Podcast
Questions and Answers
Which of the following protein motifs, present on Iga and IgB, is essential for the interaction with intracellular signaling proteins during BCR activation?
Which of the following protein motifs, present on Iga and IgB, is essential for the interaction with intracellular signaling proteins during BCR activation?
- Immunoreceptor Tyrosine-based Activation Motif (ITAM) (correct)
- Leucine Zipper Motif
- Immunoglobulin Domain (IgD)
- Nuclear Localization Signal (NLS)
What is the immediate consequence of antigen receptor clustering in B cells, which leads to the activation of intracellular signaling pathways?
What is the immediate consequence of antigen receptor clustering in B cells, which leads to the activation of intracellular signaling pathways?
- Recruitment of proteases to cleave the BCR.
- Direct activation of gene expression in the nucleus.
- Phosphorylation of ITAMs by receptor-associated kinases. (correct)
- Internalization of the antigen-BCR complex for degradation.
How do thymus-independent (TI) antigens, specifically TI-1 antigens, activate B cells in the absence of T cell help?
How do thymus-independent (TI) antigens, specifically TI-1 antigens, activate B cells in the absence of T cell help?
- By signaling through receptors of the innate immunity system. (correct)
- Through very strong signaling via the B cell receptor alone.
- By directly inducing MHC class II expression on B cells.
- By bypassing the need for B cell receptor engagement.
Which of the following events is essential for the successful activation of B cells by thymus-dependent antigens?
Which of the following events is essential for the successful activation of B cells by thymus-dependent antigens?
A researcher is studying B cell activation and observes that B cells can bind antigen and internalize it, but fail to effectively activate. Which of the following is most likely to be deficient?
A researcher is studying B cell activation and observes that B cells can bind antigen and internalize it, but fail to effectively activate. Which of the following is most likely to be deficient?
During Tfh cell interaction with a B cell, what is the primary role of CD40 ligand secreted by the Tfh cell?
During Tfh cell interaction with a B cell, what is the primary role of CD40 ligand secreted by the Tfh cell?
Why is talin required for stable cell adhesion between Tfh and B cells?
Why is talin required for stable cell adhesion between Tfh and B cells?
Following the formation of a stable B-T cell cognate pair, where do these cells migrate, and what is the significance of this location?
Following the formation of a stable B-T cell cognate pair, where do these cells migrate, and what is the significance of this location?
During B cell activation in the germinal center, Tfh cells interact with B cells via CD40L and CD40. What is the PRIMARY downstream effect of this interaction?
During B cell activation in the germinal center, Tfh cells interact with B cells via CD40L and CD40. What is the PRIMARY downstream effect of this interaction?
Follicular dendritic cells (FDCs) play a critical role in B cell maturation within germinal centers. What PRIMARY mechanism do FDCs use to trap and present antigens to B cells?
Follicular dendritic cells (FDCs) play a critical role in B cell maturation within germinal centers. What PRIMARY mechanism do FDCs use to trap and present antigens to B cells?
Centrocytes in the germinal center can differentiate into either memory B cells or plasma cells. What is the KEY cytokine driving differentiation into memory B cells?
Centrocytes in the germinal center can differentiate into either memory B cells or plasma cells. What is the KEY cytokine driving differentiation into memory B cells?
Isotype switching in B cells is influenced by various cytokines. Which cytokine is PRIMARILY responsible for inducing a switch to IgE and IgG1 antibody production?
Isotype switching in B cells is influenced by various cytokines. Which cytokine is PRIMARILY responsible for inducing a switch to IgE and IgG1 antibody production?
FcRn is an important receptor involved in antibody transport. What is the PRIMARY function of FcRn?
FcRn is an important receptor involved in antibody transport. What is the PRIMARY function of FcRn?
Dimeric IgA is transported across epithelial cells via transcytosis, providing crucial immune protection at mucosal surfaces. Which receptor mediates this transcytosis?
Dimeric IgA is transported across epithelial cells via transcytosis, providing crucial immune protection at mucosal surfaces. Which receptor mediates this transcytosis?
Passive immunity is transferred from mother to child through antibodies. Which antibody isotype is PRIMARILY transferred to the developing fetus via the placenta?
Passive immunity is transferred from mother to child through antibodies. Which antibody isotype is PRIMARILY transferred to the developing fetus via the placenta?
