3.3.1 Tumor and Transplant Immunity Flashcards
(37 cards)
What are the three phases of immunoediting?
Elimination, equilibrium, escape
What are three therapeutic usages of Ab’s in regards to tumor treatment?
Immunodepletion, Receptor blockade, Toxin/drug/radio-conjugated Ab’s
What is Rituximab?
Anti-CD20
What is T cell exhaustion?
Repeated stimulation of T cells results in anergy
Mediated, at least in part, by negative regulators of T cell signaling (CTLA-4 and PD-1)
What is CTLA-4?
Inhibitory co-receptor on activated T cells .
Binds B7-1/2
What does CTLA-4-Ig block?
Blcoks CD28 co-stimulation by binding B7-1/2 (Abatacept)
inhibitory signaling
What is the drug name of CTLA-4-Ig? Does it enhance or diminish T cell activity?
Abatacept; Diminishes T cell activity by blocking CD28 binding
What does ipilimumab bind? Does it enhance or diminish T cell activity? When would you use this drug?
CTLA-4. Enhances T cell activation. When trying to fight cancer.
Other than CTLA-4, what is the inhibitory co-receptor on T cells? What is its binding partner?
PD-1; PD-L1 and PD-L2 on DCs
What drug blocks tolerance through an anti-PD-1 mechanism?
Nivolumab, approved for melanoma and NSCLC
What is the process of creating the Supleucel-T vaccination?
Isolate APCs from patient, incubate with PAP (prostatic acid phosphatase- the tumor Ag)/GM-CSF, reinfuse the cells back into the patient
What is unique about synthetic Ab’s?
They can have have two different variable regions specific for different targets (tumor Ag and immune receptors on T and NK cells)
What would be a successful target for B cell leukemias/lymphomas?
CD19
What does scFv stand for?
Single chain Ab
What do they use to fuse a scFv to a T cell?
A zeta chain
Define syngenic.
Genetically identical
Define congenic.
genetically identical except for a single locus (e.g. knock-out mouse line)
Define allogenic.
different members of the same species
Define Xenogeneic
Members of a different species
What is autologous transplantation?
Transplantation within the same individual (e.g. Skin grafts)
What are the two immunologic mechanisms of transplant rejection?
Ab’s and T cells especially CTLs
Differentiate b/t direct and indirect allorecognition.
Direct: recipient T cells recognize donor cells
Indirect: recipient APCs present donor antigens via cross-presentation
What is the mixed lymphocyte reaction used for? How does it work?
Tests T cell-mediated rejection.
Mixed recipient cells with irradiated donor cells. If recipient cells respond, they proliferate.
What are the 3 different phases of allograft rejection. Describe the time frame and processes involved in each.
Hyperacute: pre-existing Ab, often occurs if not correctly blood matched, activates complement and clotting (within minutes to hours)
Acute: CTLs target graft or BVs within graft (days to weeks)
Chronic: Th1-mediated (CTL, macrophages), to lesser degree Ab and complement, progressive loss of graft function, fibrosis of graft and graft arteriosclerosis (months to years)
