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Questions and Answers
What is primarily mediated by B cells in adaptive immunity?
What is primarily mediated by B cells in adaptive immunity?
What do T cells require for the recognition of foreign proteins?
What do T cells require for the recognition of foreign proteins?
Naive lymphocytes refer to which of the following?
Naive lymphocytes refer to which of the following?
What is the role of Helper T cells in adaptive immunity?
What is the role of Helper T cells in adaptive immunity?
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Which pathway is involved in presenting intracellular pathogen proteins to T cells?
Which pathway is involved in presenting intracellular pathogen proteins to T cells?
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What happens to B cells in the bone marrow if they do not successfully complete receptor editing?
What happens to B cells in the bone marrow if they do not successfully complete receptor editing?
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What characteristic distinguishes memory cells in adaptive immunity?
What characteristic distinguishes memory cells in adaptive immunity?
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Which T cell type is specifically recognized by MHC Class I molecules?
Which T cell type is specifically recognized by MHC Class I molecules?
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Which of the following is NOT one of the three signals required for T cell activation?
Which of the following is NOT one of the three signals required for T cell activation?
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How do B cells recognize antigens?
How do B cells recognize antigens?
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What role does CD40L on the activated Helper T cell play in B cell activation?
What role does CD40L on the activated Helper T cell play in B cell activation?
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Where does the interaction between lymphocytes and antigens primarily take place in the body?
Where does the interaction between lymphocytes and antigens primarily take place in the body?
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Which of the following statements about lymphoid tissues is correct?
Which of the following statements about lymphoid tissues is correct?
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What mechanism allows B cells to recognize antigens?
What mechanism allows B cells to recognize antigens?
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How are antigens delivered to lymph nodes from tissues?
How are antigens delivered to lymph nodes from tissues?
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What type of antigens lead to full B cell activation through the interaction with Helper T cells?
What type of antigens lead to full B cell activation through the interaction with Helper T cells?
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What is the primary consequence of CD8 T cell interaction with MHC class I molecules?
What is the primary consequence of CD8 T cell interaction with MHC class I molecules?
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Which molecules are recognized by CD4 T cells?
Which molecules are recognized by CD4 T cells?
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Which of the following cells are classified as professional antigen-presenting cells?
Which of the following cells are classified as professional antigen-presenting cells?
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What is the structural composition of a BCR/antibody?
What is the structural composition of a BCR/antibody?
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How is the diversity of TCRs and BCRs generated?
How is the diversity of TCRs and BCRs generated?
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What occurs during the process of negative selection for T cells in the thymus?
What occurs during the process of negative selection for T cells in the thymus?
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What is the primary role of dendritic cells in the immune system?
What is the primary role of dendritic cells in the immune system?
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What polymorphic genes are associated with MHC Class I molecules in humans?
What polymorphic genes are associated with MHC Class I molecules in humans?
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What is the primary function of the spleen in the immune system?
What is the primary function of the spleen in the immune system?
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Which class of antibody is the first one produced during an immune response?
Which class of antibody is the first one produced during an immune response?
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What do B cells require to undergo isotype switching and produce different classes of antibodies?
What do B cells require to undergo isotype switching and produce different classes of antibodies?
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What characteristic of antibodies allows Natural Killer (NK) cells to recognize and eliminate antibody-coated cells?
What characteristic of antibodies allows Natural Killer (NK) cells to recognize and eliminate antibody-coated cells?
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Which of the following roles do antibodies NOT directly participate in?
Which of the following roles do antibodies NOT directly participate in?
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What is the main effect of T regulatory cells (Treg) in the immune system?
What is the main effect of T regulatory cells (Treg) in the immune system?
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During an immune response, what typically happens to most lymphocytes generated through clonal expansion?
During an immune response, what typically happens to most lymphocytes generated through clonal expansion?
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Which type of T cell is primarily involved in direct killing of infected cells?
Which type of T cell is primarily involved in direct killing of infected cells?
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Study Notes
Adaptive Immunology
- Adaptive immunity is a feature of the immune system that is characterized by the ability to recognize specific antigens.
- Key features of adaptive immunity include antigen presentation, lymphocyte activation, B cell effector function, T cell effector function, and memory.
- A microbe is engulfed by a phagocyte and encased in a phagosome.
Lesson Plan
- Features of adaptive immunity
- Antigen presentation
- Lymphocyte activation
- B cell effector function
- T cell effector function
- Memory
Adaptive Immunity
- Innate immunity occurs within hours after infection, whereas adaptive immunity takes days.
- B lymphocytes and T lymphocytes make up the adaptive immune system.