Breast milk provides passive immunity to newborns. Which antibody isotype is PRIMARILY transferred through breast milk?
Breast milk provides passive immunity to newborns. Which antibody isotype is PRIMARILY transferred through breast milk?
Neutralizing antibodies are crucial for preventing viral infections. What is the PRIMARY mechanism by which neutralizing antibodies protect against viral infection?
Neutralizing antibodies are crucial for preventing viral infections. What is the PRIMARY mechanism by which neutralizing antibodies protect against viral infection?
The B cell receptor (BCR) signaling pathway activates several downstream molecules. What is the IMMEDIATE function of PLC-γ in BCR signal transduction?
The B cell receptor (BCR) signaling pathway activates several downstream molecules. What is the IMMEDIATE function of PLC-γ in BCR signal transduction?
Flashcards
BCR-associated proteins for signaling
BCR-associated proteins for signaling
Iga and IgB proteins, which have long cytoplasmic tails containing ITAMs, associate with the BCR and are required for signal transduction.
Role of ITAMs in BCR signaling
Role of ITAMs in BCR signaling
ITAMs (Immunoreceptor Tyrosine-based Activation Motifs) get phosphorylated by kinases upon antigen receptor clustering, leading to Syk binding and activation, ultimately changing gene expression.
Thymus Independent (TI) Antigens
Thymus Independent (TI) Antigens
These antigens don't need T cells to activate B cells, activating signals come from receptors of the innate immunity system. An example is LPS of gram-negative bacteria
Thymus Dependent Antigens
Thymus Dependent Antigens
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Steps of Thymus Dependent Activation
Steps of Thymus Dependent Activation
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Tfh cell role in B cell activation
Tfh cell role in B cell activation
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CD40 ligand and IL-4 in B cell activation
CD40 ligand and IL-4 in B cell activation
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Role of Talin
Role of Talin
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Medullary Cord B Cell Differentiation
Medullary Cord B Cell Differentiation
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Germinal Center Formation
Germinal Center Formation
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Activation-Induced Cytidine Deaminase (AID)
Activation-Induced Cytidine Deaminase (AID)
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Follicular Dendritic Cell Function
Follicular Dendritic Cell Function
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Memory B Cell Differentiation
Memory B Cell Differentiation
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Plasma Cell Differentiation
Plasma Cell Differentiation
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IL-4 and Isotype Switching
IL-4 and Isotype Switching
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FcRn Function
FcRn Function
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IgA Transcytosis
IgA Transcytosis
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Antibody Transfer
Antibody Transfer
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Study Notes
BCR and Signal Transduction
- B cell receptors (BCRs) associate with Igα and Igβ proteins, crucial for signal transduction.
- Igα and Igβ have Immunoreceptor Tyrosine-based Activation Motifs (ITAMs) in their long cytoplasmic tails.
- ITAMs interact with intracellular signaling proteins.
- Clustering of antigen receptors enables receptor-associated kinases to phosphorylate ITAMs.
- Syk binds to doubly phosphorylated ITAMs and is activated upon binding.
- These changes ultimately affect gene expression in the nucleus.
ITAMs In BCR Signal Transduction
- ITAMs are phosphorylated by receptor-associated kinases after antigen receptor clustering.
- Phosphorylated ITAMs serve as binding sites for signaling molecules like Syk.
- Syk activation leads to downstream signaling cascades affecting gene expression.
B Cell Activating Antigens
- Two types of B cell-activating antigens exist: thymus-independent and thymus-dependent.
- Thymus-independent antigens (TI-1 and TI-2) activate B cells without T cell help, while thymus-dependent antigens require it.
- TI-1 antigens activate B cells via innate immunity receptors; LPS of gram-negative bacteria is a classical example.
- Successful B-cell activation requires a strong signal or two distinct signals.
Thymus-Dependent Antigen Activation of B Cells
- BCR binds to its cognate antigen which is then internalized through endocytosis.
- The antigen is processed into smaller pieces.
- These peptide fragments are presented on the B cell surface via MHC II molecules.
CD40, IL-4, and Talin in B Cell Activation
- Tfh cells interact with B cells, delivering IL-4 and other cytokines through cell-cell contact.
- Strong cell-cell adhesion between Tfh (LFA-1) and B cells (ICAM) is essential.
