Basic principles and evolution
According to the classical definition by R.V. Petrov, immunity is the ability of multicellular organisms to maintain homeostasis (constancy of macromolecular composition) by eliminating foreign molecules. Anything considered foreign includes any products of foreign genetic information that the organism can distinguish from its own. If an immune response is mistakenly directed against self-tissues, pathology develops.
Evolutionarily, the emergence of adaptive immunity is closely linked to an increase in the size of living organisms. The more cells there are, the higher the risk of random mutations and viral transformation. Therefore, a mechanism of defense against aggression from within—malignant neoplasms—became necessary.
Adaptive immunity itself is an extremely cumbersome, potentially dangerous, and energetically costly tool. However, it was fixed in evolution due to one crucial property: the ability to generate clones of memory cells.
The basic operating algorithm includes three stages:
- Antigen recognition: identification of foreign objects using clonally distributed receptors.
- Elimination: direct destruction and removal of the antigen.
- Memory formation: fixing the 'experience' of contact for effective protection in the future.
Antigen recognition
Three types of molecules are responsible for specific antigen recognition:
- Immunoglobulins (antibodies).
- αβ-type T-cell receptors (TCR).
- γδ-type T-cell receptors (TCR).
All of these molecules exist as membrane receptors on the surface of lymphocytes. In addition, immunoglobulins are unique in that they can also exist as free, soluble molecules in body fluids.
Structure of immunoglobulins
The term 'immunoglobulin' reflects the protein nature of the molecule, while 'antibody' reflects its functional specificity for a specific antigen. The basic unit (monomer) has a mass of 150–170 kDa and consists of four polypeptide chains connected by disulfide bonds (which can be cleaved with dithiothreitol or mercaptopurine):
- Two heavy H-chains (heavy): mass 100–120 kDa, consist of 4–5 domains.
- Two light L-chains (light): mass 50–60 kDa, consist of 2 domains.
Each domain contains about 110 amino acids. Functionally, the molecule is divided into two zones:
- Variable domains (V-domains): located at the N-terminus. The V-domains of the heavy ($V_H$) and light ($V_L$) chains together form the antigen-binding site. It recognizes the epitope through spatial complementarity.
- Constant domains (C-domains): have a constant structure. The L-chain contains one such domain ($C_L$), while the H-chain contains three or four ($C_H1$, $C_H2$, etc.). They do not bind antigen, but determine the effector functions of the antibody (e.g., complement activation).
Under the action of the enzyme papain, the molecule is cleaved into three fragments: two Fab (Fragment antigen binding) and one Fc (Fragment cristallizable).
Brief history of study
The study of antibodies has a rich history marked by several breakthroughs:
- 1890 — E. Behring and S. Kitasato discovered antibodies, proving that rabbit serum can neutralize diphtheria toxin.
- 1937 — A. Tiselius identified immunoglobulins using electrophoresis in serum protein fractions.
- 1975 — G. Köhler and C. Milstein developed hybridoma technology to produce monoclonal antibodies.
- Late 1970s — S. Tonegawa discovered somatic gene rearrangement, explaining the colossal diversity of antibodies.
Briefly: answers to topical questions
What effector functions do the constant domains (C-domains) of immunoglobulins perform?
The constant domains (C-domains) of immunoglobulins determine the effector functions of antibodies and are not involved in antigen recognition. The main effector functions they provide include:
- Interaction with cell receptors — binding to cellular structures to execute the immune response.
- Complement activation — triggering the complement cascade.
How do immunoglobulin classes (IgG, IgA, IgM, IgE, IgD) differ from one another?
Immunoglobulin classes differ from one another in the structure of their heavy chains (H-chains) and spatial organization.
| Class | H-chain isotype | Spatial organization | Features |
|---|---|---|---|
| IgG | $\gamma$ | Monomer | Main monomeric form |
| IgD | $\delta$ | Monomer | Main monomeric form |
| IgE | $\epsilon$ | Monomer | Higher number of constant domains in the heavy chain |
| IgA | $\alpha$ | Dimer | Contains a J-chain linking 2 monomers |
| IgM | $\mu$ | Pentamer | Contains a J-chain linking 5 monomers |
What are the main differences between innate and adaptive immunity?
The main differences between innate and adaptive immunity lie in the conditions of their formation, recognition targets, and the presence of memory.
| Characteristic | Innate immunity | Adaptive immunity |
|---|---|---|
| Conditions of formation | Formed during ontogeny regardless of 'demand' | Formed in response to 'demand' |
| Recognition target | Groups of foreign molecules (pathogen-associated molecular patterns) | Individual molecules (antigens) |
| Effector cells | Myeloid cells, partially lymphoid cells | Lymphoid cells |
| Response type | The cell population reacts as a whole | Clonal reaction to the antigen |
| Risk of autoaggression | Minimal | Real |
| Presence of memory | Absent | Immunological memory is formed |
Which cells are effector cells in the adaptive immune response?
Effector cells in the adaptive immune response are differentiated T and B lymphocytes. These include:
- Cytotoxic T lymphocytes (CTL) — destroy infected cells.
- T helper cells (Th1, Th2, Th17) — secrete cytokines, activate macrophages, and recruit neutrophils.
- Plasma cells — develop from B lymphocytes and directly secrete antibodies.
What is the cellular mechanism of immunological memory formation?
The cellular mechanism of immunological memory formation consists of the parallel differentiation of naive lymphocytes during the primary immune response.
- Memory B cells — develop in the apical light zone of germinal centers from B centroblasts/centrocytes. In these cells, somatic hypermutation, isotype switching, and affinity maturation are completed.
- Memory T cells — form with alterations in signaling pathways and the spectrum of chemokine receptors. They begin to express the CD45R0 isoform, which promotes faster activation, and their receptors move into lipid rafts.
Memory cells are not involved in the ongoing response, persisting to provide protection upon re-exposure to the antigen.
To easily remember the results of papain digestion, imagine scissors: they cut off two identical antigen-binding "ears" (2 Fab fragments) from the whole molecule, leaving one base (1 Fc fragment). Total: 1 molecule = 2 Fab + 1 Fc.
Class and exam questions
What is the difference between innate and adaptive immunity?
Adaptive immunity has narrow specificity, generates effector cells de novo, creates immunological memory, and is capable of effectively defending against malignant tumors.
What is the difference between an immunoglobulin and an antibody?
These are two names for the same molecule. "Immunoglobulin" describes the chemical structure of the protein, while "antibody" emphasizes its ability to bind to a specific antigen.
Where is the active site of an antibody located?
The antigen-binding active site is formed by the variable domains (V domains) of the light and heavy chains located at the N-terminus of the molecule.
What else to study on this topic
- Mechanisms of somatic recombination of immunoglobulin genes (S. Tonegawa's discovery)
- Principles of function and structure of T-cell receptors (TCR αβ and γδ)
- Effector functions of the antibody Fc fragment
- Hybridoma technology and monoclonal antibody synthesis
- Interaction of adaptive immunity with tumor cells
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