Immunology Test 2 Study Guide PDF

Test 2 studyguides Chapter 9 1. Dendritic cells (DCs) play a crucial role in antigen capture and presentation. They are specialized antigen-presenting cells (APCs) that patrol tissues, capturing antigens through processes like phagocytosis, receptor-mediated endocytosis, or pinocytosis. Following an...

Test 2 studyguides Chapter 9 1. Dendritic cells (DCs) play a crucial role in antigen capture and presentation. They are specialized antigen-presenting cells (APCs) that patrol tissues, capturing antigens through processes like phagocytosis, receptor-mediated endocytosis, or pinocytosis. Following antigen capture, DCs undergo changes in their location, gene expression, and activation. They migrate to secondary lymphoid organs, such as lymph nodes, where they mature and upregulate the expression of major histocompatibility complex (MHC) molecules and co-stimulatory molecules. This maturation process is crucial for efficient antigen presentation to T cells. 2. Antigen-presenting cells (APCs) include dendritic cells (DCs), macrophages, and B cells. These cells function to present antigens to T cells, initiating immune responses. Class II MHC molecules on APCs present antigens to CD4+ helper T cells. Upon activation by APCs, helper T cells can stimulate B cells to produce antibodies, activate cytotoxic T cells, or enhance the activity of other immune cells, thereby coordinating the immune response. 3. False. While APCs are specialized in antigen presentation, other cells such as nucleated cells can also display antigens on their surface via MHC class I molecules. However, APCs are particularly efficient in antigen presentation due to their high expression of MHC molecules and co-stimulatory molecules, which are essential for T cell activation. 4. MHC molecules, also known as HLA molecules in humans, are responsible for displaying antigens to T cells. MHC class I molecules present endogenous antigens, typically viral or intracellular bacterial antigens, to CD8+ cytotoxic T cells. MHC class II molecules present exogenous antigens, typically from extracellular pathogens, to CD4+ helper T cells. The antigenic peptides are displayed on the surface of APCs. T cell receptors (TCRs) on T cells recognize and bind to these displayed antigens. 5. The MHC locus refers to the chromosomal region where genes encoding MHC molecules are located. These genes are highly polymorphic and essential for immune recognition and response. 6. The two main classes of MHC proteins are MHC class I and MHC class II. CD8+ cytotoxic T cells recognize antigens presented by MHC class I molecules, while CD4+ helper T cells recognize antigens presented by MHC class II molecules. 7. MHC proteins are polymorphic, meaning they exist in multiple allelic forms within a population. An MHC haplotype refers to the specific combination of MHC alleles inherited from one parent. MHC haplotypes are considered co-dominant because both maternal and paternal alleles are expressed, resulting in a diverse MHC repertoire in an individual. 8. HLA (human leukocyte antigen) is the human counterpart of MHC (major histocompatibility complex). HLA genes encode MHC molecules in humans. 9. MHC molecules are heterodimers consisting of two polypeptide chains: an α chain and a β chain in MHC class II, and an α chain and a β2-microglobulin in MHC class I. Each individual typically expresses multiple isoforms of MHC molecules due to the polymorphic nature of MHC genes. 10. Class I MHC molecules consist of a transmembrane α chain and a non-covalently associated β2-microglobulin, whereas class II MHC molecules consist of α and β chains. Both classes of MHC molecules have antigen-binding clefts formed by α helices, but the peptide binding grooves of class I molecules are closed at the ends, while those of class II molecules are open at both ends. To produce a stable MHC molecule, a peptide antigen must bind within the antigen-binding cleft. 11. The antigen binding cleft of MHC molecules is highly polymorphic and can accommodate a diverse range of peptide antigens, facilitating the recognition of a wide array of pathogens by the immune system. 12. True. Each MHC heterodimer can potentially bind many different peptide sequences, but it can only bind a single peptide at any given time, ensuring specificity in antigen presentation to T cells. Chapter 10 1. MHC-peptide interactions involve specific binding between peptides and the peptidebinding groove of MHC molecules. These interactions are predominantly mediated by non-covalent bonds, including hydrogen bonds, van der Waals forces, and hydrophobic interactions. Anchor amino acids within the peptide sequence play a crucial role in peptide binding to MHC molecules. These anchor residues interact with specific pockets within the peptide-binding groove of the MHC molecule, contributing to peptide binding specificity. 2. False. Not everyone displays the same peptides, and individuals may react differently to the same peptides. This is due to the polymorphic nature of MHC molecules, which results in different individuals expressing unique combinations of MHC alleles. Additionally, the diversity of the peptide repertoire generated from various pathogens and self-proteins further contributes to individual differences in peptide presentation and immune responses. 3. Antigen processing for display by class I MHC molecules involves the degradation of endogenous proteins in the cytosol by the proteasome. Peptide fragments generated from these proteins are transported into the endoplasmic reticulum (ER) by the transporter associated with antigen processing (TAP), where they bind to newly synthesized class I MHC molecules. In contrast, antigen processing for display by class II MHC molecules occurs through the endocytic pathway. Extracellular antigens are internalized via endocytosis, and in endosomes, they are proteolytically processed into peptide fragments, which then bind to class II MHC molecules in the endosomal compartment. 4. Immunodominant epitopes are specific regions within antigens that elicit a robust immune response, dominating the overall immune reaction against a particular pathogen or antigen. The immunodominance of an epitope is determined by factors such as its affinity for MHC molecules, its accessibility to T cells, and its ability to activate a large number of T cells. 5. The purpose of a T cell receptor (TCR) is to recognize specific peptide antigens presented by MHC molecules on the surface of APCs. TCRs play a central role in antigen recognition and T cell activation, thereby initiating adaptive immune responses against pathogens and foreign antigens. 6. False. An individual T cell typically expresses receptors (TCRs) that are specific for a single antigenic peptide presented by MHC molecules. Each T cell undergoes clonal selection and expansion to generate a population of T cells with identical TCRs, ensuring specificity in antigen recognition. 7. Co-receptors, such as CD4 and CD8, are molecules expressed on the surface of T cells that interact with MHC molecules to enhance TCR-mediated antigen recognition. Costimulators, on the other hand, are molecules expressed on APCs that provide additional signals to T cells to promote their activation and proliferation. CD4 and CD8 are termed co-receptors because they directly interact with MHC class II and MHC class I molecules, respectively, facilitating TCR-mediated antigen recognition. 8. Ligand binding to the TCR-MHC-peptide complex triggers intracellular signaling cascades within the T cell, leading to T cell activation. This activation process involves the recruitment of signaling molecules to the TCR complex, resulting in the phosphorylation of intracellular signaling proteins and the activation of transcription factors, ultimately leading to T cell proliferation, cytokine production, and effector functions. 9. A TCR is a heterodimeric protein composed of α and β chains in α/β T cells. Each TCR chain consists of a variable (V) region responsible for antigen recognition and a constant (C) region responsible for intracellular signaling. TCRs are similar to antibodies in that they exhibit antigen specificity and diversity generated through somatic recombination and V(D)J gene rearrangement. However, unlike antibodies, TCRs are membrane-bound receptors expressed on the surface of T cells and recognize peptide antigens in the context of MHC molecules. Chapter 11 1. The purpose of the TCR complex is to recognize specific peptide antigens presented by MHC molecules on the surface of antigen-presenting cells (APCs) and transmit signals to the interior of the T cell upon antigen recognition. The TCR complex consists of the TCR itself, which is composed of α and β chains, and associated signaling molecules such as CD3δ, CD3ε, CD3γ, and CD3ζ chains. Interactions between the TCR and MHC-peptide complex occur primarily through the variable regions of the TCR chains and the peptide antigen bound within the peptide-binding groove of the MHC molecule. Additionally, interactions between the CD3 signaling chains and the cytoplasmic tails of the TCR chains stabilize the TCR complex and facilitate signal transduction. 2. ITAM stands for Immunoreceptor Tyrosine-based Activation Motif. ITAMs are short amino acid sequences found in the cytoplasmic tails of signaling molecules associated with immune receptors, including CD3ζ, CD3γ, CD3δ, and CD3ε chains in the TCR complex. ITAMs are phosphorylated upon TCR engagement and play a crucial role in initiating intracellular signaling cascades upon T cell activation. 3. CD4 and CD8 are considered co-receptors because they enhance the binding of the TCR to the peptide-MHC complex, thereby facilitating T cell activation. CD4 recognizes MHC class II molecules, while CD8 recognizes MHC class I molecules. The human immunodeficiency virus (HIV) is capable of binding to CD4 as part of its entry mechanism into CD4+ T cells, which are primary targets for HIV infection. 4. The protein responsible for modifying ITAM-containing proteins in a T cell is a tyrosine kinase called Lck (lymphocyte-specific protein tyrosine kinase). Lck is brought into close proximity with ITAM-containing proteins upon TCR engagement through interactions between its SH2 domain and phosphorylated ITAM motifs. 5. An immune synapse is a specialized junction formed between a T cell and an APC during antigen recognition. The function of the TCR and the peptide-MHC complex within the synapse is to facilitate specific antigen recognition and signal transduction. LFA-1 (lymphocyte function-associated antigen-1) on the T cell surface interacts with ICAM-1 (intercellular adhesion molecule-1) on the APC surface, stabilizing the interaction between the two cells and promoting signal transduction. 6. Examples of immune synapse function include the polarization of signaling molecules towards the T cell-APC interface, the formation of a stable adhesive contact between the T cell and APC, and the secretion of cytokines and lytic granules by the T cell to mediate effector functions. 7. Signaling steps leading to T cell activation include TCR engagement with peptide-MHC complexes, phosphorylation of ITAM motifs within the CD3 signaling chains by Lck, recruitment and activation of ZAP-70 (zeta-chain-associated protein kinase 70), phosphorylation of downstream signaling molecules such as LAT (linker for activation of T cells) and PLC-γ1 (phospholipase C-gamma 1), calcium influx, activation of protein kinase C (PKC), and activation of transcription factors such as NFAT (nuclear factor of activated T cells) and AP-1 (activator protein 1). 8. When a TCR binds to its peptide/MHC ligand, the maturation/activation state of the T cell before the interaction could be naïve or primed/memory. Naïve T cells have not encountered their specific antigen before and are activated upon first antigen encounter, leading to clonal expansion and differentiation into effector T cells. Primed/memory T cells have encountered their specific antigen before and may require less stimulation to become activated, potentially leading to a more rapid and robust immune response upon antigen re-encounter. B cells use B cell receptors (BCRs) as their antigen recognition molecules. BCRs are membranebound immunoglobulins (Ig) that are structurally and functionally similar to antibodies secreted by plasma cells. BCRs and antibodies both recognize antigens through their antigen-binding domains, which are highly specific for particular antigenic epitopes. However, BCRs are anchored to the B cell membrane, whereas antibodies are secreted into the extracellular environment. The signaling steps and components involved in B cell receptor (BCR) signaling are similar to those involved in T cell receptor (TCR) signaling but with some differences. Both BCRs and TCRs initiate signaling cascades upon antigen binding, leading to B cell or T cell activation, respectively. However, BCR signaling involves the activation of Src family kinases, such as Lyn, which phosphorylate immunoreceptor tyrosine-based activation motifs (ITAMs) present within the cytoplasmic tails