[HISTO]LEC_001_INTRODUCTION TO CELL V1.pdf

(001) HISTOLOGY DR. CABUENA | 09/14/2020 A. TWO INTERACTING COMPONENTS: 1. Cells- p...

(001) HISTOLOGY DR. CABUENA | 09/14/2020 A. TWO INTERACTING COMPONENTS: 1. Cells- produce the ECM OUTLINE 2. Extracellular matrix (ECM)- supports the cells and I. HISTOLOGY the fluid that transports nutrients to the cells, and A. Two Interacting Components of Histology carries away their catabolites and secretory 1. Cells products. 2. Extracellular Matrix (ECM) II. CELLS II. CELLS A. Cell Differentiation III. CYTOPLASMIC ORGANELLES Cells are the basic structural and functional units, the smallest A. Cytoplasm living parts of the body. B. Cytosol IV. PLASMA MEMBRANE (PLASMALEMMA)  Animal cells are eukaryotic (Gr. eu, good, + karyon, nucleus), A. Lipids B. Proteins Eukaryoticcells contain true nucleus enclosed by a 1. Integral Proteins nuclear membrane or envelope. 2. Peripheral Proteins  Bacteria are prokaryotic V. TRANSMEMBRANE PROTEINS & MEMBRANE TRANSPORT A. General Mechanism Has cell wall around the plasmalemma and lack 1. Simple Diffusion other membranous structures, including an envelope 2. Osmosis around their DNA. B. Mechanism of Transport of Molecule C. Vesicular Transport Prokaryotic cell lacks a nuclear envelope and the nuclear substances are mixed or in direct contact 1. Endocytosis with the rest of the protoplasm. Phagocytosis Pinocytosis  The principal parts of the cell are the Cell Membrane, Receptor-mediated endocytosis Cytoplasm, and Nucleus. VI. SIGNAL RECEPTION & TRANSDUCTION  In Hematoxylin and Eosin stained preparations, cell A. Gap Junctions membrane is not clearly distinguishable, cytoplasm B. Different Routes of Signal Molecules appears pinkish or reddish, and nucleus appears intensely 1. Endocrine Signaling blue or purple in color (See Figure 1) 2. Paracrine Signaling 3. Synaptic Signaling 4. Autocrine Signaling 5. Juxtacrine Signaling VII. MEMBRANE RECEPTORS A. Channel-linked receptors B. Enzymatic receptors C. G-protein–coupled receptors VIII. RIBOSOMES IX. ENDOPLASMIC RETICULUM X. GOLGI APPARATUS XI. LYSOSOMES XII. PROTEASOMES XIII. MITOCHONDRIA XIV. PEROXISOMES XV. CYTOSKELETON Figure 1: Cell under the microscope. The nucleus appears XVI. INCLUSIONS as blue or purple while the cytoplasm is pinkish or reddish. XVII. NUCLEUS XVIII. NUCLEOSOME A. CELL DIFFERENTIATION XIX. THE CELL CYLE A. Four Distinct Cycle  Specialization process B. Meiosis  cells synthesize increased quantities of specific proteins and become very efficient in specialized functions Example: Muscle cell precursors elongate into fiber I. HISTOLOGY like cells containing large arrays of actin and myosin. All animal cells contain actin filaments and myosin, Histo meaning “tissue” or “web” but muscle cells are specialized for using these - The microscopic study of the tissues of the body and how proteins to convert chemical energy into forceful these tissues are arranged to constitute organs. contractions Tissues – a group of cells with similar structure and function PREPARED AND EDITED BY: LIMBAUAN, J., LIVED, R., LOCQUIAO, C., LOPEZ, F., PADOLINA, J., PALAGANAS, B., PANG-AG, L.  (001) HISTOLOGY DR. CABUENA | 09/14/2020  CYTOSOL ○ contains hundreds of enzymes, e.g. glycolytic pathway, that produce building blocks for larger molecules and break down small molecules to liberate energy ○ All the machinery converging on the ribosomes for protein synthesis (mRNA, transfer RNA, enzymes, and other factors) is also contained within the cytosol ○ Oxygen, CO2, electrolytic ions, low-molecular weight substrates, metabolites, and waste products all diffuse through cytosol, either freely or bound to proteins, entering or leaving organelles where they are used or produced IV. PLASMA MEMBRANE (PLASMALEMMA) outermost component of the cell, separating the cytoplasm from its extracellular environment defines the outer limit of the cell contains proteins called integrins linked to both cytoplasmic protein filaments and ECM components functions as a selective barrier regulating the passage of materials into and out of the cell and facilitating the transport of specific molecules IMPORTANT FUNCTION: keep constant the ion content of cytoplasm, which differs from that of the extracellular fluid III. CYTOPLASMIC ORGANELLES Two basic parts:  Membranes range from 7.5 to 10 nm in thickness ○ Cytoplasm (Gr. kytos, cell, + plasma, thing formed) that  Membrane phospholipids are amphipathic: surrounds ○ Nucleus (L. nux, nut) - consisting of two nonpolar (hydrophobic or water repelling) long-chain fatty acids linked to a charged  PLASMA MEMBRANE (Plasmalemma) polar (hydrophilic or water-attracting) head that bears a  CYTOPLASM phosphate group ○ consists largely of a fluid component, cytosol, bathing  Membranes of animal cells have as their major lipid components metabolically active structures, the organelles, which may phospholipids and cholesterol be membranous (such as mitochondria) or nonmembranous protein complexes (such as ribosomes A. LIPIDS (in the membrane structure) and proteasomes) ○ the colloidal suspension of the