Chapter 1Introduction to Cytology
🔬 Definition
Cell biology is the discipline that studies the cell as the basic unit of life, both in its structural organization and in its physiological functioning.
📖 Brief history
| Date | Scientist | Discovery |
|---|---|---|
| 1665 | Robert Hooke | 1st observation of cells (cork) → cornering of the term “cell” |
| 1674 | Leeuwenhoek | 1st protozoa & bacteria under the microscope |
| 1838–39 | Schleiden & Schwann | Cell theory: all living things are made up of cells |
| 1855 | Virchow | “Omnis cellula e cellula” — every cell comes from a cell |
| 1931 | Ruska & Knoll | Electron microscope → ultrastructural revolution |
Cell theory is the foundation of all modern biology. All pathology is fundamentally a cellular pathology.
🧬 General principles of cellular life
Chapter 2Cell Study Methods
🔭 Microscopy
| Type | Power of resolution | Use |
|---|---|---|
| Optical microscopy (OM) | 0.2 µm (200 nm) | Living cells, colored tissues, general structure |
| ME with transmission (MET) | 0.2nm | Fine ultrastructure, organelles, membranes |
| Scanning ME (SEM) | 10nm | Raised cell surface, 3D morphology |
| Confocal microscopy | 0.2 µm | Fluorescence, 3D imaging of living cells |
| Atomic force microscopy (AFM) | <1nm | Molecular surface, biological membranes |
Resolving power = smallest distance between 2 distinct points. The smaller it is, the better the resolution.
🎨 Colorings
Hematoxylin-Eosin (HE):
- Hematoxylin (basic) → nuclei in blue-violet
- Eosin (acid) → cytoplasm in pink
Gram stain (Bacteria):
- Gram+ → violet (thick wall)
- Gram− → pink/red (thin wall)
Feulgen's reaction: specific to DNA (red-purple coloring). PAS : reveals the polysaccharides (magenta coloring).
⚙️ Biochemical techniques
Differential centrifugation: fractionation of cellular organelles by increasing centrifugation speeds.
Supernatant → 10,000 g → Mitochondria, lysosomes
Supernatant → 100,000 g → Ribosomes, ER, Golgi
Supernatant → Rest = Cytosol
Autoradiography: monitoring of radioactive molecules to study their cellular fate.
Immunofluorescence: localization of proteins using antibodies coupled to fluorochromes.
Western blot: separation and identification of proteins by electrophoresis + antibodies.
🧪 Histochemical & cytochemical techniques
Allows you to locate in situ specific molecules in cells or tissues.
Enzyme-linked immunosorbent techniques (ELISA, immunohistochemistry): detection of antigens using antibodies coupled to a revealing enzyme (peroxidase, alkaline phosphatase).
Chapter 3Cell Types: Prokaryotes & Eukaryotes
⚖️ Comparison Prokaryote / Eukaryote
| Character | Prokaryote (Bacteria) | Eukaryote |
|---|---|---|
| Size | 1–10 µm | 10–100 µm |
| Core | Absent (nucleoid) | Present (nuclear envelope) |
| Membranous organelles | Absent | Present (RE, Golgi, mito…) |
| ADN | Circular, naked, haploid | Linear, histone associated, diploid |
| Ribosomes | 70S (30S + 50S) | 80S (40S + 60S) |
| Cell wall | Peptidoglycan (Gram+/−) | Absent (plants: cellulose) |
| Division | Scissiparity (binary) | Mitosis / Meiosis |
| Cytoskeleton | Absent (rudimentary) | Present and elaborate |
The 70S ribosomes of prokaryotes are the target of antibiotics (aminoglycosides, macrolides, etc.) — a fundamental difference in pharmacology.
🦠 Bacterial Cell (Prokaryotic) — Structure
Envelopes (from outside to inside):
- Capsule : polysaccharides, protection, virulence
- Wall : peptidoglycan (rigidity, shape)
- Plasma membrane : lipid bilayer
Internal structures:
- Nucleoid : circular DNA + RNA + proteins
- Plasmids : extrachromosomal DNA (resistance)
- 70S ribosomes
- Mesosome : membrane invagination (≈ mitochondria)
Appendices: Flagella (mobility), Pili (fixation and conjugation).
