Podcast
Questions and Answers
A researcher is investigating the effects of aging on immune function in a population of mice. They observe a significant reduction in the size and cellularity of the thymus in older mice. Based on this observation, which of the following immunological consequences is most likely to arise due to thymic involution, considering its impact on T cell development and repertoire diversity?
A researcher is investigating the effects of aging on immune function in a population of mice. They observe a significant reduction in the size and cellularity of the thymus in older mice. Based on this observation, which of the following immunological consequences is most likely to arise due to thymic involution, considering its impact on T cell development and repertoire diversity?
- Selective impairment in the development of T cell receptor (TCR) repertoires capable of recognizing novel viral pathogens, with preserved responses against previously encountered antigens.
- Augmented positive selection efficiency, leading to an expanded repertoire of high-affinity MHC-restricted T cells and enhanced responses to a broad range of antigens.
- Compromised negative selection of autoreactive T cells, resulting in an increased risk of autoimmune disorders due to the escape of self-reactive T cells into the periphery. (correct)
- Enhanced production of regulatory T cells (Tregs) specific for neo-self antigens, leading to increased immune tolerance and reduced autoimmunity.
Consider a scenario where a novel therapeutic intervention aims to enhance T cell reconstitution in patients with DiGeorge's Syndrome. Which of the following strategies would likely yield the most effective restoration of T cell function, specifically addressing the underlying developmental defect in the thymus?
Consider a scenario where a novel therapeutic intervention aims to enhance T cell reconstitution in patients with DiGeorge's Syndrome. Which of the following strategies would likely yield the most effective restoration of T cell function, specifically addressing the underlying developmental defect in the thymus?
- Systemic administration of high-dose IL-2 to promote peripheral expansion of existing T cells, bypassing the requirement for thymic education and diversification.
- Administration of a broad-spectrum immunosuppressant to eliminate residual autoreactive T cells, creating immunological space for homeostatic proliferation of newly generated T cells.
- Targeted ablation of thymic nurse cells (TNCs) to enhance thymocyte egress and increase the flux of mature T cells into the periphery.
- Ex vivo transduction of patient-derived hematopoietic stem cells (HSCs) with a constitutively active NOTCH1 receptor, followed by autologous transplantation to restore thymic epithelial cell (TEC) function. (correct)
A research team is investigating the mechanisms underlying the preferential localization of plasma cells and memory T cells within the bone marrow. Which of the following molecular interactions is most critical for the establishment and maintenance of these cells within the bone marrow niche, considering the bone marrow's unique microenvironment and cellular composition?
A research team is investigating the mechanisms underlying the preferential localization of plasma cells and memory T cells within the bone marrow. Which of the following molecular interactions is most critical for the establishment and maintenance of these cells within the bone marrow niche, considering the bone marrow's unique microenvironment and cellular composition?
- Secretion of granzyme B by memory T cells, facilitating the remodeling of the extracellular matrix and promoting their migration through the bone marrow parenchyma.
- Expression of high-affinity IL-7 receptors (IL-7Rα) on plasma cells, enabling their survival and proliferation in response to IL-7 produced by thymic epithelial cells.
- Upregulation of E-selectin ligands on memory T cells, facilitating rolling and adhesion to activated endothelial cells within the bone marrow vasculature during inflammatory conditions.
- Interaction between CXCR4 on plasma cells and CXCL12 (SDF-1) expressed by bone marrow stromal cells, promoting chemotaxis and retention within the bone marrow microenvironment. (correct)
In a study examining the developmental origins of innate lymphoid cells (ILCs), researchers discover a novel subset of ILCs that expresses both T cell receptor (TCR) and natural killer (NK) cell markers. Based on current understanding of lymphocyte development, which of the following developmental pathways would be most consistent with the emergence of this hybrid ILC population?
In a study examining the developmental origins of innate lymphoid cells (ILCs), researchers discover a novel subset of ILCs that expresses both T cell receptor (TCR) and natural killer (NK) cell markers. Based on current understanding of lymphocyte development, which of the following developmental pathways would be most consistent with the emergence of this hybrid ILC population?
