Podcast
Questions and Answers
Which characteristic is most likely to make an antigen a strong immunogen?
Which characteristic is most likely to make an antigen a strong immunogen?
- Simple, repeating structure.
- High degree of foreignness. (correct)
- Small molecular weight.
- Originating from the host.
What is the primary function of class switch recombination (CSR)?
What is the primary function of class switch recombination (CSR)?
- To change the antibody isotype, thus altering its effector function. (correct)
- To enable B cells to respond to a wider variety of antigens.
- To accelerate the rate of antibody production.
- To increase the affinity of the antibody for its antigen.
Which of the following is NOT a major mechanism of antibody effector function?
Which of the following is NOT a major mechanism of antibody effector function?
- Antibody-dependent cell cytotoxicity (ADCC)
- Neutralization
- Opsonization
- Antigen Internalization (correct)
Which antibody isotype is MOST associated with allergic responses?
Which antibody isotype is MOST associated with allergic responses?
What is a key characteristic of haptens?
What is a key characteristic of haptens?
Which factor is LEAST likely to affect the immunogenicity of an antigen?
Which factor is LEAST likely to affect the immunogenicity of an antigen?
What is the primary role of circulating antibodies?
What is the primary role of circulating antibodies?
Where does class switch recombination (CSR) occur?
Where does class switch recombination (CSR) occur?
Which enzyme is essential for the process of class switch recombination (CSR)?
Which enzyme is essential for the process of class switch recombination (CSR)?
Following activation by antigen, what is the immediate fate of IgM and IgD produced within a B cell?
Following activation by antigen, what is the immediate fate of IgM and IgD produced within a B cell?
Which statement accurately describes the function of the secretory component associated with IgA?
Which statement accurately describes the function of the secretory component associated with IgA?
Which antibody isotype is transported across the placenta to provide passive immunity to the developing fetus?
Which antibody isotype is transported across the placenta to provide passive immunity to the developing fetus?
What is the primary mechanism by which IgA protects mucosal surfaces?
What is the primary mechanism by which IgA protects mucosal surfaces?
How does IgM initiate the classical pathway of complement activation?
How does IgM initiate the classical pathway of complement activation?
An individual is bitten by a venomous snake. Which therapeutic approach would MOST directly employ neutralization?
An individual is bitten by a venomous snake. Which therapeutic approach would MOST directly employ neutralization?
What is the role of Fc receptors in antibody-mediated effector functions?
What is the role of Fc receptors in antibody-mediated effector functions?
What is the correct order of events in the classical pathway of complement activation, beginning with antibody binding?
What is the correct order of events in the classical pathway of complement activation, beginning with antibody binding?
Which of the following is true regarding the transport of IgG across the placenta?
Which of the following is true regarding the transport of IgG across the placenta?
Which process BEST describes how antibodies contribute to the neutralization of a virus?
Which process BEST describes how antibodies contribute to the neutralization of a virus?
In antibody-dependent cell cytotoxicity (ADCC), which cell type is MOST critical for mediating the killing of target cells?
In antibody-dependent cell cytotoxicity (ADCC), which cell type is MOST critical for mediating the killing of target cells?
An individual with a genetic defect has a complete absence of Fc&RI (Fc epsilon receptor I). Which immune function would be MOST impaired in this individual?
An individual with a genetic defect has a complete absence of Fc&RI (Fc epsilon receptor I). Which immune function would be MOST impaired in this individual?
Which characteristic distinguishes IgA1 from IgA2?
Which characteristic distinguishes IgA1 from IgA2?
After the classical C3 convertase (C4bC2a) is formed, what is its DIRECT enzymatic activity?
After the classical C3 convertase (C4bC2a) is formed, what is its DIRECT enzymatic activity?
What is the MAIN role of C3b in complement activation?
What is the MAIN role of C3b in complement activation?
How are immune complexes (ICs) removed from circulation?
How are immune complexes (ICs) removed from circulation?
Which statement is TRUE regarding fetal and neonatal immunity?
Which statement is TRUE regarding fetal and neonatal immunity?
Which cytokine involved in class switch recombination biases towards IgE and IgG4?
Which cytokine involved in class switch recombination biases towards IgE and IgG4?
What is the implication of low molecular weight for a potential immunogen?
What is the implication of low molecular weight for a potential immunogen?
How does the 'staple' form of IgM contribute to complement activation?
How does the 'staple' form of IgM contribute to complement activation?
If C4bC2a is the classical C3 convertase, what is the alternative C3 convertase?
If C4bC2a is the classical C3 convertase, what is the alternative C3 convertase?
During an infection, an individual's B cells undergo class switching to produce IgE. What is the MOST likely effector function that will be enhanced by this switch?
