introduction to cells & tissues by vijay kapal graduate studies course cmm 5001 the pathological...
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INTRODUCTION TO CELLS & TISSUES
ByVijay Kapal
Graduate Studies Course CMM 5001
The Pathological Basis Of Disease
FertilizationFertilization of egg by the sperm
Egg + Sperm
(23 Chromo) (23 Chromo)
Fertilized egg (Zygote)
(46 Chromosomes)
Human body
Sperm
Ovum (Egg)
Sperm
Zygote
3-layered Flat EmbryoEctoderm (1)
Mesoderm (3)
Endoderm (2)
Fertilized egg or Zygote (Single cell)
3-layers of cells
All Tissues & Organs of Human body
Nucleus
Cytoplasm
Cell membrane
Cell
Human Genome
Chromosomes (2N = 46)
Each cell has 46 chromosomes
Form 23 homologous pairs
Each parent contributes = 23
Autosomes = 44
Sex chromosomes = 2
(Male = XY, Female = XX)
Each autosome of a homologous pair look alike
But each sex chromosome do not look alike
Cell CycleNondividing cells (Fixed postmitotics)
Resting cells (Reverting postmitotics)
Methotrexate
Bleomycin Etoposide
Paclitaxel Vincristine Vinblastine Colchicine G0
G1
S
G2
M
Mitosis & MeiosisA Homologous Pair (2 Chromosomes)
1
2
46
1 pair
23 pair
Daughter Somatic Cells (2) Gametes (4)
2nd Division
1st Division
MeiosisTakes place only in testes and ovaries
Is a reductional division
Main purpose is to reduce the number of chromosomes from 2N to 1N in sperms & eggs
(Chromosomes of each homologous pair will separate from each other)
Homologous pair = 1 chromosome from each parent (at fertilization)
2N = 46 chromosomes (2 sets)
1N = 23 chromosomes (1set)
So
Sperm = 1N chromosomes (23)
Egg = 1N chromosomes (23)
Fertilization restores chromosome number again to 2N = 46 chromosomes (2 sets)
Cell Organelles
• Nucleus Chomatin, Transcription• Rough ER Protein synthesis & Segregation• Smooth ER Fat & Steroid synthesis &
Detoxification• Golgi Complex Concentrating, Modifying & Packaging of
secretory products• Lysosomes Intracellular digestion• Peroxisomes Contain oxidative enzymes; Use catalase to
degrade H2O2 = H2O + O2
• Mitochondria Oxydative phosphorylation & ATP production• Cell Membrane Lipid bilayer layer with intramembranous proteins• Cell cytoskeleton Actin filaments, Microtubules, intermediate filaments
Cells, Tissues & Various Topics Of Research
• Subcellular localisation & trafficking of molecules and oganelles• Cell-cell and cell-extracellular matrix interactions• Cell cytoskeleton and receptor dynamics and functions• Cell and tissue differentiation and remodelling• Genetically engineered cells and tissues• Three-dimensional reconstructions, particularly of expression patterns
over time• Cell cycle and cell lineage analysis involving gene expression profiles• Apoptosis• Gene expression analysis from histological preparations• Functional genomics & proteomics• Techniques used in molecular histology
General Features
• Diversity• Metaplasia• Lining and Covering• Basal Lamina• Renewal• Avascularity• Cell Packing• Derivation
Classifying Principles
1. Number of cell layers:1. Simple epithelia
2. Stratified epithelia3. Pseudostratified epithelia
2. Shape of the surface cells:1. Squamous cells
2. Cuboidal cells3. Columnar cells
3. Luminal surface modifications:1. Microvilli (Brush border)
2. Cilia3. Stereocilia
Specific Epithelial Types
• Simple squamous epithelium:• Simple cuboidal epithelium:• Simple columnar epithelium:• Pseudostratified epithelium:• Stratified Squamous epithelium:
a) Keratinizedb) Nonkeratinized
• Stratified cuboidal epithelium:• Stratified columnar epithelium:• Transitional epithelium:
