Exam 4 Study Guide

This guide covers chapters 10, 11 and 12. The three fit together as one story. Chapter 10 shows how a single microbe does harm to a single body. Chapter 11 widens the view to how that microbe travels between bodies. Chapter 12 turns around and shows the first defenses the body throws back. Work one chapter at a time. Read the "what to know" prose first. Then cover the tables and say them out loud from memory. Then run the ten self-test items. The cram sheet at the end holds every table and list in one place.

Chapter 10How Microbes Cause Disease

What to know

A pathogen follows a script. Get in. Hold on. Multiply. Do damage. Then dodge the immune system. Every step runs on a specific molecule, and every one of those molecules is a target.

Pathogenicity is the ability to cause disease at all. It is a yes or no trait. Virulence is the degree of that ability. Two microbes can both be pathogens and still sit far apart on the virulence scale.

A primary pathogen can sicken a healthy host with working defenses. Influenza, Salmonella and Mycobacterium tuberculosis all qualify. An opportunistic pathogen needs an opening. A broken barrier. Normal flora wiped out by a drug. A weakened host.

Virulence factors are the genes and molecules that do the work. They sort into four jobs. Attaching, which is the adhesins. Spreading, which is the invasins and tissue-cutting enzymes. Damaging, which is the toxins. Evading, which is capsules and antigenic variation. A microbe needs a tool from each stage. Take the right one away and the attack stalls.

Virulence can be put into numbers. The ID₅₀ is the dose that infects half of an exposed group. The LD₅₀ is the dose that kills half of them. A lower number means a more dangerous agent. Shigella has an ID₅₀ of only 10 to 100 cells, so it moves person to person with ease. Vibrio cholerae needs roughly a hundred million cells, so it usually takes dirty water to deliver that much.

A microbe enters through a portal of entry. Most come in through the mucous membranes. The respiratory tract is the most common one by far. Then the gastrointestinal tract, then the genitourinary tract, then the conjunctiva of the eye. Others enter through breaks in the skin. The parenteral route is a special case, where the organism is placed straight into deeper tissue or blood.

Here is the point that gets tested. The same organism can be harmless at one portal and deadly at another. Escherichia coli lives in peace in the colon. In the bladder it causes a urinary tract infection. In the blood it can cause fatal sepsis. Every catheter, line and breathing tube is a new portal of entry that nature never built.

Getting in is not enough. Mucus, urine and tears all sweep a loose microbe away. So the next step is attachment, and it is done with adhesins. These are surface molecules that bind host receptors like a key in a lock. They sit on fimbriae, on pili, or in the capsule. That tight fit explains tropism, which is why one microbe infects one tissue and not another.

Many organisms stick down together and wrap themselves in slime. That is a biofilm. Drugs and immune cells struggle to get inside one. Biofilms grow on catheters, artificial joints and heart valves, and that is why device infections are so stubborn.

Damage comes mostly from toxins, and there are two families. Exotoxins are proteins that bacteria build and secrete. Both Gram-positive and Gram-negative cells make them. Being proteins, they are exact in what they hit, and they can be shockingly strong. The toxins of tetanus, botulism and diphtheria are the deadliest known. Roughly a nanogram of botulinum toxin per kilogram of body weight can kill.

Exotoxins come in three styles. An A-B toxin has two parts. The B, or binding, part latches onto a target cell. The A, or active, part slips inside and wrecks one process. Diphtheria toxin halts protein building. Cholera toxin drives the fluid loss of rice-water diarrhea. Botulinum and tetanus toxins block neurotransmitter release and paralyze muscle. Membrane-disrupting toxins punch holes instead. Hemolysins burst red cells and leukocidins kill white cells. Superantigens short-circuit the immune system, so the body dumps out a huge untargeted flood of cytokines. That is the shock of toxic shock syndrome.

Two facts follow from exotoxins being proteins. They are usually heat-labile, so cooking destroys them. And a protein toxin can be treated chemically into a toxoid, which no longer harms but still brings out protective antibodies. The tetanus and diphtheria parts of routine vaccines are toxoids. Ready-made antitoxin can also be given to soak up toxin already loose in the blood.

