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1. 3/23/2017 1 transmission electron microscope light microscope Cytology - study of cell using microscope

2. 3/23/2017 2 HUMAN ANATOMY By- Yitades A .   CELLULAR ORGANIZATION OF THE BODY

3. Cells 3/23/2017 3 Basic structural & functional ,smallest living units of the body The human organism has more than 200 different cell types Pancreatic islets. eosinophils neutrophils basophils

4. Two basic cell types 3/23/2017 4 Eukaryotic cells Animal cells ( i.e human cells) Have a distinct membrane-limited nuclei Contains many varied membrane-limited organelles in cytoplasm Prokaryotic cells Found in bacteria and algea - they are small Have a cell wall around the plasmalemma Lack other membranous structures including an envelope around the genetic material (DNA).

5. Organization of Cells 3/23/2017 5 The cell is composed of two basic parts: cytoplasm & nucleus 1. CYTOPLASM Limited by cell membrane Contains three structural components Organelles – “ little organs” which are metabolically active Cytoskeleton – structural framework ( fibrillar elements) Inclusions – cell products, metabolites (metabolically inactive) Cytosol - fluid component 2. NUCLEUS Genetic material, Nuclear envelope

6. Rough ER Smooth ER Centrosome CYTOSKELETON Microfilaments Microtubules Microvilli Peroxisome Lysosome Golgi apparatus Ribosomes Nucleolus Chromatin NUCLEUS Flagelium Intermediate filaments ENDOPLASMIC RETICULUM (ER) Mitochondrion Nuclear envelope Plasma membrane Cell Components 3/23/2017 6

7. 3/23/2017 7 STRUCTURAL COMPONENTS OF CELL

8. The outermost component of the cell Separate the cytoplasm from its extracellular environment Thickness about 7.5 nm . Composition: lipid bilayer & associated proteins . Ratio of lipid to protein is variable: 1:1 (by wt) in most cells 4:1 in myelin. Plasma lemma ( Plasma membrane/Cell membrane ) 3/23/2017 8

9. Plasma lemma Con’ The fluid mosaic model of membrane structure A membrane consisting of a phospholipid bilaye r also contains proteins . Integral proteins Peripheral proteins Many of these proteins move within the fluid lipid phase . Both the proteins & lipids may have externally exposed oligosaccharide chains .( glycoprotein, glycolipid ) b . Membrane splitting occurs along the line of weakness formed by the fatty acid tails of membrane phospholipids 3/23/2017 9

10. The fluid mosaic model of membrane structure 3/23/2017 10

11. Plasma lemma Con’ 3/23/2017 11 1. Lipid bilayer Freely permeable to small nonpolar lipid-soluble molecules. Impermeable to charged ions. Molecular structure of the Lipid bilayer Plasmalemma lipids A. Phospholipids – forms the bilayer A mphipathic : have - a polar ( hydrophilic ) head & - two nonpolar ( hydrophobic ) fatty acid tails.

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13. Plasma lemma Con’ B. Glycolipids Outer leaflet only , form part of glycocalyx . Major glycolipids : 1 . Galactocerebroside (component of myelin) 2 . Gangliosides ( 10% of lipid in nerve cell membrane) C. Cholesterol In both leaflets , constitute about 2% of plasmalemma lipids. Assists in maintaining structural integrity of the cell membrane. Fluidity ↑ rise in temperature ↓ by ↑ in membrane’s cholesterol content. Crucial to cellular activities: exocytosis , endocytosis , membrane trafficking e.t.c 3/23/2017 13

14. Plasma lemma Con’ 2. Plasma Membrane Proteins - are synthesized in the RER A. Integral proteins (often glycoproteins ) Are firmly (permanently) embedded in the lipid layers Are amphipathic – they have both polar & nonpolar parts. May extend into both leaflets or into the inner leaflet only . Transmembrane proteins : proteins that completely span the bilayer One-pass - span the membrane only once from one side to the other Multipass transmembrane proteins - span the membrane more times Function- as membrane receptors and/or transport proteins . 3/23/2017 14

15. Plasma lemma Con’ 3/23/2017 15 B. Peripheral proteins : do not extend into lipid bilayer exhibit a looser association with one of the two membrane surfaces they associate more loosely with the polar heads of membrane lipids or with integral proteins at the inner or outer surface of the membrane Function - serve as cytoskeleton , enzymes and linkers.

