Cell is the fundamental unit of life. Cell biology is the study of cell structure and function. In this we are going to study the cell composition, cell metabolism, cell communication, cell cycle and cell death events ( Apoptosis, Necrosis, and autophagy).
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Cell Biology
1. Cell Biology
Presented by,
Avinash Gunjal
F. Y. M-pharm (Pharmacology)
Dr. D Y Patil College of Pharmacy,
Akurdi.
Guided by,
Dr. Nikita Saraswat
Assistant Professor
Dept. of Pharmacology
Dr. D Y Patil College of Pharmacy,
Akurdi.
3. Cell cycle and it’s regulation :
Cell cycle :
✓ “The cell cycle is an orderly sequence of events in which a cell
duplicates it’s content and divides into daughter cells”
✓ In somatic cell cycle, a cell undergoes a nuclear division called mitosis
and a cytoplasmic division called cytokinesis.
✓ Mitosis produce two genetically identical cells, each with the same
number of chromosomes as the parent cell.
✓ In germ cell cycle, a cell undergoes a two step nuclear division called
miosis and a cytoplasmic division called cytokinesis.
✓ Miosis produce four genetically identical cells, in which the number of
chromosomes in the nucleus is reduced by half.
4. Somatic cell cycle :
✓ “Somatic cell cycle is an orderly sequence of events in which a somatic cell
duplicates it’s content and divides to produce two identical diploid (2n) cells”.
✓ Somatic cell cycle consist of two major phases,
1) Interphase : (Cell is not dividing)
2) Mitotic (M) phase : (Cell is dividing)
1. Interphase :
✓ Interphase is the phase of the cell cycle in which a typical cell spends most of
its life.
✓ Interphase is the metabolic phase of the cell, in which the cell obtains nutrients
and metabolizes them, grows, replicates its DNA.
✓ Interphase consists of three phases, First gap phase (G1), Synthesis of DNA (S)
and Second gap phase (G2).
6. 1. Mitotic (M) Phase :
✓ In this phase, a cell undergoes a nuclear division (karyokinesis) called mitosis
and a cytoplasmic division called cytokinesis to form two genetically identical
cells.
✓ Mitotic phase divide into four phases are as follow, Prophase, Metaphase,
Anaphase and Telophase.
➢ Prophase :
✓ First phase of mitosis, begins after interphase
✓ DNA has been replicated before prophase begins
✓ Prophase is longest phase of karyokinesis.
✓ Prophase divides into two phases,
▪ Early prophase
▪ Late Prophase
7. ❑ Early prophase :
✓ Chromatin fibers condense and shorten into chromosomes (called chromatid at
this stage)
✓ Nucleolus disappears and nuclear membrane break down
❑ Late Prophase :
✓ Separation of centrosomes
✓ Centrosome start to form mitotic spindle..
✓ Cell organelles and nuclear membrane start to disappear.
8. ➢ Metaphase :
✓ The microtubule of the mitotic spindle
align the centromeres of chromatid pair at
the centre of mitotic spindle.
✓ This plane alignment of the centromeres is
called metaphase plate.
➢ Anaphase :
✓ The centromeres are seprated, each pair of
sister chromatid migrate towards end of
spindle.
✓ Separated chromatids (called chromosome)
move to opposite pole of the cell.
✓ As microtubule pulled chromosome
towards pole they appear V-shaped.
9. ➢ Telophase :
✓ Final stage of mitosis, begins after
chromosomal movement stop.
✓ The mitotic spindle disappears, nuclear
membrane and nucleoli reappears.
✓ The chromosome are uncoil and nuclear
envelope reforms.
❑ Cytokinesis :
✓ “Division of cell’s cytoplasm and
organelles into two identical cells called
cytokinesis”
✓ This process usually begins in late
anaphase (formation of cleavage
furrow).
10. Reproductive cell cycle :
✓ In germ cell cycle, a cell (diploid) undergoes a two step nuclear division called
miosis and a cytoplasmic division called cytokinesis.
✓ Miosis produce four genetically identical haploid (n) cells, in which the
number of chromosomes in the nucleus is reduced by half.
✓ Reproductive cell cycle occurs in two major phases,
1. Interphase : (Cell is not dividing)
2. Meiosis (m) phase : (Cell is dividing)
❑ Interphase I :
✓ Replication of chromosomes is similar to the mitosis.
