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Cellular Structures, Genes, Immunity, and Diseases

Week One Lecture

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Cellular Functions

Movement Conductivity Metabolic absorption Secretion Excretion Respiration Reproduction Communication

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Eukaryotic Cell

Nucleus Nuclear envelope Nucleolus DNA

• DNA replication, repair, and transcription Histone proteins Cell division Genetic information

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Eukaryotic Cell (cont’d)

Nucleus (cont’d)

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Eukaryotic Cell (cont’d)

Nucleus (cont’d)

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Eukaryotic Cell (cont’d)

Cytoplasm Cytoplasmic matrix Cytosol Function Cytoplasmic organelles

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Eukaryotic Cell (cont’d)

Cytoplasm (cont’d)

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Eukaryotic Organelles

Ribosomes RNA protein Free ribosomes Attached ribosomes

Endoplasmic reticulum Site of protein synthesis Smooth vs. rough endoplasmic reticulum

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Eukaryotic Organelles (cont’d)

Golgi complex Flattened, smooth membranes Secretory vesicles Proteins from the endoplasmic reticulum are

packaged in the Golgi complex Cisternae

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Eukaryotic Organelles (cont’d)

Lysosomes Originate from the Golgi Catalyze proteins, lipids, nucleic acids, and

carbohydrates Role in autodigestion

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Eukaryotic Organelles (cont’d)

Peroxisomes Contain oxidative enzymes Break substances down into harmless products

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Eukaryotic Organelles (cont’d)

Mitochondria Surrounded by a double lipid–bilayer

membrane Participates in oxidative phosphorylation Increased inner membrane surface area

provided by cristae

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Eukaryotic Organelles (cont’d)

Cytoskeleton “Bones and muscles” of cell Maintains the cell’s shape and internal

organization Permits movement of substances within the

cell and movement of external projections Microtubules

• Centrioles Macrofilaments

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Plasma Membrane

Controls the composition of a space or compartment they enclose

Structure Caveolae Lipids

• Amphipathic lipids Hydrophilic and hydrophobic

• Phospholipids, glycolipids, and cholesterol Carbohydrates

• Glycoproteins

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Plasma Membrane (cont’d)

Proteins Integral, peripheral, transmembrane Functions

• Receptors• Transport• Enzymes• Surface markers• Cell adhesion molecules (CAMs)• Catalysts

Fluid mosaic model

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Plasma Membrane (cont’d)

Fluid mosaic model Flexibility Self-regulating Impermeability to some substances Fluidity impacted by temperature, amount of

cholesterol

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Membrane Fluidity

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Plasma Membrane

Plasma membrane protein functions

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Cellular Communication

Plasma membrane bound receptors Intracellular receptors Gap junctions (contact signaling) Chemical signaling

Paracrine Autocrine Hormonal Neurohormonal

Neurotransmitters

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Cellular Communication (cont’d)

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Cellular Communication (cont’d)

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Cellular Metabolism

Metabolism Chemical tasks of maintaining essential cellular

functions Anabolism

• Energy using Catabolism

• Energy releasing

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Adenosine Triphosphate

Created from the chemical energy contained within organic molecules

Used in synthesis of organic molecules, muscle contraction, and active transport

Stores and transfers energy

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Cellular Energy

Digestion Extracellular breakdown of proteins, fats,

polysaccarides to subunits Glycolysis

Intracellular breakdown of subunits to pyruvate, then to acetyl CoA

Anaerobic Limited ATP produced

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Cellular Energy (cont’d)

Citric acid cycle Also called Krebs cycle or the tricarboxylic acid

cycle (TCA) Much ATP produced via oxidative

phosphorylation if oxygen present Waste products excreted

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Cellular Energy (cont’d)

Oxidative phosphorylation Occurs in the mitochondria Mechanism producing energy from fats, CHO,

proteins Involves the removal of electrons from various

intermediates via a co-enzyme such as nicotinamide adenine dinucleotide (NAD) to transfer electrons

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Cellular Energy (cont’d)

Oxidative phosphorylation (cont’d) Anaerobic glycolysis: if oxygen not available,

CHO is converted to pyruvic acid (pyruvate) in cytoplasm with production of two ATP molecules which is insufficient for energy needs; pyruvate then converted to lactic acid