- Tfh cells secrete CD40 ligand, which binds to CD40 on B cells, providing a crucial activation signal.
- Talin is required for stable cell adhesion between the Tfh and B cell.
- The Tfh cell reorients and directs its secretory apparatus towards the B cell, secreting cytokines into the space between the cells.
B-T Cell Cognate Pairs migrating to Medullary Cords
- The primary focus for expansion of antigen-activated B cells is in the medullary cords.
- B-T cell cognate pairs migrate here, proliferate, and some differentiate into plasma cells.
- Plasma cells in the medullary cords mainly produce IgM antibodies upon IL-5 and IL-6 exposure.
B-T Cell Cognate Pairs Migrating to Primary Follicles
- Some B-T cognate pairs move from medullary cords to primary follicles, forming germinal centers.
- Follicular dendritic cells secrete IL-6, IL-5, 8D6, and BAFF, stimulating rapid B cell division into centroblasts.
- Tfh cells divide, produce cytokines, and interact with B cells via CD40L, inducing AID production.
- In the medullary area, B cells produce mostly IgM antibodies.
- In the germinal center, somatic hypermutation and class switching occur, leading to diverse antibody isotypes.
Somatic Hypermutation
- Involves rapid mutations in the immunoglobulin genes of B cells within the germinal center.
- It is an activation-induced cytidine deaminase (AID) enzyme that removes the amine group from the cytidine base in DNA.
- This process refines the affinity of the antibody for its antigen.
Function of AID
- AID is essential for somatic hypermutation and isotype switching.
- It deaminates cytidine to uridine in DNA, leading to mutations in the variable regions of immunoglobulin genes and enabling class switching.
Follicular Dendritic Cell Functions
- Follicular dendritic cells (FDCs) use complement receptors to bind and preserve intact antigens and pathogens for extended periods.
- FDCs present these antigens to B cells, facilitating B cell activation and selection.
- Complement activation leads to C3b fragments being cleaved into C3d fragments.
- CR1 and CR2 receptors on FDCs bind these fragments, retaining virus particles on the cell surface.
Centrocytes Differentiating into Memory or Plasma Cells
- Memory cells: Antigen-selected centrocytes, influenced by IL-4 secreting helper T cells, differentiate into memory B cells that provide long-term immunity.
- Plasma cells: Antigen-selected centrocytes, influenced by IL-10 secreting helper T cells, differentiate into plasma cells to combat the current infection.
Isotype Switching
- Cytokines determine the specific antibody isotype a B cell will switch to.
- For example, IL-4 induces switching to IgG1 and IgE isotypes.
FcRn Function
- FcRn transports IgG from the bloodstream into extracellular spaces, enhancing humoral immunity.
Transcytosis
- Transcytosis of dimeric IgA across epithelia is mediated by the poly-Ig receptor.
- IgA binds to the receptor on the basolateral surface of epithelial cells, followed by receptor-mediated endocytosis.
- IgA is transported to the apical face of the cell.
- The receptor is cleaved, and IgA is bound to mucus through the secretory piece, providing immune protection on mucosal surfaces.
Antibody Transfer
- Breast milk also provides dimeric IgA to the nursing infant.
- IgG antibodies are transferred from the mother to the fetus during development.
Benefits of Breastfeeding
- It is important to breast feed the baby for its optimal health so they acquire IgA from the mother promoting optimal health.
Neutralizing Antibodies
- Neutralizing antibodies prevent pathogens from infecting cells.
- For example, anti-influenza virus IgA antibodies can neutralize the virus, preventing infection.
Antibody Suppression of Infections
- Antibodies suppress infections through:
- Opsonization: enhancing phagocytosis,
- Complement activation: leading to pathogen lysis,
- Neutralization: preventing pathogen entry into cells.
IgM Initiates Complement Activation
- IgM initiates the classical pathway of complement by binding to antigens on the surfaces of pathogens.
Importance of Second Infections or Infections After a Vaccine
- A second infection or infection after a vaccine leads to a quicker, more robust response due to immunological memory.
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Description
B cell receptors (BCRs) associate with Igα and Igβ proteins, which are crucial for signal transduction. ITAMs are phosphorylated by receptor-associated kinases after antigen receptor clustering. These changes affect gene expression in the nucleus.