❑ Meiosis (m) phase :
✓ Meiosis occur in two successive stages :
1. meiosis I : (Reductional division)
2. meiosis II : (Equational division)
11. ➢ Meiosis I :
✓ Meiosis I produces two haploid cells each containing one set of
chromosome consisting of paired sister chromatid so, it is known as
Reductional division.
✓ Meiosis I consist of four stages,
▪ Prophase I
▪ Metaphase I
▪ Anaphase I
▪ Telophase I
❑ Prophase I :
✓ Prophase I is the longest in duration compared to Prophase in mitosis.
✓ It takes about 85- 95 percent of the total time for meiosis and also much
more complex.
✓ The Prophase I divided into 5 stages, Leptotene, Zygotene, Pachytene,
Diplotene and Diakinesis .
12. 1. Leptotene :
✓ The first stage of Prophase I is called
Leptotene or leptonema.
✓ All the chromosomes begin to condense,
so, they looks as fine thread.
✓ There is marked increase in the nuclear
volume.
2. Zygotene :
✓ The zygotene stage also known as
zygonema.
✓ This stage begins with the initiation of
pairing between homologous
chromosomes and it ends with complete
pairing.
✓ The process of pairing (at end to end)
between homologous chromosomes is
known as Synapsis (Homologous
dyads).
13. 3. Pachytene :
✓ The pachytene stage also known as
pachynema.
✓ The process of synapsis is complete.
✓ The two homologous of each bivalent
appears to be attached with each other
at one or more points, these
attachments are known as chiasmata.
4. Diplotene :
✓ The diplotene stage also known as
diplonema.
✓ DNA recombination is complete.
✓ The chromatids continue to shorten
and thicken and the four sister
chromatids in a group is called a tetrad.
✓ The paired chromatids begins to pull
apart, causing strands to separate.
14. 5. Diakinesis :
✓ The chromosomes become shorter
and thicker due to condensation.
✓ Nucleolus and nuclear envelope
disappear towards the end of
diakinesis.
✓ The spindle apparatus becomes
organized and the centrioles migrate
away from one another.
15. ❑ Metaphase I :
✓ All the homologous chromosome
(bivalents) migrate within a cell migrate
to metaphase plate.
✓ One homologue is pulled above the
metaphase plate and the other below.
✓ The centromeres of homologous
chromosomes of each bivalent stretch out
on either side.
✓ The centrioles are at opposite poles of the
cell.
✓ Spindle fibers from one pole of the cell
attach to one chromosome and spindle
fibers from the opposite pole attach to the
homologous chromosome.
16. ❑ Anaphase I :
✓ Chromosomes move to the opposite
poles.
✓ The microtubules and the kinetochore
fibers interact, which cause the
movement.
✓ A difference between mitosis and
meiosis is that sister chromatids
remain joined after metaphase in
meiosis I, whereas in mitosis they
separate.
✓ During Anaphase I original
chromosomes separate so, reduction in
the number of chromosomes from 2N
to N number, yet the sister chromatids
remain together.
17. ❑ Telophase I :
✓ The homologous chromosome
complete their migration towards the
two poles i.e. shortning of spindles.
✓ The nuclear envelope organized
around two groups of chromosomes.
✓ The nucleolus also reappears.
➢ Cytokinesis I :
➢ Cytokinesis involves the formation of
a cleavage furrow, resulting in the
formation of two cells.
➢ At the end of Telophase I and
Cytokinesis, two daughter cells are
produced, each with one half of the
number of chromosomes (haploid set
of replicated chromosomes) of the
original parent cell.
18. ➢ Meiosis II :
✓ Meiosis II is the second part of the meiotic process.
✓ It separates sister chromatids to produce four haploid cells.
✓ Unlike meiosis I DNA does not replicate before miosis II begins.
✓ The Meiosis II consists of,
Prophase II, Metaphase II, Anaphase II and Telophase II .
❑ Prophase II :
✓ Each dyad is composed of a pair of sister chromatids attached by a
common centromere.
❑ Metaphase II :
✓ Centromeres are positioned at the equatorial plane.
❑ Anaphase II :
✓ Centromeres divide and the sister chromatids of each dyad (duplicated
chromosome) are pulled to opposite poles
19. ❑ Telophase II :
✓ One member of each pair of
homologous chromosome present in
each pole.