During an infection, an individual's B cells undergo class switching to produce IgE. What is the MOST likely effector function that will be enhanced by this switch?
What is the direct mechanism by which an antibody mediates neutralization?
What is the direct mechanism by which an antibody mediates neutralization?
Which factor primarily determines whether an antibody will promote inflammation or suppress it?
Which factor primarily determines whether an antibody will promote inflammation or suppress it?
While studying the immune system, a researcher discovers a novel protein that, when bound to IgA, prevents its interaction with the polymeric immunoglobulin receptor (pIgR). What is the MOST likely consequence of this interaction?
While studying the immune system, a researcher discovers a novel protein that, when bound to IgA, prevents its interaction with the polymeric immunoglobulin receptor (pIgR). What is the MOST likely consequence of this interaction?
Consider a scenario where a new bacterial strain has evolved a mechanism to cleave C3b into inactive fragments. What is the MOST likely immediate consequence of this bacterial adaptation within the host?
Consider a scenario where a new bacterial strain has evolved a mechanism to cleave C3b into inactive fragments. What is the MOST likely immediate consequence of this bacterial adaptation within the host?
A researcher is investigating a new drug that aims to modulate class switch recombination (CSR) to enhance the production of IgG3 in response to a specific viral infection. Which cellular interaction should the drug MOST directly target to achieve this outcome?
A researcher is investigating a new drug that aims to modulate class switch recombination (CSR) to enhance the production of IgG3 in response to a specific viral infection. Which cellular interaction should the drug MOST directly target to achieve this outcome?
Which antibody isotype is MOST effective at neutralizing toxins in the bloodstream, and why?
Which antibody isotype is MOST effective at neutralizing toxins in the bloodstream, and why?
A neonate is diagnosed with a genetic defect that impairs the function of the neonatal Fc receptor, FcRn. Which immunological consequence is MOST likely to occur in this infant?
A neonate is diagnosed with a genetic defect that impairs the function of the neonatal Fc receptor, FcRn. Which immunological consequence is MOST likely to occur in this infant?
A researcher discovers that a particular antigen is able to activate the alternative pathway of complement, but is resistant to opsonization. Which modification of the antigen would MOST likely render it susceptible to opsonization?
A researcher discovers that a particular antigen is able to activate the alternative pathway of complement, but is resistant to opsonization. Which modification of the antigen would MOST likely render it susceptible to opsonization?
An experimental drug is designed to completely inhibit the function of C1q. What downstream effects would result from the use of this drug?
An experimental drug is designed to completely inhibit the function of C1q. What downstream effects would result from the use of this drug?
Which of the following characteristics would render a molecule LEAST likely to be recognized as foreign by the immune system?
Which of the following characteristics would render a molecule LEAST likely to be recognized as foreign by the immune system?
Which event is LEAST likely to occur as a direct result of class switch recombination (CSR)?
Which event is LEAST likely to occur as a direct result of class switch recombination (CSR)?
Which mechanism enables antibodies to prevent a pathogen from infecting cells?
Which mechanism enables antibodies to prevent a pathogen from infecting cells?
If the gene encoding for AID (Activation-Induced Cytidine Deaminase) were non-functional, which process would be MOST directly impaired?
If the gene encoding for AID (Activation-Induced Cytidine Deaminase) were non-functional, which process would be MOST directly impaired?
A patient with a respiratory infection is found to have high levels of IgD in their respiratory tract. This is MOST indicative which immunological process?
A patient with a respiratory infection is found to have high levels of IgD in their respiratory tract. This is MOST indicative which immunological process?
A novel therapeutic approach aims to enhance the recruitment of immune complexes (ICs) to erythrocytes via the CR1 receptor, but unexpectedly leads to severe systemic inflammation. Which mechanism BEST explains this paradoxical outcome?
A novel therapeutic approach aims to enhance the recruitment of immune complexes (ICs) to erythrocytes via the CR1 receptor, but unexpectedly leads to severe systemic inflammation. Which mechanism BEST explains this paradoxical outcome?
A researcher engineers a novel immunotherapeutic fusion protein consisting of a target antigen linked to a modified Fc region that selectively binds to FcγRIIB with picomolar affinity. Contrary to expectations, in vivo administration exacerbates inflammation. What is the MOST likely reason for this outcome?
A researcher engineers a novel immunotherapeutic fusion protein consisting of a target antigen linked to a modified Fc region that selectively binds to FcγRIIB with picomolar affinity. Contrary to expectations, in vivo administration exacerbates inflammation. What is the MOST likely reason for this outcome?
A patient presents with recurring parasitic worm infections despite producing high levels of IgE. Further investigation reveals a mutation in the gene encoding a key signaling molecule downstream of FcεRI in eosinophils. Which signaling defect would MOST likely explain this patient's susceptibility to parasitic infections?
