IMMUNITY of the PERSON

It is now very fashionable to speak about immunity of the person. Various articles, books on this question are written. One offer miracle diets on increase of immunity. Others advertise various food additives, the vitamins ostensibly raising your immunity. The third try to enter into your organism the stem cells ostensibly raising your immunity and making you more healthy and young. The information on the ordinary reader is strewed in abudance about miracle ways of increase of his immunity.

However all this information is in most cases used by various charlatans and the rascals trying on your ignorance of this question to earn more money.

Therefore we for the first time from the scientific point of view in this book consider the questions connected to functioning of your immune system. That to you it was clear and understandable.

What is the immunity and of what it consists?

The immune system of the person is a system of protection of human organism from any antigenes against which various antibodies are developed. As antigenes the immune system of the person can distinguish as extraneous microorganisms, toxic substances and alien subjects, bodies, inclusions, and proteins blocks, cells of an own organism which have distinguished reception system from generated in the organism at present.

First of all, the immune system of the person protects he from many microorganisms which occupy our planet. So in one drop of water can contain up to tens millions microorganisms and to kill all of them it is impossible. Many microorganisms are useful to the person and with their help the person has learned to receive various food stuffs - bread, beer, a wine, sour-milk products, yogurts, cheese, cottage cheese and many, many other products. But there are also pathogenic microorganisms which at reduction of protective functions of an organism can result in those or other diseases. To kill all microorganisms just in case it is impossible. Then we shall stay without many traditional products and all the same we shall not protect an organism from infections.

Therefore always it is necessary to have reliable own immune system of protection of an organism from harmful microorganisms instead of to hope for antibiotics. Of what it consists our system of protection.

The immune system of the person consists from innate (natural, transferred in the genetic way) and acquired immunity (generated during his life). On innate immunity it is necessary 60-65 % from all immune status of the organism, and accordingly on acquired immunity it is necessary only 35-40 % (see fig. 1.).

Fig. 1. A ratio of innate and acquired immunity in the immune status of human organism.

In turn innate and acquired immunity in human organism is formed by cellular components and soluble components.

When and how is formed innate immunity?

Innate ( natural) immunity is formed in human organism from intra-uterine development. So, on 2th month of pregnancy it is already possible to find out the first phagocytes - granulocytes, and monocyte appear on 4th month. These phagocytes is formed from stem cells which are synthesized in a bone brain, and then these cells, get in a spleen where with the purpose of their activation is added to them the carbohydrate block of reception system "Self"-"Nonself". After birth of the child and further he is supported due to work of cells of a spleen where soluble components of innate immunity are formed.

Thus, in a spleen is carried out constant synthesis of cellular and not cellular components of innate immunity.

The main cellular components of innate immunity are phagocytes.

The basic soluble components of innate immunity are Complement system, cytokinines, interleukines and others glycoprotein complexes.

Accordingly each of these components has proteins structure, but the basic compounds responsible for reception system such as "Self"-"Nonself" are carbohydrates. Therefore all components of innate immunity are complex systems type of the glycoprotein, instead of pure proteins as sometimes it is possible to read in the popular literature.

innate immunity causes the same simple reactions of the organism to any alien antigens. Thus phagocytes are not acquired cellular components to those or other antigens. They work against all antigens under one "script". The basic function of phagocytes is to grasp and digest microorganisms penetrating from the outside in human organism.

To phagocytes concern neutrophile and monocytes which are present at blood of the person, and also macrophage which contain in tissue of human organism.

Macrophages are widely distributed in human organism and borrow strategic positions, settling down between parenchyma this or that body and the cells which are taking place on a surface of blood vessels and cavities. Those, for example, are alveolar macrophage, contained in easy, the synovial cells filling articulate cavities and others.

The main soluble components of system of innate immunity which contain in blood, are proteins of a sharp phase, Complement system, cytokinin.

The Complement system consists of group serous globulin's which, cooperating in the certain sequence, destroy walls of cells both the organism, and the cell of microorganisms, penetrating in a body of the person. Simultaneously the Complement system makes active acquired immunity of the person. The Complement system is capable will destroy incorrectly constructed cells erythrocyte, tumoral cells. Most active of these globulin is �3 reactive proteins. It very much frequently determine at patients. Activization of Complement system is carried out also for the account immunoglobulins IgA, either mono-or polysaccharides (including of inulin).

Who responds in human organism for destruction of tumoral cells?

