Histology Course for Medical Students - الصفحات الشخصية ...site.iugaza.edu.ps/sizaqout/files/2012/02/The-Cell.pdf• The compartment located between the two membranes

Histology Course for

Medical Students

Dr. Sami Zaqout Faculty of medicine - IUG

Topic Week

The Cytoplasm Week 1

The Cell Nucleus Week 2

Epithelial Tissue Week 2

Connective Tissue Week 3

Cartilage Week 4

Bone Week 4

Muscle Tissue Week 5

Nervous Tissue Week 6

The Circulatory System Week 8

Blood Cells Week 8

Lymphoid System Week 9

Digestive Tract and its Associated Organs Weeks 9+10

The Respiratory System Week 11

The Urinary System Week 11

The Male Reproductive System Week 12

The Female Reproductive System Week 12

Endocrine glands Week 13

Skin Week 13

Receptors Week 14

Dr. Sami Zaqout Faculty of Medicine IUG

The Cell

Types of cells

• Cells are the structural units of all living organisms .

• Prokaryotic cells are found only in bacteria.

• These cells are small (1–5 µm long),

• Typically have a cell wall outside the plasmalemma,

• Lack a nuclear envelope separating the genetic material (DNA) from other cellular constituents.

• Have no histones (specific basic proteins) bound to their DNA.

• Usually no membranous organelles.


Types of cells

• Eukaryotic cells are

larger.

• Have a distinct nucleus

surrounded by a nuclear

envelope.

• Histones are associated

with the genetic material.

• Numerous membrane-

limited organelles are

found in the cytoplasm.


Cellular Differentiation

Zygote Blastomeres Cell

Differentiation



Cell Components

Nucleus Cytoplasm

Cell Components


Cytoplasm

Cytoplasm


Plasma Membrane

• Phospholipids double layer

• Cholesterol

• Proteins (integral proteins) and (peripheral proteins)

• Chains of oligosaccharides covalently linked to

phospholipids and protein molecules.


Plasma Membrane

• Proteins, which are a major molecular constituent of membranes (about 50% in the plasma membrane), can be divided into two groups: – Integral proteins are directly incorporated within the lipid

bilayer.

– Peripheral proteins exhibit a looser association with membrane surfaces.


Plasma Membrane

• Some integral proteins span the membrane one or more times, from one side to the other. – One-pass transmembrane proteins

– Multipass transmembrane proteins


Plasma Membrane

• Membrane cleavage occurs when a cell is frozen and fractured (cryofracture).

• Most of the membrane particles (1( are proteins or aggregates of proteins that remain attached to the half of the membrane adjacent to the cytoplasm (P, or protoplasmic, face of the membrane).

• Fewer particles are found attached to the outer half of the membrane (E, or extracellular, face).


Plasma Membrane

• For every protein particle that bulges on one surface, a corresponding depression )2) appears in the opposite surface.

• Membrane splitting occurs along the line of weakness formed by the fatty acid tails of membrane phospholipids, since only weak hydrophobic interactions bind the halves of the membrane along this line .


• The ultrastructure and molecular organization (right) of the cell membrane.

• The dark lines at the left represent the two dense layers observed in the electron microscope; these are caused by the deposit of osmium in the hydrophilic portions of the phospholipid molecules.

Plasma Membrane


Plasma Membrane

• Membranes range from 7.5 to 10 nm in thickness

• Exhibit a trilaminar structure after fixation in osmium tetroxide

• The three layers seen in the electron microscope are apparently produced by the deposit of reduced osmium on the hydrophilic groups present on each side of the lipid bilayer.


Plasma Membrane

• Membrane proteins are synthesized in the rough

endoplasm reticulum, their molecules are

completed in the Golgi apparatus, and they are

transported in vesicles to the cell surface


Functions of Plasma Membrane

• A selective barrier that regulates the

passage of certain materials into and out

of the cell and facilitates the transport of

specific molecule.

• Keep constant the intracellular milieu

• Carry out a number of specific recognition

and regulatory functions .


Fluid-Phase Pinocytosis

• Small invaginations of the cell membrane form and entrap extracellular fluid and anything in solution in the fluid.

• Pinocytotic vesicles (about 80 nm in diameter) pinch off from the cell surface and most eventually fuse with lysosomes.

• Pinocytotic vesicles may move to the surface opposite their origin.


Receptor-Mediated Endocytosis

• Ligands, such as hormones and growth factors, bind to specific surface receptors and are internalized in pinocytotic vesicles coated with clathrin and other proteins.

