L23/24 - Vaccines

Q: What are the two types of acquired immunity?

A: Active immunity and passive immunity. Both can be acquired naturally or artificially.

_________ immunity = Immunity in which the body produces its own protective immune response and lymphocyte memory following exposure to an antigen.

active

________ immunity = Immunity acquired through the transfer of preformed antibodies, providing immediate but temporary protection.

passive

________ acquired _____ immunity = Immunity developed after recovering from a natural infection; antigens inter the body naturally annd the body produces Ab and specialzed lymphocytes

naturally acquired active immunity

________ acquired _____ immunity = Transfer of maternal antibodies to the child through the placenta (IgG) or breast milk (IgA)

naturally acquired passive immunity

________ acquired _____ immunity = Immunity developed through vaccination, which stimulates the body's own protective immune response and lymphocyte memory; antigens enter the body (via vaccines) and the body produces Ab and specialzed lymphocytes

artificially acquired active immunity

________ acquired _____ immunity = Immunity acquired through injection of preformed antibodies, such as antivenom, antitoxin, or immunoglobulin therapy.

artificially acquired passive immunity

Q: Why is passive immunity considered transient?

A: It provides immediate but temporary protection because transferred antibodies do not establish lymphocyte memory.

Q: How do antivenom and antitoxin antibodies provide protection?

A: They are injected to rapidly neutralize toxins, providing immediate passive immunity.

Q: What is intravenous immunoglobulin (IVIG) therapy, and who can benefit from it?

A: Administration of pooled human immunoglobulins from blood donors to provide passive immunity, particularly in immunocompromised patients.

Q: What are the two major outcomes of active immunization?

A: A protective effector immune response and lymphocyte memory.

what do the terms vaccination and immunization refer to?

A: Artificially acquired active immunity that protects against infectious diseases.

What are the major routes of vaccine administration?

A: Parenteral (intradermal, intramuscular, subcutaneous), oral, and nasal routes.

What antibody response should all routes of immunization generate?

IgG responses.

Q: Which routes of immunization can generate both IgG and IgA responses?

A: Mucosal immunization through oral and nasal routes.

Q: What is the primary goal of vaccination?

A: To provide active, artificial immune memory that protects individuals against infectious diseases.

Q: How can vaccination establish protective immune memory?

A: Through a single vaccination or multiple doses of the same vaccine (booster vaccinations).

Q: What is herd immunity?

A: Protection of unvaccinated individuals that occurs when a large portion of the population is immunized against an infectious disease.

(Makes it harder to spread due to lacks or hosts)

Q: How does mass vaccination contribute to herd immunity?

A: By reducing the reservoir and prevalence of an infectious disease within the population, helping protect unvaccinated individuals.

_______ was a disease eradicated through worldwide immunization, wheras _______ and _______ have experienced outbreaks associated with declining vaccination rates

Smallpox

Measels and mumps

What are the main features of effective vaccines? (theres 5)

Safety, protection, inducing of neutralizing Ab, inducting of T cell responses and is overal pratical

Features of effective vaccines (3/5)

Safety?

Protective?

Practical?

•Safety: the vaccine itself will not cause illness or death.

•Protective: the vaccine most prevent (or reduce) illness for several years.

•Practical:  cost-effective, transportable, easy administration, low side-effects

Features of effective vaccines (5/5)

•Safety: the vaccine itself will not cause illness or death.

•Protective: the vaccine most prevent (or reduce) illness for several years.

•Practical:  cost-effective, transportable, easy administration, low side-effects

•Induces T cell responses ?

•Induces neutralizing antibodies: ?

•Induces T cell responses: CD8+ T (cytotoxic) cells will kill virally infected cells. 

CD4+ T cells will promote B cell activation which leads to somatic hypermutation, affinity maturation, isotype switching and immune memory.

•Induces neutralizing antibodies: some cells cannot be replaced (such as neurons). Neutralizing antibody will prevent viral infection of these cells.

• _______ (Helper T cells): Help activate B cells to produce antibodies and support immune memory. (IgG Ab)

• ________ (Cytotoxic T cells): Recognize and kill infected cells, particularly those infected with viruses.

• CD4+ T cells

• CD8+ T cells

Both CD4+ and CD8+ T cells can contribute to vaccine-induced immunity, but_______ cells are the major T-cell helpers for IgG production.

CD4+ T

The significance of IgG production during vaccination is that it provides ______ and _______ protection against infectious diseases.

effective; long-lasting

4 roles of IgG?

