Podcast
Questions and Answers
What is the primary mechanism by which Th cells direct immunity?
What is the primary mechanism by which Th cells direct immunity?
Which type of pathogens does cell-mediated immunity specifically target?
Which type of pathogens does cell-mediated immunity specifically target?
Which cells predominantly mediate cell-mediated immunity?
Which cells predominantly mediate cell-mediated immunity?
What is essential for T cell full activation?
What is essential for T cell full activation?
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What role does cytokine signaling play in T cell activation?
What role does cytokine signaling play in T cell activation?
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What is one of the critical functions of cell-mediated immunity?
What is one of the critical functions of cell-mediated immunity?
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Which type of T helper (Th) cells is primarily responsible for cell-mediated immunity?
Which type of T helper (Th) cells is primarily responsible for cell-mediated immunity?
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What effect do molecules like CD2 and LFA-1 have during T cell activation?
What effect do molecules like CD2 and LFA-1 have during T cell activation?
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What is the primary cytokine secreted by Th2 cells that does NOT contribute to strong antibody production?
What is the primary cytokine secreted by Th2 cells that does NOT contribute to strong antibody production?
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Which of the following cytokines is pivotal for Th cell proliferation and differentiation following TCR binding to the MHC class II-peptide complex?
Which of the following cytokines is pivotal for Th cell proliferation and differentiation following TCR binding to the MHC class II-peptide complex?
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Which type of immune response do Th2 cells predominantly engage in?
Which type of immune response do Th2 cells predominantly engage in?
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What is the role of CD40 ligand expressed by effector Th1 cells in the immune response?
What is the role of CD40 ligand expressed by effector Th1 cells in the immune response?
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Which of the following statements correctly describes the Th1 and Th2 cell functions?
Which of the following statements correctly describes the Th1 and Th2 cell functions?
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Which signal is considered the most important costimulatory signal for T cell activation during macrophage-Th cell interaction?
Which signal is considered the most important costimulatory signal for T cell activation during macrophage-Th cell interaction?
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How do activated macrophages assist with B cell function during the immune response?
How do activated macrophages assist with B cell function during the immune response?
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What is the main effect of IL-12 produced by macrophages on Th cells?
What is the main effect of IL-12 produced by macrophages on Th cells?
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What is the primary role of IL-2 secreted by activated Th cells?
What is the primary role of IL-2 secreted by activated Th cells?
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Which phase of CTL action involves the rearrangement of the cytoskeleton?
Which phase of CTL action involves the rearrangement of the cytoskeleton?
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What is the effect of perforin released from CTLs?
What is the effect of perforin released from CTLs?
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Which cytokine is primarily secreted by Th1 cells to assist in the differentiation of CD8+ T cells?
Which cytokine is primarily secreted by Th1 cells to assist in the differentiation of CD8+ T cells?
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What role do interferons play in the context of CTL activity?
What role do interferons play in the context of CTL activity?
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Which interaction is necessary for the effective differentiation of CTLs?
Which interaction is necessary for the effective differentiation of CTLs?
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How do cytokines such as IFN-γ contribute to CTL function?
How do cytokines such as IFN-γ contribute to CTL function?
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What mechanism do activated CTLs use for inducing apoptosis in target cells?
What mechanism do activated CTLs use for inducing apoptosis in target cells?
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Cell-mediated immunity primarily relies on antibodies produced by B cells.
Cell-mediated immunity primarily relies on antibodies produced by B cells.
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Obligate intracellular pathogens can replicate outside of host cells.
Obligate intracellular pathogens can replicate outside of host cells.
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Macrophages are crucial for the elimination of facultative intracellular pathogens.
Macrophages are crucial for the elimination of facultative intracellular pathogens.
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Th1 cells produce cytokines that primarily strengthen antibody production and suppress macrophage function.
Th1 cells produce cytokines that primarily strengthen antibody production and suppress macrophage function.
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Three signals are required for full T cell activation, including costimulatory signals.
Three signals are required for full T cell activation, including costimulatory signals.
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Th2 cells are associated with strong immune responses against intracellular pathogens.
Th2 cells are associated with strong immune responses against intracellular pathogens.
