Exam 5 Study Guide

This guide covers chapters 13, 14 and 15. Chapter 13 builds the immune system's precise half, the one that learns and remembers, and ends with the vaccines that run on it. Chapter 14 shows the same system misfiring, whether it overreacts, turns on the body, or gives out. Chapter 15 puts every organism back on a real body, region by region. Read the "what to know" prose first. Then cover each table and rebuild it from memory. Then run the ten self-test items. The cram sheet at the end pulls all three chapters into one page.

Chapter 13Adaptive Immunity and Immunization

What to know

Adaptive immunity is slow to start, extremely precise, and it remembers. It can pick one microbe out of millions, build an attack cut to fit, then file that microbe away for years. Two cell families do the work, the T cells and the B cells.

Adaptive immunity splits into two branches. The humoral branch is the antibody branch, run by B lymphocytes that pour antibodies into blood and body fluids. Those go after threats outside of cells, such as bacteria in the bloodstream, loose toxins and viruses in transit. The cell-mediated branch is run by T lymphocytes, and T cells handle threats inside cells. Virus-infected cells and cancer cells are the main targets.

An antigen is any molecule the immune system can spot and react to. Most are proteins or long sugar chains on a microbe's surface. An adaptive cell does not read a whole antigen. It reads a small patch called an epitope. One bacterium carries many epitopes, which is why one infection wakes up many different lymphocytes at once.

Here is the part that is hard to believe. The body builds millions of different lymphocytes in advance, each tuned to a different epitope, all before it has ever met the microbe. When a matching antigen turns up, the one rare cell that fits is picked out and told to multiply. That step is clonal selection.

Three properties define adaptive immunity. Specificity means one response is aimed at one antigen and nothing near it, so immunity to measles does nothing for mumps. Memory means the system keeps a record and reacts faster and harder on a second meeting, and that is the property vaccines are built on. Self-tolerance means the system learns to leave your own molecules alone. Your own molecules are self and foreign ones are non-self. Lymphocytes that would attack self are normally deleted or switched off early, and when that check fails the result is autoimmune disease.

T lymphocytes are born in the bone marrow and finish training in the thymus, and the T stands for thymus. During training the cells that would attack self get weeded out. A mature T cell cannot grab a free-floating antigen the way an antibody can. It reacts only to antigen chopped up and put on display, and the display molecule is MHC, short for major histocompatibility complex. Picture MHC as a serving tray. A cell holds up a scrap of protein and a passing T cell leans in and inspects it. That step is antigen presentation, and it is how a T cell can tell an infected cell from a healthy one.

There are two kinds of tray. MHC class I sits on almost every nucleated cell, and it shows scraps of whatever that cell is building inside. So a virus-infected cell advertises the virus without meaning to. MHC class II sits only on professional antigen-presenting cells, which are dendritic cells, macrophages and B cells. Those swallow microbes on purpose, then hold up the pieces to call for help.

Helper T cells wear the surface marker CD4 and read antigen on MHC class II. They kill nothing. They conduct. When a helper T cell meets its antigen it releases cytokines that switch the rest of the response on. They push B cells to make antibody, help arm cytotoxic T cells, and rev up macrophages. Losing them is a disaster, and that is exactly what makes HIV so dangerous.

Cytotoxic T cells wear CD8 and read antigen on MHC class I. A cell showing viral or tumor protein on its class I tray is marked for death. The CD8 cell fires perforin, which drills pores in the target membrane, and granzymes, enzymes that slip inside and trip the self-destruct switch. The target dies by apoptosis, which is programmed cell death, and the virus factory goes down with it.

There is a tidy way to keep the pairings straight. Call it the rule of eight. CD4 times MHC II is 8. CD8 times MHC I is 8. Each T cell works with the MHC class whose number multiplies out to eight.

B lymphocytes mature in the bone marrow, and the B is a handy match for bone marrow. Each B cell carries one unique receptor. When that receptor binds its matching antigen the B cell wakes up, and most of the time it also needs a push from a helper T cell. Then it divides. Most daughters become plasma cells, short-lived factories that pump out thousands of identical antibodies every second. A smaller share become memory B cells that linger for years.

