Cellular and Tissue Overview

Elongation and Translation

• Elongation Process: The ribosome advances one codon along the mRNA, and this process is repeated.
• Termination: Elongation continues until a stop codon is encountered, at which point the peptide chain is released from the tRNA.
• mRNA Reuse: A single mRNA molecule can be read repeatedly to produce multiple copies of a polypeptide.
• tRNA Recycling: Once a tRNA molecule releases its amino acid, it can return to the cytoplasm to bind to another molecule of its specified amino acid.

Post-Translational Modifications

• Newly synthesized polypeptides undergo modifications to become fully functional.
• Some proteins are used in the cell membrane, remain in the cytoplasm, or are transported out of the cell.
• Protein chains bind to the endoplasmic reticulum (ER) to initiate secretion.
• Proteins are released into the lumen of the ER, where they are modified by enzymes.
• These proteins then travel through the Golgi complex for further modification.
• In the Golgi, proteins are packaged into vesicles and secreted via exocytosis through either constitutive or regulated secretion pathways.

Transcription and Translation Overview

• Transcription: RNA is transcribed from a DNA template.
• RNA Processing (Eukaryotes): The pre-mRNA transcript is spliced and modified to produce mRNA, which moves from the nucleus to the cytoplasm.
• mRNA to Ribosome: mRNA leaves the nucleus and attaches to a ribosome.
• Amino Acid Activation: Each amino acid attaches to its proper tRNA with the help of a specific enzyme and ATP.
• Translation: tRNAs add their amino acids to the polypeptide chain as the mRNA moves through the ribosome one codon at a time, until the polypeptide is completed and released.

Intended Learning Outcomes

• Understand different stages of the cell cycle and its regulation.
• Comprehensive knowledge of mitosis and meiosis, including the ability to identify stages.
• Basic awareness of transcription and translation processes.
• Ability to describe post-translational modifications with examples.

Tissue Types

• Epithelial Tissue
• Connective Tissue
• Muscle Tissue
• Nerve Tissue

Subtypes of Connective Tissue

• Loose Connective Tissue
• Dense Connective Tissue
• Adipose Tissue
• Cartilage
• Bone
• Blood

Subtypes of Epithelial Tissue

• Simple Squamous
• Simple Cuboidal
• Simple Columnar
• Stratified Squamous
• Pseudostratified Ciliated Columnar

Subtypes of Muscle Tissue

• Skeletal
• Cardiac
• Smooth

Neurone Excitation

• Signal Reception: Dendrites receive signals, which then travel to the soma (cell body).
• Action Potential: An action potential travels along the axon, which can be up to 1.5 meters long.
• Signal Transduction: This involves neurotransmitters.
• Membrane Potential Changes: Brief, rapid, and large changes occur in the membrane potential.
• Localized Activity: Only a small part of the axon plasma membrane is involved.
• Communication Method: It’s a basic method of communication in the nervous system.
• Long-Distance Signaling: Allows for long-distance signaling.

Myelination

• Function of Myelin Sheaths: Axons are insulated by myelin sheaths, which greatly increase the rate at which axons conduct action potentials and conserve energy.
• Composition of Myelin: Myelin is made of the lipid sphingomyelin and is formed by glial cells.
• Formation Process: Glial cells wrap layers of their plasma membrane in a tight spiral around the axon.
• Current Leakage: This process generates little current leakage.
• Nodes of Ranvier: The myelin sheath is regularly interrupted at nodes of Ranvier, where almost all $Na^+$ channels in the axon appear.
• Myelinated Retinal Nerve Fibres: White clouds surrounding the optic disc represent a congenital anomaly called myelinated retinal nerve fibres.
  • Myelination typically does not extend onto the retina.
  • When it does, these clouds appear permanently adjacent to the optic disc but do not interfere with vision.

Synapses

• Connection Type: Synapses connect neurones to other neurones or other cells.
• Electrical Synapses (Rare): Charge flows directly from one neurone to the next, requiring direct contact for rapid, unbroken transmission.
• Chemical Synapses: These use neurotransmitters like acetylcholine to transmit information in one direction across the gap between two neurones.
• Neurotransmitters: These are endogenous chemicals that transmit signals from a neurone to a target cell across a synapse.
• Action Potential and Neurotransmitter Release: When the action potential reaches the synapse, a chemical neurotransmitter is released from synaptic vesicles.

