8, 9.

The role of resistance, nonspecific and specific (immune) reactivity in pathology

8. The role of reactivity in pathology

8.1. What is reactivity?

Reactivity is a property of organism and its structures to reply by changes of life activity to the influence of the
environmental factors.
Reactivity provides the interaction of organism with an environment. It influence essentially on the developing
and current of diseases.

8.2. Give the examples of display of reactivity on different levels of live objects organization.
On the molecular lever – the movement of the line of dissociation of oxyhemoglobin to the right in conditions of
acidosis, caused by hypoxia Bore’s effect.
On the cellular level – the realization of phagocytosis by leukocytes in reply to the inculcation of
microorganisms into the tissues.
On the tissue level – the development of complicated complex of reactions, named “inflammation” in reply to
damaging factors (l. part. 14)
On the organs’ level – the augmentation of frequency of heart beat rate during the elevation of blood
temperature.
On the level of physiological systems – the reactions of the external breath systems, blood circulation during the
oxygen starvation (hypoxia) (l. part. 19)
On the level of organism in general –complicated oriental reactions in reply to the influence of the sound and
light signals.

8.3. What kinds of reactivity can be (picked out)?

The reactivity can be:
a) specific, group and individual.
The specific reactivity is inherent in the all individuals of concrete kind, group - is inherent in constant group of
individuals, individual – is inherent in constant individual;
b) nonspecific and specific.
Not specific (primitive, simple) reactivity appears at the acting of different factors on organism. In it’s ground –
genetically programmed standard variants of an answer (for example, defensive-compensative reactions during the
acting of high and low temperature, during the oxygen deficiency; phagocytosis, etc.)
Specific reactivity is an immunologic reactivity (l.part.9);
c) physiological and pathologic.
Physiological reactivity contains the reactions of healthy organism. Pathologic reactivity is a qualitatively
changed reactivity during the acting of pathogenic factors on the organism. The example of it is the allergy (l.part.10);
d) heightened (hyperergia), lowered (hypoergia) and perverse (dysergia).
A great importance in the development of learning about different species of reactivity belongs to the works of
N.N. Syrotinin and his pupils.

8.4. What factors make influence on the reactivity of man?

1. Age. For the early child age a low reactivity is typical. It increases gradually, becomes maximal in adults, and
in old age begins to fall.
2. Sex.
3. Heredity.
4. Constitution.
5. Functional condition of nervous, thyroid, immune systems and connective tissue.
6. Factors of environment (climate, character of nutrition, social conditions).

8.5. What is resistance?

Resistance is a stability of organism to the acting of pathogenic factors.

8.6. What are the lands of resistance?

Resistance can be passive and active, not specific and specific .An immunologic reactivity is in the ground of
specific resistance. (l. part.9)

8.7. What is passive and active resistance? What is the difference between them?
A passive resistance is an insensibility to the action of pathogenic factor, insusceptibility to it. It appears when
the interaction between the organism and pathogenic factor is impossible or difficult. Passive resistance is
energetically dependent and can be stimulated by the following mechanisms:

Page 1 from 10 1
Reactivity
 1) existence of barriers for interaction between the pathogenic factor and the structure of organism (biological
barriers);
2) absence or destruction of the organism’s structures, which can interact with the pathogenic factor, for
example, an absence of the receptors to the pathogenic viruses;
3) the destruction of the pathogenic factor by the mechanisms, which are not connected with the reaction of
organism to the acting of this factor (for example, the destruction of choleric vibrious by gastric juice);
4) the moderation of realization of pathogenic mechanisms, which are started up by the interaction of the
organism with the pathogenic factor (for example, the increasing of passive resistance during hypothermia)
An active resistance (resistibility) is a stability, which is provided with a complex of defensive-compensation
reactions, directed on the destruction of pathogenic factor and the results of its acting. The active resistance is
energetically dependent; the mechanisms of reactivity form its ground (for example, phagocytosis, synthesis of
antibodies, the reactions of cellular immunity).

