Transplantation and Tumor Immunology Flashcards
Define autograft.
Self-donation
Define syngraft.
Genetically identical recipient
Define allograft.
Genetically different recipient
Define xenograft
Graft to/from a different species
What are the two ways a recipient’s T cells recognize a graft?
- T cells regognized processed donor peptides that are presented by recipient APCs.
- Recipient T cells recognize unprocessed donor MHC molecules on graft APCs.
What are the three types of rejection?
- Hyperacute
- Acute
- Chronic
How long does it take for hyperacute rejection to occur?
Minutes or hours
How long does it take for acute rejection to occur?
10-14 days
How long does it take for chronic rejection to occur?
Months or years
What is hyperacute rejection mainly due to (what is the mechanism)?
Due to pre-formed antibodies in the recipient, activating complement system - Abs could have been formed due to a previous blood transfusion.
What are the four mechanisms involved in acute rejection?
- Direct contact between CD8+ cells and the graft - release of perforin and granzyme, Fas L expression.
- Locally released cytokines and chemokines –> inflammation, macrophage activation, infiltration of phagocytic cells.
- Antibody attack against donor HLA molecules –> complement binding and ADCC by NK cells.
- Direct NK cell attack
What cells/factors are responsible for chronic rejection?
Ab, T cells and NK cells attack the graft.
What major disease sometimes arises after stem cell transplantation?
Graft vs. host disease (GVHD).
How does graft vs. host disease (GVHD) work?
Some CD4+ T cells that were present in the graft recognize the host antigens and proliferate and cause a “cytokine storm” that recruits cell-mediated effectors and results in inflammation.
What are three requirements for graft vs. host disease (GVHD) to occur?
- Graft must contain live T cells
- Recipient must be immunosuppressed
- Donor and recipient must have different HLA types (no identical twins)
Name two drugs that block calcineurin.
Cyclosporine and FK506
What does calcineurin do?
A phosphatase that is activated during T-cell binding of MHC+peptide that stabilizes IL-2 and IL-2R mRNA —> T cell activation
Do corticosteroids block cytokine production?
For sho
What do anti-CD3 and anti-IL2R monoclonal antibodies do?
Block T cell activation!
What might virally-induced cancer cells express on their surfaces?
Virally-controlled antigens, modified glycoproteins, etc.
What are oncofetal antigens and how do they relate to cancer?
They are normally only expressed during fetal development that can be expressed in adulthood in malignant cells.
Name two oncofetal antigens.
- Alpha-fetoprotein (primary hepatocellular carcinoma)
2. Carcino-embryonic antigen (colon/GI cancers and breast cancers)
Name an anti-Her2/neu drug
Herceptin (MAb with immunotoxin attached)
Name tissue-specific differentiation antigens that are often increased in prostate cancer and separately in lymphomas.
Prostate-specific antigen (PSA) in prostate cancer.
B and T cell markers are examples (CD19, 20, CD3, 4, 8 etc.) in lymphomas.