A team of immunologists is exploring the evolutionary conservation of immune organs across diverse vertebrate species. They identify a novel lymphoid structure in a primitive fish species that lacks a well-defined thymus. Which of the following experimental approaches would provide the strongest evidence that this novel structure serves an analogous function to the mammalian thymus, facilitating T cell development and repertoire diversification?
A team of immunologists is exploring the evolutionary conservation of immune organs across diverse vertebrate species. They identify a novel lymphoid structure in a primitive fish species that lacks a well-defined thymus. Which of the following experimental approaches would provide the strongest evidence that this novel structure serves an analogous function to the mammalian thymus, facilitating T cell development and repertoire diversification?
Consider a scenario where a novel immunosuppressant drug selectively inhibits the maturation of T-helper cells within the thymus, but paradoxically enhances the differentiation of B cells into plasma cells in the bone marrow. Which of the following immunological consequences is MOST likely to arise from this drug's action, considering potential disruptions in immune homeostasis and cellular interactions?
Consider a scenario where a novel immunosuppressant drug selectively inhibits the maturation of T-helper cells within the thymus, but paradoxically enhances the differentiation of B cells into plasma cells in the bone marrow. Which of the following immunological consequences is MOST likely to arise from this drug's action, considering potential disruptions in immune homeostasis and cellular interactions?
A researcher is investigating the metabolic requirements of lymphocytes during an immune response. They discover that T cells undergoing clonal expansion exhibit a significantly higher rate of glutamine uptake compared to resting T cells, even when glucose availability is abundant. Which of the following explanations BEST accounts for this observation, considering the multifaceted role of glutamine in lymphocyte metabolism and function?
A researcher is investigating the metabolic requirements of lymphocytes during an immune response. They discover that T cells undergoing clonal expansion exhibit a significantly higher rate of glutamine uptake compared to resting T cells, even when glucose availability is abundant. Which of the following explanations BEST accounts for this observation, considering the multifaceted role of glutamine in lymphocyte metabolism and function?
In a study examining the kinetic differences between primary and secondary immune responses, researchers observed that memory B cells, upon re-exposure to their cognate antigen, undergo a more rapid and robust activation compared to naive B cells. Which of the following mechanisms BEST explains the enhanced responsiveness of memory B cells, considering the multifaceted cellular and molecular changes that characterize immunological memory?
In a study examining the kinetic differences between primary and secondary immune responses, researchers observed that memory B cells, upon re-exposure to their cognate antigen, undergo a more rapid and robust activation compared to naive B cells. Which of the following mechanisms BEST explains the enhanced responsiveness of memory B cells, considering the multifaceted cellular and molecular changes that characterize immunological memory?
Consider a scenario where a patient with a genetic defect exhibits a complete absence of germinal centers in their lymph nodes. This defect directly impairs the development and function of which specific immune cell population, leading to a cascade of downstream consequences in the humoral immune response?
Consider a scenario where a patient with a genetic defect exhibits a complete absence of germinal centers in their lymph nodes. This defect directly impairs the development and function of which specific immune cell population, leading to a cascade of downstream consequences in the humoral immune response?
A novel therapeutic strategy aims to enhance T cell activation by engineering artificial antigen-presenting cells (aAPCs) that express both MHC-peptide complexes and costimulatory molecules. However, researchers observe that prolonged stimulation with these aAPCs paradoxically induces T cell exhaustion. Which of the following mechanisms BEST explains this phenomenon, considering the complex interplay of signaling pathways and regulatory mechanisms involved in T cell activation and exhaustion?
A novel therapeutic strategy aims to enhance T cell activation by engineering artificial antigen-presenting cells (aAPCs) that express both MHC-peptide complexes and costimulatory molecules. However, researchers observe that prolonged stimulation with these aAPCs paradoxically induces T cell exhaustion. Which of the following mechanisms BEST explains this phenomenon, considering the complex interplay of signaling pathways and regulatory mechanisms involved in T cell activation and exhaustion?