16. molecular structure of the plasma membrane 3/23/2017 16

17. Plasma lemma Con’ 3/23/2017 17 Main functions of Membrane Proteins: serve as Ion channels - through which specific ions can flow to get into or out of the cell Carriers/Transporter - Transport molecules to or out of the cells Receptors - cellular recognition sites for chemical signaling b/n cells (e. g. hormone receptors) Ligand - a specific molecule that binds to a receptor Enzymes - catalyze specific chemical reactions at the inside or outside surface of the cell Cell adhesion molecules - attach cytoskeletal filaments to cell membrane Linker proteins - attach cell’s cytoskeloton to extracellular matrix Cell-identity markers ( glycoproteins & glycolipids ) R ecognize other cells of the same kind during tissue formation or to recognize and respond to potentially dangerous foreign cells

18. Plasma lemma Functions 3/23/2017 18 Physical isolation ( barrier ) • Semipermeable membrane • Receptor • Structural support

19. Glycocalyx 3/23/2017 19 Sugar coat(fuzzy) in outer leaflet of plasma lemma Thickness = 50nm. • Consists of polar oligosaccharide side chains linked covalently to most protein & some lipid ( glycolipid ). Functions • Cellular attachment to extracellular matrix components. • Binding of antigens & enzymes to the cell surface. • Facilitate cell-cell recognition & interaction (e.g., sperm – egg adhesion).

20. Cytoplasm 3/23/2017 20 Consists cellular contents b/n the plasma membrane & the nucleus Limited by cell membrane Contains three structural components Organelles – “little organs” which are metabolically active Cytoskeleton – structural framework ( fibrillar elements) Inclusions – cell products, metabolites (metabolically inactive) Cytosol – fluid component ( cytoplasmic matrix, intracellular fluid)

21. Cytosol (Intracellular Fluid ( ICF ) 3/23/2017 21 Cytoplasmic matrix Is the fluid portion of the cytoplasm that surrounds organelles Constitutes about 55% of total cell volume. Composition and consistency ~75–90% water Various dissolved and suspended components (ions, glucose, amino acids, fatty acids, proteins, lipids, ATP, and waste products) Function Site of many chemical reactions required for a cell’s existence

22. Organelles 3/23/2017 22 “little organs” which are metabolically active Specialized structures within the cell that have characteristic shapes Numbers and types of organelles vary in different cells, depending on the cell’s function. Classified as Membranous Organelles N on-membranous Organelles

23. Membranous Organelles 3/23/2017 23 Membrane - enclosed organelles Mitochondria Rough Endoplasmic Reticulum (RER) Smooth Endoplasmic Reticulum (SER) Golgi apparatus Vesicles transport vesicles secretory vesicles lysosomes peroxisomes ( microbodies )

24. Mitochondria 3/23/2017 24 Membrane-enclosed organelles Rod-shaped Size: 0.5-1µm wide, ~7µm long. Proliferate by fission of pre existing mitochondrion Mitochondria are maternally derived Cells with a high-energy metabolism have many Mitochondria (e.g. liver, kidney tubule , cardiac muscle, sperm cells) Lifespan ~10 days. Mitochondria are present in all cells except RBCs and terminal keratinocytes

25. Mitochondria Cont’ 3/23/2017 25 Consists outer & inner membranes. Both contain a large number of protein molecules a. Outer membrane Smooth layer b. Inner membrane Has folds - cristae Cristae increase its surface area Contains enzymes

