Eukaryotic ultrastructure and the secretory pathway

At A-level you must link each organelle's structure to its function, and be able to trace a protein from gene to secretion.

• Nucleus — double membrane with nuclear pores; chromatin (DNA + histones); nucleolus makes rRNA and assembles ribosomes.
• Rough ER — folded membranes studded with ribosomes; folds and transports proteins.
• Golgi apparatus — modifies proteins (e.g. adds carbohydrate → glycoproteins), packages them into vesicles, and forms lysosomes.
• Lysosome — vesicle of hydrolytic enzymes (lysozymes); digests engulfed pathogens and worn-out organelles.
• Mitochondrion — double membrane; the inner is folded into cristae (large surface area for the electron transport chain); the matrix holds Krebs-cycle enzymes, plus its own DNA and 70S ribosomes.
• Chloroplast — thylakoids stacked into grana (light-dependent reaction) surrounded by the stroma (Calvin cycle).

Prokaryotic cells and the acellular problem

Prokaryotic cells are much smaller (typically 0.5–5 µm) and have no membrane-bound organelles and no nucleus.

• DNA is a single circular molecule, free in the cytoplasm and not associated with histone proteins.
• Cell wall of murein (a glycoprotein / peptidoglycan) — not cellulose.
• 70S ribosomes (smaller than the eukaryotic 80S) — which is exactly why some antibiotics can bind bacterial ribosomes without harming ours.
• Extras: plasmids (small DNA rings, often carrying antibiotic-resistance genes), a capsule, and flagella.

Viruses are acellular and non-living. They have nucleic acid (DNA or RNA) inside a protein capsid, plus attachment proteins that bind complementary receptors on the host. They have no cytoplasm, no ribosomes and no metabolism, so they can only replicate inside a host cell. Some are enveloped in host-derived lipid membrane (e.g. HIV).

Magnification, resolution and cell fractionation

Magnification is how much bigger the image is. Resolution is the minimum distance between two points at which they can still be distinguished as separate — and it is limited by the wavelength of the radiation used.

• Optical (light) microscope — max magnification ~×1500, resolution ~200 nm (limited by the wavelength of light). Living specimens can be viewed; colour is possible.
• TEM — electrons pass through an ultra-thin section; resolution ~0.1 nm; gives internal ultrastructure. Specimens must be dead and in a vacuum; artefacts are a real risk.
• SEM — electrons bounce off the surface; 3-D surface image; lower resolution than TEM but the specimen need not be thin.

Cell fractionation: (1) homogenise tissue in a solution that is ice-cold (slows enzyme activity), isotonic (prevents osmotic damage to organelles) and buffered (stops pH change denaturing proteins); (2) filter to remove debris; (3) ultracentrifuge at increasing speeds. Pellets form in order of density: nuclei → chloroplasts → mitochondria → lysosomes → ER → ribosomes.

Unit discipline: 1 mm = 1000 µm = 1 000 000 nm. Convert both lengths to the same unit before dividing, or you will be an order of magnitude out.

Your turn — magnification

Why the electron microscope wins

The cell cycle, mitosis and the mitotic index

The cell cycle is interphase (G1 growth and organelle synthesis → S phase DNA replication → G2 growth and checking) followed by mitosis and cytokinesis. Interphase occupies most of the cycle.

• Prophase — chromosomes condense and become visible as two sister chromatids joined at a centromere; the nuclear envelope breaks down; spindle fibres form from the centrioles.
• Metaphase — chromosomes align on the equator, attached by their centromeres to the spindle.
• Anaphase — the centromeres divide and the spindle fibres shorten, pulling the sister chromatids to opposite poles (which is why anaphase requires ATP).
• Telophase — chromatids reach the poles, uncoil, and nuclear envelopes re-form.

Cancer: mutations in genes controlling the cell cycle cause uncontrolled mitosis → a tumour. Many chemotherapy drugs exploit this: some inhibit DNA replication in S phase; the vinca alkaloids prevent spindle formation, so metaphase cannot complete.

Your turn — mitotic index

Your turn — how long is mitosis?

The fluid mosaic model and transport

The membrane is a phospholipid bilayer — fluid because phospholipids move laterally, a mosaic because proteins are scattered through it. Cholesterol sits between the tails, restricting movement and reducing permeability to water and ions.