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Th2 cells are primarily responsible for cell-mediated immunity.
Th2 cells are primarily responsible for cell-mediated immunity.
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The binding of the TCR of Th cells to MHC class II–peptide complexes provides the second signal necessary for T cell activation.
The binding of the TCR of Th cells to MHC class II–peptide complexes provides the second signal necessary for T cell activation.
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Cytokines secreted by Th cells enhance the immune system's ability to respond to pathogens.
Cytokines secreted by Th cells enhance the immune system's ability to respond to pathogens.
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Classically activated macrophages produce substances like nitric oxide which are crucial for the destruction of phagocytosed microbes.
Classically activated macrophages produce substances like nitric oxide which are crucial for the destruction of phagocytosed microbes.
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Macrophages need IL-2 to directly activate T cells during the immune response.
Macrophages need IL-2 to directly activate T cells during the immune response.
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Costimulation via CD28 is a secondary signal that is not really important for T cell activation.
Costimulation via CD28 is a secondary signal that is not really important for T cell activation.
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Interferon-gamma and interleukin-2 are produced by Th1 cells.
Interferon-gamma and interleukin-2 are produced by Th1 cells.
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B cells can be induced to produce IgG antibodies through Th2 cell activation.
B cells can be induced to produce IgG antibodies through Th2 cell activation.
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The balance between Th1 and Th2 cell activation does not influence the outcome of infections.
The balance between Th1 and Th2 cell activation does not influence the outcome of infections.
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The most important costimulatory signal for T cell activation is the interaction between B7 protein and CD28 protein.
The most important costimulatory signal for T cell activation is the interaction between B7 protein and CD28 protein.
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Activated CTLs kill target cells exclusively by delivering granzymes without perforin involvement.
Activated CTLs kill target cells exclusively by delivering granzymes without perforin involvement.
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The presence of Th1 cells enhances the differentiation and cloning of CTLs.
The presence of Th1 cells enhances the differentiation and cloning of CTLs.
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Fas ligand (FasL) binding to Fas on target cells is involved in a mechanism independent of cytokines.
Fas ligand (FasL) binding to Fas on target cells is involved in a mechanism independent of cytokines.
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Cross priming does not facilitate CTL activation and differentiation.
Cross priming does not facilitate CTL activation and differentiation.
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Intracellular pathogens can be recognized by CTLs through the binding of their TCRs to an MHC class I/non-self-peptide complex on infected cells.
Intracellular pathogens can be recognized by CTLs through the binding of their TCRs to an MHC class I/non-self-peptide complex on infected cells.
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CTLs require physical attachment to their target cells before the exocytosis of toxic granule contents.
CTLs require physical attachment to their target cells before the exocytosis of toxic granule contents.
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Cytokines such as TNF-α and IFN-γ solely act through MHC class II to mediate CTL function.
Cytokines such as TNF-α and IFN-γ solely act through MHC class II to mediate CTL function.
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Granules in CTLs contain perforin and cytokines, which together contribute to the death of target cells.
Granules in CTLs contain perforin and cytokines, which together contribute to the death of target cells.
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What role does IL-2 play in T cell function following Th cell activation?
What role does IL-2 play in T cell function following Th cell activation?
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Describe the four phases of how CTLs kill their target cells.
Describe the four phases of how CTLs kill their target cells.
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How do CTLs enhance their differentiation and cloning in the presence of Th1 cells?
How do CTLs enhance their differentiation and cloning in the presence of Th1 cells?
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What are the two distinct mechanisms through which CTLs can induce apoptosis in target cells?
What are the two distinct mechanisms through which CTLs can induce apoptosis in target cells?
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What influence does the expression of Fas ligand (FasL) have on target cells?
What influence does the expression of Fas ligand (FasL) have on target cells?
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Explain the significance of cross presentation in CTL activation.
Explain the significance of cross presentation in CTL activation.
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What is the effect of interferons produced during CTL activity?
What is the effect of interferons produced during CTL activity?
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What is the primary purpose of the TCR's interaction with the MHC class I peptide complex?
What is the primary purpose of the TCR's interaction with the MHC class I peptide complex?