cell ○ provide important antigenic and functional properties to the cell surface - cytoplasmic cytoskeleton - determines the shape and motility of eukaryotic cells ○ Phospholipid and Cholesterol – major lipid components - Inclusions - minor cytoplasmic structures that are of membranes of animal cell generally deposits of carbohydrates, lipids, or pigments - Organelles – permanent components of the cytoplasm Phospholipid – amphipathic; phosphate group charge on polar head; two, long nonpolar fatty acid chains (straight if saturated or kinked if unsaturated) Cholesterol – also amphipathic; affects the packing of the fatty acid chains, with a major effect on membrane fluidity ○ Glycolipids – has carbohydrate chains that extend outward from the cell surface; contribute to a delicate cell surface coating called glycocalyx Figure 2. The amphipathic nature of phospholipids produces the bilayer structure of membranes PREPARED AND EDITED BY: LIMBAUAN, J., LIVED, R., LOCQUIAO, C., LOPEZ, F., PADOLINA, J., PALAGANAS, B., PANG-AG, L.  (001) HISTOLOGY DR. CABUENA | 09/14/2020 Figure 3. General structure of a phospholipid B. PROTEINS ○ Major constituents of membranes (~50% by weight in the plasma membrane) 1. Integral proteins - directly incorporated or firmly embedded within the lipid bilayer - Can be extracted only by using detergents to disrupt the lipids 2. Multipass proteins – polypeptide chain of many integral Figure 4. Membrane proteins proteins that span the membrane, from one side to another, several times 3. Channels – multipass proteins forming transmembrane pores through which ions or small molecules pass selectively V. TRANSMEMBRANE PROTEINS & MEMBRANE 4. Transmembrane proteins – protein that completely span TRANSPORT the bilayer 5. Peripheral proteins - exhibit a looser association with Plasma membrane is the site where materials are exchanged between the cell and its environment. one of the two membrane surfaces, particularly on the A. GENERAL MECHANISM cytoplasmic side - Can be extracted with salt solutions ○ Passive Transport – movement of substances down/along a concentration gradient due to the kinetic energy of the ○ Membrane proteins serve as receptors for various signals substance. coming from outside cells, as parts of intercellular - Energy is NOT required. connections, and as selective gateways for molecules - It continues until it reached equilibrium entering the cell. 1. Simple diffusion ○ Membrane proteins comprise a moveable mosaic within - Small, lipophilic (fat-soluble) molecules can pass the fluid lipid bilayer (fluid mosaic model). through lipid bilayers ○ Unlike lipids, lateral diffusion of many membrane proteins - requiring no energy is often restricted by their cytoskeletal attachments. - unassisted movement of small non-polar substances along the concentration gradient. - Example: exchange of O2 and CO2 in the blood and tissues 2. Osmosis - passive movement through multipass transmembrane proteins called aquaporins - requiring no energy - diffusion of water across a selectively permeable membrane 3. Facilitated Diffusion  movement of ions and small polar molecules along the concentration gradient by a transport protein or by carrier molecules  Channel-mediated – movement through a protein channel (ex. Sodium moves through a sodium channel)  Carrier-mediated – movement through a carrier protein (ex. Transport of Glucose) ○ Active Transport - movement of substances up/against the concentration gradient. It requires energy. 1. Primary Active Transport - powered by ATP (ex. Sodium-Potassium Pump, Calcium Pump) PREPARED AND EDITED BY: LIMBAUAN, J., LIVED, R., LOCQUIAO, C., LOPEZ, F., PADOLINA, J., PALAGANAS, B., PANG-AG, L.  (001) HISTOLOGY DR. CABUENA | 09/14/2020 2. Secondary Active Transport - powered by harnessing B. MECHANISMS OF TRANSPORT OF MOLECULES the energy of a second substance. The energy comes from the concentration gradient of another ○ Ions such as Na+, K+, and Ca2+ cross membranes by passing through integral membrane proteins that act as ion 3. Symport - movement of substances in the same channels or ion pumps direction of Sodium (ex. Sodium/Glucose Transport) ○ Lipophilic and some small, uncharged molecules can 4. Antiport - movement of substances opposite to the cross membrane direction of sodium (ex. Sodium/Hydrogen Transport) ○ Most ions are transported through membranes in proteins whose structure includes an ion specific channel ○ Larger, water-soluble molecules require binding to sites on selective carrier proteins or transporter Figure 5. Mechanisms of Transport across the Plasma Membrane C. VESICULAR TRANSPORT – a vesicle is formed or lost as material is brought into a cell/ released from the cell ○ Endocytosis: bulk movement of substances into the cell or movement of materials into the cell by vesicles 1. Phagocytosis/Cell Eating is a type of Endocytosis wherein solid particles are ingested. A part of the cell membrane extends around the particle and fuses so that the particle is surrounded by the membrane. That part of the membrane “pinches off” to form a vesicle containing the particle. The vesicle is now within the cytoplasm of the cell. White blood cells will phagocytize the bacteria, cell debris, and foreign particles. 