• Neutralization: IgG binds to pathogens and toxins, preventing them from causing harm.

• Opsonization: IgG coats pathogens, making them easier for phagocytes to recognize and destroy.

• Complement activation: IgG can activate the classical complement pathway to help eliminate pathogens.

• Long-term protection: Long-lived plasma cells can continue producing IgG after vaccination.

• _____: Often becomes prominent after class switching and provides effective, potentially long-lasting protection.

• _____: Allow rapid production of antibodies upon re-exposure.

• IgG

• Memory B cells

Q: Why are vaccine-related side effects often more concerning than drug-related side effects?

Drugs are generally given to sick individuals, while vaccines are administered to healthy individuals, often young children, making potential adverse effects a greater concern.

Q: Why are vaccine safety standards particularly high in the United States?

A: Because vaccines are administered to healthy individuals, including children, and must minimize the risk of adverse effects.

Q: How common are serious adverse reactions to vaccines, such as anaphylactic shock or death?

A: They are rare.

Q: Is there scientific evidence that vaccines cause autism or sudden infant death syndrome (SIDS)?

A: No. Scientific evidence does not support a causal relationship between vaccines and autism or SIDS.

Q: Why might individuals with certain allergies experience allergic reactions to vaccines?

A: Some vaccines may contain residual egg proteins or antibiotics that can trigger allergic reactions in susceptible individuals.

Some vaccines also contain Ab (to prevent contamination). individuals with allergies to certain Ab may also have an allergic rxn

(Influenza viruses can be cultured in eggs for vaccine production, potentially leaving residual egg proteins.)

Q: What neurological adverse effects have been associated with the Sabin live polio vaccine?

A: Rare cases of paralysis have been associated with the Sabin vaccine. The slide also lists seizures as a reported neurological reaction.

Q: What is vaccine shedding?

A: The release of vaccine-derived material, including live vaccine viruses from some live-attenuated vaccines, into the environment, potentially exposing other individuals.

Q: Which type of vaccine is associated with vaccine shedding?

A: Some live-attenuated vaccines.

This is where vaccine components are released into the enviorment (through feces or droplets) or to other people

What is a vaccine that has a chance to shed?

The oral polio vaccine (Sabin)

Q: What is the difference between the Sabin and Salk polio vaccines?

• Sabin: Live-attenuated oral polio vaccine that can undergo shedding.

• Salk: Inactivated (killed) polio vaccine.

Q: Which polio vaccine is used in the United States, and which may be used in countries where polio remains endemic?

A: The United States uses the inactivated Salk vaccine, while the live Sabin oral vaccine may be used in countries where polio remains endemic.

Why are live vaccines a concern for immunocompromised patients?

Live vaccines may cause disease in immunocompromised patients because their weakened immune systems may be unable to control the live pathogen.

Which patient populations are at increased risk of developing disease from live vaccines? (theres 5)

• Patients with HIV/AIDS

• Patients with primary (genetic) immunodeficiencies

• Patients receiving immunosuppressive therapy (organ transplant)

• Patients undergoing chemotherapy or radiation therapy

• Pregnant patients (potential risk to the fetus)

Q: What conditions may require immunosuppressive therapy, increasing the risks associated with live vaccines?

A: Organ transplantation, autoimmune diseases, and cancer.

Q: Why are live vaccines generally avoided during pregnancy?

A: Because of the potential risk that the live-attenuated pathogen could harm the developing fetus.

What are the major side effects to vaccines? What is the cause of these

• Injection site rxns: swelling, pain, erythema

• mild fever, shivering, fatigue, headache, muscle and joint pain

This is caused by the inflammatory response via the immune system (this means the vaccine is working via responding to foreign antigens)

Q: What is parenteral vaccine administration?

A: Administration of a vaccine by injection into body tissues, such as muscle.

Q: What immune responses are generated by parenteral vaccination?

A: Production of vaccine-specific memory T cells, memory B cells, and IgG antibodies.

Q: What is mucosal vaccine administration?

A: Administration of a vaccine to mucosal tissues, such as through the nasal or oral routes.

• FluMist vaccine (nasal)

• Sabin polio vaccine (oral)

• Rotavirus vaccine (oral)

Q: What immune responses are generated by mucosal vaccination?

A: Production of vaccine-specific memory T cells, memory B cells, and both IgG and IgA antibodies.

Q: What is the major difference between parenteral and mucosal vaccination regarding antibody production?

