Department of Human Anatomy
College of Medicine & Health Sciences
University of Gondar
Ayanaw Worku
Histology
Credit Hour – 4 (3 hrs lecture + 1 hr practical)
Course Code: Anat 221
1. Part I: General Histology




Cytology
Tissue of human body
General histology of glands
Histological and histochemical methods
2. Part II: Systemic Histology
2
References
1. Junqueira`s Basic Histology Text and Atlas 12th
edition
2. Wheater`s Functional Histology Text and
Atlas 5th edition
3. Histology A Text and Atlas with Correlated
Cell and Molecular Biology 6th edition
(Michael H. Ross)
4. deFore Human Histology Atlas …
3
Evaluation
4
Rules & Regulations
Rights
1. Ask questions with out any hesitation
Responsibilities
1. Punctuality (lecture & practical)
2. Switch off your mobile
3. 100% attendance
4. Active participation
5. Bring atlas and notes (practical)
6. Submit assignments on time
7. No cheating during exam (0)
5
Histology
Objectives
By the end of this course, students will be able to:
1. Define terms related to histology and histological
techniques
2. List, identify and demonstrate different
components of human cells and tissues
3. Describe some clinical correlations of histological
structural changes
6
Part I: General Histology
Introduction & History
Histology: is the study of the normal structure of tissues.
 It is derived from two Greek terms:
 Histo = tissue
 Logos = to study or learn
 The term tissue is derived from the French word ”tissue”,
which means weave, web or texture.
 This term ”tissue” was first introduced by the French
anatomist and physiologist Bichat, in 1802.
7
 Tissues are groups of similarly differentiated cells
with their intercellular substance or extracellular
matrix secreted by the cells themselves. Or,
 Groups of closely associated cells that are similar in
structure and function.
8
 When tissues malfunction, e.g. in certain disease states
such as cancer or inflammation, there are often specific
changes in the microscopic structure of the tissues.
 The study of these changes is known as histopathology.
o So, a sound knowledge of normal structure is essential
for an understanding of pathology.
9
• Tissues are made of two interacting components:
a) Cells
b) Intercellular substance /extracellular matrix
•
The small size of cells and matrix components makes
histology dependent on the use of microscopes.
•
Reading assignment about microscope
10
 The cells of a tissue are separated by a narrow gap called
intercellular space.
 This space has a variable width at different places and in
different tissues.
 It is very narrow between the cells of epithelial tissue
(about 20 nm) but wider in connective and muscular
tissues.
11
CELL
 A cell is the smallest independent functional and
structural unit of a living thing, which is viable and
capable of multiplication.
 i.e. cells are the units of tissues, organs and finally
systems of the body.
 The science that studies about cell is called cytology,
which is derived from two Greek words.
 Kytos = cell or a hollow
 Logos = to study or learn
12
 Cytology, as the study of cells, was started in
1665 by the English Scientist Robert Hook.
 Since then cytology started to deal with the
chemical composition
life characteristics and
functions of a cell
13
Cell
According to the modern cell theory:
1. All living things are made up of one or more cells
 Matthias Schleiden & Theodor Schwann
2. Cells are the basic living units within organisms and the
chemical reactions of life take place within cells.
3. All cells arise from pre-existing cells.
14
• It is estimated that the human body consists of between
80 -100 trillion cells each of which perform a specific
function.
• The human organism presents about 200 different cell
types, all derived from the zygote, the single cell formed
by fertilization of an oocyte with a spermatozoon.
 All these cells carry out certain basic functions
responsible for keeping them alive.
15
The basic functional activities or properties of the cells:
 Irritability
(excitability)
 Conductivity
 Contractility
 Absorption
 Metabolism
 Secretion
 Excretion
 Movement
 Growth &
regeneration
 Reproduction
 Aging
 Death
16
 In multicellular animals, distinct population of cells
become specialized to perform a particular function.
 Cell specialization allow division of labour
 In such cases one or more of the basic functions
amplified or modified.
e.g. Nerve cells: excitability
Muscles cells: contractility
 Cells, which assume such highly specialized
functions of this type frequently, lose one of the
fundamental attributes of cells, i.e. the ability to
divide and multiply.
17
• From the structural and functional point of view,
there are two types of cellular organization
• Protocytes
• Eucytes
1. Protocytes /Prokaryotic cells/
 They are primitive forms of cellular organization
to which the bacteria and blue green algae
belong.
 The term prokaryotic means ”before nucleus”.
18
• These cells are small in size, contain cell wall out side
their cell membrane but no nuclear membrane.
• Therefore, they have no nucleus, no histones (specific
basic proteins bound to DNA) and usually lack
membranous organelles.
• Their unbounded DNA (= Nucleoid) is used as a
nucleus equivalent.
19
Pili
Nucleoid
Ribosomes
Plasma
membrane
Bacterial
chromosome
Cell wall
Capsule
0.5 µm
Flagella
A typical
rod-shaped
bacterium
A thin section through the
bacterium Bacillus
coagulans (TEM)
20
2. Eucytes /Eukaryotic cells/
 The word eukaryotic means ”true nucleus”.
 They have more complex level of organization.
 They contain nucleus
 These cells are larger in size and their nucleus is
distinct being surrounded by a nuclear envelope.
 Their cytoplasm contains numerous membrane limited
organelles.
 They possess histones associated with their genetic
material
 Found in unicellular & multicellular organisms
21
Eukaryotic Cell
22
Comparison of Prokaryotic & Eukaryotic Cells
23
Cell Diversity
 Not all cells are alike. Even cells within the same
organism show enormous diversity in size, shape,
and internal organization.
 Each cell’s specialization, how it lives and what it can
do depends on
o its shape
o its size and
o the particular organelles it contains
24
a. Cell Size
 A few types of cells are large enough to be seen by the
unaided eye.
 The human egg (ovum) is the largest cell in the body, and
can just be seen without the aid of a microscope.
o The size of cells is limited, they do not grow
constantly.
o Cell size is independent of body size but it shows
relations to differentiation and function.
o Because of the various functions that exist in our
body, we have cells with variable sizes
25
Most cells are small for two main reasons:
I.
The cell’s nucleus can only control a certain volume
of active cytoplasm.
II. Cells are limited in size by their surface area to
volume ratio.



o
A group of small cells has a relatively larger surface area
than a single large cell of the same volume.
This is important because the nutrients, oxygen, and other
materials a cell requires must enter through its surface.
As a cell grows larger at some point its surface area
becomes too small to allow these materials to enter the cell
quickly enough to meet the cell's need. Fick’s law
Rate of diffusion = Surface Area x Concentration Difference
Distance
26
For example:
•
The human egg cell (ovum) has a diameter of about
0.15 - 0.20 mm.
•
The human red blood cell (RBC) measures about 7.4
µm.
•
A small human lymphocyte measures about 6 µm.
•
The striated muscle fibre can be as long as 15 cm.
•
The nerve cells with their processes can be more
than 1 meter long.
