Mechanism Of Disease 1: Cell Growth and Cell Differentiation Flashcards
What is cell growth and cell differentiation? (which comes first)
Cell growth = multipotent cells (stem cells) divide to produce more cells
Differentiation = cells become specialised + more complex (lose potency) ending growth
How can cell grwoth + differentiation lead to disease?
Developmental conditions (e.g. neural tube defects - spina bifida)
Neoplasia (+ metaplasia) - cancer and tumours
Cell growth related e.g. cardiac hypertrophy
What is metaplasia?
Replacement of one differentiated somatic cell type to another in same tissue (uncontrolled during reproduction = metaplasia, otherwise normally required)
What is a somatic cell?
Any cell apart from a gamete, germ cells and undifferentiated stem cells.
What are the 2 types of cell growth?
Hypertrophy - bigger cells
Hyperplasia - more cells - more common
What causes hypertrophy? + example
Cells grow bigger due to elevated protein synthesis so more proteins, lipid and nucleotides produced.
Example - heart (cardiac hypertrophy)
What causes hyperplasia?
Increased cell division/proliferation due to cell cycle - more cells produced
What are the steps in cell differentiation?
- Cell exits cell cycle becoming “post-mitotic”
- Cell type specific expression
- Specific gene expression causes cell morphology and function changes
(terminally differentiated and can’t return to cell cycle)
Which mechanism controls cell growth and differentiation?
Intra and extracellular signals e.g. checks on cells, growth and inhibitory factors, cell adhesion
What do intra/extracellular signals interact to cause cell growth/differentiation?
On promoters as co-incidence detectors. (multiple factors required to decide if gene will be expressed or not)
Wha are the steps for extracellular signals?
Ligand (e.g. a growth factor) binds to receptor causing intracellular cascade (e.g. kinase cascade)
Cascade causes transcription factor activation in nucleus + downstream genes are expressed.
mRNA produced and proteinsynthesis occurs (translation).
Proteins produced go onto directly affect the cell or cause more transcription factors to affect downstream genes.
What are the 3 types of extracellular signals?
Paracrine
Autocrine
Endocrine
What are paracrine extracellular signals?
Cell non-autonomous example
Ligands produced locally (near cell) to stimulate proliferation of a different cell type with correct cell surface receptor
What are autocrine extracellular signals?
Cell autonomous example
Ligand produced by own cell and affects itself by attaching to own appropriate receptors (produces own cascade)
What are endocrine extracellular signals?
Like hormones. Released systemically (into general circulation) for distant effects
What are the 4 different effects of the extracellular signalling proteins? + example proteins for each
- Stimulate proliferation via mitogens (e.g. EGF, IL2)
- Induce differentiation + inhibit proliferation (e.g. TGFbeta)
- Can do either cell proliferation or differentiation (e.g. Wnt ligands)
- Induce apoptosis (e.g. TNF family e.g. TNFa)
What are mitogens? + examples
Protein that induces cell division e.g Growth factors and interleukins such as EGF, FGF, NGF, IGF1, IL2, IL4)
What are the phases of the cell cycle?
G1 phase (growth) S phases (synthesis of DNA) - DNA replication G2 phase (growth) M phase (mitosis) G0 phase - quiescent cells (left cell cycle)
What happens to quiescent cells? - entire journey
Cells in G0 phase either rejoin cell cycle or undergo terminal differentiation (post-mitotic cell) which after it’s lifespan undergoes apoptosis (cell shedding)
Which part of cell cycle is ploidy 2N?
Diploid in G1 phase before DNA replication in S phase
Which part of cell cycle is ploidy 4N?
Tetraploid in G2 phase after DNA replication in S phase