Microbiology · Exam 1 — Professor Webster’s Review

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This is not a second study guide. It is a record of what Professor Webster told the class to study, on 11 September 2026, in the last seventeen minutes of the Nonspecific Immunity lecture. She went through her instructional objectives one at a time, said which ones to skip, asked the questions she expected the class to be able to answer, and confirmed that one calculation is examinable.

Each item below carries her actual words and then the answer from the slides. The tier badge on each heading is her weighting, not an editorial guess — where she said to skip something the badge says so, and her instruction is quoted next to it so you can check the call rather than trust it.

1 · Lecture 1 — Review of General Microbiology

1.1 · Molecular mechanisms in health and disease Light touch

Her one explicit skip in this lecture. The material is real but it is taught again elsewhere, so read it once and move on.

Pathogen surface proteins bind specific host receptors — influenza uses hemagglutinin to bind sialic acid receptors. Virulence factors are pathogen molecules that enhance the ability to cause disease: toxins, adhesins and invasins, which between them handle colonization, invasion and evasion of the host immune response. Adhesion is the initial attachment (Escherichia coli type I fimbriae binding mannose receptors, colonizing the urinary tract); invasion allows entry into cells (Salmonella enterica injects effector proteins into gut cells to establish a niche for replication). Host immune status often determines the outcome, and environmental factors — temperature and humidity, where vectors can flourish, hygiene, vaccination rates and travel — sit on top of all of it. Lecture 1, Slides 10–12.

1.2 · Types of infectious pathogens Know it

The general division first: prokaryotic — bacteria. Eukaryotic — fungi, protozoa, helminths. Noncellular — viruses, and alongside them prions and viroids. Lecture 1, Slide 13.

Lecture 1, Slide 14.

The specialized bacteria — her actual question

She asked the class directly why mycoplasmas are special and let the silence sit. The answer is on the slide: they lack a cell wall. Everything else follows from that — no wall means nothing for the Gram stain to hold and nothing for a cell-wall antibiotic to attack.

Lecture 1, Slide 15. She added in the review that these atypicals have a different lifestyle because they are intracellular parasites, and named Mycoplasma pneumoniae as the cause of walking pneumonia — hard to diagnose.

The eukaryotic microbes

Fungi — around 100,000 species, divided into two groups and differentiated by the spores they produce. Macroscopic (mushrooms, puffballs, gill fungi) and microscopic: yeasts are unicellular (Saccharomyces cerevisiae, Candida albicans), molds are multicellular and filamentous (Penicillium notatum). Lecture 1, Slide 17.

Protozoa — around 65,000 species, mostly unicellular, differentiated by motility: flagella, cilia, pseudopods, or nonmotile. Many have two forms, a motile feeding trophozoite and a dormant resistant cyst. The groups: Mastigophora (flagellates — Trypanosoma, Chagas disease), Sarcodina (amoebas — Entamoeba, amoebic dysentery), Ciliophora (ciliates — Balantidium), Apicomplexa (essentially nonmotile, unique reproductive structures — Plasmodium, malaria). Lecture 1, Slides 18–19.

Helminths — flatworms are flat with no definite body cavity, a blind digestive pouch and simple excretory and nervous systems, and include cestodes (tapeworms) and trematodes or flukes (flattened, nonsegmented, sucking mouthparts). Roundworms (nematodes) are round with a complete digestive tract, a protective surface cuticle, spines and hooks on the mouth, and poorly developed excretory and nervous systems. Lecture 1, Slide 20.

1.3 · Bacterial cell structures, especially those that enhance pathogenicity Know it

“Definitely” was the strongest word she used in Lecture 1. She then named three structures unprompted, which makes those three the ones to have cold.

Lecture 1, Slides 28, 38, 39, 40.

The rest of the structures

Projections from the wall — the flagellum gives true directional motility; the pilus is coded by a plasmid and used in bacterial conjugation; fimbriae are used for adhesion to membrane surfaces. All three are specialized features. Lecture 1, Slide 27.

Internal structures — cytoplasm, organelles performing specific metabolic functions, a nuclear area with a circular chromosome of DNA, 70S ribosomes, and inclusions holding storage or waste products such as phosphate and oil droplets. Lecture 1, Slide 37.

Peptidoglycan itself — a polymer of alternating N-acetylglucosamine and N-acetylmuramic acid crosslinked by a short peptide bridge, between the terminal D-alanine and the penultimate diamino-containing amino acid. The crosslinking is catalyzed by transpeptidases, which are also the target of the beta-lactam antibiotics — the single fact that ties this lecture to the next one. Crosslinking can be direct or indirect through a pentaglycine spacer, as in Staphylococcus aureus. Lecture 1, Slide 29.