8.8. How is the reactivity and resistance connected?

There is a complicated connection between the reactivity and resistance. There can be different variants of it:
1. The increasing of active resistance is caused by the increasing of reactivity. For example, during the increase
of temperature of body, the appearing of antibodies increases also, it raises the active resistance to the infections.
2. The increase of reactivity causes the diminution of active resistance. So, the precipitation of appearing of
antibodies can be a reason for allergy, during which the stability of organism diminishes to the aching of substances of
antigen nature.
3. The diminution of reactivity causes the diminution of active resistance. For example, the diminution of
antibodies’ appearing diminishes the active resistance to infections.
4. The diminution of reactivity causes the precipitation of passive resistance. So, during hypothermia the passive
resistance to infections, intoxication and acting of other pathogenic factors increases (for example, animals during the
time of hibernation).

8.9. Name the mechanisms of nonspecific resistance, which provide the stability of organism to the acting
of infections agents.
1. Areactivity of cells.
2. Physical and physicochemical factors.
3. Biological barriers.
4. Antagonistic interrelation between the normal and pathogenic microflora.
5. The functioning of physiological system of connective tissue.
6. Humoral factors of nonspecific resistance.
7. Phagocytosis.
8. Inflammation.
The works of one of A.A. Bogomoletz pupils – E.A. Tatarinov were dedicated for studying nonspecific
mechanisms of antinfection immunity.

8.10. What is areactivity of cells, characterizing the mechanisms of not specific resistance to infections?
The areactivity of cells is their inability to interact with infections agent. It can be caused by: a) absence of
receptors’ cells to the viruses on the surface; b) absence in cells the receptors to the bacterial toxin; c) connection of
toxin with the receptors of cells, which are not sensitive to its acting.

8.11. What physical and physicochemical factors are the factors of nonspecific resistance of organism to
infections?
1. The temperature. Birds have the level of temperature which provides their insensitivity to the bacteriums of
Siberian ulcer. During the increasing of body’s temperature, the reproduction of many viruses decreases and they die.
2. The importance of pH habitat. In acid habitat of stomach many maters of infections diseases die, mainly, the
choleric vibrious. In the focus of inflammation a high concentration of ions of hydrogen appears, that causes the
damage of microorganisms, staying here.
3. Pressure of oxygen in tissues. In usual conditions pO2 in tissues prevent the development of anaerobic
infections.

8.12. How are the biological barriers of organism classified?

The biological barriers are divided into external and internal. The external barriers are skin and mucous
membranes. Among internal there are organs-barriers (liver) and histohematic barriers.
The histohematic barriers divide the blood and tissues. They are subdivided on not specialized and specialized
barriers. Not specialized is a capillary wall and consist of endothelium and basilar membrane. The structure of
specialized barriers includes complementary structures, which essentially influence on their permeability. The
specialized barriers are hematoencephalitic, hematoophthalmic, hematotesticular, hematothyroid and hematocochlear.
Page 2 from 10 2
Reactivity
 A great contribution to the studying of biological barriers belongs to L.S. Shtern and his pupils.
8.13. What are the functions of the physiological system of connective tissue?
For the first time A.A. Bogomolets pointed to important role of connective tissue in ensuring of resistance of
organism. He introduced the term “physiological system of connective tissue”.
This system has next functions: 1) defensive (creation of biological barriers, phagocytosis, reactions of humoral
and cellular immunity); 2) trophic (providing nourishing to the parenchyma’s elements); 3) supportive, plastic.

8.14. What is Bogomolets’ serum? What is the mechanism of its acting?

Bogomolets’ serum is the antireticular cytotoxic serum (ACS), gotten and suggested to the medical practice by
A.A. Bogomolets. This serum contains of the antibodies against the components of connective tissue. The injection of
its little quantity accelerates the healing of wounds and ulcers, the remission of flaccidly inflammatory process takes
place.
The mechanisms of acting of ACS are connected with the development of cytotoxic immune reactions (l. part.
10)

8.15. Give the examples of humoral factors of nonspecific resistance of organism to the acting of infection
agents.
Such factors are lysocime, C-reactive protein, leukins and β-lysine, inhibitors of bacterium’s enzyme, inhibitors
of viruses, interferon, and the system of the complement.

8.16. What is interferon?

Interferon is a protein, which appears in cells, which are infectioned by the viruses and preserves other cells
from affection of them by viruses.
Under the acting of interferon in noninfected cells stimulates the appearing of proteins-inhibitors, which inhibit
the synthesis of virus nucleic acids and break in such way the reproduction of viruses.
Interferon defends the cells not only from the kind of virus, which infects the organism, but also from other kind
of viruses.

