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Questions and Answers
What mechanism allows memory B cells to move quickly to lymph nodes during a secondary immune response?
What mechanism allows memory B cells to move quickly to lymph nodes during a secondary immune response?
What characteristic distinguishes long-lived plasma cells from short-lived effector plasma cells?
What characteristic distinguishes long-lived plasma cells from short-lived effector plasma cells?
What is a key factor in the phenomenon known as original antigenic sin?
What is a key factor in the phenomenon known as original antigenic sin?
Why might a vaccine require multiple doses?
Why might a vaccine require multiple doses?
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Which of the following best describes attenuated vaccines?
Which of the following best describes attenuated vaccines?
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What role do adjuvants play in vaccine formulation?
What role do adjuvants play in vaccine formulation?
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Which type of vaccine involves inactivated toxins?
Which type of vaccine involves inactivated toxins?
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What protects long-lived plasma cells in the absence of antigen?
What protects long-lived plasma cells in the absence of antigen?
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What is a consequence of high mutation rates in pathogens like influenza?
What is a consequence of high mutation rates in pathogens like influenza?
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What is a common outcome when memory B cells suppress naïve B cell activation during a secondary response?
What is a common outcome when memory B cells suppress naïve B cell activation during a secondary response?
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What distinguishes the secondary immune response from the primary immune response?
What distinguishes the secondary immune response from the primary immune response?
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Which statement about memory T cells is correct?
Which statement about memory T cells is correct?
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What is the primary role of immunologic memory?
What is the primary role of immunologic memory?
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Which cytokines are suggested to stimulate the survival and proliferation of memory cells?
Which cytokines are suggested to stimulate the survival and proliferation of memory cells?
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Which characteristic is generally NOT true for memory B cells?
Which characteristic is generally NOT true for memory B cells?
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Where are memory T cells predominantly located?
Where are memory T cells predominantly located?
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What is a unique feature of central memory T cells?
What is a unique feature of central memory T cells?
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Which of these statements about the primary immune response is true?
Which of these statements about the primary immune response is true?
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Study Notes
Immunologic Memory & Vaccination
- Vaccination is the clinical application of immunization to help the body defend itself, acting as a preventative therapy.
- Vaccines use a modified form of a natural immunogen (antigen), including whole pathogens, components of pathogens, or toxins.
- A typical infection has four phases:
- Establishment of infection
- Inductive phase
- Effector phase
- Memory phase
Learning Objectives
- Understanding primary and secondary immune responses is crucial.
- Distinguishing between naive, effector, and memory lymphocytes is key.
- It is important to understand the basis of vaccination and how various vaccines function.
Course of a Typical Infection
- The innate immune response initially establishes and controls infection.
- The adaptive immune response follows, eventually clearing the pathogen.
- Levels of microorganism rise and fall over the duration of infection.
Stages of Infection & Host Response
- Infections typically begin locally, penetrating the epithelium.
- Localized infections progress to lymphatic spread.
- The adaptive immune response clears the infection.
- Protection against infection involves complement activation, dendritic cell migration to lymph nodes, phagocyte action, NK cell activation, and cytokine/chemokine production.
Immunological Memory
- Primary immune response clears the pathogen and builds immunological memory.
- Adaptive responses are specific to B and T cells.
- Secondary immune responses are faster and more potent than primary responses due to memory B and T cells.
- Memory cells include long-lived plasma cells and memory T cells.
Memory Cells & Their Persistence
- Memory cells persist due to metabolic changes.
- Naive T cells have a different metabolic profile than effector T cells, which, in turn, has a different profile from memory T cells.
- T cells are activated for hours, effector T cells for days, and memory T cells for weeks to years.
Immunological Memory is Long-lasting
- Antibody-specific responses are maintained for years.
- CD4+ T cells decline compared to CD8+ T cells, despite memory T cells remaining.
- Protective immunity varies between different pathogens.
- Vaccination with a virus, such as vaccinia, exhibits different response times depending on the frequency of vaccination (one vs. two).
Maintenance of Immunological Memory
- Memory persists independently of antigen presence.
- Most memory cells are quiescent, but some fractions renew.
- Cytokines, such as IL-7 and IL-15, may influence survival and proliferation.
Memory T Cells
- A portion of activated CD4 and CD8 T cells survive downregulation, becoming memory T cells.
- Memory T cells are located in peripheral tissues and inflammatory sites.
- Minimal co-stimulation is needed for activation.
- Rapid response to antigen encounter.
- Self-renewal maintains long-term survival.
- Distinct populations of central, effector, and resident memory T cells exist.
Memory B Cells
- Memory B cells are activated B cells that have undergone somatic hypermutation and isotype switching.
- Morphologically similar to naive B cells, but distinct from plasma cells.
- Secondary responses are more efficient.
- Memory B cells have enhanced adhesion molecules, have high affinity for antigen, and express more co-stimulatory molecules.
- Progeny of memory B cells differentiate into additional plasma cells.
Plasma B Cells
- Short-lived effector plasma cells are made during the primary immune response.
- High production stress and speed result in cellular damage and genomic mutations.
- Immune complexes binding to FcgRIIb1 on plasma cells induce apoptosis.
- Long-lived plasma cells survive in the absence of antigen, and exist in the bone marrow.
