Immunoglobulins

INTRODUCTION:
Igs are glycoproteins, produced in response to an immunogen by plasma cells
SYNTHESIS OF IMMUNOGLOBULINS:
  • After antigenic stimulation, B-cells form plasma cells that secret immunoglobulin
  • The secretory component of immunoglobulin molecule is Formed by epithelial cells of lining mucosa
  • All immature B cells carry Ig M immunoglobulins on their surface and most also carry Ig D
  • These immunoglobulins serve as receptors for a specific antigen, so that each B cell can respond to only one antigen or a closely related group of antigens. The C gene for the gamma heavy chain is on chromosome 14 and the C gene for the kappa light chain gene is on chromosome 2.
  • For C (constant) regions of the heavy chains only genes are present on one chromosome 
  • The V gene for the kappa light chain is on chromosome 2. The C gene for the epsilon heavy chain is on chromosome 14.
  • The V gene for the lambda light chain gene is on chromosome 22. The C gene for the kappa light chain gene is on chromosome 2.
  • Differential RNA processing decides whether an immunoglobulin will remain membrane bound or secreted.
STRUCTURE OF ANTIBODIES:
  • Simply Y shape structure
  • Composed of 

  1. 2 identical heavy polypeptide chains and 
  2. 2 identical light chain.
  • Heavy chain means have high molecular weight i.e 50,000-77,000d and composed of 450 amino acid.
  • Light chain are smaller having molecular weight 25ooo and composed of 212 amino acid
  • Light chain may be further divide into either kappa or lambda.
  • Immunoglobulin may contain either kappa or lambda but not both
  • Light and heavy chain are join to each other by disulfid bond
  • The light and heavy chain is composed of constant and variable region.
  • The first 110-120 amino acid of the light and heavy region form variable sequence and thought to antigen binding site.
  • Class specific antigenic determinants of an immunoglobulin is associated with H-chain
  • The constant region is further divide into CH1,CH2 and CH3 each have their own function. In the middle of antibody a region called hinge region which gives feasibility to antibody.
  • Complementary to the structure of the epitope - complementarity determining regions
  1. CH2 region in IgG & IgM binds C1q in the classical complement sequence
  2. CH3 domain mediates monocyte adherence
  3. The area of the H chain in the C region between the first and second C region domains (CHI and CH2) is the Hinge region
  4. Papain acts in the hinge region and splits each Ig molecule into 3 parts: 1 Fc and 2 Fab
  5. Pepsin digests Fc portion, resulting in a 5S portion - 2 Fab fragments held together: F(ab)2
  • Immunoglobulin molecule:
  • Immunoglobin molecule represents hetero-tetrameric quarternary structure between 4 polypeptide (2 heavy + 2 light) chains.
  • Amino terminus
  1. Variable unit
  2. Antigen binding site
  3. Composed of both L and H chains
  • Carboxy terminus
  1. Constant unit
  2. Fc fragment of Ig(complement fixation, placental transfer, skin fixation and catabolic rate)
  3. Determines the biological properties of Ig 
HUMAN IMMUNOGLOBULINS CLASSES: 
  • Antigen determinants on Immunoglobulins
  • Isotype:
  • Immunoglobulin isotype class switching is determined by Constant region of heavy chain
Refers to a particular constant region of the light or heavy chain
Shared by all members of the same species
Variations in the heavy chain constant region (CH)
  1. Classes of Ig are differentiated on the basis of isotypic markers on H chains IgG, IgA, IgM, IgD, IgE
    Immunoglobulin class Heavy chain
    IgGγ (gamma)
    IgA α (alpha)
    IgM μ(mu)
    IgD δ(delta)
    γ (gamma)
  • Allotypes
  1. Refers to allelic differences in both the variable and constant regions of Ig
  2. Individual specific determinants within a species
  3. Present in some but not all members of a species
  • Idiotypes

  1. Found in the hypervariable region of the Fab portion
  2. Specific for each antibody molecule
Exam Question
  • C gene for gamma chain and C gene for alpha chain are linked on a single chromosome
  • Differential RNA processing decides whether an immunoglobulin will remain membrane bound or secreted.
  • Immunoglobin molecule represents hetero-tetrameric quarternary structure between 4 polypeptide (2 heavy + 2 light) chains.
  • After antigenic stimulation, B-cells form plasma cells that secret immunoglobulin
  • All immature B cells carry Ig M immunoglobulins on their surface and most also carry Ig D that serves as serve as receptors for a specific antigen. A single immunoglobulin molecule contains 2 light chains, 2 heavy chains
  • Complement attaches to immunoglobulin at Fc fragment
  • Immunoglobulin isotype class switching is determined by Constant region of heavy chain
  • Class specific antigenic determinants of an immunoglobulin is associated with H-chain
  • Immunoglobulin changes in variable region in idiotype
  • The secretory component of immunoglobulin molecule is Formed by epithelial cells of lining mucosa
  • The H chain has molecular weight of 50, 000.
  • Complement binding immunoglobulin via the classical pathway is IgG & IgM

Don't Forget to Solve all the previous Year Question asked on Immunoglobulins