Cell Bio 2 Flashcards
Altered proliferative states that are reversible/stoppable if the stimulus is removed.
Regeneration.
Hyperplasia.
Metaplasia.
Dysplasia.
Irreversible proliferation.
Neoplasia.
regeneration
1-for-1 replacement of lost cells by the SAME cell type.
Ex: endothelial cell regeneration after vascular surgery, liver cell regeneration after partial hepatectomy.
hyperplasia
Increase in number of cells in a tissue. Either physiological/helpful, or pathological/harmful.
Ex: hematopoietic cells in bone marrow after altitude changes (helpful); hyperthyroidism in Graves Disease (harmful); restenosis of smooth muscle cells in arterial wall after atherosclerosis/vascular surgery (harmful).
metaplasia
Adaptive substitution of one cell type for another.
Ex: replacement of ciliated columnar epithelium by stratified simple squamous due to smoking or chronic inflammation.
dysplasia
Activated metabolic pathways for proliferation; loss of orientation in a tissue. Often leads to cancer. Abnormal in appearance. High mitotic rate.
Ex: Cervical dysplasia in a Pap smear; dysplastic moles
Neoplasia
Benign: loss of proliferation controls only.
Ex: fibroids
Malignant: loss of both proliferation and positional controls.
Ex: metastatic tumors
fibroids
Example of benign neoplasia.
No medications help, must be surgically removed.
Termed “benign,” but it could out-compete a fetus and expel it from the womb.
Symptoms: abnormal/heavy bleeding, pain & pressure, fertility problems.
positional control of proliferation
Regulated by extracellular matrix.
Ex: epithelial cells of vili and crypts.
most cells are in which phase of the cell cycle?
G0
G1 phase of cell cycle
Prepares cell for replicating DNA.
Doubles its content in preparation for cell division.
S phase of cell cycle
DNA replication
G2 phase of cell cycle
Prepares cell for segregation/division of genome and cytoplasm
M phase of cell cycle
Chromosome segregation (mitosis) and separation of daughtercells (cytokinesis)
R-point
The G1/S checkpoint.
Cell determines if it has enough nutrients/growth factors/hormones to continue cycle.
cyclin/Cdk for G1/S phase
cyclin D/ Cdk4-6
cyclin E/ Cdk2
cyclin/Cdk for M phase
cyclin B/ Cdk1
cyclin-Cdk activity is regulated by…
activating and inhibiting kinases
inhibitors of Cdk2 and Cdk4 are now used in what type of treatment
Cancer chemotherapy.
Prevent cancerous cells from bypassing the R-point.
key substrates of cyclin B/ Cdk1
lamins (membrane dissembly)
histones (chromatin condensation)
cyclin D/Cdk4-6 and cyclin E/ Cdk2 activate _______
They activate/phosphorylate the Rb protein.
normal state of the Rb protein
Hypophosphorylated.
Sequesters transcription factors so transcription cannot occur.
phosphorylated state of Rb protein
Rb changes conformation and is inactive.
Releases transcription factors.
Activates the transcription of genes needed to push it from the G1 phase to the S phase.
As DNA synthesis starts, a protease is activated that destroys cyclin D and E, inactivating the complex.
MPF activation
Cyclin B/cdk1 activation.
1) phosphorylates lamins (nuclear membrane dissembly.
2) phosphorylates histones (chromatin condensation).
necrosis
Triggered by unexpected, sustained trauma (chemical or physical).
Cell swells, organelles damaged, chromatin randomly degraded.
Cell lyses, organelles destroyed.
Leads to inflammation.
apoptosis
Triggered by specific signals.
Cells shrink, organelles intact, chromatin degraded.
Membrane blebs, cell contents retained.
Leads to phagocytosis.
polycystic kidney disease
Due to too much apoptosis.
intrinsic pathway to apoptosis
MODULATED BY Bcl-Family proteins
1) injury –> DNA damage –> p53 increases –> mitochondrial leakage
2) withdrawal of GF/hormones –> mitochondial leakage
mitochondrial leakage –> cytochrome c –> capase-3 –> DNA fragmentation/cytoskeletal breakdown –> bleb–> phagocytosis
Extrinsic pathway to apoptosis
receptor-ligand interactions (FAS, TNS, “death receptors”) –> adapter proteins –> caspase-3 –> DNA fragmentation/cytoskeleton breakdown –> bleb –> phagocytosis
caspase-3
the chief executioner for both the intrinsic and extrinsic pathways
stroke
neuronal IAPs (inhibitors of apoptosis) can prevent excessive loss of neurons, if given in time
Hashimoto’s hypothyroidism
Decreased immune cell death causes autoimmune response.