1.4 · Gram-positive versus Gram-negative Know cold

She spent longer here than on anything else in the review, and she did not ask the class to recite the wall — she made them reason forward from it, twice, to what would and would not kill the organism. Build the answer in that direction.

Lecture 1, Slides 33–34. The lysozyme contrast is the one she worked through live, having just covered lysozyme that morning as a first-line chemical defense.

What is in the outer membrane

Lipopolysaccharide has three parts: Lipid A, which carries the endotoxin activity; the core polysaccharide; and the O-polysaccharide, used in bacterial classification. Only Gram-negatives have this membrane, which is why only Gram-negatives carry endotoxin. Lecture 1, Slide 34.

The stain itself

1. Flood with crystal violet, 1 minute; wash.
2. Flood with Gram’s iodine, 1 minute; wash.
3. Decolorize carefully with acetone alcohol until the thinnest parts of the smear are colorless, about 10 seconds; wash. The slide calls this the most critical step and the one most affected by technical variation in timing and reagents.
4. Flood with safranin, 1 minute; wash, then air dry or blot.

Lecture 1, Slide 31. Morphology sits alongside this — cocci (spherical), bacilli (rod) and spiral (helical, comma, twisted rod, spirochete) — and the slide answers its own question about why shape matters: identification. Lecture 1, Slide 22.

1.5 · Methods of bacterial identification and the culture media Know it

Identification methods: microscopic morphology; macroscopic morphology (colony appearance); physiological and biochemical characteristics; chemical analysis; serological analysis; and genetic and molecular analysis — guanine-plus-cytosine base composition, DNA analysis using genetic probes, and nucleic acid sequencing with ribosomal RNA analysis. Lecture 1, Slide 41.

Lecture 1, Slides 43–44.

Growth requirements sit behind all of this — chemically: water, energy nutrients (carbohydrates, proteins, lipids), vitamins, minerals and oxygen levels; physically: temperature, pH and osmotic pressure. Lecture 1, Slide 42.

1.6 · The bacterial growth curve Know it

Growth means an increase in number, not size, by binary fission — which is why it is exponential rather than arithmetic. Lecture 1, Slide 48.

Lecture 1, Slide 50.

1.7 · Phage replication — lytic versus lysogenic Know it

The six steps first, because both cycles share the opening: adsorption (binding of virus to a specific molecule on the host cell), penetration (genome enters), replication (viral components produced), assembly, maturation and release. Lecture 1, Slide 55.

Lecture 1, Slide 57. The last row is the one she pointed at: integration is not a quieter version of infection, it is how a bacterium inherits a new weapon without ever looking infected.

1.8 · Phage replication compared with animal virus replication Know it

Three differences, and she asked for all three in sequence. Lecture 1, Slide 58.

• The entire virion is engulfed, rather than only the genome entering.
• It therefore requires uncoating to release the genetic material — driven by the difference between the pH of the cytoplasm and that of extracellular fluid.
• Release is by budding rather than lysis, and budding may assist in the acquisition of an envelope.

Structure sits underneath this: all viruses have capsids, protein coats that enclose and protect their nucleic acid, in helical, icosahedral or complex (phage) form. They contain DNA or RNA, and may have an envelope or spikes. Lecture 1, Slide 52.

1.9 · Cytopathic effects of viruses Know it

Cytopathic effects are virus-induced damage to cells: changes in size and shape; cytoplasmic inclusion bodies; nuclear inclusion bodies; fusion of cells into multinucleated cells; cell lysis; alteration of DNA which may activate oncogenes — the slide notes radiation and chemical exposure can do the same — and transformation of cells into cancerous cells. Lecture 1, Slide 59.

The other noncellular infectious agents sit beside these: prions are misfolded proteins containing no nucleic acid, causing spongiform encephalopathies (holes in the brain) — scrapie in sheep and goats, bovine spongiform encephalopathy or mad cow disease, and Creutzfeldt–Jakob disease in humans. Viroids are short pieces of RNA with no protein coat, identified only in plants so far. Lecture 1, Slide 60.

1.10 · Health implications of nucleic acid mutations Light touch

Her second explicit skip. Read it once for the shape of it: mutations occur naturally at a low level but may be induced by radiation, chemicals and viruses, and may be beneficial, neutral or deleterious to the organism. Lecture 1, Slide 61.

For completeness: in viruses, high mutation rates change surface antigens, which can weaken or eliminate immunity from vaccination or previous exposure, and can let animal viruses cross to humans who have no immunity to them at all. In human hosts, chemical or radiation exposure and oncogenic viruses may transform normal cells into cancer cells, and viruses may affect cells of the immune system. Lecture 1, Slides 62–63.

1.11 · Mechanisms of microbial control and the death curve Know it

Start with the two definitions the slide separates: aseptic or sterile means removal of all forms of microbial contamination; disinfection means elimination of some. Depending on circumstances, lowering numbers rather than total elimination may be good enough. Lecture 1, Slide 65.

The basic mechanisms — there are only two, which is why she asked for them as a short list: alteration of membrane permeability and denaturation of proteins and nucleic acids. The types are physical, chemical, and clinical (antimicrobial chemotherapeutic agents). Lecture 1, Slide 67.

Lecture 1, Slide 68.

Disinfectant versus antiseptic — she asked for this by name

Disinfectants are used on inanimate objects — the slide's example is Lysol. Antiseptics are used on tissues — Listerine mouthwash. There are very few true chemical sterilants: ethylene oxide (plastics, spices) and beta-propiolactone (vaccines, tissue grafts, surgical instruments). Sometimes control is adequate for the purpose, using halogens such as chlorine or bromine, or alcohol. Lecture 1, Slide 69.

The death curve, and her worked problem

When a microbial control method is used on a bacterial population, the rate of death is constant. The decimal reduction time is the time it takes to kill 90 per cent of the organisms — that is, to drop the count by one power of ten. Lecture 1, Slide 66.

2 · Lecture 2 — Antibiotics and Resistance

2.1 · Major historical events and names Light touch

Her third explicit skip — but she named four people while skipping it, which effectively tells you the four to know. Learn these and let the rest of the timeline go.

Lecture 2, Slides 7–8.

The terminology these names hang on

• Chemotherapy — the use of drugs to treat a disease.
• Antimicrobial drugs — interfere with the growth of microbes within a host.
• Antibiotic — a substance produced by a microbe that, in small amounts, inhibits another microbe.
• Selective toxicity — a drug that kills harmful microbes without damaging the host.

Lecture 2, Slide 4.

2.2 · Criteria for drug selection — prokaryotes versus eukaryotes Know it

She gave the answer in the question, and it is exactly the slide’s: there are not as many drugs in the pharmacopeia against eukaryotic pathogens because treatment is more difficult — their cell structure and some physiology is like that of the human host, so there is a great possibility of toxic side effects. Selective toxicity needs a target the invader has and we do not, and against a fellow eukaryote there are far fewer such targets. Lecture 2, Slide 38.

The properties a good antimicrobial should have, which is the same objective from the other direction: Lecture 2, Slides 12–13.

• Selective toxicity — achieved by interfering with processes or structures found in the pathogen's cells and not in host cells.
• Bactericidal (kills organisms directly; minimal bactericidal concentration is the minimum level that kills 99.9 per cent of test organisms) versus bacteriostatic (inhibits growth; minimal inhibitory concentration is the minimum level that inhibits growth).
• Favorable pharmacokinetics — reaching the target site at an effective concentration, which depends on distribution, crossing barriers, metabolism and excretion.
• Spectrum of activity — broad (large range of organisms) or narrow (small range).
• Lack of side effects — low direct toxicity, low potential for hypersensitivity.
• A good therapeutic index, and little resistance development.

There is no perfect drug — the slide opens with that line, and the list above is a set of trade-offs rather than a specification anything actually meets.

2.3 · Therapeutic index Know cold

The therapeutic window is the range of plasma concentrations spanning the minimum concentration for clinical efficacy and the concentration at which toxicity begins.

The therapeutic index is a calculation used to assess the safety and efficacy of a drug. The slide gives it two ways:

Lecture 2, Slide 15.

How to read the number. The toxic quantity is on top, so a larger therapeutic index means a wider margin of safety. A small index means the effective and toxic doses sit close together, so dosing has to be precise and monitored.

2.4 · Drug clearance and the dosage schedule Know it

Drug clearance = renal clearance + hepatic clearance + clearance from all other tissues. That total is what determines the dosage schedule, and the rule the slide states is the one she asked the class to say back: you do not want to go below the minimum inhibitory concentration. The slide adds a second timing point that is easy to miss — it takes time for the drug to enter the system in the first place, so the trough between doses is not the only place the concentration can fall short. Lecture 2, Slide 15.

2.5 · Antibiotics and the organisms of the major drug lines Know it

She asked for three genera and one pattern, so take those first and treat the full table as reference: Penicillium, Bacillus and Streptomyces are the producers, and Streptomyces makes a whole range of them, many of which are protein synthesis inhibitors.

Lecture 2, Slides 19–33, 40. Five of the protein synthesis inhibitors in that table come from Streptomyces, which is the pattern she wanted rather than the rows themselves.

2.6 · Basic mechanisms of action, with examples Know cold

She listed all five without pausing, which is the clearest signal in the lecture that the five-way division is the thing being tested. The objective asks for examples of each, so each row below carries them.