🧫 Eukaryotic Cell — General Organization
The eukaryotic cell is compartmentalized. Its main regions:
- Plasma membrane : cellular border, exchanges
- Cytoplasm = Hyaloplasm (cytosol) + Organelles
- Membranous organelles : ER, Golgi, mitochondria, lysosomes, peroxisomes
- Non-membranous organelles : ribosomes, cytoskeleton, centrosome
- Core : separated by the nuclear envelope, contains the genome
Chapter 4Viruses & Non-Cellular Agents
🧬 Definition and characteristics of Viruses
🔩 Viral structure
| Component | Description | Role |
|---|---|---|
| Nucleic acid | DNA or RNA, single/double stranded, linear/circular | Genetic information |
| Capsid | Proteins (capsomers): helical, icosahedral or complex symmetry | Protection of the genome, attachment to cells |
| Envelope | Double lipid membrane (derived from the host cell) + viral glycoproteins | Membrane fusion, tropism |
| Peplos | Envelope + glycoprotein spicules | Recognition of cellular receptors |
Viruses naked (without envelope) are more resistant in the environment than viruses wrapped.
🔄 Viral multiplication cycle
Genome replication → Protein synthesis → Assembly → Liberation
Two possible cycles:
🦠 Classification of viruses
| Criterion | Types |
|---|---|
| Nature of the nucleic acid | DNA viruses / RNA viruses |
| Nucleic acid structure | Single strand (+/−) / Double strand |
| Presence of envelope | Naked / Wrapped |
| Capsid symmetry | Helical / Icosahedral / Complex |
| Target cell (tropism) | Neurotropic, hepatotropic, lymphotropic… |
Retroviruses (e.g. HIV): RNA virus using reverse transcriptase to synthesize DNA → integration into the host genome.
Bacteriophages (phages): viruses infecting bacteria. Structure with icosahedral head, tail and tail fibers.
Let us pray: Infectious protein agents, without nucleic acid. Form pathological aggregates (e.g. Creutzfeldt-Jakob disease).
Chapter 5Plasma Membrane
🏗️ Structure — Fluid Mosaic Model (Singer & Nicolson, 1972)
Thickness: 7–10nm. Visible only in TEM (trilamellar appearance: dark-light-dark).
🧪 Lipid constituents
| Lipid | Proportion | Role |
|---|---|---|
| Phospholipids | ~50% | Two-layer framework, impermeability to polar molecules |
| Cholesterol | ~25% | Regulates fluidity (neither too rigid nor too fluid) |
| Glycolipids | ~5% | Cellular recognition, blood groups (external side only) |
| Sphingolipids | ~20% | Signaling, microdomains (lipid rafts) |
Lipids are distributed in a way asymmetrical : phosphatidylcholine and sphingomyelin on the external side; phosphatidylserine and phosphatidylethanolamine on the inner side (cytoplasmic).
🔬 Membrane proteins
Functions of membrane proteins:
- Transport (channels, pumps, transporters)
- Receiving signals (hormonal receptors)
- Enzymatic catalysis
- Intercellular junctions
- Cellular recognition (surface antigens)
🍬 Glycocalyx
Roles: cellular recognition (ABO blood groups), mechanical protection, lubrication, intercellular and ECM interactions.
Chapter 6Membrane Transport
🚪 Passive transport (without energy)
| Type | Mechanism | Examples |
|---|---|---|
| Single broadcast | Concentration gradient, lipophilic or small molecules | O₂, CO₂, alcohol, steroid hormones |
| Easy distribution | By protein channels or transporters, without energy | Glucose (GLUT), ions (aquaporins) |
| Osmosis | Movement of water from hypotonic to hypertonic solution | Water transport (aquaporins) |
⚡ Active transport (with energy = ATP)
| Type | Mechanism | Example |
|---|---|---|
| Primary active transport | ATPase ion pump, against gradient | Na⁺/K⁺ ATPase pump (3 Na⁺ out, 2 K⁺ in) |
| Secondary active transport | Coupled with the Na⁺ gradient created by the pump | Symport Na⁺/glucose (enterocytes) |
| Antiport | Two molecules in opposite directions | Na⁺/H⁺ exchanger |
The Na⁺/K⁺ ATPase pump is crucial for the membrane potential of excitable cells (neurons, cardiomyocytes). It consumes ~30% of cellular ATP.
🫧 Vesicular transport (cytosis)
Endocytosis
- Phagocytosis : ingestion of large particles (bacteria), by pseudopods (macrophages, neutrophils)
- Pinocytosis : ingestion of liquid and small molecules
- Receptor-mediated endocytosis : mediated by clathrin (eg: LDL, transferrin). Very specific.
Exocytosis
- Constitutive : continuous, e.g.: collagen secretion
- Regulated : triggered by signal (Ca²⁺), e.g.: neurotransmitters, insulin
Endocytosis by interposed receptors is the entry route for many viruses (HIV, influenza) and toxins (diphtheria toxin).
