Specific immunity: development and development

Specific immunological reactions are performed by the body's immune system, consisting of central and peripheral immunogenesis organs. Specific immunity when exposed to a specific antigen is carried out by T- and B-lymphocytes. The intrauterine period demonstrates the intensive dynamics of maturation of the lymphoid system.

Sequential change of different stages of maturation of B- and T-cell cells can be monitored by immunological markers of the corresponding stages of maturation or differentiation.

Differentiation markers of cells participating in the immune response

CD Marker	Type of carrier cell marker	Function
CD1	T-lymphocyte	Participation in antigen presentation
CD2	T-lymphocyte	Adhesion of cytotoxic T-lymphocytes to the endothelium, to epithelial cells of the thymus gland
CCD	T-lymphocyte	The T-cell activation signal, the marker of most mature T-lymphocytes
CD4	T-lymphocyte	Co-receptor for TCR, marker of T-helpers
CD8	T-lymphocyte	Maturation and selection of GCS of restricted lymphocytes in the thymus gland, a marker of cytotoxic T-lymphocytes
СD25	T-, B-, NK-cells, thymocytes, macrophages	Induction of the activity and proliferation of T- and B-lymphocytes, natural killers, thymocytes and macrophages, the α-subunit of the receptor for IL-2
СD28	T-lymphocyte	Co-stimulatory signaling molecule independent of TCR
СDЗ0	T-lymphocyte	The signal for triggering apoptosis of T-lymphocytes
CD5	T- and B-lymphocyte	Specific for autoimmune diseases
CD9	B-lymphocyte	Presented on pre-B cells, responsible for the aggregation and activation of platelets
СD19, 20, 21	B-lymphocyte	Regulation of activation and proliferation of B-lymphocytes
CD22	B-lymphocyte	Responsible for adhesion to erythrocytes, T- and B-lymphocytes, monocytes and neutrophils
CD40	B-lymphocyte	B-cell activation, proliferation and differentiation
СD16	The natural killer	Activation of antigen-dependent complement-mediated cytotoxicity and cytokine production
CD56	The natural killer	Activation of cytotoxicity and production of cytokines
CD94	The natural killer	Inhibition / activation of cytotoxicity of natural killers
СD11α СD18	Monocyte Granulocyte	Adhesion of leukocytes to endothelium and leukocyte to leukocyte
CD11β СD18	Monocyte Granulocyte	Adhesion of monocytes and neutrophils to the endothelium, opsonization of complement-bound particles
С11с СD18тов	Monocyte Granulocyte	Adhesion of monocytes and granulocytes to the endothelium, phagocytic receptor in inflammation
СD45	Granulocyte	Receptor for tyrosine phosphatase
CD64	Macrophages	Activating macrophages
CD34	A stem cell or a committed colony-forming precursor	Attachment of L-selectin lymphocytes to the endothelium, attachment of stem cells to bone marrow stroma

Markers for the differentiation of B-lymphocytes

Pro / pre-B-1-cell	Large pre-B-97-H cell	Small pre-B-97-II cell	Immature B-cell	Mature B cell
CD34	CD40	CD40	CD21	CD40
CD40	CD43		CD22	CD19
CD43	CD19		СD80	CD20
B220			CD86
СD25			CD54
			CD79

Markers for differentiation of T-lymphocytes

Pro-T cells TH	Pre-T cells	Immature T cells TH	DP cells	Mature
СD25	СD25	СDЗeу	CCD	CD4
CD44	СDЗeу	CD4	СD4 +, 8+	CD8
CD117	CD4-	CD8	CD4	CCD
C3-	CD8-	CD117	CD8	CD4
C4-	CD117			CD8
CD8 "
TKP-β
Re-Arrangement

The emergence of all systems of both nonspecific and specific immunity, especially cellular, begins at a period of about 2-3 weeks, when multipotent stem cells are formed. The common stem-cell precursor of all subpopulations of lymphocytes, neutrophilic leukocytes and monocytes, can be identified as CD34 + T cell.

T-precursors perform a cycle of maturation in the thymus gland and there pass the processes of negative and positive selection, the result of which is the elimination of more than 90% of lymphoid cells, potentially dangerous for the body in terms of the risk of developing autoimmune reactions. The remaining cells after the selection migrate and colonize the lymph nodes, spleen and group lymph follicles.

