By

Dr Iram Iqbal

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 Cells are the basic structural and
functional unit of all multicellular
organisms. Cells can be divided into two
major components:
Cytoplasm
Nucleus.

2
With the L/M, Cytoplasm
generally has an even,
homogenous, amorphous
appearance but may show
granular, fibrillar, or
vacuolated areas.
Cytoplasm contains
“organelles” and
“inclusions”in aqueous
gel called cytoplasmic
matrix,

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 Organelles are living,
structural components
of cell.
Organelles are
described as
◦ membranous (cell
membrane – limited)
◦ non membranous.

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1. Plasma (cell)
membrane
2. rER
3. sER
4. Golgi apparatus
5. Endosomes
6. Lysosomes
7. Transport vesicles
8. Mitochondria
9. Peroxisomes

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1. Microtubules
2. Filaments
3. Centrioles
4. Ribosomes

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MEMBRANOUS ORGANELES

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 Plasma membrane is a
lipid bilayered structure
that form the cell boundary
as well as the boundaries of
many organelles within the
cell. It is visible with TEM.
 It is a dynamic structure
that actively participates in
many physiologic and
biochemical activities
essential to cell function and
survival.
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 When plasma membrane is
properly fixed, sectioned,
stained and viewed on edge with
TEM, it appears as two electron
dense layers separated by an
intermediate, electron lucent
(non staining) layer.
 Total thickness is about 8 – 10
nm.

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 PROTIENS
 PHOSPHOLIPIDS
 CHOLESTEROL

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11
 Integral
membrane
proteins
 Peripheral
membrane
proteins

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 PRESENT ON ONE
SIDE OF
MEMBRANE

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 Inserted in
membrane
 Some entirely
extend through
membrane
 Perform many
important
functions

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 Integral membrane proteins can be visualized with the
special tissue preparation technique of freeze fracture.
 Usually the P-face display more particles ,thus
more protein ,than the E-face.

E face

P-face
Micro domains of plasma membrane known as lipid rafts
control the movement and distribution of proteins within lipid
bilayers.

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 Localized regions with in the plasma
membrane contain high concentration of
cholesterol and glycosphingolipids. These
regions are called lipid rafts.
 Owing to high concentration of cholesterol and
the presence of longer, highly saturated fatty
acid chain, the lipid raft area is thicker and
exhibits less fluidity than the plasma
membrane.

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 Lipid rafts contain a verity of integral and
peripheral membrane proteins involved in
cell signalling.
 They can be viewed as “signalling platforms

” floating in the ocean of lipids.

 Signal transduction in lipid rafts occurs

more rapidly and efficiently because of

close proximity of interacting proteins.

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Integral membrane proteins have important
functions in cell metabolism, regulation and
integration.
Six broad categories of membrane proteins have
been defined in terms of their function:
1. Pumps
2. Channels
3. Receptor proteins
4. Linker proteins
5. Enzymes
6. Structural proteins
Integral membrane proteins move within lipid
bilayers of membrane
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 TRANSPORT IONS serve to
transport certain ions such
as Na + actively across
membrane.
 Also transport metabolic
precursor of
macromolecules, such as
sugar and amino acid across
membrane either by
themselves or linked through
Na+ pump.

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 Allow Passage of
small ions and
molecules,and
water across the
plasma membrane
in either direction
i.e ,passive
diffusion

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 For recognition and
binding of substances
to the outer surface of
plasma membrane
Like hormonal
stimulation and
antibody recognition

23
 Anchor the
intracellular
cytoskeleton to the
extracellular
matrix.e.g,family of
integrins that link
cytoplasmic actin
filament to a
extracellular matrix
protein

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 Protineous
structures which
have specific roles
in ion pumping and
digestion

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 Found in epithelial
cells
 Form junctional
complexes with
neighbouring cells
 Visualized by
freeze fracture
method.

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Channel
proteins
Carrier
proteins

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 Some substances (fat-soluble and small un
charged molecules cross the plasma
membrane by simple diffusion down their
concentration gradient.
 All other molecules require membrane

transport proteins to provide them with

individual passage across the plasma
membrane.

