BIOL 1107 Immunity

• Acquired immune deficiency syndrome (AIDS)


  A constellation of disorders that follows infection by the human immunodeficiency virus (HIV)
• Three lines of defense against pathogens

  • Physical barriers (not part of the immune system)
  • Innate immune system: inherited mechanisms that protect the body from pathogens in a nonspecific way
  • Adaptive immune system: inherited mechanisms leading to the synthesis of molecules that target pathogens in a specific way
• Physical barriers


  • Tight junctions between epithelial cells, mucus layer, ciliated cells, chemicals (acids, enzymes, lysozyme) that are hostile to pathogens
• Innate immunity


  Provides an immediate, nonspecific response to cellular pathogens such as bacteria and viruses - targets any invading pathogen and has no memory of prior exposure
• Adaptive (acquired) immunity


  Specific - recognizes individual pathogens and mounts an attack that directly neutralizes or eliminates them, and retains a cellular memory of a pathogen and reacts quickly upon second exposure
• Leukocytes


  White blood cells and their derivatives, responsible for the activities of the two immune systems
• Phagocytes


  White blood cells that engulf bacteria or other cellular debris (phagocytosis)
• Most leukocytes originate from stem cells in bone marrow, and are released into the blood - lymphocytes form in the bone marrow and then migrate to the thymus
• Major types of leukocytes

  • Lymphocyte
  • Neutrophil
• Pathogen-associated molecular patterns


  Patterns associated with pathogenic organisms but absent in the host, recognized by pattern recognition receptors of phagocytic cells
• Toll-like receptors


  Pattern recognition receptors found on the cell surface and within the cell on various membrane-bound compartments
• Defensins


  Antimicrobial peptides that protect epithelial surfaces, attack the plasma membranes of pathogens, disrupting and killing them
• Inflammation


  The heat, pain, redness, and swelling that initially or exclusively occur at the site of an infection
• Inflammation


  1. Cell-surface receptors on macrophages recognize and bind to surface molecules on the pathogen, activating the macrophage to phagocytize

  2. Activated macrophages secrete cytokines, which bind to receptors on other host cells and trigger a response

  3. Tissue damage activates mast cells, which release histamine, an inflammatory signaling molecule

  4. Histamine and cytokines dilate local blood vessels and increase their permeability

  5. Cytokines make the blood vessel wall stickier, causing circulating neutrophils and monocytes to attach to it

  6. Neutrophils and monocytes are attracted to the infection site by chemokines secreted by activated macrophages

  7. Monocytes differentiate into macrophages and, along with the neutrophils, engulf the pathogens

  8. Engulfed pathogens are destroyed by enzymes and defensins located in lysosomes, or by production of toxic chemicals
• Antigen


  A foreign molecule that triggers an adaptive immune response
• Types of antigens


  • Large proteins (glycoproteins or lipoproteins)
  • Polysaccharides (lipopolysaccharides)
  • Some nucleic acids
  • Various large, artificially synthesized molecules
• B cells


  Lymphocytes that differentiate from stem cells in the bone marrow and are carried in blood to capillary beds serving the tissues and organs of the lymphatic system
• T cells


  Lymphocytes that differentiate from stem cells in bone marrow and are carried in blood to the thymus - two types are helper T cells and cytotoxic T cells
• Antibody-mediated immunity


  1. cell derivatives called plasma cells secrete antibodies - highly specific protein molecules that circulate in the blood and lymph recognizing and binding to antigens and clearing them from the body
• Cell-mediated immunity


  A particular type of T cell becomes activated and, with other cells of the immune system, attacks foreign cells directly and kills them
• Four steps of the adaptive immune response

  1. Antigen encounter and recognition: lymphocytes encounter and recognize an antigen

  2. Lymphocyte activation: lymphocytes are activated by binding to the antigen and divide to produce clones

  3. Antigen clearance: large clones of activated lymphocytes clear the antigen from the body

  4. Development of immunological memory: memory cells circulate in blood and lymph, prepared for a rapid response
• 1. cell receptor


  Specific receptors on the plasma membrane of T cells that bind to one specific antigen structure
• Epitopes


  Small regions of an antigen that a B-cell receptor or T-cell receptor binds to
• Antibodies


  Large, complex molecules that belong to a class of proteins known as immunoglobulins (Ig)
• Constant (C) region


  Region of an antibody polypeptide chain that determines the antibody class
• Variable (V) region


  Region of an antibody polypeptide chain that has a different amino acid sequence for each antibody molecule, giving the antigen-binding sites their specificity
• Five classes of antibodies

  • IgM
  • IgG
  • IgA
  • IgE
  • IgD
• Ten steps in the antibody-mediated immune response

  1. Engulfment of bacterium by dendritic cell

  2. Degradation of bacterium and release of antigens within dendritic cell

  3. Presentation of antigens on dendritic cell surface

  4. Interaction of antigen-presenting cell with lymphocyte

  5. Activation of T cell

  6. Production of helper T cells

  7. Presentation of antigens on B cell surface

  8. Interaction of B cell with helper T cell

  9. Clonal expansion of activated B cells

  10. Differentiation of B cells into plasma cells that secrete antibodies and memory B cells
• Activation of T cell

  The bound antigen-presenting cell secretes a cytokine (interleukin) that activates the associated T cell
• Production of helper T cells

  1. Activated T cells secrete other interleukins, which act in an autocrine manner to stimulate clonal expansion - proliferation of activated CD4+ T cells by cell division

  2. Clonal cells differentiate into helper T cells, which assist with activation of other lymphocytes (B cells)
• Helper T cell


  An effector T cell, involved in effecting the specific immune response to the antigen
• Presentation of antigens on B cell surface

  1. Antibodies are produced in activated B cells

  2. Activation requires the B cell to present the antigen on its surface, then link with a helper T cell that has differentiated as a result of recognizing the same antigen

  3. Antigen presentation on a B cell begins when B-cell receptors bind to antigens on the surface of the bacterium

  4. The bacterium plus B-cell receptor is taken into the cell, and the antigen is processed as in dendritic cells

  5. The result is presentation of antigen pieces on the B-cell surface in a complex with class II MHC proteins
• Interaction of B cell with helper T cell

  When a B cell encounters a helper T cell displaying the same antigen, usually in a lymph node or in the spleen, the two cells become tightly linked together
• Activation of B cell

  The linkage between cells stimulates the helper T cell to secrete interleukins that activate the B cell and stimulate the B cell to proliferate, producing a clone of B cells with identical B-cell receptors
• Production of plasma cells and memory B cells


  1. Many cloned cells differentiate into short-lived plasma cells, which secrete the antibody displayed on the parental B cell's surface to circulate in lymph and blood and attach the pathogen

  2. Other cloned cells differentiate into memory B cells, which are long-lived cells that prepare for a much more rapid response if the same antigen is encountered later
• Presentation of antigens on dendritic cell surface


  Dendritic cell presents antigens of engulfed pathogen on its surface
• Interaction of APC with lymphocyte

  Antigen-presenting cell interacts with CD4+ T cell, activating it
• Activation of T cell


  Helper T cell and antigen-presenting B cell interact, activating B cell
• Production of helper T cells

  Activated T cell produces helper T cells and memory helper T cells
• Degradation of bacterium and release of antigens


  Engulfment of bacterium