Simple squamous Stratified squamous
Simple cuboidal stratified cuboidal
Simple columnar Pseudostratified
Transitional
Types of Epithelia
Full Empty
Bladder
Epithelium
Cilia
Ciliated cells
Goblet cells
Basal lamina
Lamina propria
Trachea (Pseudostratified Epithelium)
Basal Lamina• Next to epithelia an acellular sheet like structure is the Basal Lamina.• Component Layers & Constinuent Macromolecules:
A. Component LayersLamina lucidaLamina densaB. Constituent MacromoleculesLamina lucida (Laminin that binds to cell surface integrins, collagen IV) Lamina densa (Type IV Collagen)Basement Membrane:Basal lamina accompanied by reticular lamina (Type III Collagen) is called the basement membrane.Functions:Forms sieve-like selective barrier between the epithelia & connective tissue.Aids in cell organization, cell adhesion & maintainence of cell shape.Has a role in maintaining specific cell function. Helps guide migrations of cells during development and regeneration of injured tissue
Polarity & Specialization of Epithelial CellsA. Specialization of the Apical Surface:
1. Microvilli (Enterocytes & Proximal convoluted tubule cells))2. Cilia (Trachea, Bronchus etc.)3. Stereocilia (Epididymis)4. Flagella
B. Specialization of the Lateral Surfaces:1. Zonula occludens (Tight junctions)2. Zonula adherens (Intermediate junctions)3. Macula adherens (Desmosomes)4. Gap junction (Nexus)
C. Specialization of the Basal Surface:1. Basal lamina2. Hemidesmosome3. Sodium-potassium ATPase
D. Intracellular Polarity:
Microvilli
Zonula occludens
Zonula adherens
Terminal web
Macula adherens
Gap junction
Nucleus
Hemidesmosome
Cell Junctions
Mucous Membranes
• Components of Mucous Membrane:
1. Epithelium
2. Basement membrane
3. Lamina propria
Serous Membranes
A. Components of Serous Membrane:
1. Epithelium called mesothelium
2. Basement membrane
3. Submesothelial connective tissue layer
Functions of Epithelia1. Protection from:Mechanical traumaDehydrationPathogens
2. Secretion of:Hormones, milk, sweat etc.
Enzymes, HCl, glycoproteins,Mucous & serous products
3. Lubrication of:Contents of GI tract
Fetus in birth canalJoints
4. Filtration of wastes: (Urine)
5. Absorption of food: (Aminoacids, Glucose, Fatty acids)
6. Neuroepithelium: (Taste, Smell, Hearing)
7. Reproduction: (Germ cells)
Major Types of Epithelial Cells
A. Epithelial Cells Specialized for Transport:1. Ion-transporting cells (Kidney tubules, Gall bladder etc.)2. Cells that transport by pinocytosis (Endothelial cells of
blood capillariesB. Absorption: (Enterocytes, Proximal convoluted tubule cells)C. Secretion:
1. Protein-secreting cells (Acinar cells of pancreas, Hepatocytes)2. Polypeptide-secreting cells (APUD cells)3. Mucous cells (Goblet cells)4. Serous cells (Acinar cells of pancreas & secretory cells of parotid
salivary glands.5. Steroid-secreting cells (Adrenal cortex, Leydig cells etc.)
D. Contractile Epithelial Cells: (Myoepithelial cells of glands)
GLANDSA. Exocrine & Endocrine Glands:B. Classification of Exocrine Glands:
1. By structure:a) Number of cellsb) Duct systemc) Secretory portion
2. By secretory producta) Mucous secretionb) Serous secretionc) Seromucous secretion
3. By mode of secretiona) Merocrineb) Apocrinec) Holocrine
Unicellular Multicellular Simple tubular Coiled tubular Branched
Simple branched Simple acinar Compound tubular Compound tubulo-alveolar
Connective Tissue
• Is one of the 4 basic tissues of the body.• Structurally it is made up of cells and large
amount of intercellular space containing extracellular matrix.
