Summary

These notes provide an overview of the cell membrane, including its structure, function, and associated processes. The text details the lipid bilayer, proteins, and carbohydrates involved in the membrane, along with various transport mechanisms such as endocytosis and exocytosis. The document is intended for undergraduate-level students.

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1st Year Histology (Plasma membrane - Plasma lemma -Limiting membrane)  Not seen? Very thin (But could be seen with special stains e.g. silver).  1. 7.5 to 10 nm in thickness. 2. Trilaminar appearance: 2 electron dense layers. 1 el...

1st Year Histology (Plasma membrane - Plasma lemma -Limiting membrane)  Not seen? Very thin (But could be seen with special stains e.g. silver).  1. 7.5 to 10 nm in thickness. 2. Trilaminar appearance: 2 electron dense layers. 1 electron lucent in-between (Unit membrane) 3. Stained by Osmium Tetroxide.  (1) Lipid : (bilayer) - It's formed mainly of phospholipid, glycolipid & cholesterol. - Phospholipid molecule consists of: 1. One Head: hydrophilic, directed inside & outside the cell (charged) ‫راس وا ﺪﻩ ﺮا و ﺟﻮا ﺑﺘﺤﺐ اﳌﯿﻪ و ﻠﳱﺎ ﴮﻨﺔ‬ 2. Two Tails: hydrophobic, directed to the center of the membrane (nonpolar) ‫ذﯾﻠﲔ ف اﻟﻨﺺ ﳛﺒﻮا ا!ﻫﻮن وﻣﻦ ﲑ ﴮﻨﺔ‬ So, Trilaminar appearance is due to deposition of stain in head in both side & not in tails ‫ﻋﻠﻝ ؟‬ DR. Ahmed Ammar 1 1st Year Histology (2) Protein :  It's the major molecular part of the membrane (in size).(1/2 of the mass)  Present in 2 forms: I. Peripheral protein: located on the inner & outer surfaces of cell membrane (mainly inner) ‫ﻫﺎﻡ‬. II. Integral proteins: embedded in lipid bilayer may arise from one surface but if arise from both surfaces it is called (Transmembrane protein). They form channels & carrier that help passage of molecules & ions across the membrane. (3) Carbohydrates:  Located on the outer surface of cell membrane attached to phospholipid (glycolipid) or protein (glycoprotein), called (Glycocalyx) ‫ﻏﻄﺎء اﻟﺴﻜﺮ‬.  They are polysaccharide. 1- Keep constant intracellular environment. 2- Keep the shape of the cell (e.g. Nerve cell). 3- Contain antigenic receptors: for recognition. 4- Contain signaling receptors: regulate the function of the cell. 5- Selective barrier: control the passage of substance in & out of the cell. DR. Ahmed Ammar 2 1st Year Histology : ‫ٔﻧﻮاع‬4 ‫ﻧﻮاع اﻟﻨﻘﻞ ﱪ ﻏﺸﺎء اﳋﻠﯿﻪ ﺛﻼﺛﺔ‬4ٔ 1). 2) : (vesicle ‫)ﺣﻭﻳﺻﻠﺔ‬ ♥ Changes at cell membrane at localized site followed by vesicle formation. ♥ There are 2 main types of Vesicular transport: 1. Endocytosis. 2. Exocytosis. 1. Endocytosis: (A)Pinocytosis: cell drinking. Occur by invagination of the cell membrane that entrap the fluid then pinch off of the vesicle. Not depend on clathrin. ‫ﻫﺗﻔﻬﻡ ﺍﻟﺻﻔﺣﻪ ﺍﻟﺟﺎﻳﻪ‬ Occur in endothelial cells of blood vessels :‫ﻣﺛﺎﻝ‬ (B)Phagocytosis: cell eating. Occur by cytoplasmic processes that surround the foreign substance, then the processes fuse together to form vesicle called phagosome. Occur in Macrophage & Neutrophils. May be Receptor-Mediated → phagocytosis of bacteria or Non-Receptor-Mediated → phagocytosis of dust & carbon. DR. Ahmed Ammar 3 1st Year Histology (C) Receptor mediated endocytosis: It's endocytosis of protein & hormone (ligand). Occur as following: 1- The ligand has 2 types of receptors → one present on the surface of the cell & others present on area called (coated pit). 2- The coat is formed of polypeptide (clathrin). 3- When the ligand bind to receptors on the surface→ They will invaginate to form coated pit → the invagination ↑↑ till it pinch off & form coated vesicle or early endosome.