8.17 What is the system of complement? How is it activated?

Complement is a system of serum proteins of blood, a successive activity of which causes the damage
(perforates) of cellular membrane and, as a result, destruction (lysis) of bacteriums. The system of complement
consists of 11 proteins, which form 9 fractions, denoted C1, C2,...C9. Complement’s proteins are regulated by the
same number of inhibitors and inactivators.
There are few mechanisms of complement’s activation:
1. A classical way (antibody dependent). The activation of complement is connected with appearing of
complexes of antigen-antibody on the surface of bacterium cell.
2. An alternative way (properdinal). Polysaccharides and liposaccharides of bacterium wall cause the activation
of complement. This mechanism needs the participation of serum proteins, named properdin.
3. Nonspecific activation. Can be realized by active proteases (trypsin, plasmin, callicrein, lysosomal enzymes,
etc.) during any period of the activation process.

8.18. Name the functions of complement and products of its activation.

The main function of active complement is lysis of bacterium cells, stipulated by the perforation of their
membranes.
Intermediate products of activation, in particular C3b, are the opsonins and provide the immune clinging; and a
product C4a causes the neutralization of viruses.
Accessory products of activation of complement (C3a and C5a) take part in pathogenesis of allergy, causing the
degranulation of tissue basophils, stimulate chemotaxis of leukocytes.

8.19. What primary breaches can appear in the complement’s system?

There are two groups of such breaches.
1. Deficit of the complement’s components. Deficit of C1, C2, C3 and other components of this system can be
inherently stipulated. Acquired breaches, as a rule, are connected with general disorders of biosynthesis of proteins
and increased inactivation of the complement’s components.
2. Deficit of inhibitors and inactivators of the complement’s components. The example is the deficit of inhibitor
C1, that causes the plenty of complement’s activation and, as a result, an advance of angioneurotic edema - Quenkis
edema.

8.20. What is phagocytosis? What cells possess the property of phagocytes?

Phagocytosis is an active absorption of hard material by cells.
Cells, which have the property to accomplish phagocytosis, got the name of phagocytes.
Page 3 from 10 3
Reactivity
 The polymorphonuclear (neutrophiles) and mononuclear phagocytes are distinguished. To mononuclear
obligetic phagocytes we refer, the phagocytes which make the system of mononuclear phagocytes. This system
consists of monocytes and cells, which are their derivatives: macrophages of connective tissue, Kypfer’s cells in liver,
alveolar macrophages of lungs, macrophages of red bone marrow, free and fixed macrophages of spleen, macrophages
of serous cavities, osteoclasts, microglial cells of central nervous system.

8.21. What functions do the phagocytes have?

1. Migration is the ability to disorderly moving in wideness.
2. Chemotaxis is the ability to direct moving in wideness.
3. Adhesiveness is the ability of phagocytes to stick substrates and detain on them.
4. Endocytos is the ability to catch and absorb hard particles and drops of liquid.
5. Bactericidal action is the ability to destroy and digest the bacteriums.
6. Secretion is the ability to secrete the substances into surrounding tissue.

8.22. Name the stages of phagocytosis.

1. The stadium of approchement. 2. The stadium of adhesion. 3. The stadium of absorption. 4. The stadium of
digestion.

8.23. What is the cause of phagocytes’ chemotaxis?

Chemotaxis of phagocytes appears with an acting of substances, named chemotaxins. Exogenous and
endogenous chemotaxins are distinguished.
Exogenous, in particular, are bacterium liposaccharides (endotoxins), products of damage of bacteriums walls
(myramildipeptid).
Endogenous are chemotaxins, which appear in organism. Among them the main importance have accessory
products of complement’s activation (C3a, C5a), leucotriens, lymphokins and monokins, factor of emigration of
neutrophiles.

8.24. What mechanism provides the adhesion of phagocyte to the object of phagocytosis?
Nonreceptoral and receptoral mechanisms are distinguished.
Nonreceptoral mechanisms are electrostatic and hydrophobic interaction of the phagocyte’s surface with an
object of phagocytosis. As a superficial electrical charge of phagocytes is negative, so the particles with a positive
electrical charge stick well. Also particles with hydrophobic surfaces stick well.
Receptoral mechanism caused by the existence of special receptors on the surface of phagocytes to substances-
opsonins. An interaction of phagocyte with an object of phagocytosis takes place with the help of opsonins, which are
connected with receptors.

