Transplantation Flashcards
What is autologous transplant vs xenograft?
Transplant from the same individual
Xenograft = transplant from another species
What is syngeneic vs allogeneic transplant?
Syn - transplant from a twin
Allo - from a different individual of the same species
What is a common autologous transplant?
Skin grafting or hematopoeitic stem cells
What is a haploidentical donor?
Donor with a match on 50% of HLA alleles (all one one chromosome). It will be 50% of siblings. Another 25% will be a perfect match.
Children and parents will always be haploidentical
What is graft rejection?
Host immune system recognizes graft as foreign and causes immune-mediated dysfunction of the graft
What is first-set vs second-set rejection?
First-set: Primary response which is delayed
Second-set: antibodies to foreign graft have been made, graft rejection is very quick
What is hyperacute rejection? What is its primary mechanism?
Graft rejection happening in minutes to hours mediated by IgG
Primary mechanism is intravascular thrombosis to decrease blood delivery to the organ
What gives a majorly increased risk for hyperacute rejection?
Multiple blood transfusions (WBCs can come from this and our immune systems can attack this), previous transplantation, or multiple pregnancies
What causes acute-rejection and what mediates it?
This is the “First-set rejection”
Occurs in a few days to weeks, mediated by CD4/CD8 T cells, leading to humoral response.
Mechanism: parenchymal damage / inflammation
What is chronic rejection?
Occurs at 6 months to years,
mediated by Th2 CD4+ and CD8+ cells as well as macrophages
Mechanism: Chronic fibrosis and accelerated atherosclerosis
What is graft-versus-host disease (GVHD)?
When immune cells are transplanted into immune suppressed host, the immune system can treat body organs as foreign
What describes acute GVHD?
T cell mediated, early after transplant, usually has skin, liver, or GI tract involvement (especially CD8+)
What describes chronic GVHD?
T and B cell mediated, after 100 days. Make antibodies to self antigens and also CD8+ T cells will attack
Multiple organ involvement is likely
What is overlap syndrome?
Something that has features of acute and chronic GVHD
What cytokines increase MHC Class 1 expression?
IFN alpha and IFN beta
How does the Mixed Lymphocyte Reaction (MLR) work?
T cells from donor are mixed with irradiated lymphocytes from recipient. If T cells proliferate and attack lymphocytes of recipient, indicates high chance of GVHD
How does the complement-dependent cytotoxicity (CDC) test for lymphocyte testing work?
Lymphocytes are placed in wells with antibodies specific for each HLA type, if complement is fixed it means you have the HLA type expressed, and lysed cells can pick up dye in the well
How can you antibody test a given HLA type for a recipient?
Mix the organ donor’s lymphocytes with the recipient’s serum and see if the cells are lysed in the presence of complement, allowing them to pick up dye.
We don’t want the recipient to have antibodies against donor HLA.
How is HLA testing done now?
Sequence-based testing via PCR
Why are calcineurin inhibitors effective?
Calcineurin activates nuclear factor of activated T cells, which promotes expression of IL-2
Inhibiting this blocks T cell proliferation
How does cyclophosphamide work?
Used in haplo-matches, kills proliferating T cells, works as a cytotoxic chemotherapy / immunosuppresant
What are IMPDH inhibitors good for?
Inhibiting guanine synthesis
What does inhibition of mTOR do?
Inhibits IL-2 signalling
What marker do hematopoietic stem cells express?
CD34
How can the recipient immune system be killed off?
Administration of high dose chemo / radiation therapy
What type of conditions is full hematopoeitic stem cell transplant preferred?
In non-malignant hematologic conditions, in which the entire immune system can be replaced to correct a genetic defect
What is cord blood?
The storing of baby’s umbilical stem cells away for later use. Anyone can donate their baby’s leftover cord blood from umbilical cord and placenta
How is a peripheral blood harvest used to get bone marrow?
Patient given granulocyte-CSF to stimulate proliferation
Patient given CXCR4 blocker for stem cells to migrate out of the marrow into the blood
Blood drawn by apheresis, stem cells can be cryopreserved without loss of function
How is bone marrow injected?
IV infusion of stem cells allowed them to “home” into bone marrow space naturally
When is autologous stem cell transplant used?
When chemotherapy is limited by marrow toxicity
-> take a bone marrow draw, do chemotherapy, and re-inject stem cells
What is the major risk of autologous stem cell transplant?
If the tumor has metastasized to lymph nodes, stem cells transplanted can be abnormal
What is one possible big benefit of allogeneic stem cell transplant?
New immune system can recognize cancer cells as foreign and aid in their removal (possible graft-versus-tumor reaction)
What are three major disease treated with autologous stem cell transplant?
1/2. Hodgkins / Non-Hodgkins Lymphoma
3. Multiple Myeloma
What three general classes of disorders are treated by allogeneic hematopoeitic stem cell transplantation?
- Leukemias
- Congenital immune disorders
- Hemoglobinopathies like sickle cell
What are the three phases of stem cell transplant?
- Conditioning regiment (chemo)
- Transplantation
- Recovery phase of stem cells
Why is corneal transplant so successful?
Cornea is an immune-privileged site, transplants have a high success rate
What is one major complication of stem cell transplant?
Cytopenia can lead to predicable infections of viruses, fungi, and bacterial agents.
Especially bad since skin barrier is temporarily inactive (innate immune system) + puncture wound from IV
What does HLA-G actually do?
Helps fetal cells evade immune response even though they don’t have MHC Class 1 or 2 because it inhibits the NK cells response