At the 3rd month, a positive reaction of blast transformation to phytohemagglutinin is already observed, which coincides with division in the thymus gland into the cortex and the medullary part. By the 9-15th week of life there are signs of the functioning of cellular immunity. The reaction of delayed type hypersensitivity is formed at later stages of intrauterine development and reaches its maximum functioning after birth - by the end of the first year of life.

Primary lymphoid organ - thymus gland - is placed on the period of about 6 weeks and finally histomorphologically matures to the gestation age of about 3 months. From 6 weeks at a fetus begin to be typified antigens HLA. This means that from that time on, the fetus becomes an "immunological personality" with its individual antigenic constitutional "portrait" and a host of constitutional features in all reactions of the immunity system. From the 8th to 9th week, small lymphocytes appear in the thymus gland. They are recognized as descendants of lymphoid cells that migrated first from the yolk sac, and later from the liver or bone marrow. Then there is an intensive increase in the number of lymphocytes in the fetal peripheral blood - from 1000 to 1 mm ³ at the 12th week to 10,000 in 1 mm ³ by the 20-25th week.

Under the influence of humoral stimulators and partially local micro-environment, T-lymphocytes can take the functions of cytotoxic cells, helpers, suppressors, memory cells. By the time of birth, the absolute number of T-lymphocytes in a child is higher than that of an adult, and this system is functionally functional, although many characteristics of the function of T-lymphocytes are at a lower level than in older children and adults. Their ability to produce interleukins 4 and 5, interferon-γ is weakened, and the CD40β antigen is poorly expressed, which is necessary for organizing the interaction of T and B systems in the immune response.

Characteristics of the characteristics of the immune response are largely determined by the ability of participating cells to produce substances of humoral communication and regulation of cytokines or interleukins. In scientific research, several dozens of such information and regulatory molecules have been identified and quantified. In clinical immunology, the most important is the determination of 10-15 biologically active substances of this group.

Early morphological and functional maturation of the thymus gland coincides with the advancing development of the T-cell system. The reactions of rejection of the graft, starting from 12 weeks of gestation, are described. By the time the baby is born, lymphoid tissue of the thymus gland already has considerable dimensions.

The first peripheral lymph glands are formed starting from the third month of gestation, but their "colonization" with lymphoid elements occurs during the subsequent (4th) month. Lymph nodes and the formation of the gastrointestinal tract are formed only after the 21st week of gestation.

The differentiation of B cells also begins in the liver or bone marrow, and there is a close relationship between this differentiation and the Bruton tyrosine kinase gene. In the absence of this gene, differentiation is impossible and the child will suffer from agammaglobulinemia. During the differentiation of B-lymphocytes, deletion recombination with immunoglobulin genes is carried out. This allows B cells to present on their surface the structure of immunoglobulin M and, as a consequence, migrate and repopulate in the spleen and lymph nodes. For a long period of intrauterine development, pre-B lymphocytes remain in the liver and peripheral blood as dominant B cells, containing heavy M-globulin chains in their cytoplasm but not carrying surface receptors to immunoglobulins. The number of these cells is significantly reduced by the time of birth. The transformation of pre-B cells into cells capable of producing immunoglobulins is carried out under the influence of factors of the thymus gland. For the final maturation of B cells with the possibility of transforming them into plasma ones, it is necessary to participate in a direct microenvironment, i.e. Stromal elements of the lymph nodes, group lymphatic follicles of the intestine, and spleen.