A patient presents with recurring parasitic worm infections despite producing high levels of IgE. Further investigation reveals a mutation in the gene encoding a key signaling molecule downstream of FcεRI in eosinophils. Which signaling defect would MOST likely explain this patient's susceptibility to parasitic infections?
A research team is developing a novel vaccine strategy that aims to elicit broadly neutralizing antibodies against a highly variable virus. They discover that including a specific adjuvant leads to a dramatic increase in the avidity of the resulting IgG antibodies, but also results in reduced somatic hypermutation. What is the MOST probable explanation for this observation?
A research team is developing a novel vaccine strategy that aims to elicit broadly neutralizing antibodies against a highly variable virus. They discover that including a specific adjuvant leads to a dramatic increase in the avidity of the resulting IgG antibodies, but also results in reduced somatic hypermutation. What is the MOST probable explanation for this observation?
A biotechnology company is designing a bispecific antibody to treat cancer. One arm binds to a tumor-associated antigen, while the other arm is designed to enhance ADCC. Which modification to the Fc region would MOST effectively augment NK cell-mediated cytotoxicity while minimizing complement activation?
A biotechnology company is designing a bispecific antibody to treat cancer. One arm binds to a tumor-associated antigen, while the other arm is designed to enhance ADCC. Which modification to the Fc region would MOST effectively augment NK cell-mediated cytotoxicity while minimizing complement activation?
A researcher is investigating the role of IgA in preventing bacterial translocation across the intestinal epithelium. They discover a novel bacterial protease that specifically cleaves IgA2 within the hinge region. What is the MOST likely consequence of IgA2 cleavage in the context of intestinal immunity?
A researcher is investigating the role of IgA in preventing bacterial translocation across the intestinal epithelium. They discover a novel bacterial protease that specifically cleaves IgA2 within the hinge region. What is the MOST likely consequence of IgA2 cleavage in the context of intestinal immunity?
A neonate is diagnosed with a rare genetic defect that results in the complete absence of the neonatal Fc receptor (FcRn) in all tissues except the placenta, where its expression and function are normal. What is the MOST likely immunological consequence for this infant?
A neonate is diagnosed with a rare genetic defect that results in the complete absence of the neonatal Fc receptor (FcRn) in all tissues except the placenta, where its expression and function are normal. What is the MOST likely immunological consequence for this infant?
A research scientist is investigating a novel strategy to enhance mucosal immunity against respiratory pathogens. They engineer a modified IgA antibody that exhibits enhanced binding to surfactant protein D (SP-D). What is the MOST likely outcome of this modification in the context of lung immunity?
A research scientist is investigating a novel strategy to enhance mucosal immunity against respiratory pathogens. They engineer a modified IgA antibody that exhibits enhanced binding to surfactant protein D (SP-D). What is the MOST likely outcome of this modification in the context of lung immunity?
A patient with a history of recurrent bacterial infections is found to have normal levels of all antibody isotypes, but their IgM exhibits a significantly reduced capacity to activate the classical complement pathway. Further investigation reveals a mutation affecting the Cµ4 domain of IgM. Which functional consequence is MOST likely associated with this mutation?
A patient with a history of recurrent bacterial infections is found to have normal levels of all antibody isotypes, but their IgM exhibits a significantly reduced capacity to activate the classical complement pathway. Further investigation reveals a mutation affecting the Cµ4 domain of IgM. Which functional consequence is MOST likely associated with this mutation?
A researcher discovers a novel viral evasion mechanism involving a virally encoded protein that specifically binds to C4b, preventing its association with C2a. Which step in the classical complement pathway is MOST directly inhibited by this viral protein?
A researcher discovers a novel viral evasion mechanism involving a virally encoded protein that specifically binds to C4b, preventing its association with C2a. Which step in the classical complement pathway is MOST directly inhibited by this viral protein?
A clinician is treating a patient with a severe autoimmune disease characterized by the formation of pathogenic immune complexes. They decide to administer a high dose of intravenous immunoglobulin (IVIg) to modulate the immune response. Which Fc-mediated mechanism is MOST likely responsible for the therapeutic effect of IVIg in this context?
A clinician is treating a patient with a severe autoimmune disease characterized by the formation of pathogenic immune complexes. They decide to administer a high dose of intravenous immunoglobulin (IVIg) to modulate the immune response. Which Fc-mediated mechanism is MOST likely responsible for the therapeutic effect of IVIg in this context?
A researcher is studying the impact of glycosylation on the effector functions of IgG antibodies. They produce two versions of an IgG1 antibody, one with normal glycosylation and one with completely removed N-linked glycans from the Fc region. How would the removal of N-linked glycans from the Fc region of IgG1 MOST likely affect its effector functions?
