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Immunology

Classes & Subclasses

Let’s talk about the “business end” of the humoral immune system—the actual weapons that the B-cells produce. These are the Immunoglobulins, also known as antibodies

Think of the immune system’s toolbox. You wouldn’t use a hammer to turn a screw. In the same way, the body produces different classes of immunoglobulins, each with a unique structure and specialized function, perfectly designed for a specific job. For a Medical Laboratory Scientist, knowing the “who, what, and where” of these molecules is fundamental to interpreting nearly every serology test we run

Basic Immunoglobulin Structure: The Blueprint

Before we dive into the classes, let’s remember the basic blueprint. A single antibody molecule (a monomer) is a Y-shaped protein made of four polypeptide chains:

  • Two identical Heavy Chains: These long chains form the body of the “Y.” The type of heavy chain determines the antibody’s class (isotype)
  • Two identical Light Chains: These shorter chains are attached to the arms of the “Y.”
  • Fab Region (Fragment, antigen-binding): These are the two “arms” of the Y. The tips of the Fab region are the variable portions, forming the unique, highly specific pocket that binds to the antigen. This is the “what it recognizes” part
  • Fc Region (Fragment, crystallizable): This is the “stem” of the Y. It’s the constant region that is the same for all antibodies of a given class. The Fc region determines the antibody’s biological function—it’s the “what it does” part. It dictates if the antibody can activate complement, cross the placenta, or bind to specific immune cells

Five Classes (Isotypes) of Immunoglobulins

Now, let’s open the toolbox and look at the five different classes, which you can remember with the mnemonic GAMED

IgG: The All-Purpose Workhorse

Think of IgG as the versatile and reliable Swiss Army knife of antibodies. It is the most abundant immunoglobulin in the blood (~75-80% of total Ig), making it the major player in protecting the body against bacteria and viruses

  • Structure: Monomer (the classic Y-shape)
  • Function
    • Major Secondary Response Antibody: This is the key antibody produced during the anamnestic (memory) response. High levels of IgG indicate a past infection or vaccination and signal long-term immunity
    • Placental Transfer: IgG is the only immunoglobulin class that can cross the placenta. This provides the developing fetus and newborn with passive immunity from the mother for the first few months of life
    • Opsonization: The IgG Fc region can be recognized by receptors on phagocytes (like macrophages), coating pathogens to make them more “tasty” for phagocytosis
    • Complement Activation: It can activate the classical complement pathway, leading to pathogen lysis
  • Subclasses: There are four subclasses (IgG1, IgG2, IgG3, and IgG4) that differ slightly in their heavy chains. They have varying abilities to fix complement and cross the placenta. For example, IgG1 and IgG3 are very effective at complement activation
  • Lab Relevance: Detecting specific IgG is crucial for determining immunity (e.g., Rubella or Varicella titers). In blood banking, maternal IgG antibodies against fetal red blood cells are the cause of Hemolytic Disease of the Fetus and Newborn (HDFN)

IgM: The First-Response SWAT Team

Think of IgM as the first responder to a 911 call. It’s the first antibody produced during a primary immune response, making its presence a critical clue for diagnosing an acute infection

  • Structure: Pentamer. It’s a massive molecule made of five Y-shaped monomers joined together by a J chain. This structure gives it 10 antigen-binding sites!
  • Function
    • Primary Response Antibody: The first Ig class produced during an initial infection
    • Most Efficient Complement Activator: Because of its multiple Fc regions clustered together, IgM is a potent activator of the classical complement pathway, making it extremely effective at killing bacteria
    • Agglutination: Its large size and 10 binding sites make it fantastic at clumping (agglutinating) antigens, like bacteria or red blood cells, which helps in clearing them from the body
  • Lab Relevance: Detection of specific IgM is the cornerstone of diagnosing a current or recent infection (e.g., IgM for Hepatitis A). In the blood bank, the naturally occurring anti-A and anti-B antibodies are IgM, which is why they are so good at causing rapid agglutination. Because of its large size, IgM cannot cross the placenta

IgA: The Mucosal Guardian

Think of IgA as the bouncer at the door of all your mucosal surfaces. Its job is to prevent pathogens from ever getting inside the body in the first place

  • Structure: It exists as a monomer in the serum but is found as a dimer (two monomers joined by a J chain) in secretions. Secretory IgA also has a secretory component, a protein that protects it from being broken down by enzymes in harsh environments like the gut
  • Function
    • Mucosal Immunity: It is the main immunoglobulin found in secretions such as tears, saliva, breast milk, and mucus lining the respiratory and gastrointestinal tracts
    • Neutralization: It prevents pathogens and toxins from binding to and entering host cells at mucosal surfaces
  • Lab Relevance: IgA levels are measured to investigate certain immunodeficiencies (IgA deficiency is the most common primary immunodeficiency). It is also passively transferred to newborns through breast milk, providing crucial gut protection

IgE: The Allergy and Parasite Specialist

IgE is the highly specialized, but powerful, alarm system of the immune response. It is present in the lowest concentration in serum but is responsible for some of the most dramatic immune reactions

  • Structure: Monomer
  • Function
    • Allergic Reactions: The Fc region of IgE binds very strongly to receptors on mast cells and basophils. When the Fab region binds to an allergen (like pollen), it causes the cell to degranulate, releasing a flood of inflammatory mediators like histamine. This causes the classic symptoms of a Type I hypersensitivity reaction (allergies, anaphylaxis)
    • Defense Against Parasites: It plays a key role in fighting off parasitic worm infections
  • Lab Relevance: The clinical lab measures levels of total IgE and, more importantly, specific IgE against various allergens (e.g., peanut, pollen, pet dander) to help diagnose allergies

IgD: The B-Cell’s Antenna

IgD remains the most enigmatic of the immunoglobulins in terms of its serum function. Its primary role is not in the bloodstream but on the surface of the cell that made it

  • Structure: Monomer
  • Function
    • B-Cell Receptor: Found in low concentrations in the serum, its primary function is to act as a surface receptor on mature, naive B-lymphocytes, alongside IgM. It helps signal the B-cell to become activated when it encounters its specific antigen
  • Lab Relevance: IgD has very limited clinical diagnostic use in a routine serology lab