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Transcript
Semiology of immune system Department of pediatrics Notion Immune system reunites the organs, tissues and cells, which ensure the defense of human organism against the genetically strange substances (antigens) by exogenous and endogenous origin. Immune system Two possibilities of IS response manifesting were distinguished for to understand how the organism succeeds to put up resistance to the external medium factors (infectious agents) : elimination of pathogenic agents with the nonspecific means of IS response or producing of some cellular and molecular components for adopting the pathogenic agent (specific means). Physiologic importance The function of IS consists in the Ag identifying and generation of specific response – synthesis of antibodies, accumulation of sensibilized lymphocytes, which will neutralized, destroyed and eliminated the Ag from organism. Components of immune system 1. Lymphoid organs: a) Central b) Peripheral 2. Humoral components a) Nonspecific b) Specific 3. Cellular components a) Nonspecific b) Specific Immune system Central lymphoid organs The central lymphoid organs (primary) are represented by: hematogene marrow thymus Central lymphoid organs The central lymphoid organs have a major significance in immunity because they represent the place of lymphopoiesis. At their level, the cellular components of IS: B lymphocytes and T lymphocytes, are differentiating from derived precursors originated from stem cell, proliferating and se maturating in functional cells. Hematogene marrow Hematogene marrow is localizing in the trabeculae of osseos spongious tissue from long bones epiphyses, from flat bones and from short bones. From the histologic point of view, it is formed from stroma, blood, lymphatic vessels and nerves. The stroma is formed from conjunctive reticular cells, forming a network where are sitting the stem cells. Here the B lymphocytes are differentiating. Thymus The thymus is sitting retrosternally. From the anatomic point of view, the thymus is formed from two lobes connected by isthmus. Each lobe is formed from lobules delimited by conjunctive septa which proceed from the capsula covering the entire organ. Two zones are described in the thymic lobule: cortical and medullar. The thymic cells are lymphocytes, epithelial and non-epithelial cells. The process of differentiation is developing under the influence of local hormones (thymosine, thymopoietine, thymuline) secreted especially by subcapsular and subtrabecular epithelium. Thymus Thymus The thymus is forming at the end of first month of intrauterine development. It is positioned retrosternally. It is covered by conjunctive tissue capsula which separates the organ in lobules. Each lobule has cortical and medullar layer. The cortical layer contains Tlymphocytes, and epithelial cells of medullar layer form the Gassale corpuscles. Thymus The thymus releases in the systemic circulation T-lymphocytes, hormones (thymosine, thymopoietine, thymic factor etc.) which regulates the proliferation and differentiation of lymphocytes. The thymus achieves the maximal degree of development in early childhood. In the period of 3 – 13-15 yrs the stabilization of gland mass has place, and ulterior it involutes. The cortical layer becomes more poor in Tlymphocytes, the Gassale corpuscles from medullar layer disappear, these structures being replaced with conjunctive and adipose tissue. Thymus In rare cases the physiologic involution is not producing. These clinical situations usually are associated with diminishing of GCS secretion by cortical layer of suprarenal glands. Such patients are more receptive to intercurrent infections, have increased risc for neoplastic processes appearance. Peripheral lymphoid organs Peripheral (secondary) lymphoid organs are represented by: Spleen Lymph nodes Lymphoid tissue from mucosae Spleen The spleen is situated in the left superior part of abdomen. It has exterior capsula from conjunctive tissue which sends in parenchyma prolongations forming trabeculae. These together with the reticular cells network form a support for a great lot of cells. Two types of tissue enter in the spleen structure : the tissue responsible for grown old blood cells destruction and urgent generation of new erythrocytes, platelets and granulocytes (red pulp) and tissue populated by immune competent cells (white pulp). Spleen Spleen white pulp is a lymphoid tissue situated in two zones: T-dependent zone, situated around central arteriola and B-dependent zone, which surrounds the Tzone, as a muff. In B-zone the cells are organized in primary follicles (non stimulated) and in secondary follicles (stimulated). At the periphery of B-zone, to the exterior, the splenic macrophages are sitting. Lymph nodes The lymph nodes are oval formations by different dimensions, situated in the confluence place of great lymph vessels. Lymph nodes The forming of LN begins in the 2-nd month of intrauterine development and is finishing in the postnatal period. In new-born the LN capsula is very thin and fine, the trabeculae are weakly differentiated, and their palpation is difficult. LN are soft and they are included in good developed adipose tissue at this age. At 1 year age the LN can be palpated at the majority of children. Parallel with their growing their differentiation has place. Lymph nodes In the 3 yrs age the capsula is good formed. At 7-8 yrs the forming of trabeculae in the interior of LN begins. At 12-13 yrs the structure of LN is definitized, being good differentiated all their structures: capsula, trabeculae, follicles, sinuses. Lymph nodes In the puberty period the LN growing is finishing, and sometime even partially regresses. The maximal number of LN is achieved around10 years age. The mature has approximatively 460 LN, having total mass by1% from corporal mass (500 – 1000g). Lymph nodes Each lymph node (LN) is covered at surface with conjunctive tissue capsule, and in interior contains lymphoid tissue. The lymphoid tissue of LN is separated in two layers: cortical and medullar. Cortical layer is formed from follicles– conglomerates of B lymphocytes. In paracortical layer the T-lymphocytes are placed In medullar layer the plasmocytes, secreting immunoglobulins are placed. Lymph nodes LN are placed in groups, through them the lymph drainage from distinct anatomic zones has place. Due to their structure and localization the LN have a role of barrier in the pathway of infection spreading, preventing its generalization. LN filter the particles with antigenic properties, and the lymphocytes and plasmocytes from LN ensure the synthesis of antibodies. The lymphoid system of respiratory and digestive tract ensures the good functioning of local immunity at the level of their mucosa. Lymph nodes The reaction of LN at different stimuli, especially infectious can be observed from 3 months age. In 1-2 yrs age children the barrier function of LN is not good expressed, therefore in this age the infections easily are generalized (septicemia, meningitis, generalized forms of TBC). Immaturity of lymphoid system at the level of digestive tube predisposes the suckling babies at intestinal infections and allergization of organism on enteral pathway. Lymph nodes In the antepreschool age the LN are still good structured and can serve as mechanical barrier against the infection spreading. In this age the lymphadenites, including these purulent and caseous (TBC) are frequent. In the age of 7-8 years the LN become functional and can suppress the infection through immunologic mechanisms. Lymph nodes Occipital – placed on occipital tuberozities – they collect the lymph from the scalp skin and cervical posterior region. Mastoidian – placed in region of mastoid apophises, retroauricular – placed postrior from ears pavilion – both groups collect the lymph from medium ear, external auditive conduct, ears pavilion, paraauricular teguments. Submandibular – placed under inferior bundles of mandiba – collect the lymph from face skin and gums mucosa. Mentoniar – placed one self bilaterally in the region of chin – collect the lymph from the inferior lip skin, mucosa of gums and from inferior incissives. Lymph nodes Anterior cervical and tonsilar – placed anterior from the sternocleidomastoidian muscle, in superior cervical triangle– collect the lymph from face teguments, from parathyroid gland, nasal, faringeal and buccal mucosa. Posterior cervical – placed posterior from the sternocleidomastoidian muscle, anterior from trapezium muscle, in cervical superior triangle – collect the lymph from cervical region and partially from larynx. The LN from above mentioned groups are frequently catalogued as a unique group – cervical LN. Lymph nodes Supraclavicular – placed in supraclavicular fossa – collect the lymph from superior part of thorax, pleural domes and pulmonary apexes. Subclavicular – placed in infraclavicular fossa – collect the lymph from the thoracic wall and pleura. Axillary – placed în axillary fossa – collect the lymph from superior members (exception fingers V, IV, III and palm). Thoracic – placed on the inferior margin of big pectoral muscle – collect the lymph from thoracic wall teguments, parietal pleura, partially from lungs and mammal glands. Lymph nodes Cubital – placed in the cubital region at the level of biceps tendon – collect the lymph from V, IV, III fingers and palm. Inguinal – placed on line of inguinal ligament– collect the lymph from the teguments of inferior member, hypogastrium, buttocks, anal region, perineum, genital organs. Popliteal – placed in the popliteal fossa – collect the lymph from the teguments of leg. Lymph nodes The knowledge of LN localization and of their draining zones has a major role in the identifying of infection gateway, especially in the case when the modifications of infection gateway are minimal or even absent, but regional LN will react in the all cases. The semeiology of LN affection Complaints. In the case of LN marked enlargement, the child or the parents can remark this modification and can present the respective complaints. In the case of lymphadenitis the child can accuse pain, tumefaction and hyperemia at the level of affected LN. Semeiology of LN affection Inspection. Only LN which are placed superficially and are very enlarged in volume (lymphogranulomatosis, infectious mononucleosis) can be observed. In lymphadenitis the hyperemia of teguments covering the involved LN, which usually is tumefied and painful at palpation can be observed. Semeiology of LN affection Palpation. At palpation the LN the following Characteristics are appreciated: Dimension – usually the LN have a diameter around 0,3-0,5 cm (pea seed). The dimension of LN is gradated as the following: I degree – dimension of millet seed II grad – dimension of lentil seed III grad – dimension of pea seed IV grad – dimension of horse bean V grad – dimension of peanut VI grad – dimension of pigeon egg. Increasing of LN dimension poate can be isolated or in group, symmetrical or unilateral. Semeiology of LN affection Number If in each group 3 or less LN are palpable – they are considered solitary, If in some group more than 3 LN are palpated – they are considered multiple. Semeiology of LN affection Consistence Can be soft, elastic, hard. It depends from the oldness and nature of process: in chronic pathology the LN are hard, in the case of recent affection they have soft consistence. Physiologically the consistence of LN is elastic. Semeiology of LN affection Mobility – usually the LN are mobile. Report with teguments, adipose subcutaneous tissue, other LN. Physiologically the LN don’t connect with adiacent tissues and not between them. Sensibility. LN are painless at palpation. The presence of pain at palpation indicates an acute inflammatory process at the level of LN. Semeiology of LN affection The palpation of symmetrical LN is performing with both hands concomitantly. (exception – cubital LN). In healthy children until 3 groups of LN are palpable. In physiological conditions the The chin, supra- and subclavicular, thoracal, cubital and popliteal LN are not palpating. Semeiology of LN affection The LN can be considered normal, if: their dimension does not exceed the dimension of pea seed, are solitary, by elastic consistence, mobile, don’t adhere between them and adjacent tissues, are not painful. Semeiology of LN affection For the performing of certain diagnosis, the clinical examination of LN is supplemented at necessity with special paraclinical examinations: puncture of LN, biopsy of LN, lymphography. Semeiology of LN affection In children the modifications of LN both local and generalized are frequently observed. Local/regional enlargement of LN accompanies the suppurative processes at the level of teguments: folliculites, pioderma, furunculosis, miliary multiple abscesses , infected sores, hydroadenitis etc. Semeiology of LN affection Lymphadenopathy – enlargement of LN in dimensions, sometimes with modification of their consistence. Polyadenia – increasing of number of palpable LN. Semeiology of LN affection In diphtheria, scarlet fever, tonsillitis the cervical LN react. În felinosis the cubital and/or axillary LN are modified. Semeiology of LN affection TBC of peripheral LN usually is limiting at the affection of one group of LN, most often cervical. The LN represent a voluminous, hard, painless conglomerate (packet). They are adherent between them and adjacent tissues. They have tendency of evolution to the caseous necrosis, with forming of local fistula, after that the „ stellated scars” remain. Semeiology of LN affection In the infectious mononucleosis all groups of peripheral LN are affected, but the affection of cervical posterior LN predominates. In rujeola the occipital LN are affected. For rubeola the diffuse LN affection, more pronounced in cervical, occipital and axillar LN groups is characteristic. Semeiology of LN affection In adenoviral and paragrippal infection the anterior and posterior cervical and occipital LN are predominantly involved. In mumps the auricular LN are palpating as firm formations which are placed superiorly to parotidian tumefiated glands. In toxoplasmosis most frequently the groups of cervical, axillary, inguinal LN are affected. The LN have the dimensions of a nut, sometimes can have a form of pockets, but each node can be palpated separately. Semeiology of LN affection In HIV/AIDS the generalized lymphadenopathy is a precocious and constant symptom. The diameter of LN is 2-3 cm, the contur net delimitated, hard at palpation, not adhere between them and not to adjacent tissues, usually are sensible at palpation, sometimes painful. Semeiology of LN affection Lymphosarcoma is manifesting by affection of isolated LN group, usually cervical or supraclavicular. LN are very hard, painless at palpation, the local signs of inflammation are absent. The generalized lymphadenopathy can be present in a lot of acute or chronic infectious pathologies and in noninfectious pathologies. Semeiology of LN affection The diffuse diseases of conjunctive tissue can be around the noninfectious causes of generalized lymphadenopathy. Lymphogranulomatosis as a rule begins with peripheral LN affection, more frequently cervical or/and mandibular. In the same time with disease evolution the LN grow in conglomerates. LN are painless, at palpation creates a sensation of „sack of potatoes”. The diagnosis is confirmed by the hystologic examination of LN (BerezovskiSternberg cells). In ALL (acute lymphoblastic leukaemia) all groups of LN are rapidly growing in dimensions. They are soft and painless at palpation. Lymphoid tissues associated to mucosae The lymphoid tissues associated to mucosae also enter in the category of secondary lymphoid organs. These can be: good individualized anatomically structures or lympho-epithelial diffuse structures. Lymphoid tissues associated to mucosae The individualized anatomically structures are: 1. Componentele of Valdayer lymphatic ring a) lingual tonsils b) palatine tonsils c) tubar tonsils d) faringean tonsils 2. Payer’s patches 3. Vermiform appendix Lymphoid tissues associated to mucosae The diffuse lympho-epithelial tissues Are localized at the level of digestive, respiratory, genito-urinary tracts etc. After their localization these tissues were named: MALT – mucosae associated lymphoid tissue SALT – skin associated lymphoid tissue BALT – bronchia associated lymphoid tissue GALT – gut associated lymphoid tissue IS. Nonspecific immunity The factors of nonspecific protection have a large spectrum of action, that is possess a high specificity. The nonspecific forces of protection are sufficient for to combat the majority of pathogen agents. Nonspecific reactions are at the basis of natural immunity and offer to organism the immunity even against the pathogen agents which the organism didn’t anteriorly met. IS. Nonspecific immunity These factors being phylogenetically older have a decisive role In the protection of nevborns until the maturation of specific immune mechanisms. IS. Nonspecific immunity Nonspecific protection is ensured by the physiologic barriers and humoral nonspecific factors. IS. Nonspecific immunity In the physiologic barriers enter: teguments and intact mucosae, LN, ciliary epithelium, acid gastric medium, Hematoencephalic barrier, kidneys (which excrete some microorganisms, especially viruses). IS. Nonspecific immunity Nonspecific humoral protection is ensured by: lysozyme, properdin, present in blood and other BL, interferon, complement system , phagocytosis. The last two components have special status being mechanisms of nonspecific and specific protection in the same time. IS. Nonspecific immunity Lysozyme– a protein which possesses enzymatic qualities. It destroy the structure of mucopolysacharides of cellular bacterial membranes. It is very active on Gramm “-” bacterias. Secretory Ig A potentiates the action of lysozyme. The most high level of lysozyme is in newborns, and further decreases gradually. IS. Nonspecific immunity Properdin – a plasmatic globulin, which activates alternatively the complement and together ensure the elimination of viruses and bacterias from organism. The contain de properdin in children is low, at the 1-3 weeks its level rapidly increases and remains high during all childhood. IS. Nonspecific immunity Interferon – a protein with antiviral action, which is manifesting in the phase of de intracellular virus replication. It can be synthesized by each cell of human organism, but especially by leucocytes. IS. Nonspecific immunity Interferon also: blocks the multiplication of chlamidias, plasmodium malariae, ricketsies, increases the organism cells resistance to the action of exo- and endo toxins, stimulates the phagocytosis, increases the cytotoxicity of lymphocytes, blocks the cangerogenesis, Influences the antibodies forming (small doses – stimulates it, and high doses – inhibates it). IS. Nonspecific immunity In newborns the capacity of interferon synthesis is low, increases gradually and achieves the maximum at the age of 12-16 years. IS. Nonspecific immunity The complement (C) – enzymatic system, formed from plasmatic globulins, the biologic role of al which is the cellular antigens lysis (viruses, virus infected cells, bacterias, mycoplasmas, protozoa, tumoral cells) fixed by Ab. It includes 11 complement fractions and 3 inhibitors. IS. Nonspecific immunity All components of complement system circulate in blood under the form of precursors which can be activated on 2 pathways: classic or properdinic. The trigger of classic activation pathway is the Ag-Ab complex. In the absence of Ab the complement system can be activated through alternative pathway – properdinic. IS. Nonspecific immunity Phagocytosis – a process of capture and digestion of Ag by tissular macrophages (monocytes) and circulant macrophages (neutrophils and monocytes). The phagocytes are the first cells which enter in contact with exo- or endogenous Ag. IS. Nonspecific immunity The immune protection is ensured by 2 specific mechanisms : cellular and humoral, which are differing from one another by the mechanisms of neutralization and Ag elimination. Cellular immunity. The immune response is ensured by T-lymphocytes (thymodependent) and B-lymphocytes (bursodependent). The both cellular lines have a common predecessor –stem cell, which migrates from bone marrow in thymus and in analog of Fabricius burse, when the differentiation and their maturation have place. Then these cells populate the T şi B zones of LN. Here, at the first meeting with Ag their sensibilization and ulterior differentiation in another 2 subpopulations have place: effector cells and memory cells. Cellular immunity Effector cells – participate directly in the „liquidation” of antigenic aggressor. In the cell immunity there are cytotoxic T-lymphocytes (Tkiller). They neutralize the antigen directly or through some special biologic active substances – lymphokines. Cellular immunity The memory cells are the lymphocytes which are transforming in the inactive form, but preserve the information about the Ag. These cells are going in again in the sanguine and lymphatic circulation and „patrol” the organism. Humoral immunity The humoral immunity is ensured by B-lymphocytes. Initially theT-lymphocytes are stimulated, And they will be transforming in T-helpers. These through interleukins will stimulating the transforming of B-lymphocytes in plasmocytes, which will synthesize the specific antibodies. So, the effector cells of humoral immunity are plasmocytes. B-lymphocytes receive also information about the nature of Ag and from macrophages which captivate these antigens and remake them primarly. IS. Specific immunity In this way for good functioning of IS an harmonious collaboration between these three types of immunocompetent cells is necessary: T-, B-lymphocytes and macrophages. In the same time during antigenic stimulation the T-suppressors are forming. They block Thelperis, in this way blocking the Ab synthesis by B-lymphocytes. This capacity of the organism is the basis of immunotolerance. Cytokines There are the soluble molecules, synthesized by a great variety of cells, inclusively by lymphocytes, with the role of humoral messengers, which realize the communication between different cells, controlling their growing, differentiation, maturation, division, metabolism, functions. T lymphocyte B lymphocyte Macrophage IS. Specific immunity T- and B-lymphocytes can be found from the age of 10-12 weeks of intrauterine development. T-lymphocytes become functionally after the age of 14-15 weeks of intrauterine development. The newborns have a more number of T- and B-lymphocytes comparatively with another age and adults, but these cells are not completely functional. IS. Specific immunity B-lymphocytes synthesize more classes of Ig: G, M, A, D, E. In each antigenic aggression a lot of Ig classes are synthesized As a response to primary contact with Ag the Ig M, after that IgG, ulterior IgA are synthesized. At repeated contact with Ag the IgG from start is synthesized. Humoral immunity IgG constituies 70-80% from the