27
28
b. Cell Shape
• Cells has different shapes. For example,
Rod shaped e.g. bacterium Escherichia coli
Slipper shaped e.g. paramecium (protozoan)
Irregular form e.g. amoeba (protozoan)
Box or cubic shaped e.g. plant cells
• In humans cell posses different forms
Outermost layers of skin cells are flat
Muscle cells are long and thin
Some nerve cells, with their elongated, tentacle-like
extensions, suggest an octopus
29
Cell Shape & Types
Animal Cell
Plant Cell
Bacterial Cell
30
• In multicellular organisms, shape is typically tailored
to the cell’s job. For example,
Flat skin cells pack tightly into a layer that protects
the underlying tissues from invasion by bacteria.
Long, thin muscle cells contract readily to move
bones.
Numerous extensions from a nerve cell enable it to
connect to several other nerve cells in order to
send and receive messages rapidly and efficiently.
Absorptive cells of the gut has microvillus
31
• In addition to this the shape of the cell depends on the
surrounding structure. For example,
– In a fluid medium the cells have rounded shape, e.g.
white blood cells.
– But in cells organized in groups, the form of a cell is
influenced by other cells surrounding it and can
therefore have variable form, e.g. epithelial cells.
32
Structural Composition of a Cell
 Cells contain chemical compounds the major constituent
of which is water (60%) .
 The remaining 40% is formed by different compounds
like.
 Proteins - 19%
 Fat - 15%
 Inorganic salts - 5%
 Carbohydrates - 1%
 Generally we can say that each cell is composed of water,
proteins, lipids, electrolytes, carbohydrates, and nucleic
acids.
 But the specific components of a cell are the proteins
and its nucleic acids.
33
The proteins of a cell are divided into three functional
units:
a. Enzymes:
 Catalyze a chemical reaction (metabolism) in cells.
b. Structural proteins:
 used for the formation of the structure of the cell
itself, e.g. microtubuli, microfilaments and
intermediate filaments.
 these proteins form the cytoskeleton that confers
structural support to the cell and help to direct the
functions of organelles to specific cellular localities.
c. Export (Secretory) proteins:
 these are proteins synthesized in the cell and
transported to the exterior for the formation of
specific intercellular substances like collagen and
elastic fibers of connective and supportive tissues.
34
The cellular proteins can also be categorized into fixed
and reserve proteins:
1. Fixed cell proteins: which are vital for any activity of
the cell.
2. Reserve cell protein: two types
a. Dispensable reserve proteins: are those which can
be used for energy production and other
purposes during starvation.
b. Labile reserve protein: are proteins which can be
released into the blood stream to maintain the
plasma protein concentration.
35
o Structurally those protein molecules associated with
cells are:
1. Rounded (globular proteins)
 Water soluble
 Abundant than fibrillar proteins
2. Fibrillar proteins (appear as fibres).
– Partly soluble
– Found mainly in the extracellular space
– Examples of fibrillar proteins are actin, myosin, collagen
and elastin.
36
 Additionally there are molecules containing
combinations of proteins with carbohydrates in the form
of:
 (glycoproteins or glycoconjugates) and
 Proteins with lipids in the form of:
 lipoproteins which are very important for the
cellular function and the formation of its structures.
• The nucleic acids serve as carriers of information
during protein synthesis and they may also take part in
the synthesis of proteins.
37
Parts of a Cell
• Although cells differ in size, shape, and function, each
cell consists of two major components:
a) Nucleus: contains the hereditary or genetic
material and is completely surrounded by
cytoplasm, from which it is separated by a nuclear
envelope.
b) Cytoplasm: limited by a plasmalemma (cell
membrane), which separates the cell from the
external environment
38
 The cytoplasm and the nucleus in a given cell have
certain relations in volume.
o This is called nucleus- cytoplasm relation.
o This relation is specific to a given cell.
 By measuring this nucleus- cytoplasm relation we can
 Differentiate between normal & abnormal cells &
 Identify the functional state in which a given cell is
found
Functional nuclear swelling
39
 For example, when there is increased cellular activity
water uptake by the nucleus will be enhanced (water of
hydration) resulting in the enlargement of the nucleus.
o This enlargement of the nucleus is called functional
nuclear swelling.
o The swelling of the nucleus thus changes the
proportion between the nucleus and the cytoplasm.
40
Nucleus
Cell
Nuclear membrane
Chromatin skeleton
Nucleolus
Nucleoplasm
 Cell membrane
Cytoplasm  Cytoplasmic matrix
(cytosol or hyaloplasm)
 Organelles
 Inclusions
41
Generalized Cell
42
Cilia
Cell membrane Microvilli
Junctions
Endocytotic vesicles
43
Commonly
found
Organelles
Specialized
 Mitochondria
 Endoplasmic reticulum
 Golgi apparatus
 Centrioles
 Lysosomes
 Ribosomes
 Microbodies
 Microfilaments
 Microtubuli
 Myofilaments (fibrils)
 Tonofilaments
 Neurofilaments
 Synaptic vesicles
44
Inclusions
Fat
Glycogen
Proteins
Crystals
Granules
Pigments
45
46
A. Cytoplasm
 It is a watery-transparent colloidal medium
 Its consistency varies from solution to jell
 It consists of
 cytoplasmic matrix
 organelles
 cytoskeleton
 inclusions
 various organic compounds
 salts and water
 It is a site of various cellular activities that are
mediated by its different parts.
47
i. Cytoplasmic Matrix (Cytosol)
• It is part of the cytoplasm occupying the space between
the organelles and inclusions.
• It is a concentrated aqueous gel consisting of molecules
of different sizes and shapes e.g.,
 electrolytes
 metabolites
 RNA
 synthesized proteins
 substrates and products of different enzymatic
reactions
 enzymes
• It is site of physiologic processes that are basic to the
cell’s existence
48
ii. Organelles (little organs)
 These are intracytoplasmic metabolically active
structures which are partly capable of multiplication.
 They are the specific cellular machinery suspended in
the cytoplasmic matrix.
 The organelles include:
 Membranous organelles
 Non-membranous organelles
49
1. Cell (plasma) membrane
A. Membranous
2. Endoplasmic reticulum
3. Golgi apparatus
4. Mitochondria
5. Lysosomes
6. Peroxisomes
50
B. Non- membranous
1. Ribosomes
2. Centriole
3. Microtubuli
4. Microfilaments
51
A. Membranous Organelles
• The membranes of membranous organelles form
vesicular, tubular, and other structural patterns within
the cytoplasm
• Function of the membrane
– Greatly increase the surface area on which essential
physiologic and biochemical reactions take place.
– Help to localize the different organelles in discrete
areas of the cytoplasm so that they and their
associated metabolic processes remain separate
from other components of the cell.
52
Cell Membrane (Plasma Membrane, Plasmalemma,
Cytolemma)
 It is a 7 - 10 nm thick barrier between the intra and
extracellular spaces.
53
 Function of plasma membrane
 Provides a protective barrier against substances
and forces outside the cell
 It is selectively permeable to substances entering
and leaving the cell
 It is a closed compartment that allows cellular
individuality
 Act as receptors; i.e, they have the ability to bind to
specific molecules arriving from outside the cell
(communication)
 Sensory tool that permits the cell to recognize & be
recognized by other cells & macromolecules.