1 · Inhibitors of cell wall synthesis

Bacteria constantly remodel their walls, which is what makes the wall a target at all.

• Penicillins — interfere with cell walls in three ways: binding penicillin-binding proteins (inactivating membrane proteins involved in wall synthesis and maintenance), inhibition of transpeptidase (blocking formation of the peptide cross-links), and production of autolysins (breaking down wall without accompanying synthesis). Natural, semisynthetic and extended-spectrum forms exist. The beta-lactam family also includes penicillinase-resistant penicillins, penicillins combined with beta-lactamase inhibitors, carbapenems (a carbon substituted for a sulfur, plus a double bond) and monobactams (a single ring).
• Cephalosporins — mechanism similar to the transpeptidase activity of penicillin. First generation is narrow spectrum and Gram-positive; second extends to Gram-negatives; third includes pseudomonads and is injected; fourth is oral.
• Bacitracin — interferes with bactoprenol, the membrane transporter that moves peptidoglycan monomers across the membrane to the growing wall, preventing it from being dephosphorylated so no new monomers are inserted. The wall weakens and the bacterium bursts from osmotic lysis. Topical only — too toxic for parenteral use. Against Gram-positives.
• Vancomycin — a glycopeptide that binds the NAG and NAM subunits and prevents their incorporation into the wall. An important “last line” against antibiotic-resistant Staphylococcus aureus.
• Antimycobacterial agents — mycobacteria have different cell walls. Isoniazid inhibits mycolic acid synthesis; ethambutol inhibits its incorporation.

Lecture 2, Slides 18–25.

2 · Injury to the plasma membrane

Polymyxin B disrupts both the outer membrane of Gram-negative cells and the inner membrane by attaching to lipid components. Topical — combined with bacitracin and neomycin in over-the-counter preparations. Lecture 2, Slide 32.

3 · Inhibitors of protein synthesis

Lecture 2, Slides 27–31. Her “lots of different ways to inhibit that” is literally this table — five drugs, five distinct points of attack on one process.

4 · Inhibitors of nucleic acid synthesis

• Rifamycin — inhibits RNA synthesis by inhibiting RNA polymerase. An antituberculosis medication.
• Quinolones and fluoroquinolones — artificially produced. Nalidixic acid was first generation; later generations are ciprofloxacin, levofloxacin and moxifloxacin. They inhibit DNA gyrase, preventing DNA from unwinding. Used for urinary tract infections and hospital-acquired infections.

Lecture 2, Slide 33. Her aside that “a lot of your antivirals work against nucleic acids” points at the nucleoside and nucleotide analogs — remdesivir, for instance, binds viral RNA-dependent RNA polymerase and terminates transcription prematurely. Lecture 2, Slide 53.

5 · Competitive inhibitors — blocking metabolic reactions

Sulfonamides (sulfa drugs) are synthetic, made from coal tar dyes by Domagk in 1935. They are similar to PABA and so inhibit folic acid synthesis. Broad spectrum. Lecture 2, Slide 34.

And how you pick one

The disk-diffusion (Kirby–Bauer) method, where the reading chart corrects for concentration, molecular weight and other factors affecting diffusion; and the E test (epsilometer test, or “MIC on a stick”), where the minimum inhibitory concentration is read in micrograms per milliliter at the point where the zone of inhibition meets the strip. Lecture 2, Slides 36–37.

2.7 · Mechanisms of drug resistance Know cold

She spent more words on this than on any other item in Lecture 2, and she spent them on the framing rather than the list. Get the framing first.

The definition

Resistance is the ability of a microorganism to avoid the harmful effects of an antibiotic by destroying it, transporting it out of the cell, or undergoing changes that block its effects. Those three verbs map onto the biochemical mechanisms below. Lecture 2, Slide 62.

Genetic mechanisms — how a cell acquires resistance

• Random genetic mutation.
• Plasmid swapping during conjugation.
• Movement of transposons to plasmids or chromosomes.
• Transduction by bacteriophages.
• Transformation — acquisition of resistance genes from a recently killed cell, incorporated into a chromosome or plasmid.
• Binary fission can then share any of the above.

Lecture 2, Slide 68. These are the same three mechanisms flagged back in item 1.10 — which is why that “skip” needs the caveat attached to it.

Cellular and biochemical mechanisms — how resistance actually works

Lecture 2, Slide 70.

What makes it worse — her list

Resistance is natural, but it increases when antibiotics are used carelessly: Lecture 2, Slide 73.

