Immunoglobulins

Introduction

·         Immunoglobulins (Ig) or Antibodies: Gamma globulins produced by plasma cells, specific to antigens.

·         Respond to foreign proteins or complex molecules not accepted by the host.

·         Exist as approximately 20% of proteins in body fluids.

·         Functions: Antigen binding, complement fixation, facilitation of phagocytosis, neutralization of toxic substances.

 

Classification

·         Based on the molecular structure of their heavy chains.

·         Five classes: IgA (α), IgD (δ), IgE (ε), IgG (γ), IgM (µ).

·         Each class has unique roles and characteristics.

 

Immunoglobulin/Antibody Structure

·         Common biochemical structural configuration.

·         Glycoproteins made of light (L) and heavy (H) polypeptide chains.

·         Basic unit: Four polypeptide chains (two identical light chains and two identical heavy chains).

·         Simplest antibody: Y-shaped.

 

Antigen Binding Fragment (Fab) Region

·         End of the Y with two identical pieces that bind the antigen.

·         Composed of:

·         Variable region of the L chain (VL)

·         Variable region of the H chain (VH)

·         Constant region of the L chain (CL)

·         First constant region of the H chains (CH1)

 

Immunoglobulin Structure

·         L and H chains bind antigen through hypervariable regions (5-10 amino acids).

·         Antigen-antibody binding involves non-covalent forces: Electrostatic, Van der Waals, Hydrogen bonds, Hydrophobic bonds.

 

Fc Fragment/Region

·         Single stalk at the other end of the Y, the constant “crystallizable” fragment (Fc).

·         IgG and IgA: Three CH domains; IgM and IgE: Four CH domains.

·         Functions:

·         Attachment to host cells via Fc receptors.

·         Activation of complement cascade at CH2 domain.

·         Formation of multimers (IgM, IgA).

·         Transport of IgA across epithelial barriers.

·         Transport of IgG from mother to fetus through placenta.

 

Light Chains

·         Types: κ (kappa) and λ (lambda).

·         Each B cell produces immunoglobulins with one type of light chain.

·         Typical κ to λ ratio in humans is 2:1; deviations may indicate monoclonal immunoglobulin-producing malignancies (e.g., multiple myeloma).

 

Major Functions

·         IgM: Primary response, fixes complement, antigen receptor on B cells, does not cross placenta.

·         IgG: Secondary response, opsonizes bacteria, fixes complement, neutralizes toxins/viruses, crosses placenta.

·         IgA: Prevents attachment of bacteria/viruses to mucous membranes, does not fix complement.

·         IgD: Uncertain function, found on B cell surface and in serum.

·         IgE: Mediates immediate hypersensitivity, defense against worm infections, does not fix complement.

 

Characteristics

·         IgA: Alpha heavy chain, 5.8-day half-life, no placental transfer, no complement fixation.

·         IgD: Delta heavy chain, 2.8-day half-life, no placental transfer, no complement fixation.

·         IgE: Epsilon heavy chain, 2.3-day half-life, no placental transfer, no complement fixation.

·         IgG: Gamma heavy chain, 21-day half-life, crosses placenta, fixes complement.

·         IgM: Mu heavy chain, 5.1-day half-life, does not cross placenta, fixes complement.

 

Genes of Immunoglobulins

·         Organized into clusters on specific chromosomes:

·         Kappa light chain (κL) genes: Chromosome 2.

·         Lambda light chain (λL) genes: Chromosome 22.

·         Heavy chain genes: Chromosome 14.

·         Heavy and light chain assembly involves gene segment recombination within clusters, facilitated by recombinase enzymes RAG1 and RAG2.

 

Genes Rearrangement

·         Heavy chain locus recombination produces various B-cell receptor (IgM) clones.

 

References

1.      Harmening, D. (7th Ed.). Modern Blood Banking & Transfusion Practices.

2.      Levinson, W., Chin-Hong, P., Joyce, E. A., & Nussbaum, J. (15th Ed.). Review of Medical Microbiology and Immunology.