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  • Antibodies, also known as Immunoglobulins, are large, rigid multi-protein structures which can bind nuanced molecular moieties with extremely high specificity and affinity. Antibodies are synthesized by B-cells as part of Humoral Immunity to bind extracellular microbes,
  • Once bound to their respective antigen, antibodies recruit immune effector cells or Complement to destroy the bound pathogen. In some cases, binding of antibodies to microbial proteins can directly interfere with critical functions of the microbe required for replication and survival. How and when antibodies are generated is discussed in B-cell Development and how they are utilized within the context of an immune response is discussed in Humoral Immunity. Here we discuss the molecular structure of antibody and how its structure directs its capacity to bind antigen and recruit other immune effector cells or complement.
Basic Structure
  • Shape
    • Antibodies appear similar to the letter "Y" with two arms and a single base. The actual antigen binding pockets of the antibody are located at the tips of the arms whereas the region which recruits immune effector cells and complement is the base.
  • Molecular Components
    • Antibodies are composed of two pairs of identical protein chains, or in other words four total molecules. The two heavy chains are longer, run the length of the antibody from its arms all the way to its base, and are composed of four large domains. The two light chains only run along the arms of the antibody and are composed of two large domains. The four chains of the antibody are held together by disulfide bonds between the separate molecules. The heavy chain is also somewhat flexible as it transitions between its arm region and its base region, allowing for some movement in the antibody structure.
Antibody Regions
  • Overview
    • Each antibody is divided into variable and constant regions, thus highlighting where sequence differences between antibodies exists.
  • Variable Region
    • The variable region refers to the outer half of the antibody arms and thus includes the outer domain of the heavy chain as well as the light chain. The variable region is so named because there is significant sequence and structural differences between individual antibodies in this section. The major sequence differences occur at the tips of the arms which correspond to the antigen-binding groove of an antibody. This makes sense given that binding to different antigens will require differences in the amino acid sequence between different antibody molecules.
  • Constant Region
    • The constant region refers to the rest of the antibody which includes the lower half of the antibody arms and the base. The sequence of this constant region is precisely the same within a single isotype of antibodies (see below) and directs the recruitment of other immune effector cells and complement.
Antibody Fragments
  • Overview
    • During the process of understanding how antibody structure was related to its function, immunologists identified several functional fragments of the antibody following proteolytic cleavage of the molecule. Although these fragments play no role in physiology they played important roles in our scientific understanding of antibody. These fragments are derived following proteolytic cleavage at sites close to the center of the antibody "Y".
  • Fab Fragment
    • The Fab Fragment refers to a single arm of the antibody Y, released following proteolysis. It includes an entire light chain along with the attached upper half of the heavy chain which together form the arm. The Fab Fragment possesses the antigen-binding functionality of the antibody but cannot recruit immune effector cells or complement.
  • Fc Fragment
    • The Fc Fragment, or Fc Region, refers to the base of the antibody Y, released following proteolysis. It includes just the conjoined bottom halves of the two heavy chain which together form the base. The Fc Fragment can recruit immune effector cells and complement but cannot does not possess any antigen-binding functionality.
Light Chain Subtypes
  • Two subtypes of Light Chain exist, Kappa Light Chain and Lambda Light Chain, which are encoded by different genes. For any single B-cells, antibody will be synthesized from only one of the light chain genes and therefore the light chains in each arm of an antibody will always be of the same light chain subtype. Regardless, there does not appear to be any functional differences between antibodies formed using kappa or lambda light chains.
Heavy Chain Isotypes
  • Overview
    • Five different subtypes of heavy chain have been described which are often referred to as "Isotypes". These heavy chain isotypes possess structural differences in their Constant Region, especially in the Fc Region, which impart different functionalities to antibodies which possess them. As for the light chain, a single antibody's two heavy chains will always be of the same isotype and will never be a mixture of two. These isotypes have been given letter names M, D, G, A, and E and antibodies are classified according to their heavy chain usage as IgM, IgD, IgG, IgA, and IgE. Prior to encounter with antigen, all B-cells express antibody of IgM isotype as a membrane protein on their surface which is termed the "B-cell Receptor (BCR)". During a Humoral Immune Response, the B-cell may "Class Switch" its antibody to a different isotype (See: Humoral Immunity). The links below provide some information regarding the specific immune functionality of the different .antibody isotypes
  • Specific Isotypes
Antibody Effector Functions
  • Opsonization
    • Opsonization refers to the binding of antibody to microbial antigens, resulting in the coating of the microbial surface with antibody. When this occurs, phagocytic cells such as Macrophages, Neutrophils, and Dendritic Cells recognize the Fc Region of opsonizing antibody and phagocytose the bound material. In this way, antibody can identify microbes for phagocytosis and degradation by phagocytes.
  • Complement Activation
    • When bound to microbe, the Fc Region of antibody can activate the Classical Pathway of the Complement cascade. Although further discussed in Complement, activation of complement proteins can directly injure microbial membranes, enhance opsonization of the microbe, and release of chemotactic factors which recruit phagocytes.
  • Neutralization
    • In many cases, binding of antibody to an enzyme or receptor will interfere with the protein's functioning. If microbial surface enzymes or receptor are critical for the organism's survival and proliferation, their binding by antibody can severely inhibit microbial growth and spread.