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The Development and Function of Cells in the Immune Response “Helpful Secretions” Ag Ag B cell CD4 T cell makes antibodies that target Ag, such as bacteria becomes activated to help CD8 T cell becomes activated to kill Ag Ag Ag Ag Ag Ag APC Ag Ag Body Barrier Immune Locations • • • • Outside/Inside Lymph Nodes Spleen Thymus QuickTime™ and a GIF decompressor are needed to see this picture. The Antigen Presenting Cell (APCs) • Include macrophages, monocytes, dendritic cells, and B cells • Detection of Foreign Invasion (Innate Immune Function) • Collection Delivery of Antigen to “Immune Locations” • Processing of Antigen APC Ag – Cutting up antigen into little segments that are the right size to be presented and shuttling them to presenting molecules • Presentation of Antigen Via Special Cell Surface Molecules – Displaying peptide fragments of antigen on the cell surface Ag Ag MHC Class II • A molecule that is expressed only on “professional” APCs such as macrophages, dendritic cells, and B cells. – Known as HLA DR, DQ, or DP in human – Known as MHC I-A and I-E in mice – These genes are each designated by an allele marker, so I-Ad is a class II allele • The molecule contains a groove that allows it to bind processed peptides – Each allele has preferred lengths and sequences • Class II molecules “present” peptides from molecules that are taken up from outside the cell via processes such as phagocytosis (known as exogenous processing pathway) • Together the peptide and MHC form a shape (3-D structure) that may match (complement) the surface of a T cell receptor • MHC class II molecules also have a special area that binds CD4; hence CD4 T cells are “Class II restricted”. MHC Class I • A molecule that is expressed on all cells of the human body with few exceptions – HLA-A, B, C genes in human – K, D, and L genes in mice • The molecule contains a groove that allows it to bind processed peptides – Each allele has preferred lengths and sequences • Class I molecules “present” peptides from molecules that are made inside the cell (endogenous processing pathway). Viral particles, for example, are made internally. • Together the peptide and MHC form a shape (3-D structure) that may match (complement) the surface of a T cell receptor • MHC Class I molecules also have a special area to bind to CD8; hence CD8 T cells are “Class I restricted”. B Lymphocyte • Produced in the bone marrow where they undergo most of their maturation and selectio • Production of antibody when bound to its antigen • Interaction via Antigen with T Lymphocytes – Class Switching – T Cell Differentiation – Immune interactions are reciprocal, both cells are affected Ag B cell Effector Mechanisms 1: Antibody • • • • Neutralization Opsonization Complement Activation Antibody Dependent Cellular Cytotoxicity T Lymphocyte • Two Classes: CD4+ and CD8+ – CD4+: “Helper” T Cells – CD8+: Cytotoxic T Cells • Activation Results in Proliferation and Differentiation to Effector Cell Types • T cells also originate in the bone marrow but migrate to the thymus for their selection and development T cell Cell-Cell Interactions and Activation Requirements • Surface-Surface Antigen Presentation – MHC and T Cell Receptor • Costimulation – Cell surface proteins – Secreted Factors • Cytokines (a.k.a. interleukins) Ag T cell Ag APC Effector Mechanisms 2: Cell Mediated • Target Cell Lysis (Perforin/granzyme) • Induced Cell Death – Cytokines – Other Secreted Factors • Activation of Other Immune Cells (help) Genetic Rearrangement in Lymphocyte Development • Enormous diversity in the immune response— trillions of lymphocytes and possibly no two recognize the same structure and fewer than 100 recognize even the same organism • If each receptor were encoded by a separate gene, these genes might take up more space than our entire DNA • The solution is the Nobel winning work of Susumu Tonegawa…. Genetic Structure and recombination process for antibody A similar process is used for the T cell receptor. For each region labeled above (V-D-J), there are numerous gene segments (i.e., many V gene segments from which to choose). Tolerance: How? • 1 • 2 • 3 • 4