Epithelial Cells: Structure, Function & Classification

Epithelial Cells

• Covers surfaces and lines cavities
• Forms a protective barrier
• Small intercellular spaces exist between them
• Attached to one another via tight junctions, desmosomes, and gap junctions
• Polarized, with distinct apical and basal surfaces
• Separated by a basement membrane that anchors to connective tissue

Epithelial Cell Functions

• Protection against mechanical damage, bacterial attacks, and toxins
• Permeability control by absorption and secretion in the GI tract
• Surface cleaning by ciliated epithelium, which moves mucus in the respiratory tract
• Sensation through detection of environmental stimuli
• Secretion of specialized substances from glandular epithelium

Epithelial Cell Classifications

• Based on layers:
• Simple epithelium has one layer of cells
• Stratified epithelium has multiple layers of cells
• Based on shape:
• Squamous epithelium consists of flattened cells found in blood vessels and lung alveoli
• Cuboidal epithelium consists of cube-shaped cells in kidney tubules and glands
• Columnar epithelium consists of column-shaped cells in intestines
• Pseudostratified epithelium appears stratified but is a single layer, found in the trachea
• Transitional epithelium can change shape, found in the bladder

Cell Junctions

• Tight junctions prevent fluid leakage in stomach lining
• Gap junctions allow small molecules to pass in the heart
• Desmosomes provide mechanical strength in the skin

Comparison of Junction Types

• Tight junctions
• Structure: Interlocking membrane proteins
• Function: Prevents leakage of fluids
• Location: Digestive tract and kidney tubules
• Gap junctions
• Structure: Connexon protein channels
• Function: Allows direct passage of ions and molecules
• Location: Heart, neurons, and smooth muscle
• Desmosomes
• Structure: Adhesive protein complexes (desmoglein, desmocollin)
• Function: Provides mechanical strength
• Location: Skin and cardiac muscle
• Hemidesmosomes
• Structure: Anchors cells to the basement membrane
• Function: Stabilizes epithelial attachment
• Location: Epidermis and cornea

Glandular Epithelium

• Endocrine glands release hormones directly into the bloodstream, as exemplified by the thyroid
• Exocrine glands secrete substances through ducts, such as sweat glands

Modes of secretion for Glandular Epithelium

• Merocrine: Exocytosis, like in salivary glands
• Apocrine: Cytoplasm loss, like in mammary glands
• Holocrine: Cell rupture, like in sebaceous glands

Membrane System

• Essential for cellular compartmentalization, signaling, and homeostasis

Membrane Structure:

• Lipid bilayer composition:
• Phospholipids are amphipathic molecules that form bilayers
• Cholesterol maintains fluidity and stability
• Glycolipids are important for cell recognition
• Membrane proteins:
• Integral proteins span the bilayer acting as transporters or receptors
• Peripheral proteins attach to the membrane surface, linking to the cytoskeleton
• Fluid-mosaic model: dynamic and flexible structure
• Lateral diffusion of lipids and proteins ensures adaptability

Membrane Function

• Selective permeability and transport:
• Small, nonpolar molecules such as O2 and CO2 diffuse freely
• Ions and large molecules require specific transport mechanisms
• Passive transport occurs through simple or facilitated diffusion and osmosis
• Active transport requires energy
• Cell signaling and communication occurs via receptors, G-protein signaling, or tyrosine kinases

Organelles Involved in the Membrane System

• Endoplasmic Reticulum (ER):
• Rough ER has ribosomes for protein synthesis, folding, and post-translational modifications (PTMs)
• Smooth ER is responsible for lipid synthesis, detoxification, and calcium (Ca2+) storage
• Golgi apparatus: modifies, sorts, and packages proteins and lipids
• Forms vesicles for secretion and organelle targeting
• Lysosomes: Contain hydrolytic enzymes for degrading macromolecules
• Key role in autophagy and waste management
• Mitochondria: ATP production through oxidative phosphorylation (oxphos)

Membrane Dynamics

• Vesicle trafficking:
• Coated vesicles (clathrin, COP 1, COP 2) direct vesicle movement
• Endocytosis: Process includes phagocytosis, pinocytosis, and receptor-mediated endocytosis
• Exocytosis: Process releases materials from the cell
• Membrane fusion and recycling:
• SNARE proteins mediate vesicle fusion
• Lysosomal degradation recycles membrane components

Phospholipid Composition in the Membrane Bilayer

• Outer leaflet: phosphatidylcholine and sphingomyelin
• Inner leaflet: phosphatidylserine and phosphatidylethanolamine