Phases of Adaptive Immunity
- Antigen is a molecule specifically recognised by lymphocytes or antibodies.
- Naive lymphocytes (B and T cells) haven't encountered foreign antigens.
- Binding to specific antigens leads to activation, proliferation, and differentiation of B and T cells. This takes time.
Functions of Adaptive Immunity
- B cells mediate humoral immunity by producing antibodies.
- Helper T cells orchestrate an effective immune response by interacting with other immune cells.
- Cytotoxic T cells kill infected or malignant host cells.
Memory in the Adaptive Immunity
- Following infection resolution, some cells persist (memory cells), responding faster the next time, preventing or lessening the infection's severity.
- The primary response involves initial encounter with an antigen; the secondary response is a quicker, more potent reaction due to memory cells.
TCR and BCR
- Surface immunoglobulin (B cell receptor) and T cell receptor (TCR) allow cells to recognize an antigen.
- BCR can directly recognize an antigen
- TCR cannot directly recognize an antigen; proteins must be processed into peptides before antigen presentation via MHC to the T cell.
Recognition of Antigen
- B cells express a B-cell receptor (BCR) and T cells express a T-cell receptor (TCR).
- BCR can directly recognize antigens
- TCR cannot directly recognize antigens; proteins must be processed before presentation in MHC.
Antigen Presentation
- T cells cannot directly recognize foreign proteins.
- Proteins must be processed into peptides, bound to self molecules known as MHC (Human Leukocyte Antigen).
- MHC Class I pathway is for intracellular pathogens (where the foreign protein is made by a host cell).
- MHC Class II pathway is for extracellular pathogens.
Antigen Presentation Class I and Class II
- MHC Class I molecules bind to peptides from inside cells, used for cells infected by intracellular microbes.
- MHC Class II molecules bind to peptides from outside the cell, and are used for cells infected by extracellular microbes.
MHC Class I Pathway
- Foreign proteins produced inside cells are presented on MHC Class I molecules.
- Cytotoxic T cells recognize the MHC Class I-protein complex, leading to the infected cell's death.
- The marker CD8 acts as a co-receptor for MHC Class I.
MHC Class II Pathway
- Foreign proteins taken up by presenting cells are presented on MHC Class II molecules.
- Helper T cells recognize the MHC Class II-protein complex leading to the helper T cell's activation.
- The marker CD4 act as a co-receptor for MHC Class II.
MHC Pathways
- Proteins made inside cells (e.g. virally infected), are digested into peptides in proteasomes for MHC class I presentation.
- Proteins taken up from outside (e.g., phagocytosis), are digested into peptides by lysosomal enzymes for MHC class II presentation.
MHC Class I
- Expressed on all nucleated cells.
- The most polymorphic genes in the human genome (variants of HLA-A, HLA-B, HLA-C, differing in peptide-binding).
MHC Class II
- Expressed by immune cells (dendritic cells, macrophages, and B cells).
- Six main MHC class II genes in humans (HLA-DPA1, HLA-DPB1, ..., HLA-DRB1).
- Very polymorphic genes.
Dendritic Cells (DCs)
- Play a central role in antigen processing and presentation.
- Immature DCs capture antigens in the periphery and become mature DCs in lymph nodes; presenting antigens to helper T cells.
- DCs are professional antigen-presenting cells (APCs), along with macrophages and B cells.
Diversity of TCR and BCR
- Variable domains of both BCR and TCR are generated via recombination of gene segments, resulting in a large number of different receptors from a limited number of gene segments.
BCR/Antibody Structure
- BCR/antibody molecules are composed of two identical heavy chains and two identical light chains, held together by disulphide bonds.
- Each chain contains constant and variable regions. The variable regions are on the antigen-binding site.
- Light chain: one V domain, one C domain.
- Heavy chain: one V domain, 3-4 C domains.
TCR Structure
- TCR consists of two chains (α and β), held together by disulphide bridges.
- Each chain has one constant and one variable region. The variable regions are on the antigen-binding site.
Negative Selection
- Random generation of BCR and TCR from gene segments means some may recognise self antigens.
- Immature T cells in the thymus recognising self-peptides on MHC undergo apoptosis (negative selection).
- B cells in bone marrow may undergo receptor editing or apoptosis (negative selection).
Activation of Adaptive Cells
- T helper cells are activated via three signals:
- Antigen recognition by TCR
- Co-stimulation by presenting cell
- Cytokine signaling
- Recognition of the antigen by TCR without costimulation and/or cytokine signals will not result in T helper cell activation. APC (antigen-presenting) cells are activated with PRR (pattern recognition receptor) engagement; APC costimulation without antigen recognition does not lead to activation.
