PHARM106

• Immune system


  Cells, tissues, and molecules that mediate resistance to infections
• Immunology


  The study of the structure and function of the immune system
• Immunity


  Resistance of a host to pathogens and their toxic effects
• Immune response


  The collective and coordinated response to the introduction of foreign substances in an individual mediated by the cells and molecules of the immune system
• Role of the immune system

  • Defense against microbes
  • Defense against the growth of tumor cells
  • Homeostasis
  • Destruction of abnormal or dead cells
• Components of the immune system

  • Organs
  • Cells
  • Molecules
• Immune system organs


  • Tonsils and adenoids
  • Thymus
  • Lymph nodes
  • Spleen
  • Payer's patches
  • Appendix
  • Lymphatic vessels
  • Bone marrow
• Immune system cells


  • Lymphocytes
  • T-lymphocytes
  • B-Lymphocytes, plasma cells
  • Natural killer lymphocytes
  • Monocytes, Macrophage
  • Granulocytes (neutrophils, eosinophils, basophils)
• Immune system molecules


  • Antibodies
  • Complement
  • Cytokines (Interleukins, Interferons)
• Innate (non-adaptive) immunity


  First line of immune response, relies on mechanisms that exist before infection
• Acquired (adaptive) immunity


  Second line of response (if innate fails), relies on mechanisms that adapt after infection, handled by T- and B-lymphocytes
• Innate immunity(first line of defense)


  • Based on genetic make-up
  • Relies on already formed components
  • Rapid response: within minutes of infection
  • Non-specific (same molecules/cells respond to a range of pathogens)
  • Has no memory (same response after repeated exposure)
  • Does not lead to clonal expansion
• Innate immunity mechanisms


  • Mechanical barriers/surface secretion (skin, acidic pH in stomach, cilia)
  • Humoral mechanisms (lysozymes, basic proteins, complement, interferons)
  • Cellular defense mechanisms (natural killer cells, neutrophils, macrophages, mast cells, basophils, eosinophils)
• Mast cell


  Dilates blood vessels and induces inflammation through release of histamines and heparin, recruits macrophages and neutrophils, involved in wound healing and defense against pathogens but can also be responsible for allergic reactions
• Macrophage


  Phagocytic cell that consumes foreign pathogens and cancer cells, stimulates response of other immune cells
• Natural killer cell


  Kills tumor cells and virus-infected cells
• Dendritic cell


  Presents antigens on its surface, thereby triggering adaptive immunity
• Monocyte


  Differentiates into macrophages and dendritic cells in response to inflammation
• Neutrophil


  First responders at the site of infection or trauma, abundant phagocytic cell, releases toxins that kill or inhibit bacteria and fungi and recruits other immune cells to the site of infection
• Basophil


  Responsible for defense against parasites, releases histamines that cause inflammation and may be responsible for allergic reactions
• Eosinophil


  Releases toxins that kill bacteria and parasites but also causes tissue damage
• Adaptive immunity


  • Based upon resistance acquired throughout life
  • Relies on genetic events and cellular growth
  • Responds more slowly, over few days
  • Is specific (each cell responds to a single epitope on an antigen)
  • Has anamnestic memory (repeated exposure leads to faster, stronger response)
• Types of adaptive immunity


  • Active (natural, vaccination)
  • Passive (natural, artificial)
• Cell-mediated immune response (CMIR)

  1. lymphocytes eliminate intracellular microbes that survive within phagocytes or other infected cells
• Humoral immune response (HIR)

  1. lymphocytes mediated by antibodies, eliminate extra-cellular microbes and their toxins
• Humoral immune response


  1. B lymphocytes recognize specific antigens, proliferate and differentiate into antibody-secreting plasma cells

  2. Antibodies bind to specific antigens on microbes, destroy microbes via specific mechanisms

  3. Some B lymphocytes evolve into memory cells
• Cell-mediated immune response


  1. T-cell recognizes peptide antigen on macrophage in association with MHC class I

  2. T-cell goes into effectors cells stage that is able to kill infected cells
• T lymphocytes


  • Helper T-lymphocytes (CD4+)
  • Cytolytic T-lymphocyte (CD8+)
• Primary response (cell-mediated)


  • Production of specific clones of effector T cells and memory clones, develops in several days, does not limit the infection
• Secondary response (cell-mediated)


  • More pronounced, faster, more effective at limiting the infection
• Antibodies (immunoglobulins)


  1. shaped or T-shaped polypeptides with 2 identical heavy chains and 2 identical light chains, 5 kinds (IgG, IgM, IgA, IgD, IgE)
• IgG


  70-75% of total immunoglobulin, secreted in high quantities in secondary exposures, crosses the placenta, neutralizes microbes and toxins, opsonizes antigens for phagocytosis, activates the complement, protects the newborn, participates in agglutination and precipitation reactions
• IgM


  Secreted initially during primary infection, activates the complement, used as a marker of recent infection
• Antibodies

  IgG, IgM, IgA, IgD, IgE
• Antibody structure

  • Antigen-binding site
  • Light chain
  • Heavy chain
  • Variable region
  • Constant region
• Immunoglobulin types

  • IgG
  • IgM
  • IgA
  • IgD
  • IgE
• IgG


  • 70-75% of total immunoglobulin
  • Secreted in high quantities in secondary exposures
  • Cross the placenta
  • Neutralize microbes and toxins
  • Opsonize antigens for phagocytosis
  • Activate the complement
  • Protect the newborn
  • Participate in agglutination and precipitation reactions
• IgM


  • Secreted initially during primary infection
  • Activates the complement
  • Used as a marker of recent infection
• IgA


  • Monomeric in serum (IgA1)
  • Dimeric with secretory component in the lumen of the gastro-intestinal tract and in the respiratory tract (IgA2)
  • Neutralize microbes and toxins
• IgD


  • Extremely scarce (<0.2% of total immunoglobulin)
  • Present on the surface of B lymphocytes
  • Functions as membrane receptor
  • Role unclear
  • Has a role in antigen stimulated lymphocyte differentiation