A researcher is studying the impact of glycosylation on the effector functions of IgG antibodies. They produce two versions of an IgG1 antibody, one with normal glycosylation and one with completely removed N-linked glycans from the Fc region. How would the removal of N-linked glycans from the Fc region of IgG1 MOST likely affect its effector functions?
A pharmaceutical company is developing a novel therapeutic antibody that targets a cytokine involved in allergic inflammation. They aim to minimize the risk of off-target effects mediated by Fc receptor interactions. Which modification to the Fc region of the antibody would BEST achieve this goal?
A pharmaceutical company is developing a novel therapeutic antibody that targets a cytokine involved in allergic inflammation. They aim to minimize the risk of off-target effects mediated by Fc receptor interactions. Which modification to the Fc region of the antibody would BEST achieve this goal?
A researcher is investigating the mechanisms underlying the development of food allergies. They hypothesize that impaired IgA production in the gut leads to increased sensitization to food antigens. Which experimental approach would BEST test this hypothesis in a mouse model?
A researcher is investigating the mechanisms underlying the development of food allergies. They hypothesize that impaired IgA production in the gut leads to increased sensitization to food antigens. Which experimental approach would BEST test this hypothesis in a mouse model?
A patient with a history of severe asthma experiences a life-threatening exacerbation triggered by exposure to a specific allergen. Despite aggressive bronchodilator therapy, their airway inflammation persists. Which antibody-mediated mechanism is MOST likely contributing to the persistent airway inflammation in this patient?
A patient with a history of severe asthma experiences a life-threatening exacerbation triggered by exposure to a specific allergen. Despite aggressive bronchodilator therapy, their airway inflammation persists. Which antibody-mediated mechanism is MOST likely contributing to the persistent airway inflammation in this patient?
A researcher is investigating the influence of different cytokines on class switch recombination (CSR). They stimulate B cells with anti-CD40 and IL-4, but also add a novel compound that inhibits the activity of STAT6. What is the MOST likely consequence of STAT6 inhibition on CSR in these stimulated B cells?
A researcher is investigating the influence of different cytokines on class switch recombination (CSR). They stimulate B cells with anti-CD40 and IL-4, but also add a novel compound that inhibits the activity of STAT6. What is the MOST likely consequence of STAT6 inhibition on CSR in these stimulated B cells?
A researcher discovers that a particular antigen, while possessing high molecular weight and chemical complexity, fails to elicit a strong antibody response in vivo. Further analysis reveals that the antigen is rapidly degraded in the endosomes of antigen-presenting cells. Which strategy would MOST effectively enhance the immunogenicity of this antigen?
A researcher discovers that a particular antigen, while possessing high molecular weight and chemical complexity, fails to elicit a strong antibody response in vivo. Further analysis reveals that the antigen is rapidly degraded in the endosomes of antigen-presenting cells. Which strategy would MOST effectively enhance the immunogenicity of this antigen?
A biotech company is developing a novel therapeutic antibody to neutralize a soluble inflammatory mediator. To optimize its pharmacokinetic properties, they aim to engineer the antibody to maximize its interaction with FcRn. Which strategy would MOST effectively increase FcRn binding affinity while minimizing the risk of inducing unwanted effector functions?
A biotech company is developing a novel therapeutic antibody to neutralize a soluble inflammatory mediator. To optimize its pharmacokinetic properties, they aim to engineer the antibody to maximize its interaction with FcRn. Which strategy would MOST effectively increase FcRn binding affinity while minimizing the risk of inducing unwanted effector functions?
A patient is diagnosed with a rare genetic deficiency in activation-induced cytidine deaminase (AID) specifically affecting somatic hypermutation in B cells, but not class switch recombination. Which downstream effect would MOST likely be observed in this individual?
A patient is diagnosed with a rare genetic deficiency in activation-induced cytidine deaminase (AID) specifically affecting somatic hypermutation in B cells, but not class switch recombination. Which downstream effect would MOST likely be observed in this individual?
A research team discovers a novel bacterial pathogen that expresses a surface protein with high affinity for polymeric immunoglobulin receptor (pIgR). What is the MOST likely functional consequence of this interaction for the host's immune response?
A research team discovers a novel bacterial pathogen that expresses a surface protein with high affinity for polymeric immunoglobulin receptor (pIgR). What is the MOST likely functional consequence of this interaction for the host's immune response?
A researcher is investigating mechanisms of immune evasion employed by a newly discovered virus. They identify a viral protein that selectively inhibits the formation of the alternative C3 convertase (C3bBb). How would this viral protein MOST directly affect the host's immune response?