Connective Tissue Functions

• Mechanical Support and Strength: Provides structural integrity.
• Protection, Cushioning, and Insulation: Protects against damage and maintains temperature.
• Organisation/Compartmentalisation: Structures tissues and organs.
• Metabolic Support: Facilitates nutrient transport and waste removal.
• Cell-Dependent Immune Response: Some cells are involved in the immune response.
• Function Dependence: Functions depend on connective tissue type, matrix constituents, proportions of matrix components, organisation, and ability to interact.
• Functional Property Changes: Any change in quantity, structure, type, or organisation results in a change in functional property.

Connective Tissue Structures

• Rope-like: Tendons, ligaments.
• Tubular: Blood vessels, intestine.
• Gels: Vitreous.
• Membrane-like: Basal lamina/basement membrane, such as in the lens capsule and Descemet’s membrane.
• Protective: Skin, sclera, cornea; also has a repairing function (scar tissue).
• Weight-bearing: Cartilage, intervertebral disc.
• Skeletal: Bone.
• Transparent: Cornea.

Types of Connective Tissue

• Areolar (Loose) Connective Tissue
  • Holds organs and epithelia in place.
  • Contains a variety of loose fibres (high in levels of protein), including collagen and elastin.
• Fibrous (Dense) Connective Tissue
  • Forms dermis, ligaments, and tendons.
  • May be ‘irregular’ or ‘regular’ dense.
  • Densely packed collagen fibres with high tensile strength.
• Special Types of Connective Tissue
  • Blood: Fluid matrix with cells.
  • Adipose: Predominantly cells surrounded by thin matrices; comprised of adipocytes that store energy via triglycerides.
  • Bone: Hard connective tissue with a rigid matrix of collagen fibres embedded in a mineralised matrix containing hydroxyapatite $(CaPO_4)$.
  • Cartilage: Matrix produced by chondroblasts, which form chondrocytes (found in chambers called lacunae); types include hyaline, fibrous, and elastic cartilage.

Connective Tissue Component Cells

• Resident Cells
  • Fibroblasts: These are the predominant cells in connective tissue, responsible for secretion and maintenance of the matrix; fibroblasts can differentiate into myofibroblasts.
  • Other cell types include osteocytes, osteoclasts, and osteoblasts (in bone), as well as chondrocytes and chondroblasts (in cartilage).
  • Macrophages and Mast Cells: These cells are involved in immune response.
  • Adipose Cells: Responsible for fat (energy) storage.
• Transient Cells
  • Blood Cells: Including erythrocytes, lymphocytes, neutrophils, eosinophils, basophils, monocytes, and platelets.

Blood Characteristics

• Circulation: Blood circulates throughout the body, transporting substances essential to life.
• Physical Properties: It is denser and more viscous than water.
• Temperature: Approximately 37°C.
• pH: Ranges from 7.35 to 7.45.
• Weight: Accounts for approximately 8% of body weight (5-6 litres in males; 4-5 litres in females).
• Composition: Comprises approximately 55% plasma and 45% cells.

Plasma Functions

• Temperature Regulation: Regulates body temperature.
• Water Content Regulation: Regulates water content of cells (osmotic pressure).
• pH Maintenance: Maintains a pH of approximately 7.4.
• Biomolecule Transport: Plasma assists in the transport of small molecules such as vitamin C and iron (hydrophilic), and triglycerides, cholesterol, and vitamins A and E (hydrophobic).
• Blood Clotting: Role in blood clotting (fibrinogen).
• Immunology: Roles in immunology (immunoglobulins and complement protein).