Destructive Cell Processes

Types of Cell Death

• Apoptosis (Type I): programmed and non-inflammatory form of cell death
• Caspase-dependent
• Requires energy, tightly controlled, and occurs without inflammation
• Characterized by cell shrinkage, membrane blebbing, and the formation of apoptotic bodies
• Non-random DNA fragmentation
• Causes: normal development, aging, tissue homeostasis, and low-dose injuries (heat, radiation, hypoxia, cytotoxic drugs)

Pathways of Apoptosis

• Intrinsic (Mitochondrial) Pathway: triggered by cellular stress
• Involves BAX/BAK activation and mitochondrial outer membrane permeabilization
• Cytochrome c release that then activates Apaf-1, resulting in apoptosome formation, which subsequently activates caspase 3 and caspase 9, leading to cell death
• Extrinsic (Death Receptor) Pathway: initiated by ligands binding to death receptors
• Formation of the DISC (death-inducing signaling complex) activates caspase 8, which directly activates caspase 3, thereby linking to the intrinsic pathway
• ER Stress-induced Apoptosis: caspase 12 activation leads to apoptosis via caspase 9 and caspase 3
• Occurs due to misfolded proteins in the ER causing stress
• Necrosis (Type III): uncontrolled and inflammatory form of cell death
• Triggered by severe damage
• Leads to inflammation due to lysosomal enzyme release
• Characterized by cell and organelle swelling
• Plasma membrane rupture releasing cytoplasmic content
• ATP-independent and caspase-independent
• Causes: extreme conditions, hyperthermia, hypoxia, toxins, and viral infections

Regulated Pathways of Necrosis

• MPTP-dependent
• Necroptosis, when caspase 8 is inhibited
• PARP-dependent necrosis
• Autophagy (Type II): self-eating and stress response mechanism
• Survival mechanism for degrading and recycling damaged proteins and organelles

Types of Autophagy

• Macroautophagy: Autophagosomes engulf cargo and fuse with lysosomes
• Microautophagy: Lysosomal membrane directly engulfs cytoplasmic material
• Chaperone-mediated autophagy: Hsp70 binds to proteins

Protein Quality Control and Intracellular Degradation

• Ubiquitin-Proteasome System (UPS): degrades short-lived proteins
• Ubiquitination involves E1 (activation), E2 (conjugation), and E3 (ligation to substrate)
• 26S Proteasome Degradation: 19S cap recognizes and unfolds proteins
• 20S core performs proteolysis by caspase-like, trypsin-like, and chymotrypsin-like activities
• Functions: degrades misfolded proteins and regulates cell cycle, apoptosis, and immune responses

Proteasome Dysfunction in Disease

• Heart failure: UPS dysfunction leads to protein aggregates
• Neurodegeneration: Impaired proteasome leads to Alzheimer's and Parkinson's

Heat Shock Proteins (HSPs)

• Hsp70, Hsp90, and Hsp110 prevent protein aggregation
• HSPs are upregulated during cellular stress

Key Differences Between Cell Death Types

• Apoptosis (Type I):
• Energy-dependent
• Not inflammatory
• Triggered by DNA damage, stress, and normal turnover
• Exhibits cell shrinkage, membrane blebbing, and apoptotic bodies
• Follows intrinsic and extrinsic pathways
• Necrosis (Type III):
• Not energy-dependent
• Inflammatory
• Triggered by severe injury, toxins, and ischemia
• Exhibits swelling and membrane rupture
• Follows MPTP, necroptosis, and PARP-dependent pathways
• Autophagy (Type II):
• Energy-dependent
• Not inflammatory
• Triggered by starvation and stress
• Exhibits autophagosome formation
• Follows macroautophagy, microautophagy, and CMA

Genome Evolution and Genetic Variation

• Types of Genetic Variation
• Point Mutations: Single nucleotide changes
• Silent mutations have no effect on the protein
• Missense mutations are an amino acid change
• Nonsense mutations result in a premature stop codon and truncated protein
• Mutation in Regulatory DNA: affects when and where genes are expressed
  • Lactase persistence mutation
• Gene Duplication: Entire genes or segments duplicate
• One copy retains the function, while the other mutates and evolves
• Hemoglobin genes (α, β) evolved from gene duplicates
• Exon Shuffling: Recombination between exons of different genes
• Transposable Elements: Sequences that move within the genome
• LINES: encode reverse transcriptase
• SINES (Alu sequences): depend on LINE enzymes for movement
  • Move via DNA transposons (cut-paste) and retrotransposons (copy-paste)
• Horizontal Gene Transfer: Occurs between species and is common in bacteria
  • Bacterial antibiotic resistance, sometimes

Percentages of the Human Genome

• 5% of the human genome is conserved across mammals
• Protein coding genes are ~1.5%
• Regulatory DNA is a significant portion of the genome, providing control
• Repetitive DNA includes short tandem repeats (STRs) and transposons
• Copy number variations (CNVs) are large DNA segments that vary in copy number between individuals
• STRs (CA repeats) are highly variable and used in DNA fingerprinting

