Download Allergy. Immunodeficiency conditions

Allergy.
Immunodeficiency
conditions
• Allergy is an immune response, which is followed
by damage of own tissues.
• If damage is followed by such changes in
organism, that are typical for a disease, than
allergic diseases arise.
• Allergic diseases – is a group of diseases, in
development base of which damage lies, caused
by an immune reaction on allergens.
• Allergic diseases are widely spread among people.
It is considered that they cover about 10 % of
earth population. In different countries these sizes
vacillate from 1 to 50 % and more.
• The cause of allergic diseases is the allergen, the conditions of
their appearing are the specific peculiarities of the environment
and state of organism reactivity.
• Allergen – is a substance that causes development of an
allergic reaction.
• Allergens have all properties of antigens (macromolecularity,
mainly protein nature, foreign for a particular organism).
• However allergic reactions can be caused by substances of not
only antigen nature, but also substances, not possessing these
properties. To this group belong many officinal preparations,
bacterial products, polysaccharides, simple chemical
substances (bromine, iodine, chrome, nickel). These substances
are called haptens. While entering the organism they become
antigens (allergens) only after binding with tissues proteins.
Herewith complex antigens, which sensitize the organism are
formed.
Two groups of allergens
• exogenous allergens
• endogenous allergens
(autoallergens).
• Exogenous allergens come into the
organism from outside
• Endoallergens are formed in the
organism
Allergens classifications
According to the origin exogenous allergens are divided into
following groups:
• a) allergens of
noninfectious origin:
• home
• epidermal
• pollen
• food
• industrial
• officinal
• b) allergens of
infectious origin:
• bacterial,
• fungous,
• viral
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Domestic allergens. Main role among
them domestic dust plays, which includes
particles, bed-clothes, furniture, bacteria.
Epidermal allergens. To this group refer:
scurf, wool, birds, fur, fish, scales.
Professional sensitization by epidermal
allergen is observed in sheepmen,
horsemen, poultry farms workers,
hairdressers.
Officinal allergens. Any officinal
preparation with a little exception causes
the development of an officinal allergy.
Medicines or their metabolites are, as
usual, haptens. In case of sensitization of
the organism to one preparation, allergic
reactions to other medicines, having alike
chemical structure can arise.
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Pollen allergens. Allergic diseases are
caused by shallow plants, pollen. It is called
pollinosis. The diverse types of pollen can
have the general allergens, therefore in
people, sensitive to one type of pollen, a
reaction on its other kinds is possible.
Food allergens. Many food products can
be by allergens. They are usually fish,
wheat, beans, tomatoes, milk, eggs.
Chemical substances added to food
products (dye-stuffs, antioxidants, aromatic
and other substances) may also be
allergens.
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,
dye-stuffs, metals and their salts, wood
products, latex, perfumer substances,
washing means, synthetic cloths and
others.
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Allergens of infectious origin.
All the different causative agents of infectious
diseases and products of their life activity cause the
development of allergic processes.
Those infectious diseases, in pathogenesis of which
allergy plays a leading role, were named infectiously
allergic. These are all the chronic infections
(tuberculosis, lepra, brucellosis, syphilis,
rheumatism, chronic candidosis etc.).
The widespread allergens are the fungi. Many
nonpathogenic fungi while entering the organism
cause sensitization and development of diverse
allergic diseases (bronchial asthma).
Such fungi are contained in atmospheric air,
dwellings, domestic dust, food products. With
biotechnological development a possibility of
sensitization on enterprises on production of stern
squire, vitamins, antibiotics, enzymes arises.
Pathogenesis of allergy
reactions
• There are different classifications
of allergic reactions
• R.A.Cook picked out
• allergic reactions of immediate
type and
• allergic reactions of delayed-type
or hypersensitization of delayedtype
• In the base of classification the time of
appearing of reaction after contact with
allergen has been placed.
• The reactions of immediate type developed
during 15-20 minutes, delayed-type – after
1-2 days.
• However it does not envelop all the variety
of allergy displays. For example, some
reactions develop over 4-6 or 12-18 hours.
• Therefore the distinctions between allergic
reactions were interconnected with different
mechanisms of their development and the
classifications based on pathogenic
principle were put together.