• Parenteral: Primarily generates IgG.

• Mucosal: Can generate both IgG and IgA.

Q: What is the significance of IgA production during mucosal vaccination?

A: IgA provides a first line of defense at mucosal surfaces by neutralizing pathogens and preventing their attachment and entry into tissues.

Q: Why do many vaccines, especially nonviable vaccines, require multiple doses?

A: To generate a robust immune memory response.

Q: What is boost vaccination (booster vaccination)?

A: Administration of multiple doses of the same or similar vaccine to strengthen immune memory.

Q: At what age are live-attenuated viral vaccines usually administered?

A: After 12 months of age.

Q: How do maternal antibodies provide protection to infants?

A: Maternal IgG antibodies are passively transferred to the infant, providing protection against infectious diseases.

Q: Why can maternal antibodies reduce the effectiveness of live-attenuated viral vaccines in infants?

A: Maternal IgG can bind to and neutralize the vaccine virus, preventing it from entering host cells and reducing vaccine effectiveness.

What is the goal of vaccines?

To induce a robust and protective immune memory respone

Q: When are memory B and T cells generated during the primary immune response to vaccination?

A: During the late stage of the primary immune response (takes about 2 weeks).

Q: What is the function of memory B and T cells after vaccination?

A: They recirculate throughout the body and survey for their specific antigen.

Q: How does the secondary (memory) immune response compare to the primary immune response?

A: The secondary response is faster and produces a larger peak immune response (due to memory).

Q: What pre-existing B cells and antibodies are present during the memory immune response?

A: High-affinity, isotype-switched memory B cells and antibodies, such as IgG.

Q: How does the amount of antigen stimulation required differ between primary and secondary immune responses?

A: The secondary immune response requires less antigen stimulation than the primary response.

Q: Do memory cells require persistent antigen exposure to maintain their population?

A: No. Memory cells can persist without continued antigen exposure.

Q: What is the overall effect of vaccination on morbidity and mortality?

A: Vaccination reduces both morbidity (disease-related illness) and mortality (death).

due to them not requiring antigens to persist and maintain their population, the main goal of vaccines is to utilize?

memory cells

Vaccines can generate _________ that prevent viruses and bacteria from infecting cells and ___________ antibodies

high affinity neutralizing antibodies; high affinity opsonizing antibodies

Q: How do neutralizing antibodies protect against viral infections?

A: They bind to viral proteins and prevent the virus from attaching to and entering host cells.

Q: What protein does influenza use to bind to host cells? What does it bind to?

A: Hemagglutinin (HA).

A: Sialic acid attached to proteins on the host cell surface.

Q: What are the major steps of influenza viral infection and replication?

• Hemagglutinin binds to sialic acid on host cells.

• The virus is internalized into the cell.

• Viral and endosomal membranes fuse.

• Viral RNA is released, allowing replication to occur.

Q: How do neutralizing antibodies against influenza hemagglutinin prevent infection?

A: They cover the hemagglutinin binding site, preventing attachment to sialic acid and subsequent entry into host cells.

Q: Which antibody is particularly important for neutralizing influenza at respiratory mucosal surfaces?

A: Secretory IgA dimers.

Q: Why is IgA particularly effective against influenza infection?

A: Influenza infects respiratory epithelial cells, and IgA provides protection at mucosal surfaces by preventing viral attachment and entry.

Q: What happens when influenza enters a host without pre-existing neutralizing antibodies?

A: The virus can attach to host cells, enter them, and replicate, potentially causing illness.

Q: What is the role of IgG antibodies in opsonization?

A: IgG antibodies coat pathogens, allowing phagocytes to recognize and engulf them through Fc receptors.

Q: What are the 5 steps of Fc receptor-mediated phagocytosis of an antibody-coated bacterium?

1. IgG antibodies bind to antigens on the bacterial surface, exposing their Fc regions.

2. Fc receptors on macrophages bind to the exposed Fc regions, triggering activation signals.

3. The macrophage membrane surrounds and engulfs the bacterium.

4. The membrane fuses around the bacterium, forming a phagosome.

5. Lysosomes fuse with the phagosome to form a phagolysosome, where the bacterium is destroyed.

Q: What region of IgG binds to Fc receptors on phagocytes?

A: The Fc region of IgG.

Q: How does Fc receptor binding enhance phagocytosis?

A: It activates phagocytes, promoting the engulfment and destruction of antibody-coated pathogens.

