Autoimmune diseases of animals

Occurrence mechanisms

Autoimmune pathology can be characterised as attack of immune system against organs and tissues of own organism in which result there are their structurally functional damages. The antigens involved in reaction which are usually present at the human or an animal and characteristic for them, are called as autoantigens, and antibodies, capable to react with them - autoantibodies.

Organism autoimmunization is closely bound to disturbance of immune tolerance, i.e. a condition of areactivity of immune system in relation to antigens of the organs and tissues.

Mechanism of autoimmune processes and illnesses is similar to the mechanism of an allergy of the immediate and slowed down types and is reduced to formation of autoantibodies, cell-bound immune complexes and sensibilized T-T-killers. Both mechanisms can be combined or one of them prevails.

Essence of autoimmune processes consists that under the influence of originators infectious and invasion illnesses, chemical materials, medicines, a combustion ionising irradiatings, fodder toxins the antigenic structure of organs and organism tissues variates. The arisen autoantigens suscitate synthesis in immune system of autoantibodies and formation of sensibilized T-T-killers, capable to carry out aggression against the variated and normal organs, causing damages of a liver, nephroses, hearts, a brain, joints and other organs.

Morphological changes at autoimmune diseases are characterised by inflammatory and dystrophic changes in damaged organs. In parenchyma cells the acinose dystrophia and a necrosis are taped. In veins the mucoid both fibrinoid swelling and a necrosis of their sides, a clottage becomes perceptible, round pots lymphocyte-macrophages and plasmocytic infiltrates are formed. In a copulative tissue of a stroma of organs the necrosis and a sclerosis are taped a dystrophia in the form of a mucoid and fibrinoid swelling. In a lien and lymph nodes the hyperplasia, intensive infiltration by lymphocytes, macrophages and plasmocytes is expressed.

Autoimmune reactions play the important role in a pathogenesis of many illnesses of animals and the human. Studying of autoimmune processes represents the big practical interest. Autoimmunity research has led to appreciable achievements in the field of diagnostics and therapy of some diseases of the human and animals.

There is a certain spectrum of implication of an autoimmune pathology.

For one lesions of organs are characteristic. As an example the autoimmune thyroiditis at which the specific lesions of a thyroid gland including mononuclear infiltration are observed, destruction of follicular cells and formation of the germinal centres accompanied by appearance of circulating antibodies to certain components of a thyroid gland can serve.

Generalised are characterised by autoimmune reaction with antigens, the general for various organs and tissues, in particular, with antigens of a cellular kernel. An example of such pathology is the system lupus erythematosus at which autoantibodies do not possess organ specificity. Pathological changes in these cases affect many organs and represent basically lesions of a copulative tissue with a fibrinoid necrosis. Formulated elements of blood are often amazed also.

At the same time, an antiself response on own antigens with participation of cellular and humoral parts of immunodefence are referred first of all on linkage, neutralisation and elimination from an organism of the old, blasted cells, products of a histic metabolism. In the conditions of a normal physiological condition degree of possibility of autoimmune processes is strictly supervised.

Appearance of antigens from such tissues as lens, the excitatory tissue, testicle, a thyroid gland, the antigens which have appeared under the influence of inadequate influences on an organism of environmental factors of an infectious or not infectious parentage, genetical caused defects of immunocytes can be signs of an autoimmune pathology when the autoimmune homeostasis is broken. The sensibilization to autoantigens educes. Autoantibodies co-operating with them can be is conditional parted on some bunches: the autoantibodies causing damage of cells that underlies autoimmune diseases; autoantibodies in itself not causing, but making heavier flow of already arisen disease (a myocardial infarction, a pancreatitis and others); the autoantibodies-witnesses which are not playing an essential role in a pathogenesis of disease, but which ascending of titer can have diagnostic value.

Diseases bound to a lesion of tissues autoantibodies, can be caused:

1. antigens
2. antibodies
3. pathology of organs of an immunogenesis

Autoimmune pathology caused by antigens

Feature of this pathology is that tissues of own organism, or without changes of the antigenic structure, or after its change under influence of environmental factors are accepted by the immunologic apparatus as foreign.

