Collaboration of B Cells and T Cells

Chapter 7 The third line of defense in the human body is adaptive immunity, which consists of lymphocytes and antibodies. Unlike innate immunity and inflammation, adaptive immunity is inducible and develops more slowly. It is highly specific to the infecting microbe and provides long-term protection through memory. The innate and adaptive immune systems are interactive and complementary, working together for complete protection against infectious disease. Bullet points Immune Response: Collaboration of B Cells and T Cells  First phase: Generation of clonal diversity  Occurs before birth and throughout life in specialized lymphoid organs (bone marrow for B cells, thymus for T cells)  B and T cells differentiate from lymphoid stem cells and can recognize almost any foreign antigen  Lymphocytes are released into circulation as immunocompetent cells Generation of Clonal Diversity vs Clonal Selection  Generation of Clonal Diversity: purpose is to produce a large number of T and B lymphocytes with maximum diversity of antigen receptors  Clonal Selection: purpose is to select, expand, and differentiate clones of T and B cells against specific antigen  Generation of Clonal Diversity primarily occurs in the fetus, while Clonal Selection primarily occurs after birth and throughout life  Central lymphoid organs (thymus, bone marrow) involved in Generation of Clonal Diversity, peripheral lymphoid organs (lymph nodes, spleen) involved in Clonal Selection Development of B Lymphocytes  Lymphocyte stem cells destined to become B cells circulate through the specialized regions of bone marrow  Hormones and cytokines induce proliferation and differentiation into B cells  B-cell receptor (BCR) is formed which consists of antibody bound to the cell surface and other molecules involved in intracellular signaling  BCR's role is to recognize an antigen and communicate that information to the cell's nucleus  Somatic recombination occurs during B-cell development in the primary lymphoid organs to generate receptors that can recognize and bind to any possible antigen  Clonal deletion or central tolerance occurs to eliminate autoreactive B cells that recognize the individual's own antigens  Remaining pool of immunocompetent B cells target foreign antigens and are tolerant to self-antigens Note: The remaining part of the text was not clear and could not be summarized. B-cell differentiation  B-cell differentiation is characterized by the development of surface molecules such as CD21 and CD40  CD21 is a complement receptor and CD40 is an adhesion molecule required for interactions with T cells  "CD" refers to cluster of differentiation, which are specific cell surface proteins assigned unique numbers T-cell development  T-cell proliferation and differentiation process is similar to B-cell development  The thymus is the primary lymphoid organ for T-cell development  Thymic hormones and the cytokine IL-7 influence T-cell development  T-cell receptors (TCRs) are gained against antigens encountered throughout life  Mature T cells with antigen-specific receptors establish residence in secondary lymphoid organs T-cell characteristics  T cells have T-cell receptors (TCRs) consisting of alpha (α) and beta (β) chains  Each T cell expresses only one type of TCR  T cells express CD3, a complex of signaling molecules  CD4 and CD8 are surface molecules expressed by differentiating T cells  CD4-positive T cells become Th cells, while CD8-positive T cells become T-cytotoxic (Tc) cells  Approximately 60% of immunocompetent T cells express CD4, and 40% express CD8 Clonal selection  Clonal selection is the processing of antigens for a specific immune response  Antigen-presenting cells (APCs) play a crucial role in antigen processing and presentation  APCs include dendritic cells, macrophages, and B cells  Interaction among APCs, T-helper cells (Th), and B/T cells leads to differentiation into active plasma cells or Tc effector cells  Activation of the immune system produces long-lasting protection against specific antigens Defects in cellular collaboration  Defects in cellular collaboration can lead to deficiencies in cell-mediated immunity, humoral immunity, or both  The specific defect determines the nature of the immune deficiency Processing and Presentation of Antigens  Antigens can be exogenous or endogenous  Exogenous antigens undergo phagocytosis and destruction by APCs  Endogenous antigens are generated by abnormal cells due to injury, infection, or mutation Major Histocompatibility Complex (MHC)  MHC molecules are glycoproteins found on the surface of human cells (except red blood cells)  There are two classes of MHC molecules: class I and class II  Class I molecules are found on all nucleated cells and have an alpha chain and a smaller chain called beta2microglobulin  Class II molecules are found only on APCs and have alpha and beta chains  MHC genes are highly polymorphic, resulting in unique MHC molecules for each individual Antigen Presentation  MHC class I molecules present endogenous antigens and are recognized by Tc cells  MHC class II molecules present exogenous antigens and are recognized by Th cells  APCs, which have both MHC class I and class II molecules, can present both types of antigens Antigen Processing and Presentation  Endogenous antigens are processed in the endoplasmic reticulum and presented by MHC class I molecules  Exogenous antigens are processed in phagolysosomes and presented by MHC class II molecules Antigen Processing and Presentation  Large exogenous and endogenous antigens are cut up into small antigenic fragments  MHC class I presents antigen to Tc cells  MHC class II presents antigen to Th cells  CD1 presents lipid antigens Cellular Interactions in the Immune Response  Intercellular collaborations lead to production of effector cells and memory cells  Three complementary intracellular signaling events are required: antigen-specific recognition, intercellular communication, and response to specific cytokines  Activation of Th cells requires TCR recognition, CD4 binding, and intracellular signaling  Intercellular communication involves adhesion molecules and co-stimulatory signals  Interleukin-1 (IL-1) provides an additional signal for Th cell activation Development of T-Cell Subsets  Antigen-presenting cells (APCs) influence differentiation of Th cells  Differentiation is initiated by antigen signal, costimulatory signals, and cytokine interactions  Th cells can differentiate into Th1, Th2, Th17, or Treg cells  IL-2 plays a crucial role in Th cell differentiation and proliferation