Antibodies have a second name, immunoglobulins, usually shortened to Ig. Every one is built on the same shape, a Y made of four protein chains. Two identical long heavy chains and two identical short light chains, held together by disulfide bonds. The two tips of the Y are the variable regions, and their amino-acid order differs from one antibody to the next, which gives each its own antigen-binding site. The stem of the Y is the constant region, the same in every antibody of a class. The stem works as a handle that phagocytes and complement proteins grab. So one end recognizes and the other end recruits.

Antibodies rarely destroy a microbe on their own. They tag it and disable it, in four main ways. In neutralization they coat a virus or a toxin so it can no longer dock onto a host cell, and antitoxins work this way. In opsonization they coat a microbe so a phagocyte can grip it, using the constant stem as the handle. In agglutination they cross-link many microbes into clumps that are easier to clear and cannot spread. In complement activation a cluster of antibodies sets off the complement cascade, which can then punch holes in a bacterial membrane.

The five classes differ in their constant stems, and that is why each travels somewhere different. IgG is the most abundant in blood, about 75 to 80 percent of serum antibody, and it crosses the placenta. IgM is a pentamer of five Y units, the first antibody made in a new infection, and the strongest trigger of complement. IgA is a dimer that guards mucous membranes and secretions, including saliva, tears, mucus and breast milk. IgE is present in trace amounts, binds mast cells, and drives allergy and defense against parasitic worms. IgD sits mostly on the surface of naive B cells and helps switch them on.

The first time the body meets a new antigen it has work to do. Find the one rare lymphocyte, switch it on, let it multiply. Only then does a real defense appear. That primary response has a lag of roughly one to two weeks and makes a modest amount of antibody. IgM leads the way, with IgG building up behind it. During that lag the person is often sick, fighting from behind.

As the primary response winds down it leaves memory B cells and memory T cells behind, and some last for decades. Memory is the physical basis of immunity. It is what having had a disease, or having had a vaccine, actually means at the level of cells.

When the same antigen comes back, memory cells are already waiting, so the body skips most of the delay. The secondary response starts in hours to a few days. It makes far more antibody, often ten to a hundred times more. And it is dominated by high-affinity IgG, which means the antibody grips its target more tightly than the first batch did. Often the microbe is cleared before any symptom appears. Every booster dose sets off a secondary response on purpose.

Immunity sorts along two lines. The first is active against passive. In active immunity the person's own system makes the antibody and builds the memory, so it lasts. In passive immunity ready-made antibody is handed over, which protects right away but only until that borrowed antibody breaks down, and no memory forms at all. The second line is natural against artificial. Natural means it happened through ordinary life. Artificial means it was given on purpose. Cross the two lines and you get four boxes.

Every vaccine does the same job. It shows the immune system an antigen so memory can form. They differ in how they present it, and that difference drives the precautions.

Live attenuated vaccines use a weakened but living microbe. MMR, varicella, oral polio and the intranasal flu vaccine all work this way. They give strong, long-lasting immunity. They are also held back from pregnancy and from a badly weakened immune system, because even a weakened live microbe can cause trouble there. Inactivated vaccines, also called killed vaccines, use a dead microbe, and hepatitis A, the injectable polio vaccine and most flu shots are in this group. They are safer in a vulnerable host and often need boosters.

Three types use only a part of the microbe. Subunit vaccines use one purified piece, such as the surface protein in the hepatitis B vaccine or the acellular pertussis pieces in DTaP. Conjugate vaccines glue a sugar coat to a carrier protein, which is how the Hib and pneumococcal conjugate vaccines work. That glue matters more than it sounds, because a bare sugar antigen barely recruits helper T cells and so protects young children poorly. Attach it to a protein and the helper T cells join in. Toxoid vaccines use an inactivated bacterial toxin, and the tetanus and diphtheria toxoids are the classic pair.

Last come mRNA and viral vector vaccines. These deliver the genetic instructions for a single antigen, so your own cells make that antigen briefly and learn to spot it. The COVID-19 mRNA vaccines are the best known. None of the non-live types can give a person the real infection.

When enough of a community is immune, a microbe runs out of hosts. That effect is herd immunity, and it shelters the few who cannot be vaccinated. Newborns, people with weakened immune systems, and people with a true contraindication all ride on it.

