Levels of immunological defense
The protective functions of our body are implemented at two main levels, each with its own evolutionary and functional features.
Innate (natural) immunity is a phylogenetically older mechanism. Its main feature is the lack of narrow specialization. These defense systems operate continuously and are directed against absolutely any foreign factor. The very ability to recognize pathogenic microorganisms is genetically embedded in us. If the pathogen impact is massive, innate immunity triggers an inflammatory reaction that proceeds according to a single scenario regardless of the type of pathogen.
Key nonspecific barriers of innate immunity include:
- Intact skin, which serves as a reliable mechanical barrier against the penetration of agents.
- Gastric juice, whose high acidity is lethal to most bacteria.
- Respiratory mucous membranes, where the cilia of the ciliated epithelium physically remove foreign particles, and protective reflexes (coughing and sneezing) accelerate this process.
Adaptive (acquired) immunity acts as the "second line of defense." It is activated when natural barriers prove powerless. This level requires more time to launch, but provides fine-tuning and a specific (selective) response to a strictly defined antigen. T helpers, cytotoxic lymphocytes, NK cells, B lymphocytes, as well as generated antibodies and memory cells, take part in the implementation of the adaptive response.
Cellular and humoral immunity
Both innate and acquired defense are carried out with the help of cells and specialized humoral factors.
- Cellular immunity. Its function is based on the generation of cytotoxic T lymphocytes (so-called T killers). The ultimate goal of this mechanism is to produce a pool of T killers tuned to a specific antigen in order to subsequently physically destroy it and eliminate it from the body.
- Humoral immunity. In this case, antibodies (immunoglobulins) serve as the main weapon. They are synthesized by plasma cells, which in turn are formed during the differentiation of B lymphocytes. As in the cellular link, the main task of the humoral response is the destruction and elimination of the antigen, and the ultimate goal is the targeted production of antibodies.
Classification of antibodies
Depending on the conditions of formation, antibodies are divided into two groups:
- Natural antibodies. They constantly circulate in the bloodstream and do not require any external stimuli to appear. Their targets are the most common damaging agents in the environment.
- Specific antibodies. They are a crucial component of acquired immunity. Their synthesis starts exclusively after the immune system recognizes a specific viral or microbial agent. To combat each new antigen, specialized plasma cells are formed in the body.
Genetic basis of antibody diversity
The body's ability to create antibodies against virtually any threat lies in the unique structure of immunoglobulin genes. Genes encoding the light and heavy chains of antibodies consist of variable and constant segments. In young, undifferentiated cells, these genetic regions are located at a distance from each other.
During the embryonic period, when B lymphocyte maturation occurs, a genetic rearrangement (recombination) mechanism is triggered:
- Stretches of intermediate DNA between the segments are deleted.
- Variable sequences approach each other, and their new combinations join the constant segment.
- A physical movement of nucleotide sequences occurs within the DNA molecule.
In immunogenetics, this unique phenomenon is called regulated somatic mutations. As a result of such rearrangements, during the synthesis of an immunoglobulin molecule, proteins encoded by one of the heavy chain gene variants and one of the light chain gene variants are combined. It is this combinatorial mechanism that allows our body to produce about 100 million different types of antibodies.
Briefly: answers to topical questions
What classes of immunoglobulins (isotypes) are distinguished in humans?
There are five classes (isotypes) of immunoglobulins; isotypes are determined by the type of heavy chain.
- Immunoglobulin G (IgG) — acts as antitoxins and antibacterial substances; the only class of Ig capable of crossing the placental barrier.
- Immunoglobulin A (IgA) — implements immune responses on the surface of mucous membranes; is the main class of Ig present in epithelial cell secretions.
- Immunoglobulin M (IgM) — macroglobulins, synthesized first.
- Immunoglobulin E (IgE) — effector of allergy and antiparasitic immunity; functions as a receptor for mast cells and basophils.
- Immunoglobulin D (IgD) — serves as an antigen-recognizing receptor of B lymphocytes.
What is the major histocompatibility complex (MHC) and what are its functions?
The major histocompatibility complex (MHC) includes MHC class I, II, and III genes; MHC class I and II proteins belong to the immunoglobulin superfamily. The main function of MHC class I and II genes is to encode molecules that present antigens to T lymphocytes. For binding and presenting the antigenic peptide, MHC molecules of both classes have a peptide-binding cleft.
- MHC class I molecules activate CD8 T killers, leading to the destruction of cells bearing the antigen; CD8 binds to MHC class I.
- MHC class II molecules are associated with CD4 T helpers: CD4 binds to MHC class II, and stimulation of CD4 T helpers leads to B cell stimulation and the synthesis of antibodies against the antigen.
- MHC class III genes encode soluble immune mediators not directly involved in presentation: cytokines and complement system components.
How does V(D)J recombination of the T cell receptor (TCR) occur?
T cell receptor recombination occurs by rearrangement of germline genes at the pro-T and pre-T cell stages with the participation of RAG1, RAG2, and TdT enzymes. Rearrangement is carried out on only one chromosome.
- Rearrangement of β and δ chains — first, D and J segments approach each other, then full-scale rearrangement occurs involving the V gene with the formation of the VDJ sequence.
- Rearrangement of the γ chain — due to the absence of the D segment, the V gene connects directly to the J segment, forming the VJ sequence.
Successful rearrangement stops the process on the second chromosome, ensuring the expression of only one variant.
What mechanisms of antibody diversity formation exist besides somatic mutations?
In addition to somatic hypermutations of variable genes, immense antibody diversity is provided by DNA recombination mechanisms and changes at fragment junctions.
- Gene combinatorics — random combination of fragments (V, D, J segments) during B lymphocyte differentiation, which creates a unique continuously functioning gene.
- Junction inaccuracy — addition of extra nucleotides at the junctions of recombining DNA regions.
These processes make it possible to generate millions of different antibody variants from a limited number of structural genes.
To easily remember innate immunity barriers, use the "Three S" rule: Surface (skin — mechanical barrier), Secretion (gastric juice — chemical barrier), Mucous membranes (respiratory tract — mechanical barrier and reflexes).
Class and exam questions
What is the fundamental difference between innate and adaptive immunity?
Innate immunity works constantly and strikes any foreign agents indiscriminately. Adaptive immunity takes time to activate and strikes precisely at a specific antigen.
What is the role of plasma cells in humoral immunity?
Plasma cells, formed from B lymphocytes, act as the main "factories" for the production of antibodies (immunoglobulins) aimed at destroying the antigen.
What are regulated somatic mutations in the context of immunogenetics?
This is a specific genetic process of immunoglobulin gene rearrangement in which intervening DNA is excised, and variable and constant segments are joined in novel combinations to generate unique antibodies.
What else to study on this topic
- Pathophysiological mechanisms and stages of the inflammatory response in massive infection.
- The role of NK cells and T helper cells in the adaptive immune system.
- The process of B lymphocyte differentiation into plasma cells.
- The functioning of immunological memory and memory cells.
- Structure of the immunoglobulin molecule: interaction of heavy and light chains.
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