[1], [2], [3], [4], [5], [6], [7], [8],

Specific immunity and interleukins

Interleukin	Source of Education	Functions
IL-1	Macrophages, dendritic cells, fibroblasts, NK cells, endothelial cells	Acceleration of antigen presentation, stimulates production by Th cells IL-2, maturation of B-lymphocytes, pro-inflammatory and pyrogenic action
IL-2	Activated T-lymphocytes (predominantly Th1)	The growth factor for T and B lymphocytes, activates the differentiation of Th and cytotoxic T lymphocytes, stimulates NK cells and Ig synthesis by B lymphocytes
IL-3	T-cells and stem cells	Growth factor for plasma cells, multicolony stimulating factor
IL-4	Th2 cells, mast cells	Differentiation of Th0 into Th2 cells, B-differentiation, acceleration of IgE synthesis, growth of plasma cells, inhibits the formation of cytotoxic lymphocytes and NK cells, inhibits the formation of interferon-γ
IL-5	Th2 cells	Acceleration of the synthesis of immunoglobulins, especially IgA, acceleration of eosinophil production
IL-6	T- and B-lymphocytes, macrophages, fibroblasts, endothelial cells	Accelerating the synthesis of immunoglobulins, stimulates the proliferation of B-lymphocytes, hepatocyte growth factor, antiviral protection
IL-7	Stromal cells, fibroblasts, endothelial cells, T-lymphocytes, bone marrow cells	Acceleration of growth of pre-T and pre-B cells
IL-8	T-cells, macrophages, endothelial cells, fibroblasts, hepatocytes	Activation of neutrophils, chemoattractant for lymphocytes, neutrophils, macrophages and eosinophils
IL-9	Th2-cells	Synergism with IL-4 in increasing the synthesis of IgE, the growth of plasma cells, stimulates the proliferation of T-lymphocytes and basophils
IL-10	Th0 and Th2 cells, CD8 +, macrophages, dendritic cells	The inhibition of the synthesis of proinflammatory cytokines, the suppression of macrophage functions, the acceleration of growth of B-lymphocytes and mast cells
IL-12	Macrophages, neutrophils, B-lymphocytes and dendritic cells	Stimulation of natural killers, maturation of cytotoxicity of lymphocytes, stimulates the growth and differentiation of TM-into Th1 cells, inhibits the synthesis of 1de, the pro-inflammatory cytokine
IL-13	Th2 cells and mast cells	Acceleration of IgE synthesis, growth acceleration of B-lymphocytes, inhibition of macrophage activation
IL-14	T- and B-lymphocytes	Reduces the production of Ig, increases the proliferation of B-lymphocytes
IL-15	Monocytes and epithelial cells	The growth factor for T-lymphocytes, activates the differentiation of Th- and cytotoxic T-lymphocytes, stimulates NK cells and Ig synthesis by B lymphocytes
IL-16	Eosinophils, CD8 +, mast cells	Activates chemotaxis of Th cells, eosinophils and monocytes
IL-17	T-lymphocytes of memory and NK cells	Enhances the production of IL-6, IL-8, enhances the expression of ICAM-1, stimulates the activity of fibroblasts
IL-18	Macrophages	Acceleration of the synthesis of interferon-γ
IL-19	Monocytes	Homologue IL-10
IL-20	Keratinocytes	Participates in skin inflammation in psoriasis
IL-21	T-lymphocytes and mast cells	Increases the proliferation of T-, B-lymphocytes and NK cells
IL-22	T-lymphocytes	Homologue IL-10
IL-23	Activated dendritic cells	Increases the proliferation of CD4 + T-lymphocytes in memory and stimulates the formation of interferon-γ
IL-24	Activated monocytes, T-lymphocytes	Homologue IL-10
IL-25	Bone marrow stromal cells	Increases the production of Th2-cytokines
IL-26	Activated monocytes, T-lymphocytes, NK cells	Homologue IL-10
Interferon-γ	T-cells	Activation of macrophages, inhibition of IgE synthesis, antiviral activity
Tumor Necrosis Factor	Monocytes, macrophages, T- and B-lymphocytes, neutrophils, NK cells, endothelial cells	It induces the synthesis of macrophages IL-1 and IL-6, the formation of proteins of the acute phase, stimulates angiogenesis, induces apoptosis, hemorrhagic necrosis of tumors
Chemokines (RANTES, MIP, MCP)	T-cells, endothelium	Chemoattractant (chemokine) for monocytes, eosinophils, T cells

Relatively mature B lymphocytes are identified by the presence of immunoglobulin receptor antigens on their surface. In the liver, such cells begin to appear after 8 weeks. First, they are receptors for immunoglobulins G and M, later for A. After the 20th week, cells with receptors are detected already in the spleen, peripheral blood.

The ability to produce antibodies by the B-system's own cells is confirmed in the fetus, starting from the 11th to 12th week. The earliest the fetal organism acquires the ability to form immunoglobulin M (from the 3rd month), somewhat later immunoglobulin in (from the 5th month) and immunoglobulin A (from the 7th month). The timing of the synthesis of immunoglobulin D in the intrauterine period has not been studied sufficiently. Own production of immunoglobulin E is detected in the fetus from the 11th week in the lungs and in the liver, and from the 21st week in the spleen. In the cord blood, many lymphocytes carrying immunoglobulin E are found, but the content of immunoglobulin E itself is very low. Until the 37th week of gestational age, it is no more than 0.5 IU / ml. At the age of 38 weeks, immunoglobulin E is detected in 20% of newborns, and after the 40th week - in 34%.

