relate the molecular structure of antibodies to their functions

Published by Patrick Mutisya · 14 days ago

Cambridge A-Level Biology 9700 – Antibodies and \cdot accination

Antibodies and \cdot accination

Learning Objective

Students will be able to relate the molecular structure of antibodies to their biological functions and to explain how vaccination exploits these relationships.

1. Basic Structure of an Antibody

Antibodies (immunoglobulins, Ig) are Y‑shaped glycoproteins composed of four polypeptide chains:

  • Two identical heavy (H) chains

  • Two identical light (L) chains

Each chain has a constant (C) region and a variable (V) region. The two arms of the Y contain the antigen‑binding sites, while the stem (Fc region) mediates effector functions.

Suggested diagram: Y‑shaped antibody showing Fab (antigen‑binding) and Fc (effector) regions.

2. Variable and Constant Regions

The variable regions of the heavy and light chains (VH and VL) together form the antigen‑binding site. Diversity is generated by somatic recombination of V, D, and J gene segments, producing a vast repertoire of antibodies.

Mathematically, the antigen‑binding site can be represented as:

\$\text{Binding site} = VH + VL\$

The constant regions (CH and CL) determine the antibody class (isotype) and dictate how the Fc region interacts with immune cells and complement proteins.

3. Functional Regions

  1. Fab (Fragment antigen‑binding): Each arm of the Y contains one Fab fragment (one VH + VL + CL). It confers specificity and binds to epitopes on antigens.

  2. Fc (Fragment crystallizable): The stem of the Y is formed by the constant domains of the heavy chains. It interacts with:

    • Fc receptors on phagocytes, NK cells, and mast cells

    • Complement component C1q, initiating the classical pathway

4. Antibody Classes (Isotypes)

IsotypeHeavy‑chain typeStructure (subunits)Primary locationKey functions
IgGγY‑shaped (2H + 2L)Serum, extracellular fluidNeutralisation, opsonisation, complement activation, placental transfer
IgMμPentamer (5 × (Y‑shaped))Serum (early response)Strong complement activation, agglutination
IgAαMonomer (serum) / Dimer (secretory)Mucosal surfaces, secretionsNeutralisation of pathogens at entry points
IgEεY‑shapedBound to mast cells & basophilsAllergic responses, defence against parasites
IgDδY‑shapedSurface of mature B cellsRole in B‑cell activation (still not fully understood)

5. How Structure Determines Function

  • Antigen specificity: The hypervariable complementarity‑determining regions (CDRs) within VH and VL form a unique paratope that fits a specific epitope.

  • Valency: IgM’s pentameric form provides ten binding sites, increasing avidity and enabling efficient agglutination.

  • Fc region interactions: Different constant domains dictate binding to distinct Fc receptors (e.g., FcγR for IgG, FcεR for IgE) and complement component C1q.

  • Isotype distribution: Secretory IgA’s dimeric form, linked by a J chain and secretory component, resists proteolysis in mucosal secretions.

6. Vaccination – Harnessing the Antibody Response

Vaccines aim to induce a protective antibody response without causing disease. The key steps are:

  1. Antigen presentation: A vaccine delivers an antigen (live‑attenuated, inactivated, subunit, toxoid, or mRNA‑encoded) that is taken up by antigen‑presenting cells.

  2. Activation of naïve B cells: B‑cell receptors (membrane‑bound Ig) bind the antigen, leading to clonal expansion.

  3. Isotype switching: Cytokines from helper T cells induce class‑switch recombination, producing IgG (or IgA for mucosal vaccines) with higher affinity.

  4. Affinity maturation: Somatic hypermutation in germinal centres refines the variable region, increasing binding strength.

  5. Memory formation: Long‑lived plasma cells secrete antibodies; memory B cells persist for rapid secondary responses.

7. Types of \cdot accines and Their Structural Implications

  • Live‑attenuated: Replicate in host, stimulating strong IgG and IgA responses; mimic natural infection.

  • Inactivated/killed: Primarily induce IgG; often require adjuvants to enhance Fc‑mediated functions.

  • Subunit / protein‑based: Present specific epitopes; design can focus on exposing neutralising epitopes on the Fab region.

  • Toxoid: Inactivated toxins elicit antibodies that neutralise the toxin’s active site.

  • mRNA / viral vector: Encode antigenic proteins that are expressed in host cells, leading to endogenous processing and presentation, favouring robust IgG and cytotoxic T‑cell responses.

8. Clinical Correlation – Antibody Deficiencies and \cdot accine Efficacy

Individuals lacking certain isotypes (e.g., IgG subclass deficiencies) may have reduced vaccine efficacy because the Fc‑mediated clearance mechanisms are compromised. Understanding the structural basis of each isotype helps predict which vaccine formulations will be most protective.

9. Summary

  • The variable regions of antibodies confer antigen specificity; the constant Fc region determines effector functions.

  • Isotype structure (monomer, dimer, pentamer) influences valency, location, and interaction with immune components.

  • Vaccines are designed to stimulate the production of high‑affinity, class‑switched antibodies that can neutralise pathogens and recruit Fc‑mediated mechanisms.

  • Memory B cells and long‑lived plasma cells provide durable protection, the cornerstone of successful vaccination programs.