26. Mitochondria Cont’ 3/23/2017 26 Has 2 Compartments Matrix the innermost compartment Possess genetic apparatus composed of DNA (circular), mRNA, tRNA & rRNA (with limited coding capacity) b. Intermembrane space Narrow tubular fluid-filled space

27. Rough Endoplasmic Reticulum (RER) 3/23/2017 27 Continuous with the nuclear membrane Usually is folded into a series of flattened sacs Outer surfaces are studded with poly ribosomes Has receptors = ribophorins , to which large ribosomal subunits bind Prominent in cells specialized for protein secretion (e.g. pancreatic acinar cells (digestive enzymes), fibroblasts (collagen), and plasma cells ( immunoglobulins )

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29. RER Cont’ 3/23/2017 29 Functions • Segregation and synthesis of proteins • Glycosylation of glycoproteins . • Synthesis of phospholipids. • Assembly of multichain proteins. • Certain post transitional modifications of newly formed polypeptides

30. Smooth Endoplasmic Reticulum (SER) Irregular network of membrane-bounded channels Lacks ribosomes Usually appears as branching anastomosing tubules, or vesicles . Less common than RER Predominates in cells synthesizing steroids , triglycerides, & cholesterol . SER membranes arise from RER membranes . 3/23/2017 30

31. SER Cont’ 3/23/2017 31 Functions Steroid hormone synthesis : i.e Leydig cells, Zona fasiculta (Suprarenal gland) Drug detoxification : Hepatocytes ( Oxidation,Conjugation & methylation ) Muscle contraction & relaxation : Skeletal m ( sarcoplasmic reticulum, release & recapture of Ca ⁺⁺ ) Metabolism of lipid & cholesterol Glycogen synthesis, storage & breakdown in the liver

32. Golgi Complex (Apparatus) Named for histologist Camillo Golgi , Italian, who discovered it in 1898 Consist of several disc-shaped cisternae ( saccules ) arranged in stack. Cisternae are slightly curved with flat centers & dilated rims. 3/23/2017 32

33. Golgi Complex Con’ 3/23/2017 33

34. Golgi Complex Con’ 3/23/2017 34 Functions Processing of noncytosolic proteins synthesized in RER. Memb . retrieval, recycling & redistribution Glycosylation , sulfation & phosphorylation Initiation of packing, concentration & storage of secretory products Limited proteolysis of proteins

35. Lysosomes 3/23/2017 35 Spherical ,membrane limited vesicles Cells' garbage disposal system Diameter 0.05 - 0.5µm Contains > 60 digestive & hydrolytic enzymes Particularly abundant in cells with great phagocytic activity ( eg , macrophages, neutrophils ).

36. 3/23/2017 36 Functions of Lysosomes Intracellular digestion Degeneration of glycogen & its removal Initiate mitosis Release of thyroid hormones Destruction of bone matrix ( osteoclasts )

37. Peroxisomes ( microbodies ) 3/23/2017 37 Spherical single membrane-limited organelles S imilar in structure to lysosomes but smaller Contain oxidative enzymes, such as D- aminoacid oxidase , ureateoxidase , and catalase

38. Peroxisomes Con’ 3/23/2017 38 Function Regulates H 2 O 2 within cells Gluconeogenesis (formation of glucose from noncarbohydrate precursors) Enzymes for lipid metabolism: β -oxidation of long chain fatty acids Detoxification (e.g., ethanol) Formation of bile salts

39. N on-membranous Organelles 3/23/2017 39 Ribosomes Length = 25 nm; width = 12 nm . • Sites where mRNA is translated into protein . Carry out protein synthesis • Consist roughly of 60% RNA and 40% protein rRNA is manufactured in the nucleolus! • Exist as free , bounded (fixed) as in RER & outer nuclear membrane, and as clusters ( polyribosomes ).