✓ Each chromosome is referred as
monad. (Combination of maternal
and paternal genetic information).
✓ Nuclei reform around chromosomes
at the poles.
➢ Cytokinesis II :
✓ Cytokinesis involves the formation
of a cleavage furrow, resulting in
the formation of four haploid
gametes result of a single meiotic
event.
20. Regulation of cell cycle
✓ Homeostasis is maintained when there is a balance between cell proliferation
and cell death.
✓ Cell cycle regulators are as follows,
1. cyclins
2. cyclin-dependent kinases (cdk’s)
3. cyclin-dependent kinase inhibitors
❑ Cyclins :
✓ Cell contains enzymes called cyclin-dependent protein kinase (cdk’s), that
transfer phosphate group from ATP to a protein to activate the protein.
✓ The activation and deactivation of cdk’s depend on cellular protein called,
cyclins.
✓ It is crucial in the initiation and regulation of DNA replication, mitosis and
cytokinesis.
✓ The level of cyclins in the cell are very important in determining timing and
sequence of cell division.
21. ❑ cyclin-dependent kinases (cdk’s) :
✓ These are a family of protein kinases that regulate cell cycle.
✓ Initially they are inactive but activate when attach to cyclins.
✓ cyclin-dependent kinase inhibitors :
✓ These are proteins which inhibits cdk’s.
22. Cell death events :
✓ The body is very good at maintaining a constant number of cells for that, cell
death is a necessary event in the life of a multicellular organism.
✓ There has to exit mechanism for ensuring other cells in the body are removed.
✓ There are three mechanism of cell death,
1. Apoptosis : Suicide (programmed cell death)
2. Autophagy : Self-eating (autophagocytosis)
3. Necrosis : Killing (decay or destruction)
23. ❑ Apoptosis :
✓ In human body billions of cell were produced (by mitosis) and died (by
apoptosis) at every second.
✓ Apoptosis is the process of programmed cell death (PCD) that may occur in
multicellular organisms.
✓ In apoptosis suicide program is activated within the cell and it may leads to,
✓ Shrinkage of cytoplasm/cell, Nucleus fragmentation, Fragmentation of the DNA,
Membrane changes and cell death without lysis/damage.
➢ Characteristics :
➢ Occurs frequently in a multicellular organism.
➢ There is no inflammation in apoptosis
➢ Death of single cell, without damaging its neighbours.
➢ The cell shrinks and chromatin undergoes condensation.
➢ Phagocytosis of apoptotic bodies by macrophages.
24. ➢ Importance :
✓ Needed for proper and normal development as mitosis.
• Ex. The moldiness of the tadpole tail in frog.
• Ex. Incomplete differentiation in two fingers (due to lack of apoptosis).
✓ Destroy cells that represent as threat to the integrity of the organism.
• Ex. Cells infected with viruses.
• Ex. Cells with DNA damage/cancer cells.
➢ Mechanism of apoptosis :
25. ▪ Apoptosis occurs in two phases,
✓ Initiation phase : (Apoptosis enzyme are getting activated).
✓ Execution phase : (Activating enzymes are causing cell death).
1. Initiation phase :
✓ In this phase enzymes that are involved in apoptosis are get activated.
✓ Caspases (cysteine-aspartic proteases) are a family of protease enzymes playing
essential roles in programmed cell death.
26. ▪ Activation of caspases :
✓ When initiator caspases activated, they are going to activate executioner
caspases.
✓ Once the executioner caspases activated they are going to perform the
apoptosis by two pathways, extrinsic pathway and intrinsic pathway.
27. 1. Extrinsic pathway :
✓ This pathway triggers apoptosis in response to external stimuli (viral infection).
✓ This pathway are also called as death receptor pathway, because of mediated by
death receptor.
✓ Death receptor activated by using (Fas-L, Tumour Necrosis Factor).
28. 2. Intrinsic pathway :
✓ It is occur due to increase permeability of mitochondria, so it is also known as
mitochondrial pathway.
29.
30. ❑ Necrosis :
✓ Necrosis, is the morphological changes that follow cell death in living tissue or
organ.
✓ It is a form of cell injury which results in the premature death of cells in living
tissue by autolysis.
✓ It is an unregulated digestion of cell components by hydrolytic enzymes.
➢ Causes of necrosis :
✓ External causes : Mechanical trauma,
Damage to blood vessel,
Thermal effect.
