Ch. 19 Cancer and the Immune System Flashcards
benign
unable to invade healthy surrounding tissue
malignant
becomes progressively more invasive
metastasis
invasion of other distant tissues
Carcinomas arise from
epithelial cells; skin, gut, glands, lining of internal organs
Sarcomas arise from
mesodermal connective tissues; bone, fat, cartilage
Sarcomas arise from
mesodermal connective tissues; bone, fat, cartilage
Myelomas arise from
plasma cells
Leukemia’s arise from
WBCs in blood
Lymphomas arise from
WBCs in lymphatic tissues
3 carcinogens that can promote development of cancer
- chemical subs (formaldehyde)
- physical agents (asbestos)
- Irradiation (x-rays)
- viruses
What agency is responsible for tracking possible links to cancer?
International Agency for Research on Cancer (IARC)
What did Dr. Rous discover?
observed that a cancer-causing retrovirus (Rous sarcoma virus) leads to malignant transformation; malignant sarcomas in chickens could be transferred to another via cell-free filtrate
What did Dr. Temin discover?
suggested that oncogenes may be normal in cells and viruses might acquire these growth-promoting genes from previously infected cells (proto-oncogenes)
Proto-oncogenes
produce essential growth-controlling proteins; may lead to cancer if altered to lose control of expression or protein function.
What ways can convert a proto-oncogene to a v- or c-oncogene?
- actions of transforming viruses
- exposure to carcinogenes
- genetic predispositions
How can malignant transformation be accomplished by a virus like RSV?
RNA retroviruses reverse transcribe their genomes into DNA and integrate into the host genome–> viral genome has close contact with neighboring genes –> RSV acquires a copy of src causing infected cells to misregulate their growth because they have an extra copy of the src once infected
Oncogenes
enhance cell survival when their control mechanisms fail; become enemy when activity is enhanced
Tumor-suppressor genes
allow cancer cell survival when they fail; become the villain when activity is depressed
Which one needs to be underactive to promote cancer (oncogene or tumor suppressor gene)?
tumor suppressor gene
Which one needs to be overactive to promote cancer (oncogene or tumor suppressor gene)?
oncogene
What are five categories of cancer-promoting activity of oncogenes?
- growth factors/growth factor receptors
- products for signal transduction pathways and transcription factors
- chromosomal translocations
- mutations in proto-oncogenes
- viral integration into the host cell genoome
growth factors/ growth factor receptors
-one cell population secretes GF, which binds receptors on another cell population and promotes proliferation (receive more GF and proliferate more often)
ex. of growth factor cancer-promoting activity
GF sis and GF receptor fms, erbB, neu, and erbA can cause cancer when overexpressed
products for signal transduction pathways and transcription factors
src, able, and ras overexpression can transform cells; Jun, fos, and myc well known cancer-promoting transcription factors
chromosomal translocations
translocations involving BCR and TCR loci; movement of c-myc from chom. 8 to chrom. 14= overexpression of myc
mutations in proto-oncogenes
chemical carcinogens or irradiation converts proto-oncogenes into cancer-inducing oncogenes
ex. of mutation in proto-oncogenes leading to cancer
single point mutation in c-ras leads to overactive ras= highly active epidermal growth factor (EGF) signaling
viral integration into host cell genome
2 v-onc gene products (E6 and E7) made by high risk HPVs interfere with cell functions that normally prevent excessive growth –> tsp p53 and prB
p53 is a tumor suppressor protein that
promotes apoptosis
pRB regulates
cell cycle
retinoblastoma (Rb) gene
encodes a cell cycle regulator that inhibits progression through G1
TP53 gene coding for p53
encodes a nuclear phosphoprotein with multiple roles, including involvement in growth arrest, apoptosis, and DNA repair
BCl-2 gene
anti-apoptosis gene that is important in the survival of selected B and T cells during maturation
Two phases of malignant transformation
initiation and promotion
What causes XP to lead to cancer?
- defects in nucleotide excision repair (NER)
- unable to repair UV induced mutations, so build in skin cells over time
XP can often lead to early onset of
malignant melanoma or squamous cell carcinoma
human colon cancer can occur due to the inactivation of TSGs:
APC, DCC, TP53
human colon cancer can occur due to the activation of:
k-ras
neoplastic cells
self cells; most Ags are subject to tolerance processes
Which of these is easier for the immune system to handle: TAAs, TSAs, or neoplastic cells?
TSAs
Tumor specific antigens
unique to tumor cells
tumor associated antigens
normal cellular proteins with unique expression patterns
What intrinsic mechanisms do we have to prevent cancer?
- DNA repair mechanisms
- apoptosis
What are the three phases of immunoediting?
- elimination
- equilibrium
- escape
elimination phase
attacking cells that can be targeted
equilibrium phase
state of balance between destruction/survival of toughest cells
escape phase
most aggressive/least immunogenic cells thrive and spread
What is the role of NK cells in cancer prevention?
target neoplasmic cells
What causes Chediak-Higashi syndrome?
mutations resulting in loss of NK cells
effects of Chediak-Higashi syndrome
- improper lysosomal trafficking
- albinism
- peripheral neuropathy
- decrease in phagocytosis and impairment of secretory lysosome trafficking, impairing NK fxn
