The study of cells and its components. The plasma membrane, nucleus and other organelles.

1. Cytology
Lecture two

2. Cell

3. Introduction
• Cells are the basic structural and functional unit of the living organism showing a
variety of functional specializations which perform all the activities necessary for the
survival, growth and reproduction of the organism
• It is a self replicating, self regulating and self governing biological system
➢Metabolism (absorption, synthesis, respiration and excretion),
➢Growth and regeneration
➢Irritability (excitability)
➢Movement
➢Reproduction
➢Aging and death

4. Cont.…
• Number (around 100 trillion
(1012) cells
• Type (more than 250 named
cell types)
• Shape (round, oval, columnar,
multipolar, polygonal,
cylindrical, fusiform, pyramidal,
pyriform, etc.)
• Size (5µm - 120µm in
diameter)
• Functions

5. Cellular Functions in Some Specialized Cells
Function Specialized Cell(s)
Movement Muscle cell
Synthesis and secretion of enzymes Pancreatic acinar cells
Synthesis and secretion of mucous
substances
Mucous-gland cells
Synthesis and secretion of steroids Some adrenal gland, testis, and ovary
cells
Ion transport Cells of the kidney and salivary gland
ducts
Intracellular digestion Macrophages and some white blood
cells
Transformation of physical and chemical stimuli into
nervous impulses
Sensory cells
Metabolite absorption Cells of the intestine
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6. Cont.…

7. Components of Eukaryotic Cell
1. Cell membrane
2. Cytoplasm
3. Karyoplasm (Nucleus)

8. • In electron micrographs of osmium-stained tissue, appears as trilaminar layer, each layer
2.5 nm in diameter
• Because all membranes have this appearance, it is called the unit membrane
1. Cell membrane

9. Cell membrane
➢ about 7.5 nm thick
➢ Biochemically made by the following components
1. Lipids
2. Proteins
3. Carbohydrates

10. Phospholipids
• Such as phosphatidylcholine (lecithin)
• With an amphipathic character (both hydrophobic and hydrophilic)
• Arranged in a bilayer, each with:
• Hydrophilic polar phosphate-containing head - towards water
• Hydrophobic nonpolar pair of fatty acid tails – away from water

11. Cholesterol
• Modulate the fluidity and movement of all membrane components maintaining the
structural integrity of the plasma membrane

12. Proteins
• 50% w/w in the plasma membrane
• Most are globular proteins forming the following two groups:
1. Integral membrane proteins
2. Peripheral membrane proteins

13. Integral membrane proteins
• Some protrude from only one membrane surface, while others are transmembrane
proteins and protrude from both sides

14. Peripheral membrane proteins
• Are more loosely associated, mostly on the inner membrane surface
• Bound to the polar groups of the membrane phospholipids or integral membrane proteins
• Usually functions as part of the cytoskeleton or an intracellular secondary messenger
proteins of the cell

15. Cell membrane proteins
• Functionally there are 6 broad categories of membrane proteins as:
1. Pumps
2. Channels
3. Receptors
4. Linkers
5. Enzymes
6. Structural proteins

16. Carbohydrates
• Occur as oligosaccharide attached to plasma membrane proteins as glycoproteins and lipid
as glycolipids
• Branch and project from the outer surface of the outer leaflet of the plasma membrane
• They form a cell coat called glycocalyx that participates in:
• Cell adhesion to the extracellular matrix
• Binding of enzymes and antigens to the cell surface.
• Cell-to-cell recognition and interaction

17. Organization of the cell membrane
• Are asymmetrical because of:
• Different composition of lipids
• Peripheral proteins are mainly on inner leaflet
• Oligosaccharides are on outer leaflet

18. Functions of the cell membrane
1. Selective permeability & transportation
2. Communication
3. Physical barrier
4. Intercellular connections

19. 2. Cytoplasm
• It is the cellular material outside the nucleus but within the plasma
membrane; consists of the following:
• Cytosol - cellular fluid (mainly water) with dissolved proteins, salts, sugars, and other
solutes
• Organelles - ultramicroscopic structures that perform various cellular functions;
ribosomes, ER, mitochondria, etc.
• Cytoskeleton - protein filaments and tubules that provide support, movement within
the cell; cellular skeleton
• Inclusions - chemicals such as glycogen, fat, and pigments

20. Cytosol, cytoplasm matrix (or ground substance)
• In between the three dimensional cytoskeletal structure
• Contains proteins, electrolytes, and metabolites dissolved in water (which makes 75-90%)
• Could generally be divided into an inner and outer domains