Endotoxin is a different animal. It is the lipid A part of lipopolysaccharide, or LPS. LPS is a fixed part of the Gram-negative outer membrane. So endotoxin is released only when the cell is damaged or dies, including the moment a drug bursts a mass of them at once. One molecule is far weaker than one strong exotoxin, but the body's answer to it is broad. Fever. Vessels widen and blood pressure falls. Clotting switches on all over. At flood level that becomes septic shock, with tiny clots everywhere in disseminated intravascular coagulation, or DIC. Endotoxin is heat-stable. It survives an autoclave, it cannot be made into a toxoid, and there is no vaccine against it.

A pathogen also has to stay hidden. The classic tool is the capsule, a thick slippery polysaccharide coat. It works two ways at once. A phagocyte cannot get a grip on it, and it hides the surface molecules antibodies and complement latch onto. Capsular vaccines aim straight at that coat. Licensed ones cover Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae type b. Klebsiella pneumoniae leans just as hard on its capsule, but no vaccine against it is licensed yet.

In antigenic variation a microbe keeps changing its disguise. Influenza does it every year with small mutations, which is antigenic drift. Now and then it swaps whole gene segments, which is antigenic shift. That is why the flu vaccine is remade yearly, and why a true shift can start a pandemic. Neisseria gonorrhoeae reshuffles the proteins on its pili, so gonorrhea leaves no lasting immunity and can reinfect the same person again and again.

Some pathogens turn intracellular and live inside host cells, where circulating antibodies cannot reach them. M. tuberculosis survives inside the very macrophages sent to kill it. Listeria and Salmonella do the same. Others attack the defenses head on. IgA proteases chop up the antibodies guarding mucous membranes. Coagulase walls the organism off inside a clot of the host's own fibrin, and that is a Staphylococcus aureus specialty.

Keep two look-alike terms apart. Antigenic masking is the microbe coating itself in host proteins so it looks like self. S. aureus protein A grabbing the tail of IgG is the standard case. Molecular mimicry is the other way round. The microbe's own antigens happen to resemble host tissue, so antibodies made against the microbe attack the host. Streptococcal M protein resembling cardiac myosin in rheumatic fever is the classic example.

Most acute infections then unfold on the same timeline. Five stages, in a fixed order. Knowing them tells you when a person is most able to pass the infection on, and that does not line up with how sick they look.

The names worth memorizing

Four tables carry most of chapter 10. Learn the left column, then cover the rest and rebuild it.

The sequences, in order

Two orders from this chapter get asked about directly. Say each one out loud until it comes without effort.

The disease process, step by step.

1. Enter through a portal of entry.
2. Attach with adhesins to a matching host receptor.
3. Multiply, and often build a biofilm.
4. Damage with toxins and tissue-cutting enzymes.
5. Evade the immune system long enough to reach the next host.

The five stages of an acute infection.

1. Incubation. Exposure to the first symptom. The microbe multiplies and the host feels fine. Hours for staph food poisoning, years for HIV and TB.
2. Prodromal. Short and vague. Mild fever, tiredness, aching. Load and immune response both climb. Shedding often starts here.
3. Illness. The peak. The microbe is at its most numerous and the signs are at their worst. Untreated, the risk of dying is highest now.
4. Decline. The immune system gains control. Symptoms fade, but the host is worn down and open to a second infection.
5. Convalescence. Recovery. Tissue repairs and strength returns. Some people shed here, and a few become long-term carriers.

How to reason through the question types

The traps

Chapter 11Infection and Epidemiology

What to know

One sick person is one story. A whole ward of sick people is a system. Chapter 11 is about that system, and it works at two scales. The six-link chain of infection explains one transmission event. Epidemiology counts disease across a whole population.

Infection is never a single event. A sequence has to line up. The microbe must exist, live somewhere, get out, travel, get in, and find a host weak enough. Those are the six links. All six must connect. Break any one and the whole chain fails.