The names worth memorizing

The sequences, in order

How a B cell becomes an antibody factory.

1. A receptor binds its antigen. Each B cell carries one unique receptor.
2. A helper T cell gives a push. Needed most of the time.
3. Clonal selection. That one cell is told to multiply.
4. Most daughters become plasma cells. Short-lived factories pumping out antibody.
5. A few become memory B cells. They linger for years and wait.

How a cytotoxic T cell kills.

1. The target displays antigen on MHC class I. A virus-infected cell gives itself away.
2. The CD8 cell binds it. The receptor and the MHC-antigen complex must fit.
3. Perforin drills pores in the target membrane.
4. Granzymes slip inside and trip the self-destruct switch.
5. The target dies by apoptosis. The virus factory goes down with it.

The four antibody jobs.

1. Neutralization. Coat a virus or toxin so it cannot dock.
2. Opsonization. Coat a microbe so a phagocyte can grip the stem.
3. Agglutination. Cross-link many microbes into clumps.
4. Complement activation. A cluster of antibodies fires the cascade.

How to reason through the question types

The traps

Chapter 14Immune Disorders

What to know

The immune system is the body's best guard. When it misfires it becomes one of the body's worst threats. Chapter 14 covers four ways that happens. It overreacts. It turns on the body. It gives out. Or it attacks help that was given on purpose.

A hypersensitivity reaction is an immune response that runs too strong, aims at the wrong thing, or is simply not needed. All of them share one feature. The damage comes from the immune system's own activity, not straight from the trigger.

Almost every hypersensitivity needs a first quiet exposure called sensitization. That first meeting causes no symptoms. The immune system just learns the antigen and builds a stock of antibodies or primed T cells. The big reaction comes on a later exposure, when that stock fires. So a drug can go in with no trouble the first time and cause a violent reaction the second time. "No reaction last time" never means a drug is safe.

In the 1960s Gell and Coombs sorted hypersensitivities into four types by mechanism. The first three run on antibodies. The fourth runs on T cells. A handy memory aid is ACID. Type I is Anaphylactic, or allergic. Type II is Cytotoxic. Type III is Immune-complex. Type IV is Delayed. Types I to III strike within minutes to hours, because the antibodies are already in place. Type IV takes a day or more, because T cells have to be called to the site.

Timing is a real clue, not a trivia item. Hives within minutes of a bee sting is type I. A rash two days after a new skin cream is type IV.

A type I reaction is what most people mean by an allergy, and it runs in two acts. In sensitization, a first exposure to a harmless allergen is taken up and shown to the immune system. The allergen might be pollen, peanut, penicillin or bee venom. The immune system answers by making IgE against that one allergen, and the IgE coats mast cells in the tissues and basophils in the blood. Those cells are now armed, and nothing dramatic happens yet.

On the next exposure the allergen bridges two IgE molecules sitting side by side on a mast cell. That bridging is cross-linking, and it is the trigger. Within seconds the mast cell goes through degranulation, dumping stored histamine and other mediators and starting to build leukotrienes and prostaglandins.

Those mediators cause the whole familiar package. Vessels widen, so you see redness, warmth and falling blood pressure. Vessels leak, so you see swelling and hives. Smooth muscle squeezes, so you get bronchospasm and cramping. Glands pour out fluid, so you get a runny nose and watery eyes.

Where the reaction happens decides how serious it is. A localized reaction stays near the point of contact, which gives allergic rhinitis, hives on one patch of skin, or asthma in the airways. A systemic reaction is anaphylaxis, where mediators pour out body-wide, usually because the allergen got into the bloodstream. An injected drug, an IV contrast agent, a sting or a swallowed food can all do that.

Anaphylaxis is a life-threatening emergency. Vessels widen everywhere, so blood pressure crashes, and that is distributive shock. At the same time the airway swells and the bronchi clamp down, which can shut off breathing within minutes.

The drug that reverses anaphylaxis is epinephrine. It goes intramuscularly into the outer thigh, and it has to be given at the first sign. Not after antihistamines. Not after a wait-and-see. Epinephrine squeezes vessels to bring blood pressure back up, relaxes airway muscle to open breathing, and calms mast cells. Antihistamines and corticosteroids help alongside it, but they are far too slow and far too weak to carry the job alone.

