REACTIVITY, RESISTANSE IMMUNOLOGICAL REACTIVITY. ALLERGY

1. REACTIVITY, RESISTANSE IMMUNOLOGICAL REACTIVITY.ALLERGY Lecturer: PhD IvanitsaArina

2. Reactivity is ability of an organism and its structures to react on the different environmental factors by changes of vital activity.

3. Reactivity may be:-Species, group and individual.-nonspecific and specific reactivity -Physiological and pathological reactivityHyperergya (rise reactivity), hypoergya (decrease reactivity) and dysergy (perversion reactivity).

4. On reactivity influence the following factors:-Age,-Sex,-Heredity, -Constitution,-Functional state of the nervous, endocrine, immune systems and connecting tissue,-Factors of environment.

5. Resistance is stability of the organism to the action of pathogenic factors. Resistance may be:- passive and active, - inherited and acquired,- specific and nonspecific.

6. Specific resistance is defense against concrete agent-immunological reactivity lies in basis of specific resistance.Nonspecific resistance is defense against many factors (body temperature, рН, phagocytosis, inflammation, system of complement, interferon, and biological barriers).

7. Biological barriers divide into external and internal:External barriers(skin, mucus membranes). Internal barriers are:- organs (liver)-histohematological barriers (hemato encephalic, hemato ophthalmic, hematotesticularion, hematothyreoidus and hematocohlearicus).

8. Immunological reactivityis ability of an organism to answer on the action of an antigen by formation of antibodies and complex of cellular reactions specific against to the antigen.

9. Mechanisms:Humoral- the action of antibodies (Ig), directed on extracellular bacteria and viruses.Cellular - the action of T-cell, directed on intracellular infections, mycosis, vermin and tumours cells.

10. Immunological insufficiencyis hereditary or the acquired defect of the immune system, which is characterized inability of an organism to carry out the reactions of humoral and cellular immunity.

11. Immunological insufficiencyPrimary: Reasons:1. Genes mutations: а) sex-linked mutation; б) autosomal-recessive mutation.2. Chromosomal mutations.3. Pre-natal infections.Secondary: acquiredReasons:1. Exogenous (ionizing radiations, chemical, biological factors). 2. Endogenous (ageing, intoxication)

12. Hereditary diseases – are the diseases caused by disorders of genetic information (mutations), obtained by the body with germ cells of their parents.Congenital disease- which are manifested at birth. They can be caused by both hereditary and exogenous (teratogenic) factors.Depending on the extent of the infringement of genetic information there are three different types of hereditary diseases:1) monogenic;2) polygenic (multifactorial);3) chromosome.

13. The total number of chromosomes in human somatic cell 46 (23 pairs), and gamete - 23. Chromosomes from the 1st to the 22nd pair -autosomes, and 23rd - sex (X - women's, Y - male).Syndromes associated with genomic mutations: Associated with changes in the number of somatic chromosomes1. Down Syndrome - trisomy of chromosome 21. It is characterized by mental retardation, a characteristic appearance (low growth, short fingers, Mongoloid eye shape, delay physical development), anomalies of internal organs (especially the heart).

14. 2. Patau Syndrome - trisomy of the 13th chromosome. Characterized by the splitting of the lips and palate ("hare lip", "palate"), impaired vision, changes nervous and cardiovascular systems.

15. II. Associated with changes in the number of sex chromosomes: 1. Trisomy of the X chromosome (karyotype XXX). Total number of chromosomes – 47, sex - 3, Bar bodies - 2, sex - female, there is a slight mental retardation and hypoplasia of ovaries.

16. 2. Turner's syndrome (karyotype X0). Total number of chromosomes – 45, sex - 1, Bar’s bodies-0, sex- female. Characterized by underdevelopment of the gonads and other reproductive organs (sterility), violations of the skeleton (short stature, deformation of the chest, etc.), mental retardation – usually absent.

17. 3. Klinefelter's syndrome (karyotype XXY may be XXXY, XXXXY). Total number of chromosomes – 47, sex - 3, Bar’s bodies - 1, sex - male. Manifested hypoplasia of male gonads and genital organs (sterility), the emergence of female secondary sexual characteristics (feminization), retardation of mental development).

18. ALLERGY

19. Allergy - is the state of the hypersensitiveness of the organism to the repeated penetrating of allergen which is characterized by immunological mechanisms and self injury. • Allergy is an immune response, which is followed by damage of own tissues. 

20. Allergic diseases are widely spread among people. • It is considered that they cover about 10 % of earth population. In different countries these numbers fluctuated from 1 to 50 % and more.