A researcher investigating novel cancer immunotherapies discovers a molecule that selectively disrupts the interaction between CD4 and MHC class II molecules, while paradoxically enhancing the avidity of the TCR for its cognate peptide-MHC complex. Assuming this molecule does not affect co-stimulatory signals, what is the MOST likely outcome of treating naïve T cells with this molecule in vitro?
A researcher investigating novel cancer immunotherapies discovers a molecule that selectively disrupts the interaction between CD4 and MHC class II molecules, while paradoxically enhancing the avidity of the TCR for its cognate peptide-MHC complex. Assuming this molecule does not affect co-stimulatory signals, what is the MOST likely outcome of treating naïve T cells with this molecule in vitro?
A graduate student is studying T cell activation and mutates the ITAM motifs within the cytoplasmic tails of the CD3 subunits of the TCR complex. This mutation prevents phosphorylation of the ITAMs. What downstream effect would MOST DIRECTLY result from this mutation during T cell activation?
A graduate student is studying T cell activation and mutates the ITAM motifs within the cytoplasmic tails of the CD3 subunits of the TCR complex. This mutation prevents phosphorylation of the ITAMs. What downstream effect would MOST DIRECTLY result from this mutation during T cell activation?
In a clinical trial evaluating a novel vaccine adjuvant, researchers observe a significant increase in the CD4:CD8 ratio in the peripheral blood of vaccinated subjects compared to the control group. This change is MOST likely indicative of:
In a clinical trial evaluating a novel vaccine adjuvant, researchers observe a significant increase in the CD4:CD8 ratio in the peripheral blood of vaccinated subjects compared to the control group. This change is MOST likely indicative of:
Given the crucial role of Gut-Associated Lymphoid Tissue (GALT) in immune surveillance and homeostasis, what specific immunological consequence would invariably arise from a complete and irreversible ablation - not dysfunction, but complete absence - of M cells within the GALT?
Given the crucial role of Gut-Associated Lymphoid Tissue (GALT) in immune surveillance and homeostasis, what specific immunological consequence would invariably arise from a complete and irreversible ablation - not dysfunction, but complete absence - of M cells within the GALT?
A research team engineers a novel chimeric antigen receptor (CAR) T cell that, upon binding to its target antigen on tumor cells, constitutively activates the NFAT transcription factor, bypassing normal TCR signaling requirements. However, these CAR T cells exhibit severely impaired cytotoxic function in vivo. What is the MOST plausible explanation for this observation?
A research team engineers a novel chimeric antigen receptor (CAR) T cell that, upon binding to its target antigen on tumor cells, constitutively activates the NFAT transcription factor, bypassing normal TCR signaling requirements. However, these CAR T cells exhibit severely impaired cytotoxic function in vivo. What is the MOST plausible explanation for this observation?
Considering the multifaceted roles of Dendritic Cells (DCs) in bridging innate and adaptive immunity, what specific alteration in DC trafficking and function would most severely compromise the establishment of robust T cell memory responses following a cutaneous viral infection?
Considering the multifaceted roles of Dendritic Cells (DCs) in bridging innate and adaptive immunity, what specific alteration in DC trafficking and function would most severely compromise the establishment of robust T cell memory responses following a cutaneous viral infection?
A pharmaceutical company is developing a new immunosuppressant drug that selectively inhibits the interaction between the TCR and peptide-MHC complex with very high affinity, but only after the initial co-stimulatory signal has been received by the T cell. Assuming the drug effectively blocks continued TCR signaling, what is the MOST likely consequence of administering this drug to a patient undergoing an acute organ transplant rejection?
A pharmaceutical company is developing a new immunosuppressant drug that selectively inhibits the interaction between the TCR and peptide-MHC complex with very high affinity, but only after the initial co-stimulatory signal has been received by the T cell. Assuming the drug effectively blocks continued TCR signaling, what is the MOST likely consequence of administering this drug to a patient undergoing an acute organ transplant rejection?
In the context of adaptive immunity, how would the absence of a spleen most critically impair the immune system's ability to respond to novel bloodborne pathogens in a pediatric patient, considering the unique immunological functions of the spleen?
