(Cancer Biology - Tumor Immunology)
1. Tumor simply means what?
2. but is equated with what?
3. which means what?
3. new growth occuring in an excessive or unregulated manner
(Two types of neoplasms)
1. Which type invade into adjacent tissue layers and/or deposit in distal tissues via the circulatory or lymphatic systems?
2. Which type are noninvasive?
1. malignant tumors
(Cancers can arise from almost any tissue cell in body)
1. malignant tumors of mesenchymal tissues (fibroblasts, muscle cells, and fat cells)
2. Malignant tumors of epithelial cells
3. neoplastic growth lymphocytes that often originate in lymph nodes
4. a cancer of the blood or bone marrow leukocytes
4. leukemia (lymphoblastic or lymphocytic leukemias are myeloid or myelogenous leukemias)
1. Typically the result of a multi-step process - called what or what?
(1. Tumor initiation)
2-4. Caused by what three things?
5. What type of cells are induced?
(2. Tumor Promotion)
6. Results in growth of what?
7. Agents that cause what can be promoters?
(3. Tumor Progression)
8. Induction of what?
1. carcinogenesis or oncogenesis
2. Unrepaired alterations in cellular DNA [chemical (nitrosamines)]
3. physical (UV rays)
4. genetic mutations to cellular DNA (genetic/somatic)
6. neoplastic cells
7. Agents that cause mitogenesis (cell division) - (eg saccharin, estrogen, phorbol esters, cytokines)
8. invasive growth
He says this is for our information - but learn it
(Tumor Immunology - Immunosurveillance)
1. What is the ability of the immune system to detect tumor cells and destroy them?
2. Do tumors show evidence of immunological control?
3-8 - What are five ways that tumors avoid immune system?
1. Tumor immunosurveillance
2. Most tumors show little evidnce of immunological control
3. low immunogenecity (doesn't express molecules to be bound to)
4. tumor treated as self-antigen
5. antigenic modulation (down-regulation of antigens)
6. secrete cytokines (TGF-B) to inhibit T cells
7. create physical barrier (tumor-induced privileged site)
1. What are unique or altered proteins and sugars (glycans) expressed by tumor cells
2. What are proteins derived from mutated, silent, or viral genes expressed by tumor cells? What does this result in? What can these antigens invoke?
1. tumor antigens
2. tumor-specific antigens; presentation of essentially foreign antigens by MHC; a T cell or antibody response because they are foreign to the immune system
(Tumor antigens - cont)
(Products of mutated genes)
1. What type of gene (when dysregulated), makes a protein product that participates in the onset and development of cancer?
2. What is a normal gene that can become an oncogene due to mutations or increased expression? What do these encode for? When they are altered they participate in what?
(Products of Viral Genes)
3. Viruses can incorporate what into host cells?
4. These can make the cells what?
5. Their protein products can also serve as what?
2. proto-oncogene; encode for proteins that help to regulate the cell growth and differentiation; onset and development of cancer
3. genes and genetic material
5. tumor antigens recognized by the immune system
1. What are normal cellular antigens expressed by tumors in an atypical fashion? These antigens are typically less efficient at what? Can be beneficial for what?
2. What are proteins that are typically present only during fetal development but are found in adults with certain kinds of cancer?
3. What can occur by the abnormal addition of glycan strutures to cell surface proteins and lipids?
1. tumor-associated antigens; less effecint at invoking an immune response since they may not be perceived as foreign; dianostics/therapeutics
2. oncofetal antigens
(fyi) an example of an oncofetal antigen is alpha-fetoprotein (AFP), a predominant serum protein in the fetus produced by hepatocytes, which disappears upon birth. In some dogs with hepatocellular carcinoma, serum levels of AFP will increase
3. altered glycosylation of cell surface lipids
1. These cells play a well established role in killing tumor cells. Are particularly effective in immunosurvillance for what?
2. These are generally not cytotoxic, but can play a role in anti-tumor responses. By providing what that do what?
3. These cells attach to and kill antibody coated tumor. By their what?
4. B cells - antibodies attach to cell surface tumor antigens and activate what?
5. Specialized lymphocytes (but not T or B) thatn do not express antigen specific receptors (ie no T or B cell receptor)
1. Cytotoxic T lymphocytes (CD8); viral-induced tumors
2. Helper-T lymphocytes (CD4); providing cytokines that stimulate CD8 T cells, B cells, and macrophages
3. Macrophages and neutrophils; Fc receptors
4. activate complement or Fc receptor expressing leukocytes
5. Natural killer cells
(Natural Killer Cells)
1. Arise from what lineage?
2. innate or adaptive?
1. lymphoid (therefore a lymphocyte)
1. How are NK cells similar to CD8 T cells?
2. How are NK cells different from CD8 T cells?
3. What enzymes do both of these release to kill stuff?
1. both cytotoxic lymphocytes and recognize class 1 MHC on tumor cells
2. Don't express T cell receptor (TCR) and kill target cells when they don't recognize MHC
3. perforin and granzyme release
learn this slide
(Antibody-Dependent Cell Cytotoxicity (ADCC))
1. What is an Fc receptor expressed by NK cells?
2. What does it bind to acomplish what?
3. What signals the NK cell to kill the target cell?
1. CD16 (FcyRIII)
2. binds antibodies attached to tumor cells and mediates their killing
3. cross-linking of Fc receptors (target cells die by apoptosis)
1. What are three standard therapies?
1. surgical, chemotherapy, and radiation
1. Which type stimulates the immune system in the patient?
2. What is it called when there is a non-specific stimulation of the immune system? Examples (+ composition)? That do what? Used in the treament of what?
3. What type specifically induces and immune response against tumor antigens?
1. ACTIVE THERAPIES
2. augmentation; Acemannan (complex carbs) and Mycobacterium Bovis (bacteria); induce macrophages to secrete pro-inflammatory factors; fibrosarcoma in dogs and cats
1. Administration of isolated immune components into the patient is called what? directly activating immune system?
2. What is it called when Leukocytes from the patient (what kinds?) are expanded in the lab and then reinjected back into the patient?
3. What is it called when you administer antibodies specific to tumor antigens? Like what?
1. Passive therapies; no
2. (NK cells or T cells); leukocyte adoptive transfer
3. Anti-tumor antibodies; ADCC
(look at slide)