Process reverses when oxygen becomes available and lactic acid is converted back to either pyruvic acid or glucose, which moves into the mitochondria and enters the citric acid cycle

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Cellular Cellular Energy (cont’d)

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Cellular Energy (cont’d)

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Membrane Transport

Cellular intake and output Cells continually take in nutrients, fluids, and

chemical messengers from the extracellular environment and expel metabolites, or the products of metabolism, and end products of lysosomal digestion

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Body Fluids

Electrolytes, which are electrically charged, make up 95% of solutes Cations are positively charged and migrate

toward the negative pole (e.g., Na+) Anions are negatively charged and migrate

toward the positive pole (e.g., Cl-)

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Movement of Body Fluids and Electrolytes

Water and electrolytes move across cell membranes via multiple passive (no energy required) and active (energy required) mechanisms

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Membrane Transport

Passive transport (small uncharged solutes) No energy expended Diffusion of solutes

• Concentrated gradient Filtration

• Hydrostatic pressure (BP) Osmosis of water

• Osmolarity vs. osmolality Tonicity

• Isotonic, hypertonic, and hypotonic Passive mediated transport

• Integral or transmembrane proteins• Channel protein (ion channels) (gating)

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Membrane Transport (cont’d)

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Membrane Transport (cont’d)

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Membrane Transport (cont’d)

Active mediated transport (active transport) Energy expended Protein transport pumps

• Na/K ATPase pump Transport by vesicle formation

• Endocytosis Pinocytosis Phagocytosis Receptor mediated Caveolae

• Exocytosis

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Active Transport

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Membrane Transport

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Electrical Impulses

Resting membrane potential Action potential

Depolarization Threshold potential

• Hyperpolarized vs. hypopolarized Repolarization Refractory period

• Absolute and relative

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Propagation of an Action Potential

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Theory of AgingTheory of Aging

Accumulation of injurious eventsAccumulation of injurious events Genetically controlled programGenetically controlled program Theories:Theories:

Genetic and environmental lifestyle factorsGenetic and environmental lifestyle factors Alterations of cellular control mechanismsAlterations of cellular control mechanisms Degenerative extracellular and vascular Degenerative extracellular and vascular

changeschanges

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AgingAging

Cellular agingCellular aging Atrophy, decreased function, and loss of cellsAtrophy, decreased function, and loss of cells

Tissue and systemic agingTissue and systemic aging Progressive stiffness and rigidityProgressive stiffness and rigidity SarcopeniaSarcopenia

FrailtyFrailty Mobility, balance, muscle strength, motor Mobility, balance, muscle strength, motor

activity, cognition, nutrition, endurance, falls, activity, cognition, nutrition, endurance, falls, fractures, and bone densityfractures, and bone density

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Tissue Formation

Extracellular matrix Pattern formation

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Types of Tissue

Epithelial tissue Simple vs. stratified squamous Transitional Cuboidal Simple vs. stratified columnar Pseudostratified ciliated

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Types of Tissue (cont’d)

Connective tissue Dense regular or irregular Fibers Loose and dense connective tissue Elastic and reticular connective Cartilage, bone, vascular, and adipose

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Types of Tissue (cont’d)

Muscle tissue Smooth Striated (skeletal) Cardiac

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DNADNA

Pentose sugar (deoxyribose)Pentose sugar (deoxyribose) Phosphate molecule Phosphate molecule Four nitrogenous bases:Four nitrogenous bases:

Pyrimidines: cytosine and thyminePyrimidines: cytosine and thymine Purines: adenine and guaninePurines: adenine and guanine

Double helix modelDouble helix model NucleotideNucleotide

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RNARNA

RNA is synthesized from the DNA RNA is synthesized from the DNA templatetemplate

RNA polymerase binds to promoter siteRNA polymerase binds to promoter site Results in the formation of messenger Results in the formation of messenger

RNA (mRNA)RNA (mRNA) RNA polymerase detachesRNA polymerase detaches mRNA moves out of the nucleus and into mRNA moves out of the nucleus and into

the cytoplasmthe cytoplasm Transcription continues until termination Transcription continues until termination

sequence is reachedsequence is reached

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ChromosomesChromosomes

Somatic cells:Somatic cells: Contain 46 chromosomes (23 pairs)Contain 46 chromosomes (23 pairs) Diploid cellsDiploid cells