Plasma Components

• Albumins: Maintain osmotic balance and bind to lipophilic molecules; produced by the liver.
• Globulins: α and β types transport chemicals (e.g., thyroid hormone and iron), clotting factors (produced by the liver); γ globulins are immunoglobulins (antibodies) produced by lymphocytes.
• Fibrinogen: Involved in blood clotting, produced by the liver.
• Other Proteins: Include lipoproteins and complement (enzyme cascade that helps defend against infection via activation of a local inflammatory response).
• Other Solutes: Include inorganic constituents (e.g., $Na^+, Cl^-, K^+, Ca^{2+}$), nutrients (e.g., glucose, amino acids, micronutrients), waste products (e.g., urea), dissolved gases (e.g., $O<em>2$ & $CO</em>2$), and hormones.

Cells and Cell Fragments (Formed Elements)

• Erythrocytes (Red Blood Cells): >99% - transport $O<em>2$ to cells and remove $CO</em>2$.
• Leucocytes (White Blood Cells): Immunity, allergic reactions, phagocytosis.
• Thrombocytes (Platelets): Blood clotting.

Erythrocytes (RBCs)

• Shape: Flattened cells - biconcave discs.
• Size: ~7-8 µm in diameter.
• Organelles: RBCs lack a nucleus and mitochondria.
• Function:
  • Carry $O<em>2/CO</em>2$ via haemoglobin.
  • One Hb carries 4 $O_2$ molecules.
  • Hb has 4 polypeptide chains: $α<em>1, β</em>1, α<em>2, β</em>2$, each carrying a haem group (containing an Fe group).
• Haemoglobin Count: 280 million haemoglobin molecules / erythrocyte.
• Haematocrit: % of total blood volume occupied by RBCs; about 42% for females & 45% for males.
• Total Count: Humans have a total of $25 \times 10^{12}$ RBCs (about 1/3 of all the cells in the body).

Erythrocyte Manufacture

• Continuously manufactured in red marrow of long bones, ribs, skull, and vertebrae.
• Iron from dietary sources ($\sim 0.5-2$ mg) and stored in the liver ($\sim 1000$ mg) and muscle ($\sim 300$ mg).
• Iron is transported via transferrin ($\sim 3$mg).
• Macrophages also contribute to the process.

Leucocytes (WBCs)

• Volume: < 1% blood volume
• Types: 5 different types
• Function: Function in the cellular immune response
• Size and Structure: Larger than RBCs, have a nucleus and typical organelles - lack Hb
• Lifespan: Live for a few hours or a few days (B and T lymphocytes remain in the body for years)
• Characteristics: Chemotaxis, amoeboid movement, leak through walls of blood vessels, phagocytic

Functions of Granular WBCs

• Neutrophils: Respond first to bacteria, enter tissue by entering capillary walls; phagocytic (bacteria & cellular debris); release enzymes destroying bacteria (e.g., lysozyme); important in inflammation.
• Basophils: Similarly to mast cells, synthesise & store vasodilator histamine (released during inflammation) & heparin (an anticoagulant); histamine and serotonin in allergic reactions that assist the inflammatory response.
• Eosinophils: Combat the effects of histamine in allergic reactions, phagocytise antigen-antibody complexes, produce reactive oxygen species; help break down blood clots; fight against parasites.

Functions of Agranular WBCs

• Monocytes: Release WBC growth factors (increasing numbers of WBCs); transform to macrophages, which phagocytose debris.
• Lymphocytes: Fight infection and provide an immune response.
  • B-cells have receptors for antigens; endocytose antigens; interact with Helper T cells and produce antibodies.
  • T-cells include Helper T cells, Cytotoxic T cells, and Memory T cells.
  • Natural killer cells attack infectious microbes and some tumour cells.

Platelets

• Nucleus: No nucleus.
• Importance: Important to clotting.
• Secretions: Secrete numerous chemicals.
• Contraction: Contain actin and myosin.
• Formation: Formed from cell fragmentation (fragments that bud off from megakaryocytes in bone marrow).
• Lifespan: Functional for approximately 10 days before being removed by macrophages in the liver and spleen.