Chapter 7Adhesion & Intercellular Communication
🤝 Intercellular junctions
| Type | Structure | Role | Examples |
|---|---|---|---|
| Tight junctions (tight junctions) | Claudins and occludins, closure of the intercellular space | Sealing (blood-brain barrier, intestinal epithelium) | Intestinal epithelium |
| Adherent junctions | Cadherins + actin | Mechanical cohesion | Epidermis |
| Desmosomes | Cadherins + intermediate filaments | Maximum mechanical resistance | Heart, skin |
| Gap junctions (communicating junctions) | Connexins (connectons) | Direct ionic and chemical communication | Myocardium, neurons |
| Hemidesmosomes | Integrins + basal lamina | Cell-MEC anchoring | Epithelia |
📡 Intercellular communication by chemical signals
Types of membrane receptors:
- G protein-coupled receptors (GPCRs) → adenylyl cyclase → cAMP
- Receptors with tyrosine kinase activity (RTK) → phosphorylation cascade
- Channel receptors (ionotropics) → direct opening of ion channels
🔗 Cell adhesion molecules (CAMs)
| Family | Ligand | Role |
|---|---|---|
| Cadherins | Cadherin (homo) | Ca²⁺-dependent cell-cell junctions |
| Integrins | MEC (fibronectin, lamininin, etc.) | Cell-ECM adhesion, inside-out/outside-in signaling |
| Selectins | Carbohydrates | Leukocyte adhesion to the endothelium (inflammation) |
| IgCAMs | Varies | Ca²⁺-independent adhesion, nervous system |
Chapter 8Cytoskeleton
🏛️ Overview
It consists of 3 main types of filaments:
🔴 Actin microfilaments (F-actin)
Organization: cortical network under the membrane, parallel bundles, three-dimensional network.
Functions:
- Muscle contraction (with myosin)
- Cellular movements: pseudopodia, lamellipodia, filopodia
- Cytodieresis (contractile ring in mitosis)
- Microvilli (brush edge of enterocytes)
Associated proteins: myosin (molecular motor), cofilin (depolymerization), profilin, ABP, gelsolin.
🟡 Intermediate filaments
| Type | Protein | Cell |
|---|---|---|
| Keratins | Acid/Basic Keratin | Epithelial cells |
| Vimentine | Vimentine | Mesenchymal cells, fibroblasts |
| Desmine | Desmine | Muscle cells |
| Neurofilaments | NF-L, NF-M, NF-H | Neurons |
| Laminates | Lamina A, B, C | Nuclear envelope (all cells) |
| GFAP | GFAP | Astrocytes |
Role: mechanical support, resistance to tensile stress, anchoring of desmosomes.
The vimentin is used as a marker in pathology to identify tumors of mesenchymal origin.
🟢 Microtubules
Polarity: + end (rapid growth) and − end (at MTOC = centrosome).
Functions:
- Rails for vesicular transport (kinesin towards +, dynein towards −)
- Formation of the mitotic spindle
- Structure of cilia and flagella (microtubule doublets)
- Centrioles and centrosome
→ Axonemal dynein: motor of ciliary movement
Drugs targeting microtubules: colchicine (depolymerizes, anti-inflammatory); taxol/paclitaxel (stabilized, anti-cancer).
Chapter 9Endomembrane System
🏭 Overview
🧵 Endoplasmic Reticulum (ER)
Rough RE (RER)
- Dotted with ribosomes
- Synthesis of secreted and membrane proteins
- Protein glycosylation (N-glycosylation)
- Quality control (chaperones: BiP/GRP78)
Smooth RE (REL)
- Without ribosomes
- Synthesis of lipids and steroid hormones
- Detoxification (liver, kidney) → cytochrome P450
- Storage of Ca²⁺ (muscles: REL = sarcoplasmic reticulum)
📦 Golgi apparatus
Functions:
- Post-translational modifications of proteins (O-glycosylation, phosphorylation, sulfation)
- Sorting and directing proteins to their final destination
- Synthesis of proteoglycans and glycolipids
- Formation of lysosomes (vesicles containing lysosomal enzymes)
Addressing signal to lysosomes: mannose-6-phosphate (M6P) → recognized by M6P receptor at the trans Golgi.
🗑️ Lysosomes
Lysosomal enzymes: proteases, lipases, nucleases, glycosidases, phosphatases.
Functions:
- Heterophagy: digestion of extracellular materials (phagosomes + lysosomes = phagolysosomes)
- Autophagy: digestion of aged cellular components (autophagosome + lysosomes)
- Recycling of cellular components
The lysosomal storage diseases (e.g. Gaucher disease, Tay-Sachs) result from a deficiency in lysosomal enzymes → accumulation of substrates.