With the drug, protect the airway and give oxygen. Lay the person flat with the legs raised, unless breathing is easier sitting up. Run IV fluids for the shock. Then watch closely, because a biphasic reaction can return hours later even after everything looks fine. Anyone with a severe allergy needs an epinephrine auto-injector, and needs to know to call emergency services and go to the hospital even after using it.

Early in life the immune system learns to leave the body's own molecules alone, and that state is self-tolerance. Autoimmunity is the failure of that screening. Self-reactive T cells, or antibodies called autoantibodies, slip past the controls and attack the body's own tissues. The attack uses the same weapons as any hypersensitivity. Often type II, with autoantibodies against cell-surface targets. Sometimes type III, with immune complexes. Sometimes type IV, with self-reactive T cells.

Why tolerance fails is usually a mix. A genetic risk sets the stage, and many autoimmune diseases run in families and link to certain HLA or MHC types. Then something in the environment pulls the trigger, and that something is often an infection. One well-studied route is molecular mimicry, where a microbial antigen looks so much like a human protein that antibodies made against the microbe attack the body too. The classic case is rheumatic fever, where antibodies raised against Streptococcus pyogenes cross-react with heart tissue. Autoimmune diseases also fall more often on women, and many come and go in flares and remissions.

Sort these diseases by how much of the body they hit. Organ-specific diseases aim autoantibodies or T cells at a single tissue, so the damage stays focused. Systemic diseases, such as systemic lupus erythematosus, make autoantibodies against parts found all over the body, such as the cell nucleus, so they injure many organs at once.

Most autoimmune diseases have no cure, so care aims to hold back the attack and manage what it has damaged. Treatment leans on immunosuppression, meaning corticosteroids and other drugs that quiet the immune response, and that brings its own hazard. Someone deliberately immunosuppressed is also more open to infection. Some organ-specific diseases are handled another way, by simply replacing what was lost. Insulin does that in type 1 diabetes and thyroid hormone does it in Hashimoto disease.

Immunodeficiency is the immune system doing too little. Some part is missing or not working, so infections a healthy body would shrug off cannot be cleared, and opportunistic organisms move in.

Primary immunodeficiencies are congenital. The person is born with a genetic defect in some part of immunity, and they run from mild to catastrophic. Selective IgA deficiency is often silent and causes no trouble. The most severe is severe combined immunodeficiency, or SCID, where both B cells and T cells are missing or do not work. An affected infant has almost no defense and does not survive infancy without treatment such as a bone-marrow transplant.

Secondary, or acquired, immunodeficiencies are far more common. They build up after birth from an outside cause. Malnutrition is the leading cause worldwide. Certain cancers do it too, above all the leukemias and lymphomas. So do chemotherapy and other immunosuppressive drugs, radiation, aging and viral infection. Anyone on chemotherapy, high-dose steroids or anti-rejection drugs is in this group.

The most important virus here is HIV, the human immunodeficiency virus, which is a retrovirus. It targets the one cell that coordinates the whole immune response, the CD4 helper T cell. Over years HIV infects and destroys those cells, and as the CD4 count falls the immune system loses its conductor. HIV spreads through blood, through sexual contact, and from mother to child in pregnancy, at birth or through breastfeeding. It does not spread through casual contact.

AIDS stands for acquired immunodeficiency syndrome. It is the advanced stage of HIV infection and it is defined two ways. Either the CD4 count drops below 200 cells/µL, where normal is roughly 500 to 1,500. Or an AIDS-defining opportunistic illness appears. That list takes in Pneumocystis jirovecii pneumonia, Candida of the esophagus, widespread tuberculosis, cytomegalovirus and Kaposi sarcoma. The lower the CD4 count, the wider the range of opportunists that can take hold.

The story is far more hopeful than it once was. Antiretroviral therapy, or ART, uses combinations of drugs that block different steps of the viral life cycle. ART can push HIV down to undetectable levels. It protects the CD4 count, stops the slide into AIDS, and makes the virus untransmittable through sex.