2. Pinocytosis/Cell Drinking is a type of Endocytosis wherein it is similar to phagocytosis; however, smaller vesicles are formed, and the vesicles contains fluid rather than particles. The vesicles are described as “drop-like invaginations” 3. Receptor-mediated endocytosis includes membrane proteins called receptors that bind specific molecules (ligands). When many such receptors are bound by their ligands, they aggregate in one membrane region, which then invaginates and pinches off to create a vesicle or endosome containing both the receptors and the bound ligands. ○ Exocytosis – cytoplasmic vesicle containing the molecules to be secreted fuses with the plasma membrane, resulting in the release of its contents into the extracellular space without compromising the integrity of the plasma membrane Exocytosis occurs via either of two pathways: 1. Constitutive secretion – used for products that are released from cells continuously as soon as PREPARED AND EDITED BY: LIMBAUAN, J., LIVED, R., LOCQUIAO, C., LOPEZ, F., PADOLINA, J., PALAGANAS, B., PANG-AG, L.  (001) HISTOLOGY DR. CABUENA | 09/14/2020 synthesis is complete. Ex: collagen 2. Regulated secretion – occurs in response to signals coming to the cells. Ex: release of A. GAP JUNCTIONS digestive enzymes from pancreatic cells in response to specific stimuli ○ Communicating junctions that couple adjacent cells and allow the exchange of ions and small molecules B. Signal molecules can take different routes: 1. Endocrine Signaling – the signal molecules (called hormones) are carried in the blood to target cells throughout the body. These signals affect the cells that are distal from their source 2. Paracrine Signaling – the chemical mediators are rapidly metabolized after release so that they act only on local cells very close to the source (ex. Histamine) 3. Synaptic Signaling – a special kind of paracrine interaction, neurotransmitters act only on adjacent cells through special contact areas called synapses 4. Autocrine Signaling – stimulates the cell that originally secreted it (ex. WBC) 5. Juxtacrine Signaling – important in early embryonic tissue interactions, signaling molecules such as proteins remain part of a cell membrane and bind surface receptors of the target cell when the two cells make direct physical contact. VII. MEMBRANE RECEPTORS MAJOR TYPES OF MEMBRANE RECEPTORS A. CHANNEL-LINKED RECEPTORS – bind ligands such as neurotransmitters and open to allow influx of specific ions B. ENZYMATIC RECEPTORS – usually protein kinases that are activated to phosphorylate (and usually activate) other proteins upon ligand binding. C. G-PROTEIN–COUPLED RECEPTORS – bind ligand, changing the conformation of its G-protein subunit, allowing it to bind GTP, and activating and releasing this protein to in turn activate other proteins such as ion channels and adenyl cyclase Figure 6. Three major forms of endocytosis ○ Membrane Trafficking – Process of membrane movement and recycling.  In endocytosis – portions of cell membrane become part of the endocytotic vesicles or vacuoles  In exocytosis – membrane is returned to the cell surface VI. SIGNAL RECEPTION & TRANSDUCTION Cell use about 25 families of receptors Each cell type contains a distinctive set of cell surface and cytoplasmic receptor protein Cells bearing receptors for a specific ligand are referred to as target cells for that molecule Ligands binding to receptors in a cell membrane can be considered first messenger, beginning a process of signal transduction. PREPARED AND EDITED BY: LIMBAUAN, J., LIVED, R., LOCQUIAO, C., LOPEZ, F., PADOLINA, J., PALAGANAS, B., PANG-AG, L.  (001) HISTOLOGY DR. CABUENA | 09/14/2020  Export the polypeptide produced to the cytoplasm where it will form a functional pattern. IX. ENDOPLASMIC RETICULUM A convoluted membranous network in the cytoplasm of most cells It is described as an extensive system of membrane-bound canaliculi Provides a major site for vital cellular activities, incl. biosynthesis of proteins and lipids Figure 7. Major types of membrane receptors VIII.RIBOSOMES Ribo (ribonucleic acid), soma (Latin for body) small electron-dense particles, about 20 × 30 nm in size Cell organelle Figure 8. Differentiation of free polysomes and bound polysomes Micro machine for protein making An anastomosing network of intercommunicating channels or cisternae formed by a continuous membrane, with some regions Temporary existence (when they have synthesized a polypeptide, that bear polysomes appearing rough and other regions the 2 subunits separate and either reused or broken up) appearing smooth Ribosomes can join up amino acids at a rate of 200/min FUNCTIONS: Ribosomes found in the cytosol are composed of four segments 1. Synthesis: Provides a place for chemical reactions of rRNA and approximately 80 different proteins a. Smooth ER is the site of lipid synthesis and carbohydrate metabolism The rRNA molecules in the ribosomal