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What cytokines are primarily produced by Th2 cells, and what immune responses do they facilitate?
What cytokines are primarily produced by Th2 cells, and what immune responses do they facilitate?
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Describe the interaction necessary for T cell activation during macrophage-Th cell interactions.
Describe the interaction necessary for T cell activation during macrophage-Th cell interactions.
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How do IFN-γ and CD40 ligand from Th1 cells activate macrophages?
How do IFN-γ and CD40 ligand from Th1 cells activate macrophages?
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What role does IL-2 play in the proliferation of T cells after activation?
What role does IL-2 play in the proliferation of T cells after activation?
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Explain how the balance between Th1 and Th2 cells influences infection outcomes.
Explain how the balance between Th1 and Th2 cells influences infection outcomes.
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What substances do classically activated macrophages produce, and what is their significance?
What substances do classically activated macrophages produce, and what is their significance?
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In what way does IL-12 produced by macrophages affect Th cell activation?
In what way does IL-12 produced by macrophages affect Th cell activation?
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What is the importance of costimulatory signals during T cell activation?
What is the importance of costimulatory signals during T cell activation?
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What immunological role do Th1 cells play in combating obligate intracellular pathogens?
What immunological role do Th1 cells play in combating obligate intracellular pathogens?
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Describe the importance of costimulatory signals in T-cell activation.
Describe the importance of costimulatory signals in T-cell activation.
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How do cytokines influence the role of Th cells in the immune response?
How do cytokines influence the role of Th cells in the immune response?
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What mechanism do CD8+ T cells use to induce apoptosis in infected target cells?
What mechanism do CD8+ T cells use to induce apoptosis in infected target cells?
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Explain the significance of the Th1 and Th2 cytokine balance in immune responses.
Explain the significance of the Th1 and Th2 cytokine balance in immune responses.
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What role do macrophages play in the pathogenesis of delayed hypersensitivity reactions?
What role do macrophages play in the pathogenesis of delayed hypersensitivity reactions?
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How does the absence of signals from specific cytokines affect T cell activation?
How does the absence of signals from specific cytokines affect T cell activation?
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In what way do NK cells contribute to cell-mediated immunity?
In what way do NK cells contribute to cell-mediated immunity?
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Type 2 Th (Th2) cells produce IL-4, IL-5, IL-10, and IL-13, which are responsible for strong ______ production.
Type 2 Th (Th2) cells produce IL-4, IL-5, IL-10, and IL-13, which are responsible for strong ______ production.
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Th1 cells mainly develop following infections by intracellular ______ and some viruses.
Th1 cells mainly develop following infections by intracellular ______ and some viruses.
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The most important costimulatory signal is the interaction between B7 protein on the APC and ______ protein on the helper T cell.
The most important costimulatory signal is the interaction between B7 protein on the APC and ______ protein on the helper T cell.
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IL-2 secreted by activated Th cells is the most important factor for T cells that stimulates the ______ of clones of T cells.
IL-2 secreted by activated Th cells is the most important factor for T cells that stimulates the ______ of clones of T cells.
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Classically activated macrophages produce substances, including ______ oxide, that kill ingested microbes.
Classically activated macrophages produce substances, including ______ oxide, that kill ingested microbes.
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The ______ response activates both macrophages and B cells via the cytokine IFN-γ.
The ______ response activates both macrophages and B cells via the cytokine IFN-γ.
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The production of IL-12 by the macrophage helps to activate the ______ cells.
The production of IL-12 by the macrophage helps to activate the ______ cells.
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Macrophages produce cytokines that induce ______, which is essential for the inflammatory response.
Macrophages produce cytokines that induce ______, which is essential for the inflammatory response.
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Cell-mediated immunity primarily combats ______ pathogens.
Cell-mediated immunity primarily combats ______ pathogens.
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The primary cells involved in cell-mediated immunity are ______ and CD8+ T cells.
The primary cells involved in cell-mediated immunity are ______ and CD8+ T cells.
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T cells need ______ signals for complete activation.
T cells need ______ signals for complete activation.
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Th1 cells primarily produce ______-gamma, which activates macrophages.
