Transplantation Immunology

Question 1

What are the different types of transplant rejection? How are they classified?

Answer 1

Acute - 1 weeks to 6 months post transplantation
Hyper-acute - minutes to hours
Chronic - months to years

Question 2

What are the 2 types of acute rejection?

Answer 2

Acute cellular rejection (cell mediated)

Acute antibody-mediated rejection (humoral)

Question 3

What is the mechanism of action of acute cellular rejection?

Answer 3

• CD4+ (T helper lymphocytes) activate CD8+ (cytotoxic T cells) and macrophages via a cell mediated response
• CD8+ cells produce lymphocyte infiltration, interstitial tubulitis and endarteritis

Question 4

What is endarteritis?

Answer 4

Tunica intima inflammation

Question 5

What is the mechanism of action of acute antibody-mediated (humoral) rejection?

Answer 5

• CD4+ T cells activate B lymphocytes to produce antibodies via a humoral response
• Antibodies form against ABO antigens, MCH class 1 and 2 antigens and MICA
• Antibodies target the endothelium of arteries and capillaries
• C4D gets deposited in the endothelium as a product of the antigen-antibody complex forming complement

Question 6

What is MICA?

Answer 6

MHC class 1 related chain a
Glycoprotein encoded by MICA gene in MHC

Question 7

What can be used as a marker for rejection?

Answer 7

C4D levels (complement component 4)

Question 8

How would you confirm an acute antibody-mediated (humoral) rejection?

Answer 8

Acute renal injury (histology)
Antibody activity (C4D staining in peritubular capillaries)
Circulating anti-donor specific abnormalities

Question 9

What is the main different between acute cellular rejection and acute antibody mediated rejection?

Answer 9

There are more CD4+ cells between connecting cells in acute cellular rejection whereas there are more around the peritubular capillaries in acute antibody mediated rejection

Question 10

When would hyper-acute rejection occur?

Answer 10

previous transplants/transfusion/pregnancy means pre-formed antibodies are already in circulation before transplant occurs

Question 11

What is the mechanism of action of hyper-acute rejection?

Answer 11

Pre-formed antibodies in circulation bind to endothelium = activates complement = thrombosis occurs = tissue breaks down = infarction

In the 1st hour => there are neutrophils in the peritubular capillaries and glomeruli

12-24 hours => intravascular coagulation/cortical necrosis

Question 12

When would chronic rejection occur?

Answer 12

From pre-transplantation graft damage, original disease recurring or rejection

Question 13

How do you prevent acute rejection?

Answer 13

HLA matching

Minimise ischemia

Question 14

What is HLA?

Answer 14

Human body form of MHC
Presents the antigen peptide of the graft/foreign pathogen to the T cell receptors
Individual with several different MHCs will have an increased number of antigen peptides it can bind

Question 15

What are the types of MHC?

Answer 15

Class I is on almost all nucleated cells

Class II is on APCs (HLA-DR is the most common, DR4)

Question 16

Why would minimising ischemia be beneficial?

Answer 16

• Ischemia upregulates adhesion molecules
• increased adhesion during reperfusion after ischaemia
• non specific damage and acute rejection
• increases toxin levels and reactive species

Question 17

How is hyper-acute rejection prevented?

Answer 17

ABO compatibility

Checking pre-formed anitbiotics

Question 18

How is chronic rejection prevented?

Answer 18

• choose the best organ

- minimise surgical damage, acute rejection, drug toxicity

Question 19

What is the relationship between the immune system and the graft?

Answer 19

Evolving

Early on very aggressive and then reduces.

Question 20

Why does the aggression between the immune system and the graft reduce over time

Answer 20

Bone marrow derived cells of the donor are lost

Develop an active regulation

Question 21

What is the purpose of immunosuppression? Which ones are used?

Answer 21

Prevents activation of CD4+ cells

If CD4+ cell activated = secrete IL2 = clonal expansion

Question 22

What immunosuppressants can be used?

Answer 22

Calcineurin inhibitors - anti-IL2 receptor blockers prevent binding of IL2 so there is less clonal expansion

Corticosteroids used to prevent cytokine gene activation