Immunoglobulin classes and their age-related dynamics

Human immunoglobulins are quite heterogeneous and are represented by 5 classes and several subclasses. They are detected in the blood at different age periods and reach concentrations typical of adults at different times.

It is accepted to distinguish 5 classes of immunoglobulins: A, M, G, E, D. Each class of immunoglobulins has differences in both the molecular weight, sedimentation coefficient, and their participation in immune reactions. The content of immunoglobulins is one of the important indicators of the humoral link of immunity.

Main characteristics of immunoglobulins of different classes

Indicator	IgG	IgA	IgM	IgD	IgE
Molecular form	Monomer	Monomer and dimer	Pentamer	Monomer	Monomer
Number of subclasses	4	2	2	-	-
Molecular weight, daltons	150,000	160,000 - monomer	950,000	175,000	190,000
Percentage of all serum Ids	75-85	7-15	5-10	0.3	0.003
Half-life, days	23	6	5	3	2
Antibody valency	2	2	5 or 10	2	2
Transplacental passage	+	-	-	-	-
Participation in opsonization	+	+	+	-	-
Complement fixation	+	+	+	-	-

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Immunoglobulin G

Immunoglobulin G contains antibodies that play a leading role in protecting against many viral (measles, smallpox, rabies, etc.) and bacterial infections caused mainly by gram-positive microorganisms, as well as tetanus and malaria, anti-Rhesus hemolysins, antitoxins (diphtheria, staphylococcal, etc.). IgG antibodies have a destructive effect with the help of complement, opsonization, activation of phagocytosis, and have a virus-neutralizing property. Subfractions of immunoglobulin G and their ratios can not only be determined by the specificity of the antigenic stimulus (infection), but also be evidence of incomplete immunological competence. Thus, a deficiency of immunoglobulin G2 can be associated with a deficiency of immunoglobulin A, and an increase in the concentration of immunoglobulin G4 for many children reflects the likelihood of atopic predisposition or atopy, but of a different type than the classical one, based on the production and reactions of immunoglobulin E.

Immunoglobulin M

Immunoglobulin M plays an important role in protecting the body from infections. It contains antibodies against gram-negative bacteria (shigella, typhoid fever, etc.), viruses, as well as hemolysins of the ABO system, rheumatoid factor, and anti-organ antibodies. Antibodies belonging to the immunoglobulin M class have high agglutinating activity and are capable of activating complement via the classical pathway.

Immunoglobulin A

The role and significance of serum immunoglobulin A have not yet been sufficiently studied. It does not participate in complement activation, in the lysis of bacteria and cells (for example, erythrocytes). At the same time, it is reasonable to assume that serum immunoglobulin A is the main source for the synthesis of secretory immunoglobulin A. The latter is formed by lymphoid cells of the mucous membranes of the digestive and respiratory systems and, thus, participates in the local immunity system, preventing the invasion of pathogens (viruses, bacteria, etc.) into the body. This is the so-called first line of defense of the body from infection.

Immunoglobulin D

Little is known about the function of antibodies related to immunoglobulin D. Immunoglobulin D is found in the tissue of the tonsils and adenoids, which suggests its role in local immunity. Immunoglobulin D is located on the surface of the B-lymphocyte (together with monomeric IgM) in the form of mIg, controlling its activation and suppression. It has also been established that immunoglobulin D activates the alternative complement and has antiviral activity. In recent years, interest in immunoglobulin D has increased due to the description of an acute febrile disease of the rheumatic fever type (enlarged lymph nodes, polyserositis, arthralgia and myalgia) in combination with hyperimmunoglobulinemia D.

Immunoglobulin E

Immunoglobulin E, or reagins, is associated with the concept of immediate-type allergic reactions. The main method for recognizing specific sensitization to a variety of allergens is the study of total or total immunoglobulin E in blood serum, as well as titers of immunoglobulin E antibodies to specific household allergens, food substances, plant pollen, etc. Immunoglobulin E also activates macrophages and eosinophils, which can enhance phagocytosis or the activity of microphages (neutrophils).

In the postnatal period, there is a significant dynamics in the content of immunoglobulins of different classes in the blood of children. It is associated with the fact that during the first months of life, the decay and removal of those immunoglobulins of class B that were transferred transplacentally from the mother continues. At the same time, there is an increase in the concentration of immunoglobulins of all classes of their own production. During the first 4-6 months, maternal immunoglobulins are completely destroyed and the synthesis of their own immunoglobulins begins. It is noteworthy that B-lymphocytes synthesize mainly immunoglobulin M, the content of which reaches the indicators characteristic of adults faster than other classes of immunoglobulins. The synthesis of their own immunoglobulin B occurs more slowly.

As was stated, at birth the child has no secretory immunoglobulins. Their traces begin to be detected from the end of the first week of life. Their concentration gradually increases, and the content of secretory immunoglobulin A reaches its maximum values only by 10-12 years.

