BioSci: Vaccines and Memory

What antibody does the fetus produce, and which is primarily provided by the mother?

The fetus can produce IgM, but maternal IgG provides most protection via placental transfer

How long does maternal IgG protect the infant, and what happens after?

Maternal IgG lasts up to 6 months; it declines by 3–6 months, increasing infection risk

What antibody in breast milk protects the infant’s gut, and for how long should breastfeeding ideally continue?

Secretory IgA protects the GI tract; breastfeeding is recommended for up to 1 year

When do infants begin producing their own IgG and IgA, and when do vaccines start?

Infants start making IgG and IgA soon after birth, but they become effective by 1 year. Vaccines begin at 2 months.

Why are newborn B and T cells less effective despite being more numerous?

They are less mature and functionally limited, adapting to antigens outside the sterile womb

What natural barriers and innate functions are underdeveloped in newborns?

Physical barriers like the gut (matures at 3–4 weeks) and phagocytes are immature and less responsive

Why must newborns be immunologically “tolerant” at first?

To avoid overreacting to the flood of new microbes and antigens encountered after birth.

Why are vaccine schedules critical in early life?

They must be timed to ensure the infant can respond effectively but not given too early to be ineffective

What happens to the thymus with age, and how does it affect T cells?

The thymus atrophies by age 60, so new T cell production declines, relying mostly on memory T cells.

Why are older adults more prone to infections and less responsive to vaccines?

Due to immunosenescence, B cell exhaustion, and reduced T cell function, vaccine responses weaken—boosters or adjuvants like Shingrix are needed.

Which infections can reactivate in elderly due to declining immune surveillance?

Latent infections like varicella (shingles) and tuberculosis may reactivate

Why is autoimmunity more common in the elderly?

Fewer regulatory T cells (Tregs) allow autoreactive T cells to escape control and cause disease

Why must the immune response be stopped after clearing a pathogen?

To prevent persistent inflammation and damage to healthy tissue.

What is anergy, and how does it prevent inappropriate immune responses?

Anergy is when T or B cells become unresponsive after recognizing antigen without signal 2 (e.g., no B7-CD28 binding), preventing activation without proper danger signals.

What is the role of CTLA-4 in T cell regulation?

CTLA-4 is expressed after T cell activation and competes with CD28 for B7 binding on APCs, preventing further T cell activation and restoring homeostasis

How do Tregs use CTLA-4 to suppress immune responses?

Tregs constantly express CTLA-4, binding B7 on APCs to block CD28 interaction, thereby preventing activation of other T cells

How can CTLA-4 be targeted in therapy?

Blocking CTLA-4 can boost cancer immunity; mimicking it can cause immunosuppression

How does PD-1 inhibit T cell activation, and how do tumors exploit this?

PD-1 on T cells binds PD-L1 on APCs (or tumor cells), blocking signal 1 (TCR–MHC interaction). Tumors overexpress PD-L1 to evade CTL destruction

How is the PD-1/PD-L1 pathway targeted in cancer therapy?

Blocking PD-1 or PD-L1 can restore T cell activity against tumors—this is the basis of several current immunotherapies

What is the role of IL-10 in immune regulation?

IL-10, made by Th2 cells and Tregs, shuts off the Th1 response and dampens inflammation.

What does TGF-β do in the immune system and healing?

TGF-β inhibits T cell growth/activation and promotes wound healing by increasing collagen synthesis; it's made by Tregs, B cells, and macrophages.

How do memory cells enhance immune responses upon re-exposure?

They allow for a faster, stronger response to previously encountered antigens—greater than the primary response

How long do memory cells last, and what can they do?

Memory cells can live for years and may self-renew to maintain long-term immunity.

Can all T cells become memory cells?

Any T cell can become a memory cell, but only a few actually do after an immune response

How are memory T cells more efficient than naïve T cells?

They respond to lower antigen levels, need less costimulation, and expand faster due to a larger starting pool.

How do memory T cells support the immune response upon reactivation?

They produce more cytokines than naïve T cells and help boost antibody production by memory B cells.

Which B cells become memory cells?

Only B cells activated by T helper cells can become memory B cells

What are key features of memory B cells?

They stay quiescent for long periods but respond quickly upon reexposure and usually express surface IgG as their antigen receptor.