subunits provide structural b. Rough ER synthesizes proteins for secretion, support. It also positions tRNA molecules bearing amino acids in incorporation into the plasma, membrane, and as the correct reading frame and catalyze formation of the peptide enzymes within lysosomes bonds 2. Transport: Moves molecules through cisternal space from During protein synthesis, many ribosomes bind the same strand one part of the cell to another, sequestered away from the of mRNA to form larger complexes called polyribosomes or cytoplasm polysomes 3. Storage: Stores newly synthesized molecules 4. Detoxification: Smooth ER detoxifies both drugs and Bound to mRNA, all ribosomes have two subunits of different alcohol. sizes and act to catalyze the process of protein translation A. ROUGH ENDOPLASMIC RETICULUM/ GRANULAR TRANSLATION of information and the Linking of AMINO ACIDS RETICULUM are at the heart of protein production ○ Appears as parallel stacks of flattened cisternae Under the Electron Microscope, the Ribosomes appear as dense granules. The ribonucleoprotein of the ribosome is largely ○ Prominent in cells specialized for protein secretion. Ex: responsible for the affinity of the cytoplasm to basic dye. Hence, pancreatic acinar cells (making digestive enzymes), in light microscope, areas rich in Ribosomes are intensely fibroblasts (collagen), and plasma cells (immunoglobulins) basophilic. ○ Site for synthesis of most membrane-bound proteins, proteins of many membranous organelles, and proteins to FUNCTIONS: be secreted for exocytosis  Translate encoded information from the cell nucleus ○ RER has a highly regulated system to prevent provided by mRNA (determines the order by which the nonfunctional proteins from being forwarded to the pathway amino acids are linked together) for secretion or to other organelles  Link together amino acids selected and collected from the ○ Destinations of proteins synthesized by RER: cytoplasm by transfer RNA (tRNA) PREPARED AND EDITED BY: LIMBAUAN, J., LIVED, R., LOCQUIAO, C., LOPEZ, F., PADOLINA, J., PALAGANAS, B., PANG-AG, L.  (001) HISTOLOGY DR. CABUENA | 09/14/2020 2. detoxification of potentially harmful compounds Intracellular storage (lysosomes and specific  Alcohol, barbiturates, and other drugs granules of leukocytes)  In liver cells, these enzymes also process Provisional storage in cytoplasmic vesicles prior to endogenous molecules such as the components of exocytosis (in the pancreas and some endocrine bile cells) 3. sequestration and controlled release of Ca++ ions  well developed in striated muscle As integral membrane proteins  SER has an important role in the contraction process and assumes a specialized for call sarcoplasmic MOVEMENT OF POLYPEPTIDES INTO THE RER reticulum i. RER are prominent in cells specialized for protein secretion (pancreatic acinar cells making digestive enzymes), fibroblasts (collagen), and plasma cell (immunoglobulins) ii. 5′ ends of mRNAs for proteins destined to be segregated in the ER encode an N-terminal signal sequence of 15-40 amino acids that includes a series of six or more hydrophobic residues iii. Newly translated signal sequence is bound by a protein complex called the signal-recognition particle (SRP) iv. SRP-ribosome-nascent peptide complex binds to SRP receptors on the ER membrane. v. SRP releases the signal sequence, allowing translation to continue with the nascent polypeptide chain transferred to a translocator complex vi. Inside the lumen of the RER, the signal sequence is removed by an enzyme, signal peptidase vii. With the ribosome docked at the ER surface, translation continues with the growing polypeptide pushing itself while chaperones and other proteins serve to “pull” the nascent polypeptide through the translocator complex Figure 9. Movement of polypeptides into the ER Figure 9.1 a. Schematic diagram rER and sER; b. EM B. SMOOTH ENDOPLASMIC RETICULUM/ AGRANULAR showing rER, sER, and ribosomes; C. IFM showing ER RETICULUM (green) and mitochondria (orange) ○ its cisternae appear as profusion of interconnected channels of variable shape and size. X. GOLGI APPARATUS ○ lacking polyribosomes, not basophilic, best seen with the ynamic organelle TEM, SER cisternae are more tubular Also called Golgi complex or Dictyosomes ○ Three diverse activities of smooth ER: 1. lipid biosynthesis Has two distinct functional sides or faces: cis face (receiving)  phospholipids and steroids of cell membrane and trans face (shipping)  these lipids are transferred from SER to other Completes posttranslational modifications of proteins membranes by lateral diffusion into adjacent synthesized in the RER and then packages and addresses membranes, by phospholipid transfer proteins, or by these proteins to proper destinations (“LBC”) vesicles  In cells that secrete steroid hormones (cells of Composed of smooth membranous saccules containing adrenal cortex), SER occupies a large portion of the enzymes for these functions cytoplasm Forms transport vesicles and secretory vesicles PREPARED AND EDITED BY: LIMBAUAN, J., LIVED, R., LOCQUIAO, C., LOPEZ, F., PADOLINA, J., PALAGANAS, B., PANG-AG, L.  (001) HISTOLOGY DR. CABUENA | 09/14/2020 Autolysis Materials move from the RER cisternae to the Golgi apparatus in small, membrane-enclosed carriers called transport vesicles XII. PROTEASOMES Cylindrical structure made of four stacked rings, each composed of seven proteins including proteases. At the end of each cylinder is a regulatory particle that contains ATPase and recognizes proteins with attached molecules of ubiquitin. Are very small abundant protein complexes not associated with membrane, each approximately the size of the small ribosomal subunit FUNCTION: 1. to degrade denatured or otherwise nonfunctional polypeptides 2. remove proteins no longer needed by the cell 3. provide an important mechanism for restricting activity of a specific protein to a certain window of time XIII. MITOCHONDRIA (Gr. mitos, thread, + chondros, granule) are membrane-enclosed organelles with array of enzymes specialized for aerobic Figure 10. Diagram of the Golgi apparatus respiration and production of adenosine triphosphate (ATP), with high-energy phosphate bonds, which supplies energy for most cellular activities XI. LYSOSOMES New mitochondria originate by growth and division (fission) of Lysosomes (Gr. lysis, solution + soma, body) are sites of preexisting mitochondria. During cell mitosis, each daughter cell intracellular digestion and turnover of cellular components. receives approximately half the mitochondria in the parent cell. membrane-limited vesicles that contain about 40 different Mitochondrial enzymes yield 15 times more ATP than is hydrolytic enzymes and are particularly abundant in cells with produced by glycolysis alone great phagocytic activity (e.g., macrophages, neutrophils) Usually elongated structures with diameters of 0.5-1 μm and lysosomes digest organelles or membranes by autophagy lengths up to 10 times greater Primary Lysosomes – contains inactive enzymes Are highly plastic, rapidly changing shape, fusing with one another and dividing and are moved through the cytoplasm along microtubules Secondary Lysosomes – involved in enzymatic activities Common lysosomal enzymes are acid hydrolases such as Number of mitochondria is related to the cell’s energy needs: proteases, nucleases, phosphatase, phospholipase, sulfatases, ○ Cells with a high-energy metabolism (eg, cardiac muscle, β-glucuronidase. cells of some kidney tubules) have abundant mitochondria, Lysosomal hydrolases are synthesized and segregated in the whereas cells with a low-energy metabolism have few mitochondria RER and then transferred to the Golgi apparatus, where the enzymes are further modified and packaged in vacuoles and The outer membrane is smooth and the inner membrane has form lysosomes. many sharp folds called cristae Autophagy – removal of excess or nonfunctional organelles. A ○ The number of cristae also corresponds to the energy primary Lysosome with an ingested organelle is called needs of the cell autophagosome and it becomes secondary Lysosome ○ Cristae are more numerous in mitochondria of highly active cells. It enhances the surface area to increase the - During digestion of macromolecules, released efficiency of the organelle in generating energy nutrients diffuse into the cytosol through the lysosomal membrane. Indigestible material is Innermost mitochondrial matrix is a gel containing numerous retained within a small vacuolar remnant called a enzymes residual body. Contain the ATP synthase complexes that generate most of the In some long-lived cells (neurons, heart muscle), residual bodies cell’s ATP can accumulate over time as granules of lipofuscin In pathologic conditions, Lysosomes may rupture, release their enzyme, and destroy the cell from within and it is called PREPARED AND EDITED BY: LIMBAUAN, J., LIVED, R., LOCQUIAO, C., LOPEZ, F., PADOLINA, J., PALAGANAS, B., PANG-AG, L.  (001) HISTOLOGY DR. CABUENA | 09/14/2020 Intermediate Microtubules Microfilaments filaments Arrayed Radiating through Concentrated throughout cytoplasm from beneath cell General cytoplasm; at concentration at membrane; in locations desmosomes; centrosomes; cell extensions inside nuclear axonemes like microvilli envelope Maintains cell’s Contract and Strengthen cell shape and move cells; and tissue polarity; provide change cell structure; Key tracks for shape; maintain cell functions organelle and cytokinesis; shape; maintain chromosome cytoplasmic nuclear shape movement; move transport and (lamins) cilia and flagella streaming Figure 11. Parts of the mitochondria A. MICROTUBULES Mitochondrial Structure & ATP Formation ○ fine tubular structures, organized into larger, more stable 1. Metabolites - pyruvate and fatty acids enter mitochondria via arrays (axonemes) in the cytoplasmic extensions called membrane porins and are converted to acetyl CoA by matrix cilia enzymes of the citric acid cycle (or Krebs cycle) ○ maintains cell shape and rigidity 2. Yield – ATP and NADH (nicotinamide adenine dinucleotide) – major source of electrons for the electron-transport chain ○ move organelles 3. Inner membrane is impermeable