Link one is the infectious agent, the microbe itself. Link two is its reservoir, the place it normally lives and multiplies. Link three is the portal of exit, how it leaves. Link four is the mode of transmission, the route it travels. Link five is the portal of entry, how it gets into the next person. Link six is the susceptible host, someone whose defenses are low enough.

Reservoirs come in three kinds. Human reservoirs include people who look clearly sick, and they include carriers, who are the bigger danger. A carrier holds and sheds a microbe with no symptoms at all. Mary Mallon, known as Typhoid Mary, infected roughly 50 people and three of them died, while she felt perfectly well. Animal reservoirs give us zoonoses, which jump from animals to people. Rabies, Lyme disease and salmonellosis are three. Environmental reservoirs are not alive. Soil holds Clostridium tetani and fungal spores. Water holds Legionella, which breeds in cooling towers and warm plumbing.

There are five modes of transmission, and the mode decides the barrier. Direct contact is skin to skin or fluid to fluid. Indirect contact runs through a contaminated object called a fomite. A bed rail, a stethoscope and a shared glucometer are all fomites. Droplet spread carries large respiratory droplets about 1 to 2 meters, which is 3 to 6 feet. The droplets are too heavy to float, so they fall fast. Airborne spread is the dangerous cousin. Tiny droplet nuclei stay up in the air and ride air currents, so tuberculosis, measles and varicella can infect someone who was never close by. Vehicle spread uses one shared medium such as food, water or blood, so a single bad batch reaches many people at once. Vector spread uses a living carrier, almost always an arthropod. A fly carrying microbes on its feet is mechanical. A mosquito letting Plasmodium multiply inside it is biological.

Epidemiology is the study of how disease is spread across populations, and what drives that pattern. Its two basic numbers get mixed up constantly. Incidence counts new cases over a set stretch of time, so it measures how fast a disease is arriving. Prevalence counts all cases, new and old, present at one moment, so it measures how much disease is out there now.

Duration links them. Prevalence runs close to incidence times average duration. A short sharp illness like influenza has high incidence in season but low prevalence at any snapshot, because people get better fast. A lasting illness like HIV has low incidence but high and climbing prevalence, because cases pile up. Two more words finish the set. Morbidity is the amount of illness. Mortality is the amount of death.

Patterns have names too. Endemic means always present at a steady expected level. The common cold is endemic everywhere, and malaria is endemic in parts of the tropics. An epidemic is a rise above the expected baseline for that place and time, and a smaller or more local one is called an outbreak. A pandemic is an epidemic across countries and continents, and COVID-19 is the defining example. Sporadic means turning up now and then with no steady pattern.

One number says how hard a disease pushes. The basic reproduction number, written R₀ and said as "R naught," is the average number of new cases one infected person causes in a population with no immunity. Above 1 and cases grow. Below 1 and the outbreak dies out. Measles sits near 12 to 18, which is why it tears through a school. Seasonal influenza sits near 1.3.

Immunity changes the math. The effective reproduction number, written R, is what the microbe actually achieves once some people are protected. Protect a big enough share and R drops under 1. Then the chain keeps breaking on its own, and even people with no immunity are shielded. That share is the herd immunity threshold, and it is 1 minus 1 divided by R₀. For measles at an R₀ of 15 that is about 93 percent. For a disease with an R₀ of 2 it is only 50 percent.

Then the chapter comes back to one room. A healthcare-associated infection, or HAI, is one a person picks up while receiving care. They did not have it on arrival and were not incubating it then. On any given day about 1 in 31 hospital patients in the United States has at least one. Most are preventable, which is why they are counted and reported.

Most of the big HAIs share one villain, the biofilm. Thread a catheter into a bladder or a line into a vein and microbes settle on the plastic. Every indwelling device is both a portal of entry and a scaffold for biofilm. So the rule is blunt. If the device is not needed, it comes out.

