 • HA-2
 • HA-8
 • HB-1

These Ags have certain HLA restrictions

In an ideal world, recipients would be HLA typed before transplant to make sure that they do not have the HLA molecules that will present these minor H Ags

23
Q

List the different types of rejection reactions

Describe the following features of each:
• Time frame
• Cause

A
  1. Hyperacute
    • Minutes - hours
    • Pre-formed Abs against donor Ags
  2. Acute
    • Days - weeks
    • Primary activation of T cells
  3. Chronic
    • Months to years
    • Causes unclear
24
Q

Describe the pathogenesis of hyperacute allograft rejection

In what situations can it occur?

A

Can occur when:
1. Individual presensitised to graft Ags
• Blood group
• MHC

  1. Previously experienced Ags:
    • Blood transfusion
    • Transplant
    • Pregnancy

Pathogenesis:
1. Transplantation of organ

  1. Abs immediately bind to Ags in vasculature
  2. C’ activation
  3. Recruitment of inflammatory cells
    • PMNs
  4. Lytic enzymes released by neutrophils
  5. Formation of thrombi
  6. Occlusion of blood vessels of graft
  7. Graft haemorrhages
25
Q

What does one look for in histologic diagnosis of hyper acute rejection?

A

Fixation of C’

esp. C4d

26
Q

Describe the two ways that allorecognition can occur

A
  1. Indirect allorecognition
  • Self MHCs take up donor Ag in graft
  • Foreign peptide presented in self MHC
  • Now appears ‘foreign’ to T cells
  1. Direct allorecognition
  • Donor APCs migrate to recipient LNs
  • Allogeneic MHC recognised strongly by recipient T cells
27
Q

Describe the role of the various lymphocytes in acute rejection

A

– CD8+ T cells –

  1. Direct / indirect Ag presentation
  2. CD8+ T cells become activated
  3. CTLs infiltrate into graft
  4. CTLs recognise graft Ag and kill the cells (perforin dep.)

– CD4+ T cells –

  1. Direct / indirect Ag presentation
  2. CD4+ T cells become activated
  3. Th1 produce IFN-gamma, helping macrophages
    Macrophages phagocytose graft cells

– B cells –

Th2 produce IL-4 and IL-5, helping B cells produce Ab against graft Ag

Abs bind graft vascular endothelium

C’ activation and ADCC in graft vasculature

28
Q

List the various cytokines secreted by Th1

A
  1. IFN-gamma
    • Helps macrophages to kill ingested pathogens
  2. TNF and LT
    • Causes local tissue destruction
  3. GM-CSF
    • Stimulates monocyte production in BM
  4. Chemokines
    • Recruits macrophages
29
Q

Describe the pathogenesis of chronic rejection

A 
1. Smouldering injury:
 • Ischemia / reperfusion injury
 • Infection
 • Dyslipidaemia
 • Hypertension
  1. Chronic low level injury and repair of graft vasculature
  2. Fibrosis of graft vasculature
  3. Progressive narrowing of graft vasculature / tubules
    • Bronchioles → Bronchiolitis obliterans syndrome
    • Renal tubules → chronic allograft nephropathy
    • Coronary arteries
    • Bile ducts → Vanishing bile duct syndrome
30
Q

Compare the ‘pathology’ in each of the types of rejection

A

Hyperacute rejection:
→ Pathology of coagulation

Acute:
→ Pathology of inflammation

Chronic:
→ Pathology of tissue remodelling

MIIM30003 - Medical & Applied Immunology (30 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions