; Antibodies
Learning Center
Plans & pricing Sign in
Sign Out



  • pg 1
									The structure of Antibody
                     Immunoglobulin’s are made of 4 polypeptide chains
                     The light chains and heavy chains are joined together by di-sulphide bonds.
                     The front portion (forked area) are the part of the Ab that will bind to the
                      Ag and is called Fragment Ag Binder (FAB)
                     The tail end can be crystallized using papain so it is called the Fragment
                      Crystalline (FC)
                     In the experiment using papain the Ab was completely separated into FAB
                      and FC
                     The Ab could still bind to the Ag, but it did not neutralize the Ag
                     In another experiment using pepsin still got 2 FAB segments, but each one
                      had a small fragment of the FC on the end

 This allowed the Ab to bind to the Ag and also for the Ag to be neutralized
 Therefore, the FAB is important for binding to the Ag and the FC is important for destroying
 The FC region allows complement to bind to it for opsonisation
 Light chains have 210 amino acids
 The Ab has a N terminal that is variable and contains 105 aa and is coded for in genes
 The sequence of the Ab binding site is changed by rearranging the aa
 This allows Ab’s to change to fit different Ag’s
 It also has a C terminal (meaning carboxyl and constant) that is constant with 105 aa
 Between the N and C terminals are a diversity and a joining region

      V1       V2        V3      Diversity   Joining       IgG       IgM       IgD    IgE       IgA

  If you had this Ab at resting stage and had an infection that required IgA it would change becoming

  Note that the V region does not change (it could be any of them based on what was needed) but
  the diversity and joining regions are always the same and always present.

 Class switch is stimulated by constant Ag stimulation of the B cells
 Class switch is a process whereby the B cell, as it develops into a plasma cell, can switch the
  class (also called isotype) of antibody it produces while retaining the same antigen specificity.
 Class switch involves rearrangement of the FC area of the immunoglobulin gene.
 Class switch does not occur until after B cell activation and proliferation.
 Class switch is under the control of cytokines such as (IL-4, IL-5, IL6, and IFNγ
      o The cytokines for this are produced from CD4 T cells.
 Since B cells initially express IgM they are initially using the constant (C) heavy chain gene
  for IgM (the mu gene).
 In class switch to IgG for example the mu gene is spliced out such that the portion of the
  gene that defines the variable region of the heavy chain is brought into apposition with the
  gamma gene. This results in IgG being produced
 The heavy chain determines the class of the antibody (5 possible)
 The light chains can be either kappa (κ) or lambda (λ). They cannot be both at the same time,
  but must be one or the other.
 There are 5 possible classes of antibody (immunoglobulin’s)
      o IgG – denoted by gamma (γ) - monomer
      o IgM – denoted by meu (μ) - pentamer
      o IgA – denoted by alpha (α) – monomer in serum and dimer in secretory form
      o IgE – denoted by epsion (ε) - monomer
      o IgD – denoted by delta (δ) – monomer
 All of the Ig’s have different functions and molecular weights

      colonizes in the mucus membranes
      the main immunoglobulin found in mucous secretions, including tears, saliva, colostrum,
       intestinal juice, vaginal fluid and secretions from the prostate and respiratory epithelium
      It is also found in small amounts in the blood
      IgA is a poor activator of the complement system, and opsonises only weakly.
      Female animals come in contact with the pathogens of its infant by kissing/licking the
       infant. This will cause the mother to build up Ab’s (by stimulating B cells) causing a
       class switch in Ig’s. The IgA that is produced will pass to the infant through the breast
       milk. The IgA will then coat the infants mucosal lining as well. The IgA has no need to
       go to the lymph system as it is secreted by getting into the goblet cells.

      Makes up about 1% of proteins in the plasma membranes of immature B-lymphocytes
       where it is usually co expressed with another cell surface antibody called IgM.
      IgD is also produced in a secreted form that is found in very small amounts in blood
      IgD's function is to signal when the young B cells in the spleen are ready to be activated.
       By being activated, they are ready to take part in the defence of the body in the immune

      Originally evolved to be good for worm infestations
      Now a common cause of allergies caused by IgE attaching to mast cells where an
       allergen would attach resulting in degranulation
      Least present Ig

      the main antibody involved in primary response is IgM
     IgM forms polymers where multiple immunoglobulins are covalently linked together
      with disulfide bonds as a pentamer.
     Because each monomer has two antigen binding sites, a pentameric IgM has 10 binding
      sites. Typically, however, IgM cannot bind 10 antigens at the same time because the large
      size of most antigens hinders binding to nearby sites.
     Because IgM is a large molecule, it cannot diffuse well
     IgM is primarily found in serum; however, because of the J chain, it is also important as a
      secretory immunoglobulin.
     Due to its polymeric nature, IgM possesses high avidity, and is particularly effective at
      complement activation.
     It is also the first immunoglobulin expressed in the fetus (around 20 weeks) and also
      phylogenetically the earliest antibody to develop


     Each IgG has two antigen binding sites.
     It is the most abundant immunoglobulin and is approximately equally distributed in blood
      and in tissue liquids, constituting 75% of serum immunoglobulins in humans.
      IgG molecules are synthesised and secreted by plasma B cells.
     IgG antibodies are predominately involved in the secondary antibody response, which
      occurs approximately one month following antigen recognition, thus the presence of
      specific IgG generally corresponds to maturation of the antibody response.
     Active in the blood and tissues
     Can activate complement and phagocytosis
     Pro-inflammatory cytokines particularly IL-4 and IL-2, have a crucial role in activation
      of the IgG antibody response.
     This is the only Ig that can pass through the human placenta, thereby providing protection
      to the fetus.
     Can bind to many kinds of pathogens, for example viruses, bacteria, and fungi, and
      protects the body against them by agglutination and immobilization, complement
      activation (classical pathway), opsonisation for phagocytosis and neutralization of their
     It also plays an important role in Antibody-dependent cell-mediated cytotoxicity(ADCC).
     There are four IgG subclasses (IgG1, 2, 3 and 4) in humans, named in order of their
      abundance in serum (IgG1 being the most abundant).
           o Class 1 good for complement activation, opsonization for phagocytosis, reaches
               extra vascular spaces, transfers across the placenta
           o Class 2 Same as Class 1 but less efficient
           o Class 3 same as class 1 and same efficency
           o Class 4 everything but complement activation
Antibody Functions

Neutralization and Blocking
   Antibodies are able to neutralize bacterial toxins – this forms the basis of vaccines against
    diseases such as tetnus
   The Ig molecule blocking the binding of the toxin to the cell receptor via which it enters and
    damages cells
   IgM can prevent the movement of bacteria that use flagellae to move
   Good for agglutination bacteria. The clumping of cells such as bacteria or red blood cells in
    the presence of an antibody. The antibody or other molecule binds multiple particles and
    joins them, creating a large complex.
Phagocytosis and Degranulation
   The presence of Ab bound to pathogens extends the recognition of phagocytic cells because
    now the cell can recognize the Ab Fc receptors
   Eosinophils contain granules with contents that are particularly toxic to some worms
Complement Activation
   Ab bound to Ag can activate the classical complement pathway, this leads to better
    phagocytosis because phagocytes have receptors for the cleavage fragment C3b

To top