Signals for T cells Activation
- APC activation is necessary for T cell activation. Activated APCs produce co-stimulatory molecules and cytokines.
- Antigen recognition in the absence of signal (2 & 3) does not lead to T cell activation.
Signals for B cell Activation
- B cell receptor (BCR) recognizes antigen.
- Co-stimulation from helper T cell.
- Cytokines.
B cell activation
- Antigen recognition by BCR leads to internalization and processing of the antigen.
- Processing of the antigen with MHC Class II presentation.
- Recognition of the antigen-MHC complex by TCR on activated helper T cells (CD4+ T cells).
- This allows co-stimulation and full B cell activation.
- This process only occurs with T cell-dependent protein antigens
B cell- T cell interactions
- Co-stimulation occurs between CD40L on the activated helper T cell and CD40 on the B cell.
- Cytokines from the helper T cell can influence the type of antibody produced.
Lymphocyte Trafficking
- Antigens from body tissues are delivered to lymph nodes via lymphatics.
- Antigens in the blood are delivered to the spleen.
- Primary lymphoid tissues (bone marrow and thymus): generate and mature immune cells.
- Secondary lymphoid tissues (lymph nodes and spleen): allow lymphocytes to interact with antigens and become activated.
Lymph Node
- Encapsulated organs in the body, filtering antigens from the periphery.
- Ag is moved through lymphatics by antigen-presenting cells (APCs).
- Follicles allow T and B cells to encounter their antigens and proliferate, leading to mature effector B cells.
The Spleen
- A highly vascular organ that filters blood and eliminates pathogens (blood-borne pathogens)
- Follicles (like those in lymph nodes): antigen-encountering areas where proliferation leads to fully mature T and B cells.
Effector Functions of Adaptive Lymphocytes
- B cell function involves antigen recognition, plasma cell production, and antibody production, including neutralization of microbes, phagocytosis, and complement activation.
Antibody Isotypes
- 5 classes/isotypes of antibodies (IgG, IgA, IgE, IgM, IgD)
- Different constant regions (Fc fragments) affect the biological activity (e.g., complement fixation).
- IgM is the first antibody produced.
Antibody Isotype Switching
- Depending on signals, B cells can change antibody isotype (e.g. IgM to IgG, IgE, IgA).
- Different isotypes mediate different effector functions (e.g., complement activation).
Antibody Isotype Differences
- Antibody forms (monomer or dimer), percentage in serum.
- Locations in the body/ where they function.
- Specific antibody functions (e.g., protection from external openings, reacting to infection).
- Transferability (via colostrum, breast milk, placenta).
Role of Antibodies
- Antibodies are produced by the adaptive immune system (many effector functions are dependent on innate immunity - such as phagocytosis and complement activation).
Antibodies: Neutralisation
- Antibodies block the entry of microbes or toxins.
- Prevents microbes or toxins from interacting with cells.
Antibodies: Opsonisation
- Opsonization is the process of coating a pathogen with antibodies (IgG).
- Phagocytes (Fc receptors) engulf the coated pathogen, promoting phagocytosis.
Antibodies: ADCC
- Antibody-dependent cell-mediated cytotoxicity (ADCC)
- Antibody-coated cells (e.g. some microbes or infected cells) are recognized by natural killer (NK) cells that have Fc receptors, leading to elimination of the targeted cell.
T cell Function
- Helper T cells (CD4+) produce cytokines that activate macrophages, which activate T and B cells.
- Cytotoxic T cells (CTL, CD8+) kill infected cells.
Cytotoxic T Cells
- Kill infected cells
- Cytotoxic T cell mechanism similar to NK cells.
- Accessory protein (CD8) aids in recognition of Class I MHC molecule on the infected cell via TCR.
- Perforin and granzymes induce infected cell apoptosis.
T Helper Cells
- Distinct T helper cell subsets (Th1, Th2, Th17, Treg) depending on the cytokine environment during T helper activation.
- Important for maintaining self-tolerance and inhibiting immune responses.
T Helper Cell Subsets
- Th1 cells activate macrophages.
- Th2 cells activate eosinophils and mast cells.
- Th17 cells recruit neutrophils.
- Treg cells inhibit immune responses.
Memory
- Most lymphocytes generated during an immune response eventually die, but some become memory B and T cells.
- Memory cells can quickly be reactivated compared to naïve B and T cells.
Second Response
- Secondary response is more potent and faster than the primary response due to memory cells.
- Fewer antigens are required for a robust response to be initiated and maintained.
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