(ligand receptors complex) 4- Early endosome moves deep in the cytoplasm to form late endosome. 5- The clathrin coat is separated & return to the surface then receptors also separated by the help of lysosome & return to the surface. DR. Ahmed Ammar 4 1st Year Histology 2. Exocytosis:  It's the process by which a cytoplasmic vesicle release its content outside the cell.  Exocytosis is affected by Ca++ in the cytoplasm. (↑ Ca → ↑ exocytosis)  2 Pathway for exocytosis: 1. Constitutive pathway: the vesicle leave the cell after its formation & not stored. e.g. antibodies. 2. Regulated pathway: the vesicle stored in cytoplasm & released by nervous or hormonal stimuli e.g. pancreatic enzyme. 3) Definition: It's communication between cells → to control their growth & coordinate their functions. DR. Ahmed Ammar 5 1st Year Histology Shape: Spherical or rod organelle. Stain: Not visible with H & E but stained with Janus green B (supra-vital) stain (1 x 10 µm). Site: according to energy utilization e.g.: → Apical part of ciliated cell. → Basal part of ion transferring cell. → Middle part of spermatozoa. Number: according to energy utilization e.g.: → ↑ Number of mitochondria in active cells as cardiac ms. cells. → ↓ Number of mitochondria in inactive cells as osteocyte. Fate: Can divide by simple binary fission & Contain their own circular DNA & RNA ‫ﺑﺄﻧﻭﺍﻋﻪ‬. Life span → 10 days. DR. Ahmed Ammar 6 1st Year Histology 1- Outer membrane: Smooth & have receptors for proteins to enter intercellular space. 2- Inner membrane: Contain folds called cristae: Directed into the the interior. The Cristae Flat in shape. Contain enzymes of oxidative phosphorylation & electron transport chain → produce ATP. N.B: The cristae is tubular in shape in steroid secreting cell. N.B2: The cristae is ↑ in number in active cells. 3- Intermembrane space: between outer & inner membrane. 4- Matrix space: contain → Protein & ribosomes. → Enzymes for kerbs cycle. → Ca++ (electron dense granule). → Mitochondrial DNA & RNA. ‫ﺍﻟﺗﻔﺎﺻﻳﻝ ﻟﻠﻔﻬﻡ‬ 1- Energy production (power house of the cell) be oxidation of CHO, fat & protein to produce energy then use this energy to convert ADP→ ATP (phosphorylation). 2- Regulation of Ca++ level in the cell & other ions (keep cytoplasmic Ca++ low). DR. Ahmed Ammar 7 1st Year Histology  Definition: It's an anastomosing network of channel & sacs formed by continuous membrane & contain space called cisternae.  Types: - Rough (RER): contain ribosomes (‫)ﻣﺣﺑﺑﺔ‬ - Smooth (SER): no ribosomes. (‫)ﻧﺎﻋﻣﺔ‬ Appear as basophilic area in cytoplasm due to ribosomes Not seen e.g. fibroblast. + ‫ﺍﻟﺗﻌﺭﻳﻑ‬ + ‫ﺍﻟﺗﻌﺭﻳﻑ‬ Attached to nuclear It differ from RER in: membrane. 1- No ribosome →smooth. With many ribosomes on 2- The cisternae is tubular surface ‫ﺃﻛﻳﺩ ﻁﺑﻌﺎ‬ not flat like RER. 1- Synthesis of protein that 1- Synthesis of steroid hormone released or secreted outside in suprarenal gland. the cell. 2- Synthesis of phospholipid for 2—Modification of protein all membranes in the cell.. 3- Storage & release of Ca++ for muscle contraction. 4- Detoxification of drugs in liver cells. 5- SER contain G-6–P enzyme which important in glycogen metabolism. DR. Ahmed Ammar 8 1st Year Histology  - Stain: Not seen by H&E but may appear as empty space called (-ve Golgi image). It can be seen by silver impregnation. - Site: a) Supranuclear: between nucleus & apical cell membrane e.g. epididymis. b) Infranuclear: between nucleus & basal cell membrane e.g. endocrine cell. c) Perinuclear: around the nucleus e.g. neuron.  ‫ﺍﺭﺳﻡ‬ - It formed of several saccules arranged in stacks with dilated periphery. - The apparatus has 2 faces: 1- Entry, convex, cis or immature face. 2- Exit, concave, trans or mature face - The cis face is associated with small vesicle containing immature protein from RER. while → The trans face is associated with large secretary vesicles with mature protein.  1- Concentration & packaging of protein in secretary vesicle. 2- Modification of protein e.g. glycosylation. 3- Formation of Lysosome. 4- Recycling of cell membrane. 5- Synthesis of CHO DR. Ahmed Ammar 9 1st Year Histology - Lysosomes are sites of intracellular digestion. - They increase in phagocytic cells e.g. macrophage. - Lysosomal enzymes like acid phosphatase are synthesized in RER & packed in Golgi apparatus. - They have optimal activity in acidic PH.  Can be demonstrated by histochemical reactions for their enzymes.  Rounded, electron dense vesicle surrounded by 2 membrane,. 0.5 µm in diameter.  1- Primary lysosome: not share in digestive event (homogenous). 2- Secondary lysosome: (heterogeneous) 1ry lysosome + phagosome → heterophagic vacuole. 1ry lysosome + pinocytotic vesicle → multivesicular bodies. 1ry lysosome + autophagosome → Autophagic vacuole. Autophagosome: (membrane surround old organelle or part of cytoplasm).  1. Nutrients: diffuse to the cytoplasm. 2. Indigestible substance: execrated by the cell (exocytosis) 3. In long lived cells as neuron & cardiac muscle, Indigestible substance retain ‫ & ﺗﻔﺿﻝ‬called (residual bodies). When residual bodies ↑ in amount in long – lived cell, they called (lipofuscin pigment). N.B: ‫ ﻟﻠﻔﻬﻡ‬The cell protect itself from lysosome by: 1- Membrane of lysosome 2- PH of cytoplasm. DR. Ahmed Ammar 10 1st Year Histology  Can be demonstrated by cytochemical reactions for catalase enzyme.  Like lysosome but → surrounded by 1 membrane. → Contain oxidative enzymes. → Arise from RER directly not Golgi. → Self-replicating like mitochondria  1- Produce H2O2 → remove H2 from organic substance& transfer it to molecular O2 2- Destroy H2O2 → H2O + O2 by catalase enzyme. 3- Catalase can degrades also toxin & drugs in liver cells. 4- Peroxisome involved in lipid metabolism & formation of bile acids & cholesterol. Secretary vesicle → They are found in cells that store their product until its release such as pancreatic cells & cells of thyroid gland Coated vesicle → see receptor mediated endocytosis. DR. Ahmed Ammar 11 1st Year Histology 20 - 30nm in size. Composed of 4 types of rRNA + 80 proteins. 2 forms of ribosome - Free: in the cytoplasm. - Attached: RER. Formation: 1- rRNA is synthesized in the nucleolus. 2- Proteins are synthesized in the cytoplasm. 3- Proteins enter the nucleus, associate with rRNA, return to cytoplasm as mature ribosome.  Very small to be seen but when aggregate they cause basophilic area In cytoplasm due to rRNA. (May be Diffuse, localized or spotty)  ♥ Formed of 2 subunit → large & small that held together by mRNA. ♥ Polysomes→ several ribosomes on the same mRNA strand. ♥ Ribophorins→ is a specific receptor on RER bind to large subunit of ribosome.  1- Translate mRNA to amino acids (polypeptide chain). 2- Free ribosome produce proteins retain in cytoplasm for use within cell e.g. Hb in RBCs. 3- Attached ribosome produce protein secreted by the cell e.g. (enzymes & hormones), lysosomal enzymes & produce integral protein of cell membrane. DR. Ahmed Ammar 12 1st Year Histology Non membranous protein complex that responsible for proteolysis of mal-formed proteins ! ‫ﺑﺱ‬ DR. Ahmed Ammar 13 1st Year Histology Cytoskeleton is formed of microtubule & filaments.  