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2204/19/23
Cancer & the Immune System
Assigned Reading Content Outline Performance Objectives
– Key terms– Key Concepts
Short Answer Questions
3304/19/23
Assigned Reading Janis Kuby’s Immunology 4th Ed
Chapter: 22 pp 539-561 Janis Kuby’s Immunology 3rd Ed Chapter: 24 pp 573-596
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Content Outline Origins & Terms Malignant Transformation Tumours of the Immune System Tumour Antigens TATAs on human melanomas Immune Response to Tumours Tumour Evasion of Immune Response Cancer Immunotherapy
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Growth of Breast Cancer
Dia
mete
r of
Tu
mou
r (m
m)
Tumour Cell doubling
Tumour visible by X raysTumour first palpable
Death of Patient
108cells
109cells
1012cells
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Tumour Antigens Tumour specific Antigens
– chemically induced– virally induced
Tumour associated antigens– oncofetal tumour antigens– oncogene proteins
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Malignant Transformation Oncogenes Induction of cell proliferation Inhibition of cell proliferation Regulation of apoptosis
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Tumour Evasion of Immune Response
Immunologic enhancement Modulation of tumour antigens Reduce MHC-I No co-stimulatory signal
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Cancer Immunotherapy Modify Co-stimulatory signal Enhance APC activity Cytokine therapy MABs Tumour cell vaccines
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Cancers Treatable by Bone Marrow Transplants
Allogenic/syngenic Transplant– Breast cancer– aplastic anemia– leukemia– ALL– CML– Myeolodysplasia– multiple myeloma– Non- Hodgkin’s lymphoma– Hodgkin’s disease
Autologous Transplants– Leukemia– AML– ALL– Multiple Myeloma– Non Hodgkin’s lymphoma– Hodkin’s disease– Solid tumours– Breast– ovarian– testicular– Neuroblastoma
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Tumour Cell VaccineImmune Response to MCA or
PVTransplant killed cells
of MCA induced sarcoma A
Challenge with Sarcoma A- No Growth
Challenge with Sarcoma B- growth
Transplant killed cells of Polyoma Virus
induced sarcoma A Challenge with
sarcoma A no growth challenge with
sarcoma B no growth SV40 induced
sarcoma C- growth
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Key Terms antibody dependent cell mediated
cytotoxicity (ADCC), benign tumour, cancer,
carcinogens, proto oncogens, immune surveillance, Specific immunotherapy,
non specific immunotherapy, immunotoxins,Lymphokine activated killer cell(LAK),
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neoplasm, oncofetal antigens, oncogens, tumour, tumour associated antigens,
tumour associated transplantation antigens, tumour specific antigens,
tumour specific transplantation antigens
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Key Concepts Differentiate between a benign tumour and a
malignant tumour. Describe the concept of immunosurveillance Describe the different ways that tumours
can camouflage themselves to evade immune defenses,
Discuss the advantages of immunotherapy over other forms of cancer therapy.
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Distinguish between specific and nonspecific immunotherapy with the use of specific examples.
Describe immunotoxins. Describe the development of humanized
antibodies to tumour antigens Evalulate the contribution of T cells, NK
cells, Macrophages, and B cells to tumour immunity.
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Distinguish between tumour specific transplantation antigens and tumour assoicated transplantation antigens.
Describe oncofetal antigens.
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Explain how some cancer cells that can make TGF-beta are immunosuppressive.
Tumours and transplants are similar to one another,yet very different. Explain this observation in the context of what the immune system recognizes and the result of this recognition.
The qualities of proliferation and differentiation are essentially all that distinguishes a normal cell from a cancer cell. Explain.
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Design an experiment using mice that proves that the immune system provides immunity against tumours.
Distinguish between tumour-specific transplantation antigens (TSTA) and tumour associated transplantation antigens (TATA).
Design an experiment to show Tumour associated Transplantation Antigens (TATA).
What is the main difference separating cell surface antigens from chemically induced and virually induced cancers?
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Speculate on why this difference leads to difficulty in designing anticancer vaccines.
What are oncofetal antigens? Are they important in tumour immunity? Why?
What is immune surveillance? All evidence for immune surveillance is
indirect. Speculate on how you could get direct evidence.
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What immune cells play a role in tumour rejection? Briefly describe how each accomplishes this task. Include such things as cytokines, perforins, ADCC etc.
Cancers camouflage themselves to evade antitumour defenses. Pick three possible forms of camouflage that you think are most important, describe them and state why you think they are most important.
What are immunotoxins?