• Matrix is the dominating component of this tissue.• It forms framework, connecting, supporting and
packing tissue of the body.• It also plays a dynamic role in the development,
growth and homeostasis of other tissue types.
Loose connective tissue
Dense connective tissue
Connective Tissue
Fibroblasts
Extracellular matrix
Mammary Glands
Epithelial tissue
Types of Cells in Loose Connective Tissue
1. Residents:Fibroblasts
MacrophagesReticular cells Mesenchymal cells
2. Visitants:Mast cells
Plasma cellsLeukocytesFat cellsMelanocytes
Loose Connective Tissue
Elastic fibers
Capillary
Neutrophil
Plasma cell
Fibroblast
Collagen fibers
Macrophage
Adipocyte
Mast cell
Lymphocyte
Collagen Producing Cells
1. Fibroblast-More than one type of collagen
2. Chondroblast- Type II collagen
3. Osteoblast-Type I
4. Reticular cell- Type III
5. Smooth muscle-Type I & III
Extracellular Matrix• Extracellular matrix (Fibers & Ground substance) is synthesized and
secreted mainly by the fibroblasts & the fibers are assembled in the extracellular space.
• FibersPrime function is support & plays strengthing role in
• Ground substanceFunctions are1. Acts as a molecular sieve & stops the spread of noxious substances2. Plays very important role in cellular nutrition & waste removal3. Plays a vital role in aging. Its amount diminishes with age and
wrinkles start appearing.
Fiberous Components
Connective tissue fibers are long, slender protein polymers
that are present in variable proportions in different types of
connective tissue.
In many cases the predominant fiber type is responsible for
conferring specific properties on the tissue.
• Collagen Fibers:
• Elastic Fibers:
• Reticular Fibers:
Collagen Fibers
Collagen Fibers:Most abundant protein in the body.Synthesis & assembly:Collagen types-Type I- most abundant & occurs in loose and dense connective
tissue & bone.Type II- occurs in cartilage.Type III- occurs in hematopoitic tissues.Type IV- occurs in basal laminae & does not form fibers or fibrils.Type V- in placental basement membranes & blood vessels.Type X- around hypertrophic, degenerating chondrocytes of the
growth plate where bone formation is to occur.
Synthesis of Collagen
Fibroblast
Procollagen (Triple-helical units)
Procollagen peptidaseTropocollagen
Collagen fibril
Collagen fiber
Extracellular
Intracellular
Collagen’s main amino acids
Glycine (34%)
Proline (12%)
Hydroxyproline (10%)
Ground SubstanceProteoglycans:
They are made up of a core protein to which glycosoaminoglycans (GAGs) are attached. GAGs are polysacharides that contain aminosugars.GAGs-Chondroitin sulphate, Dermatan sulphate, Keratan sulphate & Heparin sulphate.Hyaluronic acid is a GAG but do not form proteoglycans.Matrix viscosity and rigidity are determined by the amount and types of GAGs, their association with the core protein to form proteoglycans, GAG-fiber association, and GAG-GAG associations.
Glycoproteins:Fibronectin-mediates the attachment of cells to the extracellular matrix.Laminin-a component of basal laminae that mediates the attachment of epithelial cells.
Tissue fluids:Salts:
Connective Tissue Types
A. Connective Tissue Proper:
1. Loose connective tissue
2. Dense connective tissue
a) Dense regular connective tissue
b) Dense irregular connective tissue
B. Reticular connective tissue:
C. Elastic connective tissue:
D. Mucous connective tissue:
Connective Tissue Proper
A. Connective Tissue Proper:
1. Loose connective tissue (lamina propria)
2. Dense connective tissue
a) Dense regular connective tissue (Tendon, ligament)
b) Dense irregular connective tissue (Dermis, organ capsule)
Loose CT Dense CT
Elastic Connective tissue
Elastic fibers consist of an amorphous protein called elastin and numerous protein microfibrils embedded in it.