8.25. What are opsonins? What opsonins have the main importance for phagocytosis?

Opsonins are the substances, which help the sticking of bacterial and corpuscular antigens to phagocytes and
stimulate phagocytosis in such way. Adsorption of opsonins on the surface of bacterium cells and corpuscular antigens
is opsonization.
Antibodies – IgG and intermediate products of complement’s activation, in particular C3b have the main
importance for phagocytosis among opsonins. Their opsonizative effect is connected with the presence on the surface
of mononuclear phagocytes special receptors to Fc-part of IgG and receptors to C3b.
Besides, C-reactive protein, fibronectin, taftsin also play the role of opsonins.

8.26. What processes make the essence of third stadium of phagocytosis - the stadium of absorption?
1. Invagination of plasmatic phagocytes membrane in the place of its contact with an object of phagocytosis.
2. Appearing of phagosoma surrounding by membrane, which has the object of phagocytosis.
3. Fusion of phagosoma with lysosoma, as a result of this phagolisosoma appears.

8.27. What happen during the 4-th stadium of phagocytosis - the stadium of digestion?
1. The damage (killing) of bacteriums – is intracellular cytolysis. It is accomplished with the help of bactericidal
phagocyte’s systems.
2. Strictly digestion – is the hydrolysis of components of the bacteriums killed with the help of hydrolytic
enzymes of lisosoms. The products, which appear during this process can be used by phagocytes for own necessaries.

8.28. What means of bacteriums’ destroying do the phagocytes have?

Bactericidal systems and substances of phagocytes are: 1) myeloperoxidasa system; 2) lysocim; 3) lactoferin; 4)
nonenzyme proteins; 5) lactic acid.

Page 4 from 10 4
Reactivity
 8.29. How does the myeloperoxidasa system of phagocytes functioning?
The activation of myeloperoxidasa system in phagocytes’ lisosoms produces two groups of factors:
1) hypochlorit-ion (ClO-), which causes galogenisation (chlorination) of microbe walls’ components, and as a
result of this bacteriums die.
2) free radicals and peroxides (·O2-, HO·2, OH·, H2O2), which activate lipid peroxide oxidation and, as a result,
break the barrier properties of the microbe membranes.

8.30. How are the breaches of phagocytosis classified?

1. Breaches, which are connected with peculiarities of phagocytosis’ object.
2. Breaches, caused by juncted with phagocytosis system, - breaches of opsonization.
3. Breaches, connected with qualitative and quantitative changes of phagocytes.

8.31. Give the examples of phagocytosis’ breaches, connected with peculiarities of phagocytosis’ object.
Incitants of some infections diseases - mycobacteriums of tuberculosis, toxoplasmosis, brucellosis, listerias,
incitant of lepra, many kinds of simplest, being in phagosoma, secrete substances, which perplex or make impossible
the confluence of phagosoma and lysosoma - the formation of phagolysosoma. Macrophages during this are in state of
constant activation, they secrete contents of lisosoms into surrounding tissue and in such way support the chronical
inflammation.
Phagocytes, absorbing crystals and dust particles of inorganic compounds (guarts, osbestos, cement, caolin, coal
and other.) can neither digest no utilize them. During this the damage of lisosoms takes place, crystals and dust
particles release from dead macrophages info the tissue again, where they are absorbed by new macrophages. And in
such way everything is repeated again. Constant death of macrophages and their secretion info tissue of contents of
lisosoms cause chronic inflammation and sclerosis. According such “script” the development of lungs’ diseases, well-
known under the name of pneumoconioses (silicosis, anthracosis, asbestasis and other) takes place.

8.32. What reasons can break the processes of opsonization and cause the breaches of phagocytosis?
1. Immunodeficite, which are showed by the breaches of appearing of immunoglobulin G (IgG).
2. The breaches of activation of complement system, causing to the deficit of C3b.
3. The breaches of properdin system.
4. The deficit of fibronectin.
5. The removal of spleen, causing to the deficit of taftsin.