The Role of Transposable Elements

• Nearly half of the genome
• They can disrupt gene function, rearrange DNA, and serve as recombination hotspots

Peroxisomes

• 70-90% of ATP in the heart comes from fatty acid oxidation
• 10-20% comes from glucose oxidation

Fatty Acid Metabolism in the Heart

• FA uptake is facilitated by FAT/CD36, FABPpm, and FATP
• FA oxidation pathway:
• FA → FA-CoA → Acylcarnitine → FA-CoA → Acetyl-CoA → ATP through the TCA cycle in the mitochondria

Regulation of FA Metabolism in the Heart

• AMPK activates FA oxidation under high-energy demand
• Insulin promotes glucose utilization by inhibiting FA oxidation
• Malonyl-CoA inhibits CPT1, reducing FA oxidation

Glucose Metabolism in the Heart

• Glucose uptake via GLUT1 and GLUT4
• Pyruvate enters the mitochondria to produce ATP via the TCA cycle

Metabolic Flexibility of the Heart

• After a high-carb meal → more glucose metabolism
• During fasting → FA oxidation
• Under hypoxia → more anaerobic (lactate) production

Peroxisomes

• Membrane-bound organelle
• no DNA or ribosomes

Functions

• β-oxidation of very long-chain fatty acids → shorter FAs transported later
• α-oxidation of branched-chain FAs → prevents accumulation of phytanic acid
• Metabolism of ROS → contain catalase to breakdown H2O2
• Biosynthesis of plasmalogens → essential for the nervous system
• Bile acid synthesis → in the liver
• Steroidogenesis → in adrenal glands

Peroxisome Biogenesis

• PEX 16 initiates peroxisome membrane formation
• PEX 3 helps the insertion of peroxisomal membrane proteins
• PEX 19 acts as a chaperone
• The number of peroxisomes increases in response to FAs, hypolipidemic drugs and cold adaptation

PPAR a

• A key regulator of proliferation (peroxisomal proliferation activated receptor alpha)

Three Stages of Proliferation

• Elongation (PEX 11 dependent)
• Constriction
• Fission
• Vesicles fuse together

Immunity

Innate Immunity

• Non-specific
• Fast response
• No memory
• First line: Skin (chemical, 
hair, keratin), 
Mucus (mucous, cilia, pH,
vaginal), 
Membranes (saliva, tears, 
gastric, urine, acid)
• Cells Neutrophils (granulocyte)
• All WBC except Eosinophils (they call 
lymphocytes, other cells, basophils
Maot cells, Natural killer (MHC), Dendritic (show off), monocyte Macrophages

Adaptive Immunity

• Specific, and has memory
• slower primmed, but faster on 2nd exposure
• Humoral (B Cells)
• -Naive first, the signal is to select for a pathogen
-clonal expansion (leads to memory B cells, plasma cells (filled w/ specific ab, released into blood)), signal to
• -Cell mediated (T cells (thymus))
• 
also naive first, T-helper (CD4+), T-cytotoxic (CD8+), will see MHC1 (when a cell is (infected))2(wenn a cell has
engulfed a pathogen)), clonal expansion leads to
memory CD8+ and cytotoxic T cells that Cytotoxic T NK, (macrophages), cause cytotoxicity and also call cytokines
B-cells

Immunology Notes

• 1st antigen-specific presented on the surface, and 2 - costim. signal is is needed, if the signals occur then there is good immunity

• Advantage is there is none reactivity to self", which prevents autoimmunity

• produce cytokines triggers adaptive immune system First signal is activation. and second signal is a B7 (MHC 1 to TCRCD28) T cells

Peripheral Tolerance

• Anergy means state of functional unresponsiveness


• When a T-cell recognizes an antigen, anergy occurs, but it prevent autoimmunity

• Significance is that anergy exploited and can be prevented and autoimmune

• can trigger both

• Pressure cause

Cytoskeleton Functions

• Actin filaments maintain cell shape (resisting tension), enable cell movement (muscle contraction), cell division (animal cells) and support organization and cell
• Microtubules provide cell movement (resisting compression), provide organisation and cell movement, move chromosomes during cell division, and provide tracks for intracellular
• Intermediate filaments maintain cell shape (resisting tension), hold nuclei or Support organisation

Actin Dynamics

• Actin monomers that actin filaments polymers promote promote

• Cross actin filaments that supports

• force is generated for movement by tension
Actin

• Cell adhesion the actin filaments with

• Cell cell contact.

• Act as signals, the sensors

• sense

Mechanical Forces

• Mechanotransduction Rho/ROCK pathway and TA2 gene, signals expression factors for tissue remodeling,
• Integrins and connect ecm, sense forces and activate