of Igα and Igβ subunits associated with the BCR complex. Subsequent recruitment and activation of spleen tyrosine kinase (Syk) and downstream signaling molecules, such as Btk (Bruton's tyrosine kinase), lead to calcium influx, activation of phospholipase Cgamma 2 (PLC-γ2), and activation of transcription factors such as NF-κB (nuclear factor kappalight-chain-enhancer of activated B cells) and NFAT (nuclear factor of activated T cells). Chapter 12 1. Key features associated with the maturation of both B and T lymphocytes include: o Commitment to lineage-specific differentiation pathways. o Sequential rearrangement of antigen receptor genes. o Expression of lineage-specific surface markers. o Positive and negative selection processes to ensure self-tolerance and functional capacity. o Migration to secondary lymphoid organs for further maturation and activation. 2. Stages of B and T lymphocyte maturation: o B Lymphocyte Maturation: § Early Progenitor Stage: Occurs in the bone marrow. Commitment to B cell lineage. § Pro-B Cell Stage: Heavy chain gene rearrangement (VDJ recombination). § Pre-B Cell Stage: Expression of pre-B cell receptor. Proliferation and heavy chain allelic exclusion. § Immature B Cell Stage: Light chain gene rearrangement (VJ recombination). Negative selection for self-reactivity. § Mature B Cell Stage: Exit from bone marrow to secondary lymphoid organs. o T Lymphocyte Maturation: § Early Thymocyte Stage: Occurs in the thymus. Commitment to T cell lineage. § Double-Negative (DN) Stage: Lack expression of CD4 and CD8 coreceptors. § Double-Positive (DP) Stage: Expression of both CD4 and CD8 coreceptors. Positive selection for MHC recognition. § Single-Positive (SP) Stage: Expression of either CD4 or CD8 co-receptor. Negative selection for self-reactivity. § Mature T Cell Stage: Exit from thymus to secondary lymphoid organs. 3. Commitment and proliferation depend on the process of antigen receptor gene rearrangement. 4. Features of antigen receptor gene rearrangement: o Occurs during B and T cell development. o Involves recombination of V (variable), D (diversity), and J (joining) gene segments. o Mediated by the RAG complex (recombination activating genes). o Generates combinatorial diversity in antigen receptor genes. 5. Antigen receptor gene rearrangement is necessary to generate the diverse repertoire of antigen receptors required for recognizing a wide range of foreign antigens. 6. True. The basics of gene rearrangement are the same for Ig heavy chains & light chains and TCR chains. Both involve the recombination of V, D, and J gene segments to generate diversity in antigen receptor genes. 7. Basic germline organization: o Ig Heavy Chain Locus: Contains V, D, and J gene segments. Expressed protein consists of variable (V), diversity (D), joining (J), and constant (C) domains. TCR Alpha Chain Locus: Contains V and J gene segments. Expressed protein consists of V, J, and constant (C) domains. o TCR Beta Chain Locus: Contains V, D, and J gene segments. Expressed protein consists of V, D, J, and constant (C) domains. 8. Combinatorial diversity refers to the generation of diversity through the random combination of V, D, and J gene segments during gene rearrangement. Junctional diversity refers to the additional diversity introduced by the imprecise joining of gene segments, leading to the insertion or deletion of nucleotides at the junctions between gene segments. o Chapter 13 1. At the two major checkpoints in lymphocyte maturation: o The first checkpoint (central tolerance) in the thymus asks whether T cells can recognize self-MHC molecules. Cells that can recognize self-MHC molecules survive, while those that cannot are eliminated through apoptosis. o The second checkpoint (peripheral tolerance) in secondary lymphoid organs asks whether mature lymphocytes recognize self-antigens presented by APCs. Cells that do not react strongly to self-antigens survive, while those that react strongly undergo apoptosis or become functionally inactive (anergic). 2. The primary reason for why a cell would be unable to pass either checkpoint is inappropriate recognition of self-antigens. This event, known as auto-reactivity, occurs when lymphocytes recognize and respond to self-antigens, leading to autoimmune reactions. While potentially dangerous, auto-reactivity is relatively rare due to the mechanisms of central and peripheral tolerance. 3. Positive selection ensures that T cells recognize self-MHC molecules, allowing them to interact with APCs. It occurs in the thymus and ensures the survival of T cells capable of recognizing self-MHC molecules. Negative selection eliminates T cells that strongly recognize self-antigens presented by self-MHC molecules, preventing the development of auto-reactive T cells. Both positive and negative selection contribute to the production of useful lymphocytes by ensuring self-tolerance and the ability to recognize foreign antigens. 4. Key events in B cell maturation: o Early Progenitor Stage: Commitment to B cell lineage in the bone marrow. o Pro-B Cell Stage: Heavy chain gene rearrangement (VDJ recombination). o Pre-B Cell Stage: Expression of pre-B cell receptor (pre-BCR). Proliferation and heavy chain allelic exclusion. o Immature B Cell Stage: Light chain gene rearrangement (VJ recombination). Negative selection for self-reactivity. o Mature B Cell Stage: Exit from bone marrow to secondary lymphoid organs. 5. The pre-B cell receptor consists of two Ig heavy chains (μ chains) and two surrogate light chains (VpreB and λ5). It requires the association of Igα and Igβ signaling chains for activation and signaling in the B cell. 6. In response to signaling from the pre-B cell receptor, the B cell undergoes proliferation and differentiation, leading to the generation of a large pool of B cells with identical antigen receptors. 7. Key events in T cell maturation: o Early Thymocyte Stage: Commitment to T cell lineage in the thymus. o Double-Negative (DN) Stage: Lack expression of CD4 and CD8 co-receptors. o Double-Positive (DP) Stage: Expression of both CD4 and CD8 co-receptors. Positive selection for MHC recognition. o Single-Positive (SP) Stage: Expression of either CD4 or CD8 co-receptor. Negative selection for self-reactivity. o Mature T Cell Stage: Exit from thymus to secondary lymphoid organs. 8. The pre-T cell receptor consists of an α chain and a surrogate β chain. It requires the association of CD3 signaling chains (ε, δ, γ) for activation and signaling in the T cell. 9. In response to signaling from the pre-T cell receptor, the T cell undergoes proliferation and differentiation, leading to the generation of a large pool of T cells with identical antigen receptors. Chapter 14 1. T cell development in the thymus proceeds through several key events and stages: o Early Thymocyte Stage: Commitment to T cell lineage. o Double-Negative (DN) Stage: Lack expression of CD4 and CD8 co-receptors. o Double-Positive (DP) Stage: Expression of both CD4 and CD8 co-receptors. o Single-Positive (SP) Stage: Expression of either CD4 or CD8 co-receptor. o Mature T Cell Stage: Exit from the thymus to secondary lymphoid organs. o Location: Thymus, specifically within the cortex and medulla regions. 2. Three types of effector T cells produced in the thymus: o Helper T cells (Th cells): Express CD4 co-receptor. o Cytotoxic T cells (CTLs): Express CD8 co-receptor. o Regulatory T cells (Tregs): May express either CD4 or CD8 co-receptor, but typically express CD4. 3. Maturation refers to the process of development and differentiation of cells to acquire specific functional characteristics, such as the ability to recognize antigens. Activation refers to the process by which mature cells respond to antigenic stimulation by proliferating and acquiring effector functions. 4. Key stages in the overall life history of a T cell: o Naïve T Cell: Resting state, ready to respond to antigen. o Activation: Antigen recognition by the T cell receptor (TCR) and co-stimulatory signals. o Proliferation: Clonal expansion of activated T cells. o Differentiation: Development into effector T cells (e.g., Th cells, CTLs) or memory T cells. o Migration: Movement of effector or memory T cells to sites of infection or inflammation. o Effector Function: Execution of immune responses against pathogens or aberrant cells. 5. Naïve T cells circulate throughout the body via the bloodstream and lymphatic vessels, patrolling secondary lymphoid organs such as lymph nodes and spleen. They encounter antigen presented by antigen-presenting cells (APCs), such as dendritic cells, within secondary lymphoid organs. The consequence of antigen encounter is T cell activation and differentiation into effector T cells. Effector T cells typically encounter antigen at sites of infection or inflammation, where they execute effector functions. 