Table of Contents
Structure and Basic Properties of Antibodies
Antibodies (immunoglobulins, abbreviated Ig) are Y‑shaped proteins produced by certain white blood cells in response to specific antigens. They are soluble forms of the receptors found on B lymphocytes and are key tools of the specific (adaptive) immune response.
General Architecture
Each antibody molecule is built in a similar modular way:
- Four polypeptide chains
- 2 identical heavy (H) chains
- 2 identical light (L) chains (either κ or λ, but both light chains in one antibody are the same type)
These chains are linked by disulfide bonds (covalent S–S bridges) to form a Y‑shaped structure.
Constant and Variable Regions
Each chain has:
- A variable (V) region at the tip (N‑terminal part), and
- A constant (C) region along the rest (C‑terminal part).
Key points:
- Variable regions (V regions)
- Present on both heavy and light chains (V\_H and V\_L).
- Form two identical antigen‑binding sites at the tips of the Y.
- Contain highly variable short stretches called complementarity‑determining regions (CDRs), which physically contact the antigen.
- Differences in amino acid sequence here determine antibody specificity.
- Constant regions (C regions)
- Much less variable in sequence.
- Determine the antibody’s class (isotype) and many effector functions (how the antibody interacts with other parts of the immune system).
Fragments: Fab and Fc
If an antibody is treated with specific proteases, it can be split into functional fragments:
- Fab (Fragment antigen binding)
- Contains one whole light chain + part of one heavy chain.
- Has one antigen‑binding site.
- Responsible for binding the antigen.
- Fc (Fragment crystallizable)
- Composed of the constant parts of the two heavy chains.
- Does not bind antigen directly.
- Binds to Fc receptors on immune cells and to complement proteins, thus triggering downstream immune reactions.
So, each antibody has:
- 2 antigen‑binding sites (2 Fab arms),
- 1 Fc region (the stem of the Y) that recruits effector mechanisms.
Antigen Binding and Specificity
Epitopes and Paratopes
- An antigen usually has several distinct regions called epitopes (or antigenic determinants).
- Each antibody binds one specific epitope using a matching paratope (the binding surface formed by the CDRs in its variable regions).
Binding:
- Is based on non‑covalent interactions: hydrogen bonds, ionic bonds, hydrophobic interactions, and van der Waals forces.
- Is highly specific: a good “fit” between paratope and epitope is needed (often described with the “lock‑and‑key” or “induced fit” analogy).
- Can be high affinity (strong binding to a single epitope) and high avidity (overall strength when multiple binding sites and epitopes interact simultaneously).
Diversity of Antibodies (Overview)
The body can produce an enormous variety of antibodies, each with a different specificity, by:
- Combining different gene segments for V regions,
- Introducing additional variation at the joining sites,
- Modifying antibody genes later during immune responses.
The detailed genetic mechanisms (V(D)J recombination, somatic hypermutation, etc.) are covered in genetics‑related chapters. For this chapter, the key idea is:
- Different amino acid sequences in the variable regions = different shapes of antigen‑binding sites = different specificities.
Classes (Isotypes) of Antibodies
Antibodies can be grouped into five main classes (isotypes), defined by the constant region of their heavy chains. Each class has typical locations and functions.
IgG
- Heavy chain type: γ (gamma)
- Basic structure: monomer (Y‑shaped)
- Location:
- Main antibody in blood and tissue fluids
- Also found in lymph
- Functions:
- Dominant antibody in secondary (memory) responses
- Neutralization of toxins and viruses
- Opsonization: coats pathogens so phagocytes can bind and ingest them more easily
- Activates complement (classical pathway)
- Crosses the placenta in humans, providing passive immunity to the fetus/newborn
IgM
- Heavy chain type: μ (mu)
- Basic structure:
- On B cell surface: monomer (as B cell receptor)
- Secreted form: mostly pentamer (five Y‑shaped units linked by a J chain)
- Location:
- Mainly in blood (because of large size, poorly diffuses into tissues)
- Functions:
- First antibody produced in a primary response
- Very high avidity (many binding sites per pentamer: 10 potential antigen‑binding sites)
- Very effective at complement activation
- Helps to agglutinate (clump) pathogens, making them easier to clear
IgA
- Heavy chain type: α (alpha)
- Basic structure:
- In blood: monomer
- At mucosal surfaces: mostly dimer (two units linked by a J chain and a secretory component)
- Location:
- Main antibody in mucosal secretions: saliva, tears, mucus, intestinal fluid, respiratory tract, urogenital tract
- Important in breast milk (colostrum), providing mucosal protection for the newborn
- Functions:
- Protects mucosal surfaces by neutralizing pathogens and toxins
- Prevents microbes from adhering to and penetrating epithelial cells
- Typically does not strongly activate complement; more focused on non‑inflammatory protection at mucosa
IgE
- Heavy chain type: ε (epsilon)
- Basic structure: monomer
- Location:
- Very low concentration in blood
- Binds with its Fc region to high‑affinity Fc receptors on mast cells and basophils (and some eosinophils)
- Functions:
- Key role in type I (immediate) allergies:
- When allergen binds to IgE on mast cells, it triggers degranulation and release of histamine and other mediators.
- Important in defense against parasitic worms (helminths):
- IgE‑coated parasites are recognized by eosinophils, which can attack and damage them.
IgD
- Heavy chain type: δ (delta)
- Basic structure: monomer
- Location:
- Primarily on the surface of naive B cells, together with IgM
- Only small amounts in blood
- Functions:
- Acts mainly as a B cell receptor (BCR) for antigen during early B cell development
- Helps in the activation and differentiation of B cells (detailed mechanisms are covered in chapters on B cell biology)
How Antibodies Help Eliminate Pathogens
Antibodies do not usually kill pathogens directly. Instead, they mark and neutralize them and recruit other immune components.