A researcher is investigating mechanisms of immune evasion employed by a newly discovered virus. They identify a viral protein that selectively inhibits the formation of the alternative C3 convertase (C3bBb). How would this viral protein MOST directly affect the host's immune response?
While investigating a new vaccine adjuvant, a researcher discovers it induces robust IgG responses, but the resulting antibodies exhibit unusually short half-lives in vivo. Further analysis reveals the adjuvant promotes aberrant glycosylation of the IgG Fc region. Which specific glycosylation change would MOST likely explain the reduced IgG half-life?
While investigating a new vaccine adjuvant, a researcher discovers it induces robust IgG responses, but the resulting antibodies exhibit unusually short half-lives in vivo. Further analysis reveals the adjuvant promotes aberrant glycosylation of the IgG Fc region. Which specific glycosylation change would MOST likely explain the reduced IgG half-life?
A patient is treated successfully for a venomous snake bite with antivenom containing neutralizing antibodies. However, several weeks later, the patient develops serum sickness, characterized by fever, joint pain, and glomerulonephritis. Which mechanism is MOST likely responsible for the development of serum sickness in this patient?
A patient is treated successfully for a venomous snake bite with antivenom containing neutralizing antibodies. However, several weeks later, the patient develops serum sickness, characterized by fever, joint pain, and glomerulonephritis. Which mechanism is MOST likely responsible for the development of serum sickness in this patient?
A researcher is investigating the role of Fc receptors in regulating macrophage activation. They discover that ligation of a specific Fc receptor on macrophages by IgG immune complexes triggers the production of IL-10, an immunosuppressive cytokine. Which class of Fc receptor is MOST likely mediating this effect?
A researcher is investigating the role of Fc receptors in regulating macrophage activation. They discover that ligation of a specific Fc receptor on macrophages by IgG immune complexes triggers the production of IL-10, an immunosuppressive cytokine. Which class of Fc receptor is MOST likely mediating this effect?
A researcher aims to develop a novel therapeutic strategy for treating autoimmune hemolytic anemia, an autoantibody-mediated disease where red blood cells (RBCs) are targeted for destruction. Which approach is MOST likely to be effective in reducing RBC destruction while minimizing systemic immunosuppression?
A researcher aims to develop a novel therapeutic strategy for treating autoimmune hemolytic anemia, an autoantibody-mediated disease where red blood cells (RBCs) are targeted for destruction. Which approach is MOST likely to be effective in reducing RBC destruction while minimizing systemic immunosuppression?
During an investigation of a novel immune deficiency, a researcher discovers that a patient's B cells are capable of initiating class switch recombination (CSR), but unable to complete the process efficiently. Genomic analysis reveals a mutation affecting the non-homologous end joining (NHEJ) pathway specifically within B cells. Which aspect of CSR is MOST likely impaired in this patient?
During an investigation of a novel immune deficiency, a researcher discovers that a patient's B cells are capable of initiating class switch recombination (CSR), but unable to complete the process efficiently. Genomic analysis reveals a mutation affecting the non-homologous end joining (NHEJ) pathway specifically within B cells. Which aspect of CSR is MOST likely impaired in this patient?
A researcher is developing a vaccine against a highly glycosylated virus. The vaccine elicits a strong IgG response, but the resulting antibodies exhibit poor neutralizing activity against the native virus. Which factor is MOST likely contributing to the reduced neutralizing potency of the antibodies?
A researcher is developing a vaccine against a highly glycosylated virus. The vaccine elicits a strong IgG response, but the resulting antibodies exhibit poor neutralizing activity against the native virus. Which factor is MOST likely contributing to the reduced neutralizing potency of the antibodies?
A study reveals that a particular adjuvant skews the isotype profile towards IgG2 in mice. This adjuvant causes enhanced signaling through which receptor on B cells?
A study reveals that a particular adjuvant skews the isotype profile towards IgG2 in mice. This adjuvant causes enhanced signaling through which receptor on B cells?
A newborn has significantly reduced levels of IgG but normal levels of IgM and IgA. Which condition would MOST likely explain this observation?
A newborn has significantly reduced levels of IgG but normal levels of IgM and IgA. Which condition would MOST likely explain this observation?
A novel drug is designed to enhance the presentation of antigens on MHC class II molecules by B cells. The drug MOST likely targets what aspect of B cell function?
A novel drug is designed to enhance the presentation of antigens on MHC class II molecules by B cells. The drug MOST likely targets what aspect of B cell function?
A research team discovers a novel immunodeficiency characterized by impaired somatic hypermutation and class switch recombination, but with normal germinal center formation. Comprehensive analysis reveals a specific defect in the glycosylation pathway within B cells, leading to the production of aberrant N-glycans on the activation-induced cytidine deaminase (AID) enzyme. Which consequence is MOST likely resulting from the altered glycosylation of AID?