 Cell-to-cell attachment
54
• To perform all these activities the cell membrane has
unique structure
• In order to describe the structure of the cell membrane
three models were developed:
1. Unit membrane principle Robertson in 1959
• Drawback
2. Fluid mosaic model or globular protein mosaic
model Singer & Nicolson in 1972
3. Lipid globular -protein (modified fluid mosaic)
model
55
 The cell membrane is composed of:
1. A layer of lipid molecule.
2. Protein molecules that cover the lipid layer on either
sides.
 The lipid layer consists of phospholipids and cholesterol.
 This layer contains a hydrophobic (non-polar) group directed
to the interior of the membrane and a hydrophilic (polar or
ionic) group directed towards the inner and outer surfaces of
the membrane facing the aqueous environments.
 The hydrophilic groups are covered by proteins which are
arranged perpendicular to them.
 This model was designed by Robertson in 1959 as a unit membrane
principle that forms the basis of all membranous structures of a cell.
56
Lipid Molecules
57
 Singer & Nicolson found that a cell membrane consists
of two layers of lipid molecules (lipid bilayer) covered
by fibrillar protein and in the lipid layer a mosaic of
scattered globular protein molecules are found.
 They designated this as a fluid mosaic model or
globular protein mosaic model.
58
• Therefore, the plasmalemma is composed of:
 Lipids
 Proteins
 Glycolipids
 Carbohydrates
59
A. Membrane lipids
• Lipid forms about 50% of the mass of the
plasmalemma and consists of three major
classes of lipid:
a. phospholipids
b. cholesterol
c. glycolipids
60
a. Phospholipids
• These molecules line up in two parallel rows
forming phospholipid bilayer
• This arrangement occur because phosholipids are
amphipathic i.e. they posses polar & non-polar
regions.
• Polar
– Phosphate containing ‘head’
– Hydrophilic (mixes with water)
– Faces the membrane surface
• Non-polar
– Two fatty acid ‘tails’
– Hydrophobic (do not mix with water)
– Projects into the interior of the membrane
– Tails in the inner & outer leaflets form weak
bonds that attach the leaflets to one another.
6
2 6/3/2012
Fluidity of the Lipid Bilayer
• The phospholipid bilayer is dynamic because the
lipids
– Can move sideways and exchange places in
their own layer to allow small molecules (O2,
CO2, & H2O to enter)
b. Cholesterol
• Located in both leaflets of the plasma membrane.
• The stiff steroid rings of cholesterol strengthen the
membrane but decrease its flexibility.
– Assist in maintaining the structural integrity of
plasma membrane
6
4
c. Glycolipids
• Lipids with one or more sugar groups attached.
• Amphipathic - polar carbohydrate residue extend to
extracellular matrix (glycocalyx)
• Present in the outer leaflet only
• Functions
– Adhesion among cells & tissues
– Mediate cell to cell recognition & communication
– Contribute to the regulation of cellular growth &
development
B. Membrane Proteins
• There are 2 types of membrane proteins
Integral proteins
Peripheral proteins
66
a. Integral proteins
• They are firmly embedded in the lipid bilayer and
cannot be removed
• Constitute about 50% of the plasmalemma by weight
• Some integral proteins are transmembrane proteins
that span the entire width of the plasmalemma and
protrude from both sides
• Are amphipathic (hydrophilic and hydrophobic amino
acids).
• Most are glycoproteins
6
7 6/3/2012
• Function integral proteins
Some form channels (pores) through which certain
substances flow into or out of the cell.
Some act as transporters (carriers) to move
substance from one side of membrane to other.
Some serves as recognition sites i.e. receptors.
68
b. Peripheral proteins
• Do not extend across the phospholipid bilayer.
• Commonly located on cytoplasmic aspect of inner
leaflet and contribute to its stability
• They can be removed from the plasmalemma without
disrupting the lipid bilayer
• They are attached to the surface by ionic interactions
with:
 An integral protein
 Another peripheral membrane protein
 By interaction with the polar head groups of the
phospholipids.
6/3/2012
• Functions
o Some are enzymes
o Anchor elements of the cytoskeleton to the
cytoplasmic surface of the plasmalemma
o Intracellular messenger system
o Keep the molecules of the plasmalemma from
separating and the cell membrane from tearing apart.
• Some membrane proteins can diffuse laterally in the lipid
bilayers, whereas others are immobile.
• Ratio of lipid to protein is
o 1:1 (by weight) in most cells
o 4:1 in myelin
70
Glycocalyx or Cell Coat
 Surrounds the cell as an outer layer.
 It is composed of sialic acid containing glycoproteins and
glycolipids.
 The chemical structure of the polysaccharide chain in the
glycocalyx is genetically determined.
 The various combinations of the sugars in the chain are cell
specific, i.e. are unique to a given cell.
71
• Function of glycocalyx
o Acts like a molecular “signature” that enables cells
to recognize one another
o Act as antigens and determine the immunological
specificity of the cell
o Enables cells to adhere to one another in some
tissues
o Protects cells from being digested by enzymes in
the extracellular fluid
o Attract a film of fluid to the surface of many cells.
e.g. RBC, GIT & respiratory system
72
Cytoplasmic Membrane Systems & Cell Organelles
 The cytoplasm is divided in to different compartments by
the membrane systems.
 These membrane systems form permeability barrier for
the cellular reactions and are important for the regulation
of cellular function.
 These membrane system with the non-membranous
structures found in the cytoplasm constitute the so called
organelles.
 The organelles are important for the maintenance of the
cellular activities.
73
Membranous Organelles
1. Endoplasmic reticulum (ER):
•
•
•
It is a network membranes that enlarges the internal
surface area of the cell for chemical or enzymatic
reactions.
Its size depends on the functional state of the cells and it
shows changes in shape and size from the early
development on.
It consists of an irregular network of branching and
anastomosing tubules that are often continuous with the
outer layer of the nuclear envelope by forming large,
parallel and flattened saccular structures referred to as
cisternae.
74
 The cisternae may occur as single, but more often several
of them become interconnected to form lamellar
systems of parallel flattened cavities.
 Additionally there are vesicles that do not form part of the
canalicular system but considered as part of the ER.
 The degree of development of the reticulum (network)
and the relative proportion of its tubular, cisternal and
vesicular elements varies greatly in different cell types
and in the different phases of the physiological activity of
the same cell.
75
There are essentially two types of ER.
1. Rough (granular) rER:
• has ribosomes attached to its outer limiting
membrane and the membrane is studded by the
ribosomes.
• it contains ribophorins I and II (integral membrane
proteins that may provide attachment sites for the
large subsunits of ribosomes)
2. Smooth (agranular) sER: ribosomes are not attached
to it and contains no ribophorins I and II.
76
77
Rough Endoplasmic Reticulum (rER)
 The rER forms a compartment for protein synthesis
which takes place in the ribosomes attached to it.
 It is prominent in cells specialized for protein secretion
such as
1. Pancreatic acinar cells (digestive enzymes)
2. Activated fibroblasts
3. Plasma cells (Immunoglobulin)
4. Neurons
5. Glandular cells
6. Odontoblasts, ameloblasts & osteoblasts
78
• It’s membrane is continuous with the outer layer of the
nuclear membrane which is considered as part of the
rER and also studded by ribosomes, but it rarely
reaches the cell membrane.
• Due to the high ribonucleoprotein content of the
ribosomes attached to it, it appears basophilic when
stained with basic dyes (staining solutions).