Neutralization
- Antibodies bind to toxins or to viral/bacterial surface molecules that are needed for attachment or entry into host cells.
- This blocks the pathogen or toxin from interacting with host receptors.
- Neutralized toxins or pathogens are then removed by immune cells.
Neutralization is especially important for:
- Many viruses,
- Bacterial or other toxins (e.g., tetanus toxin),
- Pathogens that rely on specific adhesion molecules.
Agglutination and Precipitation
- Because each antibody has at least two binding sites, it can bind more than one antigen particle at the same time.
- This can cause agglutination (clumping) of cells (e.g., bacteria, red blood cells) or precipitation of soluble antigens.
Consequences:
- Large immune complexes are easier for phagocytes to recognize and ingest.
- Pathogens lose mobility and are trapped, for example, in mucus.
Opsonization
- Some antibodies (especially IgG subclasses) bind both:
- To the pathogen, via Fab, and
- To Fc receptors on phagocytes, via Fc.
- This makes the pathogen more "tasty" to phagocytes – hence the term opsonization (“to season” or “prepare for eating”).
Outcome:
- Enhanced phagocytosis by neutrophils and macrophages.
- More efficient destruction of pathogens in phagosomes.
Activation of Complement
Certain antibody classes (notably IgM and some IgG subclasses) can activate the classical complement pathway when bound to antigen.
Consequences of complement activation include:
- Formation of the membrane attack complex (MAC), which can lyse some bacteria.
- Opsonization with complement fragments (e.g., C3b) that further promote phagocytosis.
- Release of small fragments that act as inflammatory mediators and chemoattractants.
Antibody‑Dependent Cellular Cytotoxicity (ADCC)
- In ADCC, immune cells (such as natural killer (NK) cells) recognize target cells that have been coated with antibodies (typically IgG).
- NK cells bind to the Fc part of these antibodies via Fc receptors.
- This engagement triggers NK cells to release toxic molecules that kill the antibody‑coated target cell (often virus‑infected or tumor cells).
ADCC is a bridge between the humoral and cellular arms of the immune response.
Production and Changes of Antibodies During an Immune Response
Primary and Secondary Responses (Overview)
After exposure to an antigen:
- Primary response:
- Occurs on first contact with an antigen.
- Begins after a delay (lag phase) needed for B cell activation and differentiation.
- IgM is usually produced first, followed by class switching to other isotypes (e.g., IgG, IgA, IgE).
- Antibody affinity is initially modest.
- Secondary (memory) response:
- Triggered by the same antigen at a later time.
- Faster and stronger due to memory B cells.
- Dominated by IgG (and sometimes IgA or IgE, depending on antigen and site).
- Antibodies usually have higher affinity (affinity maturation).
Details of B cell activation, plasma cells, and memory formation are treated in other sections; here the focus is on how antibodies change over time.
Class (Isotype) Switching
- A B cell can change the class of antibody it produces (e.g., from IgM to IgG or IgA) without changing its antigen specificity.
- This process, called class switch recombination, alters the constant region of the heavy chain but keeps the same variable region.
- Result:
- Same antigen specificity,
- Different effector functions and distribution (e.g., now secreted in mucosa as IgA instead of being mostly in blood as IgM).
Class switching is influenced by:
- Signals from helper T cells, and
- Cytokines present during the immune response.
Affinity Maturation (Conceptual)
Throughout an ongoing immune response:
- B cells in certain lymphoid structures introduce mutations into their antibody variable region genes.
- B cells with higher‑affinity receptors are preferentially selected to proliferate and differentiate.
- Over time, the average affinity of antibodies for the antigen increases.
This process is called affinity maturation and explains why antibodies in a memory response are often more effective.
Forms and Uses of Antibodies Outside the Body
The same properties that make antibodies useful in the immune system make them valuable tools in medicine and research.
Monoclonal vs. Polyclonal Antibodies
- Polyclonal antibodies
- A mixture of antibodies produced by many different B cell clones.
- Recognize multiple epitopes on the same antigen.
- Commonly generated in animals for use in laboratory tests.
- Monoclonal antibodies
- Identical antibodies produced by a single B cell clone (or derived cell line).
- Recognize only one epitope.
- Can be engineered with precise characteristics (specificity, isotype, etc.).
Medical Applications
Some important uses include:
- Diagnostics
- Pregnancy tests,
- Detection of viruses or bacteria,
- Measurement of hormones or drugs (e.g., ELISA tests).
- Therapeutics
- Treatment of certain cancers, autoimmune diseases, and chronic inflammatory conditions (e.g., antibodies that block specific cytokines or cell surface molecules).
- Neutralizing antibodies against specific toxins or pathogens (e.g., antivenoms, antibodies against viral infections).
Details of these medical uses, including risks and benefits, are covered in disease‑ and therapy‑related chapters.
Summary
- Antibodies are Y‑shaped proteins made of two heavy and two light chains, with variable regions for antigen binding and constant regions that determine class and effector functions.
- Each antibody recognizes a specific epitope via its antigen‑binding site formed by CDRs in the variable regions.
- The main isotypes (IgG, IgM, IgA, IgE, IgD) differ in:
- Heavy chain type,
- Structure (monomer, dimer, pentamer),
- Location in the body,
- Role in immune defense (e.g., neutralization, mucosal protection, allergy).
- Antibodies contribute to defense by neutralization, agglutination, opsonization, complement activation, and ADCC.
- During immune responses, B cells can switch antibody class and increase antibody affinity, leading to more effective and specialized humoral immunity.
- Antibodies are also powerful diagnostic and therapeutic tools in modern medicine.