Th1 cells primarily produce ______-gamma, which activates macrophages.
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If a T cell does not receive a complete set of signals, it may become ______.
If a T cell does not receive a complete set of signals, it may become ______.
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Cytokines are secreted by Th cells to direct ______ responses in the immune system.
Cytokines are secreted by Th cells to direct ______ responses in the immune system.
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Macrophages help in immunological surveillance and immunity against ______.
Macrophages help in immunological surveillance and immunity against ______.
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Costimulation transduced via ______ is essential for T cell activation.
Costimulation transduced via ______ is essential for T cell activation.
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IL-12 and IFN-γ promote the differentiation of the naïve Th cell into a ______ cell.
IL-12 and IFN-γ promote the differentiation of the naïve Th cell into a ______ cell.
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The most important factor for T cells that stimulates the proliferation of clones of T cells specific to that antigen is ______.
The most important factor for T cells that stimulates the proliferation of clones of T cells specific to that antigen is ______.
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CTLs recognize the cell they will ultimately kill by the interaction between their TCR and the ______ class I peptide complex.
CTLs recognize the cell they will ultimately kill by the interaction between their TCR and the ______ class I peptide complex.
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During the CTL killing process, the phase that involves rearrangement of the cytoskeleton is called ______.
During the CTL killing process, the phase that involves rearrangement of the cytoskeleton is called ______.
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Perforin creates ______ in the membrane of the target cell, allowing granzymes to enter.
Perforin creates ______ in the membrane of the target cell, allowing granzymes to enter.
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Cytokines such as IFN-γ can induce ______ in target cells.
Cytokines such as IFN-γ can induce ______ in target cells.
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Activated CTLs express Fas ligand (FasL), which binds to ______ on the target cell.
Activated CTLs express Fas ligand (FasL), which binds to ______ on the target cell.
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The process of CTLs killing target cells happens in ______ phases.
The process of CTLs killing target cells happens in ______ phases.
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Study Notes
Cell-Mediated Immunity
- Cell-mediated immunity is a part of the adaptive immune system that targets and eliminates infections caused by microbes residing within cells.
- It functions against both facultative intracellular pathogens (able to live inside phagocytic cells) and obligate intracellular pathogens (rely on host cells for replication).
- Key players in cell-mediated immunity include macrophages and CD8+ T cells, driven by the Th1 response.
T cell Activation
- T cells require three signals for full activation:
- Antigenic peptide presented on an MHC molecule
- Costimulatory signals (essential for activation)
- Signals from specific cytokines
- Without all three signals, T cells might become anergic (non-responsive).
T Helper Cells (Th1 & Th2)
- Th1 cells, promoting cell-mediated immunity, produce IFN-gamma, IL-2, and TNF, activating macrophages.
- Th2 cells, promoting antibody production and eosinophil activation, produce IL-4, IL-5, IL-10, and IL-13, inhibiting macrophage functions.
- Infections by intracellular bacteria and viruses often trigger Th1 responses, while gastrointestinal nematode infestations tend to induce Th2 responses.
Macrophage-Th Cell Interaction
- The TCR of a naive Th cell binds to the MHC class II–peptide complex on a macrophage, providing the first activation signal for the T cell.
- Costimulatory molecules on the macrophage provide the second signal (B7 protein on the APC interacting with CD28 protein on the helper T cell).
- Cytokines secreted by the macrophage and the activating T cells drive proliferation (clonal expansion) and differentiation of T cells into effector and memory cells.
- IL-2, secreted by activated Th cells, stimulates the proliferation of T cell clones specific for the antigen.
Th1 Response: Macrophages & B Cells
- The Th1 response activates both macrophages and B cells through IFN-γ.
- Th1 effector cells recognize antigens presented by macrophages.
- IFN-γ and CD40 ligand, secreted by Th1 cells, activate macrophages.
- Activated macrophages release nitric oxide and lysosomal enzymes to kill ingested microbes and produce cytokines to induce inflammation.
- Th1 cells also induce B cells to produce opsonizing IgG antibodies that assist in phagocytosis.