40. Ribosomes 3/23/2017 40

41. Centrioles 3/23/2017 41 Cylindrical structures (0.15µm in diameter & 0.3–0.5 µm in length) Composed primarily of short, highly organized microtubules E ach centriole has nine microtubular triplets and adjacent microtubules share some protofilaments . ( 9+0 pattern) A pair of centrioles surrounded by a matrix close to the nucleus of nondividing cells constitutes a centrosome In each pair the long axes of the centrioles are at right angles to each other

42. Each centriole is made of 9 bundles of microtubles , with 3 microtubules per bundle. ✪ Exist as a pair of cylindrical rods oriented at right angles to one another ✪ Self-duplicate in the S-phase of the cell cycle. ✪ Associated with microtubule-organizing centers (MTOCs ) or centrosomes Centrioles Con’ 3/23/2017 42

43. Centrioles Con’ 3/23/2017 43 function Before cell division, more specifically during the S period of the interphase , each centrosome duplicates itself so that now each centrosome has two pairs of centrioles . Centrioles provide basal bodies for cilia and flagella and align the mitotic spindle during cell division During mitosis, the centrosome divide into halves, which move to opposite poles of the cell, and become organizing centers for the microtubules of the mitotic spindle.

44. Cytoskeloton 3/23/2017 44 Structural framework within the cytosol . Functions: Maintain cell shape Stabilize cell attachments Facilitate endocytosis & exocytosis , and Promote cell motility.

45. 3/23/2017 45 Maintain cell shape Aid in the transport of macromolecules within the cytosol ( axoplasmic transport, melanin transport, vesicle movements b/n ER & GC and GC & membs ) Promote the movement of cilia, flagella, and chromosomes Microtubules function

46. Microfilaments ( F actin or actin filaments) 3/23/2017 46 5-7 nm in diameter. Composed of Globular actin monomers (G actin ) linked into a double helix having a 36nm repeat. Display polarity like microtubules More stable than microtubules. Abundant at the periphery of the cell where they are anchored to the plasma membrane via one or more intermediary proteins (e.g. α- actinin , vinculin , talin ). Involve in the following cellular processes: transformation of the cytosol Endocytosis and exocytosis Locomotion of non muscle cells

47. Intermediate Filaments 3/23/2017 47 Intermediate in size b/n the other two cytoskeletal components Have variable diameter averaging 8-10 nm Are formed from nonpolar and highly variable intermediate filament subunits. intermediate filaments are much more stable vary in their protein subunit structure in different cell types All are essentially rod-like rather than globular proteins that form coiled tetramers Provide mechanical strength to cells

48. Cilia 3/23/2017 48 Numerous,short , hairlike projections contains a core of 20 microtubules The microtubules are arranged such that one pair in the center is surrounded by nine clusters of two fused microtubules (doublets) ( 9+2 configuration ) . Function Causes the steady movement of fluid along the cell’s surface Respiratory tract - sweep foreign particles trapped in mucus away from the lungs Fallopian tubes - sweep oocytes (egg cells) toward the uterus

49. 3/23/2017 49 Cilia and flagella share a common ultrastructure

50. Ciliary motion 3/23/2017 50

51. Flagella 3/23/2017 51 Similar in structure to cilia but are typically much longer Flagella usually move an entire cell The only example of a flagellum in the human body is a sperm cell’s tail , which propels the sperm toward the oocyte in the uterine tube Direction of swimming

52. Nucleus 3/23/2017 52 A membrane-limited compartment Contains the genome (genetic information) together with the machinery for DNA replication and RNA transcription and processing Shape Appears as a rounded or oval Usually in the center of the cell

53. Nucleus Con’ 3/23/2017 53 Size Exceptionally large (multiple amounts of DNA)… megakaryocytes Number ( no. Of nucleus) Binucleated cells parietal cells (stomach), hepatocytes , cardiac m. Cells Multinucleated cells osteoclasts , skeletal m. Cells No nuclei at all Erythrocytes, blood platelets