Extracellular Matrix (ECM) Components

• Collagen: Most abundant protein in the body - 28 types - collagen fibrils (e.g., sclera: types I, III; cornea: types I & V).
• Network-forming collagens (e.g., Basement membrane: type IV) surround muscle & fat cells.
• Anchoring fibrils (e.g., Type VII) in epithelial membranes and FACIT (fibril associated collagens with interrupted triple helices).
• Proteoglycans
• Resident cells
• Glycoproteins (e.g., laminin)
• Elastic fibres (elastin & fibrillin) e.g., suspensory lens zonules

Epithelial Tissue

• Location: Covers body surfaces, lines organs, body cavities (mesothelium), blood vessels (endothelium), and ducts.
• Formation: Forms glands (glandular epithelium).
• Classification: Either simple or stratified (based on morphology, i.e., shape).

Epithelial Tissue Functions

• Protection: Protects deeper tissues from injury, pathogens, and dehydration. (e.g., Skin protects underlying tissues; cilia in intestines protect against bacteria.)
• Secretion: Releases enzymes, hormones, and fluids into the body or cavities. (e.g., Glandular epithelium secretes enzymes and hormones.)
• Absorption: Allows the uptake of nutrients, gases, and other substances from the external environment or body cavities. (e.g., Intestinal epithelium absorbs nutrients from food.)
• Excretion: Removes waste products from the body or body cavities. (e.g., Kidney epithelium excretes waste; sweat gland epithelium excretes sweat.)
• Filtration: Filters and cleanses fluids or gases passing through the epithelial layer. (e.g., Respiratory epithelium filters air; kidney epithelium filters blood.)
• Diffusion: Facilitates the passive movement of molecules across the epithelial layer. (e.g., Simple squamous epithelium allows for selective diffusion.)
• Sensory Reception: Contains sensory nerve endings that detect external stimuli. (e.g., Epithelium of the ear with stereocilia for hearing and balance; taste buds in tongue epithelium.)

Simple Epithelium

• Simple Squamous
  • Very thin and flat.
  • Functions: filtration, diffusion, osmosis & secretion.
  • Found as inner lining of cornea, glomerulus of kidney, alveoli of lungs, blood and lymphatic vessels, etc.
• Simple Cuboidal
  • Functions: secretion and absorption.
  • Found in anterior lens surface, retinal pigment epithelium (RPE), duct linings of many glands, ovary surface, etc.
• Simple Columnar
  • Functions: secretion, absorption & moving substances.
  • Either ciliated (line upper respiratory tract, uterus & tubes, etc.) or non-ciliated (line GI tract - have mucus-secreting goblet cells & absorptive cells with microvilli, line ducts of many glands, etc.).
• Pseudostratified Columnar
  • Unique nature occurs as tall, thin cells intertwine.
  • Functions: Either ciliated (secretion & movement of mucus etc.) or non-ciliated (absorption & protection etc.).
  • Found either ciliated (upper/lower respiratory tract etc.) or non-ciliated (ducts of larger glands or male urethra etc.).

Stratified Epithelium

• Stratified Squamous
  • Cells flatten - forms epidermis - cells harden with age (keratinisation).
  • Functions: protection (1st line of defense).
  • Found in the epidermis (highly keratinised with nuclei absent in outer layer), lining of the mouth, oesophagus & vagina (moderately keratinised), corneal epithelium (non-keratinised), etc.
• Stratified Columnar
  • Functions: secretion & protection.
  • Found in conjunctiva (mucus-secreting membrane lining eyelids – also protects), in parts of urethra, large excretory ducts of some glands, etc.
• Stratified Cuboidal
  • Functions: protection, secretion, or absorption.
  • Found in ducts of sweat glands, glands in the oesophagus, male urethra, etc. – usually in 2 layers of cells.
• Stratified Transitional
  • Functions: allows distention.
  • Found in the transitional epithelium (squamous = stretched, cuboidal = relaxed) of the lining of the bladder, parts of the urethra, and ureters, etc.

Muscle Tissue Types

• Skeletal: attached to bone and supports and moves the skeleton – under voluntary control = striated muscle.
• Cardiac: heart muscle controlled by the autonomic nervous system, hormones etc. = striated muscle.
• Smooth: found in blood vessels and surrounds organs etc. – controlled by the autonomic nervous system, hormones etc. = unstriated muscle.

