Classes of immunoglobulins and their age dynamics

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

It is accepted to distinguish 5 classes of immunoglobulins: A, M, G, E, D. Each class of immunoglobulins has differences both in terms of 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.

The main characteristics of immunoglobulins of various classes

Index	IgG	IgA	IgM	IgD	IgE
Molecular form	Monomer	Monomer and dimer	Pentamer	Monomer	Monomer
Number of subclasses	4	2	2	-	-
Molecular weight, dalton	150,000	160 000 - monomer	950 000	175 000	190,000
Percentage of all serum levels of serum	75-85	7-15	5-10	0.3	0.003
Half-life, day	23	6th	5	3	2
Valence of antibodies	2	2	5 or 10	2	2
Transition through the placenta	+	-	-	-	-
Participation in oppression	+	+	+	-	-
Binding complement	+	+	+	-	-

[1], [2], [3], [4], [5]

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 from tetanus and malaria, antiresusnye hemolysins, antitoxins (diphtheria, staphylococcal and other). IgG antibodies have a disastrous effect with complement, opsonization, activation of phage-cytosis, and possess a virus neutralizing property. Immunoglobulin G subfractions, their ratios not only can be determined by the specificity of the antigenic stimulus (infection), but also be witnesses of incomplete immunological competence. Thus, deficiency of immunoglobulin G2 may be associated with immunoglobulin A deficiency, and increasing the concentration of immunoglobulin G4 for many children reflects the probability of atopic predisposition or atopy, but of a different type than classical, based on the production and reactions of immunoglobulin E.

Immunoglobulin M

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

Immunoglobulin A

The role and importance of serum immunoglobulin A have not yet been adequately studied. It does not participate in the activation of complement, in the lysis of bacteria and cells (eg, 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 the 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 protection of the body from infection.

Immunoglobulin D

About the function of antibodies relating to immunoglobulin D is still little known. Immunoglobulin D is found in the tissue of tonsils and adenoids, which suggests its role in local immunity. Immunoglobulin D is on the surface of the B lymphocyte (along with monomeric IgM) in the form of mIg, controlling its activation and suppression. It has also been established that immunoglobulin D activates complement in an alternative type and has antiviral activity. In recent years, interest in immunoglobulin D increases due to the description of an acute febrile illness as a rheumatic fever (an increase in lymph nodes, polyserositis, arthralgia and myalgia) in combination with hyperimmunoglobulinemia D.

Immunoglobulin E

With immunoglobulin E, or reactive, the idea of allergic reactions of immediate type is associated. The main method for the recognition of specific sensitization to a wide variety of allergens is the study of total or total immunoglobulin E of blood serum, as well as immunoglobulin-E-antibody titers for specific allergens of life, food substances, pollen of plants, etc. Immunoglobulin E also activates macrophages and eosinophils , which can enhance phagocytosis or the activity of microphages (neutrophils).

In the postnatal period, a very significant dynamics is observed 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 disintegration and removal of those immunoglobulins of class B that were transmitted transplacentally from the mother continues. At the same time, there is an increase in the concentrations of immunoglobulins of all classes already produced. During the first 4-6 months, the maternal immunoglobulins are completely destroyed and the synthesis of their own immunoglobulins begins. It is interesting to note that B-lymphocytes synthesize predominantly immunoglobulin M, the content of which quickly reaches the indices characteristic of adults, than other classes of immunoglobulins. Synthesis of its own immunoglobulin in is slower.

As indicated, the child has no secretory immunoglobulins for birth. Their traces begin to show up at 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 serum, kE / l

Children's age	Healthy children		In adults with diseases
	Minimum	Maximum	Diseases	Minimum	Maximum
Newborns	0	2	Allergic rhinitis	120	1000
3-6 months	3	10	Asthma atopic	120	1200
12 "	8	20	Atopic dermatitis	80	14,000
5 years	10	50	Aspergillosis bronchopulmonary:
10 "	15	60	Remission	80	1000
Adults	20	100	Exacerbation	1000	8000
			Hyper-IgE syndrome	1000	14,000
			IgE myeloma	More than 15 000	-

Immunoglobulins of blood serum 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 old	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 content of secretory immunoglobulin A is found in children of the first year of life in the secrets of the small and large intestine, as well as in faeces. In the washings from the nose of children of the first month of life, secretory immunoglobulin A is absent and very slowly increases in the following months (up to 2 years). This explains the lighter morbidity of young children with respiratory infections.

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

Such a complex dynamics creates changes in the quantitative relationships in the blood serum, which can not be ignored in the evaluation of 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. The low content of immunoglobulins during the first year of life is explained by the mild susceptibility of children to various diseases (respiratory, digestive, pustular skin lesions). With the increase in contact between children in the second year of life, against a background of relatively low levels of immunoglobulins during this period, their morbidity is especially high compared with children of other childhood periods.

