Immune 2

• Lines of defense in the immune system

  • 1st line: physical & chemical surface barriers
  • 2nd line: internal cellular & chemical defense (if pathogen penetrates barriers)
  • 3rd line: immune response (if pathogen survives nonspecific, internal defenses)

  
• Nonspecific defenses


  Innate immune system (natural, not learned through experience)

  
• Specific defenses


  Adaptive immune system
• Components of the adaptive immune system

  • NK cells
  • Cell-mediated immunity (T cells)
  • Antibody-mediated/humoral immunity (B cells)

  
• T cells and B cells are able to develop memory
• Natural killer (NK) cells

  • Protect against viral infections & some cancers
  • Can respond very quickly compared to other lymphocytes
  • Mechanisms: destroy target cells, release interferons & cytokines to warn uninfected cells and enhance immune response

  
• Antigen


  A molecule, often on the surface of a pathogen, that the immune system recognizes as a specific threat

  
• MHC markers


  • Proteins expressed on the cell surface that display both self & non-self antigens, used in recognition of pathogens and self recognition
  • MHC-I: found on all nucleated cells
  • MHC-II: found mostly on macrophages, B cells, & dendritic cells (APCs)

  
• T cell activation


  1. Antigen presenting cell (APC) presents antigen fragment on MHC-II

  2. Helper T cell (CD4) responds by secreting cytokines that enhance immune response

  3. Initial "priming" of lymphocytes occurs in lymph tissues

  
• Cell-mediated (T cell) immune response

  1. Threat detected

  2. Macrophage presents antigen on MHC-I to activate naive cytotoxic T cell

  3. Effector cytotoxic T cell targets and kills cells displaying foreign antigen

  4. Memory T cells provide continued surveillance

  
• Antibody-mediated (B cell) immune response

  1. Naive B cell activated by effector helper T cell

  2. Plasma cell (effector B cell) secretes antibodies to neutralize foreign proteins

  3. Memory B cells provide continued surveillance

  
• Cytotoxic T (CD8) cells


  • Targets cells displaying foreign antigen (tissue cells infected with intracellular pathogen, cancer cells, cells of organ transplants, etc.)
  • Bind to MHC-I & kill infected cells by chemical means (perforin forms pores in target cell → granzymes enter pores → target cell apoptosis)

  
• Cell-Mediated Immune Response


  1. Antibody & cell-mediated responses get activated

  2. During Step 3, helper T cell divides & transforms into effector helper T cell

  3. Step 4: Effector helper T cell activates cell-mediated (T cell) response & antibody-mediated/humoral (B cell) response

  4. Step 5: Naïve B cell divides into plasma cell (effector B cell) & memory B cell

  5. Step 6: Plasma cell (effector B cell) secretes antibodies

  6. Step 7: Memory T cells & memory B cells stored for continued surveillance

  
• Clonal Selection Theory


  • Many B cells at birth but almost all of them are different
  • B lymphocytes "inherit" ability to produce particular antibodies
  • Any given B cell can produce only one type of antibody but they are "naïve"
  • Exposure to their antigen stimulates B cell to divide many times until a large population of genetically identical B cell clones are produced
  • B cells are able to produce ~2,000 antibodies per second

  
• Primary Response


  First exposure to antigen, slower & weaker response, produces mostly IgM antibodies

  
• Secondary Response


  Lymphocyte clones & memory cells result in faster & stronger response, produces IgG antibodies

  
• Steps of Immune Response

  • Step 1: Threat
  • Step 2: Detection
  • Step 3: Alert
  • Step 4: Alarm
  • Step 5: Building Specific Defenses
  • Step 6: Defense
  • Step 7: Continued Surveillance

  
• Antibodies


  • Do not destroy pathogens, just mark them as targets for immunological attack
  • Pathogen may be attacked by innate immune cells (macrophages, neutrophils)
  • Pathogen may be attacked by complement (blood protein defense system)

  
• The Complement Pathway


  1. 9 complement proteins (C1-C9) that are inactive in the plasma

  2. Proteins become activated when antibodies mark the antigens (bacteria)

  3. There are 3 pathways which all lead to the same outcome: Classical pathway, Alternative pathway, Lectin pathway

  4. Classical & lectin pathways are very similar

  5. Activation of C1 (classical pathway)

  6. C1 catalyzes hydrolysis of C4 into C4a & C4b

  7. C4b binds plasma membrane & is active

  8. C3 cleaved into C3a & C3b

  9. C3b converts C5 into C5a & C5b

  10. C3a & C5a stimulate mast cells to release histamine & serve as chemokines

  11. C5, C6, C7, C8, & C9 inserted into bacterial cell membrane to form a membrane attack complex

  
• Membrane Attack Complex (MAC)


  Large pore that kills bacterial cell through osmotic influx of water
• Defensive Process - Inflammation

  Injured tissue releases chemical signals: Blood vessels widen, Capillaries become more permeable, Redness, Heat, Swelling, Pain
• Inflammation also occurs in response to tissue damage & stress
• Autoimmune diseases: a failure of the immune system to recognize & tolerate self-antigens

  
• Reasons why self-tolerance may fail

  • An antigen that does not normally circulate in the blood may become exposed to the immune system
  • A self-antigen that is otherwise tolerated may be altered by combining with a foreign hapten
  • Antibodies may be produced that are directed against other antibodies
  • Antibodies produced against foreign antigens may cross-react with self-antigens
  • Self-antigens may be presented to helper T cells together with MHCII
  • Autoimmune diseases may result when there is inadequate activity of regulatory (suppressor) T lymphocytes

  
• Allergies


  1. Abnormal responses by B cells: hay fever, asthma & most other allergies caused by IgE immediate hypersensitivity

  2. Abnormal responses by T cells: delayed hypersensitivity i.e. hours to days because the reaction is mediated by lymphokines instead of antibodies