6. Sequence of events following antigen recognition: o Antigen Recognition: Occurs when the TCR binds to peptide-MHC complex on APCs. o Activation: Triggering of intracellular signaling pathways, leading to T cell activation and proliferation. o Cytokine Production: Release of cytokines such as IL-2 and IFN-γ, which regulate T cell responses. o Differentiation: Development into effector T cell subsets based on cytokine signaling. o Migration: Movement of activated T cells to sites of infection or inflammation. 7. Costimulators are cell surface proteins that provide additional signals to T cells, promoting their activation and proliferation. These proteins are expressed by APCs, such as dendritic cells and macrophages, and are upregulated upon activation. Costimulators include molecules such as CD80 (B7.1) and CD86 (B7.2), which interact with CD28 on T cells. 8. IL-2 plays a critical role in T cell activation by promoting T cell proliferation and differentiation into effector cells. IL-2 is primarily produced by activated T cells themselves in an autocrine manner, but it can also be produced by other immune cells such as dendritic cells and macrophages. 9. False. CTLs do require costimulation for full activation and optimal effector function. While they can recognize antigen through the TCR, costimulatory signals are necessary for robust T cell activation and proliferation. 10. CTLA-4 and PD-1 are inhibitory receptors expressed on activated T cells. CTLA-4 competes with CD28 for binding to CD80/CD86, resulting in inhibitory signals that dampen T cell activation. PD-1 interacts with its ligands PD-L1 and PD-L2, leading to the suppression of T cell activation and proliferation. 11. Consequence of non-functional CTLA-4 or PD-1: Excessive T cell activation and proliferation, potentially leading to autoimmunity or immunopathology. Consequence of permanently active CTLA-4 or PD-1: Suppression of T cell activation and proliferation, resulting in impaired immune responses against pathogens or tumors. 12. CTLA-4 and PD-1 can be targeted for therapeutic purposes to modulate T cell responses. Antibodies targeting CTLA-4 (e.g., ipilimumab) or PD-1/PD-L1 (e.g., pembrolizumab, nivolumab) are used in cancer immunotherapy to enhance anti-tumor immune responses by blocking inhibitory signals and restoring T cell activation. Chapter 15 1. CD4+ helper T cells play critical roles in: o Activation of B Cells: By providing help for antibody production. o o Activation of Cytotoxic T Cells: By promoting their development and activity. Regulation of Immune Responses: By modulating the activity of other immune cells and maintaining immune homeostasis. The characteristic activity that allows CD4+ helper T cells to perform these functions is the secretion of cytokines and the expression of cell surface molecules that regulate immune responses. 2. Steps in T helper (Th) cell immune response: o Antigen Presentation: Antigen-presenting cells (APCs) present antigens to CD4+ T cells. o Activation: CD4+ T cells recognize antigens and receive co-stimulatory signals, leading to activation. o Clonal Expansion: Activated CD4+ T cells undergo clonal expansion to generate a pool of effector cells. o Cytokine Production: Effector cells produce cytokines that mediate immune responses. o Differentiation: CD4+ T cells differentiate into specific subsets based on environmental cues. Delayed-type hypersensitivity (DTH) is a type of immune response characterized by the recruitment of inflammatory cells, especially macrophages, to the site of antigen exposure. It typically occurs 24 to 72 hours after exposure to certain antigens and is associated with Th1 cell responses. 3. The three major subsets of helper T cells: o Th1 Cells o Th2 Cells o Th17 Cells 4. Features of development for these three subsets: o True. Production of cytokines by one subset can influence the development and activity of other subsets, creating a dynamic interplay between Th1, Th2, and Th17 responses. 5. Defining cytokines and responses for each major subset: o Th1 Cells: Produce IFN-γ; respond to intracellular pathogens (viruses, bacteria); excessive response may contribute to autoimmune diseases. o Th2 Cells: Produce IL-4, IL-5, IL-13; respond to extracellular parasites; excessive response may lead to allergic reactions. o Th17 Cells: Produce IL-17; respond to extracellular bacteria and fungi; excessive response may contribute to autoimmune inflammation. 