Low T3/T4.
TSH is increased to make more T3/T4.
Result: excess TSH, low T3/T4
Type I Collagen
Found almost everywhere (bone, skin, tendons, ligaments, cornea, internal organs).
Forms fibrils.
Connective tissue collagen.
Type II Collagen
Found almost exclusively in cartilage.
Forms fibrils.
Connective tissue/cartilage collagen.
Type IV Collagen
Found in basal lamina in basement membrane.
Forms a network.
Epithelial basement membrane/basal lamina collagen.
Type XVIII Collagen
Basal lamina around blood vessels.
Blood vessel specific.
Contains an internal peptide sequence (endostatin - antiangiogenesis protein used in cancer/macular degeneration therapy).
scurvy
Vitamin C deficiency.
Prevents cross-linking of collagens.
Ehler-Danlos Syndrome
Genetic defects in collagen synthesis/assembly.
Impaired musculoskeletal/vascular systems.
Osteogenesis Imperfecta
Genetic defect in Type I collagen.
Brittle bones.
Menkes Disease
Genetic defect causing deficiency in copper utilization.
Faulty collagen cross-linking.
Alport Syndrome
Genetic defect causing absent/nonfunctional Type IV collagen.
Causes kidney failure (2nd most common cause).
Goodpasture Syndrome
Autoimmune disease.
Antibodies to Type IV collagen destroys basement membrane in lungs and kidneys.
Managed with corticosteroids and other immunosuppressants.
endostatin
Internal peptide cleaved from Collagen Type XVIII.
Cleaved by a collagen MMP.
Targets immature vascular endothelial cells (blood vessels created by cancer).
Induces apoptosis.
Angiogenesis inhibitors used in therapy for 4 million patients.
proteoglycans
Mostly carbohydrates, some protein.
Chondritin sulfate absorbs water.
Functions:
1) regulate hydration state of tissues, esp cartilages.
2) provide resistance to impact in cartilage (shock absorbers).
3) Reservoirs for cytokines and growth factors.
4) Selectively permeable filters in kidney and lung.
chondrodysplasias
Two causes:
1) defective chondroitin sulfate proteoglycans.
2) defective collagen II
Features:
Flattened bridge of nose.
Malformed legs, feet, toes, forearms, fingers.
matricellular proteins
Secreted by the cell and remain tightly bound to cell surface receptors via integrins.
Act as co-receptors to help regulate adhesion and signal transduction pathways.
For proliferation, motility, differentiation.
Connected to cytoskeleton.
fibronectin
laminin
CCN protein
fibronectin
Type of matricellular protein.
CT matrix and mesenchymal matrix
laminin
Type of matricellular protein.
Basement membrane
Integrins
Receptors for fibronectin, laminin, and CCN.
Connect to cell signalling and cytoskeletal machinery.
Glanzmann’s Thrombasthenia
Inherited platelet integrin defect.
Slightest touch causes a bruise.
Elastin
Cross-linked with fibrillin.
Major component in elastic laminae of artery walls.
Marfan’s Syndrome
Defective fibrillin fails to cross-link elastin.
Joint laxity.
matrix metalloproteases (MMPs)
Requires a metal to degrade matrix molecules. Secretes proteases (first step in angiogenesis). Required for cancer cell metastasis, tissue remodeling, wound healing - angiogenesis
cadherins
Require calcium.
Cell adhesion molecule.
Important in maintaining tissue integrity – connects desmosomes of adjacent cells.
Defects cause blistering.
Critical in embryonic development – compacts embryo.
CAMs (cell adhesion molecules)
Control leukocyte movements.
Leukocyte rolling is due to weak “on-off” interactions between P-selectin of endothelial cell and carbohydrate ligand on leukocyte.
Inflamed tissue: express PAF (platelet activating factor).