54. Nucleus Con’ 3/23/2017 54 Nucleoplasm is nuclear content other than the chromatin and nucleolus The nucleus of a nondividing cell consists of the following Structural components Nuclear envelope (nuclear membrane) 2. Nucleolus ( pl.,nucleoli ) 3. Chromatin

55. The nuclear envelope 3/23/2017 55 Separates the nucleoplasm from the cytoplasm. Perforated at intervals by nuclear pores Nuclear pores Lipid-free spaces Contain ~30 different proteins or nuclear pore complexes (NPCs) or nucleoporins function Mediate the active transport of proteins, ribonucleoproteins , and RNAs b/n the nucleus and cytoplasm

56. Nuclear envelope Con’ 3/23/2017 56 Formed by outer & inner membranes Outer membrane Continuous with RER membrane Ribosomes are attached to it Inner membrane Supported by a rigid network of intermediate protein filaments ( laminin ) attached to its inner surface called the nuclear (fibrous) lamina which serves as an attachment site for chromatin

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58. Chromatin 3/23/2017 58 A complex of DNA and proteins Composed mainly of coiled strands of DNA Bound to basic proteins called histones and to various non histone proteins Two forms of chromatin Heterochromatin Euchromatin

59. Heterochromatin Condensed chromatin (coiled portions of chromosomes) Intensively basophilic Collective name for karyosomes (individual masses of chromatin) Visible as - chromatin granules associated with the nuclear envelope - nucleolus- associated chromatin (nucleolus) - some aggregates distributed in karyolymph( colourless ) Transcriptionally inactive (gene transcription suppressed) Chromatin Cont’ 3/23/2017 59

60. Chromatin Cont’ 3/23/2017 60 Euchromatin ( Interchromatin ) Dispersed (diffuse) region of chromosomes Transcriptionally active (active DNA, control metabolic activities) Contains Chromatin Nucleoproteins…. attachment sites for DNA RNA….ribosomal, messenger & transfer ➣ Distinction b/n Heterochromatin & Euchromatin disappears during cell division.

61. Chromatin Cont’ 3/23/2017 61 Chromosomes , is condensed chromatin , i n dividing cells Each chromosome is formed by 2 chromatids Centromere - a point that joins the chromatids Telomere- The area located at each end of the chromosome.

62. Chromatin Cont’ 3/23/2017 62 A chromosome is a highly coiled and folded DNA molecule that is combined with protein molecules Packing of DNA into a chromosome in a dividing cell.

63. Chromatin Cont’ 3/23/2017 63 Each human cell contains 46 chromosomes, organized as 23 homologous pairs homologous – b/c they contain forms (alleles) of the same genes Each chromosome in the pair has the same shape and size Somatic cells - are diploid (2n) b/c they contain paired chromosomes Egg & Sperm cell - are haploid(1n) b/c they have only 23 chromosomes , (n)for chromosome Autosomes - the 22 pairs Sex chromosomes- the twenty-third pair of chromosomes designated X and Y. - Females-(xx) - Males -( xy )

64. 3/23/2017 64 Karyotyp e of a normal male The white box inset shows the XX chromosome pair of a normal female. The red box inset reveals an abnormality in chromosomes 14 and 8. Karyotype Chromosomal mapping Pictures of chromosomes, cut out & placed in order of size and location of centromere Can show chromosomal problems

65. Nucleolus 3/23/2017 65 The nucleolus is spherical in shape highly basophilic actively making proteins A nonmembranou s region of the nucleus that surrounds transcriptionally active rRNA genes It is the site of ribosomal RNA ( rRNA ) synthesis & initial ribosomal assembly Has 2 morphologically distinct regions Fibrillar material (pars fibrosa ) Granular material (pars granulosa )

66. Cell cycle 3/23/2017 66 A sequence of events that results to the formation of new cell Consists of two major periods Interphase : interval b/n cell divisions. Mitosis : periods of cell division (M phase).