6. False. While "helper T cell," "T helper cell," "CD4+ T cell," and "Th cell" are often used interchangeably, "CD4+ T cell" specifically refers to the subset of T cells expressing the CD4 co-receptor. "Helper T cell" or "T helper cell" may refer more broadly to CD4+ T cells or any T cell that aids other immune cells. 7. Mechanisms of action for the three major helper T cell subsets: Th1 Cells: Activate macrophages, promote cytotoxic T cell responses, and enhance phagocyte activity against intracellular pathogens. o Th2 Cells: Stimulate B cells for antibody production (especially IgE), promote eosinophil activation, and enhance defense against extracellular parasites. o Th17 Cells: Recruit neutrophils, enhance epithelial barrier function, and contribute to defense against extracellular bacteria and fungi. o Chapter 16 1. Mechanisms by which each of the three major helper T cell subsets carries out their respective functions: o Th1 Cells: Activate macrophages through IFN-γ secretion, leading to increased phagocytosis and killing of intracellular pathogens. Stimulate differentiation of naïve CD4+ T cells into Th1 cells through IL-12 secretion. Promote cytotoxic T cell responses by enhancing antigen presentation and co-stimulation on APCs. o Th2 Cells: Stimulate B cell activation and antibody production, especially IgE, through secretion of IL-4, IL-5, and IL-13. Enhance eosinophil activation and recruitment to sites of parasitic infection, aiding in parasite clearance. o Th17 Cells: Recruit neutrophils to sites of infection through secretion of IL-17 and IL-22. Enhance epithelial barrier function and production of antimicrobial peptides. Contribute to autoimmune inflammation in certain contexts. 2. Common target cells for CTLs include virus-infected cells, cancer cells, and cells expressing foreign or aberrant antigens. Phagocytes are generally ineffective against such targets because they cannot directly eliminate intracellular pathogens or aberrant cells. Phagocytes primarily function to engulf and degrade extracellular pathogens or debris. 3. The activation phase of CD8+ T cell responses occurs in secondary lymphoid organs, such as lymph nodes, where naïve CD8+ T cells encounter antigen-presenting cells (APCs) presenting antigenic peptides on MHC class I molecules. The effector phase occurs at sites of infection or inflammation, where activated CD8+ T cells migrate to eliminate infected or abnormal cells. 4. Antigen cross-presentation is the process by which APCs, particularly dendritic cells, present extracellular antigens on MHC class I molecules to CD8+ T cells. This process is important for CTL generation because it allows CD8+ T cells to recognize and respond to antigens derived from infected or abnormal cells that do not express MHC class II molecules required for conventional CD4+ T cell activation. 5. Helper T cells contribute to the generation of CTLs through a process known as licensing of APCs. CD4+ helper T cells provide essential signals to APCs via CD40L (CD154) binding to CD40 on APCs. This interaction enhances APC function, including upregulation of co-stimulatory molecules and cytokine secretion, which promotes efficient priming and activation of CD8+ T cells by APCs. 6. T cell exhaustion is a state of dysfunction characterized by reduced effector function and sustained expression of inhibitory receptors on T cells, particularly CTLs, during chronic infections or cancer. This phenomenon affects the immune response by impairing the ability of T cells to eliminate infected or tumor cells effectively. Real-world examples include chronic viral infections like HIV and hepatitis C virus, as well as cancer, where T cell exhaustion limits the effectiveness of immunotherapy. 7. CTLs kill target cells through two main mechanisms: o Perforin-Granzyme Pathway: CTLs release perforin and granzymes, causing target cell membrane disruption and induction of apoptosis. o Fas-Fas Ligand Pathway: CTLs express Fas ligand (FasL), which binds to Fas receptors on target cells, leading to apoptosis. Normal cells expressing low levels of Fas receptor may not be affected by these activities, while target cells expressing high levels of Fas receptor are susceptible to CTL-mediated killing.