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.
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