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Carrier proteins
 Transfer small water-
soluble molecules.
 They are highly selective
often transporting only one
type of molecules.
 After binding to a molecule
designated for transport,
the carrier protein
undergoes a series of
conformational changes
and releases the molecules
on the other side of the
membrane.
Channel proteins
 Also transfer small,
water soluble
molecules. Channel
proteins create
hydrophilic channels
through the plasma
membrane that
regulate the transport
of the molecules.
 They are ion selective
and are regulated on
the basis of the cell's
needs
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 VESICULAR TRANSPORT process that
involves configurational changes in the
plasma membrane & also provides for the
transfer of molecules b/w different cellular
compartments
 It maintains the integrity of plasma

membrane

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 EXOCYTOSIS
 ENDOCYTOSIS

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Processes of vesicular
transport in which
substances
enter the cell are
termed as endocytosis
Uptake of fluid and
macromolecules during
endocytosis depends
on three different
mechanisms

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 PHAGOCYTOSIS

 PINOCYTOSIS

 RECEPTOR MEDIATED
ENDCYTOSIS

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 PHAGOCYTOSIS
 Also called cell eating
 It is ingestion of
large particles, such
as cell debris
,bacteria and other
foreign materials
 In this nonselective
process large
vesicles(250nm)
called phagosomes
are produced
 Best seen in
macrophages
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 PINOCYTOSIS
 Also called cell
drinking
 Is the nonspecific
ingestion of fluid
and small protein
molecules via small
vesicles usually
amaller than150nm
in diameter.

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  This is a
cargo dynamin receptor
mediated
mechanism
that allows
selected
molecules to
enter the cell.

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Exocytosis is the process
by which a vesicle moves
from the cytoplasm to the
plasma membrane, where
it discharges its contents to
edit share
the extra cellular space.
Two general pathways of
exocytosis:
Constitutive pathway
Regulated secretory pathway

Ca+

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 These are the membrane
enclosed compartments in
the cytoplasm, associated
with all the endocytotic
pathways
 Endosomes can be
viewed either as stable
cytoplasmic organelles or
as transient structures
formed as the result of
endocytosis.

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 Endosomes destined to
become lysosomes
receive newly
synthesized lysosomal
enzymes
 Early and late
endosomes differ in their
cellular localization,
morphology and state of
acidification and
function.

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 Early endosomes are restricted to portion of
cytoplasm near the cell membrane where
vesicles originating from the cell membrane
fuse.
 Large number of vesicles originating in

early endosome travell to deeper structures

in the cytoplasm called late endosomes.
 The late endosomes mature into lysosomes.

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 Major function of early
endosomes is to sort and
recycle proteins
internalized by
endocytotic pathways.

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 Early endosomes Late endosomes

 Found in more  Found near the Golgi

peripheral cytoplasm apparatus and the
 Have a tubovesicular nucleus.
structure.
 More complex structure
and often exhibit
 Lumen is subdivided in
onionlike internal
to cisternae
membrane.
 PH 6.2 - 6.5  PH 5.5

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 Lysosomes are small
membrane bound
organelles that contain a
variety of acid hydrolases.
Ribosomes are composed
of two different sized
subunits.
 The RNA molecules of
both subunits are
synthesized in side the
nucleus.
 Their numerous proteins are synthesized in the
cytoplasm and then enter the nucleus and associate
with rRNA .
 Subunits then leave the nucleus via nuclear pores, to

enter the cytoplasm and participate in protein synthesis.

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 They constitute an
intracellular digestive
system capable of breaking
down material originating
both outside and within the
cell.
 Great variety of
appearances or
pleomorphism.

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 Usually range from 0.2 – 0.4
um in diameter.
 Have a unique membrane that is
resistant to hydrolytic digestion
occurring in their lumen.
 Lysosomal membrane has an
unusual phospholipid structure
that contain cholesterol and a
unique lipid called lyso-
phosphatidic acid which play an
important role in restricting the
activity of hydrolytic enzymes
directed against the membrane.

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 Found in all cells except
erythrocytes but are
numerous particularly
in:
Macrophages
Neutrophils
Hepatic cells
Cells of Proximal tubule
of kidney

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 Identified by
Electron
cytochemistry
 Divided into main

groups:
1. Primary lysosomes
2. Secondary lysosomes

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 Newly formed
lysosomes that have
pinched of from
golgi cisternae
 Contain all enzymes
that are used in cell
digestion

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 Formed by fusion of
primary lysosomes
with the structure
that contains material
to be digested
 Also called
phagosome.digestive
vacuole or
autophagic vacuole

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 Hydrolytic breakdown of the contents of the
lisosomes often produced a debris-liked
vacule called a Residual body.which may
remain for the entire life eg residual bodies
are a normal feature of the cell aging

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 Normal feature of
cell aging
 Debris filled vacuole
 Produced by break
down of contents of
secondary lysosomes
 Found as age pigment
or lipofusin pigment

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 Depending on the nature of digested material, three
different pathways deliver material for intracellular
digestion in lysosomes:
1.Extra cellular large particles ….. Phagosome and
Phagolysosome.
2.Extra cellular small particles …..Endocytotic pathway.
3.Intracellular particles ….. autophagy

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 With TEM, RER
appears as a series of
interconnected,
membrane limited
flattened sacs called
cisternae, with particles
studding the external
surface of membrane
(ribosomes).