Th Cell/Macrophage Cytokines
- IL-12 produced by macrophages activates Th cells.
- TNF, IFN-γ, and IL-12 contribute to Th cell activation and differentiation of naive Th cells into Th1 cells.
Cytotoxic T Lymphocytes (CTLs)
- CTLs recognize their target cells by interaction between their TCR and the MHC class I peptide complex on the target cell's surface.
- This complex could be generated by an intracellular pathogen or neoantigens associated with cancer cells.
- CTLs can differentiate and clone independently in the presence of the appropriate MHC class I non-self peptide complex but are more efficient with assistance from Th1 cells.
- Th1 cells secrete IL-2, enhancing CTL differentiation and cloning.
How CTLs Kill Targets
- CTLs kill target cells by delivering toxic granule contents that induce apoptosis.
- This process involves attachment, activation, exocytosis of granule contents (perforin and granzymes), and detachment.
- Perforin creates pores in the target cell membrane, allowing granzymes to enter and activate caspases, triggering apoptosis.
- CTLs can also induce apoptosis through cytokines like IFN-γ, TNF-α, and TNF-β, or via Fas ligand (FasL) binding to Fas on the target cell.
Cell-Mediated Immunity
- Cell-mediated immunity (CMI) is an adaptive immune response that eliminates intracellular pathogens and cancer cells.
- CMI is orchestrated by Th1 cells and primarily involves macrophages and CD8+ T cells.
- It effectively fights obligate and facultative intracellular pathogens.
- Obligate intracellular pathogens cannot replicate outside host cells, while facultative intracellular pathogens can survive within phagocytic cells.
T-Cell Activation
- T cell activation requires three signals:
- Antigenic peptide presented on MHC molecules
- Costimulatory signals
- Specific cytokine signals
- Insufficient signals can lead to anergy (T cell inactivation).
- CD2 and LFA-1 molecules facilitate adhesion between T cells and antigen-presenting cells (APCs), enhancing activation.
- CD28 costimulation is crucial for T cell activation.
Th1 & Th2
- Th1 cells produce interferon-gamma (IFN-γ), interleukin-2 (IL-2), and tumor necrosis factor (TNF), activating macrophages and driving cell-mediated immunity.
- Th2 cells produce IL-4, IL-5, IL-10, and IL-13, promoting antibody production, eosinophil activation, and inhibiting macrophage function.
- Th1 cells are prominent in infections caused by intracellular bacteria and some viruses, while Th2 cells are dominant in responses to parasitic infections.
- The balance between Th1 and Th2 cell activation determines the outcome of many infections.
Macrophage-Th Cell Interaction
- The first signal for Th cell activation is TCR recognition of MHC class II-peptide complex on macrophages.
- Costimulatory molecules on macrophages, particularly B7 protein interacting with CD28 on helper T cells, provide the second signal.
- Cytokines released by macrophages and Th cells promote T cell proliferation and differentiation into effector and memory cells.
- IL-2, secreted by activated Th cells, is essential for T cell clonal expansion.
Macrophages/B Cells
- Th1 responses activate both macrophages and B cells via IFN-γ.
- Th1 effector cells recognize antigens presented by macrophages.
- IFN-γ and CD40L, secreted by Th1 cells, activate macrophages, leading to the production of antimicrobial substances like nitric oxide and lysosomal enzymes.
- Activated macrophages also release cytokines promoting inflammation and assist B cells in class switching to produce opsonizing IgG antibodies, enhancing phagocytosis.
Th Cell/ Macrophage Cytokines
- IL-12, produced by macrophages, activates Th cells.
- TNF, IFN-γ, and IL-2 secreted by Th cells further activate macrophages and contribute to Th cell differentiation.
- IL-12 and IFN-γ promote the development of Th1 cells from naive T cells.
- Effector Th cells circulate and reach the site of infection.
Cytotoxic T Lymphocytes (CTLs)
- CTLs recognize target cells through TCR interaction with MHC class I-peptide complex.
- CTLs differentiate and proliferate in the presence of specific MHC class I/non-self-peptide complex, assisted by Th1 cells.
- Th1 cells secrete IL-2, promoting CTL differentiation and clonal expansion through cross-priming.
