General structural principle
All immunoglobulins are built according to a single basic plan. They are based on two types of peptide chains: heavy (Heavy, $H$) and
Each chain consists of functional blocks—domains. The molecule always contains one variable domain and one to three constant domains. It is the variable regions of the light and heavy chains together that form the unique antigen-binding sites (ABS). Each antibody monomer has at least two such centers, allowing it to firmly anchor the antigen.
Classification of immunoglobulins
Division into classes depends on the type of heavy chains, structural features, and performed functions:
- IgM class (contains $\mu$-type heavy chains). Exists in two forms. On the B-lymphocyte membrane, it functions as a receptor in monomeric form. However, into the plasma, early plasmacytes secrete it as a large pentamer. Five basic molecules are held together by a special connecting J-chain, forming a structure with 10 antigen-binding sites.
- IgG class ($\gamma$-type heavy chains). These are classical monomers and the most abundant pool of antibodies in the blood. They are actively produced at the end of the primary immune response and dominate during secondary infections. Important feature: their $F_c$-fragment is readily recognized by macrophage and neutrophil receptors, which facilitates phagocytosis.
- IgA class ($\alpha$-type heavy chains). The main defender of mucous membranes. Inside plasmacytes, it assembles into a dimer using a J-chain. However, during transport through the surface or glandular epithelium, a secretory component (S) is added to the molecule. This detail saves the antibody from being digested by aggressive enzymes in secretions.
- IgE class ($\epsilon$-type heavy chains). Almost absent in free plasma (less than 0.01%). Nearly all IgE is pre-fixed by its $F_c$-regions to the surface of circulating basophils and mast cells, waiting for contact with an allergen.
- IgD class ($\delta$-type heavy chains). A monomer that, along with membrane IgM, sits on the surface of "naive" (unstimulated) B-lymphocytes, acting as a receptor.
Effector mechanisms: what happens after binding
Antibody-antigen binding is only the first step. Next, destruction mechanisms are triggered:
- Opsonization and phagocytosis. If the antigen is soluble, specific IgG binds it into complexes. These complexes are adsorbed onto the surface of macrophages and neutrophils (due to $F_c$-region receptors), followed by engulfment (endocytosis) and digestion.
- Complement activation. If a microorganism or foreign cell is coated with antibodies, a cascade reaction of plasma proteins is triggered. A membrane attack complex assembles on the target membrane, piercing ion channels. The result is osmotic shock and cell lysis (death).
- Hypersensitivity reactions. If an antigen (allergen) binds to IgE already resident on mast cells, the latter instantly degranulate, releasing histamine and other inflammatory mediators into the tissues.
Dynamics of the humoral response
During the first encounter with an infection (primary response), the peak of immunoglobulin production is reached only by the end of the second week. Then the fading phase begins: plasma cells do not live long (2-3 weeks) and, if the antigen has disappeared, antibody levels drop.
If the same antigen enters the body again (secondary response), immunological memory is triggered. The reaction proceeds much faster and more powerfully, with the body immediately starting to synthesize specialized molecules (IgG, IgA, IgE), skipping the prolonged IgM production phase.
There is also a special pathway—the humoral response to T-independent antigens. Large polymers (e.g., bacterial lipopolysaccharides) can activate a B-cell independently, without the help of T-helper cells. They bind multiple B-cell receptors on the membrane simultaneously. With this response, antibody class switching does not occur, and cells synthesize exclusively IgM.
Briefly: answers to topical questions
Which class of immunoglobulins is capable of crossing the placental barrier?
The only class of immunoglobulins capable of crossing the placental barrier is immunoglobulin G (IgG).
This property is due to the fact that IgG molecules have a low molecular weight, unlike IgM class antibodies. The penetration of IgG through the placenta into the fetal bloodstream ensures the establishment of its passive immunity. In clinical practice, this same mechanism underlies the development of Rhesus incompatibility and hemolytic disease, when maternal IgG attacks fetal erythrocytes.
Which classes of immunoglobulins are capable of activating the complement system via the classical pathway?
Antibodies of classes IgG and IgM are capable of activating the complement system via the classical pathway.
Activation is triggered at the stage of antigen-antibody (Ag-Ab) complex recognition, leading to the binding of the C1qrs complex. Subsequently, this initiates a cascade of blood plasma protein reactions that culminates in the formation of the membrane attack complex, causing osmotic shock and lysis of the target cell.
What enzymes are used to cleave immunoglobulins into Fab and Fc fragments under laboratory conditions?
The proteases papain and pepsin are used for the enzymatic cleavage of immunoglobulins.
- Papain cleaves the immunoglobulin molecule to form two antigen-binding Fab fragments and one Fc fragment.
- Pepsin cleaves the molecule differently: it forms one doubled bivalent antigen-binding F(ab')2 fragment and a shortened Fc' fragment.
GAMED is a simple acronym of the first letters of the classes (IgG, IgA, IgM, IgE, IgD) to make sure you don't forget any of them on the exam.
Class and exam questions
Why are class A immunoglobulins not degraded in the digestive tract?
The secret of their stability lies in the addition of a special S-component (secretory). It is added to the IgA dimer as the molecule passes through the mucous membrane epithelium and protects the antibody from local enzymes.
How does the primary immune response differ from the secondary response?
During the primary response, antibody concentration rises slowly (about two weeks), and predominantly IgM is synthesized first. The secondary response (thanks to memory cells) develops much faster, more strongly, and is characterized by an immediate switch to the production of IgG, IgA, or IgE.
How do antibodies work in allergies?
In the body of an allergic person, IgE is synthesized, which firmly attaches via its $F_c$ fragments to mast cells and basophils. Upon re-exposure to the allergen, it binds to these IgE molecules directly on the cell surface, causing an immediate release of histamine (degranulation).
What else to study on this topic
- Structure and functions of the B-cell receptor (BCR)
- Complement system activation cascade and the membrane attack complex
- Mechanisms of immunoglobulin class switching in B-lymphocytes
- Characteristics of $F_c$ receptors on macrophages and neutrophils
- Thymus-dependent and thymus-independent antigens: molecular differences
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