In the context of adaptive immunity, how would the absence of a spleen most critically impair the immune system's ability to respond to novel bloodborne pathogens in a pediatric patient, considering the unique immunological functions of the spleen?
Considering the intricacies of lymphocyte activation and the 'two-signal' hypothesis, what outcome would inevitably arise from a scenario in which T cells receive a signal through their T cell receptor (TCR) upon encountering cognate antigen presented by a professional antigen-presenting cell (APC), but simultaneously lack appropriate co-stimulation (e.g., CD28-B7 interaction)?
Considering the intricacies of lymphocyte activation and the 'two-signal' hypothesis, what outcome would inevitably arise from a scenario in which T cells receive a signal through their T cell receptor (TCR) upon encountering cognate antigen presented by a professional antigen-presenting cell (APC), but simultaneously lack appropriate co-stimulation (e.g., CD28-B7 interaction)?
Within the framework of the Clonal Selection Theory, what would be the most critical implication of a failure in the negative selection process during T cell development in the thymus?
Within the framework of the Clonal Selection Theory, what would be the most critical implication of a failure in the negative selection process during T cell development in the thymus?
Considering the intricacies of humoral immunity, what specific functional consequence would arise from a mutation that selectively impairs the ability of B cells to undergo isotype switching?
Considering the intricacies of humoral immunity, what specific functional consequence would arise from a mutation that selectively impairs the ability of B cells to undergo isotype switching?
In the context of immunological memory, how would the magnitude and kinetics of the antibody response differ between a primary and secondary exposure to the identical antigen?
In the context of immunological memory, how would the magnitude and kinetics of the antibody response differ between a primary and secondary exposure to the identical antigen?
Given the complexities of immune regulation, what specific mechanism would most effectively prevent excessive inflammation and tissue damage during a robust cell-mediated immune response against an intracellular pathogen?
Given the complexities of immune regulation, what specific mechanism would most effectively prevent excessive inflammation and tissue damage during a robust cell-mediated immune response against an intracellular pathogen?
Given the dynamic microenvironment of the thymus, which of the following cellular interactions is MOST critical for the induction of central tolerance in developing T cells, preventing autoimmune reactions?
Given the dynamic microenvironment of the thymus, which of the following cellular interactions is MOST critical for the induction of central tolerance in developing T cells, preventing autoimmune reactions?
Considering the distinct developmental niches within the bone marrow, what specific signaling pathway is MOST indispensable for the commitment of hematopoietic stem cells (HSCs) towards the B-lymphoid lineage, ensuring proper B cell maturation?
Considering the distinct developmental niches within the bone marrow, what specific signaling pathway is MOST indispensable for the commitment of hematopoietic stem cells (HSCs) towards the B-lymphoid lineage, ensuring proper B cell maturation?
Given the intricate circulatory dynamics of the lymphatic system, what cellular mechanism BEST explains the preferential migration of dendritic cells (DCs) from peripheral tissues to secondary lymphoid organs such as lymph nodes?
Given the intricate circulatory dynamics of the lymphatic system, what cellular mechanism BEST explains the preferential migration of dendritic cells (DCs) from peripheral tissues to secondary lymphoid organs such as lymph nodes?
In the context of maintaining fluid homeostasis within tissues, which molecular mechanism BEST accounts for the prevention of edema formation in tissues with compromised lymphatic drainage?
In the context of maintaining fluid homeostasis within tissues, which molecular mechanism BEST accounts for the prevention of edema formation in tissues with compromised lymphatic drainage?
Considering the architecture and function of lymph nodes, which specific structural element is MOST critical for facilitating the initial encounter between naive lymphocytes and antigens presented by antigen-presenting cells (APCs)?
Considering the architecture and function of lymph nodes, which specific structural element is MOST critical for facilitating the initial encounter between naive lymphocytes and antigens presented by antigen-presenting cells (APCs)?
Given the distinctive immunological functions of Mucosa-Associated Lymphoid Tissue (MALT), what cellular adaptation is MOST crucial for MALT's ability to initiate immune responses against pathogens invading mucosal surfaces?