A research team discovers a novel immunodeficiency characterized by impaired somatic hypermutation and class switch recombination, but with normal germinal center formation. Comprehensive analysis reveals a specific defect in the glycosylation pathway within B cells, leading to the production of aberrant N-glycans on the activation-induced cytidine deaminase (AID) enzyme. Which consequence is MOST likely resulting from the altered glycosylation of AID?
A hypothetical biopharmaceutical company is engineering a novel, multi-specific antibody construct. One arm binds to a tumor-specific antigen, while a second arm is designed to directly activate the alternative pathway of complement. To optimize the therapeutic efficacy while minimizing systemic inflammatory side effects, which of these design considerations is MOST critical?
A hypothetical biopharmaceutical company is engineering a novel, multi-specific antibody construct. One arm binds to a tumor-specific antigen, while a second arm is designed to directly activate the alternative pathway of complement. To optimize the therapeutic efficacy while minimizing systemic inflammatory side effects, which of these design considerations is MOST critical?
A research team aims to develop a novel vaccine against a highly variable viral pathogen. They engineer a virus-like particle (VLP) displaying conserved viral epitopes and administer it with different adjuvants. Unexpectedly, they observe that an adjuvant known to potently activate dendritic cells leads to significantly lower avidity of the resulting IgG antibodies compared to an adjuvant that induces weaker DC activation. Which mechanism is the MOST probable explanation for this observation?
A research team aims to develop a novel vaccine against a highly variable viral pathogen. They engineer a virus-like particle (VLP) displaying conserved viral epitopes and administer it with different adjuvants. Unexpectedly, they observe that an adjuvant known to potently activate dendritic cells leads to significantly lower avidity of the resulting IgG antibodies compared to an adjuvant that induces weaker DC activation. Which mechanism is the MOST probable explanation for this observation?
A research group is investigating the role of different IgA subclasses in maintaining intestinal homeostasis. They discover a novel commensal bacterial species that secretes a highly specific protease that cleaves IgA1, but not IgA2, within the hinge region. What is the MOST likely long-term consequence of this proteolytic activity on the host's intestinal immunity?
A research group is investigating the role of different IgA subclasses in maintaining intestinal homeostasis. They discover a novel commensal bacterial species that secretes a highly specific protease that cleaves IgA1, but not IgA2, within the hinge region. What is the MOST likely long-term consequence of this proteolytic activity on the host's intestinal immunity?
A researcher is studying the impact of passive immunization on the development of autoimmune disease in a mouse model. They transfer IgG antibodies specific for a self-antigen known to drive disease pathogenesis. Surprisingly, they observe a transient amelioration of disease followed by a significant disease exacerbation. Which Fc-mediated mechanism is MOST likely responsible for the observed disease exacerbation?
A researcher is studying the impact of passive immunization on the development of autoimmune disease in a mouse model. They transfer IgG antibodies specific for a self-antigen known to drive disease pathogenesis. Surprisingly, they observe a transient amelioration of disease followed by a significant disease exacerbation. Which Fc-mediated mechanism is MOST likely responsible for the observed disease exacerbation?
Flashcards
Immunogens
Immunogens
Substances that elicit an immune response, typically foreign, high in weight, chemically complex, and degradable.
Class Switch Recombination (CSR)
Class Switch Recombination (CSR)
Permits B cells to switch antibody isotype, enabling specific effector functions against pathogens.
Major Antibody Effector Mechanisms
Major Antibody Effector Mechanisms
Neutralization, opsonization, and antibody-dependent cell cytotoxicity (ADCC).
IgM
IgM
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IgD
IgD
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Chemical Nature of Antigens
Chemical Nature of Antigens
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Hapten
Hapten
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Four Requirements for Immunogenicity
Four Requirements for Immunogenicity
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Circulating Antibodies (Abs)
Circulating Antibodies (Abs)
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Class switch recombination
Class switch recombination
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IgM
IgM
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AID
AID
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Neutralization (of microbes)
Neutralization (of microbes)
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molecules that bind Ags on microbe surface
molecules that bind Ags on microbe surface
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Opsonization
Opsonization
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Antibody-Dependent Cell Cytotoxicity (ADCC)
Antibody-Dependent Cell Cytotoxicity (ADCC)
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FcyRIII
FcyRIII
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ADCC
ADCC
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Dark Pink
Dark Pink
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IgG Antibodies
IgG Antibodies
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IgG1
IgG1
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Activation of complement
Activation of complement
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IgG antigen-binding sites
IgG antigen-binding sites
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Red blood cells
Red blood cells
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Babies
Babies
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Breast Milk
Breast Milk
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FcRn
FcRn
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J Chain
J Chain
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Mucosal translocation of IgA
Mucosal translocation of IgA
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IgM
IgM
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IgE function
IgE function
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IgD
IgD
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Exogenous Antigens
Exogenous Antigens
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Endogenous Antigens
Endogenous Antigens
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too high a does is as bed as too low
too high a does is as bed as too low
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IgA
IgA
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Vast Majority of Immunogens
Vast Majority of Immunogens
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Polysaccharides
Polysaccharides
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Nucleic Acids
Nucleic Acids
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Lipids
Lipids
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Dosage of an Antigen
Dosage of an Antigen
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TFH cells signal B cells.