• Misuse or overuse of antibiotics; exposure to too many.
• Using outdated or weakened antibiotics.
• Using antibiotics for viral infections and other inappropriate conditions — her words: “it’s not going to do anything and only help develop resistance.”
• The wrong dosage schedule, and failing to complete the prescribed regimen.
• Using someone else’s leftover prescription — “when you’re taking your friend’s antibiotic.”
• Antibiotics in animal feed — she raised this one unprompted and at length: if you eat meat that is not organically grown, you may be exposed to antibiotics that were in the animals’ feed. Lecture 2, Slide 74.

Beyond individual behavior, the slides add environmental warming, and possible correlations with pesticide use in food production and microplastic contamination. Trends are tracked by the National Antimicrobial Resistance Monitoring System for Enteric Bacteria, an interagency partnership monitoring humans, retail meats and food animals. Lecture 2, Slide 75.

What the data show

Increased antibiotic use means increased resistance; longer treatment means increased colonization; resistance is more prevalent in healthcare facilities than in the community; areas of higher antibiotic use have the highest resistance; and antibiotic use correlates with infection by resistant strains during outbreaks. Lecture 2, Slide 64.

Biofilms

A biofilm is a physical and chemical barrier that limits dissemination and sequesters antibiotics; organisms within it are metabolically less active and therefore less susceptible; and the close spatial relationship enhances resistance gene transfer. The clinically relevant producers are the ESKAPE organisms — Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species — which colonize urinary catheters, ventilators, prosthetic joints and cardiac implants, along with chronic wounds and the lungs of cystic fibrosis patients, promoting persistent infection. Lecture 2, Slide 71.

2.8 · Other problems with antimicrobial therapy Know it

Four problems on the slide: superinfection, direct toxicity, hypersensitive reactions and resistance. Resistance has its own item above; the other three follow. Lecture 2, Slide 58.

Superinfection

Secondary infections acquired, often, following the use of broad spectrum antibiotics — the antibiotics reduce normal flora and allow opportunistic infections to take hold. Predisposing conditions include corticosteroid therapy, leukemia, human immunodeficiency virus, systemic lupus and diabetes. Typical organisms: Candida albicans, Clostridioides difficile, hepatitis C virus, human immunodeficiency virus, Aspergillus, and resistant staphylococci. Lecture 2, Slide 59.

Direct toxicity

High serum levels of some antibiotics may be directly toxic. The slide gives eight, and the pairings are the kind of thing that matches cleanly onto an exam question: Lecture 2, Slide 60.

Hypersensitivity

Most often seen with the beta-lactams — penicillins and cephalosporins — and also with quinolones. Reactions may be immediate or delayed, and may range from hives to anaphylactic shock. Lecture 2, Slide 61.

Drug combinations — her “cocktail”

One approach to resistant organisms is a cocktail of different drugs. Combining them produces one of three effects: Lecture 2, Slides 78–79.

• Indifference — no interaction between the drugs.
• Synergism — the effect of two drugs together is greater than the effect of either alone. This is the one she named.
• Antagonism — the effect of two drugs together is less than the effect of either alone.

3 · Lecture 5 — Host Defenses: Nonspecific Mechanisms

3.1 · The three lines of defense Know cold

“You need to know” was the most direct instruction in the entire review, and it was about this. The three-line structure is the frame every other item in Lecture 5 hangs on.

Lecture 5, Slide 4.

3.2 · First line — which are physical, chemical, microbiological, genetic Know cold

She named three categories. The syllabus objective names chemical, genetic and physical, and the lecture slide names physical, chemical, microbiological and genetic. All four are below, since between her list and the objective every one of them is asked for somewhere.

Physical

• Intact skin — stratified squamous epithelium; rapid desquamation physically removes transient flora; keratin, which most pathogens cannot digest because they lack keratinase; keratinocytes produce antimicrobial peptides incorporated into lamellar bodies and secreted into a waterproof lipid layer.
• Mucous membranes — line the gastrointestinal, respiratory and urogenital tracts, with a much greater area than skin. Thin, permeable, not keratinized, and therefore not as physically tough — they have to be, because communication with the external environment happens through them. Covered by mucus of glycoproteins, proteoglycans, peptides and enzymes; mucins are the gigantic glycoproteins that give mucus its protective properties.
• Ciliary escalator.
• Lacrimal apparatus — produces and drains tears, washing the eye surface.
• Nasal hairs; saliva (mechanically protects oral mucosa); urine (mechanically flushes, plus high osmolality and inhibitory pH); sweat (mechanical flush); defecation; and expulsion mechanisms — coughing, sneezing, vomiting.

Lecture 5, Slides 6–14.

Chemical

Sebum; the acid mantle of the skin; lysozyme, which acts on peptidoglycan (in tears as well as elsewhere — and the reason Gram-positives lose their whole wall to it while Gram-negatives do not, from item 1.4); lactic acid and electrolytes in sweat; digestive secretions; semen (spermine, lysozyme, lactoferrin, phospholipase); and vaginal secretions (lactic acid, beta-defensin, hydrogen peroxide). Lecture 5, Slides 13, 18.