Red blood cells carry surface molecules the immune system reads as antigens, and the most important set is the ABO system. Type A cells carry the A antigen, type B carry B, type AB carry both, and type O carry neither. Here is the rule that matters. Each person naturally makes antibodies against the ABO antigen they lack. A type A person has anti-B. A type O person has both anti-A and anti-B.

A second system, Rh, adds positive or negative. Rh-positive cells carry the D antigen and Rh-negative cells do not. Anti-Rh antibodies behave differently from the ABO ones. They are not present from birth. An Rh-negative person makes them only after being exposed to Rh-positive blood. Type O-negative red cells carry none of these antigens, so O-negative is the emergency universal donor for red cells. Type AB-positive plasma carries no anti-A and no anti-B, so AB-positive is the universal recipient.

An acute hemolytic transfusion reaction is a type II hypersensitivity and a true emergency. It is almost always caused by an ABO mismatch, and that mismatch usually traces back to an identification error. The recipient's antibodies bind the transfused donor cells and destroy them, which is hemolysis. That brings fever, chills, flank or back pain, dark urine and low blood pressure, and it can go on to kidney failure and death. The response has to be instant. Stop the transfusion. Keep the IV line open with saline. Notify the provider and the blood bank. Because these reactions start with mistaken identity, the two-person check of the person and the unit is the actual guard against a fatal error.

A related problem crosses the placenta. Hemolytic disease of the newborn, or HDN, happens when an Rh-negative mother was sensitized to Rh-positive blood in an earlier pregnancy. She makes anti-Rh antibodies, and those cross into a later Rh-positive fetus and destroy its red cells. It is largely preventable. Giving Rh immune globulin, or RhoGAM, to Rh-negative mothers stops the sensitization from ever happening.

Transplanting tissue raises the same problem in a new form. The recipient's immune system reads donor cells as foreign, chiefly by their MHC or HLA molecules, and attacks the graft. How hard it attacks depends on how closely donor and recipient are matched.

An autograft moves tissue from one spot on a body to another spot on the same body, as in a skin graft. An isograft goes between identical twins. Neither one is rejected. An allograft goes between two genetically different people of the same species, which is the usual organ transplant, and it is rejected unless the immune response is suppressed. A xenograft goes between species, and it faces the strongest rejection of all.

Rejection comes in three tempos. Hyperacute rejection hits within minutes, driven by antibodies that were already there. Acute rejection takes days to weeks and is run by T cells. Chronic rejection takes months to years. To keep an allograft alive the recipient takes immunosuppressant drugs for life, which trades rejection risk for infection risk.

One more danger runs the other way. In a bone-marrow or stem-cell transplant, the immune cells in the graft can attack the recipient's body. That is graft-versus-host disease, or GVHD.

The names worth memorizing

The sequences, in order

A type I reaction, from first exposure to shock.

1. Sensitization. A first exposure to a harmless allergen, with no symptoms.
2. IgE is made against that one allergen.
3. IgE arms mast cells in tissue and basophils in blood.
4. Re-exposure cross-links two neighboring IgE molecules.
5. Degranulation. Histamine and other mediators dump out within seconds.
6. Local or systemic. Near the site it is hives or wheeze. Body-wide it is anaphylaxis.

Anaphylaxis, what happens in order.

1. Give intramuscular epinephrine into the outer thigh, at the first sign.
2. Protect the airway and give oxygen.
3. Position for the problem. Flat with legs raised, unless breathing is easier sitting up.
4. Run IV fluids for the shock.
5. Keep watching. A biphasic reaction can return hours later.

A hemolytic transfusion reaction.

1. Stop the transfusion at once.
2. Keep the IV line open with saline.
3. Notify the provider and the blood bank.
4. Trace the identity error, because that is nearly always the cause.

The three tempos of rejection.

1. Hyperacute. Within minutes, from antibodies already present.
2. Acute. Days to weeks, run by T cells.
3. Chronic. Months to years.

How to reason through the question types

The traps

Chapter 15Infectious Diseases by Body System

What to know

Microbes do not care how a book is arranged. They land on a real body and cause trouble in one place. Chapter 15 sorts them by the place they strike. Skin. Lungs. Gut. Urinary and sex organs. Blood and brain. For each region you need the usual causes, what the illness looks like, the route it travels, and the steps that block that route.