Immunoglobulin E in blood serum, kU/l

Age of children	Healthy children		In adults with diseases
	Minimum	Maximum	Diseases	Minimum	Maximum
Newborns	0	2	Allergic rhinitis	120	1000
3-6 months	3	10	Atopic asthma	120	1200
12 »	8	20	Atopic dermatitis	80	14,000
5 years	10	50	Bronchopulmonary aspergillosis:
10 »	15	60	Remission	80	1000
Adults	20	100	Exacerbation	1000	8000
			Hyper-IgE syndrome	1000	14,000
			IgE myeloma	More than 15,000	-

Serum immunoglobulins in children, g/l

Age	Immunoglobulin G		Immunoglobulin A		Immunoglobulin M
	Minimum	Maximum	Minimum	Maximum	Minimum	Maximum
0-2 weeks	5.0	17.0	0.01	0.08	0.05	0.20
2-6 »	3.9	13.0	0.02	0.15	0.08	0.40
6-12 »	2.1	7.7	0.05	0.40	0.15	0.70
3-6 months	2.4	8.8	0.10	0.50	0.20	1.00
6-9 »	3.0	9.0	0.15	0.70	0.40	1.60
9-12 »	3.0	10.9	0.20	0.70	0.60	2.10
1-2 years	3.1	13.8	0.30	1.20	0.50	2.20
2-3 »	3.7	15.8	0.30	1.30	0.50	2.20
3-6 years	4.9	16.1	0.40	2.00	0.50	2.00
6-9 »	5.4	16.1	0.50	2.40	0.50	1.80
9-12 »	5.4	16.1	0.70	2.50	0.50	1.80
12-15 »	5.4	16.1	0.80	2.80	0.50	1.80
15-45 »	5.4	16.1	0.80	2.80	0.50	1.80

Low levels of secretory immunoglobulin A are found in children of the first year of life in the secretions of the small and large intestines, as well as in feces. In nasal washes of children of the first month of life, secretory immunoglobulin A is absent and increases very slowly in the following months (up to 2 years). This explains the lower incidence of respiratory infections in young children.

Immunoglobulin D in the blood serum of newborns has a concentration of 0.001 g/l. Then it increases after the 6th week of life and reaches values characteristic of adults by 5-10 years.

Such complex dynamics create changes in quantitative ratios in the blood serum, which cannot be ignored in assessing the results of diagnostic studies of the immune system, as well as in interpreting the characteristics of morbidity and immunological constitution in different age periods. Low levels of immunoglobulins during the first year of life explain the easy susceptibility of children to various diseases (respiratory organs, digestion, pustular skin lesions). With increased contact between children in the second year of life, against the background of a relatively low level of immunoglobulins during this period, their especially high morbidity is observed compared to children of other periods of childhood.

Blood serum contains a very small amount of immunoglobulin E. Its concentration increases with age, which largely correlates with the onset of allergic and, much less frequently, other diseases (helminthiasis, parasitosis).

Heterogeneity of immunoglobulin M class are detected by the 3rd month of life, then their content increases, but more noticeably - at 2-2 1/2 years. In newborns, the content of staphylococcal antitoxin is equal to that of an adult, and then it decreases. Again, its reliable increase is observed by 24-30 months of life. The dynamics of the concentration of staphylococcal antitoxin in the child's blood suggests that its initially high level is due to its transplacental transfer from the mother. Its own synthesis occurs later, which explains the high frequency of pustular skin lesions (pyoderma) in young children. In cases of intestinal infections (salmonellosis, coli-enteritis, dysentery), antibodies to their pathogens are rarely detected in children in the first 6 months of life, at the age of 6 to 12 months - only in 1/3 of patients, and in children in the second year of life - in almost 60%.

In case of acute respiratory infections (adenovirus, parainfluenza), seroconversion in children of one year of life is found only in 1/3 of those who have had them, and in the second year - already in 60%. This once again confirms the peculiarities of the formation of the humoral link of immunity in young children. It is no coincidence that in many manuals on pediatrics and immunology, the described clinical and immunological syndrome or phenomenon receives the rights of a nosological form and is designated as "physiological transient hypoyshunoglobulinemia of young children".

The passage of a limited amount of antigenic material from food through the intestinal barrier is not a pathological phenomenon in itself. In healthy children of any age, as well as in adults, trace amounts of food proteins can enter the blood, causing the formation of specific antibodies. Almost all children fed with cow's milk develop precipitating antibodies. Feeding with cow's milk leads to an increase in the concentration of antibodies against milk proteins as early as 5 days after the introduction of the formula. The immune response is especially pronounced in children who have received cow's milk since the neonatal period. Previous breastfeeding results in a lower antibody content and its slow increase. With age, especially after 1-3 years, a decrease in the concentration of antibodies to food proteins is determined in parallel with a decrease in the permeability of the intestinal wall. The possibility of food antigenemia in healthy children has been proven by the direct isolation of food antigens found in the blood in a free form or as part of an immune complex.

