UPSC MainsZOOLOGY-PAPER-II201420 Marks
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Q21.

What are immunoglobulins? Describe the structure of IgG and add a note on its diversity.

How to Approach

This question requires a detailed understanding of immunoglobulins, specifically IgG. The approach should begin with defining immunoglobulins and their general role in the immune system. Then, a thorough description of IgG's structure – both the basic Y-shape and its different domains – is crucial. Finally, the question asks for a note on IgG diversity, which necessitates explaining the mechanisms generating this diversity, like V(D)J recombination, somatic hypermutation, and class switching. A clear, structured answer with diagrams (though not possible here, mention their relevance) will be highly valued.

Model Answer

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Introduction

Immunoglobulins, also known as antibodies, are glycoprotein molecules produced by plasma cells (differentiated B lymphocytes) that play a vital role in the adaptive immune system. They recognize and bind to specific antigens, such as bacteria, viruses, and toxins, initiating immune responses to neutralize or eliminate these threats. These proteins are crucial for humoral immunity and are central to immunological memory. IgG is the most abundant immunoglobulin in serum, constituting about 75% of total serum immunoglobulin, and plays a significant role in long-term immunity. Understanding its structure and diversity is fundamental to comprehending the intricacies of the immune response.

What are Immunoglobulins?

Immunoglobulins are broadly classified into five classes: IgG, IgM, IgA, IgE, and IgD, each with distinct structures and functions. They are characterized by their Y-shaped structure, consisting of four polypeptide chains – two heavy chains and two light chains. The heavy chains determine the immunoglobulin class (e.g., gamma for IgG, mu for IgM), while the light chains are of two types: kappa (κ) and lambda (λ). The antigen-binding sites are located at the tips of the Y-shaped arms, formed by the variable regions of both the heavy and light chains.

Structure of IgG

IgG is a monomeric immunoglobulin, meaning it consists of a single Y-shaped unit. Its structure can be broken down into the following components:

  • Heavy Chains (γ chains): Approximately 450 amino acids long. Each heavy chain contains:
    • Variable Region (VH): Responsible for antigen binding.
    • Constant Regions (CH1, CH2, CH3): Determine the IgG subclass (IgG1, IgG2, IgG3, IgG4) and mediate effector functions like complement activation and Fc receptor binding.
  • Light Chains (κ or λ chains): Approximately 214 amino acids long. Each light chain contains:
    • Variable Region (VL): Contributes to antigen binding.
    • Constant Region (CL): Provides structural support.
  • Hinge Region: A flexible region between the CH1 and CH2 domains, allowing for flexibility in antigen binding.
  • Disulfide Bonds: Hold the heavy and light chains together, as well as the two heavy chains, maintaining the overall structure.

Diagrammatic representation (would be included in an exam setting): A clear diagram illustrating the heavy and light chains, variable and constant regions, hinge region, and disulfide bonds would significantly enhance understanding.

Diversity of IgG

The remarkable diversity of IgG antibodies, enabling recognition of a vast array of antigens, is generated through several mechanisms:

  • V(D)J Recombination: This process occurs during B cell development in the bone marrow. Gene segments encoding the variable regions of heavy and light chains (V, D, and J segments) are randomly rearranged, creating a unique combination for each B cell.
  • Combinatorial Diversity: The random pairing of different heavy and light chain variable regions further increases diversity.
  • Junctional Diversity: Addition or deletion of nucleotides at the junctions between V, D, and J segments during recombination introduces further variability.
  • Somatic Hypermutation: After antigen exposure, B cells undergo somatic hypermutation, introducing point mutations in the variable regions of the antibody genes. B cells with mutations that result in higher affinity for the antigen are selectively expanded.
  • Class Switching Recombination (Isotype Switching): B cells can switch the constant region of their heavy chain, changing the antibody class (e.g., from IgM to IgG). This alters the effector functions of the antibody while maintaining antigen specificity.

The four subclasses of IgG (IgG1, IgG2, IgG3, and IgG4) exhibit differences in their ability to activate complement, bind to Fc receptors, and cross the placenta. These differences contribute to the functional diversity of IgG in immune responses.

IgG Subclass Complement Activation Fc Receptor Binding Placental Transfer
IgG1 Strong Strong Yes
IgG2 Weak Moderate Limited
IgG3 Strong Strong Yes
IgG4 Weak Weak No

Conclusion

In conclusion, immunoglobulins, particularly IgG, are essential components of the adaptive immune system, providing crucial protection against pathogens. The unique structure of IgG, characterized by heavy and light chains, variable and constant regions, and a flexible hinge, allows for specific antigen recognition and effector function. The remarkable diversity of IgG, generated through V(D)J recombination, somatic hypermutation, and class switching, enables the immune system to respond to a vast array of antigenic challenges. Further research into immunoglobulin structure and diversity continues to refine our understanding of immune responses and inform the development of novel immunotherapies.

Answer Length

This is a comprehensive model answer for learning purposes and may exceed the word limit. In the exam, always adhere to the prescribed word count.

Additional Resources

Key Definitions

Antigen
A substance that can bind specifically to a component of the adaptive immune system, such as an antibody or T cell receptor, triggering an immune response.
Opsonization
The process by which pathogens are coated with antibodies or complement proteins to enhance their phagocytosis by immune cells.

Key Statistics

Globally, the antibody market was valued at USD 148.28 billion in 2022 and is projected to reach USD 264.89 billion by 2030, growing at a CAGR of 7.9% from 2023 to 2030.

Source: Fortune Business Insights, 2023 (Knowledge Cutoff: 2023)

According to the WHO, approximately 1.5 million deaths occur annually due to vaccine-preventable diseases globally.

Source: World Health Organization (WHO), 2022 (Knowledge Cutoff: 2023)

Examples

Monoclonal Antibody Therapy for Cancer

Monoclonal antibodies (mAbs) like Rituximab (anti-CD20) are used in the treatment of B-cell lymphomas. These mAbs specifically target cancer cells, leading to their destruction by the immune system or through other mechanisms.

Frequently Asked Questions

What is the role of the Fc region of IgG?

The Fc region of IgG mediates effector functions such as complement activation, antibody-dependent cell-mediated cytotoxicity (ADCC), and opsonization. It binds to Fc receptors on immune cells, triggering these responses.

Topics Covered

BiologyImmunologyMedicineAntibodiesImmune SystemImmunoglobulins