TFH cells signal B cells.
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Antibody effector function
Antibody effector function
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Antibody mediated Opsonization
Antibody mediated Opsonization
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First step of IgG-mediated complement activation
First step of IgG-mediated complement activation
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IgG4 Characteristics
IgG4 Characteristics
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Neutralization
Neutralization
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Study Notes
- Immunogens are antigens that trigger an immune response
- The most effective antigens are foreign, high in weight, chemically complex, and degradable
Categories of Antigens
- Antigens entering the body from the environment: inhaled macromolecules (e.g., cat hair proteins causing asthma), ingested macromolecules (e.g., shellfish proteins causing allergy), and molecules introduced beneath the skin (e.g., splinter, vaccine).
- Antigens are generated within the host's cells
- Autoantigens - Self-antigens
- Alloantigens - Tissue-specific antigens present in some individuals. Ex: ABO, HLA
- Intracellular pathogens include viruses, intracellular bacteria, and parasites
- Endogenous antigens are included in this group
Chemical Nature of Antigens
- Proteins are the most common immunogens and are generally very good for this purpose
- Polysaccharides, specifically pure and lipopolysaccharides, make good immunogens
- Nucleic acids are typically poor immunogens, but may become immunogenic when single-stranded or complexed with proteins
- Lipids are generally non-immunogenic, but may act as haptens
Haptens
- Haptens are low molecular-weight compounds
- Haptens induce an immune response only when bound to a carrier molecule, usually a protein
- The carrier protein has a unique antigenic structure different from the hapten
- The immune response targets both the hapten and the carrier protein
Immunogenicity Requirements
- Immune cells that don't recognize self survive development and training, leading to foreignness
- The molecular weight of 100 kDa or more is best, molecules under 10 kDa are typically poorly immunogenic in this respect
- Proteins are the best immunogens because they are so complex
- Antigen presentation is necessary and critical
Immunogenicity Affecting Factors
- Failure to activate enough lymphocytes can come from poor dosage of antigen
- Repeated doses (boosters) of antigen are important
- MHC molecules and the antigen binding or not plays a role
- Parental administration is favored for Route of administration ("around the gut")
- Subcutaneous, intradermal, intravenous, intramuscular, intraperitoneal, and oral GI are also routes
Role of Antibodies (Abs)
- Antibodies promote the activation of effector mechanisms and removal of the immune complex
- Soluble glycoproteins recognize and bind antigens
- Function as membrane-bound surface Ag receptors on B lymphocytes that plays a role in differentiation
- B cells can alter their antibody isotype via class switch recombination (CSR) to incorporate specific effector functions against pathogens
Surface Ig and Secreted Ig
- Five antibody isotypes exist, produced by B cells, each designated by a different H chain (μ, δ, γ, ε, α)
- IgM and IgD, are expressed on the surface of B cells due to BCR gene rearrangements.
- After encountering an antigen, new IgM and IgD is produced within the differentiated B cell and secreted as antibodies
- The newly produced IgM and IgD lack transmembrane domains, restricting them to the cell membrane
- IgM provides protection against various infections, and is produced in large amounts
- IgD is most effective in the respiratory tract and produces in small amounts
Isotype Switching
- IgM is secreted early against pathogens
- Monomeric sIgM or BCR
- Secreted IgM exhibits 10 binding sites
- There are limits with IgM’s bulk, low affinity and the reduced capacity to recruit host effector mechanisms
- In order to access the additional effector mechanisms IgM must be changed to another form while retaining it's Ag-specificity
- Class switch recombination (CSR) or isotype switching, DNA recombination of the rearranged V region with another H chain gene occurs to facilitate this.
- Cytokines drive class switching. IFN-γ, IL-4 > TGF-β
- Class switch recombination tailors the Ig response to specific groups of infectious agents
CSR in B Cells
- CSR occurs after engagement with TFH cells in GC B cells and centrocytes, cytokines, and AID are produced
- Likely follows affinity maturation
- DC produces IL-12 to program TFH cells to secrete IFN-γ and lead isotype switching through engagement of GC B cells
AID converts cytosines into uracils
- AID targets cytosines in the Sµ and Sy1 switch regions for deamination to uracil in this example.