At the characteristic of tissues of the first bunch (the excitatory, lens, testicles, a thyroid gland) it is necessary to note two cardinal features:

1. they are pawned after the immune apparatus and consequently to them immunocompetent cells (unlike the tissues pawned before the immune apparatus and excreting factors, destroying immunocompetent cells to them) remain
2. features of blood supply of these organs are that, that products of their degradation do not get to blood and do not reach immunocompetent cells. At damage of hematoparenchymatous barriers (a trauma, operation) these primary antigens get to blood, suscitate development of antibodies which inpouring through damaged barriers react on an organ

For the second bunch of autoantigens that under the influence of an external factor (the infectious or not infectious nature) the tissue variates the antigenic structure is solving and actually becomes for an organism foreign.

Autoimmune pathology caused by antibodies

Has some variants:

1. The foreign antigen getting to an organism has the determinants similar to antigens of own tissues of an organism in this connection the antibodies formed on another's antigen "are mistaken" and start to damage own tissues. The foreign antigen can be absent further.
2. The foreign hapten which is bridged to protein of an organism gets to an organism and on this complex antibodies are developed, capable to react with its each separate component, including with the protein, even for lack of a hapten.
3. Reaction is similar to a 2-type, only the foreign protein reacting with a hapten of an organism and, antibodies developed on a complex gets to an organism, continue to react with a hapten even after deducing from an organism of another's protein.

Autoimmune pathology caused by organs of an immunogenesis

The immune apparatus does not contain immunocompetent cells to the tissues of own organism pawned in an embryogenesis before immune system. However such cells can appear in the course of life of an organism as a result of mutations. In norm they either are destroyed, or depressed suppressor by mechanisms.

On an etiopathogenesis an autoimmune pathology part on primary and secondary. Autoimmune diseases are primary.

To autoimmune diseases carry diabetes, a chronic thyroiditis, an atrophic gastritis, an ulcerative colitis, a primary cirrhosis, orchites, polyneurites, a rheumatic carditis, a glomerulonephritis, a pseudorheumatism, a dermatomyositis, a hemolitic anaemia.

The pathogenesis of a primary autoimmune pathology at the human and animals has a direct communication with the genetical factors defining the nature, a localisation place, a degree of manifestation of implications accompanying them. The leading role in prodeterminancy of autoimmune diseases is played by the genes coding intensity and the nature of immune answers to antigens - genes of the main complex of a histocompatibility and genes of immunoglobulins.

Autoimmune diseases can be formed with participation of various types of an immunospecific injury, their combination and sequence. Cytotoxic action of sensibilized lymphocytes (a primary cirrhosis, an ulcerative colitis), the mutant immunocytes accepting normal histic structures as antigens (a hemolitic anaemia, a system lupus erythematosus, a pseudorheumatism), cytotoxic antibodies (a thyroiditis, a cytolytic anaemia), cell-bound immune complexes an antigen-antibody (a nephropathy, an autoimmune dermal pathology) can prevail.

The secondary autoimmune pathology educes as consequence of various primary damages of organs and tissues inadequate environmental factors and wears the name of autoimmune processes. They are not an illness first cause, but can activly participate in mechanisms of development of a pathology of an infectious and not infectious parentage. These autoimmune processes arise in connection with changes of antigenic properties of tissues under the influence of endogenous and exogenous factors, the special value in development of a secondary autoimmune pathology in animals has the infectious factor. At bacterination, bacteriemic and virus infection contaminations, parasitogenic illnesses find substantial increase of titer of autoantibodies to antigens of the cells changing the structure.

The got autoimmune pathology register and at diseases of not infectious nature. The raised immune responsiveness of horses is known at extensive wounds. At large horned livestock the ketosis, chronic fodder venenatings, disbolism, avitaminoses induce autoimmune processes. At neonatal young growth they can arise colostric by when through a colostrum from sick mothers autoantibodies and sensibilized lymphocytes are transferred.

In a radiopathology big, even the leading part shunt to autoimmune processes. Owing to sharp rising of permeability of biological barriers cells of the tissues get to a blood bed, patholologically variated proteins and the materials bound to them who become autoantigens.