Healthy skin is one of the best shields the body owns. It is dry, a little acidic, and it sheds its outer cells all day. So skin and soft tissue infections almost always start where that shield is broken. A scratch. An insect bite. A surgical cut. A pressure injury. An IV site. The cracked skin of eczema.

Two organisms show up again and again. Staphylococcus aureus and Streptococcus pyogenes, better known as group A strep. Where each one lives is not the same, and that gap matters. S. aureus is a true resident. It lives in the front of the nose in about 30 percent of adults, and it likes moist skin folds too. That is why the nose is cleared with mupirocin before some surgery. S. pyogenes is not normal skin or nose flora. It rides quietly in the throat of roughly 5 to 15 percent of children, and on skin it only passes through.

How the infection looks depends mostly on how deep it reaches. Impetigo sits in the outermost skin and is common in children, with thin blisters that break and dry into a golden, honey-colored crust. Cellulitis goes deeper, into the dermis and the fat below, so the skin turns warm, red, puffy and sore, with fuzzy edges that are hard to trace. A leg is the usual site. Erysipelas is a brighter form in the upper dermis, raised with a sharp border, and group A strep is the classic cause. Necrotizing fasciitis is the deepest and the worst. It runs along the sheets of tissue under the fat, and the pain is far worse than the skin looks. This one needs surgery, not just a drug.

MRSA is methicillin-resistant Staphylococcus aureus. It is ordinary staph that picked up a gene named mecA, which builds a changed wall-building protein called PBP2a. Beta-lactam drugs cannot grip it. The name hides how wide the problem runs. MRSA shrugs off every beta-lactam. Plain penicillins. The anti-staph penicillins, which are nafcillin and oxacillin. Cephalosporins such as cefazolin and ceftriaxone. The carbapenems. Only the newer anti-MRSA cephalosporins, such as ceftaroline, still land a blow.

So the choice moves to other drugs. Vancomycin. Linezolid. Daptomycin. A simple skin infection may get TMP-SMX, doxycycline or clindamycin instead. MRSA is a top cause of skin abscesses, often reported as a spider bite nobody saw. It moves by contact, on hands, shared equipment and dirty surfaces, so a case goes on contact precautions with gown and gloves.

One skill matters more than any drug name here. Tell colonization from infection. Swab almost any open wound and it will grow bacteria. Only a wound with signs of invaded tissue needs a drug. Growing redness, warmth, puffiness, pain and thick pus mean infection. A calm long-term wound with a positive culture and no swelling is usually just colonized, and treating that one does more harm than good.

The airway splits in two. The upper tract is the nose, sinuses, throat and larynx. The lower tract is the trachea, the bronchi and the air sacs, called alveoli. Lower-tract infections tend to be worse. Upper-tract infections are mostly mild and viral, and they clear on their own.

One big exception stands out. Strep throat, also called streptococcal pharyngitis, comes from group A strep. It brings a sudden painful sore throat, a fever and swollen tonsils. What it does not bring is the cough and runny nose of a cold, and that gap is the clue. It matters because untreated group A strep can lead to rheumatic fever, so it is one of the few sore throats worth a culture and a course of antibiotics.

The lungs are meant to be nearly sterile, and three guards keep them that way. A blanket of mucus. Cilia that sweep it along. The cough reflex. Those guards can fail, through a breathing tube, deep sedation, weakness, or breathing in stomach contents. Then organisms reach the alveoli and cause pneumonia.

Pneumonia is sorted by where it was caught, because that predicts the organism. Community-acquired pneumonia, or CAP, comes most often from Streptococcus pneumoniae. Hospital-acquired and ventilator-associated pneumonia, or VAP, bring tougher and more resistant organisms. Aspiration pneumonia follows mouth or stomach contents breathed in, which happens when swallowing is weak or the gag reflex is dulled.

Tuberculosis, or TB, is the one whose precautions must never be wrong. It comes from Mycobacterium tuberculosis, a slow-growing acid-fast rod. TB spreads on tiny airborne droplet nuclei that hang in the air for hours, so a suspected case goes into a negative-pressure airborne isolation room and a fitted N95 is worn. A surgical mask is not enough. Active TB brings a long wet cough, sometimes with blood, plus night sweats, fever and weight loss. Treatment runs for months on several drugs at once, and the hard part is sticking with it. Stopping early is exactly how drug-resistant TB is bred.