79
Principal functions of the rER
1. Segregation of proteins destined for export or
intracellular use.
2. Posttranslational modification of newly formed
polypeptides
3. Initial or core glycosylation of glycoproteins that have
N-linked oligosaccharides.
4. Assembly of multi-chain proteins
5. Quality checkpoint
6. Synthesis of phospholipids and integral proteins
80
Smooth Endoplasmic Reticulum (sER)
 The sER forms usually a close-meshed three
dimensional network and in contrary to rER it seldom
takes the form of cisternae, i.e. it is usually tubular.
 Cells rich in sER have an acidophilic staining property.
 Membranes of the sER arise from the rER and are often
in continuity with one another.
81
82
Function of sER
– Lipid metabolism (making or breaking down of fats)
– Glycogen metabolism
– Proliferates in hepatocytes when animals are
challenged with lipophilic drugs (detoxification and
conjugation of noxious substances)
– Synthesize and secrete steroids such as
adrenocortical cells and testicular Leydig
(interstitial) cells
– Sequesters Ca+2, which is essential for the
contractile process in skeletal and cardiac muscle
83
Differences between sER and rER
Elements
Ribosomes
Membranes
Ribophorins I & II
Staining
rER
sER
+
-
Often cisterna
often tubular
+
-
Basophilic
Acidophilic
84
Golgi apparatus/complex/body
• This organelle was discovered by the Italian
neurologist Camillio Golgi around 1898.
• It is composed of several smooth membrane bounded
flattened saccules (vesicles, vacuoles) or cisternae.
• The saccules and cisternae are the structural units of
the Golgi complex
85
• It occupies definite and fixed areas in the cytoplasm of
most cells and these areas are called Golgi fields.
It usually occupies a location between the rER and
the plasmalemma or
Between the nucleus and the apical plasma
membrane.
86
o Golgi apparatus is composed of three smooth
membrane limited compartments:
1. A slightly curved stack of 3-10 flattened cisternae
2. Numerous small vesicles found around the
periphery of the stack.
3. Few large vacuoles found usually at one pole of the
Golgi complex.
Cis-face
Trans-face
 GERL saccule
87
 The functional unit of a Golgi field is dictyosome, which
appears in the form of overlapping empty sacs and shows
dilatation called Golgi vesicles or vacuoles or canaliculi.
 Dictyosome is polarized, i.e. it contains a growth (forming)
pole or cis-face which is convex in shape and a maturation
pole or trans-face that is generally concave.
 The cis-face is usually the part near to the ER and contains
constricted transfer vesicles filled-with products synthesized
by the ER, i.e. it is involved in the uptake and storage of
products of the ER.
88
o The trans-face is found on the opposite side away from the
ER.
o From the trans-face much larger secretory or transport
vesicles called condensing vacuoles, secretory vesicles or
granules detach with contents of the dictyosome and
migrate to the cell membrane, where their membrane
become fused and incorporated in to the cell membrane
releasing their content.
89
o A special part on the trans-face is implicated in the
processing of lysosomal enzymes called Golgi Endoplasmic
Reticulum lysosome GERL saccule.
o The GERL saccule contains acid phosphatases and acid
hydrolases of lysosomes.
o Lysosomes usually pinch off from the bulb like distension of
the GERL saccule
90
Functions of the Golgi complex
o It performs the completion of posttranslational modifications,
packages and places an addresses on the products that have
been synthesized by cells.
91
Function of Golgi Complex
1. It chemically modifies molecules produced by the
ER:
a. Products from the ER are carried to GA by transfer
vesicles, some of them then undergo further chemical
modification.
 e.g. completion of glycosylation of
glucosaminoglycans and glycoproteins (which has
already began in the ER) for they contain glycosyl- and
galactosyltransfurases and other enzymes.
b. activation of some enzymes.
92
2. It sorts out and packages the various products reaching
its saccules:
a. In to secretory granules.
b. It sequesters the acid hydrolases in to membranous
lysosomes.
3. It is the site of storage and concentration of secretory
products by the removal of water: such an activity is
seen in glandular cells and protein secreting cells.
4. It directs certain transmembrane proteins to their
destination in the ER or the plasmalemma.
93
Lysosome
 Lysosomes (Lyse = destroy, some = body)
 Lysosomes are about 0.2 -0.5 µm in size and therefore not
resolved by a light microscope.
 They are vesicles filled with hydrolytic enzymes (acid
hydrolases) and constitute the intracellular digestive
system, that digests aged cellular structures and foreign
bodies,
o i.e. they are sites of intracellular digestion and turnover
of cellular components.
94
 Lysosomes are responsible for the resorption of tissues
that are no more needed by the organism, e.g. regression
of mammary glands.
 The lysosomal enzymes are synthesized by the ribosomes
and transported to the Golgi apparatus from the ER.
 In the Golgi apparatus they are enclosed by a membrane
to form vesicles.
 These vesicles containing enzymes detaching from the
trans-face or GERL saccule, called primary lysosomes, are
released in to the cytoplasm.
95
 Once these lysosome are involved in intracellular
digestion they become secondary (definitive) lysosome.
 The lysosomal membrane prevents the digestion of
cellular structures by enzymes.
 The lysosomal digestive system of the cell is also involved
in the normal turnover of organelles and in the internal
remodelling of the cytoplasm relevant to its physiological
function.
 In this case an intracellular structure to be digested is
segregated and enveloped by a membrane.
This lysosome is now called cytolysosome or
autophagic vacuole.
96
 Lysosomes of the cell adhere to the limiting membrane of
the heterophagosome, pinocytotic vesicle or multivesicular
bodies;
 fuse with it so that their hydrolytic enzymes are
discharged in to its cavity, killing and ultimately
digesting the bacterium or the substance in the fluid.
 Some of the substances can be completely digested where
as others may leave indigestible residues which persist in
the form of membrane bounded structures called residual
bodies.
 These will be casted out of the cell by exocytosis or
abnormally stored in the cell.
97
Lysosomal Action
98
Peroxisomes or Microbodies
• 0.5-1.2 µm spherical vesicles surrounded by a single
membrane
• Contain uniform granular matrix
• The matrix is separated from the membrane by a
narrow translucent space.
 They may vary in shape and size depending on the
type of species and cell kind.
 Formed by budding from other organelles mainly from
the sER.
99
 The single membrane of peroxisomes encloses a
homogenous matrix in which a crystalline (crystalloid)
inclusion is found & this crystalline substance is formed of
urate oxidases.
 Most cells except those of the liver and the kidneys
contain small peroxisomes with a homogenous content
called microperoxisomes, but in the liver and kidney they
are relatively large.
100
101
 Peroxisomes contain
 Oxidative enzymes that produce hydrogen peroxide
(H2O2) that participates in:
certain metabolic reactions and
used by some phagocytic cells to kill engulfed
microorganisms.
H2O2 is toxic to the cell itself
 Catalase that converts H2O2 in to water and O2.
Therefore protect the cell from the irreversible
cytotoxic effect of H2O2.
102
 Additionally peroxisomes contain enzymes for lipid
metabolism.
 They accomplish the -oxidation of long chain
fatty acids (18 carbons and longer) in contrary to
mitochondria.