8.33. What quantitative changes of phagocytes can be a reason for the phagocytosis’ breaches?
1. The breaches of receptors to chemotaxins and opsonins (inheritly caused changes, blockade of receptors by
immune complexes).
2. The breaches of specific membrane glycoprotein (GP 110), which supports adhesiveness of phagocytes’
membrane.
3. The breaches of microfilaments - the syndrome of “lazy leukocytes”. As a result of incapacity of actin to the
polymerization, the migration and the process of absorption by leukocytes the phagocytosis’ object endocytosis break.
4. The breaches of microtubules - Chediak-Higashi syndrome. It is characterized by the appearing of huge
lisosoms. It is appeared by the breaches of chemotaxis, appearing of phagolisosoms and secretoral degranulation
(exocytosis).
5. The breaches of bactericidal systems of leukocytes. The next inheritly caused confusions are described:
a) The deficit of NADPH-oxydase (develops the disease under the name of chronic granulematosis);
b) The deficit of glucose-6-phosphatdehydrogenase, as a result, the pentose cycle and the generation of free
radicals violate; c) the deficit of myeloperoxidasa (it displays by the breaches of halogenisation of membranes of
microbe cells).
6. The breaches of lysosomal enzymes. The uncompleted phagocytes is the result of it.
7. The disorders of the phagocytes’ energy-providing. During this, break the processes, such as: the emigration,
chemotaxis, endo- and exocytosis) which need the expense of energy.

9. The violations of immunological reactivity (immunity disorders)

9.1. What is immunological reactivity?

Immunological reactivity is an ability of organism to react on action of the antigens by production of antibodies
and by using complex of cellular reactions specific to the corresponding antigen.

9.2. What mechanisms provide immunological reactivity?

There are two mechanisms of immunological reactivity: humoral and cellular.
The humoral type of response is directed foremost to the extracellular bacteriums and viruses. Antibodies
Page 5 from 10 5
Reactivity
(immunoglobulin) - products of the B-lymphocytes activity are the effectoral link of this type of answer.
The cellular type of immune response is directed on defense from intercellular infection and mycosis,
intercellular vermin and tumor cells. Its effectoral link is the immune T-lymphocytes, bearing specific receptors to the
given antigen.

9.3. What are the antigens?

Antigens are the matters capable being in the organism to cause an immune answer and cooperate with the
products of this response - antibodies or activated T- lymphocytes. Antigens, as a rule, are the high molecular
compounds.
Substances with a low molecule weight, which do not possess the ability to initiate the immune response, but are
able to specifically bind with antibodies, is incomplete antigens (gaptens).

9.4. What are antibodies?

Antibodies are albumens (immunoglobulin) which are synthesized under influencing of antigens and
specifically cooperate with them.
Basic properties of antibodies are:
1) specific ability to contact with a certain antigen only;
2) variability, determined by the amount of the antideterminant in the molecule of globulin;
3) affinity, reflecting durability of communications by the determinants of antigen and antideterminants of
antibodies;
4) avidity, characterizing durability of connections between an antigen and antibody on the whole. The last
relies on valiancy and immunoglobulin affinity.

9.5. What cells take part in realization of the immune answer?

The cells that realize the immune answers are B-lymphocytes, T-lymphocytes and macrophages.

9.6. Name the B-lymphocyte’s functions.

The basic function of the B-lymphocytes is the formation of antibodies.
Under action of antigen stimulus B-lymphocyte of certain clone undergoes some changes and grow into
plasmatic cells. The last ones produce immunoglobulin of five classes: ІgM, ІgS, ІgE, ІgA, ІgV.

9.7. Name the T-lymphocyte functions.

Basic functions of the T-lymphocytes are:
1. Cytotoxicity (killing function) – is the ability to destroy (to kill) cells which bear antigens on the surface.
2. A cooperative (helper) function is the ability to provide co-operation of different subpopulations of T-
lymphocytes, B-lymphocytes and macrophages.
3. Formation of biologically active substances - lymphokines.
4. The suppressor function is the oppression of surplus immune answer, the T-lymphocyte participation in
forming of immunological tolerance.
The indicated functions are executed by specialized subpopulation T-lymphocyte: T-killers, T-helpers, T-
producents of lymphokines, T-suppressors.

9.8. What part in the realization of immune answer is taken by the macrophages?
1. Macrophages are taken in, processed and give an antigen to the immunocompetent cells (T- and B-
lymphocyte).
2. Macrophages take part in the T- and B-lymphocyte cooperation.