Production of autoantibodies descends at irradiating any kinds: unitary and repeated, choronomic and intrinsic, total and local. Rate of their appearance in blood much higher, than antibodies to foreign antigens as in an organism always there is production normal antihistic autoantibodies playing the important role in linkage and excision of solvable products of a metabolism and dying off of cells. Still above production of autoantibodies at repeated influences of radiance, that is it submits to usual patterns of the primary and secondary immune answer.

Autoantibodies not only circulate in blood, but in the end of a stage of latency, and especially in height of a radial illness, they so strongly contact tissues of an internals (a liver, nephroses, a lien, an intestine), what even repeated washing up is thin their minced tissue it is not possible to remove.

Autoantigens, capable to induce autoimmune processes, are formed also under the influence of high and low temperatures, various chemical materials, and also some medicinal preparations used for treatment of animals.

Autoimmunity of bulls and reproductive functions

The concentration of the best bulls-sires and use of their seed at artificial insemination have allowed to raise genetical potential of milk herds considerably. In the conditions of wide use of males-sires the assessment of quality of their seed has great value.

In autoimmunity cases to own seed at the males, having normal ejaculates on other parametres, depression of fertilising capacity of a seed and embryonal survival rate of their brooding is observed.

Immunologic researches of begetting power of males-sires have taped, that the overheat of spermaries causes the spermatogenesis disturbance, accompanied occurrence of autoantibodies in blood, and that their action is caused by rising of permeability of a blood-testis barrier.

There are also data, that with the years bulls-sires have in some gyrose canaliculuses of a spermary particulate vitreous degeneration of a basal membrane, a necrosis, slipping of a seed epithelium.

Circulating antibodies to autologous spermatozoons not always and oppress not at once a spermatogenesis owing to presence of a powerful blood-testis barrier between blood and cells of a seed epithelium. However a trauma, a long overheating of spermaries and all organism as well as an experimental active immunization, relax this barrier that leads to penetration of antibodies into Sertoli cells and a spermatogenic epithelium and, as consequence, to disturbance or the full termination of a spermatogenesis. More often process is intercepted at a stage of round spermatids, but after long action of antibodies division of spermatogones stops also.

Experimental autoimmune diseases

For a long time the attention of doctors and biologists involves a question, whether the sensibilization against own histic components can cause illness. Experiences on autoserotherapy reception were spent on animals.

It was revealed, that intravenous introduction of suspension of a foreign brain to a rabbit causes the antibody formation, specific to a brain which are capable to react specificly with a brain suspension, but not other organs. These anticerebral antibodies cross react with cerebral suspensions of other kinds of animals, including and a rabbit. At an animal forming antibodies, it was not revealed any pathological changes of own brain. However Freund's adjuvant application has variated an observable picture. The cerebral suspensions admixed with a full Freund's adjuvant, after intradermal or intramuscular introduction in many cases cause a paralysis and  destruction of an animal. At histological research the fields of infiltration consisting of lymphocytes, plasmatic and other cells have been found in a brain. It is interesting, that the intravenous injection of the rabbity cerebral suspension to rabbits (animals of the same kind) cannot cause formation of autoantibodies. However the suspension of the rabbity brain admixed with a Freund's adjuvant, causes an autoserotherapy in the same degree, as any foreign cerebral suspension. In other words, cerebral suspensions in certain conditions can be autoantigens, and the caused illness can be named by an allergic encephalitis. Some explorers consider, that the plural sclerosis can be caused an autoserotherapy to certain cerebral antigens.

One more squirrels possesses properties - a thyreoglobulin. The intravenous injection of the thyreoglobulin received from other kinds of animals, led to production of antibodies, precipitant a thyreoglobulin. There is a big resemblance in a histological picture of an experimental rabbity thyroiditis and a chronic thyroiditis for the human.

Circulating antibodies are found at many diseases: antirenal antibodies - at renal diseases, antiwarm antibodies - at certain diseases of heart etc.

