Which of the following statements concerning immunoglobulins (antibodies) is/are correct?

Immunoglobulins: Structure and Function

The correct answer is E: 1 and 3. Immunoglobulins are produced by plasma cells and the antigen-antibody combining sites are located on the Fab fragment of the immunoglobulin.

Structure and Production of Immunoglobulins

Immunoglobulins (antibodies) are heterodimeric proteins that serve as the principal operators of the adaptive humoral immune response 1. Their structure and production have several key characteristics:

• Production: Immunoglobulins are produced by plasma cells, which are terminally differentiated B cells 2. This is a fundamental characteristic of antibody production in the immune system.

• Basic Structure: Each immunoglobulin molecule consists of:

  • Two identical heavy chains
  • Two identical light chains
  • These chains are arranged to form a Y-shaped molecule 1

• Antigen-Binding Site: The antigen-antibody combining sites are located on the Fab (Fragment antigen-binding) portion of the immunoglobulin molecule 1. The Fab fragment contains the variable domains that interact directly with antigens.

Classes of Immunoglobulins

There are five main classes (not six) of immunoglobulins, each defined by their heavy chain constant domains 1:

1. IgG - Can be further divided into four subclasses (IgG1, IgG2, IgG3, and IgG4)
2. IgM - Important in the early immune response
3. IgA - Found predominantly at mucosal surfaces; has two subclasses (IgA1 and IgA2) 3
4. IgE - Involved in allergic reactions and parasite defense
5. IgD - Functions in B-cell development

Variable and Constant Domains

The immunoglobulin molecule can be functionally divided into:

• Variable domains: These bind to antigens and are created through a complex series of gene rearrangement events 1. Each variable domain contains:

  • Three complementarity-determining regions (CDRs) that form the antigen-binding site
  • Four framework regions of relatively constant sequence

• Constant domains: These specify effector functions such as:

  • Activation of complement
  • Binding to Fc receptors
  • Transport across mucosa (IgA and IgM) or placenta (IgG1/3) 2

Light and Heavy Chains

An important point of clarification regarding statement 4 in the question:

• An immunoglobulin molecule contains two identical heavy chains and two identical light chains 1
• The light chains are not "the same" across different immunoglobulin molecules - they are specific to each antibody
• There are two types of light chains (kappa and lambda), but any single antibody will have either two kappa or two lambda light chains, not a mixture 1

Clinical Relevance

Understanding immunoglobulin structure and function is essential for:

• Diagnosing immunodeficiency disorders
• Interpreting serological tests
• Understanding the mechanisms of passive immunization therapy
• Developing therapeutic monoclonal antibodies 2

Immunoglobulin replacement therapy is a key treatment for patients with significant hypogammaglobulinemia, documented impaired antibody production, and history of recurrent infections 4.

Common Pitfalls

• Confusing the number of immunoglobulin classes (five, not six)
• Misunderstanding the composition of light and heavy chains (two identical heavy chains and two identical light chains in each immunoglobulin molecule)
• Failing to recognize that plasma cells (not B cells directly) are the primary producers of antibodies

Therefore, statements 1 (immunoglobulins are produced by plasma cells) and 3 (the antigen-antibody combining sites are located on the Fab fragment) are correct, making E the correct answer.