Adaptive immunity

• Formation of B and T lymphocytes

  1. Arise from a common bone marrow-derived precursor that becomes committed to the lymphocyte lineage

  2. B cell maturation proceeds in the bone marrow, whereas early T cell progenitors migrate to and complete their maturation in the thymus
• B cells


  • Carry membrane-bound antibody molecules as their antigen-specific receptors
• T cells


  • Carry customized receptor molecules that allow them to recognize and respond to specific targets
• T cell recognition of antigens


  Recognize an antigen only after it is processed and presented by an antigen-presenting cell, in combination with MHC molecules
• CD4 (+) T cell receptor


  • Looks for an antigen broken down by an antigen-presenting cell such as a dendritic cell, macrophage, or B cell, combined with class II MHC protein
• CD8 (+) T cell receptor


  • Recognizes an antigen fragment produced within the cell, combined with class I MHC protein found on all nucleated cells of the body
• Problem: Our genes are not sufficient to encode millions of receptors to recognize all antigens in the environment
• Solution: Antigen receptors are formed by somatic recombination of a limited number of inherited gene segments
• Immature T lymphocytes may recognize any peptide antigen displayed by any MHC molecule, but only useful T cells are specific for foreign peptides presented by self MHC molecules
• If T cells strongly recognize self proteins, autoimmunity develops
• Maturation of T lymphocytes

  The thymus is the major site of maturation where thymocytes develop and mature, expressing TCR and CD4 or CD8
• Positive selection in the thymus stimulates thymocytes with weak binding to self peptide-self MHC complexes to survive
• Negative selection in the thymus deletes thymocytes with strong binding to self peptide-self MHC complexes
• Mature T cells leaving the thymus recognize self MHC and do not recognize self antigenic peptides
• If T Cell Receptor binds to Class I MHC, CD4 disappears (SINGLE POSITIVE, CD8 (+) T cell)
• If T Cell Receptor binds to Class II MHC, CD8 disappears (SINGLE POSITIVE, CD4 (+) T cell)
• Activation of Helper T Cell


  After an antigen-presenting cell presents an antigen fragment combined with class II MHC protein, it activates a matching CD4 (+) helper T cell, leading to the release of interleukins (cytokines) for T cell maturation
• Helper T cells secrete cytokines, which are mediators of communication
• When a dendritic cell processes an antigen


  It presents the antigen fragment combined with class II MHC protein to a matching CD4(+) helper
• Activation of macrophage


  Binding of antigen fragment with class II MHC protein activates the macrophage to release interleukins (cytokines) that allow the T cell to mature
• Helper T cells secrete cytokines


  Mediators of communication between cells of the immune system to activate macrophages, help stimulate B lymphocytes to differentiate into antibody-secreting cells (plasma cells), and activate CD8(+) cytolytic T cells
• Activation of Cytolytic T Cell

  Cytolytic T cell recognizes endogenous antigens such as virus or tumor proteins displayed by class I MHC protein. It matures with the help of CD4(+) helper T cell and attacks and kills target cells by secreting cytotoxic granule enzymes (granzymes)
• Activation of B Cell

  B cell binds a matching antigen, engulfs and processes it, combines a fragment with class II MHC protein, and is transformed into an antibody-secreting plasma cell by T cell activation and release of lymphokines (interleukins)
• Naive T and B lymphocytes need two distinct extracellular signals


  1st signal is binding of antigen to antigen receptor for specificity of the immune response. 2nd signal is provided by costimulators like B-7 on APCs binding to CD28 on T cells, inducing anti-apoptotic proteins, cytokine production, and T cell proliferation and differentiation
• Short and Long Term Immunity


  Memory cells are formed upon activation of T and B cells for quick destruction of encountered antigens. Long-term immunity is stimulated by infection or vaccines, while short-term immunity can be transferred passively via antibody-containing serum
• TH1 Subset of T Cells


  Differentiation occurs in response to intracellular bacteria and parasites, secreting IL-2, IFN-g, LT, TNF to inhibit TH2 proliferation, activate macrophages, stimulate B cells, neutrophils, and inflammation
• TH2 Subset of T Cells

  Differentiation occurs in response to helminths and allergens, secreting IL-4, IL-10, IL-5 to antagonize IFN-g, suppress macrophage activation, stimulate IgE antibodies, inhibit IFN-g synthesis, and activate eosinophils for defense against helminthic infections
• Formation of B and T lymphocytes

  1. Arise from a common bone marrow-derived precursor that becomes committed to the lymphocyte lineage

  2. B cell maturation proceeds in the bone marrow, whereas early T cell progenitors migrate to and complete their maturation in the thymus
• B cells


  • Carry membrane-bound antibody molecules as their antigen-specific receptors
• T cells


  • Carry T cell receptor system which requires antigen processing and presentation by antigen-presenting cells in combination with MHC molecules
• Problem


  There are millions of antigens in the environment but our genes are not sufficient in numbers to encode millions of receptors to recognize all of them
• Solution


  Antigen receptors are formed by somatic recombination of a limited number of inherited gene segments
• Immature or unselected T lymphocytes consist of cells whose receptors may recognize any peptide antigen (self or foreign) displayed by any MHC molecule (self or foreign)
• In every individual, the only useful T cells are the ones specific for foreign peptides presented by self MHC molecules
• If T cells strongly recognize self proteins, autoimmunity develops
• There are selection processes to ensure that only the useful T cells complete the process of maturation
• Maturation of T lymphocytes

  1. The thymus is the major site of maturation of T cells

  2. Thymocytes migrate from the cortex to the medulla, becoming mature and expressing TCR and CD4 or CD8

  3. Physical interactions between thymocytes and nonlymphoid cells of the thymus are necessary for maturation

  4. Positive selection allows thymocytes with weak binding to self peptide-self MHC complexes to survive, while negative selection deletes thymocytes with strong binding

  5. The net result is mature T cells that recognize self MHC and do not recognize self antigenic peptides
• Activation of Helper T Cell


  After an antigen-presenting cell ingests and processes an antigen, it presents the antigen fragment combined with class II MHC protein to a matching CD4 (+) helper T cell, activating the macrophage to release interleukins
• Helper T cells secrete cytokines (mediators of communication)
• When a dendritic cell processes an antigen


  It presents the antigen fragment combined with class II MHC protein to a matching CD4(+) helper