 They also take part in the formation of bile acids,
gluconeogenesis and purine metabolism.
103
Mitochondrion
5-10um X 0.5-2um
Variable shape & site
Membrane
Tubuli+saccule
RNA
Number
Eosinophilic
ATP + heat
Defects
Unusual features
(DNA+ ribosome+ self replication)104
Mitochondria
 Mitochondria (Gr. mitos, thread + chondros, granule) are
membranous ovoid or thread like organelles which are
about 5-10 µm in length and 0.5-2 µm in diameter.
 They possess an ever changing shape or form, i.e. they
are capable of actively changing their shape.
 They contain an inner and an outer membrane between
which the outer (membrane) space or
intermembranous space or outer matrix is found.
105
 The inner membrane surrounds the inner (matrix) space
or inner matrix.
 It sends some folds of membrane processes in to the inner
matrix forming the shelf-like mitochondrial cristae.
 Cells synthesizing steroids contain tubules in addition to
cristae.
 The cristae and tubules increase the internal surface area
of the mitochondria.
 The folds of the inner membrane may also form vesicles
(saccules) in addition to cristae and tubuli in the inner
mitochondrial matrix.
106
107
 The space between these processes (cristae, tubuli, or
vesicles) is filled with a fine granular mitochondrial
matrix in which enzymes of the: citric acid cycle,
 fatty acid catabolism and
 protein synthesis are found (enzymes of oxidative
phosphorylation and electron transport system).
 The mitochondrial matrix contains a strand of
deoxyribonucleic acid (DNA) arranged as a circle in a
manner analogous to the chromosomes of bacteria.
 The matrix also contains ribosomes which have similar
structure with bacteria ribosome
108
 The inner membrane of mitochondria is rich in enzyme
proteins that are important in oxidative energy
production. Attached by a stalk to this membrane there
are small particles (elementary particles) in which ATP is
synthesized.
 These particles are also known as inner membrane spheres.
 For they contain some DNA they can synthesize some of
their proteins.
 The replication of their DNA is independent of the
nuclear DNA.
 They contain also all the three forms of ribonucleic acid
(RNA) (ribosomal rRNA, messenger mRNA, and transfer
tRNA)
109
 The respiratory and phosphorylating enzyme are found
attached to the membrane, while those of the Kreb’s
cycle, protein metabolism and lipid metabolism are
found in the matrix.
 So, these highly efficient organelles transform the
chemical energy of the metabolites present in cytoplasm
into energy that is easily accessible to the cell.
 About 50 % of this energy is stored as adenosine
triphosphate (ATP) molecules and the remaining 50% is
dissipated as heat used to maintain body temperature.
110
Annulate Lamellae
o This is a term that has been applied to cytoplasmic
organelles consisting of several pairs of flat but parallel
smooth membranes (parallel arrays of cisternae).
o These membranes are released by delamination from
the ER and the nuclear envelope mainly resembling the
latter being similar to a perinuclear cisterna.
o In some cells they are also found in the nucleus.
o Each pair contains regularly spaced pores (annuli or
circular fenestrae) closely resembling those of the
nuclear envelope.
111
 They are found in rapidly growing and multiplying cells
like germ cells of both invertebrate and vertebrate
species, embryonic cells and neoplastic cells.
 In other cells they appear as a transitory component in
the life cycle.
 Their significance is to convey materials from the
cytoplasm, functioning in the nucleoplasm interaction.
112
•
•
•
•
Secretory Vesicles or Granules
Originating in the Golgi apparatus, secretory vesicles
are found in those cells that store a product until its
release by exocytosis is signaled by a metabolic,
hormonal, or neural message (regulated secretion).
These vesicles are surrounded by a membrane and
contain a concentrated form of the secretory product.
The contents of some secretory vesicles may be up to
200 times more concentrated than those in the
cisternae of the rER.
Secretory vesicles with dense contents of digestive
enzymes are referred to as zymogen granules.
113
Non - Membranous Organelles
Include organelles like:
o Ribosomes
o Centriole/Centrosome
o Microtubuli
o Microfilaments
114
Ribosome
 Small spherical ribonucleoprotein particles
 20 X 30 nm in size
 Intensely basophilic because of the numerous phosphate
groups
 Responsible for the synthesis of proteins
 Made up of two subunits (60 & 40S)- functions???
 Contain rRNA complexed by protein as
ribonucleoprotein
 Synthesized in
 Nucleoli- rRNA
 Cytoplasm (other ribosomes)- protein
115
• Functions
1. Large subunits (60-s(Svedberg)-particles): is
responsible for
o Release of the new protein
o Protein attachment to the ER via an intermediate
docking protein
o Directing the protein through its membrane into
the cisternal cavity.
2. Small subunits (40-s- particles): is the site of
attachment and translation of mRNA
116
• Attached ribosomes
– The two subunits attached to each other
– Polysomes (polyribosomes) – union of 3-30
ribosomes around mRNA
– Attached to the nuclear membrane and
endoplasmic reticulum
– produce secretory (exportable) proteins and form
some cellular products like lysosomes, peroxisomes
etc.
• Free ribosomes…
– Produce cytoplasmic proteins used for proliferation,
differentiation and regeneration of the cell itself
• Mitochonderial ribosomes (55 S)
117
Protein Synthesis
118
• The free ribosomes and polysomes are involved in
translating mRNA molecule coding for cytoplasmic
proteins used for proliferation, differentiation and
regeneration of the cell itself (they form structural
proteins).
• Therefore they occur in large numbers in cells forming
large amounts of structural proteins, e.g. embryonic cells
and haemocytoblasts.
• Mitochondrial ribosomes differ from those of the general
cytoplasm, being somewhat smaller (55S).
119
Centrosomes & Centrioles
o Centrosome (cell centre)
 Specialized zones of cytoplasm where microtubles are
produced
 It is also called the "microtubule organizing center"
 Usually centrally located in the cell, adjacent to the
nucleus and often surrounded by the Golgi apparatus.
 It contains a pair of centrioles, together known as a
Diplosome.
120
o In some epithelial cells the centrioles are not related to
the nucleus or Golgi apparatus, but located in the apical
cytoplasm beneath the free surface of the cell
o The centrosome acts as the organizing centre for the
growth of microtubules of the cytoskeleton which
radiates outwards in a star-like arrangement called as
Astrosphere, Astral fibers or Astral rays
o The centrosome surrounded by astral rays is called
Aster
121
122
Centrioles
o They are pairs of small granules or short rods
or cylinders composed primarily of highly
organized microtubuli.
o They are found in cells that retain their
capacity for division.
o The centrioles in a diplosome are
perpendicular to each other.
123
• In electron microscope investigation each centriole is
cylindrical in form, closed at one end, and consisting of
nine triplets of parallel microtubules.
• In transverse section each triplet is seen to consist of an
inner microtubule which is circular in cross-section and
two further microtubules which are C-shaped in crosssection.
• Each of the inner microtubules is connected to the
outermost microtubule of the adjacent triplet by fine
filaments, thus forming a cylinder.
124
125
126
127
IIi. Cytoskeleton
Microtubuli
• Microtubuli are electron microscopically
visible organelles composed of tubular
systems that have similarities to centriole.
