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Week 6

Dolu Falowo Foundations 4 Englisch 23 Karten

Karten in diesem Stapel (23)

  1. 1What are the 3 most common cancers in adults?-Lung
    -Bowel
    -Colorectal/breast
  2. 2What are the 3 most common cancers in children?-Leukaemia
    -CNS
    -Neuroblastoma (aggressive)
  3. 3What is the function of p53?-Inducing cell cycle arrest, senescence and apoptosis
    -Responds to stress signals
  4. 4What is p53 controlled by?-MDM2 targets p53 for ubiquitin-dependent degradation
    -MDM2 modulates p53 transcriptional activity
  5. 5Describe the feedback loop involving p53-p53 activates transcription of MDM2
    -Increased expression of MDM2 (+MDM4) decreases p53 levels and inactivates it
    -Further decrease in rate of MDM2 transactivation by p53
  6. 6What is ARF?-Tumour suppressor
    -Interacts with MDM2 and inhibits p53 degradation
  7. 7Describe elimination in terms of immunoeditingImmune-mediated destruction of most cancer cells
  8. 8Describe equilibrium in terms of immunoeditingThe immune response to enough to contain but not fully eliminate genetically unstable and mutating tumour cells
  9. 9Describe escape in terms of immunoeditingTumour cell variants selected in the equilibrium phase now grow out in an immunologically intact environment
  10. 10What does activation of T cells need?-TCR binding to MHC molecule with loaded antigen
    -CD80/86 on APC binding to CD28 on T cell
  11. 11What are some examples of tumour-associated antigens?-Mutated self proteins
    -Over-expressed self proteins
    -Lineage specific antigens
    -Abnormal post-translational modification of self protein
    -Viral proteins
  12. 12What makes a good target antigen for tumour immunotherapy?-Tumour-specific (reduced toxicity)
    -Widely applicable to patients with the same tumour
    -Critical for tumour growth/survival
    -Lack of immunological tolerance
  13. 13What is the evidence for tumour protective immunity in humans?-Immunosupressed more frequently develop cancers (esp. virus-associated)
    -Cancer patients develop spontaneous immune responses to their own tumours
    -Presence of immune cells correlates with improved prognosis
  14. 14How do tumours escape the immune response?-Loss of HLA class I (MHC) expression
    -Reduced expression of other molecules involved in antigen processing/presentation
    -Loss of co-stimulatory molecule expression (CD80/86)
    -Loss of adhesion molecule expression
    -Loss of target antigen
    -T cell infiltration inhibition
  15. 15Describe how immunosuppression at the tumour site occurs-TGF beta supresses anti-tumour T cell functions + induces Tregs
    -IDO blocks CD8+ proliferation and promotes apoptosis of CD4+ cells
    -Inhibition of dendritic cells (no APCs)
    -FAS ligand, which kills T cells
    -Recruitment of Tregs
    -Myeloid-derived suppressor cells suppress T cell function
  16. 16What triggers the non-specific T cell stimulation response to tumour cells?IL-2 (melanoma and renal cell carcinoma)
  17. 17How is it blocked? Treatment?CTLA-4 binds to CD80/86 suppressing the T cell
    Ipilimumab is a CTLA-4 inhibitory (allows T cell to work)
  18. 18What are the different vaccines for tumours made out of?-Tumour cells/lines
    -Defined peptides/protein antigens
    -Dendritic cell-based vaccines (DC taken from cells, loaded and put back in)
  19. 19Describe adoptive T cell therapy Risks?-T cells are taken from donor
    -Expansion of specific T cell populations occurs in vitro
    -Infused into patient
    Risk of graft vs. host disease
  20. 20Describe TIL therapy-Tumour biopsy is taken
    -Tumour-infiltrating lymphocytes are taken
    -Infuse a high dose of such cells into the patients (partially eliminate own immune system first)
  21. 21How can T cells be engineered for cancer therapy?-Find gene encoding for TCR
    -Clone the gene
    -Package into a retrovirus or into a cell
    -Inject into patient
  22. 22What is a consequence of immunotherapies?Autoimmunity
  23. 23Describe the mechanisms that monoclonal antibodies for cancer therapy use-Complement-mediated lysis
    -Antibody-dependent cellular cytotoxicity
    -Blocking receptor/ligand interactions
    -Anti-angiogenesis
    -Cytotoxic activity of conjugated antibodies

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Diagnosis and treatment of cancer Tumour immunology p53
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