Immunoglobulins

 

Antibodies, or immunoglobulins, are critical components of the adaptive immune system that recognize pathogens or other foreign material in a manner similar to T cell receptors.

Antibodies begin on the surface of B cells and can also be liberated into the plasma.

 

Function

 

Immunoglobulins play four primary roles in recognizing and neutralizing pathogens:

  1. Opsonization of antigens targets them for destruction by phagocytic cells
  2. Fixing complement C1 activates the classical pathway; two antibodies required
  3. Blocks attachment of pathogens to their cellular targets and induces pathogen aggregation
  4. Neutralizes toxins and induces their phagocytosis

 

 

Classes of Immunoglobulins

  • IgM
  • IgG
  • IgA
  • IgE
  • IgD
  • class switch

IgM

  • pentameric molecule
  • found on B cell cell surface and in plasma; Fc regions differ for each
  • particularly good at fixing complement, but poor at opsonization
  • first to be produced in response to infection; does not require 'class switch'

IgG

  • most abundant antibody in the blood (8-16 g/l)
  • actively transported across the placental barrier
  • very good at fixing complement and opsonization: phagocytes have a large number of FcγR
  • also good at neutralizing toxins and blocking attachment of pathogens due to their number
  • capable of leaving the blood stream and entering tissues
  • class switch is dependent on IFN-gamma

IgA

  • monomeric and dimeric
  • secreted in breast milk; works in the gut of infants
  • abundant in secretion at mucosal surfaces, in saliva, tears
  • not great at opsonization; ok at fixing complement; very good at aggregating bacteria and neutralizing toxins

IgE

  • responsible for Type I hypersensitivity reactions (allergy, asthma, anaphylaxis)
  • bound to mast cell surface and induces allergic response
  • poor at performing above-mentioned functions
  • responds to parasitic infection

IgD

  • found on cell surface of B cells
  • role unknown

Class Switch

Switch factors lead to the expression of different immunoglobulins:

 

IgA: TGF

IgG: IFN-γ

IgE: IL-4

 

 

Structure

 

Antibodies are composed of four polypeptides, or chains - two heavy chains or two light chains. Humans have two different kinds of light chain and five different kinds of heavy chains.

 

The two important regions are the Fab region and the Fc region. The Fab region binds antigen, while the Fc region binds cellular receptors.

Fc regions of antibodies of the same class are the same, while those of different antibody classes are different. The Fc region is important for fixing complement. The Fc region can bind FcR in two different ways. IgG binds to pathogen before it binds to FcR, while IgE will bind to cellular FcR before reacting with antigen.

 

 

Gene and Processing

Immunoglobulin genes are rearranged by the RAG protein, which is also involved in T Cell Receptor rearrangement.

Heavy chains are composed of VDJ-C sections, while light chains have VJ-C regions.