Diameter range 0.1-10um.
Elastic fibers are collected in thick, wavy, parallel bundles & seperated by loose collagenous tissue with fibroblasts.
Ground substance is sparse.
Elastic connective tissue provides flexible support.
Predominates in the ligamentum flava of the vertebral column & the suspensory ligament of the penis.
Reticular Connective TissueThese fibers look very similar to collagen but are thinner than them (0.1-1.5um).More highly glycosylated.Form delicate silver-staining network instead of thick bundles.Composed mainly of type III collagen and some glycoprotein.These fibers are covered by long processes of the reticular cells.There is very little ground substance.Reticular connective tissue supports motile cells & filters body fluids.It is found mainly in hematopoietic tissue (bone marrow, spleen and lymph nodes).
Reticular fibers
Lymphocyte
Reticular cell Nu
Reticular cells
Lymph Node
Reticular Connective Tissue
Mesenchyme
Mesenchyme is embryonic connective tissue.Its stellate and fusiform cells (mesenchymal cells) are derived from mesoderm.They give rise to all the connective tissue of of the body.These are multipotential cells and persist in adults to give rise to new generations of connectivetissue cells especially during wound healing, bone repair and tissue fibrosis.
Mesenchymal Tissue (Embryo)Neural tube
Mesenchyme
Somite
Notochord
Neural tube
Extracellular matrix
Mesenchymal cells
Histophysiology
A. Functions:1. Support.2. Defense.
a) Physicalb) Immunologic
3. Repair.4. Storage.5. Transport
B. Edema:C. Hormonal Effects:D. Nutritional Factors:E. Collagen Renewal:
White Blood Cells (Granulocytes)
Neutrophil Eosinophil Basophils
Functions:-
Neutrophils act as first line of defense in infections.
Eosinophils respond to allergic states & parasitic infection
Basophils release heparin & histamine
Defense SystemINNATE DEFENSES (Do not require immunization)
Physical barriers
Chemical barriers
Soluble factors
(Skin, mucous membranes)
(Low pH, Mucous)
(Lysosomes, Interferons, Acute phase proteins, Complements)
Facilitates
CELLS (Macrophages, Granulocytes)
Fast response
Limited Flexibility
Non-specific
No memory
Facilitate
ADAPTIVE DEFENSES (Requires immunization)
Directly kill infected cells
T lymphocytes
B lymphocytes
Cytotoxic
Help
Delayed response
Highly flexible
Highly specific
Memory, lasting immunity
ANTIBODIES
Mast Cells
Functions:-
Produce heparin, an anticoagulant
Produce histamine to render blood vessels permeable
Mast cells
B Lymphocytes deliver antibodies-mediated immune response
T lymphocytes deliver cell-mediated immune response
Natural killer cells kill tumor & nonself cells
LYMPHOCYTES
Plasma Cells
Plasma cells produce antibodies to fight the infections
Immunoglobulins IgG, IgA, IgM, IgE & IgD
Plasma cells
Lymphocyte
Functions:-
Phagocytose, process & present antigens to lymphocytes
Act as scavengers etc.
Macrophage
Macrophage
Cartilage
Perichondrium
Chondroblasts
Chondrocytes
Lacuna
Cartilage matrix
Isogenous group
of chondrocytes
Nervous Tissue
Cerebellum
Cortical neurons
Spinal cord
Motor neurons
Spinal ganglion
Sensory neurons
Divisions of the Nervous System
• Central Nervous System (CNS)
• Peripheral Nervous System (PNS)
• Autonomic Nervous System (ANS)
General Features
• Two Classes of Cells:1. Neurons2. Supporting cells
• Impulse Conduction:• Synapses:• Divisions of the Nervous System:• Embryonic Development of Nervous Tissue:• Aging and Repair:• Meninges:• Blood-Brain barrier:
Cells of the Nervous Tissue
Two Classes of Cells:
