CYTOLOGY - THE CELL



Prokaryotes

    Bacteria -------- pathogenic microorganisms --- <MICROBIOLOGY>

Eukaryotes 

    Protozoa -------------------------------------- <PARASITOLOGY>  

    Multicellular (Metazoan) Organisms

      Plant Cell

      Animal Cell

        basic structure (identical) --------- <CYTOLOGY>

        specialized cell structure ---------- <HISTOLOGY>

        altered, pathologic structure ------- <PATHOLOGY>




Components of the Cell
 

    Plasma (Cell) Membrane ------ Protoplasm

    Nuclear Membrane -------------- Nucleus and Cytoplasm

    Nucleus

      Chromatin, Nucleolus, Nuclear Sap

    Cytoplasm

      Cytoplasmic Organelles

        Membranous Organelles  

          ER, Golgi complex, lysosome, mitochondria, etc.

        Cytoskeleton (Filamentous Organelles)

          microtubules, microfilaments, intermediate filaments


    Biological Membrane System  

      Cell Membrane

      Nuclear Membrane ---- Nucleus

      Membranous Organelles

        endoplasmic reticulum(ER)

          r-ER (ribosome)

          s-ER

        Golgi complex

        mitochondria

        lysosome

        peroxisome


    Cytoskeleton ---- filamentous organelles  

      Microfilament

      Intermediate Filament

      Microtubule ---- Centriole




Plasma Membrane

Composition  

    phospholipid bilayer  

      phosphatidylcholine (lecithin), sphingomyelin - outer membrane

      phosphatidylethanolamine (cephalin), phosphatidylserine - inner membrane

    protein --- integral vs. peripheral  

      channels, receptors, messengers

    carbohydrate - glycocalyx

    * Fluid Mosaic Model 

Structure  

    trilaminar unit membrane, 7.5-10.5 nm,  

      outer hydrophilic layer ----- electron-dense (OsO4 deposition)

      middle hydrophobic layer - electron-lucent, 2.2-3.5 nm each

    glycocalyx - outer part of plasma membrane 

Transport through Plasma Membrane  

    Endocytosis  

      pinocytosis  

        FLUID PHASE PINOCYTOSIS

        FECEPTOR MEDIATED PINOCYTOSIS  

          ligand-receptor complex ---- clathrin

          coated pit, coated vesicle, early endosome, late endosome

      phagocytosis --- fusion of pseudopod

    Exocytosis



Nucleus  

    Nuclear Membrane  

      Nuclear Pore: octagonal, 50-70 nm (dia.),

      double membrane  

        cf. annulate lamellae

    Nucleoplasm

     

      Nuclear Sap


      Chromatin

      Euchromatin (extended chromatin):



      active site of transcription


      Heterochromatin (condensed chromatin):



      inactive site



      * Barr Body, drumstick (Lyon hypothesis)


    Dimension and Nature of Chromomatin

     

      Chromosome (entire metaphase chromosome)

      1400 nm


      Heterochromatin (condensed chromatin)

      700 nm


      Euchromatin (extended chromatin)

      300 nm



      Chromatin Fiber (solenoids)

      30 nm



      Chromatin Fiber (beads on a string)

      11 nm





      nucleosome + internucleosomal DNA





      Nucleosome (Unit Particles of Chromatin)

      11 nm





      DNA double helix, Histone Octamer






      DNA double helix

      2 nm


    Nucleolus  

      1. pars fibrosa - Christmas tree appearance  

        - synthesizing site of ribonucleoprotein

        - core: nucleolar organizing region of chromosome 

      2. pars granulosa: maturing ribonucleoprotein  

        - ribosomal RNA (rRNA)

        - trnsported to cytoplasm and incorporated as ribosome into endoplasmic reticulum




Cytoplasmic Organelles

Endoplasmic Reticulum

    - elongated, flattened, rounded, or tubular vesicle 

    Rough (Granular) ER

      - ribosome on the surface of ER

        - basophilia due to phosphate group (polyanion) of ribonucleic acid

        - site of amino acid translation from mRNA to form polypeptide chain

      - posttranslational modification and initial glycosylation

      - segregation of synthesized polypeptide chain from cytosol

      - outer membrane of nuclear envelop is part of rER membrane

      - especially abundunt in protein synthesizing cell  

        plasma cell

        gastric chief cell

        pancreatic acinar cell

        hepatic parenchymal cell

        active stage of fibroblast, osteoblast etc.

    Smooth (Agranular) ER  

      - consists of anastomosing tubules and cistern

      - involved in lipid metabolism  

        abundunt in steroid hormone-producing cells

      - glycogen synthesis in hepatic parenchymal cells

      - detoxification  

        cytochrome P450 system

        provide hydroxyl group to unsolubule harmful substance

        to transform to water soluble excretable substance

      - calcium storage in muscle cell (sarcoplasmic reticulum)

