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Flashcards in Transplantation Immunology Deck (22):

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

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


What are the 2 types of acute rejection?

Acute cellular rejection (cell mediated)
Acute antibody-mediated rejection (humoral)


What is the mechanism of action of acute cellular rejection?

- 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


What is endarteritis?

Tunica intima inflammation


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

- 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


What is MICA?

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


What can be used as a marker for rejection?

C4D levels (complement component 4)


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

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


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

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


When would hyper-acute rejection occur?

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


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

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


When would chronic rejection occur?

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


How do you prevent acute rejection?

HLA matching
Minimise ischemia


What is HLA?

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


What are the types of MHC?

Class I is on almost all nucleated cells
Class II is on APCs (HLA-DR is the most common, DR4)


Why would minimising ischemia be beneficial?

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


How is hyper-acute rejection prevented?

ABO compatibility
Checking pre-formed anitbiotics


How is chronic rejection prevented?

- choose the best organ
- minimise surgical damage, acute rejection, drug toxicity


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

Early on very aggressive and then reduces.


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

Bone marrow derived cells of the donor are lost
Develop an active regulation


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

Prevents activation of CD4+ cells
If CD4+ cell activated = secrete IL2 = clonal expansion


What immunosuppressants can be used?

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

Corticosteroids used to prevent cytokine gene activation