• The classification by P.Gell, R.Coombs is
widely spread in the world.
• It is based on pathogenic principle. The
peculiarities of immune mechanisms lay
in its base.
• In accordance to this classification there
are 4 types of allergic reactions:
• anaphylaxic
• cytotoxic
• immune-complex
• delayed hypersensitivity
Allergy development stages
• Entering into the
organism antigen causes
its sensitization
• Sensitization is an
immunological rising of
organism sensitiveness to
antigens (allergens) of
exogenous or
endogenous origin
• According to method of
receiving there are active
and passive
sensitizations
• Active sensitization
develops in artificial
introduction or natural
penetration of the
allergen into the organism
• Passive sensitization is
reproduced in the
experiment by
introduction of blood
plasma or lymphoid cells
of an actively sensitized
donor to an intact
recipient
In the development of allergic reaction
there are three stages:
• 1. Immunological stage. It covers all the changes in
immune system during the penetration of an allergen into
the organism, formation of antibodies or sensitized
lymphocytes and their binding with the repeatedly
entering allergen.
• 2. Pathochemical stage. Its sense is in formation of
biological active substances. The stimulus to their
formation is the binding of allergen to antibodies or
sensitized lymphocytes at the end of immunological
stage.
• 3. Pathophysiological stage. It is described by
pathogenic action of formed mediators onto cells, organs
and tissues of the organism with a clinical display.
• In this way the immunological mechanisms lay in
development base of allergic processes.
• Central cell of immune system is a lymphocyte.
• Lymphocytes are heterogenic according to their
functions, markers, receptors.
• They develop from a stem cell.
• A lymphoid stem cell will form from it, from which
T- and B-lymphocytes develop.
• The T-lymphocytes acquire the specific antigen
receptors, with the help of which they identify an
antigen and other markers.
• There are 3 types of T-cells:
• T-helpers
• T-suppressors
• T-effectors
• The last ones form sensitized lymphocytes or
killers, which participate in realization of allergic
reaction of delayed-type and realize cytotoxic
action on cell-target.
• The B-lymphocytes produce 5 classes of
immunoglobulins IgG, IgM, IgA, IgE, IgD.
• These cells during ripening acquire the
receptors for antigen on their membranes.
During binding of such B-cells with proper
allergens and after the signal, received from Thelper, they become activated, and proliferation
and differentiation into antibody producing cells
starts.
• The correlation between two groups of
subpopulations of T-helpers (Th-1 and Th-2)
plays an important role in the development of
immune reaction.
• They are both formed of Th-0 and differ form
each other by the set of secreted
lymphokines and quantity of Fc-receptors for
immune globulins on their surface.
• On Th-2 there are many receptors for
immune globulins A, M, E, and on Th-1 there
are a few of them or they are absent.
• During the activation of Th-1 the formation of IL2 increases, it stimulates the secretion of
immune globulins A, M and G by B-cells and
turns on cellular mechanism of immunity.
• Activation of Th-2 leads though IL-4 to changing
of synthesis of IgE by B-cells to proliferation of
fat cells and through IL-5 to increasing and
proliferation of eosinophiles.
• There are antagonistic relationship between
these two ways.
• The choice of way of activation depends on
character of allergen.
• Besides that the form of allergen, conditions on
introduction into organism and its quantity play
role.
Anaphylactic type of allergic
reactions
According to anaphylactic type a group of
atopic diseases
 atopic bronchial asthma
 pollinosis
 atopic dermatitis
 nettle-rash
 food and officinal allergy
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Immunological stage
• IgE and IgG4 are formed as an answer to penetrating of
allergen into the organism.
• They get fixed on the mast cells and basophiles of blood.
These cells have on their surface Fc receptors for
immune globulin. The state of sensitization of the
organism appears.
• If the same allergen again gets into the organism or it
still stays in the organism after the first penetration,
connection of antigen with IgE-antibodies occurs.
• The same thing is observed with IgG4. they bind with
their receptors on basophiles, macrophages,
eosinophiles, trombocytes.
• Depending on the quantity of molecules of IgEantibodies connected to antigen, quantity of antigen we
can observe either inhibition of activity of the cell or its
activation and transfer of the process to the next,
pathochemical stage.