The formation of relative impermeability for macromolecules, the so-called intestinal block, in humans begins in utero and occurs very gradually. The younger the child, the higher the permeability of his intestines for food antigens.

A specific form of protection against the harmful effects of food antigens is the immune system of the gastrointestinal tract, consisting of cellular and secretory components. The main functional load is carried by dimeric immunoglobulin A (SIgA). The content of this immunoglobulin in saliva and digestive secretions is much higher than in serum. From 50 to 96% of it is synthesized locally. The main functions in relation to food antigens are to prevent the absorption of macromolecules from the gastrointestinal tract (immune exclusion) and regulate the penetration of food proteins through the epithelium of the mucous membrane into the internal environment of the body. Relatively small antigen molecules penetrating the epithelial surface stimulate local synthesis of SIgA, which prevents the subsequent introduction of antigens by forming a complex on the membrane. However, the gastrointestinal tract of a newborn is deprived of this specific form of protection, and all of the above can be fully realized very soon, as the SIgA synthesis system fully matures. In a breastfed child, the period of minimally sufficient maturation can vary from 6 months to 1 '/2 years or more. This will be the period of formation of the "intestinal block". Before this period, the system of local secretory protection and blocking of food antigens can be provided only and exclusively by colostrum and mother's milk. The final maturation of secretory immunity can occur after 10-12 years.

The biological meaning of the significant increase in the content of immunoglobulin A in colostrum immediately before birth lies in its specialized function of immune exclusion of antigens (infectious and food) on the mucous membranes.

The SIgA content in colostrum is very high and reaches 16-22.7 mg/l. With the transition of colostrum milk to mature milk, the concentration of secretory immunoglobulins decreases significantly. The implementation of the protective functions of SIgA is facilitated by its pronounced resistance to the proteolytic action of enzymes, due to which SIgA retains its activity in all parts of the gastrointestinal tract, and in a child who is breastfed, it is almost completely excreted unchanged with feces.

The participation of SIgA in human milk in immune processes associated with food antigens has been proven by the detection of immunoglobulin A antibodies in human milk against a number of food proteins: α-casein, β-casein, β-lactoglobulin from cow's milk.

The second most concentrated immunoglobulin is immunoglobulin G, and the relatively high content of immunoglobulin G4 is of particular interest. The ratio of the concentration of immunoglobulin G4 in colostrum to the content in blood plasma exceeds the ratio of the concentration of immunoglobulin G in colostrum to the content in blood plasma by more than 10 times. This fact, according to researchers, may indicate local production of immunoglobulin G4 or its selective transport from the peripheral blood to the mammary glands. The role of colostrum immunoglobulin G4 is unclear, but its participation in the processes of interaction with food antigens is confirmed by the detection of specific immunoglobulin C4 antibodies against β-lactoglobulin, bovine serum albumin and α-gliadin in both plasma and colostrum. It has been suggested that immunoglobulin G4 enhances antigenic activation of mast cells and basophils, leading to the release of mediators necessary for chemotaxis and phagocytosis.

The immunoglobulin E content in colostrum reaches several hundred nanograms per 1 ml. In breast milk, its content quickly decreases and is determined only at high content in the mother's blood serum. It has been found that an antigen-specific factor suppressing the production of immunoglobulin E in newborns can be transmitted with mother's milk.

Thus, the state of immunoglobulin synthesis not only determines the readiness of a young child to infections, but also turns out to be a causal mechanism for the penetration of a wide flow of allergenic substances through the intestinal barrier and the barrier of other mucous membranes. Together with other anatomical and physiological characteristics of young children, this forms a special and quite independent form of "transient atopic constitution, or diathesis of young children." This diathesis can have very pronounced, primarily skin manifestations (eczema, allergic dermatosis) up to 2-3 years of age with rapid subsequent remission of skin changes or complete recovery in the following years. In many children with a hereditary predisposition to atopy, increased permeability of the mucous membranes during the period of transient atopic diathesis contributes to the implementation of hereditary predisposition and the formation of a long chain of already persistent allergic diseases.

Thus, age-related physiological features of immunity in young children determine a significant increase in their sensitivity to both infectious environmental factors and exposure to allergens. This determines many requirements for child care and disease prevention. This includes the need for special control over the risk of contact with infections, the feasibility of individual or mini-group education, control over the quality of food products and their tolerance according to the symptoms of allergic reactions. There is also a way out of the situation, developed by the many-thousand-year evolution of mammals - this is full breastfeeding of children. Colostrum and native human milk, containing a large amount of immunoglobulin A, macrophages and lymphocytes, as if compensate for the immaturity of general and local immunity in children of the first months of life, allowing them to safely bypass the age of critical or borderline state of the immune system.

The increase in serum and secretory immunoglobulin levels by age 5 coincides with a decrease in the incidence of infectious diseases during this period of childhood, as well as with a milder and more benign course of many infections.