Adaptive Immunity Chapter 4 PDF

6/27/2024 Adaptive Immunity Chapter 4 Postamble READ the TEXTBOOK for the details to answer the UNIT OBJECTIVES. USE THE UNIT OBJECTIVES AS A STUDY GUIDE All test questions come from detailed material found in the TEXTBOOK (Not this PowerPoint) and relate back to the Unit Objectives...

6/27/2024 Adaptive Immunity Chapter 4 Postamble READ the TEXTBOOK for the details to answer the UNIT OBJECTIVES. USE THE UNIT OBJECTIVES AS A STUDY GUIDE All test questions come from detailed material found in the TEXTBOOK (Not this PowerPoint) and relate back to the Unit Objectives 1  6/27/2024 Characteristics of Adaptive Immunity Specificity for individual microbes and pathogens Memory of prior exposure to antigen Enhanced response to a pathogen upon repeated exposure Takes longer to become activated but is longer lasting than innate defenses Two main branches: Cell-mediated immunity (T cells are key component) Humoral immunity (B lymphocytes and antibodies) Immune Response 2  6/27/2024 T-Cell Differentiation: Double-Negative (DN) Stage Chemokines drive migration of T-cell precursors to the cortex of the thymus. Thymocytes at this stage lack both CD4 and CD8 surface markers. T-Cell Differentiation: Double-Negative (DN) Stage Thymocytes undergo rearrangement of genes coding for the beta chain of the T-cell receptor (TCR). Gene segments are selected and joined together to produce a unique antigen-binding site. CD3/TCR complex Alpha and beta chains that recognize antigen Six other chains in three pairs that assist with signaling when antigen binds to T cells 3  6/27/2024 T-Cell Differentiation: Double-Positive (DP) Stage Thymocytes express both CD4 and CD8. Positive selection occurs: Thymocytes survive if their TCR moderately recognizes MHC antigens on stromal cells in the cortex. T-Cell Differentiation: Single-Positive (SP) Stage Cells are positive for CD4 only or CD8 only. Negative selection: Thymocytes that bind to self-antigens on thymic stromal cells undergo apoptosis. Takes place in the corticomedullary region and medulla. 4  6/27/2024 T-Cell Differentiation: Mature T Cells Survivors of positive and negative selection exit the thymus and recirculate between the blood and lymphatics. CD4 T cells are T helper and T regulatory cells—they secrete cytokines and influence antibody production. CD8 T cells are cytotoxic T cells—they kill target cells. T-Cell Differentiation: Mature T Cells T helper (Th) cells Have CD4 receptor Recognize antigen and class II MHC protein Account for two-thirds of peripheral T cells 5  6/27/2024 T-Cell Differentiation: Mature T Cells Cytotoxic T cells Have the CD8 receptor Recognize antigen and class I MHC protein Account for one third of peripheral T cells B-Cell Differentiation Involves: Starts with a hematopoietic stem Development of mature immunocompetent B cells Occurs in bone marrow cell that develops into an early Activation of B cells by antigen lymphocyte progenitor Differentiation of activated B cells into antibody-producing plasma cells 6  6/27/2024 B-Cell Differentiation (continued) Antigen-independent phase A. Pro-B cells B. Pre-B cells C. Immature B cells D. Mature B cells B-Cell Differentiation: Pro-B Cells Rearrangement of genes that code for heavy and light chains of antibody molecules occurs. This creates variable region with specificity for a particular antigen in each cell. The cells must successfully rearrange one set of heavy-chain genes to become pre-B cells. 7  6/27/2024 B-Cell Differentiation: Pre-B Cells Heavy μ chains of IgM class accumulate in cytoplasm Combine with short Ig-α and Ig-β chains to form a pre-B cell receptor (pre-BCR) on the B- cell surface B-Cell Differentiation: Immature B Cells Pre-BCR is replaced with a functional BCR containing two light chains and two heavy chains of the IgM class. BCR has a variable region that determines specificity for the antigen and serves as an antigen receptor. B cells that have receptors for self-antigens are deleted in the bone marrow. Other surface proteins include: CD21 (promotes contact between B cells and Ag) CD40 Class II MHC molecules Needed for B cell and T cell interaction 8  6/27/2024 B-Cell Differentiation: Mature B Cells Immature B cells that do not react with self- antigens and display the appropriate surface markers migrate to the spleen for further development. Marginal B cells Remain in spleen Respond quickly to bloodborne pathogens Follicular B cells Migrate to lymph nodes and other secondary organs Recirculate B-Cell Differentiation: Mature B Cells (continued_2) Exhibit cell surface IgM and IgD Surface immunoglobulins provide activating signal to B cells when contact with antigen occurs. When stimulated, enter the antigen- dependent phase, forming: Memory cells Antibody-secreting plasma cells 9  6/27/2024 B-Cell Differentiation: Plasma Cells Activated B cells Found in bone marrow and peripheral lymphoid organs Produce antibodies Abundant cytoplasmic Ig but little or no surface Ig Have CD138 on cell surface Role of T Cells in Adaptive Immune Response T cells circulate throughout the bloodstream, T cells interact lymph nodes, and APCs are Cytokines drive with APCs to secondary activated during differentiation of initiate adaptive lymphoid tissue, innate