21. Classification of allergens I. According the structure: • Complete (valuable) – at penetrating into the organism they cause the formation of antibodies or sensitized T- lymphocyte. Proteins by chemical nature. • Incomplete (partial) – at penetrating into the organism they contact with the host proteins (the conjugated connection). They are haptens by the chemical structure. II. According the origin : • Exogenous: infectious;noninfectious: domestic – home dust, home chemicals, book dust; pollen antigen (pollen of plants);epidermal - fur of animals, birds feathers, fish food;drugs allergy – anesthetics, vitamins, antibiotics ;food (fish, eggs, milk, chocolate, citrus, nuts, honey);industrial allergens – cosmetics, chemicals.

22. domestic – home dust, home chemicals, book dust, bed clothes

23. Epidermal allergens. To this group refer: scurf, wool, birds, fur, fish, scales. Professional sensitization by epidermal allergen is observed in sheepmen, horsemen, hairdressers.

24. pollen allergens (pollen of plants);

25. food (fish, eggs, milk, chocolate, citrus, nuts, honey);

26. drugs allergy – anesthetics, vitamins, antibiotics ;

27. Industrial allergens. The industrial allergens for the most are haptens. In each industrial production a particular admission of chemical matters is used. These are: resin, glue and covering materials, plastics, metals and their salts, wood products, latex, perfumer substances, washing means, synthetic cloths and others.

28. primary (natural) allergens are compounds of host tissues -behind barrier organs.

29. secondary (acquired) allergens – emerge at the change of one’s own proteins structure under the action of external environment factors. infectious: β- hemolytic streptococcus (strains 4, 12, 25, 49 are nephrotoxic; the 5th strain has common antigens determinants with the myocardium);uninfectious are antigens which emerge in the organism as a result of the action of: - high or low temperatures; - chemical factors; - ionizing radiation.

30. The ways of the allergens penetration: • Enteral (alimentary – drugs, food). • Inhalation (dust, pollen). • Parenteral (drugs). • Contact (industrial, cosmetics). • Transplantation (organs and tissues transplantation).

31. Classification of allergic reactions I. After the time of manifestations (after the secondary penetration of an allergen) • Allergic reactions of the immediate-type - the allergic reaction develops from some seconds to 2 hours) after the repeated penetration of an allergen to the sensitized organism, and in 20-30 minutes clinical manifestations become maximal). F. e.: the anaphylactic shock, the bronchial asthma, the pollinosis, the serum sickness.

32. 2. Allergic reactions of the delayed-type - the first signs appear in 48 h. or more). F. e.: the reaction of graft rejection , the contact dermatitis, the bacterial allergy (Mantoux’s and Pirquet's tuberculin skin test), autoallergy.

33. The classification by P.Gell, R.Coombs is widely spread in the world. It is based on pathogenic principle. There are 5types of allergic reactions: • Anaphylaxic • Cytotoxic • Immune-complex • Cellular-mediated; • Stimulating

34. The Pathogenesis of allergic reactions There are three stages in the development of allergic reaction: • 1. Immunological stage-the changes in immune system during the primary penetration of an allergen into the organism, formation of antibodies or sensitized lymphocytes and their binding with the repeatedly entering allergen. • 2. Pathochemicalstage -formation of biological active substances (mediators).  The stimulus to their formation is the fixationof allergen to antibodies or sensitized lymphocytes at the end of immunological stage. • 3. Pathophysiological stage (clinical manifestation) - pathogenic action of formed mediators on cells, organs and tissues of the organism with a clinical display.

35. Penetration to the organism allergens causes its sensitization. Sensitization is an immunological  rising of organism sensitiveness to allergens. Active sensitization develops in artificial introduction or natural penetration of the allergen into the organism and formation of antibodies by organism. Passive sensitization is reproduced by introduction of antibodies from actively sensitized donor to an intact recipient. The synthesis of the antibodies begins on the 3rd - 4th day after the first penetrating of the allergen and the maximal level - in 2 weeks.

36. Pathogenesis of allergic reactions of the I type (anaphylactic) Immunological stage. At the first penetrating of an allergen into the organism its absorption by the macrophage (the antigen-presenting cell) takes place. In the macrophage the antigen is decomposed into determinants (processing) which leads to the immunological form - peptide appears. The peptide joins the major histocompatibility complex (MHC) class II. The complex got as a result of it appears on the external membrane of the macrophage - expression. The macrophage interacts with the Т-helper of II class true СD4 – receptors to MCH. The Т-helper is interact with the macrophage and information about the allergen is passed from the macrophage to the Т-helper and the proliferation of the Т-helpers population takes place. Т-helper interacts with В-lymphocytes causing their blast-cell transformation into plasmocytes which produce IgE (antibodies).

