Antibodies

Overview

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Introduction
  • Antibodies are immunologically active circulating proteins that
    • are composed of two heavy chains paired with two light chains
    • serve as a primary component of humoral immunity
    • are produced by B-cells that can further
      • differentiate into plasma cells that specialize in secreting antibodies
      • mature to make antibodies with higher affinity
      • remain dormant as memory cells
    • bind antigens from a wide variety of pathogens
    • are also known as immunoglobulins (Ig)
  • Antibodies are able to fight infections through multiple mechanisms including
    • opsonization of the surface of the pathogen leading to
      • phagocytosis by innate immune cells like macrophages
      • cytotoxicity by triggering release of toxic compounds by innate immune cells
    • neutralization of pathogens and viruses by
      • blocking interaction of pathogenic proteins with host receptors
      • inactivating virulence factors expressed by pathogens
    • activation of the complement cascade through the classical pathway

Antibody Structure 

  • Antibodies are composed of two heavy chains paired with two light chains
  • Together these chains create distinct regions of the antibody such as
    • the constant fragment (Fc)
    • two identical variable antigen binding fragments (Fab)
  • These regions differ in both structure and function
Differences Between Antibody Regions
FeatureAntibody Binding (Fab)Constant (Fc)
CompositionOne heavy and one light chainLinked by disulfide bondsTwo heavy chainsLinked by disulfide bondsAttached to carbohydrate chains
TerminusN-terminus of protein chainsC-terminus of protein chains
FunctionBinds to antigen in specific manner      Binds to complement proteins Binds to effector regions of innate immune cells       
VariabilitySite of idiotype diversityChanged in affinity maturationUnique for every antibodySite of isotype diversityChanged in isotype switching 5 types that are shared among all antibodies

Antibody Variation and Diversity 

  • Antibodies are able to fight an incredible range of infections because of 
    • idiotype diversity which
      • governs what antigens can be recognized by antibodies
      • is generated by multiple diversity mechanisms including  
        • random recombination of VDJ regions of antibody coding regions
        • random addition of nucleotides to hypervariable regions by TdT
        • random assortment of heavy chains with light chains
        • affinity maturation through somatic hypermutation after antigen exposure
      • ensures that any moiety can be recognized by the variable region of an antibody
  • isotype diversity through five types of constant regions
Antibody Isotypes
FeatureIgA IgDIgEIgMIgG
Constant chain typeα chainδ chainε chainμ chainγ chain
ConcentrationHigh in mucus membranes and in secretions Low LowHigh in serum during early responseHigh in serum during late response
ValenceDimer MonomerMonomerPentamerMonomer 
FunctionMucosal immunity Transported into mucosal lumens by poly IgPresent on B-cell surfacesUnclear roleDefense against parasites Mediates allergiesLow affinityMain antibody in early response High affinityMain antibody in late reponse
Recognized byInnate immune cellsComplement UnknownMast cells BasophilsInnate immune cellsPhagocytes Complement