9.9. What are the thymus-independent antigens? What are the mechanisms of humoral immune answer
on antigens when they come in organism?
Thymus-independent antigens are the antigens, the formation of antibodies against which does not require the
T-lymphocyte participation. In general antigen-polymers have the plenty of identical repetitive determinants.
The immune answer of the organism for the receiving of thymus-independent antigens is characterized by such
sequence of processes.
1. Cooperation of antigen with the B-lymphocytes, that has on the surface the receptors specific to the antigen.
2. Blasttransformation of the B-lymphocyte is the result of such cooperation, i.e. transformation in lymphoblast.
3. Fission and proliferation of lymphoblast with the formation of a B-lymphocyte‘s clone.
4. B-lymphocyte differentiation into plasmatic cells.
5. Synthesis by the plasmatic cells of antibodies - IgM.

9.10. What are the thymus-dependent antigens? What are the mechanisms of humoral immune answer on
Page 6 from 10 6
Reactivity
such antigens when they come in organism?
This kind of antigen has such name, because formation of antibodies against thymus-dependent antigens
requires complex cooperation of macrophages, T- and B-lymphocytes.
The immune answer for these antigens is characterized by the following stages.
1. Macrophage stage. There is absorption and digestion by macrophages of antigenic cells and particles from
subsequent presentation of antigens determinant on the plasmatic membrane of macrophage.
2. Cooperation of macrophage with T-lymphocyte. As the result of such operation clone of specific T-helpers
appears.
3. The T-helpers and macrophage cooperation with B-lymphocyte. Because of the cooperation of these cells the
antigen determinants are passed to the B-lymphocytes.
4. Blasttransformation of the B-lymphocyte with the formation of plasmatic cells’ clones, that produce the
antibodies of all classes against one antigen.

9.11. Describe the mechanisms of the immune answer:

The eventual stage of the immune answer of the cellular type is the realization of the lymphocytes (T-effectors).
It is possible to divide the next stages of the immune answer of cellular type:
1. The macrophage stage.
2. Cooperation of macrophages with T-lymphocytes. Appearance of activated T-effectors is the result of such
cooperation.
3. Formation of T-effectors’ clones as a result of proliferation of activated T-killers and T-producents of
lymphokines. The appearance of the T-killers specifically cooperates with an antigen cells and destroys it. Formed by
T-producents lymphokins are engaged in the fight against foreign objects by other cells: macrophages, granulocytes,
0- and B-lymphocytes.

9.12. What is immunological insufficiency?

Immunological insufficiency is the defect of the immune system innate or acquired, which is the fully inability
of organism to carry out the humoral or cellular immune reactions.
Immunological insufficiency can be primary and secondary.

9.13. What is primary immunological insufficiency? What reasons can cause it?
Primary immunological is insufficiency which arises up because of innate defects of the immune system.
The reasons of origin of primary immunodeficiency can be:
а) gene mutations. Appeared imperfect genes pass coupled with a sex (1/3 known for today primary
immunodeficiency) or by autosome-recessive way;
b) chromosomal mutations. Most often the development of immunodeficiency connected with the anomalies in
14-th, 18-th, 20-th pair of chromosomes and the Dawn syndrome. Immunological insufficiency combines with other
difficult syndromes arising up because of chromosomal aberration here;
c) infections. Often the virus of German measles and cytomegalovirus led to the appearing of immunological
insufficiency that bring over arises, causing the difficult vices of a baby development.

9.14. How is the primary immunological insufficiency classified?

Depending on the level of the violation and localization of defect the following types of primary immunedeficite
are described: 1) humoral, or B-cellular; 2) cellular, or T- cellular; 3) combined.

9.15. What are the examples of the primary B-cellular immunodeficiency?

Primary B-immunodeficiency arises as a result of violation of processes of formation and B-lymphocytes
differentiation. To this group belongs:
а) Bruton’s agammaglobulinemia. The inherited defect is passed coupled with the X-chromosome, therefore
shows up practically only in boys. The differentiation of the B-lymphocytes cells-predecessors is violated. That’s why
the B-lymphocytes, plasmatic cells and immunoglobulines are absent in the organism. T-system lymphocyte is not
broken;
b) general variable immunodeficite. It includes a lot of forms. The gipogammaglobulinemia is the common
form, appears lately at the age of 25 - 30. Various genetic defects violate the B-lymphocyte differentiation at different
levels of ripening;
c) selective deficit of the immunoglobulin. Formation of one or a few classes of immunoglobulin is violated.
Formation of other classes of antibodies can not be broken or even increased.