Microbiological

Normal flora, which begins colonization after birth. On the epidermis, Staphylococcus epidermidis, other coagulase-negative staphylococci and coryneform bacteria. They work two ways at once: competing for living space and nutrients (a physical barrier) and producing antimicrobial substances that inhibit pathogens (a chemical barrier). In atopic dermatitis the balance is altered (dysbiosis) with fewer antimicrobial peptides — and when subjects were colonized with coagulase-negative staphylococci, colonization by Staphylococcus aureus was diminished. Gut commensals prevent colonization by pathogens, digest substances we cannot and provide vitamins, and assist in the development of gut-associated lymphoid tissue. Lecture 5, Slides 15, 17.

Genetic

Defensin gene copy number. There are 2–14 copies of the genes coding alpha-defensins and 2–12 coding beta-defensins, and copy number determines the amount of protein made — so how well defended you are is partly inherited. The slide names this explicitly as a genetic defense. Lecture 5, Slide 25.

Defensins themselves are the predominant family of antimicrobial peptides — 30 to 40 amino acids, amphipathic, damaging cell membranes, which is how they kill bacteria, fungi and enveloped viruses. They are also the only innate immune components that can neutralize a broad range of microbial toxins, by unfolding them and changing their three-dimensional configuration — they are antichaperones. Lecture 5, Slides 23, 25.

3.3 · The recognition system — PRRs, PAMPs and DAMPs Know cold

She asked for the abbreviation and then made the class expand both of the others, so know all three in both forms.

Lecture 5, Slide 32.

The receptors are expressed by all white blood cells and by some epithelial and endothelial cells, and they differentiate between healthy self tissue, non-self substances from microbes, and altered self — tissue damaged or altered by viruses or cancer. Each receptor recognizes a pattern shared by a whole pathogen family, so a wide range of pathogens can be detected, and each cell carries a unique combination of receptors, which increases the likelihood of effective defense. Once they recognize non-self or altered self, they activate effector mechanisms. Lecture 5, Slides 30–32.

The PRR families

Different families recognize different molecules and can sit on the plasma membrane, in the cytosol or in endosomes: Lecture 5, Slide 58.

• Toll-like receptors — recognize many pathogens; on the surface they stimulate inflammatory cytokines, in endosomes they stimulate interferon.
• Scavenger receptors — eliminate microbes, or in the absence of infection clear cellular debris and cells that died by apoptosis.
• Retinoic acid inducible gene — detects viral RNA, stimulates interferon.
• Cyclic GMP cyclase — detects viral DNA, stimulates interferon.

3.4 · The leukocytes — what each one does Know cold

She said this twice in one breath, which is as close to an explicit instruction as the review gets. The percentages are on the slides and are worth carrying, because a differential count is only interpretable against them.

Lecture 5, Slides 66–70.

Two more that are not counted in the differential but belong in the answer: dendritic cells trap pathogens and phagocytose in order to collect and process antigens for presentation to T cells; and mast cells are tissue resident, respond to microbes and particularly parasites, and carry granules of inflammatory mediators such as histamine which help expel parasites. Lecture 5, Slide 74.

3.5 · Macrophage versus neutrophil Know cold

She singled this pair out from the whole list, and the slide sets them side by side in exactly the form she asked for.

Lecture 5, Slide 75. The last row is the functional difference the rest follow from: the macrophage is the sentry already in place, the neutrophil is the response that has to be called in.

How the neutrophil kills — the respiratory burst

When the engulfed organism encounters the neutrophil granules, NADPH oxidase produces superoxide, which picks up hydrogen ions and raises the pH so that the digestive granules can break the organism down. Lecture 5, Slides 76–77.

Toxic oxygen species produced during the burst can diffuse out and damage host cells, so phagocytes synthesize enzymes to inactivate them — catalase degrades hydrogen peroxide into water and oxygen. Lecture 5, Slide 78.

3.6 · The white blood count with differential Know it

Two questions, so two answers. What it does: totals the number of each type of white blood cell and determines whether the cells are in normal proportion — which is why the percentages in item 3.4 matter. What it can tell us: it is useful in the diagnosis of infection types, inflammation, allergies, immune disorders, leukemia, and myelodysplastic syndrome. Lecture 5, Slide 71.

3.7 · Inflammation — the characteristics and how they come about Know cold

Two separate demands in one question. The characteristics are a list; the how is a mechanism, and she asked for the mechanism specifically.

The characteristics

Lecture 5, Slide 29. Described as early as the first century by the Roman physician Celsus — and note that functio laesa is the one most often left off a four-item answer.