🔵 Ribosomes
Polysomes (polyribosomes): several ribosomes on the same mRNA for simultaneous translation.
🌀 Peroxisomes
Functions:
- β-oxidation of very long fatty acids (chain > C20)
- Detoxification (alcohol, H₂O₂): H₂O₂ → H₂O + O₂ (catalase)
- Synthesis of plasmalogens (myelin constituents)
Peroxisome deficiency: Zellweger syndrome (serious disease of the newborn). Deficiency of a peroxisome enzyme: adrenoleukodystrophy (ALD).
Chapter 10Mitochondria
⚡ General
Size: 0.5–10µm. Number: 200–2000 per cell. Very abundant in cells with high metabolic activity (cardiomyocytes, hepatocytes).
Endosymbiotic theory (Lynn Margulis): mitochondria would be ancient α-proteobacteria engulfed by endosymbiosis → explanation of their own DNA, their 70S ribosomes, their double membrane.
🏗️ Structure of the mitochondrion
| Compartment | Description | Content/Function |
|---|---|---|
| Outer membrane | Smooth, permeable (porins) | VDAC (channels), passage of small molecules |
| Intermembrane space | Narrow, between the 2 membranes | Cytochrome c (apoptosis), protons (gradient) |
| Internal membrane | Folded into ridges (cristae) | Respiratory chain, ATP synthase (complex V) |
| Matrix | Internal space | Krebs cycle, β-oxidation, mitochondrial DNA, 70S ribosomes |
🔋 ATP Production — Cellular Respiration
Acetyl-CoA → Krebs cycle (matrix) → NADH / FADH₂
→ Respiratory chain (internal mb) → Gradient H⁺ → ATP synthase → ATP
| Step | Location | ATP produced |
|---|---|---|
| Glycolysis | Cytosol | 2 net ATP |
| Krebs cycle | Matrix | 2 GTP + NADH/FADH₂ |
| Oxidative phosphorylation | Internal membrane | ~32 ATP |
| Total | ~36–38 ATP/glucose |
Mitochondrial DNA (mtDNA): circular, 16,569 bp, codes for 13 respiratory chain proteins + rRNA + tRNA. Exclusive maternal inheritance.
Chapter 11Interphase Core
🎯 Core structure
| Component | Description | Function |
|---|---|---|
| Nuclear envelope | Double membrane (external: linked to the ER; internal: nuclear lamina) | Nucleus/cytoplasm barrier |
| Nuclear pores (NPCs) | ~3000–5000 per core, ∅ ≈ 120 nm; complex of 30+ proteins (nucleoporins) | Selective transport RNA → cytoplasm/proteins → nucleus |
| Nuclear lamina | Lamin A/B/C network under the inner membrane | Nucleus shape, chromatin anchoring |
| Nucleoplasm | Nuclear liquid | Transcription and replication environment |
| Nucleolus | 1–3 per nucleus, not bounded by membrane | Synthesis and maturation of rRNAs, assembly of ribosomal subunits |
| Chromatin | DNA + histones | Genome conservation and expression |
The progeria (Hutchinson-Gilford syndrome) is due to a mutation in lamin A → accelerated premature aging.
🧶 Chromatin & Chromosomes
→ 30nm fiber → Loops (300 nm) → Condensed chromosome (metaphase)
Normal human karyotype: 46 chromosomes = 22 pairs of autosomes + 1 pair of gonosomes (XX or XY). Diploid (2n = 46).
Chapter 12Cell Cycle, Mitosis & Meiosis
🔄 The cell cycle
| Phase | Average duration | Key events |
|---|---|---|
| G1 | 6–12 p.m. | Cell growth, protein synthesis, restriction point (G1/S) |
| S | 6–8 a.m. | DNA replication (2n → 4n), histone synthesis |
| G2 | 3–4 hours | DNA verification, mitotic protein synthesis |
| M (Mitosis) | 1–2 hours | Division of the nucleus then the cytoplasm |
| G0 | Varies | Quiescent cells (neurons, cardiomyocytes) or in differentiation |
The cyclins (D, E, A, B) associate with CDKs (cyclin-dependent kinases) to control phase transitions. The inhibitory CDKs (p21, p27, p16) slow down the cycle.
🧬 Mitosis — The 5 phases
| Phase | Events |
|---|---|
| Prophase | Chromosome condensation, nucleolus disappearance, start of the mitotic spindle |
| Prometaphase | Nuclear envelope disruption, kinetochore attachment to spindle microtubules |
| Metaphase | Chromosomes aligned on the equatorial plate (metaphase plate) |
| Anaphase | Separation of sister chromatids, migration towards the poles |
| Telophase + Cytokinesis | Chromosome decondensation, envelope reformation, cytoplasm division by the actin-myosin contractile ring |
Result: 2 diploid daughter cells genetically identical to the mother cell.