The blood serum contains a very small amount of immunoglobulin E. Its concentration increases with age, which largely correlates with the onset of manifestations of allergic and, more rarely, other diseases (helminthiases, parasitosis).

Heterogemagglutinins belonging to the class of immunoglobulins M are detected by the 3rd month of life, then their content increases, but more noticeably in 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 significant increase is observed by 24-30 months of life. The dynamics of the concentration of staphylococcal antitoxin in the blood of the child suggests that the originally high level is due to transplacental transmission from the mother. Own synthesis occurs later, which explains the high incidence of pustular skin lesions (pyoderma) in young children. In case of intestinal infections (salmonellosis, coli-enteritis, dysentery), antibodies to their pathogens in children of the first 6 months of life are rarely found, at the age of 6 to 12 months - only in 1/3 of patients, and in children in the second year of life - almost in 60%.

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

The passage of a limited amount of antigenic food material through the intestinal barrier is not in itself a pathological phenomenon. 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 by cow's milk, produce antibodies. Feeding with cow's milk leads to an increase in the concentration of antibodies against milk proteins only 5 days after the introduction of the mixture. The immune response is especially pronounced in children who received cow's milk from the period of newborns. Previous breastfeeding results in a lower antibody content and a slower build-up of antibodies. With age, especially after 1-3 years, in parallel with a decrease in the permeability of the intestinal wall, a decrease in the concentration of antibodies to food proteins is determined. The possibility of food antigenemia in healthy children is proved by direct release of food antigens that are in the blood in a free form or in the immune complex.

The formation of relative impermeability for macromolecules, the so-called intestinal block, begins intrauterine in the human and proceeds very gradually. The younger the child, the higher the permeability of his intestine 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 with respect to food antigens are to prevent the absorption of macromolecules from the gastrointestinal tract (immune elimination) and regulate the penetration of food proteins through the mucosal epithelium into the internal environment of the body. Relatively small antigenic molecules penetrating the epithelial surface stimulate the local synthesis of SIgA, which prevents the subsequent introduction of antigens by forming a complex on the membrane. However, the newborn's gastrointestinal tract is deprived of this specific form of protection, and all that has been said above can be fully realized very soon, as the SIgA synthesis system matures. In an infant, the periods of minimum sufficient maturation can range from 6 months to 1/2 years and more. This will be the period of formation of the "intestinal block". Until then, the system of local secretory protection and blockage 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 a significant increase in the content of immunoglobulin A in colostrum immediately before delivery is its specialized function of immune exclusion of antigens (infectious and food) on the mucous membranes.

The content of SIgA in colostrum is very high and reaches 16-22.7 mg / l. With the transition of milk milk to a mature concentration of secretory immunoglobulins is significantly reduced. Realization of the protective functions of SIgA is promoted by its pronounced resistance to the proteolytic action of enzymes, so that SIgA retains its activity in all parts of the gastrointestinal tract, and the child, who is naturally fed, is almost completely excreted with feces.

Participation of SIgA of female milk in immune processes associated with food antigens is proved by the detection in human milk of immunoglobulin-A antibodies against a number of food proteins: α-casein, β-casein, β-lactoglobulin of cow's milk.

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

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

Thus, the state of the synthesis of immunoglobulins not only determines the readiness of an infant of early age for infections, but also proves to be the causal mechanism for penetrating the intestinal barrier and the barrier of other mucous membranes of a wide flow of allergenic substances. Together with other anatomical and physiological features of young children, this forms a special and completely independent form of the "transitional atopic constitution, or diathesis of young children." This diathesis can have very bright, especially skin manifestations (eczema, allergic dermatosis) to 2-3 years of age with rapid subsequent remission of skin changes or complete recovery in subsequent years. In many children with a hereditary predisposition to atopy, an increase in the permeability of the mucous membranes during the transient atopic diathesis promotes the realization of a hereditary predisposition and the formation of a long chain of already impassable allergic diseases.

Thus, the 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 caring for children and preventing their diseases. This includes the need for special control over the risk of exposure to infections, the appropriateness of individual or mini-group education, control over the quality of food and their tolerability in the symptomatology of allergic reactions. There is also a way out of the situation, worked out by many thousands of years of evolution of mammals - this is a full-fledged breastfeeding of children. Colostrum and native female 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, can safely pass the age of the critical or borderline state of the immune system.

The increase in serum and secretory immunoglobulins by the age of 5 coincides with a decrease in the level of infectious morbidity during this period of childhood, as well as with the lighter and benign course of many infections.