Transplantation immunology

Question 1

3 classifications of rejection

Answer 1

Hyperacute

Acute Chronic

Question 2

When does hyperacute rejection occur

Answer 2

Minutes or hours of transplantation

Question 3

When does acute rejection occur

Answer 3

1 week to 6 months later

Question 4

When does chronic rejection occur

Answer 4

Months to years

Question 5

What mechanism happens in acute rejection

Answer 5

Acute cellular rejection

Acute antibody rejection

Question 6

How does kidney appear in cell mediated rejection

Answer 6

Interstitital tuberlitis
Endothelialitis
Lumen compromised by presence of lymphocytes

Question 7

What happens in acute cellular rejection

Answer 7

Helper T cell stimulates cytotoxic T cell to produce immune response

Question 8

What is antibody mediated rejection

Answer 8

Help T cell produces B lymphocyte which produces antibodies

Question 9

What is the primary target of antibodies in antibody mediated rejection

Answer 9

Endothelium of arteries adn capillaries

Question 10

How does blood vessel appear histologically after antidboy mediated rejection

Answer 10

Inflammation

Question 11

How is cell vs antibody mediated rejection differentiated

Answer 11

Antibody activates complement cascade

C4d forms covalent bonds with thio-ester groups on endothelial cell surfaces and these can be detected

Question 12

What happens when you have complement mediated activation

Answer 12

C1 activated, then C2 and C4

C4d is lost

Question 13

Criteria for acute AMR

Answer 13

1) Evidence of acute renal injury on histology
2) Evidence of antibody activity
3) Circulating anti-donor specific antibodies

Question 14

Is antibody or cell mediated rejection more common

Answer 14

Cell

Question 15

Is antibody or cell rejection more dangerous

Answer 15

Antibody

Question 16

In what kind of person does a hyperacute rejection occur

Answer 16

A person who has been ‘immunologically primed’- they have had a previous transplant, transfusion or pregnancy

Question 17

What kind of response is involved in hyperacute rejection

Answer 17

Antibody mediated

Question 18

How does hyperactive rejection lead to endothelial damage

Answer 18

Preformed antibodies bind to the vessel lumen, activating the endothelium into pro-coagulant state
Leads to thrombosis and damage

Question 19

Reasons why a graft can fail (4)

Answer 19

• It was damaged before transplantation
• Surgical complication
• Recurrence of original disease
• Rejection

Question 20

Define rejection

Answer 20

Recognition and destruction by recipient immune system

Question 21

How do grafts appear after chronic rejection

Answer 21

Lost majority of structure
Not as many tubules
Replaced in large measure by collagen- fibrotic process

Question 22

Who can the following blood groups receive donated organs from

a) A
b) B
c) 0
d) AB

Answer 22

a) A or O
b) B or O
c) O
d) A, B or O

Question 23

How do you prevent hyperacute rejection

Answer 23

Screen for the presence of preformed antibodies.

Question 24

What are most preformed antibodies specific for?

Answer 24

HLA

Question 25

How do you prevent acute rejection

Answer 25

HLA matching | Minimising ischaemia

Question 26

What is the HLA molecule responsible for

Answer 26

Sampling all the proteins around the presenting the antigen on an antigen presenting cell for the T cell receptor

Question 27

What is the advantage of an individual having several different MHC molecules

Answer 27

Increases the number of peptides that can be bound

Question 28

What is the difference between MHC class 1 and class 2

Answer 28

``` MHC class 1 found on every cell MHC class 2 only found on antigen presenting cells ```

Question 29

Why does ischaemia need to be minimised to prevent rejection

Answer 29

- Ischaemia upregulates adhesion molecules - Increases adhesions of leucocytes during rreperfursion - Increases non specific damage

Question 30

How to prevent chronic rejection (4)

Answer 30

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

Question 31

Why is the immune response to graft less aggresive over time

Answer 31

Loss of bone marrow derived cells of donor | Development of active regulation

Question 32

What factors affect the 'load' (how much stress the kidney undergoes)

Answer 32

``` Hypertension Hyperlipidaemia CNI toxicity Senescence Alloimmune injury Hyperfiltration CMV ```

Question 33

What can cause inflammation of the transplant (3)

Answer 33

Ischaemia reperfusion CNI toxicity Alloimmune injury

Question 34

Where can imunosuppresants target

Answer 34

- Take out T cell receptor - Calcineurin inhibitors which inhibit transduction of signal - Steroids inhibit gene activation - Anti IL-2 - Anti metabolites present cells from dividing