Pathochemical stage
• Activation of the most and basophile cells leads to releasing of
different mediators. The process of secretion of mediators need
energy, that’s why blocking of energy-formation blocks also
releasing of mediators.
• A certain role in this process play cyclic nucleotides of the cells –
cAMP and cGMP. Secretion of one of the main mediators –
histamine depends on their correlation.
• Many different mediators have been excluded from the most cells
and basophile leucocytes. Some mediators are in the cell in ready
form and are easily secreted (histamine, serotonin, eosinophiles
chemotaxic factors).
• Some mediators are formed after stimulation of the cell (leukotriens,
trombocyte activating factors). This mediators act on vessels and
target-cells, including in the development of allergic reaction
eosinophiles, trombocytes and other cells.
• As a result eosinophiles, neutrophiles, which start also to release
mediators – phosrholipase D, histaminase, leukotriens and others
come to the place of activation of the most cells.
Histamine
• 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 cells through the receptors
of two types – H1 and H2.
• Their correlation and spreading on the cells of different
cells is different. Stimulation of H1 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.
• Stimulation of H2 causes the opposite effects.
• Besides this releasing of histamine from
basophile leucocytes and from the lungs is
diminished through them, the function of the
lymphocytes modulates, formation of migration
ingibitory factor (MIF) by T-lymphocytes gets
oppressed, releasing of lysosome enzymes by
neutrophile leucocytes diminishes as well.
• In many cases the increasing of quantity of
histamine in blood is observed in the intensive
stage of bronchial asthma, nettle-rash, officinal
allergy.
Heparin
• Heparin is activated after releasing
out of the most cells.
• It possesses an antitrombine and
anticomplementar activity.
• Trombocyte activating factor (TAF) is
secreted by basophiles, lymphocytes,
trombocytes and endothelial cells.
• TAF acts on target-cells through
corresponding receptors:
• 1) it causes the aggregation of trombocytes and
releasing of histamine and serotonin out of them
• 2) it helps to chemotaxis and secretion of
granular content of eosinophiles and
neutrophiles
• 3) it causes spasm of smooth muscles
• 4) it increases permeability of vessels
Metabolites of arachidone acid
• It is metabolized in two different ways:
cyclooxygenic and lipooxygenic.
• Under the influence of
cyclooxygenase prostaglandins,
tromboxans and prostacycline are
formed from arachidone acid.
• Under the influence of lipooxygenase
leukotriens are formed from it.
• In allergy prostaglandins of F group
possess the ability to cause contraction of
smooth muscles, including bronchi, and
prostaglandins of E group provide the
relaxing action.
• Leukotriens cause the spasm of smooth
muscles, increase secretion of mucous,
decrease coronary blood flow and power
of heart contractions, increase chemotaxis
of polymorphic-nuclear leukocytes, lead to
development of prolonged bronchial
spasm.
Pathophysiological stage
• Under the influence of mediators the permeability of
vessels and chemotaxis of neutrophiles and eosinophiles
increase, which leads to development of inflammatory
reaction.
• The increasing of permeability of vessels promotes the
exit of fluid, immunoglobulins and complement into
tissues.
• With the help of mediators and also through the IgEantibodies, the cytotoxic effect of macrophages is
activated, secretion of enzymes, prostaglandins and
leukotriens, trombocyte activating factor is stimulated.
• The released mediators cause also a damaging action
onto cells and connective tissue structures.
• Bronchospasm develops in respiratory organs.
• These effects are clinically manifested by attacks of
Anaphylactic shock
• Anaphylactic shock develops in severe complication.
• Spasm of smooth muscles of internal organs with clinical
manifestation of bronchospasm (cough, expiratory
breathlessness), spasm of gastro-intestinal tract muscles
(spastic pain in the whole abdomen, nausea, vomiting,
diarrhea), spasm of uterus in women (pain below
abdomen) are observed.
• Spastic phenomena are worsened by edemas of mucous
covers of internal organs, during the edema of larynx the
picture of asphyxia may develop.
• The arterial pressure is sharply decreased, the heart
insufficiency, ischemia of brain, seizes paralysis develop,
danger for the life of the patient appears.