- Interferon production enhances MHC expression on target cells, increasing their susceptibility to killing by CTLs.
How CTLs Kill Target Cells?
- CTLs deliver toxic granules, inducing apoptosis in target cells.
- This process occurs in four phases:
- Attachment to target cells, mediated by TCR and CD8.
- Activation, involving cytoskeletal rearrangements for granule concentration.
- Exocytosis of perforin and granzymes.
- Detachment from the target cell.
- Target cell death is induced through:
- Perforin-mediated pore formation, allowing granzyme entry and activation of caspases.
- Cytokine-induced apoptosis (e.g., IFN-γ with TNF-α or TNF-β).
- FasL expressed by CTLs binding to Fas on target cells.
Cell-Mediated Immunity
- Eradicates infections by cell-associated microbes
- Targets facultative intracellular pathogens that live inside phagocytic cells
- Targets obligate intracellular pathogens that cannot replicate outside host cells
- Dictated by Th1 response, mediated by macrophages and CD8+ T cells
- Confers immunity to diseases caused by obligate intracellular bacteria, viruses, fungi and parasites.
- Plays a role in immunological surveillance and immunity against cancer
- Involved in pathogenesis of delayed hypersensitivity reactions and autoimmune diseases
T Cell Activation
- Requires three types of signals for full activation:
- Antigenic peptide presented on an MHC molecule
- Costimulatory signals
- Signals from specific cytokines
- If a cell does not receive a full set of signals, it will not divide and may become anergic
- Molecules like CD2 and LFA-1 contribute to T cell adhesion and enhance activation signals, but CD28 is essential for activation.
Th1 & Th2
- Th1 cells produce IFN-gamma, IL-2, TNF, activate macrophages, responsible for cell-mediated immunity, and phagocyte-dependent protective responses
- Th2 cells produce IL-4, IL-5, IL-10, IL-13, responsible for antibody production, eosinophil activation, inhibition of macrophage functions, and phagocyte-independent protective responses
- Th1 cells develop following infections by intracellular bacteria and viruses
- Th2 cells predominate in response to gastrointestinal nematode infestations
- The balance between Th1 and Th2 cells determines the outcome of many infections
Macrophage-Th Cell Interaction
- TCR of the naive Th cell binds to the MHC class II–peptide complex of the macrophage providing the first signal for activation
- This provides the antigenic specificity of the response
- Costimulatory molecules on the macrophage provide the second signal (B7 protein on the APC interacting with CD28 on the helper T cell)
- Cytokines secreted by the macrophage and activating T cells induce T cell proliferation and differentiation
Macrophages & B Cells
- The Th1 response activates macrophages and B cells via IFN-γ
- Effector cells of the Th1 subset recognize antigens of microbes ingested by macrophages
- T cells secrete IFN-γ and express CD40 ligand, which activates macrophages
- Classically activated macrophages produce substances that kill ingested microbes
- Macrophages produce cytokines that induce inflammation
- Th1 cells induce B cells to class switch to produce opsonizing IgG antibodies
Th Cell/Macrophage Cytokines
- IL-12 produced by the macrophage helps to activate Th cells
- T cells provide TNF-, IFN-γ, which promotes macrophage activation that also helps to activate Th cells
- IL-12 and IFN-γ also help to promote Th1 cell differentiation
- IL-2 stimulates the proliferation of clones of T cells specific to the antigen
- Effector cells leave the secondary lymphoid tissue and travel to the site of infection
Cytotoxic T Lymphocytes (CTLs)
- CTLs recognize target cells by interaction between their TCR and the MHC class I peptide complex
- CTLs differentiate and clone if assisted by signals from Th1 cells
- Th1 cells secrete IL-2, enhancing CTL differentiation and cloning via cross-priming
- Interferons increase the expression of MHC molecules making target cells more susceptible to killing
How CTLs Kill Target Cells
- CTLs deliver toxic granule contents that induce apoptosis
- CTLs bind to target cells via TCR and CD8
- Granule contents (perforin and granzymes) are released into the target cell
- Perforin creates pores in the target cell membrane allowing granzymes to activate caspases and the "death domain"
- Cytokines like IFN-γ, TNF-α, and TNF-β can induce apoptosis
- Activated CTLs express Fas ligand (FasL) that binds to Fas on the target cell
Cell-Mediated Immunity
- Cell-mediated immunity is a critical part of the adaptive immune system.