Given the distinctive immunological functions of Mucosa-Associated Lymphoid Tissue (MALT), what cellular adaptation is MOST crucial for MALT's ability to initiate immune responses against pathogens invading mucosal surfaces?
Considering the varying stages of B cell development within the bone marrow, which specific checkpoint mechanism is MOST indispensable to ensure that developing B cells express a functional and non-autoreactive B cell receptor (BCR)?
Considering the varying stages of B cell development within the bone marrow, which specific checkpoint mechanism is MOST indispensable to ensure that developing B cells express a functional and non-autoreactive B cell receptor (BCR)?
How would the disruption of the unidirectional flow of lymph, specifically within lymphatic vessels regulated by lymphatic endothelial cells (LECs), impact adaptive immune responses?
How would the disruption of the unidirectional flow of lymph, specifically within lymphatic vessels regulated by lymphatic endothelial cells (LECs), impact adaptive immune responses?
Within secondary lymphoid organs, such as lymph nodes and the spleen, what is the MOST significant role of follicular dendritic cells (FDCs) in promoting humoral immunity?
Within secondary lymphoid organs, such as lymph nodes and the spleen, what is the MOST significant role of follicular dendritic cells (FDCs) in promoting humoral immunity?
If the bone marrow's capacity for B-cell maturation were severely compromised due to a genetic defect affecting the expression of the RAG1/RAG2 recombinase complex, how would this specifically alter the adaptive immune response to a novel viral pathogen?
If the bone marrow's capacity for B-cell maturation were severely compromised due to a genetic defect affecting the expression of the RAG1/RAG2 recombinase complex, how would this specifically alter the adaptive immune response to a novel viral pathogen?
Considering the role of nTregs in maintaining immune homeostasis within the pancreatic microenvironment, which of the following scenarios would MOST likely compromise islet cell viability in a pre-diabetic individual?
Considering the role of nTregs in maintaining immune homeostasis within the pancreatic microenvironment, which of the following scenarios would MOST likely compromise islet cell viability in a pre-diabetic individual?
In the context of B cell activation and subsequent antibody production, which scenario would MOST effectively bypass the requirement for T cell help, while ensuring robust and isotype-switched antibody responses?
In the context of B cell activation and subsequent antibody production, which scenario would MOST effectively bypass the requirement for T cell help, while ensuring robust and isotype-switched antibody responses?
Given the differential kinetics and isotype profiles of primary and secondary antibody responses, which of the following vaccination strategies would be MOST effective in generating long-lasting, high-affinity IgG antibodies against a rapidly mutating viral pathogen?
Given the differential kinetics and isotype profiles of primary and secondary antibody responses, which of the following vaccination strategies would be MOST effective in generating long-lasting, high-affinity IgG antibodies against a rapidly mutating viral pathogen?
Considering the various mechanisms by which antibodies mediate effector functions, which of the following strategies would be MOST effective in eradicating intracellular bacteria residing within macrophages, while minimizing bystander tissue damage?
Considering the various mechanisms by which antibodies mediate effector functions, which of the following strategies would be MOST effective in eradicating intracellular bacteria residing within macrophages, while minimizing bystander tissue damage?
In the context of antibody feedback mechanisms, which of the following scenarios would MOST effectively suppress further antibody production by B cells during a persistent systemic infection?
In the context of antibody feedback mechanisms, which of the following scenarios would MOST effectively suppress further antibody production by B cells during a persistent systemic infection?
Given the selective theory of antibody specificity, what experimental observation would MOST directly contradict the postulates of this model regarding receptor generation and clonal selection?
Given the selective theory of antibody specificity, what experimental observation would MOST directly contradict the postulates of this model regarding receptor generation and clonal selection?
Considering the functional differences between IgM and IgG isotypes during a systemic bacterial infection, which of the following treatment strategies would MOST rapidly reduce the bacterial load and prevent sepsis?
Considering the functional differences between IgM and IgG isotypes during a systemic bacterial infection, which of the following treatment strategies would MOST rapidly reduce the bacterial load and prevent sepsis?