• After the liberation of the coating molecules, the pinocytotic vesicles fuse with the endosomal compartment, where the low pH causes the separation of the ligands from their receptors.



• Membrane with receptors

is returned to the cell

surface to be reused.

• The ligands typically are

transferred to lysosomes.

• The cytoskeleton with

motor proteins is

responsible for all vesicle

movements described.



• Internalization of low-density lipoproteins (LDL) is important to keep the concentration of LDL in body fluids low.

• LDL, which is rich in cholesterol, binds with high affinity to its receptors in the cell membranes.

• This binding activates the formation of pinocytotic vesicles from coated pits.



• The vesicles soon lose their coating, which is returned to the inner surface of the plasmalemma: the uncoated vesicles fuse with endosomes.

• In the next step, the LDL is transferred to lysosomes for digestion and separation of their components to be utilized by the cell.


Phagocytosis

• Certain cell types, such

as macrophages and

polymorphonuclear

leukocytes, are

specialized for

incorporating and

removing foreign

bacteria, protozoa, fungi,

damaged cells, and

unneeded extracellular

constituents .


Exocytosis

• Fusion of a membrane-limited structure with the plasma membrane, resulting in the release of its contents into the extracellular space without compromising the integrity of the plasma membrane.

• A typical example is the release of stored products from secretory cells, such as those of the exocrine pancreas and the salivary glands.


Organelles

Mitochondria

Ribosomes

Endoplasmic Reticulum

Golgi Complex

Lysosomes

Secretory Vesicles


Mitochondria

• Are spherical or

filamentous organelles

0.5–1 µm wide that can

attain a length of up to 10

µm.

• They tend to accumulate

in parts of the cytoplasm

at which the utilization of

energy is more intense,

such as the apical ends

of ciliated cells.


Mitochondria

• In the middle piece of

spermatozoa.

• At the base of ion-

transferring cells.


Mitochondria

• They are composed of an

outer and an inner

mitochondrial membrane;

• The inner membrane projects

folds, termed cristae ,into the

interior of the mitochondrion.

• The compartment located

between the two membranes is

termed the intermembrane

space .

• The inner membrane encloses

the other compartment—the

intercristae, or matrix, space.


Mitochondria

• Between the cristae is an amorphous matrix , rich in protein and containing circular molecules of DNA and the three varieties of RNA.

• In a great number of cell types, the mitochondrial matrix also exhibits – Rounded electron-dense

granules rich in Ca+2

– Enzymes for the citric acid (Krebs) cycle and fatty acid βoxidation


Mitochondria

• The globular

structures are a

complex of proteins

with ATP synthetase

activity.


Dr. Sami Zaqout JUST

Mitochondria

• Several diseases of mitochondrial deficiency have been described, and most of them are characterized by muscular dysfunction.

• Because of their high-energy metabolism, skeletal muscle fibers are very sensitive to mitochondrial defects.

• Mitochondrial inheritance is maternal.

• In the case of nuclear DNA defects, inheritance may be from either parent or both parents.

• Generally, in these diseases the mitochondria show morphological change.


Ribosomes

• Ribosomes are small electron-dense particles, about 20 x 30 nm in size.

• They are composed of four types of rRNA and almost 80 different proteins.

• Composed of two different-sized subunits.

• The RNA molecules of both subunits are synthesized within the nucleus.

• Ribosomes are intensely basophilic


Ribosomes

• Proteins synthesized for use within the cell and destined to remain in the cytosol are synthesized on polyribosomes existing as isolated clusters within the cytoplasm.


Ribosomes

• Polyribosomes that are attached to the membranes of the endoplasmic reticulum (via their large subunits) translate mRNAs that code for proteins that are segregated into the cisternae of the reticulum.

• These proteins can be secreted (eg, pancreatic and salivary enzymes) or stored in the cell (eg, enzymes of lysosomes, proteins within granules of white blood cells [leukocytes]).

• Integral proteins of the plasma membrane are synthesized on polyribosomes attached to membranes of the endoplasmic reticulum


Endoplasmic Reticulum

• The endoplasmic reticulum is an anastomosing network of intercommunicating channels and sacs formed by a continuous membrane.

• Smooth endoplasmic reticulum is devoid of ribosomes.

• Ribosomes (the small dark dots are present in the rough endoplasmic reticulum.

• The cisternae of the smooth reticulum are tubular, whereas in the rough reticulum they are flat sacs.