38. Patochemical stage At the repeated penetrating the allergen associates with the Fc-fragment of IgE activating of basophiles leads to releasing of different mediators (degranulation of mast cells). Activation of arachidonic acid metabolism leads to formation of prostaglandins and leukotrienes. Histamine is localized in ready form in granules of the most cells and basophile leucocytes. In the blood of healthy people histamine almost totally stays in basophile leucocytes.   Histamine acts on the tissues - promotes to contraction of smooth muscles, endothelial cells and postcapillary part of microcirculation. This leads to increasing of permeability of vessels, development of edema and inflammation.

40. II. The mediators of the late phase are secreted by eosinophils and neutrophils after 2 hours: • Histaminase– destroys and inhibits histamine. • Prostaglandins Е1, Е2 –reduces the degranulation of basophiles and BAS secretion. • Аrylsulfataze– destroys leukotrienes (SRSA). • Phospholipase B and D – inhibit the factor of thrombocytes (FAT) activating. • Polysaccharides mediators (synthesized by neutrophiles): heparin and heparan sulfate inhibit the kinins system that is promote the allergic process inhibition. • Basic protein isproduced by eosinophils.

41. Pathophysiological stage. In this stage the complex of functional, biochemical and structural changes develops at the cellular, tissue, organs and organism levels. Thise changes emerge on the basis of immunological violations and allergy mediators’ secretion. E.g.: bronchial asthma, pollinosis , nettle-rash and anaphylactic shock, Quinke’sedema.

42. the Pathogenesis of the cytotoxic type allergic reactions Stage I Performed in the same way as I type. The formed antibodies belong to IgG and IgM. They connect to corresponding antigens of the cells by their Fab-fragments. Stage II: There are three variants: -the 1st variant – complement-mediated cytotoxicity. -the 2nd variant – antibody-mediated immune clearance (phagocytosis). -the 3rd variant – antibody-dependent [cell-mediated] cytotoxicity Mediators of the cytotoxic type of allergic reactions: • Complement compounds; • Lysosomal enzymes; • Oxygen’s radicals; • Perforin (channel-forming protein).

43. Stage III: • Hemolytic anemia of newborns • Hemolytic reactions (by group, Rh) • Drug allergy; • Autoallergy

44. Pathogenesis of the immunocomplex type allergic reaction The immunocomplex type allergic reactions develop under the penetration of a big amount of a dissoluble allergen. Antibodies is accumulated in blood or other liquids The formed antigen-antibody complex circulates in blood or other liquids - circulating immune complex (CIC). CIC circulate in blood and then sediment in the places with an intensive and turbulent blood stream (valves of the heart, glomeruli of the kidneys, places of vessels bifurcations, joints). The damage of endothelium emerges when CIC sediment on the endothelium as a result the Hageman factor and the Kinins system activation

45. Mediators of the immunocomplex type allergic reactions: • The kinins system. • Lysosomal enzymes. • Oxygen’s radicals. Stage III: • Glomerulonephritis; • Serum sickness; • Allergic vasculitis; • Autoimmune diseases (scleroderma, lupus).

46. the Pathogenesis of the cellular-mediated IV type allergic reactions Stage I: The information about the allergen is passed from macrophage onto the Т-helper. After this the secretion of cytokines, IL-2, γ-interferon take place, and under their action proliferation of the Т-killers and T-memory cells population takes place.

47. Stage II: There is the interaction between the sensitized T-effectors and the cells which carry the allergen. Mediators of the cellular-mediated type reactions: • Perforin (channel-forming protein). • Lysosomal enzymes. • Oxygen’s radicals. • Factor of tumors necrosis. • Lymphokines.

48. Stage III: • Reaction of the graft rejection; • The contact dermatitis; • Bacterial allergy (Mantoux’s and Pirquet's tuberculin skin reaction); • Autoallergy.

49. the Pathogenesis of V type allergic reactions • Stimulating Thyrotoxicosis (Graves' disease) • Blocking Diabetes mellitus type II, myasthenia gravis

50. Pseudoallergic reactions • Pseudoallergy is a pathological process, which is clinically similar to allergy but doesn’t have an immune I stage of its development.  • The rest two stages – pathochemical and pathophysiological are the same both in pseudoallergy and a real one. • To pseudoallergic reactions refer only processes in the development of which the leading role play mediators, which are formed also in pathochemical stage of true allergic reactions.