Antibodies

Overview – Antibodies

Antibodies are specialised immunoglobulin proteins produced by plasma cells in response to antigen exposure. They play a central role in the adaptive immune system, with diverse effector functions including pathogen neutralisation, opsonisation, complement activation, and antibody-dependent cellular cytotoxicity. Understanding antibody structure, function, and isotype diversity is essential for grasping immune defence, vaccine mechanisms, and immunotherapy.

Definition

  • Antibodies = Immunoglobulin (Ig) proteins that bind specifically to antigens
  • Produced by plasma cells (differentiated B cells) after infection or immunisation
  • Found:

Functions of Antibodies

  • Neutralisation
    • Bind directly to viruses, bacteria, or toxins → prevent cellular entry or toxicity
    • Neutralised particles are then phagocytosed
antibodies: Neutralisation
CNX OpenStax, CC BY 4.0 <https://creativecommons.org/licenses/by/4.0>, via Wikimedia Commons
  • Opsonisation
    • Antibodies coat pathogens → enhance recognition by phagocytes via Fc receptors
Opsonisation
CNX OpenStax, CC BY 4.0 <https://creativecommons.org/licenses/by/4.0>, via Wikimedia Commons
  • Complement Activation
    • Trigger classical complement pathway → lysis of extracellular microbes
  • Agglutination
    • Cross-link multiple pathogens → form antigen-antibody complexes
    • Facilitates clearance by phagocytes
Agglutination
CNX OpenStax, CC BY 4.0 <https://creativecommons.org/licenses/by/4.0>, via Wikimedia Commons
  • Antibody-Dependent Cellular Cytotoxicity (ADCC)
    • Antibodies bind infected or abnormal cells → recruit:
      • Natural killer (NK) cells → cell lysis
      • Eosinophils (via IgE) → parasite destruction
Ab-Dependent Cellular Cytotoxicity
CNX OpenStax, CC BY 4.0 <https://creativecommons.org/licenses/by/4.0>, via Wikimedia Commons

Antibody Structure

  • Y-shaped molecule with:
    • 2x Heavy chains (long)
    • 2x Light chains (short)
    • Each chain has:
      • Constant region (Fc) → interacts with immune effectors
      • Variable region (Fab) → binds specific antigen

Functional Regions

  • Fab (Fragment Antigen-Binding):
    • Contains VH (variable heavy) & VL (variable light)
    • Recognises epitopes on antigen
    • Includes complementarity-determining regions (CDRs)
  • Fc (Fragment Crystallisable):
    • Constant region of heavy chain
    • Binds Fc receptors on phagocytes, NK cells, mast cells
    • Activates complement pathway
  • Hinge Region:
    • Formed by heavy chains
    • Provides flexibility → enables cross-linking
    • Stabilised by disulphide bonds
Antibody Structure
CNX OpenStax, CC BY 4.0 <https://creativecommons.org/licenses/by/4.0>, via Wikimedia Commons

Antibody Diversity Generation

Primary Diversification – During B cell maturation

  • Ig Gene Rearrangement:
    • Heavy chains: V, D, J gene recombination
    • Light chains: V, J gene recombination
    • Generates a wide repertoire of BCR/antibody variants
    • Mirrors T cell receptor (TCR) rearrangement in T cells
antibodies: Ig-Gene Rearrangement
Antibodies specific for nucleic acid modifications: https://www.researchgate.net/figure/Schematic-overview-of-the-organization-and-expression-of-immunoglobulin-Ig-genes_fig1_315756763

Secondary Diversification – In activated B cells

  • Somatic Hypermutation (in germinal centres):
    • Point mutations in variable region genes
    • Results in altered affinity for antigen
    • High-affinity clones are selected for clonal expansion
  • Isotype Switching:
    • Fc region genes replaced → switch from IgM to IgG, IgA or IgE
    • Requires CD4+ helper T cell interaction (via CD40/CD40L)
    • Cytokine-dependent (dictates isotype produced)
    • Antigen specificity is retained; only effector function changes

Isotype Switching

  • Naive B cells express IgM and IgD
  • First antibody secreted = IgM
  • Later, plasma cells switch to:
    • IgG1/2/3/4
    • IgA
    • IgE
  • Switch requires:
    • CD4+ helper T cell cytokines
    • CD40-CD40L interaction
    • Antigen type (thymus-dependent vs thymus-independent)
Antibodies Isotype Switching
Source: https://ruo.mbl.co.jp/bio/e/support/method/antibody-isotype.html

Antibody Isotypes

IsotypeFunctionsStructure
IgMFirst responder; neutralisation, opsonisation, complement activation; BCRPentamer (in serum), Monomer (on B cells)
IgDBCR on naive B cellsMonomer
IgGMajor serum antibody; neutralisation, opsonisation, complement activation, placental transferMonomer
IgAMucosal immunity (secretions, breast milk, GIT, respiratory tract)Dimer (in secretions), Monomer (in serum)
IgEAllergic responses, parasite defence; binds mast cells → histamine/serotonin releaseMonomer

Note: IgM and IgE have an additional constant domain (CH3) compared to other isotypes.

antibodies Isotypes
The 5 Isotypes of antibodies
CNX OpenStax, CC BY 4.0 <https://creativecommons.org/licenses/by/4.0>, via Wikimedia Commons

Summary – Antibodies

Antibodies are key effectors of the adaptive immune system, functioning through antigen binding, opsonisation, neutralisation, complement activation, and isotype-specific immune responses. Structural variation and diversification mechanisms equip them to combat a wide range of pathogens. For a broader context, see our Immune & Rheumatology Overview page.

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