Rough Endoplasmic Reticulum

• Rough endoplasmic reticulum (RER) is prominent in cells specialized for protein secretion, such as – Pancreatic acinar cells

(digestive enzymes),

– Fibroblasts (collagen),

– Plasma cells (immunoglobulins).


Rough Endoplasmic Reticulum

• The principal function of the RER is to segregate proteins not destined for the cytosol.

• Additional functions include

– The initial (core) glycosylation of glycoproteins

– The synthesis of phospholipids

– The assembly of multichain proteins, and certain posttranslational modifications of newly formed polypeptides.


Smooth Endoplasmic Reticulum

• Found in cells that

synthesize steroid

hormones (e.g., cells

of the adrenal cortex),

• SER occupies a large

portion of the

cytoplasm and

contains some of the

enzymes required for

steroid synthesis.



• SER is abundant in liver cells, where it is responsible for the oxidation, conjugation, and methylation processes employed by the liver.

• SER contains the enzyme glucose-6-phosphatase, which is involved in the utilization of glucose originating from glycogen in liver cells.



• Synthesis of phospholipids for all cell membranes.

• The phospholipid molecules are transferred from the SER to other membranes

• (1) by vesicles that detach and are moved along cytoskeletal elements by the action of motor proteins.

• (2) through direct communication with the RER.

• (3) by transfer proteins.



• SER participates in the

contraction process in

muscle cells, where it

appears in a specialized

form, called the

sarcoplasmic reticulum ,

that is involved in the

sequestration and release

of the calcium ions that

regulate muscular

contraction .


Golgi Complex (Golgi Apparatus)

• The Golgi complex completes posttranslational modifications and packages and places an address on products that have been synthesized by the cell.

• This organelle is composed of smooth membrane-limited cisternae .



• In highly polarized

cells, such as mucus-

secreting goblet cells

the Golgi complex

occupies a

characteristic position

in the cytoplasm

between the nucleus

and the apical plasma

membrane.



• Through transport vesicles that fuse with the Golgi cis face, the complex receives several types of molecules produced in the rough endoplasmic reticulum (RER).

• After Golgi processing, these molecules are released from the Golgi trans face in larger vesicles to constitute secretory vesicles, lysosomes, or other cytoplasmic components .




Lysosomes

• Lysosomes are sites of

intracellular digestion and

turnover of cellular

components.

• Lysosomes are

membrane-limited

vesicles that contain a

large variety of hydrolytic

enzymes (more than 40)

whose main function is

intracytoplasmic digestion


Lysosomes

• Lysosomal enzymes are capable of breaking

down most biological macromolecules.

• Lysosomal enzymes have optimal activity at an

acidic pH.

• The enveloping membrane separates the lytic

enzymes from the cytoplasm, preventing the

lysosomal enzymes from attacking and digesting

cytoplasmic components.


Lysosomes

• Synthesis occurs in the rough endoplasmic reticulum (RER), and the enzymes are packaged in the Golgi complex.

• Secondary lysosomes. – Heterophagosomes, in

which bacteria are being destroyed,

– Autophagosomes, with RER and mitochondria in the process of digestion.


Lysosomes

• The result of their digestion can be excreted, but sometimes the secondary lysosome creates a residual body, containing remnants of undigested molecules.

• Large quantities of residual bodies accumulate and are referred to as lipofuscin, or age pigment.

• In some cells, such as osteoclasts, the lysosomal enzymes are secreted to the extracellular environment.


Lysosomes

• Lysosomes play an important role in the metabolism of several substances in the human body, and consequently many diseases have been ascribed to deficiencies of lysosomal enzymes .


Proteasomes

• Multiple-protease complexes that digest proteins targeted for destruction by attachment to ubiquitin.

• Proteasomes deal primarily with proteins as individual molecules

• Lysosomes digest bulk material introduced into the cell or whole organelles and vesicles.


Peroxisomes

• Peroxisomes are spherical membrane-limited organelles whose diameter ranges from 0.5 to 1.2 µm

• Peroxisomes oxidize specific organic substrates by removing hydrogen atoms that are transferred to molecular oxygen (O2).

• This activity produces hydrogen peroxide (H2O2), a substance that is very damaging to the cell.

• However, H2O2 is eliminated by the enzyme catalase, which is present in peroxisomes


Peroxisomes

• Peroxisomes contain enzymes involved in lipid metabolism.

• Probably the most common peroxisomal disorder is X-chromosome-linked adrenoleukodystrophy, caused by a defective integral membrane protein that participates in transporting very long-chain fatty acids into the peroxisome for β oxidation.