9.16. Name examples of primary T-cellar immunodeficiency.

Primary T-immunedeficite appears as a result of violation of processes of formation and T-lymphocyte
differentiation. To them, in particular, belong:
Page 7 from 10 7
Reactivity
 а) the Di-George syndrome - innate aplasia of thymus gland is the result of vices of embryonic development
and often considers with a "wolfish fall", anomalies of arch of aorta, aphasia of parathyroid glands.
б) the Nezelof syndrome. A genetic defect that passes by the autosome-recessive type. Transformation of
lymphocytes in T-lymphocytes is violated, because of what can not be carried out - cellular mechanisms of the
immune answer.

9.17. Name examples of the combined primary immunedeficite.

Combined immunodeficite appears as a result of violation of transformation of trunk cell into the cell-
predecessor or as a result of combination of defects of B- and T-line of lymphocytes.
To this group belong:
а) heavy combined immunedeficite (Swiss type). A genetic defect is passed autosome-recessive or it is coupled
with X-chromosomes. The B- and T-lymphocytes formation, synthesis of immunoglobulines, is violated. Sick children
rarely reach the age of 2;
b) Luis-Bar syndrome. It is characterized by combination of immunological insufficiency (by violations of
coordination of moving) and teleangiektazias (the defects of little vessels). Life-span of the patients rarely reaches 20-
30 years;
в) Wiskott-Aldrich syndrome. Immunological insufficiency is accompanied by the development of exema
(defect of skin) and thrombocytopenia. As well as in previous case, humoral and cellular mechanisms of the immune
answer suffer. Life-span of patients does not exceed 10 years.

9.18. What are the secondary immunodeficites? What reasons cause them?
Secondary immunological insufficiency is the acquired immunological insufficiency (immunodepressive states).
The reasons of its development can be the exogenous factors of physical (ionizing the radiation), chemical (matters
possessing action, - immunodepressants) and biological (viruses) origin.
The senescence and intoxications (under uremia, burn disease, malignant tumors) are the endogenous factors
that lead to development of secondary immunedeficite.

9.19. What is the acquired immune deficiency syndrome (AIDS)? What is its reason?
AIDS is the infectious disease appears as a result of defeat by the virus of immune and other systems, as a result
an organism becomes highly-receptive for secondary infections and malignant tumors.
The reason of AIDS is the retrovirus – human immunedeficite virus (HIV).

9.20. What is the pathogenesis of immunological insufficiency in patients with AIDS?

The human immunedeficite virus (HIV strikes cells which on the surface of plasmatic membrane have the
special albumen SD4+. This albumen plays the role of receptor. The most vulnerable in relation to HIV are SD4-T-
lymphocytes. By the functional classification they belong to T-helpers.
Immunological insufficiency under AIDS is characterized by the T-helpers insufficiency foremost. The
following mechanisms lie in the basis of its development:
1) destruction by the T-helpers by viral particles abandoning cells after reproduction;
2) formation of multilayer lifeless sincition, consisting of T-helpers stroked by the virus;
3) elimination of infected T-helpers by cytotoxic T-lymphocytes (T-killers);
4) the T-killer-mediated elimination of uninfected T-helpers, with viral proteins absorbed to their surface.
The cause of the T-helpers insufficiency is: a) reduction of formation of the B- lymphocyte antibodies in reply
to action of antigens; b) violation of the T-killers activation; c) violation of regulation of the immune answer as a
result of reduction of lymphokins forming, in particular interleikin-2.

9.21. What mechanisms are the basis of development of acquired immune violation of humoral type?
I. The B-lymphocytes violations (cellular level).
1. Reduction of the B-lymphocytes maintenance: a) violations of limphopoesis; b) the destruction of B-
lymphocytes (action of viruses, autoimmune reactions).
2. Quality changes of B-lymphocytes: a) transformation into the tumor cells (leucosis, immune-proliferative
diseases), b) the violation of the B-lymphocytes transformation into plasmatic cells.
3. Violations of cooperative communications: а) repression of function of macrophages; b) reduction of the T-
helper influences; c) increasing of T-influences.
II. Violations of immunoglobulines (molecular level)
1. Violations of biosynthesis of immunoglobulines: a) slowing down of transcription processes b) oppression of
translation processes; c) deficiency of aminoacids; d) deficiency of energy; e) violations of posttranslation
modification.
2. Activation of processes of disintegration of antibodies – hypercatabolism of immunoglobulines: a) formation

Page 8 from 10 8
Reactivity
of aggregates of immunoglobulines; b) production of antibodies against immunoglobulines.
3. Loss of immunoglobulines (for example – under nephritic syndrome).

9.22. What are the characteristic for immune violations of humoral immunity?
Violations of this type appear through the reduction of resistivity of organism to the primary bacterial infections,
caused staphilo- and streptococcus, and in a less degree – enterococcus and gramnegative bacteriums.

9.23. What mechanisms can be the basis of development of acquired immune violation of cellular type?
1. Reduction of the T-lymphocytes amount: 1) violations of lymphopoesis; b) the T-lymphocytes destruction
(AIDS, autoimmune reactions).
2. Quality changes of T-lymphocytes: a) violation of cytotoxicity; b) violation of formation of lymphokines.
3. Violations of cooperative communications: a) oppression of function of macrophages; b) violation of
formation of interleikin-2; c) increasing of the T-suppressor influences.

9.24. What displays are characteristic for immune violation of cellular type?
1. Reduction of stability to the infections and mycosis, viral and protozoon infections.
2. Increasing of frequency of malignant tumors forming.
3. Increase of time of transplants acclimating.
4. Autoimmune reactions (the result of the T-suppressor deficit).

9.25. What is immunological tolerance?

Immunological tolerance- is the state of specific immunological areactivity to the given antigen, caused by the
previous contact with this antigen. But the ability of the organism to give the immune answer for all other antigens is
saved.

9.26. What mechanisms can lie in the basis of immunological tolerance?

1. Elimination or blockade of clones of lymphocytes conditioned by an antigen (passive immunological
tolerance, "classic"). This mechanism makes the basis of natural immunological tolerance to its own antigens.
2. The antigen-specific T-suppressors activation (active tolerance).

9.27. What methods are possible to get the state of immunological tolerance?
Injection of the different substances can be used for this purpose:
а) antigen in the organism of fetus in a critical period of forming of natural immunological tolerance to the
own antigens;
b) large doses of soluble antigen (immune paralysis of Felton);
c) gaptene, binded to the nonimmune carrier;
d) antigen on a background of artificially created immunedeficite state;
e) antiidiotype antibodies, i.e. antibodies against specific determinant of immunoglobulines;
f) antigen-specific T-suppressors, taken from tolerant organism.

9.28. What is the reaction of "transplant against the recipient"? Under which conditions does it arise?
The reaction "transplant against the owner" (homological disease) - is the immune aggression of the
transplanted cells of donor, directed against the antigen structures of recipient.
Its appearing requires some condition, in particular:
1) states of immunological insufficiency at a recipient (immunological immaturity at a fetus or new-born,
primary and secondary immunodeficiency);
2) transplantation of the immunocompetent cells;
3) antigen distinctions between a donor and recipient.
If such conditions are created, immunocompetent cells (lymphocytes) of donor are not limited in the
development and begin to react on tissues of owner by the complex of cellular and humoral immune reactions.

9.29. How is it possible to carry out the nonspecific immunostimulation?

There are the following methods to increase the activity of the immune system (immunostimulation):
а) injection in organism of adjuvants (biological modificators of immune answer).
Adjuvants – they are the compounds which increase immunegenity of antigen regardless of its specificity;
b) using of pharmacological immune stimulators (levamisol, derivates of vitamin A, cimethidin and others);
c) using of factors of thymus gland: timopoetin, timulin, humoral thymical factor, timopeptin, timozin;
d) injection of lymphokines and other cytokines (interleikin-1, interleikin-2, interferon);
e) substitution transplantation of red bone marrow, injection of immunoglobulines.

Page 9 from 10 9
Reactivity
 9.30. What methods of immunosuppression exist?
Suppression of function of the immune system can be carried out by a number of methods:
1. Surgical methods: 1) removal of central and peripheral organs of lymphatic tissue: thymus, spleen, lymphatic
nodes; b) removing of circulates in blood and lymph of lymphocytes in way of forming of chronic drainage of pectoral
lymphatic channel;
2. Physical methods - action of x-rays or γ-radiation.
3. Chemical influences - using of immunodepressants.
4. Immunological methods - are infusion of immune wheys (antilymphocytes, antimonocytes, antiglobulines).

Page 10 from 10 10
Reactivity