Cell-Mediated Immunity and T Cell Activation
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Questions and Answers

What is the primary mechanism by which Th cells direct immunity?

  • Secretion of antibodies
  • Directly killing pathogens
  • Secretion of cytokines (correct)
  • Producing phagocytes
  • Which type of pathogens does cell-mediated immunity specifically target?

  • All types of pathogens
  • Viruses only
  • Obligate intracellular pathogens (correct)
  • Extracellular bacteria
  • Which cells predominantly mediate cell-mediated immunity?

  • Plasma cells and dendritic cells
  • Macrophages and CD8+ T cells (correct)
  • B cells and NK cells
  • Neutrophils and Th2 cells
  • What is essential for T cell full activation?

    <p>A full set of signals including costimulatory signals</p> Signup and view all the answers

    What role does cytokine signaling play in T cell activation?

    <p>It provides specific signals necessary for full activation</p> Signup and view all the answers

    What is one of the critical functions of cell-mediated immunity?

    <p>Participating in the pathogenesis of autoimmune diseases</p> Signup and view all the answers

    Which type of T helper (Th) cells is primarily responsible for cell-mediated immunity?

    <p>Th1 cells</p> Signup and view all the answers

    What effect do molecules like CD2 and LFA-1 have during T cell activation?

    <p>They contribute to adhesion and enhance activation signals</p> Signup and view all the answers

    What is the primary cytokine secreted by Th2 cells that does NOT contribute to strong antibody production?

    <p>IL-12</p> Signup and view all the answers

    Which of the following cytokines is pivotal for Th cell proliferation and differentiation following TCR binding to the MHC class II-peptide complex?

    <p>IL-2</p> Signup and view all the answers

    Which type of immune response do Th2 cells predominantly engage in?

    <p>Response to gastrointestinal nematodes</p> Signup and view all the answers

    What is the role of CD40 ligand expressed by effector Th1 cells in the immune response?

    <p>Activates macrophages in conjunction with IFN-γ</p> Signup and view all the answers

    Which of the following statements correctly describes the Th1 and Th2 cell functions?

    <p>Th1 cells promote defense against intracellular microbes and Th2 cells suppress it.</p> Signup and view all the answers

    Which signal is considered the most important costimulatory signal for T cell activation during macrophage-Th cell interaction?

    <p>B7 protein interaction with CD28</p> Signup and view all the answers

    How do activated macrophages assist with B cell function during the immune response?

    <p>By inducing B cells to class switch to produce opsonizing IgG antibodies</p> Signup and view all the answers

    What is the main effect of IL-12 produced by macrophages on Th cells?

    <p>It activates Th cells to promote their proliferation.</p> Signup and view all the answers

    What is the primary role of IL-2 secreted by activated Th cells?

    <p>It stimulates the proliferation of T cell clones specific to an antigen.</p> Signup and view all the answers

    Which phase of CTL action involves the rearrangement of the cytoskeleton?

    <p>Activation</p> Signup and view all the answers

    What is the effect of perforin released from CTLs?

    <p>Creates pores in the target cell membrane.</p> Signup and view all the answers

    Which cytokine is primarily secreted by Th1 cells to assist in the differentiation of CD8+ T cells?

    <p>IL-2</p> Signup and view all the answers

    What role do interferons play in the context of CTL activity?

    <p>They enhance the expression of MHC molecules.</p> Signup and view all the answers

    Which interaction is necessary for the effective differentiation of CTLs?

    <p>Signals from Th1 cells.</p> Signup and view all the answers

    How do cytokines such as IFN-γ contribute to CTL function?

    <p>By upregulating the expression of MHC class I molecules.</p> Signup and view all the answers

    What mechanism do activated CTLs use for inducing apoptosis in target cells?

    <p>Expression of Fas ligand that binds Fas on target cells.</p> Signup and view all the answers

    Cell-mediated immunity primarily relies on antibodies produced by B cells.

    <p>False</p> Signup and view all the answers

    Obligate intracellular pathogens can replicate outside of host cells.

    <p>False</p> Signup and view all the answers

    Macrophages are crucial for the elimination of facultative intracellular pathogens.

    <p>True</p> Signup and view all the answers

    Th1 cells produce cytokines that primarily strengthen antibody production and suppress macrophage function.

    <p>False</p> Signup and view all the answers

    Three signals are required for full T cell activation, including costimulatory signals.

    <p>True</p> Signup and view all the answers

    Th2 cells are associated with strong immune responses against intracellular pathogens.

    <p>False</p> Signup and view all the answers

    Th2 cells are primarily responsible for cell-mediated immunity.