- Long-lived plasma cells provide maintenance of antibodies and depend on IL-6 from stromal cells for survival,
- They lack BCR expression.
Memory B Cell Response
- Primary and secondary responses are distinguished by different antibody production kinetics.
- Primary responses use naive B cells and have a longer lag time, low peak magnitude of response, and predominantly produce IgM.
- Secondary responses use memory B cells which have a shorter lag time, higher magnitude response, and predominantly produce IgG.
Memory B Cell Responses: Suppressing Naïve Cells
- Memory B cells are suppressed by antibodies from primary response.
- This suppression is mediated by FcyRIIB1.
- Naïve B cells interacting with pathogens and high-affinity IgG are less likely to respond and activate to pathogens.
- Original antigenic sin impacts responses to pathogens.
Original Antigenic Sin
- Immunological memory to antigens from previous infections can impede response to related but different pathogens.
- Individuals frequently respond to the antigen from the initial infection, even when exposed to variant pathogens.
- Response to influenza strains can present challenges.
Summary - Memory
- Primary responses are slower, smaller, and use IgM.
- Secondary responses are faster, larger, and use IgG.
- Innate and adaptive immunity cooperate in secondary responses.
Vaccination
- Vaccination is designed to artificially generate a body defense.
- Vaccines employ modified forms of natural immunogens.
- Vaccines use whole pathogens, components, or toxins to stimulate adaptive immune responses.
The Principle of Vaccination
- Vaccines induce an initial primary response.
- Subsequent exposures to pathogens create secondary and stronger responses.
- Passive immunization is antibody transfer through placental or breast milk.
Most Vaccines Require Multiple Doses
- Vaccines requiring multiple doses elicit both primary and secondary responses.
- Long-lived antibodies are important for sustained immunity.
- Vaccine schedules vary for different diseases and populations.
Generating Vaccines
- Pathogen type, location of infection, and mutagenic capacity influence vaccine design and efficacy.
- Chronic vs. short-term infections inform vaccine design.
- Risk of serious illness and/or infection is a factor in development.
- Antibody response, or the lack thereof (need for T cells), may necessitate different vaccine formulations.
Challenge to RNA Vaccine Development
- Recombination in segmented genomes occurs frequently in viruses like influenza.
- This leads to notable variations.
- Influenza pandemics are a consequence.
How the Flu Virus (Influenza) Can Change
- Antigenic drift involves subtle changes in surface proteins (antigens).
The First Vaccine- Smallpox (Vaccinia Virus)
- Cowpox and smallpox share surface antigens.
- Immunization with cowpox induces antibodies against cowpox, also neutralizing smallpox.
Types of Vaccines
- Live attenuated, killed pathogen, inactivated toxoid, and subunit/conjugate vaccines are the main categories.
Antibody Protection from Vaccines
- Antibodies can neutralize toxins, block pathogen colonization, and opsonize pathogens.
Attenuated Vaccines
- Attenuated vaccines use weakened versions of pathogens.
- These pathogens grow poorly in humans, and not harmful enough to cause disease.
- They effectively mimic a real infection.
Conjugate Vaccines
- Conjugate vaccines combine a weak antigen (such as a polysaccharide) to a strong antigen (such as a toxoid protein).
- This combination prompts the activation of both B cells and T cells.
- This approach enhances antibody production and complement activation for improved protection.
Available Vaccines
- A list of vaccines for various human diseases.
- Categorized by disease type (bacterial or viral) and vaccine type (live attenuated, killed, etc.).
Adjuvants
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Various adjuvants are used to enhance immunologic responses to vaccines.
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These substances help the body to mount a stronger immune response.
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Different adjuvants bind various TLRs.
Coronavirus
- Coronaviruses cause common colds, SARS, and MERS.
- Coronaviruses are non-segmented genomes that don't undergo antigenic shift.
- These viruses recombine, creating new strains.
COVID-19 Vaccine: mRNA Vaccines
- mRNA vaccine encodes for viral proteins.
- mRNA is degraded within 48 hours of administration.
- Lipids enclose mRNA to induce innate immune response.
- mRNA vaccines do not require the actual virus.
HIV- Entry Via Co-receptors
- HIV entry involves interactions with CD4 and coreceptors on host cells.
- Viral proteins (gp120, gp41) drive cell fusion.
HIV Vaccine- Germline Targeting
-Broadly neutralizing antibodies in vaccines are rare. -Antibodies should recognize various epitopes on HIV proteins,
- Phase 1 clinical trials confirm vaccination is effective with a specific nanotechnology.
Vaccine Development and Hesitancy
- Effective vaccines are safe, protective, sustained protective, induce neutralizing antibodies and protective T-cells, are practical, and perceived as safe.
- Vaccine development involves rigorous evaluation during various phases.
Vaccine Safety Evaluation
- Vaccine safety is meticulously evaluated during all phases of development, including preclinical, phase 1, phase 2, phase 3, and phase 4.
- Different phases have different sample sizes and are designed to achieve different evaluation goals (efficacy, safety, and immunogenicity).
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Description
Explore the principles of immunologic memory and the role of vaccination in disease prevention. This quiz delves into the phases of infection, immune responses, and types of lymphocytes. Understanding these concepts is essential for grasping how vaccines work to protect the body.