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Basophilic component of cytoplasm,
ergastoplasm-----the areas of cytoplasm that stain
blue with basic stains
. Ergastoplasm indicates i.e. that component of
cytoplasm involved in protein synthesis..
Protein synthesis system
of the cell consists of rER
and ribosomes
The particles called
ribosomes are attached
to the membrane of
eRE by ribosomal
docking proteins

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 Membrane of reticulum
enclose an intracellular
compartment that
segregates newly
synthesized products.
 Its main function is
synthesis of a secretory
protein
 Synthesis of phospholipids
 Glycosylation of
glycoprotiens

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On E/M, appear as small, dense particles of about
15 – 20 nm in diameter, roughly spherical but
irregular, and each is formed by two subunits, one
large and one small.
Responsible for cytoplasmic basophilia and they
contain RNA and protein.
Are sites where amino acids are incorporated into
peptides and proteins i.e. site of protein synthesis
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Found in all cells except mature erythrocytes.
May be attached to granular endoplasmic reticulum
or may lie free within general cytoplasm.

Polysomes or polyribosomes----a cluster of

ribosomes along a single strand of mRNA that is
engaged in the synthesis of protein.

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Ribosomes are the sites where mRNA is translated
into protein.
Proteins destined for transport (secretory,
membrane, and lysosomal) are synthesized on
polyribosomes bound to rER .
whereas proteins not destined for transport (for
intracellular use) are synthesized on free
polyribosomes in cytosol.
Ribosomes are numerous in rapidly growing and
dividing cells.

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 SER is an irregular
network of membrane
bounded channels that
lacks ribosomes on its
surface, which makes it
appear smooth.
 SER consists of short
anastomosing tubules

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 Membranes are 6 – 7 nm
thick, and a tubular lumen
of about 50 nm.
 May exhibit distinct
cytoplasmic eosinophilia.
 Tubular elements may
connect directly with rER
and indirectly with golgi
apparatus via small
vesicles.

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Cells with large
amount of SER may
exhibit distinct
cytoplasmic
eosinophilia when
viewed under L/M.
Biochemically similar
to RER but lacks
ribosome docking
proteins
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 Abundant in cells that function in lipid metabolism,
cells that synthesize and secrete steroids (e.g.
adrenocortical cells and testicular cells of leydig,
progesterone secreting cells of corpus luteum of
ovary).
 Lipid and steroid metabolism
 Glycogen metabolism
 Membrane formation and recycling
 Synthesis of phospholipids of all cell membrane
 Drug detoxification
 Muscle contraction and relaxation (specialized
form,sarcoplasmic reticulum)

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 Well developed in secretory cells and does not
stain with H & E.
May be visible by L/M as either a positive or
negative image
After routine H & E stains, in cells with intensely
basophilic cytoplasm such as osteoblasts &
plasma cells, golgi apparatus is indicated as a
pale, clear area. This is negative image
After silver impregnation or prolonged exposure
to osmium tetra oxide, it is seen as darkly staining
network of stacked, flattened, membrane limited
sacs or cisternae and tubular extensions embedded
in a network of microtubules near MTOC-----
Positive image

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Small vesicles involved
in vesicular transport
are seen in associated
with cisternae.
Regions:
Cis golgi network
(CGN)
Trans golgi network
(TGN)
Medial golgi
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It is active in cells:
That secrete protein by exocytosis
In cells that synthesize large amounts of membrane and
membrane associated proteins such as nerve cells.
It functions in post translational modification,
storing and packaging of proteins.
It is involved in membrane flow , in transport and
concentration of secretory materials and their
release from the cells, in synthesis of certain
secretory products, particularly glycoproteins and
mucopolysacchrides and probably in lysosome
formation

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 Basolateral
plasma
membrane
 Apical plasma
membrane
 Endosomes or
Lysosomes
 Apical
cytoplasm

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 Are membrane bound
organelles and lie free
within cytoplasm. Display a
variety of shapes including
spheres, rods, elongated
filaments and even coiled
structures.
 Present in all cells except
RBSs and terminal
keratinocytes
 Abundant in cells that
generate large amounts of
energy.