immune T cells into immune looking for APCs response. subsets. response. displaying specific antigen fragments complexed with MHC. 10  6/27/2024 Th Subsets and Tregs (CD4+ T cells) T Helper Cell Subsets Produce IFN-g, IL-2, TNF-β Activate Tc and macrophages to fight intracellular pathogens in cell-mediated immunity Th1 cells: Produce interleukins 4, 5, 6, 9, 10, 13 Help B cells produce antibodies Th2 cells: Promote clearance of extracellular parasites and have a role in allergy Produce IL-17 and IL-22 Recruit granulocytes to fight bacterial infections Th17 May be associated with pathology in some diseases 11  6/27/2024 Action of Th Cells Exposure to antigen presented by macrophages causes production of CD25 receptors for interleukin- 2 (IL-2). IL-2 causes sensitized CD4+ T cells to secrete cytokines, resulting in CD4+ effector cells that have various functions. Some CD4+ cells secrete interleukins that recruit macrophages, whereas others activate CD8+ T cells to increase cytotoxicity against virally infected cells. Activated Th cells also enhance antibody production by B cells. Cytotoxic T (Tc) Cells Positive for CD8 Bind to and destroy cells infected with intracellular parasites and viruses Release cytotoxic granules containing perforin and granzymes Ligation of death receptors 12  6/27/2024 Action of Tc Cells T cell recognizes foreign antigen along with class I MHC. When binding occurs, granules move toward the point of contact with the target cell. Granules fuse with the membrane and release perforin. Perforin inserts itself into the target cell membrane and polymerizes to form a pore. Contents of the granules are released, triggering apoptosis of the target cell. T Regulatory (Treg) Cells Have CD4 and CD25 Suppress the immune response to self-antigens and harmless antigens Secrete inhibitory cytokines to inhibit proliferation of other T-cell populations 13  6/27/2024 The Role of B Cells in the Adaptive Immune Response T cell-dependent antigens 1. Bind to immunoglobulin receptors on B cells. The antigen is processed and delivered to CD4+ T cells. 2. The Th cell binds and delivers further activating signals 3. Cytokines are released from the T cell, which enhance B- cell transformation to plasma cells. Can switch from production of IgM to another antibody class (e.g., IgG) Affinity of BCR increases during the immune response. Memory cells are generated. The Role of B Cells in the Adaptive Immune Response (continued) T cell-independent antigens Bind to B cells through immunoglobulin receptors and trigger B-cell transformation directly. Several antigen receptors must be cross-linked in order to activate a B cell directly. Antigens can also be bound to B cells’ innate immune receptors such as TLRs Does not involve Th Polysaccharides with many repeating units cross-link BCRs. Only IgM is produced. Memory is not generated. 14  6/27/2024 Laboratory Identification of Lymphocytes Malignancies Helps Immunodeficiency diseases diagnose: AIDS Uses cell flow Segregates lymphocytes into subsets cytometry Uses monoclonal antibodies Summary Adaptive immunity is characterized by: Specificity for antigen Memory — ability to remember a prior exposure to an antigen, and an increased immune response upon re-exposure to the same antigen. The two arms of the adaptive immune response are: Cell-mediated immunity, carried out by T cells Humoral immunity, involving antibody production by B cells and plasma cells 15  6/27/2024 Summary (continued_2) T cells mature in the thymus and proceed through the following developmental stages: DN, DP, SP, and mature T cells. Helper T cells and regulatory T cells are positive for CD4. Cytotoxic T cells are positive for CD8. They destroy target cells by releasing perforins and granzymes. CD3/TCR is the T-cell receptor for antigen. The alpha and beta chains have a variable region that binds to a specific antigen. T cells acquire their antigen specificity through specific gene rearrangements while they are maturing in the thymus. T cells whose receptors are specific for self-antigens are deleted in the thymus by apoptosis. Summary (continued_3) B cells mature in bone marrow during the antigen-independent stage and in the secondary lymphoid organs during the antigen-dependent phase. The phases of B-cell development are: pro-B, pre-B, immature B, mature B, and plasma cells. B-cell markers include CD19, class II MHC proteins, and surface immunoglobulins. Antigen specificity of the B-cell receptor is due to immunoglobulin gene rearrangements that occur as the B cell matures. Class II MHC proteins allow B cells to interact with T helper cells in the production of antibodies. 16  6/27/2024 Summary (continued_4) When contact with a T-dependent antigen occurs, B cells differentiate into plasma cells that produce antibodies and memory cells that are able to respond more quickly the next time the same antigen is encountered. T-independent antigens have repeating identical units and stimulate B cells in the absence of T cell help. They induce production of IgM antibody only, and memory is not generated. Chapter Overview Characteristics of adaptive immunity T-cell differentiation B-cell differentiation Role of T cells in adaptive immune response Role of B cells in adaptive immune response 17