Flashcards in MoD S8 - Cell Adaptations Deck (53)
What does the size of a cell population depend on?
How might a cell population increase in size?
Rate of cell proliferation, differentiation and apoptosis
Increased numbers seen with:
- Increased proliferation
- Decreased cell death
What regulates cell proliferation under normal conditions?
Directly controlled by chemical signals from the microenvironment that stimulate or inhibit proliferation
Signalling molecule binds to cell surface receptor (sometimes cytoplasmic or nuclear) and modulation of gene expression occurs
What are the 4 outcomes of cellular signalling that might influence the size of cell populations?
Survive - Resist apoptosis
Divide - Enter cell cycle
Die - Undergo apoptosis
Cell to cell signalling is achieved by what 3 things?
Direct cell to cell stroma contact
What are the 3 modes of cell signalling?
Give a brief description of each type
- Cell produces and secretes molecule which then acts on surface receptors of the same cell
- When molecule is not secreted and acts on internal receptors this is called 'intracrine signalling'
- Cell produces a secretes a molecule that acts on a nearby cell (normally a different type of cell)
- Molecule produced and secreted, then travels in blood to a distant cell and bind to receptors
Describe growth factors
Local mediators involved in cell proliferation
They're polypeptides that act on surface receptors
Coded by proto-oncogenes
Stimulate (can inhibit) transcription of genes that regulate entry of a cell into the cell cycle and the cell's passage through the cycle
What can growth factors affect?
Cell proliferation and inhibition
Give some examples of growth factors add their functions
Epidermal growth factor:
- Mitogenic for epithelial cells, hepatocytes and fibroblasts
- Produces by macrophages, keratinocytes and inflammatory cells
- Bind to epidermal growth factor receptor
Vascular endothelial growth factor:
- Potent inducer of vasculogenesis and angiogenesis in tumours, chronic inflammation and wound healing
Platelet derived growth factor:
- Stored in platelet alpha granules, released on platelet activation
- Also produced by macrophages, endothelial cells, smooth muscle cells and tumour cells
- Causes migration and proliferation of fibroblasts, smooth muscle cells and monocytes
What are the stages of the cell cycle?
What about when cells are not actively proliferating?
Cell not active in the cell cycle enter G0 after G1
How can the cell behaviour be altered to increase growth?
Hint: Refer to the cell cycle
Shortening the cell cycle
Converting quiescent (G0) cells into proliferating cells (making them enter the cell cycle)
What features of the cell cycle can be seen under a microscope?
Only mitosis and cytokinesis
What are cell cycle checkpoints?
Why are they important?
Events where the cells DNA is checked for errors before continuing in the cell cycle
2 important checkpoints at the end of G1 and before M
Prevents cells with abnormal DNA from passing this on to daughter cells and causing dysfunction/malignancy
What is the restriction point?
Near the end of G1, the most important checkpoint
Majority of cells that pass the R point will complete the cell cycle
It is the most commonly altered checkpoint in cancer cells
Checkpoint activation delays the cell cycle and either DNA repair mechanisms are activated or apoptosis (via p53)
What proteins are responsible for cell cycle regulation?
Cyclin-dependent kinases (CDKs)
Describe cell cycle regulation
Cyclins bind to cyclin-dependent kinases (CDKs) and the cyclin CDK complex
These phosphorylate proteins that are critical for progression to the next stage (E.g. Retinoblastoma susceptibility protein)
Cyclin-CDK complexes tightly regulated by CDK inhibitors
Growth factors also involved:
- Some stimulate cyclin production
- Some inhibit CDK inhibitor production
What is the major function of adult stem cells?
Replenish the loss of differentiated cells while maintaining their own population
They achieve this through asymmetric replication (one daughter cell is stem cell, one will mature and differentiate)
Only one mature cell type can be produced (lineage specific)
Describe the role of adult stem cell in labile, stable and permanent cell populations
- Divide persistently to replenish losses
- Normally quiescent (G0) or proliferate slowly
- Can proliferate persistently when required
- Present however cannot mount effective proliferative response to significant cell loss
Give examples of labile, stable and permanent cell populations
- Surface epithelia (E.g. Skin and gut epithelia)
- Bone marrow
- Liver hepatocytes
- Bone osteoblasts
- Brain neurones
- Cardiac and skeletal muscle
What is cell adaptation?
Changes in a cell that is stressed that help the cell survive that stress
They are ALWAYS reversible changes, irreversible cell changes are cell injury
List the 5 important types of cellular adaptation
Give a very short description of each
- Replacement of cell losses by identical cells to maintain organ or tissue size
- Increase in tissue or organ size due to increased cell numbers
- An increase in tissue/organ size due to increased cell size without increased cell number
Shrinkage of a tissue/organ due to an acquired decrease in size and/or number of cells
- Reversible change of one differentiated cell type for another FULLY differentiated cell type
Briefly explain the two major outcomes of cell regeneration?
- Harmful agent removed
- Limited cell damage
- Harmful agent persists
- Extensive tissue damage to permanent cells
What is the definition of cell regeneration?
Give examples of when complete cell regeneration might occur
Liver regeneration following partial hepatectomy
Replacement of skin epithelia
Are regenerated cells as good as cells they replace?
Sometimes immediately as good (E.g. Epidermal skin cells)
Can take weeks/months/years to be as good as predecessors if at all
How many times can a cell regenerate?
Humans = mean of 61.3
Related to telomere shortening upon replication, after telomere shortening reaches max, cannot regenerate further
What is re-constitution?
Where does it appear in humans?
The replacement of a lost body part (multiple tissues)
E.g. Regrowing lizards tail
In humans, angiogenesis occurs
In what types of cell population can hyperplasia occur?
Only in labile and stable populations
Is hyperplasia a normal or abnormal process?
Normal, under physiological control, only occurs secondary to abnormal conditions
When hyperplasia is abnormal it is called neoplasia
What is the major risk involved in a tissue undergoing hyperplasia?
Repeated cell divisions expose the cell to the risk of mutations and neoplasia
Give examples of physiological hyperplasia and the condition that example is responding to
Proliferation of endometrium:
Bone marrow producing erythrocytes: