DIFFERENTIATED LEUCOCYTES AGEING CHANGING IN CHILDREN
Differentiated leucocytes is significantly changed while ageing. Both mature and immature children have such changings beginning from the 2-nd day of life: neutrophils number decreasing (neutrophilopeny) and lymphocytes number increasing (lymphocytosis). These cellular elements number got equal to the 5-6th days (in the mature) and to the 3rd day (in the immature). It is so-called the first crossing. Segments minimal numbers and lymphocytes maximal numbers are determined in the age of 5-6 months in the mature and in the age of 1-2 months in the immature. Then neutrophils are getting increased while lymphocytes – decreased. Their number got equal again at 4-5 years (the second crossing). Direction into neutrophils and lymphocytes number changing is remained non-changed up to 14-15 years when these cellular elements content get like in the adult.
Both the mature and the immature have myelocytes and metamyelocytes in blood during the first 2 weeks of life. Monocytes number is rather low right after birth in the mature, then (during the next 2 weeks) their number get increased (in average up to 10,5%). Further changings are the following: decreasing during the first year of life up to 7-8%, then – up to 6%. Non-mature children have the same tendency but absolute numerals are less. Eosinophils content is relatively higher in the new-borns than in next age periods.
LEUCOCYTES FUNCTIONS SIGNIFICANCE IN DENTISTRY
There are more than 400 microorganisms specieces in human mouth. Some of them can be the reason of gums infectionning and the one of sublaying bone tissue.
Favourable conditions in oral cavity for microorganisms are as follows as:
· food residues;
· saliva weak-alkaline character;
· humidity;
· optimal temperature.
Microorganisms represent near 70% of dental covering: dental covering dry mass 1 ml contain up to 250 microbial cells; in 1 ml of saliva – more than 108 of microbes. Viruses and bacteries distribution is unequal in oral cavity.
The microbes biggest amount is in:
· odontal-gingival pockets;
· mucosal plicas;
· interdigital spaces.
Pathogenic microflora plays essential role at gums injury in part at parodontosis that, as it is well-known, leads to teeth loosing.
Oral microflora has relative stability mainly due to bacteriostatic and bacteriocydic features.
Main salivary compounds that have defective qualities:
1) lysozyme (muromidase);
2) lactoperoxidase;
3) myeloperoxidase;
4) mucin;
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5) beta-lysins;
6) interpherons;
7) proteolyitc enzymes with wide activity spectrum;
8) lithium ions;
9) cyanides;
10) secretory lg A (SlgA);
11) serum lg A, G, E;
12) complement system components C3 and C4.
Lysozyme bacteriolytic action deals with muramic acid decomposition in some bacteries walls as a result of which its permeability is changed and its content diffunds in surrounding environment.
Lactoperoxidase makes bacteriocydic action – participates in gram-negative bacteries lysis – due to:
· bacteriocydic aldehydes formation;
· strong oxidizers (galogens) insertion in bacterial membrane.
Myeloperoxidase – encouraging lipids peroxidative oxidation and leading to bacteries death.
Lactoferrin – make a competition with bacteries for Fe ion and, if bacteries have developed cytochrome system, - leads to their death.
Mucin – encourages bacteries attachement to desquamating epitheliocytes. Oral liquid washes desquamating cells and they are digested in stomach after saliva swallowing. Simultaneous bacterial death occurs in an acidic gastric environment.
Beta-lysines – penetrate into oral cavity from blood by passive diffusion. They influence on bacteries membrane leading to their death.
Interpherons –are present in saliva and make antiviral, immunomodulative, radioprotective and antitumorogenic qualities.
Proteolytic enzymes – are capable to damage some bacteries membranes.
Lithium ions, cyanides – their presence also leads to microorganisms death.
Secretory lg A content is higher in saliva than in blood serum. Submucosal layer contains much B-lymphocytes that are transformed into plasmocytes under interleukins action (IL are released by T-helpers of the II-nd class). Slg A main features are:
· unsensitivity to salivary proteases;
· unsensitivity to bacterial proteases.
SlgA are capable to bind bacteries exotoxins.
Ways of antibacterial activity:
· bacteries agglutination;
· their reproduction limiting;
· prevention of their attachment to epithelium.
Also SlgA possesses expressed virus-neutralizing activity.
SlgA deficiency in oral cavity is accompanied by often inflammatory diseases.
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Serum lg G, A and E – prevent infectious diseases development. lg G can be produced in little concentrations with oral mucosa plasmocytes; lg E and A passes into saliva from blood by passive diffusion.
Complement system subfraction C3 and C4 – play important role into:
· phagocytosis activation;
· T- and B-immunity stimulation.
It is proposed that complement system components come into saliva from blood stream through odontal-gingival sulcus.
Barriers play important role in protection from pathogenic microorganisms, toxins and other injuring agents. They encourage organs and tissues cells prevention from contact with damaging agents. Oral mucosa epithelium has such a function in oral cavity.
Tongue possesses especially powerful barrier function because it is covered by keratinizing multi-layered epithelium while gums are covered by keratinizing one-layered epithelium that is why their barrier function is expressed relatively weak. But this deficiency is compensated by many phagocytes in gums. Phagocytes are located directly in submucosal layer. Besides, connective tissue contains antibodies where, probably, they are produced by local plasmocytes. In part, one can find lg M, G and A in gingival mucosa.
If salivary components and tissular barrier can not perform protective functions properily and there is a possibility to get sick for organism than non-specific resistance and immunity mechanisms are involved in defense with microflora. Lymphoid tissue located in oral cavity (Pirogov-Langhans' ring) in part palatinal and lingual tonsils play important role in these reactions. Processes that take place in tonsils are as follows:
· toxins partial detoxication;
· viruses neutralization;
it is a “home” for T- and B-lymphocytes: when migrated in oral cavity lymphocytes are capable to be destroyed with lyzosomal enzymes that damage pathogenic microorganisms membranes.
Phagocytosis plays essential role in oral cavity protection but its action is realized only under pathological conditions.
It is known that leucocytes death takes place:
· directly in tissues;
· in spleen.
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About 40 billions of leucocytes die daily. These cells significant part is released from blood to mucosae surface and in oral cavity especially. There are such data that near 350-370 mln of L id est 1/80 of all WBC in vascular bed are released into oral cavity only from gums blood. This number is increased in 2-10 times at inflammation. Under physiological conditions 1 mm3 of saliva contains up to 600 leucocytes.
Leucocyte formule of saliva and parodontal pockets gingival liquid:
· 95-97% - neutrophils;
· 1-2% - lymphocytes;
· 2-3% - monocytes.
Oral liquid neutrophils in a healthy person do not possess phagocytic activity. But they release enzymes that are capable to influence on oral mucosae as well as on microorganisms here. At the same time leucocytes exhibit expressed phagocytic activity at inflammation and traumas in oral cavity.
It is important to mention that the old with adenty washing from oral liquid does not contain any WBC because they migrate only from gums margins surrounding teeth.
It has been recently established that saliva has compound partially protecting lymphocytes from AIDS virus penetration into them. It is known that saliva encourages viral particles agglutination. Probably, factor providing virus agglutination is a protein that is different from mucin by its features. This protein is received now and purified by American scientists. It took the name “fusin” (fusion – binding to smth). Its technology has been worked out and it was applied successfully for treatment the patients with lungs pathology as well as in dentistry. Fusin is synthesized by salivary glands cells. It binds to leucocytes membranes and thus protects them from virus passage into WBC. It was proposed that this protein inhibited those molecules of membrane that helped virus passage through membrane. Fusion or viral and cellular membranes merging appears in a process of virus passage into the cell. Fusin is similar to chemokine by its content and functions. Chemokines represent biologically-active substances that mediate chemotaxis, phagocytosis, cellular and humoral immunity.
Protective cells.
Oral mucosa epithelium serves as a barrier in the way of antigens penetrations in part allergens, cancerogens as well as microorganism invasion. Epithelium barrier function disorder leads to oral cavity multiplied diseases appearance. At the same time, leucocytes mostly degeneratively changed neutrophils are found in mucosal epithelium as well as on its surface. Separate neutrophils make microorganisms phagocytosis and probably represent antigen-presenting cells (APC).
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Neutrophils and monocytes big amount is under epithelium through which they migrate from proper plane vessels in gingival sulcus lumen. Neutrophils migration speed is 30000 cells per 1 min and their relative portion in epithelium is equal to 60%. T-lymphocytes mainly T-helpers of the I-st and the II-nd classes can be found in oral mucosa epithelium. Up to 40% of T-lymphocytes are in movement. They can be located in groups and separately. Interepithelial lymphocytes are undergone to apoptosis in many focuses. Their big part acquires phenotype of memory cells and participates in secondary immune response.
Langerhans' cells play important role in oral cavity epithelium barrier function providing. They comprise 2% of cellular population. They are similar to epidermis similar cells by their morphological-functional characteristics. They are mostly in constant movement. It facilitates their meeting with antigens. These are real antigen-presenting cells (APC). They migrate in regional lymphatic nodes after meeting antigens where not only contact and side agent transduction to lymphocytes takes place but the proliferation of the latest ones occurs as well. Dendritic APC with phenotype CD36 are in oral mucosa epithelium similar to macrophages by their ultrastructure.
Epitheliocytes, lymphocytes and Langerhans' cells interaction
Epitheliocytes start IL-1 and TNF-alpha (tumor-necrotic factor) production after antigen meeting. It causes Langerhans' cells stimulation. These cells are able to secrete IL-1 and IL-6 acting to T-helper of the I-st subclass after contact with antigen and antigen transformation into immunogenic form. T-helpers of the I-st subclass secrete IL-2 and gamma-interferon that leads to APC activation. At T-helpers of the II-nd subclass involvement into immune response B-lymphocytes transformation into plasmocytes occurs capable to produce lg. Immunoglobulins can be both in free and bound form in oral mucosa epithelium. Free lg are present in: serum, lymph and tissular liquid. Bound lg form immune complexes with antigens that are eliminated by phagocytes. Ig A and lg G are found in mucosa the most often, while lg M – at inflammation. Intraepithelial lg take part both in antigens elimination and in inflammation process.
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