🧪 Meiosis
→ Meiosis II (equational) → 4 n cells (1 chromatid)
Prophase I (long, 4 stages): leptotene → zygotene (synapsis) → pachytene (crossing over / recombination) → diplotene → diakinesis.
Crossover: exchange of segments between homologous chromosomes → genetic mixing → genetic diversity.
Meiosis errors (non-disjunction) cause chromosomal abnormalities: Trisomy 21 (Down), 47 XXY (Klinefelter), 45 X (Turner).
🔒 Cell cycle checkpoints
| Checkpoint | Key regulator | Role |
|---|---|---|
| G1/S (restriction) | p53, Rb, p21 | DNA integrity, cell size |
| G2/M | CDC2-cyclin B complex | Complete DNA replication verification |
| Spindle assembly | BubR1, Mad2 | Correct kinetochore-microtubule attachment |
p53 (“guardian of the genome”): TP53 mutation present in ~50% of human cancers. In the event of DNA damage: p53 activates p21 → cycle arrest → repair or apoptosis.
Chapter 13Extracellular Matrix (ECM)
🕸️ Definition and roles
🧱 Main components
| Molecule | Type | Role |
|---|---|---|
| Collagen | Fibrous protein (28 types, I the most abundant) | Tensile strength, structure, healing |
| Fibronectin | Glycoprotein | Cell-ECM adhesion (integrin binding), cell migration |
| Laminin | Glycoprotein | Major component of the basal lamina, differentiation |
| Elastin | Fibrous protein | Elasticity (vessels, lungs, skin) |
| Proteoglycans | Core protein + glycosaminoglycans (GAG) | Hydration, filtration, signaling, resistance to compression |
| Hyaluronic acid | Unsulfated GAG | Synovial fluid viscosity, hydration |
🏗️ Basal lamina
Roles: support of epithelia, filtration (renal glomerulus), epithelial/connective tissue separation, control of cell migration.
Chapter 14Apoptosis & Cancer Cell
💀 Apoptosis – programmed cell death
Morphological characteristics of apoptosis:
- Cell shrinkage
- Chromatin condensation
- DNA fragmentation
- Formation of apoptotic bodies
- Phagocytosis without inflammation
Trigger routes:
- Intrinsic pathway (mitochondrial): cellular stress → Bax → cytochrome c release → apoptosome → caspase 9 → effector caspases (3, 6, 7)
- Extrinsic pathway (death receptors): FasL/Fas, TNF → caspase 8 → effector caspases
Proteins anti-apoptotic : Bcl-2, Bcl-XL. Proteins pro-apoptotic : Bax, Bak, Bad, Bid. The Bcl-2/Bax balance determines cell fate.
☠️ Cancer cell
Cancer Hallmarks (Hanahan & Weinberg):
- Self-sufficiency in growth signals (oncogenic mutations: RAS, HER2)
- Insensitivity to antiproliferative signals (loss of Rb)
- Resistance to apoptosis (Bcl-2 overexpression, p53 loss)
- Unlimited replicative potential (activation of telomerase)
- Angiogenesis (VEGF)
- Invasion and metastasis (E-cadherin loss, MMP activation)
- Metabolic reprogramming (Warburg effect: aerobic glycolysis)
- Immune escape
📌 Summary — Key points to remember
- Prokaryote: no nucleus, 70S ribosome, bare circular DNA
- Eukaryote: membrane nucleus, 80S ribosomes, membranous organelles
- Virus: acellular, obligate intracellular parasite, no metabolism of its own
- Plasma membrane: lipid bilayer + proteins (fluid mosaic model)
- Na⁺/K⁺ pump: 3 Na⁺ out, 2 K⁺ in, consumes ATP
- Lysosome: acid hydrolases, pH 4.5 – intracellular digestion
- Mitochondrion: double membrane, cristae, Krebs cycle, respiratory chain → ATP
- Maternally inherited mtDNA, mitochondrial 70S ribosomes
- Nucleus: pores, lamina (laminas), nucleolus (rRNA), chromatin (nucleosomes)
- Cell cycle: G1-S-G2-M, controlled by cyclins/CDK and restriction points
- p53: guardian of the genome, mutated in ~50% of cancers
- Meiosis: genetic mixing, 4 haploid cells
- Apoptosis ≠ Necrosis: programmed death, without inflammation
- Cancer: accumulation of mutations, 8 hallmarks