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Immunology

Immunoglobulins

Think of immunoglobulins not just as proteins, but as a family of highly specialized tools. Each one has a unique design that makes it perfect for a particular job, whether it’s long-term defense, rapid emergency response, or guarding our most vulnerable surfaces

Part 1: Blueprint - Universal Antibody Structure

Before we look at the different models, we must understand the basic chassis they are all built upon. The fundamental unit of any antibody is a monomer, a Y-shaped glycoprotein with a precise architecture

  • Chains: The monomer is built from four polypeptide chains held together by strong disulfide bonds
    • Two identical Heavy Chains: form the body of the “Y.” Their structure determines the antibody’s class (isotype)
    • Two identical Light Chains: (either kappa or lambda) are attached to the arms
  • Functional Regions: The molecule is divided into two critical functional areas
    • Fab Region (Fragment, antigen-binding): These are the two “arms” of the Y. The tips of the Fab are the variable regions, which form a unique pocket designed to bind to one specific antigen. This is the “recognition” part of the molecule
    • Fc Region (Fragment, crystallizable): This is the “stem” of the Y. It is the constant region that is the same for all antibodies of a given class. This is the “effector” part that dictates the antibody’s biological function—what happens after the antigen is bound. It determines if the antibody can activate complement, cross the placenta, or bind to immune cells

Part 2: Toolbox - Classes and Properties

The body produces five different classes (isotypes) of immunoglobulins by using different types of heavy chains. Each class has a unique combination of physical and biological properties tailored to its specific mission. We can remember them with the mnemonic GAMED

IgG: The Workhorse of Immunity

  • Structure: Monomer. It is the most abundant Ig in the blood (~80%)
  • Properties: It’s a small, stable molecule with a long half-life (~23 days). Its size is its superpower
  • Functions & Clinical Significance
    • Memory/Secondary Response: The major antibody of the secondary (anamnestic) response. Its presence indicates past infection or immunity from vaccination
    • Placental Transfer: It is the only class that can cross the placenta, providing the fetus with critical passive immunity. This is also the basis for Hemolytic Disease of the Fetus and Newborn (HDFN)
    • Opsonization & Complement: An excellent opsonin that coats pathogens for phagocytosis and effectively activates the complement system

IgM: The Acute-Phase First Responder

  • Structure: A massive pentamer (five monomers joined by a J-chain). This structure gives it 10 antigen-binding sites
  • Properties: It is the largest antibody and has a short half-life (~5 days). Its size confines it to the bloodstream
  • Functions & Clinical Significance
    • Primary Response: The first antibody produced during an initial infection. Its presence signals a current or very recent infection
    • Complement Activation: The most efficient activator of the classical complement pathway due to its multiple Fc regions
    • Agglutination: The best agglutinating antibody. This is utilized in the lab for tests like ABO blood typing. It cannot cross the placenta

IgA: The Mucosal Guardian

  • Structure: A monomer in the blood, but a dimer (joined by a J-chain and protected by a secretory component) in bodily secretions
  • Properties: While it’s the second most abundant Ig in serum, it is the most abundant in the entire body when secretions are included
  • Functions & Clinical Significance
    • Mucosal Immunity: The primary defender found in tears, saliva, breast milk, and the mucus of the respiratory and GI tracts. It neutralizes pathogens at the point of entry
    • Passive Immunity: Transferred to newborns via breast milk, protecting their gut
    • Transfusion Reactions: IgA-deficient individuals can have severe anaphylactic reactions to blood products containing IgA

IgE: The Allergy and Parasite Specialist

  • Structure: Monomer. Found in the lowest concentration in the serum
  • Properties: Its Fc region binds with extremely high affinity to the surface of mast cells and basophils
  • Functions & Clinical Significance
    • Allergic Reactions (Type I Hypersensitivity): When an allergen cross-links the IgE on a mast cell, it triggers the release of histamine, causing allergy symptoms
    • Parasite Defense: It is a key player in the immune response to parasitic worms
    • Lab Diagnosis: We measure allergen-specific IgE to help diagnose allergies

IgD: The B-Cell Surface Receptor

  • Structure: Monomer. Very low concentration in serum
  • Functions & Clinical Significance: Its primary known function is to act as an antigen receptor on the surface of naive B-lymphocytes, helping to signal their activation. It has very little diagnostic use in the clinical lab