Following criteria which can be beneficial by treating of the diseases caused by an autoserotherapy have been established:

1. direct detection of free circulating or cellular antibodies
2. specific antigen revealing against which this antibody is referred
3. development of antibodies against the same antigen at experimental animals
4. appearance of pathological changes in the conforming tissues at active primed animals
5. reception of disease at normal animals at passive transmission of Serum, antibody-containing, or immunologically competent cells

Several years ago at deducing of pure lines the strain of chickens with a hereditary hypothyroidism has been received. At chickens the serious chronic thyroiditis spontaneously educes, and their Serum contains circulating antibodies to a thyreoglobulin. Virus searches were till now unsuccessful, and is very possible, that spontaneously observed autoimmune disease at animals takes place.

Antireceptor autoantibodies and their value in a pathology

Autoantibodies to receptors of various hormones are well enough studied at some kinds of an endocrine pathology, in particular at diabetes, a thyrotoxicosis that allows many explorers to survey them as one of leading parts of a pathogenesis of diseases of hemadens. Along with it last years interest and to other antireceptor autoantibodies - to antibodies to neurotransmitters has grown, their participation in regulation of function of cholinergic and adrenergic systems of an organism is proved, their connection with some kinds of a pathology is established.

Researches of the nature of the atopic diseases, spent within several decades, it is conclusive have proved the immunologic nature of their releaser - role IgE in the mechanism of remission of biologically active materials from mast cells. But only last years fuller data about the immune nature of disturbances have been obtained at the atopic diseases, concerning not only a releaser of allergies, but also atopic a syndrome of the complex bound to disturbance of functioning of adrenoreceptors at these diseases, and in particular at an asthma. It is a question of an establishment of the fact of existence of autoantibodies to b to-receptors at the atopic asthma, putting this disease in the discharge of an autoimmune pathology.

Open there is a question on the cause and the mechanism of development of autoantibodies to b to a-receptor though, proceeding from the general representations about development of allergic diseases, it is possible to explain appearance of autoantibodies a consequence of disturbances of functions of cells-suppressors, or, proceeding from theory Erne, that the autoimmunity is a normal physiological condition of immune system and that physiological autoantibodies under the influence of choronomic or intrinsic conditions turn in pathological and cause a classical autoimmune pathology.

Unlike autoantibodies to b to-adrenoreceptors which are studied now insufficiently, autoantibodies to acetylcholine to receptors are studied well enough both in experiment, and in clinic. There is the special experimental model showing important pathogenetic autoantibodies to acetylcholine receptors - an experimental myasthenia gravis. At immunization of rabbits by preparations of acetylcholine receptors it is possible to cause the disease reminding a myasthenia of the human. In parallel with level rising acetylcholine antibodies at animals the delicacy reminding a myasthenia on many clinical and electrophysiological implications educes. Disease proceeds in two phases: acute during which time there is a cellular infiltration and damage by antibodies of a trailer plate, and chronic. The acute phase can be caused passive transmission IgG from protected animals.

Autoallergy

At various morbid conditions blood proteins and tissues can get allergenic, foreign properties for an organism. To autoallergic diseases carry an allergic encephalitis and allergic collagenesis.

The allergic encephalitis arises at repeated introduction of a various sort of the extracts received from a cerebral tissue of all adult mammals (excepting rats), and also from a brain of hens.

Allergic collagenesis represent the original form of infectious autoallergic diseases. The autoantibodies formed in these cases cause cytotoxic effect in tissues; there is a lesion of an extracellular part of a copulative tissue collagenesis character.

To allergic collagenesis carry acute the joint rheumatic disease, some forms of a glomerulonephritis, etc. At acute articulate rheumatic disease the conforming antibodies have been found. As a result of experimental researches the allergic nature of acute articulate rheumatic disease has been proved.

Many explorers consider, that the rheumatic carditis pathogenesis is similar to a rheumatic carditis pathogenesis. Both of them educe against a focal streptococcal infection contamination. In experiment at introduction by an animal of chromic acid they had renal autoantibodies and there was a glomerulonephritis. - the nephrotoxins damaging a renal tissue, it is possible to receive autoantibodies by freezing of nephroses, at a dressing of renal pots, ureters, etc.