Q: How do Fc receptors and complement receptors work together to eliminate pathogens?

A: Fc receptors recognize antibody-coated pathogens, while complement receptors (CR1 and CR2) recognize C3 fragments deposited on pathogens following complement activation. Together, these mechanisms promote pathogen elimination.

Q: What is the role of cytotoxic CD8+ T cells generated by some vaccines?

A: To recognize and kill virally infected cells.

Q: What are the three major stages of CD8+ T-cell activation and function following vaccination?

• Antigen recognition: A dendritic cell presents an antigen on MHC I to a naïve CD8+ T cell, with B7–CD28 costimulation.

• Proliferation and differentiation: The activated CD8+ T cell produces and responds to IL-2, stimulating proliferation and differentiation.

• Effector function: Cytotoxic CD8+ T cells recognize and kill virally infected epithelial cells.

Q: What two signals are required for naïve CD8+ T-cell activation?

• Signal 1: TCR recognition of antigen presented on MHC I.

• Signal 2: B7 on the dendritic cell binds CD28 on the CD8+ T cell (costimulation).

Q: What cytokine promotes the proliferation and differentiation of activated CD8+ T cells?

A: IL-2, which binds to IL-2 receptors on activated CD8+ T cells.

Q: What is the effector function of activated cytotoxic CD8+ T cells?

A: Recognition and killing of virally infected epithelial cells.

What are the two major categories of vaccines used in the US?

Attenuated (live) andnonviable (killed)

_____ = Vaccines containing live microorganisms with reduced pathogenicity that stimulate protective immunity without typically causing disease in immunocompetent individuals.

live-attenuated vaccines

Q: How are modern live-attenuated vaccines often generated?

A: Using recombinant DNA technology.

Q: Why can live-attenuated vaccines be dangerous for immunocompromised patients?

A: The weakened pathogen may still cause severe or potentially fatal infections in patients with impaired immune function.

_______ = Vaccines that do not contain live, replicating pathogens and instead use inactivated microorganisms, microbial components, toxins that have been inactivated, or other nonliving vaccine technologies.

nonviable vaccines

Q: What are the major types of nonviable vaccines?

• Killed (inactivated) microorganisms

• Purified microbial components (subunits)

• Inactivated bacterial toxins

• Protein conjugates

• mRNA vaccines

Q: What are the two types of live-attenuated vaccines based on their ability to replicate?

A: Replicating (causes minor inflmmation) and nonreplicating (replication-deficient) vaccines.

Q: What technology is commonly used to develop modern live-attenuated vaccines?

A: Recombinant DNA technology.

Q: Why are live-attenuated vaccines considered highly potent?

A: They mimic the natural pathogen lifecycle (simulate real infection), stimulating strong immune responses.

Q: What immune responses are stimulated by live-attenuated viral vaccines?

• Memory B-cell responses

• CD4+ T-cell immunity

• CD8+ T-cell immunity

• Production of high-affinity, antigen-specific antibodies

Q: What is a major disadvantage of live-attenuated vaccines in immunocompromised patients?

A: The attenuated pathogen may cause opportunistic infections, potentially resulting in severe disease.

Q: What is a potential concern with administering live-attenuated rubella vaccines during pregnancy?

A: Theoretical risk of the attenuated virus crossing the placenta and causing fetal injury. Live MMR vaccination is therefore avoided during pregnancy.

Many vaccines, including live-attenuated vaccines, use _________technology

recombinant DNA

Q: What are the steps involved in creating a live-attenuated vaccine using recombinant DNA technology?

• Isolate the pathogenic virus.

• Identify and isolate the virulence genes (and core proteins + receptor binding proteins).

• Mutate or delete the virulence genes to reduce pathogenicity.

• The resulting virus remains viable and immunogenic but is avirulent, allowing it to be used as a vaccine.

Q: What is the purpose of mutating or deleting virulence genes when creating live-attenuated vaccines?

A: To reduce or eliminate the virus's ability to cause disease while preserving its ability to stimulate an immune response.

Q: Why must a genetically engineered live-attenuated vaccine remain immunogenic?

A: So it can mimic natural infection and stimulate a strong protective immune response without causing disease.

Q: What does it mean for a genetically engineered vaccine virus to be viable, immunogenic, and avirulent?

• Viable: The virus remains functional or capable of surviving.

• Immunogenic: It can stimulate an immune response.

• Avirulent: It lacks the ability to cause disease under normal conditions.