Not seen ?.  ♥ 25 nm in diameter & 5 nm in wall thickness. ♥ Present in 2 forms: 1- Labile: free microtubule in cytoplasm that polymerizes or depolymerizes according to temperature. 2- Stable: they form centriole, cilia & Flagella.  1) 1 microtubule is formed of 13 protofilament. 2) Each protofilament is formed of polymer of tubulin protein. 3) Tubulin protein is α & β dimer. 4) Microtubules have protein called MAP (microtubule associated protein). 5) Each microtubule ↑ in length from one end( + end)& ↓ from other end (-end). 6) Change in length (polymerization) is affected by Both (Ca++ & MAPS)  1- Maintain the shape of the cell. 2- Movement of the cell. 3- Movement of the organelle. 4- Mitotic spindle formation. 5- Formation of centriole, cilia & Flagella. N.B: Anticancer drugs stop polymerization of microtubule → colchicine, taxol & vinblastine. DR. Ahmed Ammar 14 1st Year Histology  It’s cylindrical, short highly organized microtubules. ( 0.5 µm in length)  2 small rods at right angle to each other with material called (microtubule organizing center) (MTOC).  2 centriole at right angle to each other at each cell → centrosome. Each centriole is formed of 9 triplets of microtubule. Each triplets → 3 microtubule A, B & C. A is complete microtubule (13 protofilament) but B & C are incomplete microtubule (10 protofilament) as they share in 3 protofilaments.  1- Form mitotic spindle during cell division. 2- Form the basal of cilia & Flagella. DR. Ahmed Ammar 15 1st Year Histology  Hair like processes of highly organized microtubule.  Formation: The centriole migrate to apical cell membrane to form the base of cilia. From each triplets, 2 microtubule (A & B) grow upward to form the shaft of cilia. Unorganized microtubule → Rootlet of cilia.  1- Rootlet → unorganized microtubules. 2- Base → similar to centriole. 3- Shaft → LM: acidophilic striation. EM: - Formed of 9 doublet of microtubules & 2 central singlets in a protein sheath ( axoneme) ‫ ﻳﻌﻧﻲ ﻣﺣﻭﺭ‬. - Each doublet is 2 microtubule (A) complete & (B) incomplete. - From A microtubule 3 proteins arise → 1- Radial spoke → to the center. 2- Nexin → from A to B of another doublets. 3- Dynein → 2 arms contain ATPase enzyme. Function: Brush away things from the surface of the cells Flagella  The same structure as cilia ( 100 µm ).  In human, the only cell with one flagellum is spermatozoa. DR. Ahmed Ammar 16 1st Year Histology LM: Appear as bundles of fibril by silver stain. EM: Show 3 types: 1- Thin filament (actin): 5nm in diameter. Present in 2 forms: Stable in muscle cell. Unstable in the ❶cell under cell membrane (exo & endocytosis) ❷ associated with organelle (moving them) ❸ in mitotic cell (cleavage). 2- Intermediate filament: 10nm in diameter. By immunecytochemical stain Types: - Keratin in skin epithelium. - Vimentin in cells of mesenchymal origin. - Desmin in muscles. - Glial in nervous tissue. - Neurofilament in nerve cell. 3- Thick filament (myosin): 15nm in diameter. (2 heavy chain & 4 light chains like golf stick) Present in muscle. DR. Ahmed Ammar 17 1st Year Histology ♥ 3 types → (1) Stored food :- Glycogen → LM :- not seen by H&E but appear red with best's carmine & magenta with PAS. EM :- electron dense particle 2 forms → β rosette & large α particle. Lipid → LM :- not seen by H&E but seen by Sudan III → orange Sudan black → black EM :- Electron lucent vacules. Secretion granules → Include mucous droplets & certain hormones (2) Pigments:- Endogenous pigment Lipofuscin Melanin Hemoglobin  Yellow brown Black in color  Red in color present in skin present in RBC Present in & retina neuron & Cardiac  most important muscle.  