21. Organelles
• Metabolically active structures
• include:
1. Endoplasmic reticulum
2. Golgi complex (bodies or apparatus)
3. Lysosomes
4. Peroxisomes (microbodies)
5. Mitochondria
6. Endosomes and phagosomes
7. Proteasomes
8. Ribosomes
9. Cytoskeleton
i. Microtubules
ii. Microfilaments
iii. Intermediate filaments
10. Centrioles

22. Endoplasmic reticulum
• Convoluted network of anastomosing membrane channels (cisternae ) of various shapes
• Show transfer vesicles which bud and move to the Golgi complex
• Are of two types:
1. Rough or granular endoplasmic reticulum
2. Smooth or agranular endoplasmic reticulum

23. Rough or granular endoplasmic reticulum (RER)
• Show continuity with the outer nuclear membrane
• Have docking proteins as receptors for ribosomes, and glycoprotein ribophorins
• Synthesize proteins for sequestration
• For export
• For proteins of the ER, the Golgi apparatus, Lysosomes or the cell membrane
• Transport molecules through cisternal space
• Under LM appear as basophilic patches formerly termed as:
– Ergastoplasm in glandular cells
– Nissl bodies in neurons

24. Smooth or agranular endoplasmic reticulum (SER)
• Have more tubular or vesicular cisternae than the RER
• Functions in:
o Synthesis of phospholipids and steroids
o Lipid metabolism
o Glycogen breakdown
o Detoxification
o Transport molecules through cisternal space
o Store and release calcium ions in the striated muscle cells as sarcoplasmic reticulum

25. • Stalk of 3-10 discrete flattened and slightly curved bag-like channels or cisternae
surrounded by vesicles
• Has the following two surfaces:
a. Forming, convex, entry, cis face
• Closest to the nucleus
• Surrounded by small transfer vesicles (vesicles in)
b. Maturing, condensing, exit, trans face
• Usually concave
• Has condensing vacuoles (vesicles out) and secretory granules
Golgi complex (Golgi body or Golgi apparatus)

26. • Functions in:
• Synthesis of polysaccharides
• Glycosylate proteins and lipid forming, respectively glycoproteins &
proteoglycans and glycolipids
• Sulfate glycosaminoglycans
• Packaging of secretory products
• Concentration and storage of secretory products
Golgi complex (Golgi body or Golgi apparatus)

27. Lysosomes
• Electron dense usually spherical bodies with a diameter of 0.05 - 0.5 μm
• Contain more than 40 hydrolytic enzymes (cause hydrolysis of a chemical bonds, breaking
down bigger molecules), most commonly acid hydrolyases such as proteases, nucleases,
phosphatase, phospholipases, sulfatases, and β-glucuronidase
• Most active at an acidic pH (5.0)

28. Peroxisomes (microbodies)
• Are like the lysosomes, but slightly larger in diameter (0.2–0.5 μm)
• Contain more than 40 oxidative enzymes that:
– Produce hydrogen peroxide (H2O2) to kill microorganisms and detoxifies toxic agents
• Complement certain functions of the SER and mitochondria in the metabolism of lipids
and other molecules
• Replicate by budding of precursor vesicles from the ER or fission of preexisting peroxisomes

29. Mitochondria
• Large spherical, filamentous or rod-shaped with diameters of 0.5-1 μm and 2-7 μm long
• Have double membranes
a. Outer porous smooth membrane - containing many transmembrane proteins called
porins that form channels
b. Inner less porous membrane
o Makes cristae
➢ Shelf-like in many cells
➢ Tubular in steroid secreting cells
• Able to rapidly changing shape, fusing together and dividing by fission

30. Mitochondria
• Have two spaces
a. Intermembrane space (outer chamber, intracristal)
b. Matrix space (intercristal space), which contains:
o Enzymes, water, solutes, and granules that bind Ca2+ and Mg2+
o Mitochondrial ribosomes
o mRNA, tRNA and rRNA
o Circular DNA
➢ Like those of prokaryotic cells
➢ Are maternal

31. Endosomes and phagosomes
• Endosomes are membrane bound structures in the cell
• May be released at other side in transcytosis
• Phagosomes are found in the forms of:
1. Hetrophagosomes - ingested
2. Autophagosomes – self
3. May fuse with lysosomes forming the
hetrophagolysosomes and autophagolysosomes

32. Proteasomes
• A cylindrical structure made of four stacked rings, each composed of seven proteins
including proteases
• Degrade denatured or nonfunctional polypeptides tagged for degradation with a small
protein called ubiquitin

33. Ribosomes
• About 20 × 30 nm in size
• Composed of :
1. Several types of ribosomal RNA (rRNA)
2. Specific ribosomal proteins
• Have large and small subunits
• Found in two forms: free ribosomes and polyribosomes (polysomes)