PAF binds to PAF receptor on leukocyte.
Binding activates a specific integrin that tightly binds to ICAM-1 on EC membrane.
Leukocyte sticks, initiating extraversion.
HPO axis
Hypothalamus-Pituitary-Ovary Axis
Hypothalamus secretes GNRH, stimulates the pituitary to secrete LH/FSH, stimulates the ovaries to secrete estrogen/progesterone, which affects the uterus.
GnRH
Gonadotropin Releasing Hormone.
Source: heart
Target: anterior pituitary
Action: synthesis and secretion of FSH/LH
FSH
Follicle Stimulating Hormone.
Source: anterior pituitary.
Target: ovary.
Action: stimulates ovarian follicle growth, differentiation, steroidgenesis.
LH
Leutinizing Hormone.
Source: anterior pituitary.
Target: ovary.
Action: stimulates ovulation, corpus luteum formation, steroidogenesis.
Estrogens
Source: ovary, follicle cells.
Target: uterus, vagina, oviduct, mammary glands.
Action: growth and differentiation of targets.
Progestins
Source: corpus luteum.
Target: uterus, vagina, oviduct, mammary glands.
Action: growth and differentiation of targets.
thalomide
Drug for morning sickness.
Allowed embryologists to determine timing of embryological events in humans.
rubella
Allowed embryologists to determine timing of embryological events in humans.
spermiogenesis
Golgi is rearranged into the acrosome cap.
Mitochondria move to mid piece (base of tail) to provide energy for flagellar movement.
Produced at puberty onward.
oogenesis
Oocytes in ovary are arrested in prophase of meiosis I (from fetus to menopause).
Only a few thousand complete meiosis I and enter meiosis II (10 per menstrual cycle, 40 year span).
Only a few hundred are ovulated.
Complete gametogenesis at fertilization.
follicle maturation
GnRH made by hypothalamus.
Anterior pituitary releases FSH into bloodstream.
FSH stimulates 8-12 primary follicles to grow and secrete estrogen.
Fastest growing follicle becomes the dominant follicle (more FSH receptors on supporting cells).
Dominant follicle is ultimately ovulated (after 2-3 menstrual cycles).
Non-dominant follicles degrade via apoptosis.
ovulation
FSH driven estrogen levels rise to threshold level.
LH production (pituitary) is rapidly stimulated.
LH surge triggers ovulation and release of primary oocyte from prophase of meiosis I.
Primary oocyte finishes meiosis I; enters meiosis II, arrests at metaphase, now is a secondary oocyte.
Follicle ruptures and expels a secondary oocyte (12-24 hours after LH surge) (expelled by contraction of theca cells, triggered by prostaglandin E2).
Ovulated secondary oocyte is surrounded by zona pellucida and corona radiata.
causes of spontaneous abortion
Chromosomal abnormalities (deletions, translocations, non-disjunction during gametogenesis).
Cleavage abnormalities.
Insufficient progesterone.
fertilization
Occurs in ampulla of Fallopian tube (or elsewhere in FT, but never in uterus).
Begins with contact of sperm and PM of oocyte.
24 hours to complete.
corpus luteum
When oocyte is fertilized, corpus luteum secretes even more progesterone (maintains functional endometrium).
Degeneration of CL inhibited by hCG from embryo.
Functional for 20 weeks, then placenta takes over progesterone production.
sperm capacitation
Required to before fertilization can occur.
6-8 hour process.
Glycoprotein coat & seminal proteins removed from acrosome surface.
Capacitated sperm are more active & can undergo acrosome reaction.
Mimicked in IVF by washing sperm with buffer.
acrosome reaction
ZP3 receptor induces acrosome reaction.
Sperm and follicular cells contact causes ACE to perforate acrosome membrane.
Enzymes are released that break down matrix and permits sperm penetration thru follicular cells/ZP.
Allows sperm to fuse with PM of oocyte.
fusion (“eureka moment”)
Sperm and PM of oocyte fuse.
Official start of fertilization.
Oocyte completes meiosis II and becomes a mature oocyte.
cortical reaction
Fusion triggers calcium pulses, rapid/massive exocytosis of cortical granule contents.
Zona pellucida is modified via proteolysis and protein cross-linking, making ZP denser, blocking polyspermy.