• They are formed by Alpha (α) and beta (β)
tubulin molecules which polymerise to form the
hollow tubule.
• In nerve cell processes they are known as
neurotubuli
128
Molecular organization of a microtubule
129
130
There are two types of microtubuli:
1. Labile (unstable) microtubuli
– formed or degraded on demands, that is
they are temporary components of a cell
e.g. tubuli in a mitotic spindle.
2. Stable microtubuli
– They are constantly found in the cells.
131
 They help in the maintenance of the cell shape
serving as a cytoskeletal element.
 It is also believed that they assist in intracellular
transport of substance and organelles, e.g.
o Axoplasmic transport in neurons
o Melanin transport in pigment cells
o Chromosome movement along a mitotic spindle.
o Vesicle transport between the endoplasmic
reticulum, Golgi apparatus and the cell membrane.
132
Filaments
 They are fibre like and are only electron
microscopically visible protein structures that form
fibrillar bundles.
 Many of these bundles of fibrils together form fibres.
133
• There are different categories of filaments:
1. Microfilament (about 5-7 nm in diameter)
correspond to the thin filaments in muscle cells
and non muscle cells.

Actin filament 6 to 8 nm in diameter (thin filament)
2. Microtubule (about 24 nm in diameter)

20-25 nm
3. Intermediate filaments (about 10-15 nm in
diameter) have a diameter intermediate between
the thin and thick filaments.


8 to 10 nm in diameter
Myosin II 15nm (thick filament)
134
1. Microfilaments (Thin filament)
They are mainly composed of actin, tropomyosin and
a regulatory protein troponin.
o Troponin and tropomyosin mediate the regulation of
Ca+2 in the interaction between actin and myosin.
o The microfilament in non-muscle cells are composed
mainly of several species of actin which are
structurally unstable.
o The actin filament composed of globular sub-units
organized into a double-stranded helix.
o
135
Microfilament are involved in:
 Cytoplasmic movement
 Cell division
 Cytokenesis
 Amoeboid movement
 Endocytosis and exocytosis
 Cytoplasmic streaming and transport
 Secretion of cellular material
 Microfilaments provide part of the cytoskeleton
136
2.Thick filaments
o Mainly composed of myosin.
o They are present in unpolymerized form in most
motile non-muscle cells.
o They polymerize to form filament only when
participating in cell movement.
o The thin and thick filaments are known as
contractile filaments.
o In cells other than muscle cells these filaments are
considered to form part of the cytoskeleton.
137
3. Intermediate filaments
 In addition to microtubuli & microfilament cells
contain a class of intermediate sized filament.
 Because of their diameter these filaments are also
referred to as 10 nm filament.
 However, in contrast, intermediate filaments have a
stable fibrous structure made up of a variety of
different irregular molecules which appear to be
specific to particular cell type.
138
139
Intermediate filaments…
a. Cytokeratins (prekeratins or tonofilaments):
formed of about 20 polypeptides and are found in
most epithelia coded by a family of genes and
present different chemical and immunological
properties.
b. Vimentin (Decamin): characteristic of cells of
mesenchymal and neuroectodermal origin and of
embryonic or undifferentiated cells.
 It is a single protein that may copolymerize with
desmin or glial fibrillary acid protein.
140
Intermediate filaments…
c. Desmin (skeletin): found in smooth muscles and
in the Z-disks (lines) of skeletal and cardiac
muscles
d. Glial filament (glial fibrillary acid protein,
GFAP): is characteristic to astrocytes,
ependymal cells, Schwann cells and pituicytes
e. Neurofilament: is found in neurons
141
Special Structures on the Surfaces of Cells
• A given cell is typically differentiated for a specific
function and may contain special structures on its
surface which are relevant to its function.
• For example,
 Surface of absorptive cells there are microvilli
forming the brush or striated borders
 Sensory cells contain modified cilia
 Sperm cells contain flagella etc.
142
• Microvilli are cytoplasmic process that enlarge the
surface area of absorptive cells.
• Therefore, they are characteristic to absorptive cells
like epithelial cells of the GIT, gall bladder, and renal
tubules.
• They contain microtubuli and microfilaments due to
which they are capable of movement.
 The membrane of microvilli contains enzymes for the
active transportation of absorbed substances.
143
Special Structures on the Surfaces of Cells
144
Cilia & Flagella
• Cilia (kinocilia (motile cilia) & stereocilia (non-motile
cilia)
• Cilia and flagella are lash-like projections from the
surface of a cell that are visible with a light
microscope.
• They are motile processes with a highly organized
microtubule core.
• Like microvilli they are plasmalemma covered
evaginations of the cell surface.
• Both cilia and flagella have a diameter of 0.3-0.5 µm
and possess the same core organization.
145
• The core consist of nine pairs of microtubules
surrounding two central tubules.
• These bundle of tubules, possessing the characteristic
9+2 pattern, is called axoneme
• Cilia is short and move “to-and-fro”.
– Cilia function is to move fluids
• Flagella are longer and move in an undulating
wavelike motion.
• What is the only flagellated cell in the body?
sperm
146
cross-section of a cilium
147
148
149
Iv. Cytoplasmic Inclusions
(Paraplasmatic Substances)
 Cytoplasmic inclusions are non-living parts of the
cytoplasm which can be products of intracellular
metabolism or engulfed substances from the cell’s
environment.
 These can be reserved and stored substances found
in specific cell types or in association with a
particular stage of the functional activity of a cell e.g.
 glycogen
 lipids
 proteins
 pigments (endogenous or exogenous)
150
1. Glycogen is a high molecular weight polysaccharide
(stored form of glucose).
o It can be found in the form of small droplets or free
deposits in the cytoplasmic matrix of
 liver cells (hepatocytes)
 muscle cells
 epithelial cells of the oral mucous membrane
151
2. Lipids (neutral fat and lipoids): They appear as
droplets or granules in the cytoplasm.
 These fat droplets abnormally increase in number
during hypoxia or intoxication by phosphorus or
alcohol (e.g. fatty infiltration of the liver in
alcoholics).
 Lipoid substances are normally found in the cells of
the adrenal cortex where they form the precursors of
steroid hormones.
 They are stored by fat cells of adipose tissue
(adipocytes) and the fat storing cells of the liver
(lipocytes).
152
3. Proteins: These can appear as granules, droplets or
crystals.
 In the yolk of egg cells they are found with lipids in
the form of small granules.
4. Pigments: these are colored substances stored in a
cell.
 They can be classified as either exogenous or
endogenous.
 Exogenous pigments are those taken up from the
environment in to the body by some route. e.g. coal
dust causing anthracosis and silicone dust causing
silicosis in the respiratory tract.
153
 Endogenous pigments are those pigments
produced by the cells themselves.
 E.g. haematogenic products like haemosiderin
and ferritin, nonhaematogenic pigment like
melanin and lipofuscin.
154
Nucleus
155
B. NUCLEUS
o The nucleus or karyon is the most prominent
structure in a cell
o It contains
– all the information necessary to initiate and control
the differentiation, maturation, and metabolic
activities of each cell.
– the molecular machinery to replicate its DNA and to
synthesize and process all types of RNA.
