Transplantation and Immunosuppressive Drugs Flashcards Preview

CLINICAL PATHOLOGY > Transplantation and Immunosuppressive Drugs > Flashcards

Flashcards in Transplantation and Immunosuppressive Drugs Deck (36)
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1

What is transplantation? 

Transplantation can be defined as the introduction of biological material (e.g organs, tissue, cells) into an organism 

The problem with that is that the immune system has evolved to remove anything that it regards as non-self 

2

What is an autologous transplant? 

The transplantation from one part of an organism into another part of the same organism 

  • You may see an inflammatory response but there wouldn’t be any problems as it is self-transplanted into self
  • E.g skin transplant from one site to another

3

What is a syngeneic transplant? 

This is where donor material is transplanted into a recipient, however the donor and the recipient are genetically identical 

  • These should not generate an immune response as there is no genetic difference between donor + recipient
  • E.g identical twins

4

What is an allogenic transplant? 

Allogenic transplantation is when a donor donates part of their tissue to a recipient, but they are genetically different. 

An example of this would be siblings/ relatives 

5

Describe Xenogeneic transplants? 

The transfer of tissue from an organism of one species to another 

e.g Pig heart transplant into humans, however this is not common and there have only been a few cases where this happens with success

 

 

6

What are immune responses to transplants caused by? 

Genetic differences between the donor and recipient 

7

What is the most important consideration during transplantation? 

MHC Genes 

  • The most important genetic differences are differences between the antigens forming the MHC 

8

Where are MHC genes located? 

On chromosome 6 

  • Most diverse region in the genome 

9

How is HLA classified? 

MHC I 

  • HLA-A, HLA-B, HLA-C 

MHC II 

  • HLA-DRA, HLA-DRB, HLA-DPA, HLA-DQA, HLA-DQB 

10

How can we match donor and recipient MHC? 

Via next generation sequencing

11

What are the reasons for transplant rejection? 

Either 

  • MHC protein is foreign 
  • Peptide in binding groove is foreign 
    • This can result in different rejection mechanisms 

 

12

What is allorecogition? 

Activation of T cells to react against transplant 

13

Describe indirect allorecognition 

Recipient T cells recognise a self-MHC molecule on a recipient cell with a bound peptide derived from the donor/foreign MHC molecule = T Cell Activation 

14

Describe direct allorecognition

Recipient T cells recognise an intact allogenic (unmatched/foreign) MHC molecule expressed by a donor cell = T cell activation 

15

Are dead or live donors more succesful for transplants? 

  • Live donors are more succesful 
    • This is because dead organ donors are more sensitive to MHC mismatch 
      • Organs from deceased donors are more likely to be in a inflamed condition due to ischaemia 

16

What are the types of graft  rejection? 

  • There are three types of graft rejection 
    • Hyperacute rejection (pre-exisiting anti-donor Abs bind to antigens on donor tissue)
    • Acute rejection (Direct allorecognition)
    • Chronic rejection (Indirect allorecognition) 

17

What is hyperacute rejection? 

Pre-existing anti-donor antibodies rapidly bind antigens on donor tissue and result in 

  • Complement activation 
  • Antibody dependant cellular cytotoxicity (Fc receptors on NK cells) 
  • Phagocytosis (Fc receptors on macrophages) 

18

What is the onset of hyperacute rejection? 

Within a few hours 

19

Which antigens do pre-existing anti-donor antibodies bind to in hyperacute rejection? 

  • Usually to ABO blood group antigens expressed on endothelial cells of blood vessels 
  • MHC I proteins 

20

Where is hyperacute rejection most commonly seen?

In highly vascularised organs e.g kidney 

21

What is the effector mechanism of preexisting anti-donor antibodies in hyperacute rejection? 

  • Antibodies will bind to ABO antigens expressed on endothelial cells 
  • This will lead to complement activation and accumulation of innate immune cells 
  • Endothelial damage = platelet accumulation and development of thrombi 
  • Tissue can die indirectly from this breakdown in the endothelial cells by ADCC and ADCP 

 

22

What is acute rejection? 

  • Direct allorecognition of foreign MHC 
    • Donor DC's will migrate to secondary lymphoid tissue where they encounter effector T-cells = MHC mismatch 
    • Dendritic cells express both MHC I and MHC II meaning they activate both CD8+ and CD4+ T-cells 
    • CTL will increase inflammation and destroy the transplant 

23

What is chronic rejection? 

Indirect allorecognition 

  1. Donor cells die 
  2. Membrane fragments containing donor MHC are taken up by recipient/ host dendritic cells 
  3. Donor MHC is processed into peptides which are presented by host MHC 
  4. T cell response is generated to the peptide derived from the processed donor MHC 

24

What is the onset of chronic rejection? 

Can occur months or years after transplant 

25

How can we transplant immune cells? 

Haematopoietic Stem Cell Transfer (HSCT)

  • Stem cells find their way to the bone marrow after infusion and regenerate there where they are cyropreserved with little damage
  • Often autologous (will not cause an immune response) 

26

What is the risk of transplanting immune stem cells from a donor to recipient (allogenic)? 

Graft vs Host Disease (GVHD) 

  • Risk of donor immune cells attacking the host 
  • Can be lethal 

 

27

How do we prevent graft vs host disease? 

Removing T-cells from transplant or suppressing their function reduces GVHD 

28

Explain a situation where grafting a donor immune system can be beneficial? 

Graft vs Leukaemia 

  • Sometimes mismatch and donor leukocytes are beneficial 
  • Cancer cells are derived from self, and the immune system struggles to identify it as a foreign cell 
    • However, if you have a donor's immune system transplanted it will be able to recognise the cancer as foreign and kill them because of the HLA mismatch 

29

How can we maintain a non-autolgous transplant? 

Immunosuppression drugs are essential to maintain a non-autologous transplant 

30

What are the phases of treatment to immunosuppression following a transplant? 

  • Induction (Preventing the build-up of an immune response against transplant organ) 
  • Maintenance (will be altering dosage depending on the effectiveness of individual treatment) 
  • Rescue (if the immune response mounts towards the tumour)

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