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Immunology and Cancer Folder Title: CxImmuno and Some Concepts on Non-Immunological Host-Response in Cancer Updated: April 25, 2012 TtlCxImm.

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Presentation on theme: "Immunology and Cancer Folder Title: CxImmuno and Some Concepts on Non-Immunological Host-Response in Cancer Updated: April 25, 2012 TtlCxImm."— Presentation transcript:

1 Immunology and Cancer Folder Title: CxImmuno and Some Concepts on Non-Immunological Host-Response in Cancer Updated: April 25, 2012 TtlCxImm

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4 Figure The Biology of Cancer (© Garland Science 2007) p. 673 Vaccination of Mice with Irradiated Killed Tumor Cells

5 Immune Response in Cancer 1.When it works, what does it “See”? 2.What target or targets does it attack? 3.What “weapons” does it attack with? 4.Why do some tumors regress? 5.Why doesn’t the immune response work better in cancers? 6.Can the immune response in cancer make the pathology worse? 7.How can we make the immune response works better in cancer?

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8 Specific Adaptive Immune Responses: Humoral:Antibody- Antigen (Uses Antibodies to recognize Targets) Cell-Mediated: Helper and Cytotoxic T- Cells (Uses T-Cell Receptors to Recognize Targets)

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10 Anti-Cancer Effector Mechanisms Humoral: Antibody and complement Lymphokines and other cytokines Cell-Mediated Immunity: Cytotoxic T-Cells Natural Killer Cells (NK Cells) Activated Killer Cells Activated macrophages Lymphokine-activated Lymphocytes Granulocytes Combined Humoral and Cell-mediated: Antibody-dependent Cell-mediated Cytotoxicity

11 The specific adaptive immune response recognizes specfic structures on target cells. These targets for the specific adaptive immune response are called _ _ _ _ _ _ _ _ 0 of 5

12 These specific targets for the specific adaptive immune reponse are recognized by two different majors types of recognition molecules. Name either one of the two types of structure or proteins that recognizes target molecules (antigens) of the specific adaptive immune response. 0 of 5

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14 Figure 15.3b The Biology of Cancer (© Garland Science 2007 p. 658)

15 Figure 15.12d The Biology of Cancer (© Garland Science 2007) p. 666

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19 Potential Tumor Antigen Targets CxAgsPitot From Pitot

20 Ludwig Institute For Cancer Research Academy of Cancer Immunology European Cancer Immunome Program Please, register before using the database.register Registration as a Cancer Immunome Database user is free and open, but necessary for anyone wanting access to the data. If you wish to contribute data to the CID, the username and password that you select guarantee that the information you deposit will be properly attributed, and that you alone (or members of your lab, if the lab is already registered) will have the right to modify it. Please, contact CID manager should you have questions or problems.CID manager Have forgotten your password? Cancer Antigen Database: “Immunome” ; Ludwig Institute for Cancer Research

21 Should the Biology of Cancer course be retained as an undergraduate major course in Biology? This question is set to anonymous. I will not know what choice you selected and this is not graded. Biology of Cancer is not a usual course for a Biology Department. We have had this course going for 35 years. Should we keep it or drop it? (multiple choice) Responses Drop it. It belongs in a medical school.11.28% Keep it, but it needs a lot of improvement to be as valuable as it could be in an undergraduate biology program % Keep it. It is a valuable option among our undergraduate courses % No opinion on this.00% Totals78100% 28,2%

22 This is set to anonymous. Your name will not be associated with your response. This Biology of Cancer course needs to be made more rigorous. It is too superficial and not-challenging enough for an upper division undergraduate course for majors. 0 of 5 1.Yes, I agree. It should be more challenging. 2.No. I think it is challenging enough. 3.Abstain

23 This is set to anonymous. Your name will not be associated with your response This Biology of Cancer course covers too much. It is too diffuse and not focused enough. 0 of 5 1.Yes, I agree. It is too diffuse and unfocused. 2.No. I think the coverage is about right. 3.Abstain

24 This is set to anonymous. Your name will not be associated with your response This Biology of Cancer course is set at a level which is too difficult for upper division undergraduates. It is too hard to follow what is going on. 0 of 5 1.Yes, I agree. It is too difficult the way it is now. 2.No. I think the level is about right. 3.Abstain