Four HAIs dominate the lists. CAUTI is catheter-associated urinary tract infection, and it follows the most used and most over-used device there is. CLABSI is central-line-associated bloodstream infection, less common but far deadlier, because it drops microbes straight into the blood. SSI is surgical-site infection. VAP is ventilator-associated pneumonia, which strikes when a breathing tube bypasses the filters of the upper airway. Prevention for each is a bundle, a small set of proven steps done together, every time, with nothing skipped. HAI rates are counted per 1,000 device-days.

Infection control itself rests on two tiers. Standard precautions are the base, and the founding idea is deliberately paranoid. Treat the blood and body fluids of every person as possibly infectious. You cannot tell by looking who is carrying what. Standard precautions include hand hygiene before and after every contact, PPE whenever body fluids are possible, respiratory hygiene, safe injection practice of one needle and one syringe one time, and safe handling of soiled equipment and linen.

Transmission-based precautions add a second tier for a known or suspected threat, and there are three kinds. Contact precautions mean gown, gloves and dedicated equipment, for organisms that travel by touch and on fomites. Droplet precautions mean a surgical mask within about 2 meters. Airborne precautions mean a fitted N95 respirator and a negative-pressure room with the door shut.

A handy hook for the airborne set is My Chicken Hez TB. That unpacks to Measles, Chickenpox, which is varicella, Herpes zoster when it is disseminated, and TB. One wrinkle hides in that list. Varicella and disseminated zoster need airborne plus contact precautions, because the fluid in the blisters spreads by touch and rides on linen and dressings. TB and measles are airborne only.

One more exception is worth holding. Spore formers such as Clostridioides difficile need soap-and-water washing and a bleach cleaner. Alcohol gel will not do.

The names worth memorizing

The sequences, in order

The chain of infection, link by link.

1. Infectious agent. The microbe.
2. Reservoir. Where it lives and multiplies. Human, animal or environmental.
3. Portal of exit. Respiratory droplets, stool, blood, wound drainage.
4. Mode of transmission. Contact, droplet, airborne, vehicle or vector.
5. Portal of entry. Often the same routes in reverse, plus the doorways we add.
6. Susceptible host. Someone whose defenses are low enough.

How an outbreak label escalates.

1. Sporadic. Now and then, no pattern.
2. Endemic. A steady expected baseline.
3. Epidemic, or outbreak. Above that baseline for the place and time.
4. Pandemic. Across countries and continents.

How to reason through the question types

The traps

Chapter 12Innate Immunity

What to know

Long before the body knows what hit it, it is already fighting back. Innate immunity is the defense you are born with. It answers in seconds to minutes. It answers the same way every time. It has never met the microbe before, and it will not remember it after.

Adaptive immunity is the other half, and it is the next chapter. It is slower to start, it is tuned to one microbe, and it remembers. Innate immunity buys the days adaptive immunity needs to gear up.

The system is taught as three lines of defense. Innate immunity supplies the first two. The first line is the barriers that keep microbes out. The second line is what happens inside once something breaks through, and that is phagocytes, inflammation, fever and antimicrobial proteins. Adaptive immunity is the third line.

The first line has three kinds of barrier. Physical barriers come first. The skin is the largest organ and the most important physical barrier there is. Its outer layer, the epidermis, is built of tightly packed cells stuffed with keratin, stacked into dead shingled sheets that shed all day. Any microbe stuck to a shed sheet goes with it.

Surfaces open to the outside world use a mucous membrane instead. These stay moist and carry a coat of mucus, a sticky gel that traps microbes. In the airway, cells carry hair-like cilia that beat in waves and sweep trapped debris up and out. That moving belt is the mucociliary escalator. Tears, saliva and the flushing of urine wash microbes away too. A breathing tube runs straight past the escalator, and that is why it raises the risk of pneumonia so sharply.

Chemical barriers come next. Skin puts out sebum, which is oily and acidic, along with sweat, and together they hold the surface at a low unfriendly pH. Lysozyme is an enzyme in tears, saliva and mucus that chews apart the peptidoglycan of bacterial cell walls. It hits Gram-positive cells hardest, because their wall sits bare on the surface. Stomach acid is brutally low in pH, and the vagina is held acidic by resident lactobacilli.