1. Neurons.
2. Supporting, neuroglial or glial cells.
NeuronBlood capillary
Glial cells
Dendrites
Nissl bodies
Axon hillock
Nucleus
Nucleolus
Myelinated axons
Neuron (Cell body)• Cell Body:-It is also called soma or perikaryon
-It is the synthetic & trophic center of cell -It can receive signals from axons of other neurons through synaptic contacts on its cell membrane and relay them to its axon-Nucleus usually large, central, spherical and euchromatic-Nucleus with prominent nucleolus-Cytoplasm contains many organelles like mitochondia, lysosomes etc.-Cytoplasm has abundant free polyribosomes & rough endoplasmic reticulum, appears as basophilic purplish-blue clumps called Nissl bodies-Well developed Golgi to pack & often glycosylates neurotransmitters in neurosecretory, or synaptic vesicles-Abundant neurotubules (microtubules) & neurofilaments (intermediate filaments) in soma, dendrites & axon
Neuron (Dendrites)
• Dendrites:-Extensions of cell body, specialized to increase the surface area for incoming signals-Synaptic contacts are made on them-Some synaptic sites on them look like sharp projections called dendritic spines gemmules-Proximal ends has some Nissl bodies
Neuron (Axon)• Axon:
-One axon per neuron, its cytoplasm called axoplasm & its plasma
membrane, the axolemma.-A complex cell process (uniform diameter) carries impulses away from the soma.-The part of the cell body where axon exits the soma is called the axon hillock and it lacks Nissl bodies.-Axon can be myelinated or unmyelinated.-Myelin sheath in CNS is provided by the oligodendrocyte , while in PNS by the Schwann cell-Axon diameter & myelin thickness determines the speed of nerve impulse. Internode (Myelin –covered) & Node (without myelin) -Some axons have branches called collaterals.-Terminal branching of axon is called terminal arborization.-Each branch ends as a bulb-like sac called terminal bouton, each bouton contains many mitochondria & neurosecretory vesicles. Specialized region of plasma membrane of bouton that take part in the formation of synapse is called as presynaptic membrane.
Synapses (Chemical)Synapses are specialized junctions by which a stimulus is transmitted from a neuron to its target cell.1. Presynaptic Membrane:
This is part of plasma membrane of terminal bouton.2. Synaptic Cleft:
Fluid-filled space between pre and post synaptic membranes.3. Postsynaptic Membrane:
This is part of plasma membrane of the target cell. It is thickerthan presynaptic membrane due to the presence of receptors forneurotransmitters. When enough receptors are occupied, hydrophilic channels open, resulting in depolarization of thepostsynaptic membrane. Neurontransmitter like acetylcholinethat remains in the synaptic cleft is degraded by acetylcholinesterase.This removal of extra acetylcholine allows postsynaptic mambrane to
reestablish its resting potential and prevents continuous firing of the postsynaptic neuron in response to a single stimulus.
Types of Synapses
• Axodendritic (Between an axon & a dendrite)
• Axosomatic (Between an axon & a cell body)
• Dendrodendritic (Between dendrites)
• Axoaxonic (Between axons)
Neuron (Types)• Based upon Configuration of cell processeses:
Multipolar (Motor neurons of spinal cord)Bipolar (Retina, olfactry mucosa)Unipolar(Photoreceptors, rods & cones of retina)Pseudounipolar (Sensory neurons of dorsal root ganglia)
• Based upon Cell size:Golgi type I (Motor neurons of spinal cord)Golgi type II (Interneurons of spinal cord)
• Based upon FunctionMotor neurons (Multipolar neurons of ventral horn etc.)Sensory neurons (Pseudounipolar neurons of dorsal root ganglia)Interneurons (Golgi type II neurons)
• Based upon Neurotransmitter releasedCholinergic neurons (Most somatic motor neurons)Adrenergic & noradrenergic neurons (Postganglionic sympathatic neurons)Dopaminergic (Some neurons of hypothalamus)GABAergic (Some neurons of the brain)
Supporting Cells
• Provide structural and functional support to neurons.
