Vaccines & Preventable Disease

Mechanisms, patterns, and what happens when each one fails.

• Active vs passive immunity. Active = the patient's own immune system responds to antigen (infection or vaccination) — slow onset, memory, long duration. Passive = preformed antibody given or transferred (maternal IgG across the placenta, IgA in breast milk, IVIG, rabies or tetanus immune globulin, monoclonals like palivizumab/nirsevimab) — immediate protection, no memory, fades in weeks to months. Post-exposure prophylaxis for rabies and tetanus combines BOTH: immune globulin now, vaccine for later.
• Live attenuated vaccines. Weakened replicating organism → strong, durable humoral AND cellular (CD8) immunity, often lifelong after 1–2 doses; mimics natural infection including mucosal immunity for oral/nasal routes. Examples: MMR, varicella, zoster (old Zostavax — the current recombinant Shingrix is NOT live), rotavirus, intranasal influenza (LAIV), yellow fever, oral typhoid, BCG. Contraindicated in pregnancy and significant immunocompromise (the attenuated organism can revert or disseminate).
• Inactivated, subunit, toxoid, conjugate. Inactivated whole organism (injected influenza, hepatitis A, IPV polio, rabies): killed, cannot cause disease, safe in pregnancy/immunocompromise, but weaker — needs boosters and mainly drives humoral immunity. Subunit/recombinant = purified antigen (hepatitis B surface antigen, acellular pertussis, HPV virus-like particles, Shingrix). Toxoid = inactivated exotoxin (tetanus, diphtheria) — immunity is anti-TOXIN, not anti-organism. Conjugate = polysaccharide covalently linked to a carrier protein so a T-cell-dependent response (memory, class switching) forms in infants, who respond poorly to plain polysaccharide (Hib, PCV pneumococcal, MenACWY).
• Polysaccharide vs conjugate mechanism. Pure polysaccharide (PPSV23) is a T-INDEPENDENT antigen: it crosslinks B-cell receptors directly, giving mostly IgM, no germinal centers, poor memory, and essentially no response under age 2. Conjugating the sugar to a protein carrier lets B cells present carrier peptides on MHC II to helper T cells → class switching, affinity maturation, memory, and herd effects via reduced nasopharyngeal carriage. This mechanism question is a perennial favorite.
• mRNA vaccines. Lipid-nanoparticle-delivered mRNA encoding the antigen (COVID-19 spike); host cells translate it, so antigen is presented on MHC I as well as II — good antibody plus CD8 T-cell responses. No live virus, cannot integrate into the genome, safe in immunocompromise (though response may be blunted). Key adverse-event association: rare myocarditis, mostly in young males after the second dose.
• Herd immunity. When enough of a population is immune, transmission chains break and the unvaccinated (neonates, chemo patients, the vaccine-contraindicated) are protected indirectly. The threshold rises with contagiousness (roughly 1 − 1/R0): measles, the most contagious human virus (R0 12–18), needs ~92–95% coverage — which is why measles outbreaks are the first signal of falling vaccination rates.
• The classic exanthem discriminators. Measles (rubeola): cough, coryza, conjunctivitis, Koplik spots on the buccal mucosa, then a cephalocaudal maculopapular rash; complications include pneumonia, encephalitis, and years-later SSPE. Rubella: milder 3-day rash with posterior auricular/suboccipital lymphadenopathy — the danger is congenital rubella syndrome (cataracts, sensorineural deafness, PDA) from first-trimester infection. Varicella: pruritic vesicles in crops at different stages ('dewdrop on a rose petal'); the virus goes latent in dorsal root ganglia and reactivates as zoster.
• Toxin-mediated preventables. Tetanus: Clostridium tetani tetanospasmin blocks inhibitory (GABA/glycine) neurotransmitter release → trismus, risus sardonicus, opisthotonus; wound management pairs toxoid with tetanus immune globulin when immunization is inadequate and the wound is dirty. Diphtheria: Corynebacterium diphtheriae exotoxin (ADP-ribosylates EF-2, halting protein synthesis) → gray pseudomembranous pharyngitis, 'bull neck,' myocarditis, and neuropathy; antitoxin plus antibiotics.
• Pertussis and polio. Bordetella pertussis: catarrhal (most contagious) → paroxysmal (whooping cough, post-tussive emesis, infant apnea) → convalescent stages, with marked lymphocytosis; acellular vaccine (DTaP child, Tdap adolescent/adult, and Tdap EVERY pregnancy at 27–36 weeks to protect the newborn by transplacental IgG). Poliovirus destroys anterior horn motor neurons → asymmetric flaccid paralysis with intact sensation; the US uses inactivated IPV (the live oral vaccine carries a rare vaccine-derived paralysis risk).
• Hepatitis B, HPV, and the encapsulated killers. HBV vaccine is recombinant HBsAg; immunity = anti-HBs positive with anti-HBc NEGATIVE (natural infection gives both); birth-dose plus HBIG for infants of HBsAg-positive mothers. HPV vaccine (virus-like particles, types incl. 16/18 for cancer and 6/11 for warts) prevents cervical, anal, and oropharyngeal cancer — given at 11–12, before exposure. Encapsulated bacteria (pneumococcus, meningococcus, Hib) demand vaccination in asplenia/sickle cell; meningococcal vaccines also for college freshmen in dorms, military recruits, and complement-deficient or eculizumab-treated patients.