Golgi Apparatus  

    - consists of lamellae or cisterna of flatteded fenestrated disklike structure

    - have 2 faces  

      1. forming face (unit memb. 6 ㄍm thick): convex side  

        high thiamine pyrophosphatase

      2. maturing face (unit memb. 8 ㄍm thick): concave side  

        high acid phosphatase

    - glycosylation, sulfation, phosphorylation of polypeptide chain

    - involved in synthesis of proteoglycan and glycoprotein

    - concentration of secretory products

    - distributes its contents to secretory vesicle, lysosome or plasma membrane

Transport Vesicle  

    - 50-60 nm diameter

    - transport products from ER to Golgi or Golgi to lysosome

    - have delicate radial bristles to form coated vesicle

    - some micropinocytotic vesicle is form of coated vesicle

Lysosome  

    - cell organelle containing large number of hydrolytic enzymes  

      acid hydrolases:  

        nucleases, proteases, lipases, glycosidases

        phosphatases, sulfatases, phospholipases

    * fixation prevents leakage of lysosomal enzymes 

    - divided morphofunctionally into  

      1. primary lysosome

      2. secondary lysosome  

        phagocytic vacuole  

          autophagic vacuole

          heterophagocytic vacuole

        residual body  

          lipofuscin granule

    Cf. Lysosomal storage disease, Chediak-Higashi syndrome

Mitochondria  

    - double membrane structure  

      outer membrane

      outer chamber

      inner membrane  

        cristae, tubule

        elementary particles

    - produce energy by  

      1. TCA (tricarboxylic acid) cycle

      2. oxidative phosphorylation system

    - synthesize and oxidize fatty acid (tubular cristae)  

      steroid hormone producing cell

    - concentrates ferritin

    - origin and evolution (biogenesis)  

      purple bacteria  

        1. circular DNA

        2. outer memb. - identical with ER membrane

        3. inner memb. - resembles bacterial memb.

        4. cristae - resembles bacterial mesosome

        5. chlorampenicol blocks bacterial and mitochondrial protein synthesis,

          does not block nuclear-ER protein synthesis


Peroxisome (Microbodies)  

    - contains peroxidases, catalases, D-amino acid oxidase, urate oxidases (lack in bird and primates)
     

      RH2 + O2 → R + H2O2

        peroxidases

      H2O2 + R'→ R'H2 + H2O

        catalases

    - originate from proto-eukaryotic cells  

      cf. mitochondria is originates from purple bacteria, chlorplasts is originates from blue-green algae

- neutralizes toxic oxygen and use it as powerful oxidants


Cytoskeleton

Microfilament (5-7 nm)

    Actin Microfilament  

      G-actin, F-actin

    - involved in endocytosis, exocytosis, contraction of microvilli

    - migratory activity

    - muscle contraction with myosin


Intermediate Filament (10 nm)

    - cellular framework

    - heterogenous group of proteins

    - marker substance for identifying cellular origin, especially in tumor cells

 

    Type I

    Keratin

    epithelial origin (tonofibril)

    Type II

    Vimentin

    mesenchymal origin

    Desmin

    muscle cell

    Glial Fibrillary Acidic Protein (GFAP)

    neuroglia (astrocyte)

    Type III

    Neurofilament

    neuron

    Type IV

    Nuclear Lamins

    inner nuclear membrane


Microtubule (24 nm)  

    - hollow tubular shape

    - tubular wall polymerized by tubulin dimer subunits

    - microtubule associated proteins (MAPS) plays important roles in microtubule function  

      kinesin, dynein (cytoplasmic and axonemal), dynamin

    - formation of spindle fiber (kinetochoral microtubule)

    - centriole consists of 9 microtubular triplet and synthesize ciliary axoneme

    - cilia, flagella - axoneme (9+2 doublet), basal body (9 triplet)

    cf. immotile cilia syndrome  

      chronic bronchitis, sinusitis, immotile sperm (infertility)

      dextrocardia (Kartagener's syndrome)

    - axonal transport (fast antegrade transport and retrograde transport) in neuron

    - assembly (polymerization) is blocked by colchicine, vinblastin, and vincristin




LIFE CYCLE OF CELLS

 

      G0 Phase

      interphase

      G1 Phase

      S Phase (DNA synthesis)

      G2 Phase

      M Phase

      mitosis


    Mitosis  

      Prophase

      Prometaphase

      Metaphase

      Anaphase

      Telophase

      Cytokinesis

    Meiosis in sex cell (ovum and sperm)  

      Prophase I  

        Leptotene stage

        Zygotene stage

        Pachytene stage

        Diplotene stage

        Diakinesis

      Metaphase I

      Anaphase I

      Prophase II

      Metaphase II

      Anaphase II

      Telophase II

      Cytokinesis

 

CELL DEATH  

    Necrosis  

      - from mechanical injury, exposure to toxins, anoxia

      - process of necrosis  

        1. swelling

        2. clumping of the chromatin

        3. deterioration of organelles - pale staing of cytoplasm

        4. release of cell contents followed by lysis

      - phagocitized by macrophage

    Apoptosis (Gr. falling off; apo - off, ptosis - falling)  

      - programmed cell death

      - active form of cell death

      - end of normal life span

      - process of apoptosis  

        1. early condensation of chromatin

        2. degradation of DNA by activation of endonuclease

        3. decrased cell volume ---- opposite cell swelling

        4. organelles remain intact

        5. fragmented into several membrane bounded globules

        6. phagocytized by neighboring cells

        7. prevented by compounds that inhibit protein synthesis



Lecture Note by Won Taek Lee, M.D., Ph.D.