In the context of ADCC, which cellular interaction is MOST critical for ensuring specific and efficient elimination of virally infected target cells by NK cells?
In the context of ADCC, which cellular interaction is MOST critical for ensuring specific and efficient elimination of virally infected target cells by NK cells?
Flashcards
Primary Lymphoid Organs
Primary Lymphoid Organs
Organs where lymphocytes reach functional maturity.
Secondary Lymphoid Organs
Secondary Lymphoid Organs
Organs where mature lymphocytes interact with antigens.
Lymphatic System
Lymphatic System
Network of vessels collecting and returning fluid (lymph) from tissues back to the blood.
Bone Marrow
Bone Marrow
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Thymus
Thymus
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Interstitial Fluid
Interstitial Fluid
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Edema
Edema
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Thoracic Duct
Thoracic Duct
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Lymph
Lymph
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Immune Cell Entry
Immune Cell Entry
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Lymph Node
Lymph Node
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Lymphoid Follicles
Lymphoid Follicles
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Primary Follicle
Primary Follicle
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What are Antigens?
What are Antigens?
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B Lymphocytes
B Lymphocytes
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T Lymphocytes
T Lymphocytes
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T-helper cells
T-helper cells
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T-cytolytic cells
T-cytolytic cells
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DC Migration in Adaptive Immunity
DC Migration in Adaptive Immunity
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GALT Definition
GALT Definition
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M Cells Function
M Cells Function
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Stages of Adaptive Immune Response
Stages of Adaptive Immune Response
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Qualities of Adaptive Immunity
Qualities of Adaptive Immunity
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Antigen Definition
Antigen Definition
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Diversity (Immune System)
Diversity (Immune System)
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Memory (Immune System)
Memory (Immune System)
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TCR Function
TCR Function
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Antigen Presentation to T cells
Antigen Presentation to T cells
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Cytokines
Cytokines
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TCR Recognition
TCR Recognition
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T Cell Co-stimulation
T Cell Co-stimulation
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Treg Function
Treg Function
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Antibodies (Ab)
Antibodies (Ab)
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IgG
IgG
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IgM
IgM
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IgA
IgA
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Primary Antibody Response
Primary Antibody Response
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Secondary Antibody Response
Secondary Antibody Response
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Opsonization
Opsonization
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Study Notes
- Section 5 focuses on the organs of the immune system and lymphatics.
- Section 6 is about Adaptive Immune Response
Organs Overview
- Primary organs are where lymphocytes reach functional maturity, such as the bone marrow and thymus in humans and mice.
- Secondary organs are where mature lymphocytes interact with antigens, like lymph nodes, spleen, MALT, and GALT.
- The lymphatic system is a network of vessels that collects fluid (lymph) that has escaped into tissues from the circulatory system and returns it to the blood.
Primary Lymphoid Organs
- They area also known as generative organs
- The location where lymphocytes first express antigen receptors and attain functional maturity
- Bone Marrow:
- Generates all circulating blood cells in adults
- It is the site of early B cell (immature lymphocyte) maturation.
- A preferential niche of plasma and memory T cells can be located here
- Thymus:
- Located where T cell maturation occurs
- The cortex contains a thick collection of mostly immature thymocytes.
- It is a bi-lobed organ where each lobe is divided into lobules, separated by trabeculae.
- It generates a T cell repertoire that will protect from infection.
- The thymus, thymocytes undergo gene rearrangement, which produces enormous diversity of TCR.
- More than 95% of thymocytes die by apoptosis.
- The role of the thymus can be studied in thymectomized mice or nude mice.
- The thymus is located near the thyroid, nerves, heart and diaphragm
- Each lobule inside capsule, has a cortex and a medulla
- T cell developments happens from the capsule inwards going from DN (Double Negative) -> DP (Double Positive) -> SP (Single Positive)
Thymus Size
- Total thymus weight peaks around puberty, and decreases with age.
Bone Marrow
- It facilitates hematopoiesis and B cell maturation.