    <p>False</p> Signup and view all the answers

    The binding of the TCR of Th cells to MHC class II–peptide complexes provides the second signal necessary for T cell activation.

    <p>False</p> Signup and view all the answers

    Cytokines secreted by Th cells enhance the immune system's ability to respond to pathogens.

    <p>True</p> Signup and view all the answers

    Classically activated macrophages produce substances like nitric oxide which are crucial for the destruction of phagocytosed microbes.

    <p>True</p> Signup and view all the answers

    Macrophages need IL-2 to directly activate T cells during the immune response.

    <p>False</p> Signup and view all the answers

    Costimulation via CD28 is a secondary signal that is not really important for T cell activation.

    <p>False</p> Signup and view all the answers

    Interferon-gamma and interleukin-2 are produced by Th1 cells.

    <p>True</p> Signup and view all the answers

    B cells can be induced to produce IgG antibodies through Th2 cell activation.

    <p>True</p> Signup and view all the answers

    The balance between Th1 and Th2 cell activation does not influence the outcome of infections.

    <p>False</p> Signup and view all the answers

    The most important costimulatory signal for T cell activation is the interaction between B7 protein and CD28 protein.

    <p>True</p> Signup and view all the answers

    Activated CTLs kill target cells exclusively by delivering granzymes without perforin involvement.

    <p>False</p> Signup and view all the answers

    The presence of Th1 cells enhances the differentiation and cloning of CTLs.

    <p>True</p> Signup and view all the answers

    Fas ligand (FasL) binding to Fas on target cells is involved in a mechanism independent of cytokines.

    <p>True</p> Signup and view all the answers

    Cross priming does not facilitate CTL activation and differentiation.

    <p>False</p> Signup and view all the answers

    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.

    <p>True</p> Signup and view all the answers

    CTLs require physical attachment to their target cells before the exocytosis of toxic granule contents.

    <p>True</p> Signup and view all the answers

    Cytokines such as TNF-α and IFN-γ solely act through MHC class II to mediate CTL function.

    <p>False</p> Signup and view all the answers

    Granules in CTLs contain perforin and cytokines, which together contribute to the death of target cells.

    <p>False</p> Signup and view all the answers

    What role does IL-2 play in T cell function following Th cell activation?

    <p>IL-2 stimulates the proliferation of T cell clones specific to the antigen.</p> Signup and view all the answers

    Describe the four phases of how CTLs kill their target cells.

    <p>The four phases are attachment to the target cell, activation, exocytosis of granule contents, and detachment from the target cell.</p> Signup and view all the answers

    How do CTLs enhance their differentiation and cloning in the presence of Th1 cells?

    <p>Th1 cells secrete IL-2, which enhances the differentiation and cloning of CD8+ T cells.</p> Signup and view all the answers

    What are the two distinct mechanisms through which CTLs can induce apoptosis in target cells?

    <p>CTLs can use perforin to create pores for granzymes or through cytokines like IFN-γ and TNF-α.</p> Signup and view all the answers

    What influence does the expression of Fas ligand (FasL) have on target cells?

    <p>FasL binding to Fas on target cells can induce apoptosis independently of cytokines.</p> Signup and view all the answers

    Explain the significance of cross presentation in CTL activation.

    <p>Cross presentation allows for the effective activation and differentiation of CTLs by presenting antigens on MHC class I molecules.</p> Signup and view all the answers

    What is the effect of interferons produced during CTL activity?

    <p>Interferons increase the expression of MHC molecules on target cells, enhancing their susceptibility to CTL killing.</p> Signup and view all the answers

    What is the primary purpose of the TCR's interaction with the MHC class I peptide complex?

    <p>The TCR interaction allows CTLs to recognize and bind to infected or abnormal target cells.</p> Signup and view all the answers

    What cytokines are primarily produced by Th2 cells, and what immune responses do they facilitate?

    <p>Th2 cells primarily produce IL-4, IL-5, IL-10, and IL-13, facilitating strong antibody production and eosinophil activation.</p> Signup and view all the answers

    Describe the interaction necessary for T cell activation during macrophage-Th cell interactions.

    <p>The TCR of Th cells binds to the MHC class II-peptide complex on macrophages, providing the first signal, while costimulatory molecules like B7 interact with CD28 on T cells for the second signal.</p> Signup and view all the answers

    How do IFN-γ and CD40 ligand from Th1 cells activate macrophages?

    <p>IFN-γ activates macrophages directly, while CD40 ligand enhances their activation by promoting antigen presentation and cytokine production.</p> Signup and view all the answers

    What role does IL-2 play in the proliferation of T cells after activation?