Influenza is a viral infection of both the upper airway and the lungs. It comes on fast with fever, body aches, headache and a dry cough. It travels on droplets, the heavy kind that fall within a few feet, so a case goes on droplet precautions with a surgical mask up close. Because flu is a virus, antibiotics do nothing at all. Antiviral drugs help only when started early, and the strongest move comes before the season starts, which is vaccination.

Gut microbes nearly all share one road in, the fecal-oral route. Microbes, or the toxins they make, leave one gut in stool and reach a new mouth, riding on food, water or hands. But they cause illness in two very different ways.

In a true infection you swallow the organism, it settles in the gut, and then it invades or irritates the lining. Signs take a day or more, because the microbe has to multiply first. In an intoxication the microbe already grew in the food and left a toxin behind, so you swallow the toxin ready-made and signs hit within hours. The sudden vomiting of Staphylococcus aureus food poisoning is the classic case.

The usual culprits in foodborne illness are Salmonella, Campylobacter, Shiga-toxin-producing E. coli and norovirus. Their pictures overlap: nausea, vomiting, crampy belly pain, and diarrhea that may be watery or bloody. For most healthy adults it clears on its own, and the treatment is fluids, not antibiotics. The sharp eye goes to those at risk, who can dry out dangerously fast.

Bloody diarrhea is its own warning. It can point to the Shiga-toxin-producing strain of E. coli, which harms the kidneys, and that organism needs a clear caution. It never invades the blood. It grips the lining of the colon and lets out a toxin, and the toxin is what gets absorbed. Antibiotics and antidiarrheal drugs are off the table in a suspected case, because both raise toxin release and the risk of hemolytic uremic syndrome. Watch urine output, creatinine, platelets and hemoglobin.

Clostridioides difficile, or C. diff, is the infection that antibiotics help create. A broad-spectrum drug flattens the normal gut flora, and this spore-forming organism then blooms. The result is severe, foul-smelling, watery diarrhea and an inflamed colon. Two facts shape every step around it. It makes spores, and alcohol hand rub does not kill them, so hands must be washed with soap and water. And the room needs a bleach-based cleaner. Cases go on contact precautions.

Norovirus is the explosive, wildly catching cause of what people call stomach flu. It takes only a handful of virus particles to infect someone. It travels by the fecal-oral route and on the mist from vomit. Like C. diff spores, it stands up to alcohol gel, so again the answer is soap and water for hands and bleach for surfaces. Sudden vomiting and watery diarrhea sweeping through a group points straight at it.

The urinary tract infection, or UTI, is one of the most common infections there is, and it is usually an inside job. The culprit is most often a person's own Escherichia coli, which sits harmlessly in the colon and then climbs the short gap up the urethra into the bladder. Anatomy explains why women get far more UTIs than men, since the urethra is shorter and sits closer to the anus.

A lower UTI is cystitis, meaning a bladder infection. It brings dysuria, the burning that comes with passing urine, plus a need to go often and go now, and urine that looks cloudy or smells bad. If the infection climbs to the kidneys it is pyelonephritis, and now the whole body is ill. Fever. Chills. Pain in the flank, which is the back over the kidney.

A catheter-associated UTI, or CAUTI, follows an indwelling urinary catheter. The tube is a highway that lets bacteria skip every normal defense, and the risk climbs with every day it stays in. The best prevention is also the simplest. Do not place a catheter unless it is truly needed, and pull it the moment it is not. One more point is easy to miss. A positive urine culture with no symptoms is called asymptomatic bacteriuria, and it is usually not treated, because treating it breeds resistance and helps no one.

Sexually transmitted infections, or STIs, pass through sexual contact. Some are bacterial and antibiotics cure them. Others are viral, and we manage them without clearing them out. Two things make STIs their own kind of problem. Many are silent, so they are passed on unknowingly. And all of them carry shame, so a calm, non-judging history and real privacy are part of the care itself.