Biological barriers finish the line. The normal flora take up the space and eat the food, so they crowd out would-be pathogens. That protection is competitive exclusion. Wipe the flora out with a broad-spectrum drug and opportunists move in, with Candida and Clostridioides difficile as the two classic examples.

Once a microbe slips past, it meets the cellular second line. The white blood cells, also called leukocytes, are made in the bone marrow and patrol blood and tissue. Two of them do most of the eating. Neutrophils are the most numerous white cell and the first to arrive. They are fast, aggressive and short-lived. Macrophages are larger and longer-lived, and they grow out of circulating monocytes that mature after leaving the blood. Any microbe-eating cell is a phagocyte, and the act of eating is phagocytosis.

Phagocytes do not reach a wound by luck. Chemical signals from damaged cells, from the microbes and from complement draw them in. That directed march is chemotaxis. To leave the bloodstream a white cell first sticks to the vessel wall, which is margination, then squeezes between the lining cells into the tissue, which is diapedesis, also called extravasation.

How does a phagocyte tell self from invader? It carries pattern-recognition receptors, or PRRs. These bind molecular signatures shared by whole classes of microbes, signatures human cells do not carry. The signatures are called pathogen-associated molecular patterns, or PAMPs, and the classic one is the LPS of the Gram-negative outer membrane. Because the patterns are broad, one receptor spots many microbes, and that breadth is the hallmark of innate immunity.

Recognition gets easier when a microbe is coated with tags called opsonins. Antibodies and the complement protein C3b are the main ones, and the coating is opsonization. It is like painting "eat me" on the microbe.

Inflammation is the tissue's coordinated answer to injury or infection. It makes four classic signs, recognized since ancient times. Redness, heat, swelling and pain. In Latin, rubor, calor, tumor, dolor. A fifth is often added, loss of function, or functio laesa.

Each sign has a mechanism. Resident mast cells and damaged tissue release chemical mediators, and the biggest one is histamine. Prostaglandins, bradykinin and cytokines come with it. These do two things. They cause vasodilation, so vessels widen and more warm blood floods in, which is the redness and the heat. And they raise vascular permeability, so vessel walls turn leaky and fluid, protein and cells pour out, which is the edema you see as swelling. The swelling then presses on nerve endings, and prostaglandins and bradykinin make those nerves more sensitive, which gives the pain.

The whole point is to deliver phagocytes and clotting proteins, and to wall the infection off in a mesh of fibrin. Acute inflammation settles once the threat is cleared. A threat that cannot be cleared turns it chronic, and macrophages may wall the invader off inside a ball of immune cells called a granuloma, as in tuberculosis. The same mediators spilled body-wide are a disaster, and that is sepsis.

Fever, also called pyrexia, is a core temperature that is abnormally high. It is not the infection winning. It is a deliberate, regulated defense. Body temperature is run by a thermostat in the hypothalamus, which normally holds near 37°C, or 98.6°F. Fever happens when pyrogens raise the hypothalamic set-point.

There are two kinds of pyrogen. Exogenous pyrogens come from outside the body, and the most famous is the LPS of Gram-negative bacteria, also called endotoxin. Endogenous pyrogens are made by the body's own immune cells, and they are the cytokines interleukin-1, IL-6 and tumor necrosis factor, released by macrophages when they meet a microbe. Both kinds drive the making of prostaglandin E₂ in the hypothalamus, and that is what actually pushes the set-point up.

Here is the key idea. Once the set-point is raised, the body is not overheating. It now believes 39°C is correct, and it works to get there. That is why a fever starts with shivering and a feeling of cold. Muscles contract to make heat and vessels narrow to hold it in.

A fever runs three phases. In onset, the chill phase, the set-point jumps and the person feels cold, shivers, and has cool pale skin while the temperature climbs. In plateau, also called the stadium, the body has reached the new set-point and the skin is warm, flushed and dry. In defervescence, the flush or crisis, pyrogens fall and the set-point drops, so now the body is too hot and sweats to shed the extra heat.