Innate immunity is responsible under the control of formation and destruction of cancer (tumoral) cells. Therefore creation of various vaccines against the cancer is an elementary biochemical illiteracy and profanation as any vaccine is not capable to form innate immunity, and on the contrary - it forms only acquired immunity. Precisely as well at AIDS, but about it we shall talk in the other section.

Where and how is formed acquired immunity ?

acquired immunity is formed also from stem cells, but they get in the Thymus where their acquired activization is carried out to those or other microorganisms. The Thymus it starts to be formed on 2th month of pregnancy, and on 4th month it starts to take part in the immune answer.

The Thymus it is located about a throat where inhaled air together with alien microorganisms gets. In this acquired body there is an operating time of acquired immunity. As is known, removal the Thymus at once after birth, results to:

To decrease of growth rate and development;

To occurrence of symptoms of an atrophy, exhaustion with the subsequent lethal outcome in some months;

To reduction of quantity lymphoid cells in blood and lymph nodes;

Inability of an organism to reciprocal immunological reactions.

Removal the Thymus in an adult organism usually does not result in such consequences. Therefore formation of acquired immunity also depends on normal work of the Thymus.

In the Thymus, representing bag (microbial collector), the various microorganisms getting through a mouth collect. Against the given microorganisms in Thymus begin forming the appropriate acquired antibodies. Antibodies, forming in the Thymus, then are carried on all organism as cells - T killers, T effectors, T suppressor and T helper cells and they can collect in lymphoid tissue and the lymphoid sites, located on all organism.

These cells and not cellular (soluble) components acquiredally destroy only those microorganisms against which they are generated. The more various microorganisms gets in the Thymus, the against a lot forming the appropriate acquired antibodies. Therefore since childhood the child should live not in sterile conditions, and in natural, with the big variety of microorganisms.

acquired immunity formation during enough long time from the moment of birth of the person. Thus the sizes of the Thymus in a childhood are increased, and already after 12 years the sizes of the thymus gradually decrease, and it is hardly found out in the adult, as in inhaled air meets ever less and less than alien microorganisms against which can formation acquired antibodies.

Thus, the Thymus in a childhood is that body where constant vaccination of an organism against all the new and new microorganisms getting in the organism of the child is carried out.

What role is played with vaccines in formation of acquired immunity?

Last century mankind all less often meets such microorganisms as a plague, a cholera, measles etc. However these microorganisms are very dangerous to human organism. Therefore already at children's age enter in the organism almost each person antigenes, imitatively influence of a similar microorganism ( a vaccine) so that the organism has formed out the appropriate antibodies. At penetration of similar microorganisms in human organism in which the appropriate acquired antibodies were already generated, against them acquired immunity and the person quickly starts to work recovers.

What structure has acquired immunity?

The main cellular components of acquired immunity are lymphocytes and its soluble components are immunoglobulins. Immunoglobulins and lymphocytes contain the glycoproteins, complex molecules consisting of the carbohydrate and a protein part. The ratio of the carbohydrate to the protein part in immunoglobulins varies. In IgM the carbohydrate part constitutes 11,8%, in IgE 10,7%, in IgA 7,5% and in IgG only 2,9%. In immunoglobulins D the carbohydrate part is practically absent. The lymphocytes also contain carbohydrates: galactose, mannose, fucose and N-acetylglucosamine [ 13 ]. As the half-life of immunoglobulins is only 2,5 to 23 days, the acquired immunity of man depends on constant synthesis the immunoglobulins, and that in turn is dependent on a continuous dietary supply of various amino acids and sugars.

As the half-life of lymphocytes is only 3 day and that of immunoglobulins 2,5 - 23 day, any impairment in biochemical processes of the human organism manifests itself first of all in the immune system. The protein part of the lymphocytes and of immunoglobulins is synthesized from essential and non-essential amino acids. These amino acids have to be supplied by the diet.

The carbohydrate part of the lymphocytes and the immunoglobulins consists of galactose, mannose, fucose, N-acetylglucosamine and sialic acid. For example, in Ig G the mannose and the fucose constitute 36,7 % of the carbohydrate part of a molecule. Cals M.M. et al. showed [ 14 ] that Ig M has a high oligosaccharide protein. The native Ig E VL protein precipitated with high intensity all mannose-acquired lectins as cancavelin A [15].