Cytotoxic type of allergic reactions
• Immunological stage. It is called cytotoxic
because the antibodies that developed to
antigen of the cell bind to cells and cause their
damage or even lysis (cytolytic action). For
turning on of this mechanism cells of tissues
have to acquire autiallergen properties. Than the
formation of autoantibodies starts. In this
process action of chemical substances, usually
medicines, viruses, microbes onto the cell plays
a big role. They may change the antigen
structure of cell membranes. The formed
autoantibodies belong to IgG and IgM. They
connect to corresponding antigens of the cells
by their Fab-fragments.
• Pathochemical stage. The main mediator of
cytotoxicity is the activated enzymes of
complement. Phagocytes release some
lyzosome enzymes and generate superoxide
anion-radical.
• Pathophysiological stage. The damage of the
cell with the antigen properties may be caused
by three reasons: due to activation of
complement, the components of which damage
the cell membrane; due to activation of
phagocytosis of the cells covered with
antibodies; due to activation of T-lymphocytes,
natural killers, K-lymphocytes.
Immune complex type
• Immunological stage. Many exogenous and
endogenous antigens participate in formation of immune
complexes. Among them there are officinal preparations
(penicillin, sulfanilamides,), antitoxic vaccines, allogen
gamma-globulins, food product (milk, egg white),
inhalation allergen (home dust, fungi). In case of
penetration of soluble antigen into the organism IgG and
IgM antibodies are formed. These antibodies can cause
the formation of precipitate and connection to antigen.
Immune complex can be formed in tissues or in blood
flow.
• Patochemical stage. Under the influence of immune
complexes the following mediators are formed:
fragments C3a, C5a, C4a of the complement, lyzosomal
enzymes of phagocytes, kinines, superoxyde anionradical.
• Pathophysiological stage. Usually immune
complexes are placed on vessels of cannalicular
apparatus of kidneys, inflammation with
alteration, exudation and proliferation
(glomerulonephritis) develops, in case if the
complexes are placed in the lungs alveolitis
appears, in skin – dermatitis. The inflammation
may lead to formation of ulcers, hemorrhages,
thrombosis is possible in the vessels. This type
of allergic reactions is the prominent one in
development of serum , some cases of officinal
and food allergy, some autoallergic diseases
(rheumatoid arthritis, systemic red lupus
erythematosus). In case of massive activation of
complement anaphylactic shock, bronchial
Allergic reactions of delayed type
• Immunological stage. The cellular mechanism
of immunity is usually activated in cases of
insufficiency of effectiveness of humoral
mechanisms, for example, in case of intracellular
localization of the antigen (mycobacterium,
brucella, histoplasma etc.) or when cells are
antigen themselves. They may microbes, fungi
and their spores, which get into the organism
from the outside. The cells of own tissues also
may acquire the auto allergen properties. This
mechanism may turn on as a response to
formation of complex allergens, in case of
including haptens into proteins, for example, in
case of contact dermatitis, which appears during
the contact of the skin with different medicinal,
industrious and other allergens.
• The foreign antigen is phagocyted by
macrophages and get to T-helpers. At the
same time macrophages secrete IL-1,
which stimulates T-helpers. The latest
excrete the growth factor pro-Tlymphocytes – IL-2, which activates and
supports proliferation of antigen stimulated
T-cells. This process leads to formation of
sensitized lymphocytes. They belong to
T-lymphocytes and in the cell membrane
they have receptors of the antibody type,
which are able to connect with the antigen.
In case of repeated penetration of the
allergen into the organism it binds with the
sensitized lymphocytes.
Pathochemical stage
• This leads to morphological, biochemical and
functional change in lymphocytes.
• They are presented by blast transformation and
proliferation, increasing of synthesis of DNA,
RNA and proteins and secretion of different
mediators, which are called lymphokines. With
the help of lymphokines (MIF, interleukines,
chemotaxic factors, factor of transfer)
mobilization of different cells (macrophages,
polymorph-nuclear), increasing of chemotaxic
activity and placing in the site of allergen occur.
• MIF promotes accumulation of macrophages in
the site of allergic damage, increases their
activity and phagocytosis. It takes part in
formation of granulems during infectious-allergic
diseases, increase the ability of macrophages to
destroy certain kinds of bacteria.