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 Each mitochondria is
bounded by two unit
membranes
 Inner membrane shows
folds called cristae to
increase the surface area
 The space b/w inner and
outer membrane is
continuous with the
interstitial space within
each crista
 The inner mitochondrial
membrane surrounds the
large intercristal space of
mitochondrial matrix.

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 Outer mitochondrial
membrane
 6 – 7 nm thick smooth
membrane
 Contains many anion
channels
 Possess receptors for
proteins and
polypeptides

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 Inner mitochondrial
membrane
Thinner than outer one
Arranged in cristae
Rich in phospholipids
Cardiolipin, which makes the
membrane impermeable to
ions
The internal membrane and
cristae are coated with small
particles called elementary
particles or globular units

80
 These have special heads 9-10 nm in diameter
attached to inner mitochondrial membrane by a
narrow 5nm long stalk
 Enzymes of phosphorylation and electron transfer
system are located either on elementary particles
or within the inner mitochondrial membrane that
form cristae
 Enzymes of Kreb,s cycle lies in mitochondrial matrix
 The matrix also contain calcium salts, organic
crystals, glycogen, and RNA, DNA,

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1. Performing the oxidative reactions of the
respiratory electron transport chain
2. Synthesizing ATP
3. Regulating transport of metabolites into
and out of the metrix.

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 Intermembranous
space
Contain specific
enzymes that use ATP
generated in inner
mitochondrial
membrane (e.g.
creatine kinase,
adenylate kinase and
cytochrome C)

83
Store house for energy, metabolites
within the cell are utilized by Kreb,s
citric acid cycle and energy released is
captured through oxidative
phosphorylation. thus ATPs are formed
which are high energy compound.
Involved in fatty acid B – oxidation.
Source of electron for electron
transport chain
Store Ca++ and other divalent and
trivalent cations.
Synthesis of steroid hormons

84
 Small (0.5 µm in dia.)
membrane bounded
spherical organelles
containing oxidative
enzymes (particularly
catalases and other
peroxidases)

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 Abundant in liver
and kidney cells,
but found in most
other cells
 Do not contain
hydrolases

86
 Oxidative enzymes are
perform a variety of
detoxification
processes.
 β oxidation of fatly
acids is also a major
function of
peroxisosomes

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These are nonbranching and rigid hollow tubes
of protein that can rapidly disassemble in one
location and reassemble in another.
In general, they grow from MTOC located near
nucleus and extend toward the cell periphery.

89
 The region of the cell containing the
centrioles and pericentriolar material is
called MTOC or Centrosome.
 The MTOC is the region where most

microtubules are formed and from which

they are directed to specific destinations
within the cell.
 The structures present in MTOC are cilia,

basal bodies and centrosomes

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 Development of MTOC itself depend on
presence of centrioles.
 When centrioles are missing MTOCs

disappear ,and formation of microtubules is

severely impaired.


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Complex structure
of tubulin
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These are elongated polymeric structures
composed of equal parts of α tubulin
and β tubulin.
Under appropriate conditions tubulin
subunits polimerize to form
microtubules
Microtubules grow from γ tubulin ring
within the MTOC that serve as
nucleation sites for each microtubule.
Each microtubule possesses a minus
(non-growing) end and a plus (growing)
end.
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Polymerization and depolymerization are
in equilibrium.
Length of microtubules changes
dynamically as tubulin dimers are added or
removed in a process of dynamic
instability.
These can be visualized in L/M and are
involved in intracellular transport and cell
motility

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 The figure shows the 3-dimensional
view of a microtubule being formed. The
tubulin molecules are the bead like
structures and combine to form long
hollow, dynamic polymers, microtubules

96
In general, microtubules are found in:
Cytoplasm (where they originate from MTOC)
Cilia and flagella (where they form axoneme and its
anchoring basal body).
Centrioles and mitotic spindle.
Elongation processes of cells (such as those in growing
axons)

97
Microtubules are involved in numerous essential
cellular functions:
Intracellular vesicular transport
Attachment of chromosomes to the
mitotic spindle and their movement
during mitosis and meioses.
Cell elongation and movement.
Maintenance of cell shape, particularly
its asymmetry.
Movement of cilia and flagella

98
Movement of intracellular organelles is
generated by molecular motor proteins
(associated with microtubules)
Dyneins
Kinesins
Both dyneins and kinesins are involved in
mitosis and meiosis. In these activities,
dyneins move the chromosome along the
microtubules of the mitotic spindle.
Kinesins are simultaneously involved in
movement of polar microtubule.
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 Present in virtually all cell
types.
 Abundant and may constitute
20% of total protein of some
non muscle cells.
 Similar to tubulin in
microtubules actin molecules
also assemble spontaneously
by polymerization into a
linear helical array to form
filaments 6 – 8 nm in
diameter.
 Thinner, shorter and more
flexible than microtubules.