Thus for the synthesis of the carbohydrate part of immunoglobulins minor sugars such as mannose and fucose need to be present in the blood. Absence or low levels of these sugars in blood results in the glycosylation of abnormal immunoglobulins with broken carbohydrate structure [ 15 ], and also the breakdown of other glycoproteins [ 16, 17, 18, 19 ].

The level of mannose in the blood of healthy person is 20 - 50 mkmol/L [ 20 ] that cannot be supplied by intracellular or metabolic processes. Therefore, for the synthesis of glycoproteins mannose should be supplied with the diet. We have calculated that only for the synthesis of carbohydrate portion of immunoglobulins should be in human organism approximately 80 mg/day mannose and fucose (see table 1).

Table 1 Requirement of human organism in mannose and fucose for synthesis of immunoglobulins

1 Principles of biochemistry/Abraham White et al.//McGraw-Hill, Inc. 1978

We have calculated that only for general requirements of human organism in the mannose and fucose for synthesis of immunoglobulins will makes 80,5 mg/day. For synthesis of other cells receptors and cell fragments in human organism the requirement makes approximately 300 - 1000 mg/days of the mannose and fucose.

At the correction of impairments of the carbohydrate metabolism in diabetes mellitus with the help of minor sugars we achieved normalization of acquired immunity in these patients. The patients with restored carbohydrate metabolism have not suffered from episodes of upper respiratory disease and influenza for the last few years, also symptoms of an allergy and psoriasis have disappeared.

We studied further pathway in comprehension of a problem of immune system functioning and roles in these the mannose and fucose.

In the beginning we shall be to form a new concepts in this area.

The human immune system is created for protection of an organism against stranger organisms and cells. Thus stranger for our organism can be both exterior microorganisms and viruses, and cell of a natural organism (cancer cells, cell with the broken reception system, abnormal cells, cell crushed by a mechanical expedient etc.), and also cells fragment with abnormal reception system (glycoproteins, glycolipids, lipoproteins etc.).

All these stranger bodies constructed by a genetic pathway we term by antigens. At entering these antigen's in our organism against them have our protective system that generate antibodies. How determines our organism what these antigen's stranger for it? For this purpose in an organism of the man there is an original system "self" - "nonself" [ 21 ]. This system is widely applied in military area to difference of self-aeroplanes from nonself, self ships from nonself. But in an organism of the man this system works much more effectively and is submitted by all-level duplication.

The system "self" - "nonself" in human organism works on the following a principle. At the approach of an immune cell to stranger there is an interaction of high mannose receptor with a receptor of an unknown cell. If the receptors are identical, the immune system determines the unknown cell as self. If the receptor of an unknown cell differs though on one molecule, all destruction system will include. This all-level system in human organism is submitted by complement system, macrophages, acquired immunity.

What basic structures have the cells receptors and immune system?

On a surface of cells there are receptor glycoproteins having the following high mannose carbohydrate structure - Man (9) ClcNAc (2) Fuc (1) [22, 23 ]. The same structure have also enzymes [ 24 ] vesicular-integral membrane protein [ 25 ] and other glycoproteins and glycolipids of receptors.

If on a cell surface there will be no similar receptor it will be destroyed. So our organism is protected to survive in medium of other organisms. Under action of biochemical processes in human organism can change these carbohydrate structures.

At infringement of carbohydrate nutrition and infringement of operation of a gastrointestinal tract [ 26 ] there is a downstroke of mannose level in human blood [ 27 ] and begin to be synthesized carbohydrate fragments with smaller quantity of molecules of a mannose:

eight - Man (8) ClcNAc (2) Fuc (1) [ 28 ];

seven - Man (7) ClcNAc (2) Fuc (1) [ 24 ];

five - Man (5) ClcNAc (2) Fuc (1) [ 29 ];

three - Man (3) ClcNAc (2) Fuc (1) [ 30 ].

This downstroke of quantity of mannose molecules in glycoproteins and glycolipids promotes infringement of reception system to its simplification (see fig. 1-4).

Figure 1. Healthy cell having normal high mannose system of the reception . This system consists of one molecule fucose, two molecules N-acetylglucosamine and 9 molecules of the mannose {Man(9)GlcNAc(2)Fuc(1)}. The cell receptor has big dimension for the best comprehension of incipient infringements.

Figure 2. Cell having infringement in system reception because of lack of blood mannose. One molecule of the mannose is not synthesized in carbohydrate structure of the high mannose receptor {Man(8)GlcNAc(2)Fuc(1)}.