• Take part in the formation of blood-brain barrier, thus monitoring the passage of materials from blood to neurons.
Supporting cells of CNS
1. Astrocytes:- (Blood-Brain Barrier)
a) Protoplasmic astrocytes
b) Fibrous astrocytes2. Oligodendrocytes:- (Myelin to axons in CNS)
3. Ependymal cells:- (Produce the CSF)
4. Microglial cells:- (Macrophages of the nervous system)
Supporting Cells of PNS
1. Schwann cells:A Schwann cell may envelop segments of several unmyelinated axons or provide a segment of a single myelinated axon with its myelin sheath. Each mylinated axon segment (internode) is wrapped around by layers of a Schwann cell process with most of its cytoplasm squeezed out. This multilayered Schwann cell plasma membrane (mainly of phospholipids) is called myelin. The gaps between myelin sheath segments are the nodes of Ranvier.
2. Satellite cells:Each neuron outside the CNS is surrounded by a single layer of cells, called satellite cells.
Aging and Repair
• A neuron is a terminally differentiated cell.
• And is incapable of undergoing mitosis.
• Aging neurons accumulate more of lipofuscin pigment.
• Neurons lost through injury or surgery cannot be replaced.
• If the cell body remains intact, the injured axon can regenerate itself.
• If stimulated by injury, supporting cells, unlike neurons, can divide.
Blood-Brain Barrier
• Components of the barrier:
1. Endothelial cells of continuous type capillaries (Tight junctions)
2. Basal lamina
3. Cytoplasmic processes of astrocytes.
Response of Nerve Tissue to InjuryA. Damage to the Cell Body:
A neuron is a terminally differentiated cell & is unable to divide. So damaged or dead neurons can’t be replaced.
B. Damage to the Axon:1. Degenaration:- Distal to the site of injury, axon & myelin degenerate. Within 2-3 days, they are removed & these clear endoneurial channels are occupied by Schwann cells. Proximal to the site of injury, retrograde degeneration of axon goes up to 2 internodes, then injured axon is sealed. Cell body also undergoes
changes in response to the injury. The Nissl bodies disappear (chromatolysis) & nucleus moves to the periphery. (2 Weeks)2. Regeneration:- Begins at 3rd week, Nissl bodies reappear, protein synthesis starts. Axon’s proximal stump gives off a number of small processes called neurites. One of these enters and grows in an endoneurial channel and synaptic contacts are
remade with the target cell. The target cell or organ deprived of innervation often atrophy.
Cell body
Nissl bodies
Axon
Schwann cells
Motor end plate
Muscle
Before injury 2 weeks 3 weeks 3 months No healing
A B C D ENerve Injury & Recovery
Basic Properties of Muscle Tissue
1. Excitability- ability to respond to a stimulus
2. Conductivity- ability to propagate a limited response
3. Contractility- ability to shorten
4. Relaxability- ability to relax (return to original shape after contraction)
Nucleus
IC Disc
Cardiomyocyte in Longitudinal Section
Cardiomyocyte Purkinje CellIn Cross Section
Nucleus
Myofibrils
EndomysiumCapillary
Comparison Of Types Of Muscles
Location
Cell size/shape
Nuclei
Striations Z lines
T tubules & Sarcoplasmic reticulum
Cell junctions
Muscles of skeleton
Long; cylindrical
Many; peripherally located
Yes Yes
Triads at A-I junctions
None
Heart
Short, branched
Single; centrally located
Yes Yes
Diads at Z line
Intercalated disks (Adherens, occludens & nexi)
Visceral organs
Variable, fusiform
Single: central
No Dense bodies
Caveolae replace T tubules; sparse
Nexi (Gapjunctions)
Property Skeletal Muscle Cardiac Muscle Smooth Muscle