totality of plasmatic Ig. It is the self Ig which passes the placentar barrier, ensuring the passive immunity of the new-born. Transmission of IgG from mother to fetus has place more actively in the last weeks of pregnancy, thus the level of IgG in premature babies is less than in term born baby. Humoral immunity During the time the level of maternal IgG in blood plasma of suckling baby decreases, and achieves the minimum at 6-9 months. At the age of one year the intensity of proper IgG synthesis constitutes 50% from that of adult. At 4-6 years the level of IgG in children achieves the IgG level at adult. Humoral immunity IgM constitutes 5-10% from total plasmatic Ig. They constitute the first line of defensive taking part in the complement activation on classic pathway, agglutination and opsonization of Ag, lysis of alien cells. In plasma of newborns the level of IgM is low, but increases quickly, achieving the adult level at the1-2 years age. Humoral immunity IgA constitute 10-15% from total plasmatic Ig. They are synthesized by plasmocytes, which are localized at the level of mucosa and submucosa of digestive tube and respiratory pathways. The most part of IgA remains in the place of synthesis(secretory IgA), ensuring the local immunity. Secretory IgA is finding in tears, saliva, nasal and bronchial secretions, secretions of digestive tube, colostrum. The level of secretory IgA in children is low. It increases with age and achieves the most high level at 5 years. Humoral immunity Seric IgA in children is less active. In usual newborn is absent. It appears after first week of life. At 1 year age the IgA level constitutes 20% from that of adult, which is achieved only at 10-12 years age. Humoral immunity IgD and IgE are containing in în non significant quantities(each - 0,2%). IgD is a globulin by embryonic type. It is enable to activate the complement on alternative pathway, to neutralize some viruses. Humoral immunity IgE constitutes the most part of reagines – antibodies responsible by allergic reaction releasing. They are synthesized as response to primary contact with Ag. IgE are fixed on the mastocytes and basophils surface, realizing therefore the state of sensibilization. Humoral immunity At the repeated contact with Ag the IgE provokes the degranlation of these cells with elimination from them of different BAS, their biologic effect being at the basis of pathological modifications in allergic reactions. IgE is practically absent in the plasma Of newborns. During the time their concentration increases achieving the adult level at 10-12 years age. IS. Specific immunity Therefore, the IS development is an ontogenetic process genetically programmed. The forming process is initiating intrauterine. The most important stimulus the IS receives after birth, when the exo- and endogenous antigenic aggression, determined especially by digestive tube, superior respiratory pathways and teguments microbial population by conditioned-pathogene microflora, increases considerably. IS. Specific immunity Immaturity of IS in children makes them More sensible to intercurrent infections, favour the generalization of infectious process with the development of septicemia and septicopiemia, favour the more severe evolution of infectious pathologies. Semeiology of IS affections Three types of this system functions affection are possible: Defect of one link of IS (primary and secondary immunodefficiencies) Autoaggression against the normal structures of human organism (auoimmune diseases and diseases due to immunocomplexes) Dysfunctions when some functions of IS are exagerrated in the detriment of another (lymphoproliferative syndromes) Semeiology of IS affections The states of immunodeficiency appear as a result of one or more links of IS function abolition. The states of immunodeficiency are: primary (inborn) and secondary (acquired). Semeiology of IS affections The states of primary immunodeficiency are determined by: primary affection of T-lymphocytes; primary affection of B-lymphocytes; combined affection of T- and Blymphocytes; the summary incidence of primary immunodeficiency states is by 2:1000, 50-70% being primary defects of B-lymphocytar system, and 5-10% of T-lymphocytar system. Suggestive signs for a primary immunodeficiency are: The child supports frequently infectious recurrent diseases especially of respiratory pathways, digestive tube, reno-urinary system, teguments, frequently complicated with otitis, purulent sinusitis and septicemia. They manifest unusual reactions at banal infections (ex. pneumonia at varicella). The suffering is determined by unusual causal agents (ex. Pneumocystus Carinii) Suggestive signs for a primary immunodeficiency are: Presence of some systemic reactions after vaccination with live viral attenuated vaccines or BCG Bizarre hematologic deficit (anemia, thrombocytopenia, leucopenia) Disorder of digestion with the development of malabsorption syndrome. Secondary immunodeficiencies Secondary immunodeficiencies are determined by a lot of pathological states which lead to the involution of lymphoid tissue, lymphopenia, hipogammaglobulinemia. They are the following: pathologic states associated with loss of proteins: nephrotic syndrome, combustions, exsudative enteropathy dystrophias, avitaminoses Viral (flu), bacterial (holera), micotic (candidosis) infections, helminthiases Massive surgical interventions and/or postoperatory yatrogenic complications (irradiation, imunosuppressives: GCS, CS) Lymphoreticular tumors(lymphogranulomatosis,etc.) Semeiology of IS affections In children first 3 yrs of life the state of immunodeficiency can be determined by thymomegaly, which is induced by hypothalamo – hypophysar - suprarenal axe affection. In stress situations an rapid accidental involution of thymus can be developing, in which a massive releasing of T-lymphocytes in blood has place, their massive death in thymus with their phagocytosis by macrophages has place . Transitory deficit of humoral immunity is characteristic for first year age children, between 6 – 9 months. Semeiology of IS affection Primary affection of nonspecific factors of protection includes disorders in Complement System disorder of phagocytosis. Semeiology of IS affection The genetic deficit can involve each component of Complement System, which shell alter their cascade activation. It is clinically manifesting through decreased resistance at bacterial infections (C1, C2, C3, C5), increased incidence of hipersensibility diseases (C1, C2, C4). Deficit of C1 leads to development of angioneurotic recurrent edema. Semeiology of IS affection Patients with disordered phagocytosis support frequent infections caused by microorganisms usually non pathogene. In chronic granulomatosis (syndrome of paradoxes) the patients are resistant to infections with high virulence microorganiss (streptococci, meningococci, pneumococci), but are sensible to conditioned pathogene microorganisms (Escherihia coli, staphylococci). Semeiology of IS affection A global affection of all components of Immune System And of humoral nonspecific iactors Is characteristic for HIV/AIDS Critical periods in the Immune System development Tere are a periods, when the organism immune system in growing and development Generates paradoxal or unadequate responses to antigenic stimuli. I-st critical period – first month of life. II-nd critical period – from 3 to 6 month of life. III-rd critical period – second year of life. IV-th critical period – from 4 to 6 yrs of life. V-th critical period – period of adolescence. Critical periods in the Immune System development First critical period– first month of life. A decreased activity of phagocytes is observing. Lymphocytes are capable to react at antigenic stimuli and mitogenic actions. Humoral immunity is ensured by maternal IgG. Critical periods in the Immune System development The second critical period– from 3 to 6 months of life. Maternal antibodies disappear from child’s plasma, the proper IgM is synthesizing as a response to antigenic stimuli. Deficit of IgA predisposes to frequent infections of respiratory pathways (viral). Immunocompetent cells have a diminished activity. In this period the primary immunodeficiences are manifesting. Critical periods in the Immune System development The third critical period– the second year of life. Immune system is completely functional. The capacity of IgG synthesis increases, but the mechanisms of local protection remain insufficient developed. This maintains a high receptivity of the child’s organism to different pathogene agents. Critical periods in the Immune System development The fourth critical period– from 4 to 6 years of life. The antibodies synthesis, excepting IgA, achieves the level of adult. Concomitantly the titre of IgE increases. The activity of local protection factors remains diminished. In this age the tardive congenital immune defficiencies are clinically manifesting. Critical periods in the Immune System development The fifth critical period– the period of adolescence. The gonadian hormones secreted in this period inhibate the immune reactions. As a result the autoimmune and lymphoproliferative pathologies can develop. The increased receptivity to diverse micobial agents is observing. A nice day!