In general, the synthesis of immunoglobulins during intrauterine development is very limited and intensified only with antigenic stimulation (for example, with intrauterine infection). The humoral immune response of the fetus and newborn is significantly different from that of the older child or adult in both qualitative and quantitative terms.

At the same time, during the period of intrauterine development, some immunoglobulins of the mother pass transplacentally. Among the latter, immunoglobulin has this ability. The transition of maternal immunoglobulin M to the fetus is possible only because of increased permeability of the placenta. As a rule, this is observed only with gynecological diseases of the mother, for example, with endometritis. The remaining classes of mother's immunoglobulins (A, E, D) do not transfer transplacental.

The presence of selective transport through the placenta of maternal immunoglobulin can be considered an essential factor of perinatal adaptation. This transition begins after the 12th week of gestation and increases with an increase in its timing. It is very important that the child receives from the mother a wide range of specific antibodies, both antibacterial and antiviral, aimed specifically at protecting him from precisely the range of pathogens that his mother has encountered and that matter in the local environment. Transition through the placenta of immunoglobulin B2 is particularly easy.

Obviously, it is possible, albeit in an insignificant amount, to reverse the transition of the immunoglobulins of the fetus and even the lymphocytes of the baby into the mother's blood, which raises the risk of immunization to the fetal alloantigens of all the immunoglobulins. It is believed that this mechanism can make a difference in the formation of the mechanism of suppression of fetal alloantigen synthesis. Immunodepression of a woman and mutual immunological tolerance in pregnancy are evolutionarily developed adaptations that allow, despite the antigenic difference in the mother and fetus organisms, to ensure the normal course of pregnancy and the birth of children on time.

After birth, the ratio of T- and B-cells in the blood of the newborns varies considerably. The content in the peripheral blood of T and B lymphocytes in newborns is higher, with age it decreases. The more pronounced reaction of blast transformation, both spontaneous and stimulated by phytohemagglutinin, attracts attention. However, in functional terms, lymphocytes are less active, which is explained, on the one hand, by immunosuppression by substances transmitted from the body of a woman during pregnancy, and on the other - by the absence of antigenic fetal stimulation in utero. Evidence of the latter situation is an increase in the content of immunoglobulins A and to a lesser extent immunoglobulins M in newborns who have or have suffered an intrauterine infection.

A very complex mechanism of differentiation and "learning" is represented in the selection of clones capable of producing antibodies to normal habitat factors, or in the active Extension of reactions of this genus. It may be about perinatal aspects of the formation of allergenic tolerance or allergic predisposition (atopic diathesis). The development of tolerance to allergens (atopenam) in the intrauterine period is effected by the allergens themselves, which easily penetrate the placental barrier, but mainly through the penetration of immune complexes of the allergen-antibody. The inability of allergens and immune complexes to cause tolerance often causes intrauterine sensitization. In recent decades, there has been a wide spread of food allergy, and the importance of intrauterine sensitization is convincingly confirmed.

In the development of allergic reactivity, a possible and significant effect can be provided by the features of the first "contacts" of the immune system with antigens or allergens of the external environment. It has been revealed that already in the first hours of life acquaintance with antigens related to the competence of the response chains originating from the cytokines of one of the T helper sub-populations - Th1 or Th2, can be determining with respect to the subsequent formation of atopic diathesis. The dominance at the end of the intrauterine life of Th2 production is adaptive and is aimed at protecting the placenta from the potential toxicity of Th. This dominance can persist for some more time after birth. During this period, the phenomenon of an "open window" is noted for external sensitization and triggering of stereotypy for reactions of atopic reactivity. Protecting a child from contact with atopenes or the competitive effects of antigens that include helper Th populations, according to preliminary data, can be an example of "organized early experience" for an immunocompetent system leading to the most effective prevention of allergic diseases.

There is also sufficient evidence of the significance of specific allergens affecting the newborn in the first hours and days of life. The consequence of this "early experience" or acquaintance with the allergen can be a bookmark of clinically significant sensitization with its detection through many years of life. In the complex immunological rearrangements of the primary adaptation of a newborn, the role of another participant or adaptation mechanism is evoluously defined: these are the features of the newborn's nutrition, the special functions of the mother colostrum and milk since the first hours of postnatal life.