How they come about

1. Macrophages sense infection. Products of the pathogen stimulate formation of a protein structure called an inflammasome, which activates pro-interleukin-1β into functional interleukin-1β in large quantities.
2. A second cascade forms pores in the macrophage membrane, letting the interleukin into the circulation. This kills the macrophage, by pyroptosis.
3. The interleukin activates other macrophages and creates a state of inflammation. Lecture 5, Slide 34.
4. Release of interleukin-1β initiates further cytokine release. TNF-α dilates blood vessels to increase blood volume in the infected area — and that is what produces the heat, swelling, redness and pain. Interleukin-6 also increases temperature.
5. CXCL8, CCL2 and interleukin-12 act as chemokines, attracting other white blood cells to the area.
6. Endothelial cells upregulate adhesion molecules to direct leukocytes to the area, and loosen the tight junctions between cells. Lecture 5, Slide 35.

Getting the cells out of the blood — extravasation

Leukocytes such as neutrophils have to leave the blood and enter infected tissue, using adhesion molecules on the endothelium and the leukocyte surface: L-selectin on the leukocyte binds vascular addressin CD34 on the endothelium, and integrin LFA-1 binds ICAM-1. Transient interactions make the neutrophil roll along the surface; chemokines then guide it to squeeze between endothelial cells — diapedesis — and migrate to the site. Lecture 5, Slides 36–37.

Why local inflammation is good and systemic inflammation is catastrophic

Locally, TNF-α released by macrophages acts on venule endothelium to increase blood flow and permeability, increase endothelial adhesiveness for white cells and platelets, and cause blood in the venules to clot — which prevents the spread of infection to the blood. Lecture 5, Slide 39.

Systemically, when infection develops in the blood, release of TNF-α onto venule endothelium in all tissues simultaneously induces a state of shock, organ failure and death. Lecture 5, Slide 40.

3.8 · Fever — what causes it, why it is good, why it is bad Know cold

Three questions in a row, so structure the answer in three parts.

What causes it

Interleukin-1β, interleukin-6 and TNF-α have multiple effects both locally and systemically, and the systemic effects include fever. The same three cytokines that produce local inflammation produce fever when they act at a distance. Lecture 5, Slide 38.

Why it is good — five reasons on the slide

• Decreases replication of viral and bacterial pathogens — in bacteria, by starving them of iron.
• Increases production and activity of neutrophils.
• Enhances T cell proliferation.
• Enhances immune signaling.
• Enhances tissue resistance to the damaging effects of TNF-α.

Lecture 5, Slide 38.

Why it is bad

Worth knowing where this half of the answer actually lives, because the fever slide itself lists only benefits. The harm comes through the same cytokines, acting systemically: when infection reaches the blood, TNF-α released onto the endothelium of all tissues at once induces shock, organ failure and death. The febrile response and the catastrophic one are the same mechanism at different scales — which is why the deck presents fever's benefits and TNF-α's systemic harms four slides apart rather than as two opposing lists. Lecture 5, Slide 40.

3.9 · Interferon Know cold

She asked the same question twice in a row before anyone answered, then supplied the correction herself. Both halves are the point.

Lecture 5, Slides 59, 61.

Interferons are small proteins produced by certain white blood cells and tissue cells, made in response to viruses, RNA, immune products and various antigens. They bind to cell surfaces and induce expression of antiviral proteins, and they also inhibit expression of cancer genes and suppress tumors. Lecture 5, Slides 59–60.

3.10 · Complement Know cold

The only item she drilled twice — once during the lecture itself, with a hand gesture for each pathway, and again in the review. Treat the activation order as the single most likely question in this lecture.

What complement is

One of the first immune system components to be activated; ubiquitous in blood and lymph; 30 or more proteins working in concert to destroy bacteria, viruses and parasites. They circulate as inactive zymogens — soluble proteases — and are activated by cleavage in a cascade. A molecular defense that can be used immediately, deriving its activity from a unique high-energy thioester bond. Lecture 5, Slide 42.

C3 and the thioester bond

Activation cleaves C3 into C3a and C3b. The cleavage exposes the thioester bond on C3b, which can either be attacked by water and become soluble, or react with a hydroxyl or amino group on a pathogen surface and attach to it — complement fixation, which marks the pathogen for destruction. Meanwhile C3a recruits phagocytes. Lecture 5, Slide 43.

C3 is by far the most important molecule in the cascade, and the biggest difference between the three pathways is simply how they are activated — all three converge on cleaving it. Lecture 5, Slide 45.

What the three pathways actually are

Lecture 5, Slides 44–45.

What happens once it is turned on — her three outputs

She asked “once you do turn on complement, what happens?” and answered in three parts. Keep them in that shape.