    <p>IL-2 is a crucial cytokine secreted by activated Th cells that stimulates the proliferation of T cell clones specific to the antigen.</p> Signup and view all the answers

    Explain how the balance between Th1 and Th2 cells influences infection outcomes.

    <p>The balance between Th1 and Th2 cell activation determines the immune response direction, affecting the body's ability to combat intracellular microbes versus helminth infections.</p> Signup and view all the answers

    What substances do classically activated macrophages produce, and what is their significance?

    <p>Classically activated macrophages produce nitric oxide and lysosomal enzymes, which are crucial for killing ingested microbes.</p> Signup and view all the answers

    In what way does IL-12 produced by macrophages affect Th cell activation?

    <p>IL-12 stimulates the activation and differentiation of Th cells, promoting a stronger immune response.</p> Signup and view all the answers

    What is the importance of costimulatory signals during T cell activation?

    <p>Costimulatory signals, like the interaction between B7 protein on APCs and CD28 on T cells, are critical for preventing T cell anergy and ensuring a robust immune response.</p> Signup and view all the answers

    What immunological role do Th1 cells play in combating obligate intracellular pathogens?

    <p>Th1 cells produce cytokines such as interferon-gamma that activate macrophages, facilitating the destruction of obligate intracellular pathogens.</p> Signup and view all the answers

    Describe the importance of costimulatory signals in T-cell activation.

    <p>Costimulatory signals are essential for T-cell activation, as they ensure that the T-cell receives the necessary second signal to divide and function effectively.</p> Signup and view all the answers

    How do cytokines influence the role of Th cells in the immune response?

    <p>Cytokines secreted by Th cells direct the immune response by influencing the activation and function of various immune cells, including macrophages and B cells.</p> Signup and view all the answers

    What mechanism do CD8+ T cells use to induce apoptosis in infected target cells?

    <p>CD8+ T cells induce apoptosis primarily through the release of perforin and granzymes, which create pores in the target cell membrane and trigger cell death.</p> Signup and view all the answers

    Explain the significance of the Th1 and Th2 cytokine balance in immune responses.

    <p>The balance between Th1 and Th2 cytokines is crucial in determining the outcome of immune responses, influencing whether the body effectively targets intracellular or extracellular pathogens.</p> Signup and view all the answers

    What role do macrophages play in the pathogenesis of delayed hypersensitivity reactions?

    <p>Macrophages are key players in delayed hypersensitivity reactions as they are involved in antigen presentation and the activation of T cells, leading to prolonged immune responses.</p> Signup and view all the answers

    How does the absence of signals from specific cytokines affect T cell activation?

    <p>Without signals from specific cytokines, T cells fail to undergo full activation, which is necessary for proliferation and robust immune responses.</p> Signup and view all the answers

    In what way do NK cells contribute to cell-mediated immunity?

    <p>Natural Killer (NK) cells enhance cell-mediated immunity by being activated via cytokines released by Th cells, which helps them target and kill infected or cancerous cells.</p> Signup and view all the answers

    Type 2 Th (Th2) cells produce IL-4, IL-5, IL-10, and IL-13, which are responsible for strong ______ production.

    <p>antibody</p> Signup and view all the answers

    Th1 cells mainly develop following infections by intracellular ______ and some viruses.

    <p>bacteria</p> Signup and view all the answers

    The most important costimulatory signal is the interaction between B7 protein on the APC and ______ protein on the helper T cell.

    <p>CD28</p> Signup and view all the answers

    IL-2 secreted by activated Th cells is the most important factor for T cells that stimulates the ______ of clones of T cells.

    <p>proliferation</p> Signup and view all the answers

    Classically activated macrophages produce substances, including ______ oxide, that kill ingested microbes.

    <p>nitric</p> Signup and view all the answers

    The ______ response activates both macrophages and B cells via the cytokine IFN-γ.

    <p>Th1</p> Signup and view all the answers

    The production of IL-12 by the macrophage helps to activate the ______ cells.

    <p>Th</p> Signup and view all the answers

    Macrophages produce cytokines that induce ______, which is essential for the inflammatory response.

    <p>inflammation</p> Signup and view all the answers

    Cell-mediated immunity primarily combats ______ pathogens.

    <p>intracellular</p> Signup and view all the answers

    The primary cells involved in cell-mediated immunity are ______ and CD8+ T cells.

    <p>macrophages</p> Signup and view all the answers

    T cells need ______ signals for complete activation.

    <p>three</p> Signup and view all the answers

    Th1 cells primarily produce ______-gamma, which activates macrophages.