• There are several kinds of chemotaxic factors,
each of which is called chemotaxis of
leukocytes – macrophages, neutrophiles,
eosinophiles and basophiles.
• Lymphotoxins cause damage and destroying of
all different target-cells.
• Interferon is secreted by lymphocytes and under
the influence of α-interferon and nonspecific
mitogens. It acts a modulating influence on
cellular and humoral mechanisms of immune
reaction.
• Besides lymphokines, lizosome enzymes also
provide a damaging activity. They are released
during phagocytosis and destroying of cells.
• Kallikreine-kinine system is also activated.
• Histamine doesn’t play a big role in this type of
allergic reactions.
Pathophysiological stage
• A particular form of lymphokines (lymphotoxin,
interferon) shows a cytotoxic action and
decreases activity of cell. In allergic reaction of
delayed type damaging action may develop in
several ways:
• 1) direct cytotoxic action of sensitized Tlymphocytes on target-cells, which acquired
autoallergen properties;
• 2) cytotoxic activity of T-lymphocytes, mediated
by lymphotoxin;
• 3) releasing of lysosome enzyme, which
damage tissue structures during phagocytosis.
• Inflammation that is associated to immune
reaction by action of mediators is a component
of allergic reaction of delayed-type.
• Nevertheless inflammation is at the same time a
factor of damage of function of the organs.
• Allergic reactions of delayed type make the
base of development of infectious-allergic
diseases (tuberculosis, lepra, brucellosis,
syphilis), rejection of transplant, and
autoallergic diseases (disturbance of nervous
system, endocrine glands etc.).
Pseudoallergic reactions
• Pseudoallergy is a pathological process, which is
clinically similar to allergy but doesn’t have an
immune stage of its development. Pseudoallergy
differs from a simple one by the absence of first
(immune) stage. The rest two stages – releasing of
mediators (pathochemical) and pathophysiological
(stage of clinical manifestations) 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.
• The reason of pseudoallergy is any substance
that acts directly on effector cells (fat cells,
basophiles etc.) or biological fluids and cause
releasing of mediators from the cells or
production of them in the fluids.
• Practically most of the allergens can lead to
development of both allergic and pseudoallergic
reactions.
• This depends on nature of the substance, its
phase, frequency of introduction into the
organism and reactivity of the organism.
• Pseudoallergic reactions usually occur in
officinal and food intolerance.
• Many remedies more usually lead to
development of pseudoallergy than true allergy.
• Clinical picture of pseudoallergic diseases is
close to one of allergic diseases.
• Development of such pathological processes as
increasing of permeability of vessels, edema,
inflammation , spasm of smooth muscles,
destroying of blood cells lay in the base of this
clinical picture.
• These processes may be local, organic and
systemic.
• They are presented by rhinitis, nettle-rash,
Kvinke’s edema, periodical headaches,
disturbance of gastro-intestinal tract, bronchial
asthma, vaccine disease, anaphylactic shock
and also damaging of certain organs.
Preventing of allergy.
Hyposensitization
• Prophylaxis of an allergic disease depends on its
character and group of the allergens. It consists of
measures of preventing of penetration of given
allergen into the organism and preventing of the
influence of different irritating factors on the
organism. If sensitization has already occurred
and allergic diseases has already started, the
following measures are appropriate.
• 1. Suppression of antibodies and sensitized
lymphocytes production with the help of immune
depressants, ionizing radiation, cytostatics,
specific lymphocyte vaccines and monoclonal
antibodies.
• 2. Specific desensitization by Bezredka.
Desensitization is provided by little doses of the
antigen, which do not cause severe reactions.
The doses are introduced repeatedly after
certain intervals of time, during which produced
mediators get inactivated in the organism. The
main dose of the antigen is introduced after
antibodies binding. This method is effective in
introduction of foreign medical vaccines.
• 3. Inactivation of biological active substances.
For this purpose antihistamine preparations,
inhibitors of proteolytic enzymes etc. are
introduced.
• 4. Protection of the cells from the influence of
biological active substance and also normalizing
of functional disorders in organs and systems
(narcotic, spasmolytic substances, receptor
blockers etc.).