Immune system Haixu Tang School of Informatics Human lymphoid organs Lymphocytes are required for adaptive immune responses to foreign antigens Innate immune system helps activate the adaptive immune system The development and activation of T and B cells The clonal selection theory Primary and secondary antibody responses Cellular basis of immunological memory Induction of immunological tolerance B cell activation Innate and adaptive immune responses An antibody molecule Antibody-antigen interactions The hinge region of an antibody molecule A pentameric IgM molecule Antibody-activated phagocytosis There Are Five Classes of Heavy Chains IgM, which has heavy chains, is always the first class of antibody made by a developing B cell; After leaving the bone marrow, the B cell starts to produce cell- surface IgD molecules as well, with the same antigen-binding site as the IgM molecules. The major class of immunoglobulin in the blood is IgG, which is a four-chain monomer produced in large quantities during secondary immune responses; IgA is the principal class of antibody in secretions, including saliva, tears, milk, and respiratory and intestinal secretions; The tail region of IgE molecules, which are four-chain monomers, binds with unusually high affinity (Ka ~ 1010 liters/mole) to yet another class of Fc receptors; Antigen binding to antibody Constant and variable regions The gene of an antibody heavy chain 3D structure of antibody Antigen-binding sites of antibodies DNA is rearranged during B cell development The V-J joining process The human heavy-chain gene- segment pool The four main mechanisms of antibody diversification Antibody gene-pool selection in B cell development The two main classes of adaptive immune responses DNA rearrangement that occurs in class switch recombination T cell responses differ from B cell responses in two crucial ways T cells are activated by foreign antigen to proliferate and differentiate into effector cells only when the antigen is displayed on the surface of antigen-presenting cells in peripheral lymphoid organs. Whereas B cells recognize intact antigen, T cells recognize fragments of protein antigens that have been partly degraded inside the antigen- presenting cell. The peptide fragments are then carried to the surface of the presenting cell on special molecules called MHC proteins; The second difference is that, once activated, effector T cells act only at short range, either within a secondary lymphoid organ or after they have migrated into a site of infection. They interact directly with another cell in the body, which they either kill or signal in some way. Activated B cells, by contrast, secrete antibodies that can act far away. Two main classes of T cells Effector cytotoxic T cells directly kill cells that are infected with a virus or some other intracellular pathogen. Effector helper T cells, by contrast, help stimulate the responses of other cellsmainly macrophages, B cells, and cytotoxic T cells T cell receptor heterodimer Activation of a T cell Cytotoxic T cells kill their target cells Differentiation of nave helper T cells into either TH1 or TH2 effector helper cells Recognition by T cells of foreign peptides bound to MHC proteins Class I and class II MHC proteins Human MHC genes A peptide bound in the groove of a class I MHC protein A peptide bound in the groove of a class II MHC protein The interaction of a T cell receptor with a viral peptide bound to a class I MHC protein CD4 and CD8 co-receptors on the surface of T cells An effector cytotoxic T cell recognizes some aspect of the surface of the host target cell The processing of a viral protein for presentation to cytotoxic T cells The processing of an extracellular protein antigen for presentation to a helper T cell Positive and negative selection in the thymus The two signals that activate a helper T cell The signaling events initiated by the binding of peptide-MHC complexes to T cell receptors The stimulation of T cells by IL-2 in culture The activation of TH1 and TH2 cells Signaling events activated by the binding of antigen to B cell receptors (signal I) The influence of B cell co- receptors on the effectiveness of signal I Comparison of the signals required to activate a helper T cell and a B cell