    <p>interferon</p> Signup and view all the answers

    If a T cell does not receive a complete set of signals, it may become ______.

    <p>anergic</p> Signup and view all the answers

    Cytokines are secreted by Th cells to direct ______ responses in the immune system.

    <p>immune</p> Signup and view all the answers

    Macrophages help in immunological surveillance and immunity against ______.

    <p>cancer</p> Signup and view all the answers

    Costimulation transduced via ______ is essential for T cell activation.

    <p>CD28</p> Signup and view all the answers

    IL-12 and IFN-γ promote the differentiation of the naïve Th cell into a ______ cell.

    <p>Th1</p> Signup and view all the answers

    The most important factor for T cells that stimulates the proliferation of clones of T cells specific to that antigen is ______.

    <p>IL-2</p> Signup and view all the answers

    CTLs recognize the cell they will ultimately kill by the interaction between their TCR and the ______ class I peptide complex.

    <p>MHC</p> Signup and view all the answers

    During the CTL killing process, the phase that involves rearrangement of the cytoskeleton is called ______.

    <p>Activation</p> Signup and view all the answers

    Perforin creates ______ in the membrane of the target cell, allowing granzymes to enter.

    <p>pores</p> Signup and view all the answers

    Cytokines such as IFN-γ can induce ______ in target cells.

    <p>apoptosis</p> Signup and view all the answers

    Activated CTLs express Fas ligand (FasL), which binds to ______ on the target cell.

    <p>Fas</p> Signup and view all the answers

    The process of CTLs killing target cells happens in ______ phases.

    <p>four</p> Signup and view all the answers

    Match the following components with their roles in CTL action:

    <p>Perforin = Creates pores in target cell membranes Granzymes = Induces apoptosis via caspase activation Fas ligand (FasL) = Binds to Fas on target cells to induce death IFN-γ = Increases MHC molecule expression on target cells</p> Signup and view all the answers

    Match the roles of different cytokines in T cell function:

    <p>IL-2 = Stimulates the proliferation of T cell clones IL-12 = Promotes differentiation of naïve Th cells to Th1 TNF-α = Can induce apoptosis in target cells IL-4 = Enhances B cell responses (not in Th1 function)</p> Signup and view all the answers

    Match the phases of CTL action to their descriptions:

    <p>Attachment = Binding mediated by TCR and CD8 Activation = Cytoskeletal rearrangement occurs Exocytosis = Release of toxic granules Detachment = Separation from target cell after killing</p> Signup and view all the answers

    Match the types of T cells with their key characteristics:

    <p>Th1 cells = Secrete IL-2 to support CTLs CD8+ T cells = Kill infected or transformed cells Naïve Th cells = Differentiated into Th1 or Th2 cells Activated CTLs = Can differentiate in response to MHC I</p> Signup and view all the answers

    Match the terms related to CTL and Th1 interactions:

    <p>Cross priming = Enhances CTL differentiation Costimulation = Necessary for full T cell activation MHC class I = Presents non-self peptides to CTLs Cytokines = Provide signals to aid T cell function</p> Signup and view all the answers

    Match the mechanisms by which CTLs induce target cell death:

    <p>Perforin = Forms channels in the target cell Cytokine signaling = Can activate apoptotic pathways Granzyme entry = Activates caspases to trigger apoptosis Fas-FasL interaction = Directly induces apoptotic processes</p> Signup and view all the answers

    Match the following CTL processes with their descriptions:

    <p>Cytoskeletal rearrangement = Prepares CTLs for granule delivery TCR binding = Specific recognition of target cells Granule content release = Initiates target cell apoptosis Increased MHC expression = Enhances target cell recognition</p> Signup and view all the answers

    Match the following types of immune responses with the T cells primarily involved:

    <p>Cell-mediated immunity = Primarily involves CD8+ T cells Humoral immunity = Involves Th2 cells and B cells Tumor immunity = Involves recognition by CTLs Infection control = Requires Th1 cell signaling</p> Signup and view all the answers

    Match the following types of pathogens with their descriptions:

    <p>Facultative intracellular pathogens = Can live inside phagocytic cells but are not obligate Obligate intracellular pathogens = Cannot replicate outside of host cells Mycobacterium tuberculosis = Causes diseases that require cell-mediated immunity Histoplasma capsulatum = Fungal pathogen requiring Th1 response</p> Signup and view all the answers

    Match the following components of T cell activation with their functions:

    <p>Antigenic peptide = Presented on MHC molecule to activate T cells Costimulatory signals = Essential for full T cell activation CD2 and LFA-1 = Enhance adhesion between T cells and antigen presenting cells Cytokines = Provide necessary signals for T cell proliferation</p> Signup and view all the answers

