Interactions Between Th Cell Subsets

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 Th1 cell phenotype  IL-12 and interferon-gamma (IFN-y) favor differentiation into Th1 cells  Th1 cells produce cytokines that assist in the differentiation of T-cytotoxic (Tc) cells  Th1 cells contribute to cellular immunity Th2 cell phenotype  IL-4 favors differentiation into Th2 cells  Th2 cells produce cytokines that favor B-cell differentiation and humoral immunity Th17 cell phenotype  IL-6 and transforming growth factor-beta (TGF-B) facilitate differentiation into Th17 cells  Th17 cells produce cytokines that affect phagocytes and increase inflammation Treg cell phenotype  IL-2 and TGF-B induce differentiation into Treg cells  Treg cells produce immunosuppressive cytokines to prevent excessive immune responses Interactions between Th cell subsets  IFN-y inhibits the development of Th2 cells  IL-4 inhibits the development of Th1 cells  Th1 and Th2 cells may suppress each other, influencing the immune response IL-2 and Th cell maturation  IL-2 is secreted by Th cells to stimulate their own maturation and proliferation  Without IL-2, Th cells cannot efficiently mature into functional helper cells Th cell subset differentiation  Activated Th cells differentiate into Th1, Th2, Th17, or Treg cells depending on the cytokine environment  Th1 cells support Tc cell development (cell-mediated immunity)  Th2 cells support B cell development (humoral immunity)  Th17 cells activate macrophages Superantigens  Superantigens (SAGs) activate large populations of Th cells regardless of antigen specificity  SAGs induce excessive production of cytokines, causing systemic inflammatory reactions  Examples of SAGs include toxins produced by Staphylococcus aureus and Streptococcus pyogenes Superantigens  Superantigens bind directly to the T-cell receptor (TCR) and major histocompatibility complex (MHC) class II molecule  They activate sets of VB chains independently of the antigen specificity of the TCR T-cytotoxic lymphocytes  Tc cells recognize antigen presented by MHC class I molecules on the surface of antigen-presenting cells (APCs) and infected/cancerous cells  The Tc cell CD8 binds to the MHC class I molecule and activates intercellular signaling pathways  Cytokine signals, especially IL-2, produced by Th1 cells activate cytokine receptors on Tc cells B-cell clonal selection  B cells can react with soluble antigens through the B-cell receptor (BCR)  Antigen binding through the BCR and CD21 receptor activates B cells, leading to internalization, processing, and presentation of antigen fragments  B cells preferentially present processed antigen on their MHC class II molecules and activate Th cells  Intercellular communication with Th cells induces Th2 cell differentiation and the secretion of cytokines, including IL-4, which initiates B-cell proliferation and maturation into plasma cells T-cell independent antigens  Large bacterial products that can stimulate B-cell maturation and proliferation  Capable of cross-linking several B-cell receptors (BCRs)  Usually induce plasma cells to secrete only IgM Memory cells  Formed during the clonal selection process  Long-lived cells that remain inactive until subsequent exposure to the same antigen  Upon reexposure, memory cells rapidly become new plasma cells or effector T cells without cellular interactions Antibodies (Ig)  The terms antibody and immunoglobulin (Ig) are used interchangeably  When a B cell matures in response to antigen exposure, it becomes a plasma cell capable of producing antibodies  There are five classes of antibodies: IgG, IgA, IgM, IgE, and IgD  Classes characterized by differences in structure and function Specific classes of antibodies  IgG: Most abundant class, 80-85% of antibodies in blood, protective against infections, transported across the placenta during pregnancy to protect newborn  IgM: Largest antibody, first produced during initial response to antigens, often exists as a pentamer, synthesized early in neonatal life  IgA: Found in blood and bodily secretions, exists as secretory IgA, protects against degradation by enzymes in secretions  IgD: Functions as part of the BCR antigen receptor on the surface of early B cells  IgE: Normally present at low concentrations, mediates allergic responses B-cell maturation and class switch  Class switch is the process that results in the change in antibody production from one class to another (e.g., IgM to IgG)  It is a major component of B-cell maturation  Antibody diversification is essential for the immune system to produce protective humoral responses  Before exposure to antigens and Th2 cells, B cells produce IgM and IgD as cell membrane receptors Clonal selection and antibody production  B cells proliferate and develop into antibody-secreting plasma cells during clonal selection  B cells have the option of becoming a secretor of IgM or changing the class of antibody to IgG, IgA, or IgE  The antigenic specificity of the antibody remains unchanged  B cells may produce a population of plasma cells capable of producing different classes of antibodies against the same antigen  The type of antibody produced is under the control of Th cytokines Molecular structure of antibodies  An antibody molecule consists of four polypeptide chains: two light (L) chains and two heavy (H) chains  The Fab portion contains the recognition sites for antigens and confers specificity toward a specific antigen