34. Polyribosomes or polysomes
• Clustered along a single strand of mRNA, and occur as:
1. Free polyribosomes
• Found in the cytoplasm
• Synthesize structural proteins and enzymes for intracellular use
2. Attached polyribosomes
• Attached to the outer nuclear membrane and RER
• Produce proteins to be secreted, proteins of the ER, the Golgi apparatus,
Lysosomes or the cell membrane

35. Cytoskeleton
• Gel-like network of protein filaments
• Include:
1. Microtubules
2. Intermediate filaments
3. Microfilaments

36. Microtubules
• Tubular with 24 nm outer diameter, 5 nm wall thickness and variable length up to many
micrometers
• Wall is made by tubulin heterodimers
• Each with α-tubulin and β-tubulin protein molecules
• Arranged as thread like polymers called protofilaments
• 13 protofilaments, circumferentially form wall of a microtubule

37. Microtubules
• Contain microtubule-associated proteins (MAPs), Include:
a. Kinesin
o Transport vesicles towards the plus end
b. Dynein
o Move vesicles towards the minus end
c. Dynamin
o Motor for sliding microtubules in respect to each other, for activities such as
elongation of axon at growth cone

38. Microtubules
• Functions include
• Intracellular transport
• Maintaining cell shape
• Intracellular compartmentalization
• Cell migration

39. • Are 10-12 nm wide, between microtubules and microfilaments
• Unlike microtubules and actin filaments, are stable, conferring increased mechanical
stability to cell structure and tensile strength
• Formed of tetramers of rod-like proteins making staggering helical cable-like bundles
Intermediate filaments

40. Intermediate filaments
• Several types, the most common ones include:
1. Lamins - in nuclear lamina of all types of cells
2. Keratin or Cytokeratin - in all epithelial cells
3. Vimentin - in mesenchylly derived cells
4. Desmin - in all muscle cells
5. Neurofilaments - in neurons
6. Glial fibrillary acid protein (glial filament) - in glial cells

41. Microfilaments (Actin Filaments)
• Measure 5 -7 nm in diameter
• Composed of polymers of globular G-actin monomers that assemble into a double-
stranded helix of filamentous F-actin
• G-actin is added to preexisting filaments for growth and branching, but new filaments can
also be formed

42. Microfilaments (Actin Filaments)
• Have various myosin motor transport cargo along F-actin.
• Movement is usually toward the (+) ends
• Interactions between F-actin and myosins form the basis for various cell
movements, which include:
• Transport of organelles, vesicles, and granules in the process of cytoplasmic
streaming
• Cytokinesis during mitosis
• Endocytosis
• Muscle and contractile cells contraction

43. Centrioles
• Located at the centrosome, near the nucleus and Golgi bodies
• Cylindrical shaped, as a pair, perpendicular to each other
• Made by 9 triplets of microtubules
• Each microtubule in the triplet share portion of its neighbor’s wall
• Surrounded by pericentriolar bodies or microtubule-organizing centers (MTOCs)
• The MTOCs contain γ-tubulin rings, each of which serves as the nucleation site for the
growth of a single microtubule

44. • Functions include:
• Control microtubule polymerization
• Transmit physical organizing forces
• Control movements of organelles and vesicles
• Form the poles of mitotic spindle apparatus
• Form basal bodies of cilia and flagella
Centrioles

45. Inclusions
• Metabolically inactive materials
• Include:
1. Lipid droplets
2. Glycogen granules
3. Various types of pigments
4. Crystals

46. 1. Lipid droplets
• Mainly in the adipose cells, but also in many other cells
• Triglycerides as energy source and stored cholesterol for the synthesis of steroids
Inclusions

47. 2. Glycogen granules
• As clusters of electron-dense bodies (rosettes) specially abundant in the hepatocytes
and muscle cells
• Converted to glucose
Inclusions

48. 3. Pigments
a. Hemosiderin
• Brown colored inclusion that accumulates within the macrophages
• Breakdown product of hemoglobin
Inclusions

49. b. Lipofuscin
• Yellowish-brown pigment that increase with increasing age
• Are residual bodies of lysosomal activities
Inclusions

50. c. Melanin
• Brownish pigment mainly in the cells of skin and hairs (melanocytes &
keratinocytes), but also in some neurons and in the pigment epithelium
of retina
Inclusions

51. e. Carbon particles
• Mainly in macrophages located in the lungs
Inclusions

52. d. Carotenoid
• A yellowish-orange-red pigment obtained from vegetables and fruits
Inclusions

53. 4. Crystals
• May be crystalline form of certain proteins
• In humans crystals described include:
➢Crystals of Reinke in the interstitial cells of Leydig of testis
➢Crystals of Charcot-Böttcher in the Sertoli cells of testis
Inclusions

54. 3. Nucleus
• Oval, elongated or flattened in shape.
• 5-10 µm in diameter
• Composed of:
1. Nuclear envelope
2. Chromatin
3. Nucleolus
4. Nucleoplasm