Vaccines induce ___

active immune response = leads to memory response

Booster vaccines ____

enhance affinity maturation to improve antibodies binding to antigens

Vaccines have whole pathogens or parts of pathogens (proteins or products) to

induce a protective immune response

Whole pathogens in vaccines can be

unaltered, killed, or live attenuated (weakened)

Vaccines can also contain toxins ___

inactivated with chemicals or by genetic modification to become toxoids à less toxic but still immunogenic

Vaccines can provide passive immunity by

administering preformed antibodies for certain diseases to neutralize unbound toxins (antitoxins) before they do more damage

Vaccines providing passive immunity are typically made in animals and can

cause adverse reaction like serum sickness

Vaccines can provide passive-active immunity by giving both

preformed antibodies to provide immediate protection AND a traditional vaccine to provide long-term protection (vaccine PLUS antitoxin)

Depending on the durability of memory response, you may need

1 shot or multiple boosters

We start giving some vaccines at birth, such as

HepB (just one currently) - most are given at 2 months or later

Vaccine schedules are created so you get the optimal

immune response with best durability (memory)

Which antibody response is primarily induced by IM and SC vaccines?

IgG (systemic immunity: blood and tissues)

Which antibody response is primarily induced by oral or intranasal vaccines?

IgA (mucosal immunity)

What types of vaccines are typically administered orally or intranasally?

Usually live vaccines (e.g., Polio, Influenza, Rotavirus)

Why are SC and IM sites effective for vaccination?

They have many antigen-presenting cells (APCs), aiding immune activation.

Why are carrier proteins (e.g., toxoids) added to some vaccines?

To enhance T cell activation and antibody response by making poorly immunogenic components more immunogenic.

In which population are carrier protein-conjugated vaccines especially important?

Infants, due to their underdeveloped immune responses.

What are adjuvants used for in vaccines?

To boost the immune response when the antigen alone is not sufficiently immunogenic.

How do adjuvants differ from carrier proteins in vaccines?

Adjuvants are chemically unrelated and not covalently bound to antigens; carrier proteins are covalently linked.

Name 3 ways adjuvants enhance immune responses.

• Prolong antigen release

• Promote antigen uptake by APCs

• Increase APC migration to lymphoid tissues

How do adjuvants act like PAMPs to boost immunity?

They induce costimulatory molecules (like B7) and can stimulate TLRs to enhance cytokine production and T/B cell responses.

What type of adjuvant is Alum and what does it do?

Aluminum salts (Alum) increase proinflammatory cytokine production.

Which vaccines use Alum as an adjuvant?

Havrix, Recombivax HB, Gardasil 9, Quadracel

What does MF59 (in Fluad) do and what is it made of?

MF59 is a squalene oil-in-water emulsion that prolongs antigen exposure.

Name 2 TLR-binding adjuvants and the vaccines they are used in.

• CpG (TLR9 agonist) in Heplisav-B

• AS01 (lipid A from Salmonella, TLR4 agonist) in Shingrix

Which bacteria have vaccines using capsular polysaccharide conjugates?

Haemophilus influenzae, Streptococcus pneumoniae, Neisseria meningitidis

Which bacterial vaccines are based on inactivated exotoxins (toxoids)?

Diphtheria, tetanus, and pertussis (as toxoids in Tdap)

What are examples of acellular purified protein vaccines?

Bordetella pertussis (“ap” in Tdap), Bacillus anthracis, Neisseria meningitidis serotype B

Which bacteria are targeted by killed or live attenuated vaccines?

• Killed: Vibrio cholerae, Yersinia pestis, Rickettsia rickettsii, Coxiella burnetii, B. pertussis

• Live attenuated: Salmonella typhi, Mycobacterium tuberculosis (BCG), Francisella tularensis, V. cholerae

What carrier protein is used in Prevnar 13, N. meningitidis, and H. influenzae vaccines?

Diphtheria toxoid — improves immune response, especially in young children.

What is the role of tetanus, botulinum, or diphtheria antitoxins?

Passive immunity — neutralizes circulating toxins before they bind

What monoclonal antibody is used against C. difficile toxin?

Bezlotoxumab

What is passive-active immunity and when is it used?

Immediate protection via antitoxin + long-term immunity via vaccine (e.g., tetanus toxoid + tetanus antitoxin)

Why is prevention more important than treatment for viral infections?

Few antiviral drugs are effective against most viral infections.

What types of viral vaccines are used in practice?

Live attenuated, inactivated (killed), purified viral proteins, or mRNA.

What is the main immunologic benefit of live attenuated viral vaccines?

Allow replication → prolonged antigen stimulus → strong, long-lasting IgG response (and sometimes CTLs).

How does the intranasal flu vaccine work differently from the injectable one?

It’s a temperature-sensitive live attenuated virus that replicates only in nasal passages → induces mucosal IgA

Which viral vaccines are inactivated and require boosters?

