Cancer And Immunomodulation Flashcards
_______________ induce tumor cells with identical new antigens while _____________ induce tumor cells with dissimilar new antigens
Oncogenes viruses, chemical carcinogens
_____________________ is the idea that tumors never really mature into life-threatening cancers because of immune mediated destruction of nascent malignancies
Immune surveillance
Normal cells contain what two types of genes that regulate DNA repair, cell death, and regulate cell division?
Tumor-suppressor genes
Protocol-oncogenes
Mutations in tumor suppressor genes and proto-oncogenes leads to production of ______________ that stimulates an immune response
Different proteins (antigens).
What three cell types participate in tumor cell destruction ?
Tcells
NKcells
Macrophage
Tcells release what cytokines to activate NKcells and how does this lead to tumor cell destruction?
IFNy
IL2
NK cells recognize lack of MHC
Produce perforins and grazymes leading to apoptosis
NK cells release what cytokines to activate macrophages and what role do macrophages play in tumor cell destruction?
IFNy
Phagocytosis
Transformed cells can have what three outcomes in relation to the immune system ?
Eliminated
equilibrium
Escape
How does the immune system eliminate transformed cells?
Immunosurveillance
Activation of CD4, CD8, NKcell, and Macrophages leading to apoptosis
What conditions leads to equilibrium of transformed cells with the immune system?
Genetics instability of the cells-> change antigens on surface
CD4 and CD8 cells along with INFy and IL12 work to recognize cells and apoptose some but when antigens change must recognize new antigen before it can kill it
Immune system cannot completely remove the transformed cells but works to keep them in check
How can transformed cells escape the immune system ?
Transformed cells produce immune system inhibitors (TGF-B,IDO, IL10, Galectin1) –> immunosuppression
Tumor cells grow freely without being attacked by the immune system
What are 4 important changes in the immune status of dogs with cancer?
Elevated white cell counts (increases as tumor progresses) => inflammation
Decrease in CD3+ and CD4+ cells => tumor induced immunosuppression
Increased TGF-B => immunosuppressive and stimulate angiogenesis
What are the main actions of TGF-B
Regulate Tcell and B cell activation/function
-> reduces proliferation
Regulate macrophages
Regulates cell proliferation, growth, differentiation, and motility
What is the purpose of immunopharmacology ?
To suppress or stimulate the immune response
What are 5 non-specific modes of immunosuppression
Radiation Corticosteroids Cyclophosphamide Methotrexate Azatiphrine
What non specific immunosuppression method targets DNA to induce mutations?
Radiation
Cyclophosphamide and Azatiophrine both target DNA, to ________________ and to _______________, respectively
Suppress bone marrow
Inhibit synthesis of DNA and RNA
__________________ targets dihydrofolate reductase to inhibit synthesis of thymine and purine nucleotides
Methotrexate
How does use of corticosteroids suppress the immune system??
Corticosteroid binds receptor
-> complex activates transcription of IkBa
IkBa inhibits NF-kB
Reduce gene transcription and cytokine synthesis
What are the 7 methods of selective immunosuppression?
Cyclosporine Tracolimus Rapamycin Mycophenolate Leflunomide Antiserum Antibodies
Cyclosporine and Tracolimus both target __________ to inhibit production of interleukins, IFNy, and TNFa
Cacineurin -> blocks transcription
_______________ targets mTOR to block IL 2, 4, and 6
Rampamycin -> complex with mTOR to block signal transduction and cell cycle progression
Antibodies target ___________ to inhibit the _________ immune response
CD32; humoral
Mycophenolate and lefluonmide target DNA to ____________________ and _________________________, respectively
Prevent DNA synthesis (block Tand B cell proliferation )
Produce T regulatiory cells
What are stimulators of the immune system
Bacilli Calmette-Guerin Complex carbohydrates Levamisole Vitamins Cytokines
How does Bacille Calmette-Cuerin stimulate the immune system?
Targets TLRs to enhance B and Tcell response
How doe complex carbohydrates stimulate the immune system?
Activate macrophages
How does Levasmisole stimulate the immune system?
Tcell differentiation
Increase cytokines and phagocytosis
How do vitamins stimulate the immune system
Increase IL2 production
Increase antimicrobial capacity in macrophages
Increase lymphocyte proliferation
