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Immunoglobulins: Structure, Function, and Clinical Importance

Immunoglobulins (Igs), also known as antibodies, are glycoproteins produced by B cells and plasma cells. They play a central role in the immune system by identifying and neutralizing pathogens such as bacteria and viruses. These versatile molecules are essential for immune defense, and their alterations can signal immunodeficiencies, infections, or autoimmune conditions.


1. Structure of Immunoglobulins

Basic Antibody Structure


Immunoglobulins are composed of:


  • Four Polypeptide Chains:
    • Two Heavy Chains (H-chains): Determine the antibody class (e.g., IgG, IgA).
    • Two Light Chains (L-chains): Either kappa (κ) or lambda (λ), contributing to antigen binding.
  • Variable Region: Responsible for antigen recognition; varies to bind specific antigens.
  • Constant Region: Determines the antibody's class and biological activity.
  • Hinge Region: Provides flexibility for antigen binding.

Antigen Binding


The variable regions of both the heavy and light chains form the antigen-binding site. Each antibody is specific to its target, recognizing unique epitopes on antigens.


2. Classes and Functions of Immunoglobulins

There are five major classes of immunoglobulins, each with distinct roles in the immune response:


Class
Primary Location
Functions
IgG
Blood, extracellular fluid
Long-term immunity, opsonization, neutralization of toxins, and complement activation.
IgA
Mucosal surfaces, secretions
Mucosal immunity; protects respiratory, gastrointestinal, and urogenital tracts.
IgM
Blood
First antibody produced during infection; efficient in agglutination and complement
activation.
IgE
Blood, tissues
Mediates allergic responses and defense against parasites by activating mast cells and
eosinophils.
IgD
B cell surface
Plays a role in B cell activation; function not fully understood.


Key Roles of Each Immunoglobulin


  1. IgG:
    • Most abundant antibody in the blood.
    • Provides long-term immunity after infection or vaccination.
    • Crosses the placenta to provide passive immunity to the fetus.
  2. IgA:
    • Found in saliva, tears, and breast milk.
    • Protects mucosal surfaces by preventing pathogen adherence.
  3. IgM:
    • The first antibody to respond during an initial infection.
    • Exists as a pentamer, making it highly effective in forming immune complexes.
  4. IgE:
    • Involved in hypersensitivity reactions (e.g., asthma, anaphylaxis).
    • Activates mast cells and eosinophils during parasitic infections.
  5. IgD:
    • Found in low concentrations in serum.
    • Primarily acts as a receptor on immature B cells.

3. Production of Immunoglobulins

B Cell Activation and Differentiation


  1. Naïve B Cells:
    • Express IgM and IgD on their surfaces.
    • Recognize specific antigens through their B cell receptors (BCRs).
  2. Antigen Exposure:
    • Binding of an antigen to the BCR triggers B cell activation.
    • Helper T cells provide signals to stimulate class switching and differentiation.
  3. Class Switching:
    • Activated B cells switch antibody production from IgM to other classes (IgG, IgA, or IgE) depending on the immune response required.
  4. Plasma Cells:
    • Mature B cells that secrete large amounts of antibodies into the bloodstream.

4. Clinical Importance of Immunoglobulins

Diagnostic Applications


Measurement of immunoglobulin levels can diagnose and monitor various conditions:


Condition
Associated Immunoglobulin Abnormalities
Immunodeficiencies
Low levels of one or more classes (e.g., hypogammaglobulinemia in IgG).
Autoimmune Diseases
Elevated levels, especially IgG (e.g., lupus, rheumatoid arthritis).t
Allergic Conditions
Elevated IgE levels (e.g., asthma, eczema, anaphylaxis).
Chronic Infections
Increased IgM or IgG levels due to persistent immune stimulation.
Multiple Myeloma
Overproduction of a specific monoclonal immunoglobulin (e.g., IgG or IgA).


Therapeutic Uses


  • Intravenous Immunoglobulin (IVIG):
    • Used to treat autoimmune diseases, immunodeficiencies, and inflammatory conditions.
  • Monoclonal Antibodies:
    • Engineered antibodies for targeted therapy in cancers, autoimmune diseases, and infections.
  • Allergen Immunotherapy: Modulates IgE responses to reduce allergic reactions.


5. Disorders of Immunoglobulins

Immunoglobulin Deficiencies


Condition
Description
Primary Immunodeficiency
Genetic disorders affecting antibody production (e.g., X-linked agammaglobulinemia).
Secondary Immunodeficiency
Caused by infections (e.g., HIV), chemotherapy, or malnutrition.


Hypergammaglobulinemia


  • Definition: Excess immunoglobulin production, often due to chronic infections or autoimmune diseases.
  • Examples:
    • Multiple Myeloma: Overproduction of monoclonal immunoglobulins.
    • Chronic Inflammatory Diseases: Elevated IgG levels.

Hypersensitivity and Allergies


  • Elevated IgE leads to allergic diseases like hay fever, asthma, and food allergies.
  • Targeting IgE with monoclonal antibodies (e.g., omalizumab) can manage severe allergic reactions

6. Summary Table of Immunoglobulins

Class
Concentration in Serum
Key Functions
Clinical Relevance
IgG
7-16 g/L
Long-term immunity, opsonization, complement activation.
Reduced levels in immunodeficiencies.
IgA
0.7-4 g/L
Mucosal immunity, neutralization.
Deficiency linked to recurrent respiratory infections.
IgM
0.5-2 g/L
Primary immune response, complement activation.
Elevated in acute infections or autoimmune diseases.
IgE
0.02-0.1 mg/L
Allergic reactions, parasitic defense.
Elevated in allergies or parasitic infections.
IgD
0.04 mg/L
Role in B cell activation.
Limited clinical significance.


Conclusion

Immunoglobulins are essential molecules in the immune system, providing protection against pathogens and mediating immune responses. Their diagnostic and therapeutic importance cannot be overstated, as they are integral in managing immunodeficiencies, autoimmune diseases, allergies, and infections. Advances in immunology continue to uncover their potential for targeted therapies and personalized medicine.


References

  1. Janeway, C., et al., 2001. Immunobiology: The Immune System in Health and Disease. Garland Science.
  2. Schroeder, H.W., Cavacini, L., 2010. Structure and function of immunoglobulins. Journal of Allergy and Clinical Immunology, 125(2), pp.41-50.
  3. Vidarsson, G., et al., 2014. IgG subclasses and their effector functions. Frontiers in Immunology, 5, p.520.
  4. Durandy, A., et al., 2013. Hypogammaglobulinemia in children. Pediatric Allergy and Immunology, 24(4), pp.347-357.
  5. Bonnefoy, J.Y., et al., 2001. IgE and allergy: a complex partnership. Nature Immunology, 2(2), pp.101-102.

20th Nov 2024 Shanza Riaz

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