Immunology 5 - Transplants

Question 1

What is an autologous transplant?

Answer 1

Tissue returning to individual after period outside the body

Question 2

What is an syngeneic transplant?

Answer 2

Between twins (also called isograft)

Question 3

What is an allogenic transplant?

Answer 3

Non-identical members of the same risk of species

Question 4

What is an xenogeneic transplant?

Answer 4

Different species (highest risk of rejection)

Question 5

What are the criteria for solid organ transplantation?

Answer 5

Disease must not recur
Good evidence damage is irreversible
No alternate therapy

Question 6

How is rejection chance minimised?

Answer 6

ABO compatability
Recipient must not have anti-donor HLA antibodies
Must be as close HLA as possible
Patient take immunosuppressives

Question 7

What transplant does not require immunosuppressants?

Answer 7

Corneal transplant (not vascularised)

Question 8

What is hyperacute rejection?

Answer 8

Within hours
Antibodies binding either to ABO or HLA class 1 on graft
Type 2 hypersensitivity reaction
Damage via thrombosis

Question 9

How is hyperacute rejection prevented?

Answer 9

HLA and ABO crosstyping

Question 10

What is acute rejection?

Answer 10

Type 4 (delayed) hypersensitiity 
HLA incompatibility the main cause

Question 11

What is acute antibody mediated rejection?

Answer 11

Antibodies form after grafting and cause vascular injury leading to a thrombus

Question 12

What is chronic rejection?

Answer 12

Months - years post-transplant
T-cell mediated
Can recur pre-existing autoimmune disease

Question 13

What is tolerance?

Answer 13

Unresponsiveness of immune system to the body’s own cells

Function mimicked by immunosuppressives

Question 14

Outline the pathology of graft rejection?

Answer 14

Afferent phase: donor MHC molecules on dendritic cells recognised by host CD4+ cells
Effector phase: CD4+ recruit macrophages, CD8, NK and B cells to reject

Question 15

What are the mechanisms for graft rejection?

Answer 15

Direct alloantigen recognition (T-cell recognises foreign free antigen)
Indirect alloantigen recognition (Foreign antigen processed then presented)

Question 16

How are tissues ‘typed’?

Answer 16

HLA typing
HLA cross matching 
(A, B and DR loci) 
ABO compatibility
T lymphocytes

Question 17

What are the different types of stem cell transplant?

Answer 17

Autologous SCT

Allogenic SCT

Question 18

Outline the process, pros and cons of autologous SCT?

Answer 18

Marrow removed, frozen and reinfused post-chemotherapy

Minimum risk

Question 19

Outline the process, pros and cons of allogenic SCT?

Answer 19

Can be used in blood cancers or primary immunodeficiencies
Risk of Graft vs host disease
High mortality

Question 20

What are the sources of stem cells?

Answer 20

Bone marrow
Peripheral blood (post colony-stimulating factors)
Cord blood

Question 21

What is the role of conditioning for stem cells?

Answer 21

High dose RT/chemotherapy to destroy host stem cells for engraftment

Question 22

What is Graft Vs Host disease?

Answer 22

Where donor T cells attack the allogeneic antigens
HLA mismatch antigens 
Prevented with immunosuppressives 
70% mortality risk
Skin, gut, liver, lungs affected

Question 23

What are the main groups of immunosuppressives?

Answer 23

Corticosteroids
T-cell Signalling Blockade (Cyclosporine/Tacrolimus)
IL-2 blockade
Antiproliferatives

Question 24

Give 3 side effects of Cyclosporine?

Answer 24

Increased risk infections, cancers
Nephrotoxicity
Diabetes
Hypertension

Question 25

Give 3 side effects of Rapamycin?

Answer 25

``` Raised lipds, cholesterol Hypertension Anaemia Diarrhoea Thrombocytopenia ```

Question 26

What issues are associated with xenotransplants?

Answer 26

Galactose-a1,3-galactose present on non-primate cells Recipient antibodies bind to this and activate complement Hyperacute rejection

Question 27

Outline how Corticosteroids work?

Answer 27

Inhibit antigen-presenting cells and T cells at higher doses (used early)

Question 28

Outline how Cyclosporine/tacrolimus work?

Answer 28

Interact with intracellular T-cell signalling cascade

Question 29

Outline how Monoclonal antibodies work to suppress the immune system?

Answer 29

IL-2 Blockade | Used in acute rejection

Question 30

Outline how Rapamicin works?

Answer 30

IL-2 Blockade | Prevents graft rejection

Question 31

Outline how Antiproliferatives work?

Answer 31

(Azathioprine, methotrexate) Inhibit DNA production Prevent lymphocyte proliferation Suppress the bone marrow