Asthma, Cell Morphology and membranes

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Asthma, Cell Morphology and membranes

• For those of you with the book
• Chapter 4
• Chapters 1 and 2 are highly advisable for those
  of you with less recent backgrounds in biology or
  chemistry.
• Objectives
• Review of basic cell structure
• Membrane structure and composition
• The pathogenesis of asthma attacks

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Asthma

• Volunteers?

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Asthma

• Definition Reversible airways obstruction not
  due to any other disease.
• Symptoms
• Coughing, wheezing and shortness of breath.
• Chest pain
• Expectoration of thick, stringy mucus
• In severe attacks
• Rapid breathing
• Cyanosis, indicating hypoxia
• Respiratory acidosis from hypoventilation
• Death from respiratory failure

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Attacks
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Impact

• Incidence
• Around 7 of the population under 18 years of
  age.
• Rate has doubled over the last twenty years.
• Around 2 in 10,000 dies of the disease.
• Seventh-ranked chronic condition in America.
• Economics
• Costs for asthma care in the United States are
  estimated at 14 billion, with direct
  expenditures accounting for 9.4 billion.

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Etiology

• Uncertain.
• Genetic and environmental factors play a role.
• Current opinion is that the environment does not
  cause the disease, but rather exacerbates it.

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Animal cell structure - membranes
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Membrane Functions

• Compartmentalization Raising concentrations
• Helps maintain adequately high concentrations of
  enzymes and substrates.
• Is this really a problem? Yes. Mass action
  drives many processes in cells that wound not
  normally go.
• Compartmentalization Localization of function
• Regulation of transport
• Detection of signals through receptors
• Cell-cell, and cell-substrate binding through
  adhesion receptors

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Functions, continued

• These functions are as dependent upon the
  proteins associated with membranes as of the
  membranes themselves.
• In general
• The membrane forms a transport barrier, while
• Proteins associated with the membrane provide all
  other functions.

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Phospholipid structure
Phosphatidic acid
Naming phosphatidyl_______
See figure 2-11 in your book
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Phospholipids Spontaneously Form Bilayers
See figure 2-12
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Scales

• A cell membrane is approximately 4 nanometers
  (nm) thick
• 1 nm 10-9 m
• Proteins can range over 1-100 nm, depending on
  their shape
• A typical cell is on the order of 10 microns
  (?m) in diameter
• 1 ?m 10-6 m
• Human hair 20-200 ?m in diameter

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Membrane Structure
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Fluid Mosaic Model

• Proteins are embedded in a semi-fluid lipid
  bilayer - the "fluid mosaic model"
• Consist of proteins associated with a bilayer of
  lipids
• Integral membrane proteins (include transmembrane
  proteins)
• Peripheral membrane proteins
• Lipid-anchored proteins
• The individual constituents are free to diffuse
  laterally in the plane of the membrane.

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Membrane Fluidity

• If the membrane becomes too "solid," membrane
  proteins cease to function normally.
• Important for design of drug delivery vehicles,
  and for cold-blooded animals.
• Regulated by
• The degree of unsaturation in the fatty acids.
• More double-bonds more kinks phospholipids
  cant pack close together to solidify.
• Cholesterol

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Fatty Acid Tails and Fluidity

• Palmitic acid
• Myristic acid
• Linoleic acid
• Arachidonic acid

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Membrane Fluidity

• Cholesterol
• is another component of membranes
• Serves to keep membranes fluid at low
  temperatures, yet reduces fluidity at high
  temperatures.

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The Nucleus

• Separates
• DNA from cytosol
• transcription from translation
• Key Features
• Nuclear envelope
• nuclear pores
• nucleolus

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The Smooth Endoplasmic Reticulum (SER)

• Responsible for
• most lipid synthesis
• Ca2 ion storage
• detoxification
• Key Features
• network of interconnected closed membrane tubules
  and vesicles

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The Rough Endoplasmic Reticulum (RER)

• Responsible for
• Membrane protein synthesis
• Extracellular protein synthesis
• Key Features
• Flattened sacks rather than tubules
• Studded with ribosomes

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Ribosomes

• Uses information encoded in RNA to synthesize
  protein
• Two subunits
• Free, and bound to RER

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The Golgi Complex

• Modifies and sorts most ER products
• Key Features
• series of flattened compartments vesicles
• composed of 3 regions
• cis (entry)
• medial
• trans (exit)
• each contains different set of modifying enzymes

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Secretory Pathway and Vesicles
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Lysosomes

• Responsible for degrading
• certain cell components
• material internalized from the extracellular
  environment
• Key Features
• pH of lumen ? 5
• acid hydrolases carry out degradation reactions

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Mitochondria

• Site of ATP production via aerobic metabolism
• Oxidation of fats
• Key Features
• outer membrane
• inner membrane
• cristae
• matrix
• Has its own chromosome and ribosomes

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The cytosol (cytoplasm)

• The portion of the cell enclosed by the plasma
  membrane but not part of any organelle
• Free organelles
• Not bound by membranes
• ribosomes
• the cytoskeleton

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Cytoskeleton

• Cytoskeletal proteins lend rigidity, mobility and
  intracellular organization of membranous, free
  organelles and metabolic pathways.
• Microtubules
• composed of tubulin proteins
• Intracellular transport
• Microfilaments
• formed of the protein actin and actin-binding
  proteins
• Cell shape, contraction and motility
• Intermediate filaments
• Relatively stable
• Lend lateral strength to tissues

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Asthma
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White Blood Cells in the Immune Response

• White blood cells (leukocytes) are the primary
  mediators of the immune response
• Called blood cells but most spend much of their
  time in the tissue
• Transmigration is the process of pushing through
  the blood vessel wall into the tissue.

http//step.sdsc.edu/projects95/Protein.lesson/ery
throcyte.html
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Granulocytes (Polymorphonucleocytes PMNs)

• Neutrophils
• Basophils
• Eosinophils
• Often called PMNs because of their multilobed
  nuclei

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Basophils / Mast Cells

• Basophils are similar to tissue-resident mast
  cells
• Highly granular
• Can degranulate
• Release pro-inflammatory substances
• Recruit more white cells
• Increase vascular permeability

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Eosinophils

• Distinct Golgi
• Distinctive granules
• Normally few in the circulation
• Functions
• Attack parasites

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Asthma The beginning of the cycle

• Triggers cause mast cells to degranulate,
  releasing cytokines and chemokines
• Cytokines small proteins that pass signals
  between immune cells
• Chemokines a simple compound produced by one
  cell that effects the activity of another

http//www.vetmed.ufl.edu/sacs/histo/con02.htm
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Leukotrienes

• Leukotrienes are chemokines derived from
  arachidonic acid through the action of the enzyme
  lipoxygenase.

arachidonic acid
lipoxygenase
leukotriene A4
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Leukotrienes from Mast Cells

• Increase vascular permeability, giving rise to
  edema
• Cause bronchioles to constrict due to smooth
  muscle contraction
• Cause mucus secretion by respiratory epithelial
  cells
• Promote white cell homing,eosinophils in
  particular

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Yes, weve got trouble!

• Eosinophils release their secretory granules.
• Components of these granules
• are toxic to eukaryotic, multicellular organisms
• recruit additional white blood cells (cytokines,
  including interleukins)
• Eosinophils are synthetic, which means they will
  regenerate their secretory granules

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Brainstorming

• How would YOU treat asthma?
• Current treatments?