25 General Concepts on Host-Response in Cancer (Part 1) Does the Host Respond to Prevent Oncogenesis? Does the Host Respond to Limit Neoplastic Growth and Progression? If So, How Does the Host Respond? What Exactly Is the Host Recognizing? To Prevent Oncogenesis To Limit Growth and Progression GenResp1

26 General Concepts on Host-Response in Cancer (Part 2) Is the Appearance and Growth of Cancer Related to Weakened Host Response? Genetically Weakened? Environmentally Weakened? Physiologically or Pathologically Weakened? Can Host Response Actually Facilitate Tumor Appearance and Enhance Tumor Growth and Progression? Can the Recognition and Response Mechanisms be Mobilized, Enhanced, and Directed for Cancer Management and Cancer Therapy? Can They Be Used in Cancer Prevention? GenResp2

27 Cells and Factors in the Natural Immune Response in Cancer Natural Killer (NK) Lymphocytes Non-B-Cell, Non-T-Cell "Null" Lymphocytes Activated by Interferon Activated Macrophages Includes Splenic MPh's, Liver Kupfer Cells, Alveolar (Lung) MPh's, Brain Glial Cells, and others Granulocytes (Polymorphonuclear Leucocytes) Neutrophils, Eosinophils, Basophils, Tissue Mast Cells Activated Non-Antigen-Specific T-Cells Lymphokine-activated Killer Cells (LAK) Cytokines Tumor Necrosis Factor (TNF), Interferons Interleukins (e.g. IL-2) CxNatImm

28 Tumor Escape Mechanisms and Immune-mediated Tumor Enhancement 1.Serum blocking factors 2.Surface Antigen Shedding 3.Antigenic Modulation (Internalization of antigens) 4.Defective complement components 5.Host genetic limitations 6.Absence of tumor specific rejection antigenic targets 7.Localized concentration of effector mechanisms and distant tumor sites and host unresponsiveness. 8.Immunologically privileged sites. 9.Immune suppression by viruses, tumor products, illness, or medical intervention (e.g. surgery or radiation) 10.Generation of suppressor cells and suppressor factors 11.Sneaking through by early low levels of tumor targets followed by enhancement or unresponsiveness (tolerance)

29 Non-Specific Innate Natural Immunity vs Specific Adaptive Immunity in Cancer Innate Natural Immunity Specific Adaptive Immunity No Specific Antigen Recognition Specific Antigen Recognition Not Antibody-dependent Can Involve Antibodies No Antigen-specific T-Cell Receptor Uses T-Cell Receptors Not MHC-Restricted MHC-Restricted (Recognizes Altered-self) No Memory Response Exhibits Immunological Memory No Priming & Second-set Response Enhanced Secondary Responses No Clonal Selection & Expansion Involves Clonal Selection and Expansion of T- and B-Cells Non&Spec

30 Co-stimulatory and co-receptor molecules in the specific adaptive immune response: Immune escape mechanisms in cancer

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35 In the picture below this is a macrophage bound to a T-lymphocyte. Assume that the macrophage is presenting something on a Class II MHC molecule to the T-cell. What would it be presenting to the T-Cell? 0 of 90

36 In the picture below this is a macrophage bound to a T-lymphocyte. Assume that the macrophage is presenting something on a Class II MHC molecule to the T-cell. What would the T-cell be using to recognize what is being presented? (If there is more than one thing involved, I will accept any correct component. 0 of 90

37 MHC Class I Modulation and Escape from T-Cell Lysis from Kuby, Immunology MHCEscap

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42 TnBTargets From Pitot

43 Non-Immunological Host-Responses in Cancer Anti-carcinogenic Effects: Deactivation, Elimination DNA Repair Mechanisms Genetically-directed Apoptosis (May Function in Anti-tumor Immunity Also) Differentiation-inducing Factors Oncolytic Cytokines (May Function in Anti-tumor Immunity Also) Hormonal Responses Anti-Angiogenesis Factors Affecting Tumors Psychological Factors (May Function in Anti-tumor Immunity Also) NonImmRe

44 In the figure below the NK cell is binding to and lysing a tumor target cell, but how does the NK cell know this is a tumor cell? What is actually directing the NK cell to the tumor cell target? 0 of 5


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