55. • Double membrane separated by perinuclear cisternal space (30-50 nm wide)
1. Outer nuclear membrane
– Shows occasional continuities with the RER and has polyribosomes
– Surrounded by a loose network of intermediate filament vimentin from its cytoplasmic
aspect
Nuclear envelope

56. 2. Inner nuclear membrane
– Lined internally by nuclear (fibrous) lamina with intermediate filament lamins
• Contains specific lamin receptors and several lamina-associated proteins
• Functions include:
– Serve as scaffolding for chromatin
– Involved in nuclear organization, cell-cycle regulation, differentiation, and
gene expression
Nuclear envelope

57. Chromatin
• DNA and associated 5 basic proteins called histone, and nonhistone proteins
• Each of the 46 human DNA is about 40,000 μm long in average making a total of 1.8 -
2 meter long
• Located in a nucleus with a diameter of only 5 - 10 μm
• Undergo a super helical coiling to give repeating nucleosomes connected by short
connecting strands

58. • A nucleosome is made by:
• 146-166 base pairs of the DNA strand wrapped twice around a core of a pair of 4 types
of histones (H2A, H2B, H3 and H4) called an octamer
• The connecting strand as a 2-nm filament is made by 50-80 DNA base pairs with
another type of histone (H1)
Chromatin

59. Chromatin
• Undergo further progressive super coiling and looping

60. • During interphase chromatin is identified as:
1. Heterochromatin
• As dense basophilic staining by LM and dense granular regions by EM
2. Euchromatin
• Lightly stained dispersed regions in the nucleus (not evident in the light
microscope)
Chromatin

61. • Is found as:
1. Marginal chromatin – along the inner surface of the nuclear envelope associated with
the fibrous lamina
2. Karyosomal chromatin – dispersed throughout the nucleus
3. Nucleolar associated chromatin – in the nucleolus
4. Bar body (sex chromatin) - one of the X chromosome , appears as drum stick
appendage in the neutrophils
Heterochromatin

62. Nucleolus
• Round basophilic & non-membrane bound bodies
• Is site of rRNA synthesis and initial assembly of ribosomes
• Has a protein named nucleostemin that regulates the cell cycle and influences cell
differentiation

63. Nucleoplasm
• Nuclear components other than the chromatin and nucleolus
• Although appear amorphous medium under microscopy it contains:
• Many proteins and other metabolites
• Intranuclear lamin-based structures
• Protein filaments of the nuclear pore complexes
• RNA transcription and processing apparatus

64. Cell Renewal
• Somatic cells may be classified according to their mitotic activity as:
1. Renewing cells
– Slowly renewing cells
– Rapidly renewing cells
2. Stable cells (quiescent cells)
3. Static cells (permanent cell)

65. Cell Cycle
• A self-regulated sequential events that controls cell growth and cell division
• The cell cycle stops at several checkpoints
• Driven by a family of cytoplasmic proteins called cyclins, cyclically synthesized and
degraded during each cycle in response to intracellular or environmental signals

66. Cell Cycle
• In somatic cell is comprised of:
1. Interphase
a. Gap1 (G1) phase
b. Synthesis (S) phase
c. Gap2 (G2) phase
2. Mitosis

67. The G1 (gap 1) phase
• Longest and most variable - a few hours to several days
• The cell:
• Gathers nutrients
• RNA and protein synthesis occurs
• Grow to the size of the parent cell
• Centrioles begin to duplicate

68. The G1 (gap 1) phase
• Monitored by 2 checkpoints:
1.G1 DNA-damage checkpoint
• Monitors the integrity of DNA
• If the DNA has irreparable damage it will most likely undergo programmed cell death
(apoptosis)

69. The G1 (gap 1) phase
2. Restriction checkpoint
– Is the most important checkpoint in the cell cycle
– Cell self-evaluates its own replicative potential
• If requirements are met enter the S phase
• If requirements are not met cell cycle is paused and:
1. Attempt to remedy the problematic condition, or
2. Enter into G0 and awaiting further signals permanently (for static cell) or
temporarily (for stable cells)

70. S (synthesis) phase
• Takes about 7.5 to 10 hours
• Undertake:
• DNA replication and doubling
• Histone synthesis
• Beginning of centrosome duplication
• Has S DNA-damage checkpoint
• Monitor quality of replicating DNA

71. G2 (gap 2) phase
• Is a period of :
1. Further cell growth and reorganization of cytoplasmic organelles
2. Examination of the replicated DNA by 2 checkpoints:
a. G2 DNA-damage checkpoint
b. The unreplicated-DNA checkpoint
• Prevents entry into the M phase before DNA synthesis is complete

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