1. Opsonins enhance phagocytosis. The first defensive cells a pathogen meets are usually macrophages, and their efficiency is improved by opsonins — proteins bound to the pathogen surface that facilitate phagocytosis. C3b on a pathogen surface serves as an opsonin, and complement receptor 1 binds it. Lecture 5, Slide 48.
2. The membrane attack complex. Going all the way down the cascade: C3b binding to existing C3bBb complexes forms the alternative C5 convertase, which cleaves C5 into C5a and C5b. C5b initiates the membrane attack complex, which punches holes in organism membranes. Lecture 5, Slides 49–50.
3. Enhanced inflammation along the way. The smaller fragments C3a and C5a are ligands for receptors on phagocytes, endothelial cells and mast cells, and enhance the inflammatory response; in extreme cases they can induce anaphylactic shock. C5a recruits neutrophils to the infection site and is the most potent anaphylatoxin; it makes neutrophils and monocytes adhere to vessel walls, acts as a chemoattractant, and increases their phagocytic capacity. Lecture 5, Slides 53–54.

Why it does not destroy us

Regulatory proteins control where C3b is deposited. In plasma, properdin (factor P) binds C3 convertase on microbial surfaces and increases activation, while factor H reduces it by making C3b susceptible to cleavage by factor I. On human cell surfaces, C3bBb is rapidly disrupted by decay accelerating factor or membrane cofactor protein. Human cells are protected from the membrane attack complex by S protein, clusterin and factor J, and by homologous restriction factor and CD59 (protectin). Lecture 5, Slides 46–47, 51.

3.11 · Natural killer cells Know it

She folded this back into the leukocyte item, which tells you the expected answer is a functional description rather than the full nine slides the deck gives them.

The short answer: natural killer cells are cytotoxic lymphocytes that kill cells infected by viruses, bacteria or protozoan parasites, providing innate immunity against intracellular infection. They are large lymphocytes circulating in the blood with well-developed cytoplasm and cytotoxic granules, and they migrate from blood to the infection site in response to inflammatory cytokines. Lecture 5, Slides 81–82.

They have two effector functions: cell killing, particularly of virally infected cells (the CD56 dim subpopulation), and secretion of cytokines to maintain the inflammatory state (CD56 bright). Lecture 5, Slide 82.

The balancing act

The one requirement of a natural killer cell receptor is that it must inhibit the cell from killing healthy self-cells. Killing is a balance between activating and inhibitory signals: when a cell is infected, malignant or traumatized, its protein expression changes so that activating signals exceed inhibitory signals — and then it is killed. Lecture 5, Slide 87.

The killing itself is by apoptosis: the natural killer cell contacts the target, releases cytotoxic granules, and the target shrinks, its chromatin condenses, and its contents are released — after which a macrophage does the clean-up. Lecture 5, Slide 89.

Who activates them, and who they activate

Their base level of cytotoxicity is 20 to 100-fold higher on exposure to the interferons produced in response to viral infection; type I interferons also induce their proliferation, and interleukin-12 and TNF-α from macrophages activate them too. Lecture 5, Slide 84.

The cooperation runs both ways, which is the part worth carrying: macrophages produce cytokines that recruit, activate and expand natural killer cells, and natural killer cells in turn produce interferon gamma, which enhances macrophage phagocytosis and cytokine secretion. Lecture 5, Slide 90.

And if they cannot cope: natural killer cells stimulate dendritic cells to migrate to secondary lymphoid tissue and turn on the adaptive response. Lecture 5, Slide 91.

3.12 · Coordination of the innate and adaptive systems Know it

She pointed at one diagram and told the class to pay attention to it, which is the only time in the whole review she singles out a single figure. Here is what it says, in three cases:

Lecture 5, Slide 93.

The deck closes on the same note: innate immunity is very effective — we carry vast populations of resident microbes and are well most of the time — and rare inheritable defects in innate mechanisms mean a substantial reduction in protection. Lecture 5, Slide 92.

Most of the time a third line is never needed, because natural killer cells and the rest of the innate system handle it. But the order cannot be reversed: there is no adaptive response without a preceding innate one.

What she said about the exam

Three things are worth taking from the review beyond its contents.

The objectives are the blueprint. She did not review by topic or by slide order — she read down the instructional objective list for each of her lectures and commented on each one in turn. If the review is built from the objectives, the exam is built from them too.

She expects to see the class again first. Her closing words: “I think I’ll see you before you actually take that test. So if you go through that and you have any questions, you can ask me. I think I’m here next week on problems in the immune system.” Working through this page before that session is what turns it into a list of questions to ask.

The review was one-sided by design. She reviewed her own content and said so. Nothing here should be read as a signal about the relative weight of Lectures 3, 4 and 6 on the exam — she simply was not the one who taught them.