156
Functions of the Nucleus
1. It stores DNA, the cell's hereditary material
2. It coordinates the cell's activities, which include
growth, intermediary metabolism, protein
synthesis, and reproduction (cell division)
3. It is source of ribosomal, messenger and transfer
RNA
4. It is essential for the vitality and division of the
cell.
157
• Commonly stains blue because of its:
 nucleic acids
 basic proteins
 acidic proteins
158
• The number, shape, size, & location of nucleus vary in
different types and activity of the cells.
• The size and morphologic features of nuclei in a
specific normal tissue tend to be uniform.
• In contrast, the nuclei in cancer cells often have:
– irregular shapes
– variable sizes
– atypical chromatin patterns
159
 The nucleus is generally rounded or an elongated
structure at the centre of a cell.
 In mammalian tissue it measures about 5-10 µm in
diameter.
 The shape of the nucleus usually corresponds to the
shape of the cell to which it belongs,
– i.e. it is either rounded, oval or spindle shaped.
 Its size differs from cell to cell, and even in different
functional states of the same cell.
 However, it has a specific relation to the cytoplasm
(nucleus-plasma relation).
160
• The number of nucleus varies in different cells
Uninuclated- in most cells e.g. smooth muscle cell
Binucleated- in parietal cells, cardiac muscle cells,
hepatocytes
Multinucleated- in osteoclasts, skeletal muscle cells,
megakaryocytes.
Anucleated- e.g. mature RBCs, platelets & lens fibers
 Such cells are unable to synthesize protein or are
unable to divide and are extremely restricted in
their metabolic activities.
161
4/20/2021
162
• The major components of a nucleus are:
1. Nuclear envelope
2. Nuclear matrix
3.Chromatin
4. Nucleolus
163
 The content of the nucleus which is surrounded by the
nuclear membrane is called karyoplasm.
 The karyoplasm contains a colloidal solution called
karyolymph which is composed of chromosomes and
one or more nucleoli.
164
Nuclear Envelope
• The nucleus is enclosed and separated from the
cytoplasm by a nuclear envelope.
o In an electron microscope, it is a complex structure
consisting of two parallel unit membranes each 7.5
nm thick, separated by a narrow space (40-70 nm)
called perinuclear cisterna (space).
• The outer membrane is rough but inner is smooth
• The outer membrane contains ribosomes attached to its
cytoplasmic surface and is continuous with the rough
rER.
o Therefore, the perinuclear cisterna is also
considered as the integral part of the cavity of the
rER.
165
166
 Closely associated with the internal membrane, there
is a fibrous protein structure called the fibrous lamina.
 The fibrous lamina is composed of three main
polypeptides, called lamins
 The lamins are structurally similar to intermediate
filaments and are classified as types A, B, and C
according to their location and chemical properties.
 They provide a connecting link between the
membrane and the nuclear heterochromatin
 Function in the formation and maintenance of the
nuclear envelope of interphase cells.
 They aid in maintaining the shape of the nucleus
167
• At irregular intervals around the nucleus, the inner and
outer membranes of the envelope become continuous
with one another to form small octagonal openings
called nuclear pores.
• The pores measure about 10 nm in diameter and are
closed by a nuclear pore complex that consists of
two rings, one of which faces the cytoplasm.
• Eight radial spokes extend inward from the rings
toward a central granule.
• The number and distribution of nuclear pores depend
on the type of cell and its activity. (may reach 30004000)
170
• Each pore is found to be closed by a delicate septum
thinner than the usual unit membrane called
diaphragm.
 The diaphragm controls the free passage of even
small molecules like ions by acting as a barrier for
the nucleoplasmic transportation of substances.
• The pore allows the
 entrance of proteins such as histones and gene
regulatory proteins, which are synthesized in the
cytoplasm but function in the nucleus.
 exit of molecules synthesized in the nucleus (e.g.
ribosomal subunits, tRNA and mRNA) to the
cytoplasm.
171
• Functions of nuclear envelope
 separates the contents of the nucleus from the
cellular cytoplasm
 aids in organization of the chromatin
 controls the two-way traffic of ions and molecules
moving between the nucleus and cytoplasm
Molecules less than 10 nm in diameter pass
through the nuclear pore complex by passive
diffusion, whereas large molecules require an
energy-dependent transport mechanism.
172
Nucleoplasm (Nuclear Sap)
• The semi fluid matrix found inside the nucleus is called
nucleoplasm karyolymph or nuclear matrix
• Nucleoplasm contains
– Chromatin (the less condensed form of the cell's DNA
that organizes to form chromosomes during mitosis
or cell division)
– One or more nucleoli (organelles that synthesize
protein-producing macromolecular assemblies
called ribosomes, and a variety of other smaller
components)
173
Nucleolus
• A round conspicuous structure or a dense, welldefined body, 1 to 3 µm in diameter eccentrically
located in the nucleus
• It is sites where rRNA is synthesized
• It is rich in RNA and basic proteins; intensely
basophilic due to the presence of
ribonucleoproteins.
• It is non-membraneous organelle within the nucleus
174
175
• Nucleoli show two regions, each associated with a
particular form of ribonucleoprotein.
1. Pars granulosa (nucleolonema)
• Dominant region
• Consists of a network of dense granules of RNA 13
to 15 nm in diameter.
• Site where rRNAs are processed and then
assembled after transcription
2. Pars fibrosa
• Tends to be centrally placed
• Consists of dense masses of filaments 5 nm in
diameter
• Site where ribosomal gene transcription occurs
176
• Deoxyribonucleoprotein also is associated with the
nucleolus
• Nucleoli are found only in interphase nuclei and are
especially prominent in cells that are actively
synthesizing proteins.
• They are dispersed during cell division but reform at
the nucleolus-organizing regions during
reconstruction of the daughter nuclei after cell
division.
177
Chromatin & Chromosomes
Structure of the DNA
• Nearly all of the genetic material of eukaryotic cells
is sequestered in the nucleus.
o the exceptions being certain other organelles
such as mitochondria and the chloroplasts of
plants which contain some DNA themselves
• The structure of the DNA molecule was discovered
by Watson and Crick & comprises two polynucleotide
strands that are oriented in opposite directions
178
 Each strand is a polymer of the four
nucleotides:
 Purines
Adenine
Guanine
 Pyrimidines
Cytosine
Thymine
179
• The two strands are held together by specific basepairing interactions
o Guanine binds to Cytosine (G-C)
o Adenine to Thymine (A-T)
• The two chains together form a helical structure 2 nm
in diameter with 3.4 nm between turns.
180
Chromatin
• In nondividing nuclei, chromatin is the chromosomal
material in a largely uncoiled state.
• Or it is DNA attached with protein
• Two types of chromatin can be distinguished with both
the light and electron microscopes, which reflect the
degree of chromosomal condensation
a) Heterochromatin
b) Euchromatin
181
• Heterochromatin
– It is electron dense, appears as coarse granules in
the electron microscope
– It appears as basophilic clumps in the light
microscope
– Mostly located at the periphery and around
nucleolus
• Euchromatin
– It is the less coiled portion of the chromosomes
– Visible as finely dispersed granular material in the
electron microscope and as lightly stained
basophilic areas in the light microscope.
182
• The regions of heterochromatin and euchromatin
account for the patchy light-and-dark appearance of
nuclei in tissue sections as seen by both light and
electron microscopy.
