Topic I Flashcards
cell necrosis
injured cells rupture and damage neighbouring cells (to be avoided)
apoptosis
cells that 1) are no longer required or 2) are a threat are dismantled and provide nutrients for other cells (preferred way)
examples of cells that perform apoptosis
- cells holding leaves to branches
- tails of tadpoles
- human cells that are cancerous or infected with viruses
preparation for apoptosis
- procaspases are present - Bcl2 protects mitochondria
- DNases are inactive
- phosphatidylserines are hidden
(Apoptosis) step 1: the trigger
- damage to mitochondria
- damage to DNA
(severe DNA damage has p53 turn on PUMA gene) - absence of survival signals (eg cell death of overproduced neurons to match # of neurons to # of target cells)
- death signal from a T cell (uses its Fas Ligand memb. proteins to trigger apoptosis)
The T cell using its Fas Ligand memb. proteins is ____ signalling
contact dependent
(Apoptosis) Step 2: Activation of procaspases
- procaspases when brought together are activated by proteolysis
- damage to mitochondria releases Cyt c and procaspases are brought together
- damage to DNA -> p53 -> PUMA -> Bcl2 inhibited -> Cyt c release
- no survival signals -> no Bcl2 -> Cyt c release
- death signal from a T-cell (Fas ligand -> Fas receptors -> procaspases brought together)
(Apoptosis) Step 3: Caspase cascade
caspases activate other procaspases = caspase cascade
caspases also ____ target proteins
cleave
(Apoptosis) Step 4: Cell Destruction
- chromosomes destroyed (caspases indirectly activate DNases)
- nuclear envelope dismantled (caspases directly destroy nuclear lamins)
- cells round up and become apoptopic bodies
what technique labels apoptotic cells?
TUNEL technique
(Apoptosis) Step 5: Phagocytosis
apoptotic bodies consumed by neighbour cells (non-professional phagocytes) or macrophages (professional phagocytes)
why does phagocytosis happen
apoptotic bodies display phosphatidylserine phospholipids (“eat me” signal)
why chop up DNA?
to make apoptosis irreversible and to make apoptotic bodies safe to eat (destroy virus/cancer genes)
how many cell types are in the human body (mammals)
200
when do cells become specialized
when transcription cells turn on/off specific genes
when does cell differentiation begin in mammals
early in development
stem cells
cells that both reproduce & differentiate
are embryonic stem cells multipotent or pluripotent?
pluripotent - can become any cell type
where are stem cells found?
in tissues and organs where cell reproduction occurs
types of stem cells
- blood (hematopoietic)
- skin (epidermis)
- gut (small intestine)
blood stem cells
produced in the blood marrow, adult stem cells are multipotent (can become one or more related cells)
skin stem cells
can reproduce (make another stem cell) or become differentiated (mature skin cell)
gut stem cells at the base of villi can become what?
absorptive and goblet cells
what can embryonic stem cells be used for?
- research (eg. adding heart TFs)
- scams (stem cell therapy)
what can skin stem cells be used for?
to treat burns and wounds using autograph transplantation (person A -> person A)
what can bone marrow stem cells be used for?
treat blood and bone marrow diseases using allograft transplantation (person A -> person B), donor = a family member or related stranger
where are the bone marrow stem cells harvested from a donor?
the pelvis which has the most blood stem cells
what can umbilical cord blood stem cells be used for?
- research
- allograft for another child
- scams (private cord blood banks that promote autographs which won’t work)
what can induced pluripotent stem (iPS) cells be used for?
- research
- potential treatment (eg. to replace damaged neurons)
cancer
cancer cells reproduce and spread inappropriately, risk of cancer goes up with age
benign cells
reproduce when they are not supposed to
malignant/cancer cells
reproduce when they are not supposed to and go where they are not supposed to
what cancer is the most common cause of cancer deaths in mem and women?
lung cancer
stages of cancer
- initiation
- progression
- spread (metastasis)
initiation
one mutation in one cell causes it and its offspring, to divide inappropriately.
progression
more random mutations that increase reproduction, survival and spreading of the cancer
spread (metastasis)
cells leave the primary tumour and establish secondary tumours
are cancer cells ‘trying’ to get worse?
no, this is a misconception. Mutations are random and are detrimental or have no effect
do cancer cells reproduce quickly?
no, a misconception. Cancer cells are defective and reproduce ~100 days per cell cycle (vs ~25 days for a healthy cell)
are cancer cells in a tumour identical?
no, a misconception. Cells have different properties and vulnerabilities
are cells in a tumour cancer cells?
most cells in a tumour are not cancer cells, cancer cells recruit normal cells for support
what are three main reasons why cells become cancerous?
- cancer critical genes
- new (somatic) mutations
- inherited (germline) mutations
- ## viral infection
cancer critical genes
encode proteins involved in the cell cycle. Tumor suppressor genes that inhibit cell cycle and proto-oncogenes that promote cell cycle can have mutations occurring
new (somatic) mutation
mutation happens within the person
inherited (germline) mutations
mutation is inherited from a parent
viral infection
some viruses deliberately cause cancer to facilitate their own reproduction. Viral proteins inhibit or activate the proteins made by critical cancer genes
(initiation) unregulated cell reproduction due to loss of tumour supressor genes
normal function: inhibit cell proliferation
cause cancer when non-functional (eg. RB1 gene, without Rb proteins, cells can’t pause at the G1 checkpoint)
(initiation) unregulated cell reproduction due to proto-oncogene -> oncogene
normal function: stimulate cell cycle
cause cancer when the normal proto-oncogene becomes an over active oncogene (eg. HER2 gene)
(progression) genetic instability
cancer cells acquire new mutations at more than the spontaneous rate (eg. mutations in the TP53 tumor suppressor gene)
(progression) no apoptosis
some cancer cells do not perform apoptosis because genes such as TP53, PUMA, BCL2 have mutations
PUMA is a _____ because too ___ PUMA proteins is dangerous
tumour suppressor gene… few
BCL2 is a ___ because too __ BCL2 proteins is dangerous
proto-oncogene… many
what proportion of human cancers have mutations in TP53?
> 50%
(spread) induce angiogenesis
tumours cannot grow beyond 1-2mm in diameter without recruiting blood vessels
(spread) invade neighbouring tissue
cancer cells spread if some of them dismantle the extracellular matrix (as if they were fibroblasts)
(spread) metastasis to new cites
0.1% of cells survive to reach new sites to make a secondary tumour
what proportion of human cancers are due to viral infection?
> 10%