- Bone marrow B cells generate 90% of Immunoglobulin G and A (antibody isotypes) in plasma
- B cell development occurs in different places for different animals:
- The Bursa of Fabricus in birds
- The Fetal spleen → ileal peyer's patch in sheep and cattle
- The Appendix in rabbits
Lymphatic System
- As blood travels under pressure, plasma seeps through thin capillary walls into surrounding tissues
- Around 2.9 liters of interstitial fluid are generated in adults per day, which bathes tissues and cells.
- Most fluid is returned back to the blood through walls of the venules and the remainder passes through primary lymphatic vessels; cells like Macs, DCs, and lymphocytes can also pass through thin wall.
- The thoracic duct empties into the left subclavian vein, which is the largest lymphatic vessel.
- Muscle contractions help move the lymph in a unidirectional path.
- Vessels form a unidirectional movement to return fluids, now called interstitial fluid, to the circulatory system
- Macrophages, lymphocytes, and dendritic cells, and other immune cells gain entry to lymph/tissues
- The lymphatic drains all tissues so when foreign antigens enter tissues, it is eventually picked up by lymph.
- Lymph carries lymphocytes and antigens from connective tissues to lymphoid tissues where lymphocytes can be used
Secondary Lymphoid Organs
- These includes locations where mature lymphocytes interact with antigens.
- Spleen, lymph nodes, Mucosa-Associated Lymph Tissue (MALT), and Gut-Associated Lymph Tissue (GALT) are secondary lymphoid organs
- All secondary lymphoid organs include lymphoid follicles-collections of lymphoid and non-lymphoid cells surrounded by draining lymphatic capillaries
- Lymph nodes and the spleens are the most organized with distinct B- and T-cell regions and fibrous capsules, in addition to lymphoid
Lymphoid Follicles (Present in 2nd Lymphoid Organs)
- Primary follicles contain follicular dendritic cells and resting B cells before activation with no germinal center (GC).
- Secondary follicles are packed circular rings of B cells surrounding GC, which contain rapidly dividing B cells, non-dividing B cells, Follicular T Helper Cells (TFH), Follicular DCs, and Macs after activation.
Lymph Node
- Encapsulated bean-shaped structures that are full of lymphocytes, dendritic cells, macrophages
- The first organized lymphoid structure to encounter antigens entering tissue spaces
- Antigens become trapped for antigen presentation.
- Key parts of lymph node:
- Cortex: B cells, Follicular DCs, Follicular T cells, and Macrophages (primary and secondary follicles)
- Paracortex: B- and T- cells and DCs (MHCII)
- Medulla: sparse lymphocytes, Ab-secreting
- In the paracortex, antigen gets trapped, DCs internalize, process, and express in MHCII to T cells, soluble antigen binds to BCR specific to antigen.
- Efferent (outgoing) lymph has antibodies and 50x lymphocytes, mostly via migration of blood-borne lymphocytes, and some due to proliferation
- The migration of cells through HEV is called extravasation.
Spleen
- A large oval structure in the left abdominal cavity
- The spleen plays a major role in mounting immune responses to blood-borne antigens arriving through splenic artery.
- The spleen structure consists of the following:
- Surrounded by capsule with projections (trabeculae) extending into interior
- Red pulp (mostly RBCs and macrophages) and white pulp (lymphocytes) are separated by a marginal zone
- Within the white pulp, the PeriArteriolar Lymphoid Sheath (PALS) is dominated by T
- Antigen enters through splenic artery empties in marginal zone; antigen is trapped by DCs, and processed there; DCs move to PALS, where they present MHCII-Ag → T cell activation
- Loss of spleen results in increase of bacterial sepsis in children.
Gut-Associated Lymphoid Tissue (GALT)
- M cells separate internal and external environments
- Intraepithelial cells are a key component.