• Accumulation of these fatty acids in body fluids destroys the myelin sheaths in nerve tissue, causing severe neurological symptoms.


Peroxisomes

• Deficiency in peroxisomal enzymes causes the fatal Zellweger syndrome, with severe muscular impairment, liver and kidney lesions, and disorganization of the central and peripheral nervous systems.

• Electron microscopy reveals empty peroxisomes in liver and kidney cells of these patients .


Secretory Vesicles and Granules

• Secretory vesicles are found in those cells that store a product until its release 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 products.


Secretory Vesicles, or Granules

• Secretory vesicles

containing digestive

enzymes are referred

to as zymogen

granules.


The Cytoskeleton

Microtubules

Actin filaments

Intermediate filaments


Functions of the Cytoskeleton

Shaping of cells

Movements of organelles and intracytoplasmic vesicles.

Participates in the movement of entire cells.


Microtubules

• Found within the cytoplasmic matrix.

• Also found in cytoplasmic processes called cilia and flagella.

• It is a polarized structure has an alternation of the two subunits α and β of the tubulin molecule.

• Tubulin molecules are arranged to form 13 protofilaments .


Microtubules

• Changes in microtubule length are due to the addition or loss of individual tubulin subunits.

• Polymerization of tubulins to form microtubules in vivo is directed by a variety of structures collectively known as microtubule-organizing centers. – Cilia

– Basal bodies

– Centrosomes.


Microtubules

• Cytoplasmic microtubules are stiff structures that play a significant role in the development and maintenance of cell shape.

• They are usually present in a proper orientation, either to effect development of a given cellular asymmetry or to maintain it.

• Microtubules also participate in the intracellular transport of organelles and vesicles. – Axoplasmic transport in neurons

– Melanin transport in pigment cells

– Chromosome movements by the mitotic spindle

– Vesicle movements among different cell compartments


Microtubules

• Microtubules provide

the basis for several

complex cytoplasmic

components:

– Centrioles

– Basal bodies

– Cilia

– Flagella


Centrioles

• Centrioles consist of nine microtubule triplets linked together in a pinwheel-like arrangement.

• In the triplets, microtubule A is complete and consists of 13 subunits, whereas microtubules B and C share tubulin subunits.

• Under normal circumstances, these organelles are found in pairs with the centrioles disposed at right angles to one another .


Centrosome

• Close to the nucleus

of nondividing cells is

a centrosome made

of a pair of centrioles

surrounded by a

granular material.

• In each pair, the long

axes of the centrioles

are at right angles to

each other .


Cilia and flagella

• Cilia and flagella are motile processes, covered by cell membrane, with a highly organized microtubule core.

• Ciliated cells typically possess a large number of cilia, each about 2–3 µm in length.

• Flagellated cells have only one flagellum, with a length close to 100 µm.

• In humans, the spermatozoa are the only cell type with a flagellum.

• The main function of cilia is to sweep fluid from the surface of cell sheets.

• Both cilia and flagella possess the same core organization .


Cilia and flagella

• A cross section through a cilium reveals a core of microtubules called an axoneme.

• The axoneme consists of two central microtubules surrounded by nine microtubule doublets.

• In the doublets, microtubule A is complete and consists of 13 subunits, whereas microtubule B shares two or three heterodimers with A.


Cilia and flagella

• When activated by ATP, the dynein arms link adjacent tubules and provide for the sliding of doublets against each other.

• At the base of each cilium or flagellum is a basal body essentially similar to a centriole, that controls the assembly of the axoneme.


Actin Filaments

• Contractile activity in muscle cells results primarily from an interaction between two proteins: – Actin

– Myosin.

• Actin is present in muscle as a thin (5–7 nm in diameter) filament composed of globular subunits organized into a double-stranded helix .


Actin Filaments

1) In skeletal muscle, they assume a paracrystalline array integrated with thick (16-nm) myosin filaments .

2) In most cells, actin filaments form a thin sheath just beneath the plasmalemma, called the cell cortex .

• These filaments appear to be associated with membrane activities such as endocytosis, exocytosis, and cell migratory activity .

3) Actin filaments are intimately associated with several cytoplasmic organelles, vesicles, and granules.

• The filaments are believed to play a role in moving and shifting cytoplasmic components (cytoplasmic streaming .


Actin Filaments

4) Actin filaments are associated with myosin and form a "purse-string" ring of filaments whose constriction results in the cleavage of mitotic cells .

5) In most cells, actin filaments are found scattered in what appears to be an unorganized fashion within the cytoplasm.


