19: Cancer and the Immune System Flashcards
Name four cancer cell characteristics.
- Altered self-cells
- Have undergone a genetic change
- Exhibit uncontrolled cell growth (immortal)
- Invade surrounding tissue
Cells that have lost control of the cell cycle will produce what?
tumor/neoplasm
Benign
Characteristics 1-3, unable to invade healthy surrounding tissue
Malignant
Becomes progressively more invasive, characteristics 1-4
Metastasize
Invade blood or lymphatic vessels and are carried to other tissues
Name the steps of cancer in order.
a. initiation, DNA repair (initially modified tumor cell)
b. promotion (localized, benign tumor)
c. progression (invasive tumor cells)
d. metastasis (tumor cells invade vessels and spread)
DNA alterations induce ________________________.
malignant transformation
Transformation can be induced by _____________ (4).
-chemical substances
-physical agents
-ionizing radiation
-viruses and other infectious agents
Genes associated with ____________ control cell ________________ and _________________.
cancer; proliferation and survival
Proto-oncogenes
enhance cell survival when their control mechanisms fail
Tumor-suppressor genes
allow cancer cell survival when they fail
Apoptosis
gene problems can also lead to abnormal cell survival
Apoptosis
gene problems can also lead to abnormal cell survival
Proto-oncogenes are found in _____________ cells.
normal
Oncogenes encode what type of factors, and what type of receptors?
growth factors, growth factor receptors
Oncogenes lead to cancer if there is loss of control of ________________.
expression
Alterations to genes can occur through:
-actions of transforming viruses
-exposure to carcinogens or x-irradiation
-genetic predispositions
What type of cancer is associated with the C-neu (HER2 protein) growth factor receptor?
breast cancer
Name three examples of overexpression/activity leading to unchecked cell activation. (3 products for signal transduction pathways and transcription)
- Src
- abl
- ras
Name and describe two examples of viral integration into the host-cell genome.
- avian leukosis virus integrates into c-myc gene, transform to B-cell lymphoma
- human papillomavirus (HPV) linked to cervical cancer
Normal expression of tumor-suppressor genes inhibits excessive cell ____________________.
proliferation
Tumor-suppressor genes require a _____________ disabling sequence (to fail).
two-hit
The two hit disabling sequence causes failure of tumor-suppressor genes which is akin to “cutting brakes” of the _________________.
cell cycle
Retinoblastoma (Rb) gene
problem in a hereditary rare childhood cancer where one copy is mutated, and the second copy is later somatically inactivated
TP53 gene codes for _________.
p53
Mutation of the TP53 gene is found in ______ percent of all tumors.
60%
TP53 gene encodes a nuclear _________________ with _______________ roles, including involvement in ____________, _________________, and DNA _______________.
phosphoprotein, multiple, growth arrest, apoptosis, repair
What is the role of pro-apoptotic genes?
-they act as tumor suppressors to inhibit cell survival
What is the role of anti-apoptotic genes?
-they behave like oncogenes to promote cell survival
Failure of _________________ genes or overactivity of ________________ genes can encourage ____________________ of cells.
pro-apoptotic, anti-apoptotic, neoplastic transformation
Name the 4 steps involved in malignant transformation.
- initiation
- promotion
- progression
- metastasis
Describe initiation.
Change or mutation alters cell proliferation that, by itself does not lead to malignant transformation.
Describe promotion.
Accumulation of preneoplastic cells.
Describe progression.
Further genetic alterations allow for rampant cell proliferation and acquisition of new mutations to potential cancer-promoting genes.
Describe metastasis.
Final stage where solid tumors lose adhesion and move outside original site.
Human colon cancer (4 steps).
- small benign tumors (adenomas) in colorectal epithelium
- adenomas grow/disorganize and acquire malignant phenotype
- inactivation/loss of 3 tumor suppressor genes
- activation of one oncogene
How does the immune system fight off cancer?
-New mutations create new self-Ag
-Difficult if oncogene is just overexpressed and no new Ag is created
Neoplastic cells are _________ cells.
self
Tumor cells may express ________ or __________________________ Ag that can be detected by the immune system.
unique, inappropriately expressed
Name the four groups of tumor Ag that are recognized by T cells (so far).
- Ag encoded by genes exclusively expressed by tumors (viral genes)
- Ag encoded by variant forms of normal genes altered by mutation
- Ag normally expressed only at certain stages of development
- Ag overexpressed in particular tumors (harder for the immune system to recognize)
Tumor-______________ antigens are unique sequences, and may result from __________ in tumor cells that generate ____________ proteins (new non-self Ag).
specific, mutations, altered
Virally induced tumors display __________ proteins that ________ can detect and kill.
foreign, CTLs
These proteins are expressed in ~80% of cervical cancers.
HPV E6 and E7
Nuclear antigen of what has been observed in some Burkitt’s lymphoma?
EBV
TAAs are unique to the cancer itself. T or F?
F; they are not unique to the cancer itself
Tumor-associated antigens (TAAs) are normal cellular proteins with ___________ expression patterns.
unique
Immunoediting is
a newly proposed model which both protects against and promotes tumor growth.
Anti-tumor immune responses select for the weakest cells. T or F?
F; selects for the toughest cells
Three phases of anti-tumor immune responses proposed:
- elimination
- equilibrium
- escape
Elimination
-attacking the cells that can be targeted (Immunosurveillance)
-but, some cells acquire mutations that allow them to resist immune detection
Equilibrium
-state of balance between destruction/survival of “best” cells
-low level of abnormal cells persist, but adaptive immune system keep in check
Escape
-most aggressive/least immunogenic cells thrive and spread
-acquire more mutations in surviving tumor cells
-immune system shifts from anti- to pro-tumor responses
Name two innate inhibitors of cancer and the mechanism by which they do so.
- NK cells can target neo-plasmic cells
- Activated macrophages bind to Ab-coated tumor cells (ADCC) and secrete TNF-alpha (strong antitumor activity)
Name 3 types of adaptive cell types involved in cancer eradication and they mechanism by which they do so.
- Anti-tumor CTLs; lack of T cells leads to increases in cancer
- Tumor-infiltrating lymphocytes (TILs); T cells, NKT cells, NK cells
- B cells generate antitumor Ab against tumor-specific Ag; Promotes tumor-cell recognition and lysis; May block CTL access to tumor Ag, so anti-tumor Abs may not always be a good thing