67. Interphase 3/23/2017 67 Considerably longer than the M phase Cell doubles in size and DNA content Non-dividing or resting stage The chromatin appears as an irregular reticular meshwork. The nuclear membrane(envelope)& the nucleolus are distinctly seen. Chromosomes are not visible

68. Interphase Con’ 3/23/2017 68 Has 3 Phases 1. G 1 Phase Cell growth & protein synthesis (restore daughter cells to normal vol. & size). Restriction point -“trigger proteins” synthesized to reach a threshold Cells that fail to reach the restriction point = resting cells, enter G0 phase. Lasts from few hours to several days Longest phase.

69. Interphase Con’ 3/23/2017 69 2. S Phase DNA replication & protein synthesis =duplication of chromosomes Centrioles self-duplicate Lasts 8-12 hours in most cells. 3. G 2 Phase Cell prepares to divide Centrioles grow to maturity Energy required for the completion of mitosis is restored RNA & proteins necessary for mitosis are synthesized Lasts 2-4 hours. ✹ Control factors S-phase activator triggers the initiation of DNA synthesis M-phase delaying factor M-phase promoting factor

70. Mitosis 3/23/2017 70 Mitosis is a process of chromosome segregation and nuclear division followed by cell division Produces two daughter cells with the same chromosome number & DNA content as the parent cell. Has 4 phases Prophase Metaphase Anaphase Telophase

71. Mitosis Con’ 3/23/2017 71 Prophase Nuclear membrane and nucleolus disappear. The thread- or rod-like character of the chromosomes is more apparent. Each chromosome consists of 2 coiled chromatids Mixing of nuclear and cytoplasmic material

72. Mitosis Con’ 3/23/2017 72 Metaphase Chromosomes appear condensed and line up in the equatorial plane (metaphase plate) of the cell. Each chromosome is still composed of two paired chromatids . Anaphase Chromatids separate & pulled to opposite poles of the cell. They remain separate and tightly coiled, and appear at this magnification to be fused. Cytoplasmic division begins.

73. Mitosis Con’ 3/23/2017 73 Telophase The two distinct groups of daughter chromosomes ( chromatids ) appear fused and tightly packed. Cytoplasmic division is completed. Nuclear membranes reform and nucleoli reappear . Karyokinesis = division of the nucleus Cytokinesis = division of the cytoplasm

74. Concept Cell division results in genetically identical daughter cells. Cells duplicate their genetic material. Before they divide, ensure that each daughter cell receives an exact copy of the genetic material, DNA In preparation for cell division : DNA is replicated and the chromosomes condense Concept The cell cycle is regulated by a molecular control system. The frequency of cell division varies with the type of cell. These cell cycle differences result from regulation at the molecular level. 3/23/2017 74

75. Meiosis Cell division that takes place in the germ cells to generate male and female gametes two cell divisions - meiosis I & meiosis II reduce the number of chromosomes to the haploid number of 23 . Meiosis I -as in mitosis, spermatocytes and primary oocytes , at the beginning replicate their DNA so that each of the 46 chromosomes is duplicated into sister chromatids . 3/23/2017 75

76. Meiosis con’ In contrast to mitosis, however, homologous chromosomes then align themselves in pairs, a process called synapsis . The pairing is exact and point for point except for the XY combination. Homologous pairs then separate into two daughter cells, thereby reducing the chromosome number from diploid to haploid . Meiosis II separates sister chromatids . Each gamete then contains 23 chromosomes 3/23/2017 76

77. Meiosis con’ In each sperm or egg. For males, 1/2 the sperm get an X chromosome, and the other 1/2 get a Y chromosome. Sometimes meiosis goes wrong (non-disjunction ), and a sperm or egg might get 2 sex chromosomes, or 0 sex chromosomes, leading people with 47 or 45 chromosomes. 3/23/2017 77

78. 3/23/2017 78 Comparison of meiosis & mitosis

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