• The intensity of nuclear staining of the chromatin is
frequently used to distinguish and identify different
tissues and cell types in the light microscope.
183
184
• Chromatin is composed mainly of coiled strands of DNA
bound to basic proteins called histones and to various
nonhistone proteins.
• The basic structural unit of chromatin and histones is the
nucleosome, which has a core of eight small histones
(two copies each of histones H2A, H2B, H3, and H4),
around which is wrapped DNA with about 150 base
pairs.
• Each nucleosome also has a larger linker histone (H1)
that binds both wrapped DNA and the surface of the
core.
• The series of nucleosomes in chromatin is also
associated with many diverse nonhistone proteins with a
wide variety of enzymatic functions.
185
Components of a Nucleosome
186
• DNA bound to nucleosomes is then folded further in the
next order of chromatin organization which is the 30-nm
fiber, but the mechanism of this folding is less well
understood.
• Higher orders of chromatin coiling into microscopically
visible stained structures, the chromosomes, also
occur, which are especially important during the
condensation of chromatin for mitosis and meiosis
187
From DNA Chromatin  Chromosome
188
• The chromatin pattern of a nucleus is a guide to the
cell's activity.
• Generally cells with lightly stained nuclei are more
active in protein synthesis than those with condensed,
dark nuclei.
• In light-stained nuclei with much euchromatin and few
heterochromatic clumps, more DNA surface is
available for the transcription of RNA.
• In dark-stained nuclei rich in highly condensed
heterochromatin, the tightly coiled DNA is less
accessible for transcription.
189
• Careful study of the chromatin of mammalian cell
nuclei reveals a mass of heterochromatin that is
frequently (90%) observed in somatic cells of females
but not males.
• This chromatin clump is the sex chromatin and is one
of the two X chromosomes present in female cells
190
• The X chromosome that constitutes the sex chromatin
remains tightly coiled and visible between mitotic
cycles, whereas the other X chromosome is uncoiled
and not visible.
• The heterochromatic sex chromatin is transcriptionally
inactive.
• The male cell has one X chromosome and one Y
chromosome; like the other chromosomes the
interphase X chromosome is uncoiled and therefore no
sex chromatin is visible in males.
191
Sex Determination  Hermaphroditism
192
Cell Cycle
193
Cell Cycle
• The body is prone to wear and tear as result cells may
be damaged or aged and needs to be replaced
• Varies in length in different types of cells
 Undergo fast cell cycle- skin
 Facultative- temporarily suspended but may reenter cell cycle
 Permanently interrupted : cells that do not divide
(e.g. cardiac muscle cells & neurons)
• Consists of 2 major periods
1. Interphase - interval between cell division
2. Mitosis - period of cell division (M phase)
194
INTERPHASE
G1
S
(DNA synthesis)
G2
195
196
•
•
•
•
•
•
Gap1 phase (G1)
Usually much longer than the other phases of the cell
cycle
The cell either continues the cycle or enters a quiescent
phase called G0
From this phase, most cells can return to the cycle, but
some stay in G0 for a long time or even for their entire
lifetime.
The checking or restriction point (R) in G1 stops the
cycle under conditions unfavorable to the cell.
When the cell passes this restriction point, it continues
the cycle
Cells differentiate and perform their specialized
functions as part of the whole tissue
Synthetic (S) phase
• Replication of DNA, centrioles and centrosomes
G2 phase originating two daughter cells
• is relatively short and is the period in which cells
prepare for mitotic division
Mitosis (M)
• Cell undergo cell division
199
• Duration of cell cycle is not the same in all cells of the
body.
• For example, the phases of the cell cycle in bone
tissue:
 G1 lasts 25 hours
 S phase (DNA synthesis) lasts about 8 hours
 G2-plus-mitosis phase lasts 2.5-3 hours
200
Phases of the Cell Cycle in Bone Tissue
Phases of Mitosis
•
•
•
•
Prophase
Nucleus enlarges, chromosome start to condense &
becomes rod-like.
Each chromosome consists of two parallel sister
chromatids attached to one another at the
centromere.
Outside the nucleus, the centrosomes with their
centrioles separate and migrate to opposite poles of
the cell.
Simultaneously with the centrosome migration, the
microtubules of the mitotic spindle appear between
the two centrosomes and the nucleolus disappears as
transcriptional activity there stops.
• In late prophase, the nuclear envelope breaks down
when proteins of the nuclear lamina and inner
membrane are phosphorylated (PO43– groups added).
• The nuclear lamina and pore complexes disassemble
and these proteins along with membrane vesicles
disperse in local cytosol and ER.
• Chromosomes appear as a line without arrangements.
Prophase: No distinct nuclear envelope, no
condensed chromosomes
nucleoli,
• Prophase I is normally extended for 3 weeks during
male gametogenesis (meiosis) in humans, whereas
oocytes arrest in this meiotic phase from the time of
their formation in the fetal ovary through the woman's
reproductive maturity, that is, for about 12 years to 5
decades
•
•
•
•
•
Metaphase
The condensed chromosomes attach to microtubules of
the mitotic spindle at large electron-dense protein
complexes called kinetochores which are located at a
constricted region of each chromatid called the
centromere.
The chromosomes are moved to the equatorial plane
then become very thick & arranged in equatorial plane
Kinetochore microtubules bound to sister chromatids
are continuous with centrosomes at opposite poles of
the mitotic spindle.
Mitotic spindle formed completely.
Nuclear envelop disappear completely.
Anaphase
In early anaphase:
– The sister chromatids separate from each other and
are slowly pulled at their kinetochores toward
opposite spindle poles by kinesin motor proteins
moving along the microtubules.
– During this time the spindle poles also move farther
apart.
– The sister chromatids separate & pulled toward each
pole of the cell by microtubules.
In late anaphase: characterized by beginning of
cytoplasmic division, & initiate the cleavage furrow.
• A belt-like contractile ring, containing actin
filaments associated with myosins, develops in the
peripheral cytoplasm at the equator of the parent
cell.
Telophase
- the two sets of chromosomes are now at their destination
and begin reverting to their uncondensed (chromatid)
state.
- Microtubules of the spindle disassemble and the nuclear
envelope begins to reassemble around each set of
daughter chromosomes
- Reappearance of nuclear envelops and nuclei appear as
2 dark dots and end of nuclear division.
- Cytokinesis cytoplasm divides by further constriction of
contractile ring and this progresses until the cytoplasm
and its organelles are divided in two daughter cells.
• Cycling in postmitotic cells (bypassing the G0 state) is
triggered by protein signals from the extracellular
environment called mitogens or growth factors, which
activate cell surface receptors.
• Nutrients and proteins required for DNA replication
accumulate and when all is ready (at the restriction
point) DNA synthesis begins.
209
• Entry or progression through each phase of the cycle
is controlled by specific sets of proteins, the cyclins
and cyclin-dependent kinases (CDKs), each of which
phosphorylates proteins in various other complexes
(such as the nuclear lamins at the beginning of
mitosis).
• In this way diverse cellular activities are coordinated
with specific phases of the cell cycle.
210
Reading Assignment on Meiosis
(Reproductive Cell Division)
Tissue Types of the Human Body
212