Reading the phase changes what should be done. Someone shivering is still climbing toward a set-point the hypothalamus has already chosen. Outside warmth will not push the temperature past it. So warm the room and add blankets to stop the shivering, because shivering burns a lot of oxygen and drives up the metabolic rate and the work of the heart. Cooling during the chill phase fights the set-point and makes shivering worse. Cooling measures belong to plateau and defervescence. Antipyretics work a different way, by blocking prostaglandin production and lowering the set-point itself.

A moderate fever helps. It slows the growth of many pathogens, speeds up immune enzymes and sharpens phagocytes. But it raises metabolic demand, heart rate and fluid loss. In young children a fast rise can set off a febrile seizure. And a temperature roughly above 40 to 41°C, which is 104 to 106°F, begins to denature the body's own proteins. That is a medical emergency.

Complement is a set of about 30 blood proteins, mostly made by the liver. They circulate inactive and wait. Once triggered they activate one another in order, which is a cascade, so the signal grows at every step. Three pathways set it off. The classical pathway is triggered by antibodies already bound to a microbe. The alternative pathway is triggered straight off microbial surfaces. The lectin pathway is triggered by carbohydrates on microbes. All three converge on C3, which is split into C3a and C3b, and that split is the hinge of the whole system.

Complement then delivers three outcomes. Opsonization, where C3b coats the microbe so phagocytes grab it far more easily. Inflammation, where the small fragments C3a and C5a act as anaphylatoxins that make mast cells release histamine, and where C5a is also a powerful chemotactic signal. Cytolysis, where the terminal proteins C5b to C9 assemble into a ring called the membrane attack complex, or MAC, which punches a hole so the microbe bursts. Three jobs, easy to hold: tag, recruit and destroy.

A virus is a different problem, because it hides inside a host cell where those defenses cannot reach. For viruses, innate immunity has interferons, a family of cytokines named for the way they interfere with viral replication. A virus-infected cell releases type I interferons, which are IFN-α and IFN-β. These do not save the dying cell that made them. They warn the neighbors. A neighbor that picks up the signal switches on an antiviral state, making enzymes that chew up viral genetic material and shut protein building down if a virus gets in. A separate interferon, IFN-γ, mainly activates macrophages and bridges over to adaptive immunity.

Two things follow. The dragging tiredness, aching muscles and fever of a viral illness like influenza are largely the work of your own interferons, not of the virus directly. And because interferons are natural antivirals, purified versions are used as medicines, for certain viral hepatitis infections, some cancers and multiple sclerosis.

The names worth memorizing

The sequences, in order

Phagocytosis, the six steps. This sequence comes back all through immunology.

1. Chemotaxis. The phagocyte migrates toward the microbe.
2. Adherence. It binds the microbe, helped by opsonins.
3. Ingestion. The membrane wraps around and pinches off a bubble called a phagosome.
4. Fusion. The phagosome merges with a lysosome to make a phagolysosome.
5. Killing and digestion. Enzymes, reactive oxygen from the respiratory burst, and low pH destroy the microbe.
6. Exocytosis. Leftovers are dumped back out. Spent neutrophils, dead microbes and tissue fluid make pus.

How a phagocyte gets out of the blood.

1. Chemotaxis. Signals from damaged cells, microbes and complement point the way.
2. Margination. The cell sticks to the vessel wall.
3. Diapedesis. It squeezes between the lining cells into the tissue.

The complement cascade.

1. Trigger. Classical by bound antibody, alternative by microbial surface, lectin by microbial carbohydrate.
2. Converge on C3. All three pathways split C3 into C3a and C3b.
3. Three outcomes. C3b tags, C3a and C5a recruit, and C5b to C9 build the MAC and destroy.

A fever, phase by phase.

1. Onset, the chill phase. Set-point rises first. Shivering, cold, pale skin. Warm the room; do not cool.
2. Plateau, the stadium. Temperature reaches the new set-point. Warm, flushed, dry skin. Watch fluids.
3. Defervescence, the flush. Set-point falls. Sweating and flushing shed the extra heat. Replace the fluid lost.

How to reason through the question types

The traps

One pageCram sheet