- It focuses on eliminating infections caused by intracellular microbes, including facultative and obligate intracellular pathogens.
- This arm of the immune system is defined by the Th1 response and primarily involves macrophages and CD8+ T cells.
- Cell-mediated immunity is essential for fighting off infections caused by several pathogens, including Mycobacterium tuberculosis, measles virus, Histoplasma capsulatum fungus, and Toxoplasma gondii parasites.
T-Cell Activation
- T cells require a combination of three signals for optimal activation:
- Antigenic peptide presented on an MHC molecule.
- Costimulatory signals, where CD28 on the T cell interacts with B7 protein on the antigen-presenting cell (APC).
- Signals from specific cytokines.
- Incomplete activation can lead to T cell anergy, where the cell can be deactivated.
TH1 & TH2
- Th1 cells produce cytokines like interferon-gamma, IL-2, and TNF, driving cell-mediated immunity and phagocyte-dependent responses.
- Th2 cells secrete IL-4, IL-5, IL-10, and IL-13, which promote antibody production, eosinophil activation, and inhibit certain macrophage functions.
- The balance between Th1 and Th2 cells determines the outcome of many infections, with Th1 dominance promoting protection against intracellular microbes, while Th2 dominance can suppress such defenses.
Macrophage-Th Cell Interaction
- The interaction between naive Th cells and macrophages involves recognition of the MHC class II-peptide complex, providing antigenic specificity.
- Macrophages deliver costimulatory signals, with the B7 protein on the macrophage binding to CD28 on the Th cell.
- Cytokines secreted by both cells lead to the proliferation and differentiation of the T cells into effector cells and memory cells.
- IL-2, produced by activated Th cells, is crucial for the proliferation of specific T cell clones.
Macrophages/B Cells & Th Cell/Macrophage Cytokines
- The Th1 response stimulates both macrophages and B cells through IFN-γ.
- Activated macrophages, under the influence of IFN-γ and CD40 ligand, produce nitric oxide and lysosomal enzymes to kill ingested microbes.
- Macrophages also release cytokines that promote inflammation.
- Th1 cells induce B cells to switch to producing opsonizing IgG antibodies, aiding in phagocytosis.
- IL-12, produced by macrophages, further activates Th cells, alongside IFN-γ and TNF.
- Together, IL-12 and IFN-γ promote the differentiation of naive T cells into Th1 cells.
Cytotoxic T Lymphocytes (CTLs)
- CTLs, also known as CD8+ T cells, recognize their targets by binding to MHC class I-peptide complexes on the surface of infected cells.
- CTLs can differentiate and clone in the presence of MHC class I - non-self peptide complexes, but this process is enhanced by signals from Th1 cells (cross-priming).
- Th1 cells release IL-2 to enhance CTL differentiation and cloning, while interferons increase MHC expression on target cells, making them more susceptible to killing.
How CTLs Kill Their Target Cells
- CTLs kill their targets by releasing toxic granules that induce apoptosis.
- The process involves four stages: attachment, activation, exocytosis, and detachment.
- The death of the target cell can occur through multiple mechanisms:
- Perforin from CTL granules creates pores in the target cell membrane, allowing granzymes to enter and activate caspases, triggering programmed cell death.
- Cytokines like IFN-γ, TNF-α, and TNF-β can induce apoptosis.
- Activated CTLs express Fas ligand (FasL), which binds to Fas on target cells, inducing apoptosis.
Cell-Mediated Immunity
- Cell-mediated immunity (CMI) is a specific type of acquired immune response that does not involve antibodies, but rather sensitized T cells.
- CMI battles facultative intracellular pathogens that live inside phagocytic cells and obligate intracellular pathogens that cannot replicate outside of host cells.
- CMI is dictated by the Th1 response and involves macrophages and CD8+ T cells.