Gametes:Gametes: Contain 23 chromosomesContain 23 chromosomes Haploid cells Haploid cells

• One member of each chromosome pairOne member of each chromosome pair

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ChromosomesChromosomes

MeiosisMeiosis Formation of haploid cells from diploid cellsFormation of haploid cells from diploid cells

MitosisMitosis Formation of somatic cellsFormation of somatic cells

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Autosomal AneuploidyAutosomal Aneuploidy

Partial trisomyPartial trisomy Only an extra portion of a chromosome is Only an extra portion of a chromosome is

present in each cellpresent in each cell Chromosomal mosaicsChromosomal mosaics

Trisomies occurring only in some cells of the Trisomies occurring only in some cells of the body body

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Down SyndromeDown Syndrome

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Single-Gene DisordersSingle-Gene Disorders

EpigeneticsEpigenetics Same DNA sequence can produce different Same DNA sequence can produce different

phenotypes due to chemical modification that phenotypes due to chemical modification that alters expression of genesalters expression of genes

Genomic imprintingGenomic imprinting One parent imprints (inactivates) the gene One parent imprints (inactivates) the gene

during transmission to offspringduring transmission to offspring

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Single-Gene Disorders (cont’d)Single-Gene Disorders (cont’d)

Autosomal recessive disorderAutosomal recessive disorder Abnormal allele is recessive and a person must Abnormal allele is recessive and a person must

be homozygous for the abnormal trait to be homozygous for the abnormal trait to express the diseaseexpress the disease

The trait usually appears in the children, not The trait usually appears in the children, not the parents, and it affects the genders equally the parents, and it affects the genders equally because it is present on a pair of autosomesbecause it is present on a pair of autosomes

Cystic fibrosis gene encodes a chloride ion Cystic fibrosis gene encodes a chloride ion channel in some epithelial cells that alters channel in some epithelial cells that alters sodium balancesodium balance

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Sex-Linked DisordersSex-Linked Disorders

Sex-linked (X-linked) disorders are usually Sex-linked (X-linked) disorders are usually expressed by males because females expressed by males because females have another X chromosome to mask the have another X chromosome to mask the abnormal geneabnormal gene

Can you name a disorder that is a sex-Can you name a disorder that is a sex-linked disorder? linked disorder?

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ImmunityImmunity

First line of defenseFirst line of defense Innate (natural) (native) immunityInnate (natural) (native) immunity

Second line of defenseSecond line of defense InflammationInflammation

Third line of defenseThird line of defense Adaptive (acquired) immunityAdaptive (acquired) immunity

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First Line of DefenseFirst Line of Defense

Physical barriers:Physical barriers: SkinSkin Linings of the gastrointestinal, Linings of the gastrointestinal,

genitourinary, and respiratory tractsgenitourinary, and respiratory tracts• Sloughing off of cellsSloughing off of cells• Coughing and sneezingCoughing and sneezing• FlushingFlushing• VomitingVomiting• Mucus and ciliaMucus and cilia

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PhagocytesPhagocytes

NeutrophilsNeutrophils Also referred to as polymorphonuclear Also referred to as polymorphonuclear

neutrophils (PMNs)neutrophils (PMNs) Predominate in early inflammatory responsesPredominate in early inflammatory responses Ingest bacteria, dead cells, and cellular debrisIngest bacteria, dead cells, and cellular debris Cells are short lived and become a component Cells are short lived and become a component

of the purulent exudateof the purulent exudate

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Phagocytes (cont’d)Phagocytes (cont’d)

Monocytes and macrophagesMonocytes and macrophages Monocytes are produced in the bone marrow, Monocytes are produced in the bone marrow,

enter the circulation, and migrate to the enter the circulation, and migrate to the inflammatory site, where they develop into inflammatory site, where they develop into macrophagesmacrophages

Macrophages typically arrive at the Macrophages typically arrive at the inflammatory site 24 hours or later after inflammatory site 24 hours or later after neutrophilsneutrophils

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Phagocytosis (cont’d)Phagocytosis (cont’d)

Steps:Steps: AdherenceAdherence Engulfment Engulfment Phagosome formationPhagosome formation Fusion with lysosomal granulesFusion with lysosomal granules Destruction of the targetDestruction of the target