• Simple diffusion — small, non-polar molecules (O₂, CO₂) pass straight through the bilayer, down the gradient, passively.
• Facilitated diffusion — large or charged particles (glucose, ions) use channel or carrier proteins. Still passive and still down the gradient, but the rate plateaus once all proteins are occupied.
• Osmosis — the movement of water from a higher (less negative) water potential to a lower (more negative) water potential across a partially permeable membrane, often via aquaporins.
• Active transport — a carrier protein uses ATP to move a substance against its concentration gradient. The carrier is phosphorylated, changes shape, releases the solute, then reverts.

Co-transport in the ileum: a Na⁺/K⁺ pump actively removes Na⁺ from the epithelial cell into the blood. The resulting Na⁺ gradient drives Na⁺ back in from the lumen through a co-transporter protein, dragging glucose in with it against its own gradient. Glucose then leaves into the blood by facilitated diffusion. This is indirect active transport — the ATP is spent on the pump, not on the glucose.

Your turn — water potential

Co-transport

Antigens, phagocytosis and antigen presentation

An antigen is a molecule (usually a protein or glycoprotein) on a cell surface that triggers an immune response. The immune system identifies cells as self or non-self by their antigens — hence organ-transplant rejection, and hence autoimmune disease when self-recognition fails.

Phagocytosis (non-specific, rapid, the same for every pathogen):

• The phagocyte is attracted by chemicals released by the pathogen (chemotaxis) and binds to its antigens.
• The membrane engulfs the pathogen into a phagosome.
• Lysosomes fuse with the phagosome and release hydrolytic enzymes (lysozymes), which hydrolyse the pathogen.
• The phagocyte displays the pathogen's antigens on its own surface — it becomes an antigen-presenting cell, which is the bridge to the specific response.

Cell-mediated and humoral responses

The specific response is slow the first time but produces memory.

• Cell-mediated (T lymphocytes): a T helper cell with a complementary receptor binds the antigen on an antigen-presenting cell. It divides by mitosis (clonal expansion) and releases cytokines that stimulate phagocytes, activate cytotoxic T cells (which kill infected cells by releasing perforin), and activate B cells.
• Humoral (B lymphocytes): a B cell whose antibody is complementary to the antigen binds it, processes it and presents it. Helper T cells then activate that B cell — clonal selection. It divides into plasma cells, which secrete large quantities of antibody, and memory B cells.

Antibody structure: a quaternary protein of four polypeptide chains with two variable regions forming antigen-binding sites complementary to one specific antigen, plus a constant region. Antibodies cause agglutination of pathogens, making them easier for phagocytes to engulf.

Secondary response: memory cells divide rapidly on re-infection, so antibody is produced faster, in greater concentration and for longer — the pathogen is destroyed before symptoms appear. That is what a vaccine buys you. Herd immunity: if enough of the population is vaccinated, transmission chains break and even the unvaccinated are protected.

HIV, AIDS and monoclonal antibodies

HIV is a retrovirus: RNA plus the enzyme reverse transcriptase, inside a capsid and a lipid envelope studded with attachment proteins.

• Attachment proteins bind CD4 receptors on T helper cells. The RNA enters and reverse transcriptase makes DNA from the viral RNA template.
• This DNA is inserted into the host's genome. When transcribed, the host cell makes viral proteins and new viruses bud off, destroying the T helper cell.
• Losing T helper cells cripples both the cell-mediated and humoral responses. AIDS is the resulting collapse: death typically follows from opportunistic infections such as TB or pneumonia.
• Antibiotics do not work on viruses — they target bacterial structures such as murein walls and 70S ribosomes, which viruses simply do not have.

Monoclonal antibodies: identical antibodies from a single clone of B cells. Used for direct targeting (attaching a cytotoxic drug to an antibody complementary to a tumour antigen), for medical diagnosis, and in the ELISA test, which uses an antibody with an attached enzyme to produce a colour change if the antigen is present.

Why HIV is so damaging

Which arm of the immune response?

Tap a card, then tap the response it belongs to.

Organelle and function

Tap an item on the left, then its partner on the right.

The big ideas to take away

That is the whole of AQA 3.2 Cells. Press Finish to see your score.