Each with the one fact that identifies it. Your course's slides are the authority; use this to check your list against.

1. 1Live attenuated vaccine — replicating weakened organism; avoid in pregnancy and immunocompromise
2. 2Toxoid — inactivated exotoxin; the tetanus and diphtheria strategy
3. 3Conjugate vaccine — polysaccharide linked to carrier protein so infants mount T-dependent memory
4. 4PPSV23 — pure polysaccharide, T-independent, poor response under age 2
5. 5mRNA platform — host cells translate the antigen; MHC I presentation gives CD8 responses
6. 6Passive immunity — preformed antibody, immediate but temporary, no memory
7. 7Herd immunity — indirect protection once coverage exceeds roughly 1 − 1/R0
8. 8Koplik spots — buccal gray-white lesions that precede the measles rash
9. 9Rubeola — cough, coryza, conjunctivitis, then a cephalocaudal rash
10. 10Rubella — mild 3-day rash with posterior auricular lymphadenopathy; devastating in the first trimester
11. 11Congenital rubella syndrome — cataracts, sensorineural deafness, patent ductus arteriosus
12. 12Mumps — parotitis with orchitis risk in postpubertal males
13. 13Varicella — pruritic vesicles in crops at different stages; latency in dorsal root ganglia
14. 14Bordetella pertussis — paroxysmal whooping cough with post-tussive emesis and lymphocytosis
15. 15Tetanospasmin — blocks GABA/glycine release, causing trismus and opisthotonus
16. 16Diphtheria — gray pharyngeal pseudomembrane and 'bull neck' from an EF-2-inhibiting exotoxin
17. 17Poliovirus — anterior horn cell destruction, asymmetric flaccid paralysis, sensation spared
18. 18Hepatitis B vaccine — recombinant surface antigen; immunity shows anti-HBs without anti-HBc
19. 19HPV vaccine — virus-like particles against 16/18 (cancer) and 6/11 (warts), given at 11–12
20. 20Hib conjugate — collapsed the leading causes of childhood epiglottitis and bacterial meningitis
21. 21MenACWY — required for asplenia, complement deficiency, dorm-living freshmen, and eculizumab
22. 22Tdap in pregnancy — dosed at 27–36 weeks each pregnancy to shield the newborn via transplacental IgG
23. 23Rabies post-exposure prophylaxis — immune globulin into the wound plus a vaccine series, active + passive together
24. 24Shingrix — recombinant (non-live) zoster vaccine, safe in immunocompromise
25. 25Rotavirus vaccine — live oral series with a small historical intussusception association
26. 26LAIV — the intranasal influenza option; live, so not for pregnancy or immunosuppression

The distinctions that lose points on this material, year after year.