Protect body pigment. ↑ with age from UV ray of the sun. DR. Ahmed Ammar 18 1st Year Histology Exogenous pigment Carbon Carotene  black color  orange color  With smoking in lung or  present in Vitamin A rich Tatoo in skin. food as carrot. (3) Crystals:- Present in some cells as sertoli cell of testis.  Colloid substance in which (organelle, inclusion & cytoskeleton) are suspended.  Form 50% of cell volume.  Function → 1- Coordinate movement of Organelle. 2- Contain enzyme that share in metabolism. 3- Transport signals from cell membrane to sites inside the cell. 4- Provide viscosity of cytoplasm. DR. Ahmed Ammar 19 1st Year Histology  The most prominent structure in the cell.  - Shape → Rounded, Oval, flat, lobulaled & irreqular. - Size → Small, medium & large. - Site → central, peripheral, apical, Basal & eccentric. - Stain→deep basophilic(inactive cell)& vesicular basophlic(active cells) - Number → usually single nucleus - 2 nuclei in liver cell mullinucleated in muscle cell -No nuclei in RBC's  not true cell.  4 Companents: A- Nuclear envelope. B- Nucleolus. C- chromatin. D- Nuclear matrix. (A) Chromatin ♥ DNA + Histone protein → chromatin. ♥ Coiled chromatin → chromatid. ♥ 2 chromatid = chromosome. ♥ In non-dividing cell, DNA present in the form of chromatin. DR. Ahmed Ammar 20 1st Year Histology ♥ 2 types of chromatin: Eu chromatin Hetero chromatin - active DNA - Inactive DNA - Extended uncoiled - Highly coiled - LM: Light basophilic (vesicular) - Deep basophilic - EM: Electron lucent granule. - Electron dense granule. - 3 types: Peripheral Nucleolus associated Islets (B) Nuclear envelope:  It's 2 unit membrane (inner & outer), separated by a space called (perinuclear space) or (intermembranous space) 40-70 nm.  The 2 membrane fuse together at certain points to form (nuclear pore) that connect between nucleus & cytoplasm. 1- Outer membrane: Continuous with RER. 2- Inner membrane: Contain fibrous lamina that:- Stabilize the nuclear envelope. Provide a site for chromatin in non dividing cell. 3- Nuclear pore: Octagonal structure: ‫ﻟﻠﻔﻬﻡ‬ Annulus: 8 large protein granule arranged in inner & outer ring in each pore. Radial spoke: from 8 granules to the center of the pare. Plug: electron dense granule in the center. DR. Ahmed Ammar 21 1st Year Histology Function of nuclear pore → 1) Allow passage of mRNA. 2) Allow passage of Ions & molecules < 9 nm without energy. 3) Molecules > 9 nm can pass by active transport utilizing energy. (C) Nucleolus: - Spherical structure up to 1mm & contain rRNA + protein. - LM: intense basophilic. - EM: 3 component: 1- Nuclear organizing region: Pale area contain DNA that code for rRNA. Chromosome (13, 14, 15, 21, 22) 2- Fibrillar components: (10 nm) Maturing ribosome , ribosomal subunit that not mature yet & waiting to be exported to cytoplasm. 3- Granular components: (20 nm) Mature ribosome → rRNA + protein. Function: rRNA synthesized in nucleolus & protein synthesized in cytoplasm then bind together & migrate to cytoplasm as mature ribosome. (D) Nuclear Matrix: - It fill the space between chromatin & nucleolus. - Contain protein, enzyme, metabolites, ions & fibril called (nucleoskeleton). N.B: Function of nucleus: 1- Carries all genetic information. 2- Formation of RNA. 3- Play major role in cell cycle & cell division. DR. Ahmed Ammar 22 1st Year Histology DR. Ahmed Ammar 23

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