    Match the following types of T helper cells with their primary cytokines:

    <p>Th1 cells = Interferon-gamma and IL-2 Th2 cells = Cytokines promoting antibody production TNF (Tumor Necrosis Factor) = Activates macrophages and promotes inflammation IL-12 = Stimulates Th1 cell differentiation</p> Signup and view all the answers

    Match the following functions of cell-mediated immunity with their descriptions:

    <p>Protection against viruses = Involves activation of CD8+ T cells Immunological surveillance = Detects and fights cancerous cells Delayed hypersensitivity reactions = Pathogenesis of certain autoimmune issues Cytotoxic activity = Direct lysis of infected cells by CTLs</p> Signup and view all the answers

    Match the following cytokines with their roles in T cell responses:

    <p>Interferon-gamma = Activates macrophages to increase phagocytosis IL-2 = Promotes T cell proliferation and differentiation IL-4 = Enhances B cell activation and antibody production TNF-alpha = Mediates inflammation and recruits immune cells</p> Signup and view all the answers

    Match the following immune responses with their associated T cell types:

    <p>Th1 response = Cell-mediated immunity against intracellular pathogens Th2 response = Humoral immunity against extracellular pathogens Cytotoxic T lymphocytes (CTLs) = Target and kill infected cells Regulatory T cells = Help maintain immune tolerance and prevent autoimmunity</p> Signup and view all the answers

    Match the following T cell activation signals with their importance:

    <p>Antigen-MHC interaction = First signal needed for T cell activation Costimulatory signal via CD28 = Critical for full T cell response Cytokine signaling = Modulates the immune response Adhesion molecules = Facilitate T cell binding to antigen presenting cells</p> Signup and view all the answers

    Match the following immune functions with their associated cells:

    <p>Macrophages = Phagocytose pathogens and present antigens CD8+ T cells = Directly kill infected or cancerous cells Th1 cells = Activate macrophages through cytokine release Natural Killer (NK) cells = Mediated by Th cells signaling</p> Signup and view all the answers

    Match the cytokine with its primary function in the immune response:

    <p>IL-4 = Strong antibody production IFN-γ = Activation of macrophages IL-10 = Inhibition of macrophage functions IL-2 = Clonal expansion of T cells</p> Signup and view all the answers

    Match the type of T helper cell with its primary characteristic:

    <p>Th1 cells = Promote defense against intracellular pathogens Th2 cells = Support response against extracellular parasites Naive Th cells = Require signals from macrophages for activation Effector Th cells = Actively participate in immune responses</p> Signup and view all the answers

    Match the interaction involved in T cell activation with its corresponding role:

    <p>TCR-MHC class II interaction = Initial activation signal for T cells B7-CD28 interaction = Costimulatory signal for T cell activation Cytokine release from macrophages = Induces T cell proliferation CD40 ligand expression = Activates macrophages and B cells</p> Signup and view all the answers

    Match the type of immune response with its associated event:

    <p>Th1 response = Classically activated macrophages producing nitric oxide Th2 response = B cell class switching to IgG Macrophage activation by Th1 cells = Secretion of TNF-α and IFN-γ Th2 cytokines = Induction of eosinophil activation</p> Signup and view all the answers

    Match the macrophage-derived cytokine with its role in T cell activation:

    <p>IL-12 = Activates Th cells TNF-α = Enhances macrophage activation IFN-γ = Stimulates macrophage functionality IL-10 = Regulates and suppresses immune response</p> Signup and view all the answers

    Match the outcome of Th cell activity with the related immune component:

    <p>Effector T cell activity = Enhancement of B cell antibody production Macrophage activation = Increased phagocytosis of pathogens Cytokine secretion = Regulation of the immune response Memory T cell formation = Long-term immunity against specific antigens</p> Signup and view all the answers

    Match the Th cell function with its effect on macrophages:

    <p>Secretion of IFN-γ by Th1 cells = Activation of nitric oxide production Expression of CD40 ligand = Facilitation of macrophage-antigen interaction Cytokine release by macrophages = Induction of Th cell proliferation Th2 cytokines = Inhibition of macrophage activation</p> Signup and view all the answers

    Match the Th cell subset with the primary infection type they respond to:

    <p>Th1 cells = Intracellular bacteria and some viruses Th2 cells = Gastrointestinal nematodes Naive Th cells = Non-existent without activation signals Effector Th1 cells = Response to previously encountered pathogens</p> Signup and view all the answers

    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.

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