Muscle Structure

• Muscle Cell: Fibre bundles contain hundreds of myofibrils that run the length of the fibre in parallel.
• Myofibril: Each myofibril is a linear arrangement of repeating sarcomere units.
• Sarcomere: Each sarcomere is capped at the end by a transverse tubule (t-tubule) that is an extension of the sarcolemmal membrane; surfaces of sarcomeres are covered by sarcoplasmic reticulum.
• Myofilaments: Myofibrils contain thin (actin, tropomyosin, and troponin) and thick (myosin) filaments.

Sarcomere Structure

• Bands: Comprise alternating dark A bands and light I bands.
• H Zone: At the centre of the A band is the H zone (lesser density).
• Z Line: At the middle of the I band is the Z line, which is very dense and narrow.
• Thick Filaments: Have a diameter of approximately 15nm (myosin).
• Thin Filaments: Have a diameter of approximately 9nm (actin, tropomyosin, and troponin).
• Sarcomere Length: Sarcomeres are 2.3µm in length - during contraction muscle shortens to 1/3 of its length.
• Sliding-Filament Model: Explains contraction as filaments slide past each other, reducing lengths of H zone and I band.

Molecular Mechanism of Contraction

• Resting State: At rest, S1 heads of myosin are unable to interact with actin due to interference by regulatory protein tropomyosin.
• Action Potential: Causes the release of $Ca^{2+}$ from the sarcoplasmic reticulum.
• Calcium Binding: $Ca^{2+}$ binds to troponin on thin filaments, causing tropomyosin to uncover cross-bridge binding sites on actin.
• Cross-Bridge Formation: Energised myosin S1 heads bind to actin, leading to cross-bridge formation.
• Power Stroke: Cross-bridge binding allows energy release from myosin, causing angular movement of each cross bridge (i.e., power stroke) with ADP and Pi release.
• ATP Binding: ATP binds to myosin, causing dissociation between actin and myosin.
• Hydrolysis: ATP bound to myosin is hydrolysed to ADP and Pi, and the conformation of myosin returns to its original state.
• Contraction: Cross-bridge binding/unbinding causes contraction and continues as long as $Ca^{2+}$ remains bound to troponin.

Muscle Type Characteristics

Visual Pathway and Receptive Fields

Lecture Contents

• Receptive Fields
• The visual pathway beyond the retina
• The importance of receptive fields in clinical vision assessment

Cell Types in the Retina

• Photoreceptors (rods and cones)
• Bipolar Cells
• Retinal Ganglion Cells
• Horizontal cell
• Amacrine cells

Retinal Ganglion Cells

• Midget (P cells)
• Parasol (M cells)

Horizontal and Amacrine Cells

• Communication between Bipolar cells or RGCs.
• Feedback information to photoreceptors (horizontals) or bipolars (amacrines).
• Communicate with other horizontal/amacrine cells through gap junctions.
• Shape receptive fields.
• Possible role in colour coding

Receptive Fields

• The receptive field of a cell that transmits visual signals is:
• The area of the retina over which a light stimulus can change the activity of that cell.

Receptive Fields: Bipolar Cells

• Each bipolar cell receives a direct input from a group of photoreceptors.
• ON-centre bipolars are excited by light hitting these photoreceptors, OFF-centre bipolars are inhibited.
• Surrounding photoreceptors also synapse with bipolar cell indirectly via horizontal cell.
• Horizontal cells add an opponent signal to receptive field and introduce centre-surround antagonism

Receptive Fields: Retinal Ganglion Cells

• Centre-surround organisation of bipolar cell receptive fields is passed on to ganglion cells.
• RGC receptive fields modified by amacrine cells.
• There are ON-centre RGCs (respond strongly to light on centre of receptive field and dark on surround)
• There are OFF-centre RGCs (respond strongly to dark on centre of receptive field and light on surround).

Consequences of Centre-Surround Organisation

• Centre-surround organisation manifests as spatial antagonism (or lateral inhibition).
• Spatial tuning
• Visual system responds strongly to luminance boundaries i.e. local contrast and less strongly to even, unchanging areas of luminance.
• Ganglion cells are spatially tuned to spots of different sizes (different RGCs are tuned to different sized spots of light).