• Egg allergy is not the influenza contraindication. Students reflexively pick 'egg allergy' as a reason to withhold flu vaccine; current guidance vaccinates egg-allergic patients with any age-appropriate product, no special precautions. The real contraindication to any vaccine is a severe allergic reaction (anaphylaxis) to a PRIOR DOSE or a vaccine component. For influenza specifically, a history of Guillain-Barré within 6 weeks of a prior influenza dose is the precaution to know.
• Zostavax vs Shingrix. MCQs bank on you tagging every zoster vaccine as live. The old Zostavax was live attenuated; the current recommended Shingrix is a recombinant subunit with adjuvant — non-live, preferred, and usable in immunocompromised adults. If the stem says 'recombinant zoster vaccine,' immunocompromise is NOT a contraindication.
• Toxoid immunity doesn't stop colonization. Tetanus and diphtheria vaccines raise antibody against the TOXIN, not the organism — a fully vaccinated person can still carry or be infected by C. diphtheriae; they just don't get toxin-mediated disease. Distractors that promise 'sterilizing immunity' or 'prevents carriage' from a toxoid are wrong.
• Anti-HBs vs anti-HBc serology. Vaccination produces anti-HBs ONLY (the vaccine is pure surface antigen). Anti-HBc positive means real exposure to the virus. The stem 'anti-HBs positive, anti-HBc negative' = vaccinated; adding anti-HBc flips the answer to resolved natural infection. This one serology pattern is asked constantly.
• Mild illness and household contacts are not contraindications. A low-grade fever or URI does NOT defer vaccination, and live vaccines (MMR, varicella) may be given to healthy household contacts of immunocompromised patients — the exception being that oral polio (not used in the US) sheds dangerously. Pregnancy in the PATIENT contraindicates live vaccines; pregnancy in a housemate does not.
• Conjugate vs plain polysaccharide in infants. Choosing PPSV23 for a 6-month-old is the classic trap: infants cannot mount a T-independent response, so plain polysaccharide is useless there. Conjugates (PCV, Hib, MenACWY) work in infancy precisely because the carrier protein recruits T-cell help. If the stem hinges on age under 2, the answer is the conjugate and the mechanism is T-dependent memory.
• Passive immunity questions disguised as vaccine questions. A neonate protected against measles for the first several months, or a needlestick managed with HBIG, is PASSIVE immunity — immediate, antibody-mediated, temporary, no memory. Students pick 'active' because a vaccine appears somewhere in the stem. Ask what is actually protecting the patient right now: transferred antibody or their own response.

Where this topic shows up again — in clinic, on rotations, and on the boards.

• The unvaccinated child with drooling and stridor. Sudden high fever, tripod positioning, drooling, muffled voice → epiglottitis, classically H. influenzae type b in the under-immunized. The Hib conjugate vaccine made this rare — vaccination history is the first question in the airway-emergency vignette, and the mechanism link is conjugation enabling infant immunity to a capsular polysaccharide.
• Rusty nail, unclear tetanus history. Dirty or puncture wound + fewer than 3 documented toxoid doses (or unknown status) = tetanus immune globulin PLUS Td/Tdap; clean minor wound = toxoid alone if >10 years since the last dose (>5 years for dirty wounds). The logic is pure immunology: passive antibody covers the gap while active immunity builds.
• Asplenic and sickle cell patients. No spleen → no efficient clearance of encapsulated organisms → overwhelming post-splenectomy infection. These patients get pneumococcal (PCV then PPSV23), meningococcal (ACWY and B), and Hib vaccination, ideally 2 weeks BEFORE elective splenectomy, plus prophylactic penicillin in children. Any 'splenectomy planned' stem is a vaccination question in disguise.
• Whooping infant, coughing parent. Infants too young to complete DTaP die of pertussis caught from adults whose immunity has waned — hence Tdap every pregnancy (transplacental IgG) and cocooning of close contacts. An infant with paroxysmal cough, apnea, and lymphocytosis needs a macrolide, and so do the household contacts regardless of symptoms.
• Pregnant woman and the rubella titer. Non-immune rubella titer found on prenatal labs: you CANNOT give MMR during pregnancy (live vaccine) — vaccinate immediately postpartum instead, and counsel avoidance of exposure meanwhile. The stakes are congenital rubella syndrome; the same logic defers varicella vaccine but allows Tdap and inactivated influenza during pregnancy.
• Measles outbreak thinking. Measles is airborne, contagious 4 days before the rash, and has an R0 of 12–18, so a single case in a low-coverage community is an emergency. Post-exposure: MMR within 72 hours for eligible contacts, immune globulin within 6 days for infants, pregnant women, and the immunocompromised — active if you can, passive if you can't.
• Shingles in a young adult. Zoster in a patient under 50 without known immunosuppression should prompt you to consider HIV testing — reactivation of latent varicella from dorsal root ganglia is held in check by T-cell immunity, so early or recurrent zoster is a T-cell red flag. Dermatomal vesicular rash that respects the midline is the pattern; antivirals within 72 hours.
• HPV and cancer prevention. HPV vaccination at 11–12 (before sexual debut) prevents cervical, anal, penile, and oropharyngeal cancers driven by types 16/18, whose E6/E7 oncoproteins degrade p53 and Rb — the one vaccine question that doubles as a genetics/oncology question. Vaccination does not replace cervical cancer screening.