Figure 3. Cell having infringement in system reception because of long-time lack of blood mannose. Two molecules of the mannose are not synthesized in carbohydrate structure of the high mannose receptor {Man (7) GlcNAc (2) Fuc (1)}.

Figure 4. Cell having infringement in system reception because of long-lived lack of blood mannose. Four molecules of the mannose are not synthesized in carbohydrate structure of the high mannose receptor {Man(5)GlcNAc(2)Fuc(1)}.

How are promptly shaped these infringements in our organism?

The downstroke of quantity of mannose molecules in structure receptor glycoproteins and glycolipids results in change of cells reception system not at once. As term of life of different cells in our organism is various, first of all is broken reception system in immunoglobulins, leucocytes, erythrocytes, liver cells term of which life make from 2 to 120 days. Therefore downstroke of mannose level in the blood promotes infringement of carbohydrate structure reception in antibodies.

Protective functions of human organism from infiltration of stranger microorganisms and from formation of abnormal cells in this case are reduced by broken this reception. The further downstroke of mannose level in human blood promotes formation of infringement of carbohydrate structure reception and in other cells (beta cells, muscle, connective tissue and others). Downstroke of mannose level in human blood for a long time (10 - 50 years) result by formation AIDS, cancer. In patients organism with AIDS the reception system of cells because of high protein diet and long-lived reception of antibiotics advisable by the doctors is so broken, that the reception system practically does not work because of absence of the mannose [ 31 ].

In what consequences results downstroke of the mannose in receptor glycoproteins and glycolipids?

The downstroke of quantity of mannose molecules in fragment of receptor glycoproteins and glycolipids results in impairment of many biochemical processes. Now these infringements are found out practically at all diseases. The obesity is connected with impairment reception of an insulin muscle and hepatic cells. Diabetes mellitus is connected with impairment of carbohydrate structure of vesicles for a deduction of the insulin from beta cells at insulin-dependent diabetes and impairment reception of the insulin in liver cells at insulin-independent diabetes [ 32, 33 ]. It results also by dystrophic retinal pigment epithelium [ 34 ], recurrent infections in adults [ 35 ] and other diseases and dysfunction. The downstroke of quantity of mannose molecules in structure of receptors results in development meningococcal disease [ 36 ]; tuberculous meningitis [ 37 ] and others illnesses.

Whether it is possible promptly to increase concentration of the mannose in human blood and thus promptly to cure the patient?

It is impossible. At augmentation of the mannose in blood first of all begin to be synthesized receptor glycoproteins and glycolipids of antibodies with the boosted content of the mannose in their carbohydrate structure. They begin to destroy all cells, which have receptor glycoproteins and glycolipids with smaller quantity of the mannose. In this case in human organism begin the autoimmune processes. The immune cells of human body begin to destroy cells of organism with broken mannose reception, determining them as "nonself".

If it is a little such cell, temperature of body does not raise. The more cells determined as "nonself", the more intensively auto immune processes of destruction of self-cells. Also proceed process to kill of various microorganisms and viruses that colonized into the human organism because of weakening the immune control. In this case temperature of human body can strongly raise down to critical. Therefore to cure the patients with AIDS it is promptly impossible. They at once can be lost from autoimmune diseases. For these patients it is necessary to raise the mannose level in blood slowly, on stages, without overloads within several years.

Thus, for synthesis of normal receptors in human organism it is necessary to support the level of receptor saccharum (mannose, fucose, arabinose and other) in the blood or with the help of nutrition, or with the help of the alimentary additives and to not suppose downstroke of the mannose in the blood for a long time. Besides basic of the mannose reception system "self" - "nonself" in human organism there are other adding systems based on fucose, arabinose. Thus is necessary to modern medicine to not block operation of immune system with the help of antibiotics at an inappreciable fervescence at absence of signs of infection by microorganisms, but to help human organism activate serviceability of this system.

As the half-life of immunoglobulin A is only 6 day, so will very well for investigation activity highmannose receptor by introduction of mannose (fucose) in diet of the patients at examples of the carbohydrate structure of immunoglobulin A.

Therefore support of basic biochemical researches on regulation of highmannose receptor activity "Self"-"Nonself" by introduction of mannose in patients is necessary for us. It will allow not only to find out the reason of many diseases connected to the functioning of the immune system, but also to develop various diets and foods for the immunorehabilitation.