101
G – actin (globular actin),free actin molecule in the
cytoplasm
F – actin (filamentous actin) polymerized actin of
the filament
Plus or barbed end,fast growing end
Minus or pointed end. slow growing end
Polymerization of actin filaments requires K+, Mg2+,
ATP
Control and regulation of polymerization process
depends on:
Local concentration of G – actin
Interaction of actin binding proteins (ABPs)

102
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Anchorage and movement of membrane
protein
Formation of the structural core of
microvilli
Locomotion of cells
Extension of cell processes

105
 Play a supporting or
general structural role.

Intermediate
filaments are
formed from non
polar and highly
variable
intermediate
filament subunits

106
These rope like
filaments are called
intermediate because
their diameter is 8 – 10
nm (intermediate
between actin filaments
and microtubules).

107
Characterized by a highly
variable central “rod shaped
domain” with strictly
conserved globular domains
at either end.
 Although various classes of
intermediate filaments differ
in the amino acid sequence
of rod shaped domain and
may show variation in
molecular weight, they all
share a homogenous region
that is important in filament
self – assembly.

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 Usually found in close
proximity to the
nucleus, partially
surrounded by golgi
apparatus and
associated with a
zone of amorphous,
dense pericentriolar
material

110
Centrioles represent the
focal point around which
the MTOC assembles.
Visible in L/M, are
paired short, rod like
cytoplasmic cylinders
built from nine
microtubule triplets.

111
 Arranged at right
angle to each other
but are not
connected with one
another

112
 The dominant feature of
centrioles is the cylindrical
array of triplet microtubules
with associated proteins.
 TEM reveals that each rod
shaped centriole is about 0.2
µm long and consists of nine
triplets of microtubules that
are oriented parallel to the
long axis of organelle and
run in slightly twisted
bundles.

113
 Functions of the
centrioles can be
organized into
two catagories.
◦ Basal body
formation
◦ Mitotic spindle
formation
 The core structure of
the cilium is composed
of a complex set of
microtubules consisting
of two central
microtubules
surrounded by nine
microtubules doublets.

115
 One of the important function ot the centriole is to
provide basal body. Which are necessary for the
assembly of cilia and flagella.
 Basal bodies are formed by the replication of
centrioles and give rise to multiple precentrioles .
 Each precentriole migrate to appropriate site on
the surface of the cell where it become a basal
body.
 The basal body act as a organizing center for
cilium

116
 Microtubules grow upward from the basal
body,pushing the cell membrane
outward,and alongated to form the
mature cilium.

117
 Inclusions contain products of
metabolic activity of the cell
and consist largely of pigment
granules, lipid droplets and
glycogen.
 Lipofuscin
 Hemosiderin
 Glycogen
 Lipid inclusions (fat droplets)
 Crystalline inclusions

118
 Lipofuscin, is con glo me rate of lipid,metals
and organic molecules that accumulate within
the cell as a result of oxidative degradation of
mitochondria and lysosomal digestion.

 Hemosiderin , it is most likely formed by the

indigestible residues of hemoglobin,and its
presence is related to phagocytosis of RBCs.

 Glycogen, is highly branched polymer used

as a storage material for glucose.
 Fat droplets, are nutritive inclusion that
provide energy for cellular metabolism.

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Hemosiderin inside macrophages

121
Glycogen in liver cells

122
Lipid droplets

123
 They are
surrounded by
membrane
 Usually present in
apical portion of
cell

124
 A concentrated aqueous solution containing
molecules of different sizes and shape( e.g,
electrolytes, metabolites ,RNA and
synthesized proteins)
 The cytoplasm matrix is the site of

physiological processes that are

fundamental to cell's existence (protein
synthesis, breakdown of nutrients)

125
 The network provides a structural
substratum on which cytoplasmic reactions
occur.

126
 Text and Atlas of Histology by Michael H. Ross, 5th
edition.
 Text book of Histology by Leeson Leeson Paparo, 5th
edition.
 Image Results --------www.google.com

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