Phylogeny
- Immune organs can be tracked through evolution with different organisms having equivalents of different organs
- Human immune organs include adenoids, tonsils, thoracic duct, left subclavian vein, right lymphatic duct, thymus, lymph nodes, spleen, peyer's patches, small instesine, bone marrow, large intestine, appendix and tissue lymphatics
Adaptive Immune Response Overview
- The adaptive immune response is characterised with stages of recognition -> activation -> effector phase -> decline -> memory
- Principles are based around: Specificty, Diversity, Memory, Optimization, Self-limiting, Safe to Self
- Antigens elicits an immune response and are usually foreign
- Some examples types of cells involved:
- B cells for Bone marrow
- T Helper for Thymus (CD4)
- T cytolytic for Thymus (CD8)
- Stem cells differentiate into B and T lymphocytes in the bone marrow, where replication continues as lymphocytes circulate and enter lymphoid tissue
Lymphocytes
- Major cells of the immune system include T cells, B cells, and NK cells (Natural Killer Cells; Outdated term: null cells-recent term innate lymphoid cell)
- Stem cells differentiate into B and T lymphocytes in the bone marrow
- After activation, replication continues as lymphocytes circulate and enter lymphoid tissue
- Some activated cells form memory cells that do not immediately replicate, but will do so later when the host is reexposed to an antigen.
- B Lymphocytes:
- Mature in bone marrow, circulate in blood, settle in lymphoid organs, then maturation and activation occurs to become plasma cells that secrete large volumes of antibodies.
- T Lymphocytes:
-Mature in thymus, then remain in thymus (most migrate out), circulate in blood, or reside in lymphoid tissue
- T cells require antigen binding to surface receptors (i.e. TCR) for activation and replication; unlike B cells, antigen must be presented to T cells by APC in the context of MHC -Activated T cells produces cytokines (proteins that have affects on other cells, changing cell surface proteins, or up-regulate cytolytic/cytotoxic molecules -Types: CD4+, CD8+, and Treg
Key Requirements:
Key Information
- CTLA4 competes with CD28; Cytokine Signaling Suppressors
Antibody Details
- Soluble glycoproteins that bind antigens with high specificity and affinity
- Antibodies can be used for neutralization of virus infectivity, neutralization of toxins, Opsonization, activation of complements and Antibody Dependent Cell Cytotoxicity (ADCC)
- The 5 major isotypes of antibodies include the following:
- IgG: most abundant immunoglobulin in the blood, present as a monomer
- IgM: the first Ab produced in response to an infection, present as a pentamer
- IgA: The major immunoglobulin in external secretions (milk, saliva, etc.), present as a dimer
- IgE Binds to allergens
- IgD assists B cells
Humoral Response and Action
- Clonal selection theory depends on antibody diversity, receptors on the cell surface , recognition of antigen and recognition stimulates maturation
- There primary antibody response is characterized by peaking at 10-17 days and mostly involve IgM. Antibody levels increase than decline
- Secondary response shows: Is more rapid (peaks in 2-7 days), mainly IgG , there results in higher levels of antibody, and it persists longer than in the primary response (years with vaccination)
Immune Dysfunction
- Examples include Allergies and asthma (hypersensitivity), Graft rejection and graft versus host disease (GVHD), Autoimmune diseases, & Immunodeficiency
- Allergies and asthma: some substance such as pollen can induce this, IgE binding to allergens releases irritations inflamation etc
- Graft rejection triggers the immune system view translated tissues as foreign whereas graft versus host disease happens when translated material contains immune function
- Autoimmunity happens when tolerance mechanisms break down damaging self tissues
- Examples of autoimmune diseases, multiple sclerosis, rheumatoid arthritis, chron’s disease, and diabetes
Additional Info - AutoImmune
- Multiple sclerosis presents as 300k cases in US, Rheumatoid 1.3 million, Type 1 diabetes has 1.22 million, and systemic lupus has 250k
Immunodeficiency:
- Any deficiency in the immune response (primary or secondary); May go unnoticed depending on the system.
- Severe Combined ImmunoDeficiency (SCID): genetic disease that causes the lack of B and T Cells, results in infection death rates if undetected.
- Acquired Immune Deficiency Syndrome (AIDS) comes from retro virus HIV, where destruction of CD4+ T cells destroys the system, with the total infected topping out at 37 million.
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