Chlamydia comes from Chlamydia trachomatis. It is the most reported bacterial STI and it is often silent, above all in women. Left alone it can scar the fallopian tubes and lead to infertility. Gonorrhea comes from Neisseria gonorrhoeae and often travels along with chlamydia, and its drug resistance is rising. Syphilis comes from Treponema pallidum, a corkscrew-shaped spirochete. Untreated it moves through stages, and it opens with a sore that does not hurt.

The viral STIs behave in their own ways, and not all alike. Genital herpes, from herpes simplex virus, stays for life and flares into crops of painful blisters. Human papillomavirus, or HPV, causes genital warts, and its high-risk types cause cervical cancer and some other cancers. That is exactly why the HPV shot counts as cancer prevention. HPV is not lifelong for most people. Roughly 90 percent of infections are cleared or held down within about two years. The cancer risk sits with lasting infection by a high-risk type, above all 16 and 18. Across all of these the same three moves apply. Push screening, since many are silent. Treat partners, or the infection just bounces back. And teach prevention without shame.

Blood is meant to be sterile, so finding microbes in it always means something. Bacteremia just means bacteria are in the blood. Sometimes it passes in minutes and does no harm, and brushing your teeth can do it. Other times it is the start of a disaster.

The danger is sepsis. Sepsis is not the infection itself. It is the body's own answer to it, running wild and out of control. Inflammation spreads everywhere. Vessels leak and widen. Blood pressure drops. Organs stop getting the blood they need. Left alone it moves on to septic shock, which is blood pressure so low that fluids will not bring it back, and after that comes failure of several organs at once. Common starting points are pneumonia, UTIs and infections inside the belly, plus an infected central line, which is a CLABSI.

Catching sepsis early is one of the highest-value skills there is, because survival is counted in hours. The picture is a person who looks and acts wrong on top of an infection. A fever, or a temperature oddly low. A fast heart rate. Fast breathing. And often the first and most telling sign of all: new confusion, or any change in how alert they are. Falling blood pressure, less urine and blotchy skin say shock is setting in. Once sepsis is spotted, care moves fast along a set bundle. Draw blood cultures. Give broad-spectrum antibiotics quickly. Run fluids to get blood moving again.

Meningitis is inflammation of the meninges, the thin covers wrapped around the brain and spinal cord. Bacterial meningitis is one of the true emergencies in this book, and it can kill a healthy young person inside a day. The classic three signs are fever, a severe headache and a stiff neck, and that last one has a name, nuchal rigidity. Often there is also photophobia, which means light hurts, plus vomiting and a fast slide in how alert the person is.

A spreading purple rash that does not fade under pressure points to the one most feared, Neisseria meningitidis. That organism rides respiratory droplets and can sweep through groups who live close together, so a suspected case goes on droplet precautions and close contacts may need antibiotics to keep them from falling ill.

The diagnosis rests on a lumbar puncture to draw spinal fluid. But the rule is speed, and antibiotics do not wait for the tap. Viral meningitis, also called aseptic meningitis, is far more common and usually much milder, and it settles on its own. The task is to keep bacterial meningitis front of mind any time a fever meets a stiff neck and a change in how alert someone is.

One thread runs through all five regions. Every organism travels a route, and each route has a matching set of steps that block it. Get the route right and the steps follow. Get it wrong and the gown, the mask or the gel does nothing.

The names worth memorizing

The sequences, in order

Skin infection by depth, shallowest first.

1. Impetigo. Outermost epidermis. Honey-colored crust.
2. Erysipelas. Upper dermis. Raised with a sharp border.
3. Cellulitis. Dermis and the fat below. Fuzzy edges.
4. Abscess. A walled pus pocket. May need drainage.
5. Necrotizing fasciitis. Along the fascia. Surgery, not just a drug.

From bacteremia to organ failure.

1. Bacteremia. Bacteria in the blood. May pass in minutes.
2. Sepsis. The body's own answer running wild. Vessels leak and widen.
3. Septic shock. Blood pressure so low that fluids will not bring it back.
4. Multiple organ failure. Several organs give out at once.

The sepsis bundle.

1. Draw blood cultures. Before the antibiotics go in.
2. Give broad-spectrum antibiotics quickly.
3. Run fluids to get blood moving again.

How to reason through the question types

The traps

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