to protons, and the result is an electrochemical gradient across the membrane ○ support cilia and flagella 4. Other membrane associated proteins make up the ATP synthase ○ separate chromosomes during cell division systems 5. Hydrophilic pathway that allows protons to flow down the B. MICROFILAMENTS (Actin Filaments) electrochemical gradient 6. Binding adenosine diphosphate (ADP) and inorganic phosphate ○ composed of actin subunits, allow motility and most 7. Production of >100 molecules of ATP/second contractile activity in cells shorter and more flexible than microtubules XIV. PEROXISOMES ○ maintains the cell shape, supports the microvilli, separates two cells during cytokinesis, participates in muscle spherical, membranous organelles, containing enzymes that use contraction O2 to remove hydrogen atoms from fatty acids; produces catalase that degrades hydrogen peroxide to water and O2 C. INTERMEDIATE FILAMENTS - inactivate potentially toxic molecules ○ stable, confer increased mechanical stability to cell Formed in two ways: structure, made up of different protein subunits in different 1. budding of precursors vesicles from ER; or cell types 2. growth and division of pre-existing peroxisomes ○ stabilize junction between cells XV. CYTOSKELETON ○ Intermediate Filaments Protein protein polymers that determine shapes of cells 1. Keratins/ cytokeratins: attach to certain junctions FUNCTIONS: between epithelial cells 1. support to cell  Keratinization: producing an outer layer of 2. stabilize junctions between cells nonliving cells that reduces dehydration 3. play an important role in movements of organelles and 2. Vimentin: most common class III intermediate cytoplasmic vesicles filament protein 4. allow movement of entire cell 3. Neurofilament 5. help move chromosomes during cell division 4. Lamins: form nuclear lamina (structural framework inside nuclear envelope XVI. INCLUSIONS Cytoskeletal Components: cytoplasmic structures filled with stored macromolecules and are not present in all cells ○ most are transitory (not enclosed by membrane) ○ contain no metabolic activity ○ temporary components of certain cells PREPARED AND EDITED BY: LIMBAUAN, J., LIVED, R., LOCQUIAO, C., LOPEZ, F., PADOLINA, J., PALAGANAS, B., PANG-AG, L.  (001) HISTOLOGY DR. CABUENA | 09/14/2020 3. Nucleolus- specialized subdomain ○ inert accumulations or aggregates of metabolites or cell products  X and Y chromosomes – genes determining whether an individual will develop male or female - 1 pair of sex chromosome, 22 pair of Examples: autosomes 1. Hemosiderin- dense brown aggregate of denaturated ferritin proteins w/ many atoms of bound iron; occurs in XVIII. NUCLEOSOME phagocytosis of RBCs, esp. macrophages of the liver & spleen structural unit of DNA and histones; produces the initial 2. Lipid / Fat droplets – accumulation of lipid filling organization of free double-stranded DNA into chromatin adipocytes ○ core of 8 histones (two copies each: H2A, H2B, H3, H4) 3. Glycogen granules – aggregates of carbohydrate polymer, where glucose is stored DNA to Chromatids 4. Melanin – dark brown granules in skin; protect cells from UV radiation 1. DNA double helix with histones to form nucleosomes 5. Lipofuscin –pale brown granule, derived from lysosomal connected by the DNA (“beads on a string”) digestion residual bodies 2. Nucleosomes on the DNA then interact to form a more compact fiber XVII. NUCLEUS 3. For transcription, DNA forms loops that remain tethered to and stabilized by interactions with protein scaffolds large, rounded structure that contains code for cell’s enzymes & 4. Heterochromatin is not transcribed and remains more highly other proteins, largest structure within the cell condensed 5. metaphase chromosome, with maximum packing of DNA. contains molecular machinery to replicate DNA and to synthesize 6. The chromosome consists of two chromatids held together at all types of RNA; produces ribosomal subunits in nucleolus ad a constriction called the centromere export them into cytosol found in all human cell except for mature RBC and platelets usually basophilic in stain due to the presence of nucleic acid Components: 1. Nuclear envelope - separates cytoplasm from nucleoplasm (selectively permeable barrier)  Perinuclear Space – separate the two membranes of nuclear envelope (30-50nm). Both perinuclear space and outer membrane: binds ribosomes and is continuous with rough endoplasmic reticulum (RER)  Nuclear lamina – composed of intermediate filament subunits called lamins; stabilizes the nuclear envelope  Nuclear pore complexes – bridge the inner and outer nuclear membranes  Nucleoporins – core proteins of nuclear pore complex 2. Chromatin – consists of DNA and all proteins in DNA function - pattern of nucleus; cells with lightly stained nuclei are more active in protein synthesis than those with condensed, dark nuclei - In humans, except eggs and sperm, each cell’s chromatin is divided among 46 chromosomes (23 Figure 12. Schematic view of DNA package in chromosome pairs) Summary of cellular structural components  Barr Body or Sex chromatin – one of two X chromosomes in females  Plasma membrane – phospholipid bilayer containing cholesterol and proteins; acts as physical barriers, regulates Two types of chromatin can be distinguished with both the material movement into and out of cell; maintains electrical light and electron microscopes: charge differences; functions in cell communication 1. Heterochromatin – appears as coarse, electron-  Cilia – membrane extensions supported by microtubules; dense material and as intensely basophilic clumps. It moves substances is made up of condensed network of chromatin and they are metabolically inert.  