LECTURE 2 (Transplants) Flashcards
What is an indication of on organ transplant?
When the organ has failed
What are Bone marrow transplants?
A special type of transplant procedure
HOW IT IS DONE
1) Recipient bone marrow is abolished with chemotherapy
2) Replace all cell lines with donor marrow
- sometimes bone marrow can come from the same person (autotransplant)
- blood type can change (if from different person because bone marrow cells that make red blood cells are altered)
What are the reasons for Bone marrow transplants?
- Malignancy (leukaemia/lymphoma)
- Inherited red cell disorders (pure red cell aplasia, sickle cell disease, beta-thalassemia)
- Failure of bone marrow (aplastic anaemia, fanconi anemia)
- Metabolic disorders (adrenoleukodystrophy, Gaucher’s disease)
- Inherited immune disorders (severe combines immunodeficiency, wiskott-aldrich)
What is an Autograft?
Donor-recipient is the same person
Explanation: Bone marrow cells are harvested from the patient -> chemotherapy is used to kill any remaining cells/leukemia cells -> Bone marrow is reintroduced into the same patient
What is a Syngenetic graft?
A graft coming from an identical twin
What is a Xenograft?
A graft coming from a donor from a different species
What is an Allograft?
A graft coming from a donor from the same species
What are the features of a good match?
- Same blood type
- Same/or close MH I and II molecules (if antigen-presenting cell has self-antigen and self MHC = T cell won’t attack BUT if APC has self-antigen but donor MHC = T cell will attack)
- Negative cross-matching screen (test donor cells against recipient plasma -> ensures no antibodies that will attack donor tissue)
Why is it important to match MHC molecules?
- Donor cells express MHC I (on most body cells) (if different from recipient -> CD8 cells will react)
- Many donor cells also express MHC II (on macrophages, dendritic cells) -> donor APCs may be carried along into tissues + vascular endothelial cells may also express MHC II
Explanation: If both MHC I and II are very different from recipient, they will be attacked by T cells
What are HLAs?
Human Leukocyte Antigens
- Antigens that make up MHC class I and II molecules
- If different between donors and recipients -> immune system will classify donor tissue as foreign
Explanation: In order to match the MHC class molecules you need to match the HLAs
How do you match the Human Leukocyte Antigens (HLAs)?
- Genes on chromosome 6 encode HLA antigens -> determine HLA type
- MHC CLASS I genes = HLA-A, HLA-B, HLA-C
- MHC CLASS II genes = HLA-DR, HLA-DM, HLA-DO, HLA-DP, HLA-DQ
HLA subtypes are polymorphic (there’s so many!) (e.g more than 50 HLA-A subtypes numbered A1, A2 etc) -> if donor-recipient do not match = rejection
HLA subtypes are associated with ________________ diseases
Autoimmune
Example: HLA subtype B27 has a higher risk of ankylosing spondylitis (inflammation of ligaments and joints in spine), psoriasis, IBS, Reiter’s syndrome (arthritis caused by infection)
How many sets of HLA genes are there per patient?
TWO SETS of HLA genes
Explanation: One set from mother, one set from father en bloc (in sets) -> siblings have 25% chance of perfect match
What are the most important HLA genes for solid organ transplants?
- HLA-A
- HLA-B
- HLA-DR
What does it mean when someone says “6 out of 6 match”?
When the donor and the recipient completely match in two sets of the HLA genes “HLA-A, HLA-B and HLA-DR” (most important genes for solid organ transplants”
Additional info: sometimes more genes are tested such as HLA-C and HLA-DQ and you hear “10 out of 10 match”
What are the two problems that may arise with mismatch?
- Rejection of new cells
- Graft vs host disease
What is Graft versus host disease?
A complication of bone marrow transplant (sometimes seen also in solid organ transplants)
Donated T-cells (CD8) react to recipient cells -> Opposite of rejection since it’s the DONATED cells that sees the recipient cells as foreign
SYMPTOMS:
- Skin: rash
- GI tract: diarrhoea, abdominal pain
- Liver: increased LFTs, increased bilirubin
Why might a small degree of “Graft versus host disease” be good?
New WBCs in bone marrow can kill residual cancer cells in recipient and is called “Graft-vs-leukemia (GVL) effect” -> associated with increased overall survival (less relapse)
What are the three different types of rejection?
- Hyperacute (minutes)
- Acute (weeks-months)
- Chronic (years)
Describe Hyperacute rejection
Occurs within minutes of transplantation
CAUSE: caused by preformed antibodies in recipient
- against ABO or HLA antigens
- antibodies formed from previous exposure to foreign antibodies (e.g pregnant women exposed to baby daddy’s antigens, blood transfusion, previous transplantation)
UNCOMMON and prevented by cross-matching screen
SYMPTOMS:
Blood vessel spasm leading to Intravascular coagulation -> organ develops acute ischemia “white rejection” -> rare but not treatable
Describe Acute rejection
Occurs weeks to months after transplant
CAUSE: recipients T-cells react to graft via HLA antigens (cell-mediated immune response) -> CD8 T-cells attack donated tissue cells -> Biopsy: infiltration of lymphocytes/mononuclear cells
TREATMENT: immunosuppression
Describe Chronic rejection
Occurs months or years after transplant
CAUSE: inflammation and fibrosis
- kidneys: fibrosis of capillaries + glomeruli
- heart: narrowing coronary arteries (transplant vasculopathy)
- lungs: bronchiolitis obliterans (fibrous tissue that blocks lumen of bronchioles)
It is a complex, incompletely understood process that involves cell-mediated and humeral systems