Spatial Tuning

• Ganglion cell will respond most strongly to a stimulus of a certain size – any larger or smaller and response is reduced
• Retina contains numerous ganglion cells with differently sized receptive fields

ON and OFF Pathways

• Bipolar & ganglion receptive fields can be ON- centre or OFF- centre.
• ON-centre respond to light pattern on dark or light ONSET.
• OFF-centre respond to dark pattern on light or light OFFSET.
• Distinct ON- and OFF- pathways through the retina

Chromatic and Achromatic Pathways

• Also have separate achromatic and chromatic pathways to visual cortex…
• Achromatic pathways = compare brightness of image across the retina (local contrast between light and dark).
  • L-cones and M–cones are responsible for achromatic pathway through retina.
• Chromatic pathways = compare wavelength of light across the retina (simultaneous colour contrast).
  • L-cones , M-cones and S-cones responsible for colour pathways through retina.

Chromatic Receptive Fields

• Some retinal receptive fields are chromatic…
• The cells with L-cone centres receive antagonistic signals from M-cones in the surround of their receptive field and vice versa.
• Blue ON- pathway receives antagonistic input from yellow light (combined response from L-cones and M-cones) feeding into the receptive field
• (Note: GC receptive fields for blue/yellow pathway don’t have a concentric centre-surround configuration. Their ON- and OFF- portions are co-extensive) Red ON / Green OFF
• Green ON / Red OFF
• Red OFF/ Green ON
• Green OFF/ Red ON
• Blue ON/ Yellow OFF
• Blue OFF/ Yellow ON

Receptive Fields: Resolution (Acuity) vs Sensitivity

• Convergence: determines size of receptive fields
• Human retina: 126 million photoreceptors : 1 million ganglion cells
• Rod system has lots of convergence (120:1) – sensitive but poor resolution
• Cone system has little convergence (6:1) – less sensitive but better resolution; Convergence even less in foveal cones (1:1)

Receptive Fields: Rods

• High Sensitivity
• Poor Resolution

Receptive Fields: Cones

• General rule of thumb:
  • Large receptive fields = high sensitivity, low resolution
  • Small receptive fields = low sensitivity, high resolution

Retinal Ganglion Cells in Primates

• P-cells (~80%)
  • Start of the Parvocellular pathway
  • Also known as tonic cells
  • They show colour anatagonism
  • Small receptive fields – Most sensitive to high spatial frequencies and have good acuity
  • Retinal midget cells
• M-cells (~10%)
  • Start of the Magnocellular Pathway
  • Also known as phasic cells
  • Big response to transient/fast moving stimuli
  • Most sensitive to low spatial frequencies, poor acuity
  • Retinal parasol cells
    *K-cells
  • About 10% of retinal ganglion cells
  • Start of Koniocellular pathway
  • Newly characterised
  • Moderately slow conduction velocity
  • Moderate spatial acuity
  • Carry blue-yellow colour component information
  • Retinal bistratified ganglion cells

Parallel Pathways

• Distinct and separate processing and transmission through visual pathway
  • e.g. ON vs. OFF / Chromatic vs. achromatic
• All carried in 3 major channels: parvocellular, magnocellular and koniocellular

Rod Processing

• Rods mainly contribute to Magnocellular pathway
• Cones contribute to both Magnocellular and Parvocellular pathways
• Parasol ganglion cells receive dual input from rods (via AII and A17 amacrines) and cones.
• Rod system has larger receptive fields which are more diffuse (less centre-surround antagonism). Also has no OFF pathway

The Visual Pathway Beyond the Eye

• The Lateral Geniculate Nucleus (LGN)(Thalamus)
• Superior colliculus
• Optic radiation
• Pulvinar nucleus

The Lateral Geniculate Nucleus (LGN)

• Contains 6 layers.
  • Layers 1-2: magnocellular layer
  • Layers 3-6: parvocellular layer
  • Between layers: Koniocellular cells

The Striate Cortex

• Located in the occipital lobe of the brain.
• Brodmann Area 17
• Primary Visual Cortex