- CMI is responsible for immunity against obligate intracellular bacteria, viruses, fungi, and parasites.
- CMI also plays a role in immunological surveillance against cancer and pathogenesis of delayed hypersensitivity reactions and autoimmune diseases.
T-Cell Activation
- T cells require three signals for full activation:
- Antigenic peptide presented on an MHC molecule.
- Costimulatory signals.
- Signals from specific cytokines.
- Without all signals, T cells may not divide and may become anergic.
- Molecules like CD2 and LFA-1 contribute to the adhesion and activation of T cells, but costimulation via CD28 is crucial for full activation.
Th1 & Th2 Cells
- Th1 cells produce interferon-gamma, IL-2, and TNF, which activate macrophages and are responsible for cell-mediated immunity.
- Th2 cells produce IL-4, IL-5, IL-10, and IL-13, which are responsible for antibody production, eosinophil activation, and inhibition of macrophage functions.
- Th1 cells develop mainly in response to intracellular bacteria and some viruses, while Th2 cells predominate in response to gastrointestinal nematodes.
- The balance between Th1 and Th2 cells determines the outcome of many infections.
Macrophage-Th Cell Interaction
- The binding of the TCR of a naive Th cell to the MHC class II–peptide complex on a macrophage provides the first signal for T cell activation.
- Costimulatory molecules on the macrophage provide the second signal, with B7 protein interacting with CD28 on the helper T cell being crucial.
- Cytokines secreted by the macrophage and the activating T cells lead to proliferation and differentiation of T cells into effector cells and memory cells.
- IL-2, produced by activated Th cells, stimulates the proliferation of clones of T cells specific to the antigen.
Macrophages & B Cells
- The Th1 response activates macrophages and B cells via IFN-γ.
- Effector Th1 cells recognize antigens of microbes ingested by macrophages.
- These T cells secrete IFN-γ and express CD40 ligand, which activate macrophages.
- Activated macrophages produce nitric oxide and lysosomal enzymes to kill ingested microbes.
- They also produce cytokines to induce inflammation.
- The Th1 response also induces B cells to produce opsonizing IgG antibodies, which assist macrophages with phagocytosis.
Th Cell/Macrophage Cytokines
- IL-12 produced by the macrophage activates Th cells.
- T cells produce TNF, IFN-γ, which promote macrophage activation and further activate Th cells.
- IL-12 and IFN-γ promote the differentiation of naive Th cells into Th1 cells.
- Effector cells leave secondary lymphoid tissue, circulates, and travel to sites of infection.
Cytotoxic T Lymphocytes (CTLs)
- CTLs recognize target cells through the interaction of their TCR with the MHC class I peptide complex on the target cell.
- If a cell is infected with an intracellular pathogen or expressing tumor-related antigens, a proportion of CD8+ T cells should be capable of binding their TCR to the MHC class I/non-self-peptide complex.
- CTLs can differentiate and clone themselves in the presence of the appropriate MHC class I non-self-peptide complex, but Th1 cell assistance enhances this process.
- Th1 cells secrete IL-2, which aids in the differentiation and cloning of CD8+ cells.
- Interferons increase the expression of MHC molecules, making target cells more susceptible to killing.
How CTLs Kill Target Cells
- CTLs kill target cells by delivering toxic granule contents to induce apoptosis.
- This occurs in four phases:
- Attachment to the target cell (mediated by TCR and CD8).
- Activation (cytoskeletal rearrangement to concentrate granules).
- Exocytosis of granule contents (perforin and granzymes).
- Detachment from the target cell.
- Target cell death can be mediated in different ways:
- Perforin creates pores in target cell membranes, allowing granzymes to enter and activate caspases, triggering the “death domain”.
- Cytokines like IFN-γ with TNF-α or TNF-β can induce apoptosis.
- Activated CTLs express FasL (Fas ligand), which binds to Fas on the target cell, triggering apoptosis.
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This quiz explores key concepts around cell-mediated immunity, focusing on mechanisms and players such as T cells and macrophages. It covers the activation signals T cells require and the roles of different T helper cells in the immune response. Test your knowledge on these critical topics in immunology.