✓ Internal causes : Trophoneurotic disorder,
Pancreatic enzymes (lipase),
Bacterial toxins and pathogens.
31. ➢ Mechanism of necrosis :
✓ Necrosis is an unregulated process of
degradation of cell organelles by lysosomal
enzymes.
✓ There are two broad pathways by which
necrosis may occurs in organism.
✓ First of these two pathways initially involves,
1. Cytoplasmic changes :
▪ Loss of metabolic functions
▪ Loss of the integrity of the cell membrane.
▪ Stop the production of proteins and ATP.
▪ Cells organelles swell and become non-
functional.
▪ Affected cell shows the blebbing on his
surface.
32. ✓ After the cytoplasmic changes these, two pathways divides as per the nuclear
changes.
2. Nuclear changes :
▪ Blebbing is followed by the pyknosis (the nucleus shrink and the chromatin
condenses).
▪ After pyknosis cell follow karyorrhexis (nucleus break down into fragments)
▪ After karyorrhexis cell follow karyolysis (cell nuclei dissolved into the
cytoplasm).
❑ Types of necrosis :
1. Coagulative necrosis :
2. Liquefaction necrosis :
3. Caseous necrosis :
4. Fat necrosis :
5. Fibrinoid necrosis :
33. 1. Coagulative necrosis :
✓ Most common type of necrosis.
✓ Mainly cause due to ischemia (low blood flow)
✓ Commonly affected organs are, heart, liver, kidney and spleen.
✓ In this necrosis, tissue architecture is preserved but, colour might be change.
✓ Coagulative necrosis does not found in brain.
✓ Pathogenesis : degeneration of enzymes and structural proteins due to,
accumulation of lactic acid, heavy metals or expose to ionizing radiation.
✓ E.g. myocardial infraction, zenker’s degenerative necrosis etc.
34. 2. Liquefactive necrosis :
✓ It is also called as, colliquative necrosis.
✓ In liquefactive necrosis, dead cell undergo softening and transform into a
liquefactive viscous mass.
✓ It is mainly cause due to, ischemic injury, bacterial or viral infection.
✓ In this necrosis, tissue architecture is not preserved.
✓ Pathogenesis : release of lysosomal enzymes within the cell due to, lysosomal
permeability.
✓ E.g. infract brain (necrotic tissue in the brain)
35. 3. Caseous necrosis :
✓ It is the combination of coagulative necrosis and
liquefactive necrosis.
✓ Mainly occours due to hypersensitivity reactions.
✓ Affected area surrounded by WBCs.
✓ E.g. Tuberculosis (Lungs)
4. Fibrinoid necrosis :
✓ It’s mainly cause due to deposition of fibrin like
material such as, phosphotungistic acid,
Hematoxylin etc.
✓ Highly eosinophilic
✓ Hyline like deposition surrounded by necrotic cell.
✓ Rupture of blood vessel cause local haemorrhage.
✓ E.g. Rheumatoid arthritis, malignant hypertension
etc.
36. 5. Fat necrosis :
✓ Necrosis found in adipose tissue.
✓ It’s cause due to action of activated lipases (pancreatic enzyme).
✓ In this necrosis adipose tissue convert to neutral fat then hydrolysed into,
glycerol and fatty acid.
✓ E.g. Acute pancreatic necrosis
37.
38. ❑ Autophagy :
✓ Degradation of cytoplasmic components with the help of auto-phagosomes.
✓ It is an intracellular process of cellular cleaning, cytoprotection and self-
degredation
✓ Mainly seen due to, physiological and pathological condition.
✓ Autophagy is survival mechanism under the stressful condition.
✓ It maintain integrity of cell by recycling metabolites and clear intracellular
debris.
➢ Autophagy Pathway :
✓ It is occurs into three steps are as follows,
1. Initiation
2. Elongation
3. Fusion and degradation
40. ➢ References :
1. Gerard J. Tortora, Bryan Derrickson, “Principles of Anatomy and Physiology”
15th Edition 2017.
2. Anne Waugh, Allison Grant, “Ross and Wilson Anatomy & Physiology” in
health and illness, 12th Edition, 2014.
3. Gerald karp, “Cell and Molecular Biology Concept And Experiment” 7th
Edition, 2016
4. www.Wikipedia.org
5. www.slideshare.net