Injectable polio, influenza shot, Hepatitis A, rabies.

How do protein subunit vaccines (like HepB) behave immunologically?

Like killed vaccines — no replication, so weaker immunity and no CTL response.

What type of immune response do oral polio and rotavirus vaccines induce?

Both IgG and IgA — mimics natural fecal-oral immunity.

Which vaccines should be avoided in patients with egg anaphylaxis?

Influenza, measles, mumps, yellow fever (grown in chick embryos).

Can patients with feather allergies receive egg-based vaccines?

Yes — feather allergy is not a contraindication

What is a rare but serious risk of live attenuated vaccines like oral polio?

They can revert to virulent forms and cause disease.

Why are live attenuated vaccines contraindicated in immunocompromised patients and pregnant women?

Because the attenuated virus can still replicate and cause disease.

How can live vaccines indirectly infect others?

The attenuated virus can be shed by the vaccinated individual and transmitted to close contacts.

Why don’t killed vaccines induce a CTL response?

No viral replication means no MHC I antigen presentation.

What type of immune response is induced by IM killed vaccines?

IgG only (no IgA, no CTLs).

What are advantages of killed vaccines?

Cannot revert to virulence; safe for immunocompromised; more heat-stable

What are limitations of killed vaccines?

Weaker, shorter protection; less IgA; require boosters

Why don’t killed vaccines induce a CTL response?

They don’t replicate, so antigens aren’t presented on MHC I.

What are 3 advantages of killed vaccines?

• Safe for immunocompromised

• More heat-stable (good for tropical use)

• No risk of reversion to virulence

What are the limitations of killed vaccines?

Shorter duration of protection, mainly IgG only, and no CTL induction.

What are recombinant live virus vaccines?

Live, nonpathogenic viruses engineered to express genes from pathogenic viruses

Name examples of recombinant viral vaccines.

• Ebola-VSV

• Human rotavirus-bovine rotavirus

• Dengue-yellow fever

• COVID-19-adenovirus

• HIV-vaccinia/polio/adenovirus

What are recombinant subunit vaccines and how are they made?

Viral antigens cloned in bacteria or yeast — no nucleic acids, just proteins.

Which vaccines are examples of recombinant subunit vaccines?

HepB, HPV, VZV (shingles), and influenza.

What are the pros and cons of recombinant subunit vaccines?

• Cannot replicate

• Cannot revert to virulence

• No contamination risk

• Mass-producible
  Cons:

• Do not induce CTL response (no intracellular replication)

How do nucleic acid vaccines (DNA/mRNA) work?

Deliver DNA plasmid or mRNA encoding viral proteins → host cells translate them → immune system responds.

What types of immune responses do nucleic acid vaccines elicit?

Both antibody and cytotoxic T cell (CTL) responses.

Which vaccine is the best-known example of a nucleic acid vaccine?

COVID-19 mRNA vaccines (Pfizer-BioNTech, Moderna)

Why are rabies and HepB vaccines effective even after exposure?

These viruses have long incubation periods, allowing time for post-exposure immunization to work

What is included in rabies post-exposure prophylaxis?

Inactivated rabies vaccine + rabies immunoglobulin (RIG), with RIG given into the bite and remainder IM

What is included in HepB post-exposure prophylaxis?

HepB vaccine + HepB immunoglobulin (HBIG), used for needlesticks and neonates born to infected mothers.

What is herd immunity and what threshold is typically required?

Community protection achieved when >90% of the population is immune, reducing spread to unimmunized individuals.

What is required for a vaccine to induce herd immunity?

It must prevent both disease and transmission of the pathogen

Why does the oral polio vaccine provide herd immunity but the injected one does not?

Oral vaccine induces intestinal IgA, preventing replication/transmission. Injected vaccine lacks this mucosal immunity.

Why can vaccine protection wane over time?

Memory cells may decline in number or function, depending on the antigen used.

What evidence shows that vaccine immunity can decrease?

In 2019, 3% of measles cases occurred in people who had received the MMR vaccine

What is a goal of vaccine research regarding long-term immunity?

To identify antigens and conditions that promote durable memory and reduce the need for boosters

What type of immune response is triggered against extracellular bacteria?

Pyogenic response, driven by neutrophils (PMNs) that produce pus.

Which cytokines do macrophages release upon extracellular TLR activation?

IL-1, IL-6, IL-8, and TNF-α.

What do Th17 cells secrete and what are their effects?

IL-17 (recruits PMNs) and IL-21 (activates B cells to class switch to IgG)