Flagellum – long, singular membrane supported by 2. Euchromatin – is visible as finely dispersed microtubules; propel sperm granular material and s lightly stained basophilic  Microvilli – numerous membrane folds projecting from cell areas in light microscope. It is made up of loose surface increase membrane surface area for greater network of chromatin fibrils and they are metabolically absorption active PREPARED AND EDITED BY: LIMBAUAN, J., LIVED, R., LOCQUIAO, C., LOPEZ, F., PADOLINA, J., PALAGANAS, B., PANG-AG, L.  (001) HISTOLOGY DR. CABUENA | 09/14/2020  Nucleus – structure enclosed within a double membrane;  Anaphase contains chromatin, nucleolus, nucleoplasm; houses the - shortest stage of mitosis DNA - centromeres divide  Nuclear envelope – double membrane boundary bet - sister chromatids (now referred as daughter cytoplasm and nuclear contents; continuous w/ rough chromosomes) are pulled apart and move toward ER the spindle poles  Nuclear pores – functions in synthesis of ribosomes  Nucleolus – functions in synthesis of ribosomes  Telophase 6. Cytoplasm – contents of cells bet plasma membrane and - final stage; reversal of many processes during nuclear envelope prophase 7. Cytosol – viscous fluid medium; provides support for - nuclear envelope begins to reassemble organelles - two sets of chromosomes uncoil and diffuse 8. Organelles – either membrane or non-membrane bound; (begin reverting to their condensed state) carry out metabolic activities - spindle fibers disappear 9. Rough ER – modifies, transports, and stores proteins produced by attached ribosomes; these proteins are  Cytokinesis secreted to the plasma membrane or serve as enzymes of - mitosis cytoplasm divides (produces a cleavage lysosomes furrow) and parent cell forms 2 daughter cells 10. Smooth ER – synthesizes, transports, & stores lipids; metabolizes carbohydrates; forms peroxisomes  Interphase: long period between mitoses (G1, S, G2 phases) 11. Golgi apparatus – saclike membranous structures;  G1 phase – time gap between mitosis and DNA replication packages materials that arrive from ER; forms lysosomes - longest and most variable part of the cycle; period of 12. Vesicles – transport cellular material active RNA & protein synthesis 13. Lysosomes – contain digestive enzymes - period in which cells accumulate the enzymes and 14. Peroxisomes – detoxify harmful substances; engage in beta nucleotides oxidation of fatty acids to acetyl CoA - required of DNA replication 15. Mitochondria – contain circular strand of DNA; synthesize most ATP during aerobic cellular respiration  S phase – period of DNA synthesis (DNA replication, 16. Ribosomes – composed of protein and rRNA; engage in histone synthesis and the beginning of centrosome protein synthesis duplication) 17. Cytoskeleton – maintains structural support; participates in cell division  G2 phase – short period gap between DNA duplication and 18. Centrosome – contains centrioles; participates in mitotic next mitosis; where proteins required for mitosis spindle accumulate 19. Proteasome – degrade damage proteins 20. Inclusions – temporary storage of molecules (melanin, glycogen, lipid)  G0 phase – cell cycle activities may be temporarily or permanently suspended XIX. The Cell Cycle Regular sequence of events that produce new cells ○ Most cells undergo repeated cycles of macromolecular synthesis (growth) and division (mitosis) before differentiation Four Distinct Phases:  Mitosis (period of cell division)- produces two diploid cells Figure 13. Cell cycle that are genetically the same - parent cell divides and each two daughter cells Checkpoints: Cyclins and cyclin-dependent kinases (CDK) – receive a chromosomal set identical to the parent cell proteins that regulate overall progression in the cycle  Prophase - Phosphorylate/activate enzymes and other proteins needed for - nuclear membrane breaks down phase specific functions - nucleolus disintegrates - centrosome duplicates to form two daughter cells - centrosomes that migrate to opposite ends - centrosomes organize the production of microtubules that form the spindle fibers that constitute the mitotic spindle - chromosomes condense into compact structures  Metaphase - chromosomes migrate further to the equatorial plane - individual mitotic spindle fibers bind to a kinetochore (protein complexes) - chromosomes condense PREPARED AND EDITED BY: LIMBAUAN, J., LIVED, R., LOCQUIAO, C., LOPEZ, F., PADOLINA, J., PALAGANAS, B., PANG-AG, L.  (001) HISTOLOGY DR. CABUENA | 09/14/2020 Major cyclin and CDK regulating human cell cycle: - meiotic crossing over  new combinations of genes Cyclin-CDK Checkpoint Ex. Of Target Proteins complex Phosphorylates Rb Meiosis Early G1 Cyclin D-CDK4 or 6 protein that activates genes for G1 activities ○ produces 4 haploid cells with new genetic combinations Activation of E2F- LateG1/Entry of ○ specialized process involving two unique and closely S Cyclin E-CDK2 mediated gene associated cell divisions; occurs only in sperm and egg transcription cells formation DNA polymerase and S Cyclin A-CDK2 proteins for DNA ○ Two key features characterizing Meiosis: replication a. synapsis: homologous chromosomes of each pair (one Specific phosphatases from mother, one from father) come together G2/entry of M Cyclin A-CDK1 and cyclin B b. cells produced are haploid (having one chromosome Nuclear lamins; Histone from each pair present in body’s somatic cells) H1; chromatin; - fertilization: union of haploid eggs and sperm forms M Cyclin B-CDK1 centrosome assoc. diploid cell (zygote)  develop into new individual proteins produced 1. Meiosis I – separates the homologous chromosomes that - every haploid cell is UNIQUE paired during synapsis - lacking synapsis and DNA recombination  Late Interphase – synapsis and crossing over begin  Prophase I – paired chromosomes condone (lasts for 3  Apoptosis weeks) - process of cell suicide; rapid, highly regulated cellular  Metaphase I – homologous chromosomes line up activity that shrinks and eliminates defective and double file unneeded cells - also known as “programmed cell death” 2. Meiosis II - Results in apoptotic bodies  undergo  Anaphase I/Telophase I – homologs separate into phagocytosis; do not rupture, release none of its haploid daughter cells; sister chromatids remain joined contents - During apoptosis, nuclear changes that may occur  Metaphase II – chromosomes line up single file in include; Pyknosis (shrinkage of nucleus), haploid cells Karyohexis (fragmentation of nucleus), Karyolysis  Anaphase II/Telophase II – sister chromatids separate (dissolution of nucleus) into non-identical haploid cells - controlled by Bcl-2 family (regulate release of death- promoting factors from mitochondria) - Bcl-2 induce apoptosis by: o Loss of mitochondrial function – activation of caspases (proteolytic enzyme) resulting in protein /degradation o Fragmentation of DNA – endonucleases activation (cleaves DNA) o Shrinkage of nuclear and cell volumes – destruction of cytoskeleton and chromatin causes the cell to shrink quickly producing dense, darkly stained pyknotic nuclei o Cell membrane changes – plasma membranes undergo dramatic shape changes (blebbing) wherein lipid mobility increases o Formation and phagocytic removal  Necrosis – cells dies as a result of injury TEST YOUR KNOWLEDGE 1. Functions as a selective barrier regulating the passage of materials into and out of the cell and facilitating the transport of specific molecules? A. Cytosol B. Plasma Membrane Figure 14. Mitosis vs. Meiosis C. Cytoplasmic Skeleton  Mitosis D. Endoplasmic Reticulum - produce two genetically THE SAME diploid cells  Meiosis 2. Na/Glucose transport is an example? - produce four haploid cells (involves two cell divisions) PREPARED AND EDITED BY: LIMBAUAN, J., LIVED, R., LOCQUIAO, C., LOPEZ, F., PADOLINA, J., PALAGANAS, B., PANG-AG, L.  (001) HISTOLOGY DR. CABUENA | 09/14/2020 A. Diffusion cytoplasmic side. B. Symport C. Osmosis A. Transmembrane proteins D. Antiport B. Integral proteins C. Multipass proteins 3. Which of the following is the mechanism of transport of D. Peripheral proteins exchange of oxygen and carbon dioxide between blood and body tissue? Answer: 1.B 2.B A. Pinocytosis 3.C B. Phagocytosis 4.A 5.B C. Simple Diffusion 6.C D. Facilitated Diffusion 7.B 8.A 9.D 4. It is a period of DNA Synthesis? 10.D A. S Phase B. G1 Phase C. G2 Phase REFERENCES D. G0 Phase Mesher, A (2016). Junqueira’s Basic Histology Text and Atlas. 5. Known as the “programmed cell death”? Van Putte, C. (2016) Seeley’s Essentials of Anatomy and Physiology Ninth Edition. A. Pyknosis B. Apoptosis C. Both D. None 6. This serves as a bridge between the inner and outer nuclear membranes. A. Perinuclear space B. Nuclear lamina C. Nuclear pore complexes D. Nucleoporins 7. This is the most common class III intermediate filament protein. A. Lamins B. Vimentin C. Keratin D. Neurofilament 8. This cytoskeletal component is commonly found concentrated beneath the cell membrane and in cell extensions like microvilli. A. Microfilaments B. Intermediate filaments C. Microtubules D. All of the above 9. In this pathway, signal molecules are carried in the blood to target cells throughout the body, thus affecting cells that are distal from their source. A. Paracrine Signaling B. Juxtacrine Signaling C. Autocrine Signaling D. Endocrine Signaling 10. These are proteins exhibiting a looser association with one of the two membrane surfaces, particularly on the PREPARED AND EDITED BY: LIMBAUAN, J., LIVED, R., LOCQUIAO, C., LOPEZ, F., PADOLINA, J., PALAGANAS, B., PANG-AG, L.