- Uracil lacking a base is removed by uracil-DNA-glycosylase
- A nick results in the DNA strand after APE1 (endonuclease) excises the abasic nucleotide
- Circular DNA contains Cµ, Cs, and Cγ3
- DNA repair now aligns the V region (not altered) with the C region
- All classes of Ig are made in two forms: Surface Ig or BCR, Secreted antibody
Immunoglobulin Isotype Functions
- Isotype effector mechanisms include neutralization, opsonization, and antibody-dependent cell cytotoxicity (ADCC)
- Unique effector functions are exhibited by IgG1-3 (IFN-γ), IgA (TGF-β), IgE, IgG4 (IL-4), and IgM (IL-2, IL-4, IL-5)
- Fc receptors mediate most antibody effector activities, their function, and the cells involved in the processes must also be in balance.
Neutralization
- The first step in successful microbial infection attaches to host tissues and colonizes
- Microbe-produced antibodies commonly target ligands used to bind host cell receptors.
- Antibodies prevent microbe attachment = neutralization
- Example-influenzas
- Virus binds to surface glycoproteins of respiratory epithelia, using hemagglutinin or H
- Vaccine generated IgG is in the mucus of the tract, and binds to prevent the virus or bacteria from attaching
Toxins Neutralizing
- Toxins are the main mechanism for pathogenesis, vaccines can generate antibodies to bind the toxins that produce disease
- Vaccinated antibodies don't stop colonization from attaching
Opsonization
- IgA and specific IgG molecules bind Ags on the microbe surface
- Fc receptors on phagocytic cells bind the Fc regions of the antibodies
- Fc receptor ligation promotes phagocytic uptake and digestion
- Enhanced phagocytosis of the microbe via the coating of antibody = opsonization
Complement Activation
- IgG1-3 (+IgM) can activate the classical pathway of complement.
- IgG and IgM activate the classical pathway.
- IgM is the first antibody produced and complement activation is the primary effector mechanism
- C1q binding activates C1r which causes cleavage and activation of C1s.
Antibody-Dependent Cell Cytotoxicity (ADCC)
- NK cells express Fc gamma receptor III (FcyRIII)
- FcyRIII of NK cells can bind to Fc regions of antibodies (IgG1 or IgG3) attached to an Ag on target cells
- Antibody directed cell killing is known as antibody-dependent cell cytotoxicity
IgE and parasitic worms
- The IL-4-helminths production of IgE is what causes the immune response against helminths
- Eosinophils attach to the Fc region of IgE
- Degranulation of the eosinophils are carried out after a number of Fc&RI attachments along worm
- IgE is driven against parasitic worms and eosinophils attack
Soluble Antigen Removal
- IgG antigen-binding sites have higher affinity than IgM → stable immune complexes (IC)
- IC form when antibody binds soluble Ag
- Activation of the classical pathway → C3b deposition on the Ag → phagocytes take up and remove these IC from the body
- IC can develop during the course of an immune response, if this occurs they develop and must be removed to prevent build-up in small blood vessels and kidney glomeruli
Fetal and Neonatal Immunity
- IgG passes the placenta efficiently, newborns typically have adult-level IgG
- Before birth, the baby begins IgM production but between birth to 12 months the antibody levels are deficient: high infection risk
- Antibodies can be provided through breast milk to protect mucosal surfaces from infection
- Breast milk has 90% IgA (IgG and IgM comprise the remaining 10%)
IgG1/IgG3-4 Fetal Immunity
- With the Fc receptor neonatal (FcRn) in the blood, IgG stabilizes interaction
- There must be an acidic pH is what promotes association of neonatal FC’s
Mucosal Immunity
- The surfaces of the mucosal epithelia are protected by IgA
- IgA is secreted to get IgA to the apical region, in the MALT from IgA-secreting PC on the basolateral.
- Receptors on epithelia bind J chain
- Secretory Piece is important
- IgA then associates with mucins via mucins
Fc receptor expression
- Constitutive expression of an Fc receptor by a cell is denoted by dark pink and "+"; inducible expression is denoted by lighter pink and (+)
IgG
- IgG is the most common serum Ig
- IgG1 and IgG3 cross the placenta.
- IgG is opsonization (IgG1, IgG3 best)
IgA
- IgA1 and IgA2 are secreted into mucus
- IgA exists in dimer form and are important in mucosal immunity. IgA is effective at neutralization.
IgE
- IgE mediates immunity to parasites
- IgE drives allergic reactions and response
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IgM is effective at complement activation and agglutination.
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Basophils eliminates bacteria via binding mlgD on the B cell surface
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