Antibodies

• Antibodies


  • Produced in response to antigens by B lymphocytes
  • Have the ability to form complexes with the antigens that stimulated their production
  • Present in blood and tissue fluids of all mammals
• Humoral Immunity


  • Mediated by antibodies and is the effector arm of the adaptive immune system responsible for defense against extracellular microbes and microbial toxins
• Production of Antibodies


  1. B lymphocytes are the only cells that synthesize antibody molecules

  2. Membrane-bound forms of the antibodies are expressed on B-cells and act as B cell receptors

  3. Secreted forms of the antibodies are present in the plasma, in mucosal secretions, and interstitial fluid of the tissues
• Antibodies act also like receptors on B cells


  Mostly they are secreted
• Structure of Antibody


  • All have a basic structure composed of four chains of polypeptides
  • Variable and Constant regions participate in antigen recognition and mediate effector functions
  • Variable regions of heavy and light chains make up the antigen-binding site
  • The stem of the Y links the antibody to effector molecules and cells of the immune system
  • The C regions of light chains do not participate in effector functions
• Each clone of B or T lymphocytes produces an antigen receptor with a unique antigen-binding structure
• Functional antigen receptor genes are produced in immature B cells in the bone marrow and in immature T cells in the thymus by a process of somatic recombination
• The DNA recombination events are not dependent or influenced by the presence of antigens
• Five Major Classes of Antibodies

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


  • The major immunoglobulin in human serum
  • Monomeric
  • The only Ig molecule able to cross the placenta
  • Provides naturally acquired passive immunity for the newborn
  • Predominant antibody of secondary immune responses
  • Four subclasses: IgG1, IgG2, IgG3, IgG4
  • Functions include opsonization, complement activation, antibody-dependent cell-mediated cytotoxicity
• IgM


  • Takes up about 10% of the total serum Ig pool
  • Pentameric polymer
  • The first Ig made during B-cell maturation
  • The first Ig secreted into the bloodstream
• It takes up about 10% of the total serum Ig pool
• IgM


  Pentameric polymer
• IgM structure


  Monomers arranged in a wheel array with the Fc ends in the center, joined by J chain
• Transmembrane monomeric form of IgM

  Present as an antigen-specific receptor on mature B cells
• IgM is the first Ig made during B-cell maturation
• IgM is the first Ig secreted into serum during a primary antibody response to an infection
• IgM is large and does not leave the circulatory system or cross the placenta
• IgM is frequently associated with the immune response to antigenically complex, blood-borne infectious organisms
• IgM activates complement
• IgA


  About 15-20% of the total serum Ig pool, over 80% of serum IgA is monomer
• Secretory IgA (sIgA) is the predominant Ig in seromucous secretions such as saliva, colostrum, milk, and tracheobronchial and genitourinary secretions
• sIgA structure


  Comprised of a dimeric form of the basic four-chain structure together with the J chain and a secretory component
• IgA is found in all mucosal surfaces: gastrointestinal system, upper and lower respiratory system, and genitourinary system
• IgA guards the entrances to the body as it is found in saliva, tears, and breast milk
• IgA plays a major role protecting mucosal tissues against infection
• IgD


  Found in trace amounts in serum, monomeric structure
• Transmembrane monomeric form of IgD

  Present as an antigen-specific receptor on mature B cells
• IgE


  Found only in trace amounts in serum, monomer, hypersensitivity antibodies
• IgE Fc portion


  Can bind to specific Fc receptors on mast cells and basophils, degranulation occurs (histamine), defense against helminthic parasites
• Antibodies against microbes and microbial toxins block their binding to cellular receptors
• Antibodies that bind to microbial structures interfere with their ability to interact with cellular receptors
• Antibodies of the IgG isotype coat microbes and promote their phagocytosis by binding to Fc receptors on phagocytes
• Mononuclear phagocytes and neutrophils express receptors for the Fc portions of IgG antibodies that specifically bind antibody-coated particles
• The efficiency of phagocytosis is enhanced if the phagocyte can strongly bind microbes
• The process of coating particles for phagocytosis is called opsonization
• The substances responsible for opsonization are called specific opsonins (antibodies and complement proteins)
• NK cells and other leukocytes bind to antibody-coated cells by Fc receptors and destroy these cells
• IgG


  • Opsonization of antigens for phagocytosis by macrophages and neutrophils, activation of the classical pathway of complement, antibody-dependent cell-mediated cytotoxicity mediated by NK cells and macrophages, neonatal immunity: transfer of maternal antibody across the placenta and gut
• IgM


  • Activation of the classical pathway of complement, antigen receptor of naive B lymphocytes