Intermediate Filaments

• Cells contain a class of

intermediate-sized

filaments with an average

diameter of 10–12 nm .

• Several proteins that form

intermediate filaments

have been isolated and

localized by

immunocytochemical

means.


Intermediate Filaments

• The presence of a specific type of intermediate

filament in tumors can reveal which cell

originated the tumor, information important for

diagnosis and treatment


Cytoplasmic Deposits

• Cytoplasmic deposits are usually transitory components of the cytoplasm, composed mainly of accumulated metabolites or other substances . – Lipid droplets

– Glycogen

– Proteins


Cytoplasmic Deposits

• Deposits of pigments

are often found in

cells.

– Lipofuscin

– Carotene

– Melanin


Cytosol

• The final supernatant produced by centrifugation , after the separation of organelles, is called the cytosol.

• The cytosol constitutes about half the total volume of the cell.

• The cytosol coordinates the intracellular movements of organelles and provides an explanation for the viscosity of the cytoplasm.

• It contains thousands of enzymes that produce building blocks for larger molecules and break down small molecules to liberate energy.

• All machinery to synthesize proteins (rRNA, mRNA, tRNA, enzymes, and other factors) is contained in the cytosol.


Cell Components & Diseases


The Cell Nucleus

• The nucleus contains a blueprint for all cell structures and activities encoded in the DNA of the chromosomes.

• It also contains the molecular machinery to replicate its DNA and to synthesize and process the three types of RNA:-

– ribosomal (rRNA)

– messenger (mRNA),

– transfer (tRNA).


The Cell Nucleus

• The nucleus

frequently appears as

a rounded or

elongated structure,

usually in the center

of the cell.


The Cell Nucleus

Nuclear envelope

Chromatin

Nucleolus

Nuclear matrix


Nuclear Envelope

• The nuclear envelope is composed of two membranes of the endoplasmic reticulum, enclosing a perinuclear cisterna.

• Where the two membranes fuse, they form nuclear pores.

• Ribosomes are attached to the outer nuclear membrane.


Nuclear Envelope

• Heterochromatin clumps are associated with the nuclear lamina, whereas the euchromatin (EC) appears dispersed in the interior of the nucleus .

• Closely associated with the internal membrane of the nuclear envelope is a protein structure called the fibrous lamina which helps to stabilize the nuclear envelope.


Nuclear Envelope

• Nuclear pores provide controlled pathways between the nucleus and the cytoplasm.

• The pores are not open but show an octagonal pore complex made of more than 100 proteins.


Chromatin

• Chromatin, in nondividing nuclei, is in fact the chromosomes in a different degree of uncoiling.

• According to the degree of chromosome condensation, two types of chromatin can be distinguished with both the light and electron microscopes.


Chromatin

• Heterochromatin which is electron dense, appears as coarse granules in the electron microscope and as basophilic clumps in the light microscope.

• Euchromatin is the less coiled portion of the chromosomes, visible as a finely dispersed granular material in the electron microscope and as lightly stained basophilic areas in the light microscope.


Chromatin

• The chromatin pattern of a nucleus has been

considered a guide to the cell's activity.

• In general, cells with light nuclei are more active

than those with condensed, dark nuclei.

– In light-stained nuclei (with few heterochromatin

clumps), more DNA surface is available for the

transcription of genetic information.

– In dark-stained nuclei (rich in heterochromatin), the

coiling of DNA makes less surface available .


Sex chromatin

• The X chromosome that constitutes the sex chromatin

remains tightly coiled and visible, whereas the other X

chromosome is uncoiled and not visible.

• Evidence suggests that the sex chromatin is genetically

inactive .


Nucleolus

• The nucleolus is a

spherical structure

that is rich in rRNA

and protein.

• It is usually basophilic

when stained with

hematoxylin and

eosin .


Nucleolus

• Nucleolar organizer DNA sequences of bases that code for rRNA.

• Pars fibrosa, which consists of primary transcripts of rRNA genes.

• Pars granulosa consists of 15- to 20-nm granules (maturing ribosomes).

• Nucleolus-associated chromatin Heterochromatin is often attached to the nucleolus


Nuclear Matrix

• The nuclear matrix is the

component that fills the

space between the

chromatin and the

nucleoli in the nucleus.

• It is composed mainly of

proteins (some of which

have enzymatic activity),

metabolites, and ions .


Histology Course for Medical Students - الصفحات الشخصية ...site.iugaza.edu.ps/sizaqout/files/2012/02/The-Cell.pdf• The compartment located between the two membranes

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