“Types of hypersensitivity.
Cell-type immune responses
(hypersensitivity of the delayed type of HRT). Clinical examples".
Cycle 1 – immunology.
Lesson No. 5 a

Allergy (ancient Greek ἄλλος - other, other, foreign + ἔργον - impact)

Allergy
(ancient Greek ἄλλος - other, different, alien + ἔργον -
impact)
1906 Austrian
pediatrician Clemens von
Pirquet suggested
the term "Allergy".
He noticed that
some symptoms in
patients are called
influence of external
agents (later
named
allergens).
Currently under
the term allergy
understand excessive
painful
immune reaction
directed against
exogenous substances
(allergens).

Atopia (Greek: Atopia – unusual, strange, alien)

In 1923 Coca and Cook
proposed the term
"atopy".
They described
hereditary
predisposition
to the development of eczema and
allergic reaction
Type I in response to
inhalation
allergens.
Currently under
the term "atopic"
diseases" unite
allergic diseases,
flowing through
hypersensitivity
immediate type –
allergic asthma,
allergic rhinitis,
atopic dermatitis
and etc.

Sensitization (lat. sensibilis - sensitive)

Specific
sensitivity
body to allergens,
which is based on
synthesis process
allergenspecific
kih IgE
followed by them
linking with
high affinity IgE receptors in obese
cells and basophils.

Anaphylaxis

French physiologist Charles
Richet (Nobel Prize
1913): anaphylaxis –
state of sharply increased
the body's sensitivity to
getting caught again
allergen organism
(medicines, food, poisons
insects, etc.), develops
by IgE-mediated
mechanism.
(Rich and Portier
first in 1902
applied
term
"anaphylaxis"
for description
systemic
reactions to
whey
a rabbit).

Hypersensitivity

Excessive or
inadequate
manifestation of reactions
acquired
immunity.
Hypersensitivity
does not appear when
first, and when
repeated hit
antigen into the body.
After the first hit
antigens develop
immune responses,
clinical manifestations
not available yet.
If hit again
antigen occur
effector
inflammatory reactions,
appearing
clinically (inflammation).

Types of hypersensitivity according to the classification of British immunologists Robin Coombs and Philip Gell 1963

Based on all types
hypersensitivity –
different types of immune
mechanisms leading to
tissue damage
body
(pathophysiological
classification).
CLASSIFICATION OF TYPES
HYPERSENSITIVITY
COOMBS and GELLA
1963
also used in
present time

4 types of hypersensitivity according to Coombs and Gell (Coombs and Gell)

Type 1 - reagin or
acute allergic
inflammation,
hypersensitivity
immediate type (GNT).
Type 2 – antibody dependent
cellular cytotoxicity
(AZKTS).
Type 3 –
immunocomplex
inflammation (IR).
Type 4 –
hypersensitivity
slow type
(HRT).

Type 1 hypersensitivity according to Coombs and Gell (Coombs and Gell)

Type 1 - reagin or acute
allergic inflammation,
hypersensitivity
immediate type (GNT).
By the time of creation
classifications
immunoglobulin E has not yet been
open.
The answer was described as
"reaginic".
In GNT, the main role is played by
IgE synthesized against
soluble proteins
(allergens); the most
common examples
are pollen, wool
animals, pollen mites,
food products,
anthropogenic toxins.
Exposure to an allergen initiates
interaction on
membrane-bound IgE with obese
cells or basophils trigger
typical inflammatory reaction:
release of neurotransmitters
immediate response (eg
histamine)
formation of prostaglandins and
leukotrienes
synthesis of cytokines – IL-4,5,13, ​​which, in
in turn, strengthen this reaction.
Typical clinical examples GNT:
allergic rhinitis, allergic
asthma, allergic urticaria,
anaphylactic shock.

Type 2 – antibody dependent
cellular cytotoxicity
(AZKTS) result of interaction
circulating antibodies
class G with surface
antigens.
Typically target antigens are
associated with red blood cells
antibiotics (penicillin),
cellular components
(for example, Rh D antigen,
components of the basal
membranes).
Such interaction
stimulates toxic
effects using
complement or
phagocytosis.
Examples – hemolytic
anemia, some forms
glomerulonephritis,
some forms
hives,
mediated
antibody formation
against Fcέ receptors.

Type 2 hypersensitivity according to Coombs and Gell (Coombs and Gell)

Diagnosis of type 2 reactions is difficult in
in vitro conditions.
Mechanisms of tissue destruction in type 2
reactions.
Antibody binds to antigens on
cell surface (Fab fragment), and
Fc fragment is capable of:
1. Activate NKs that have F receptors. Activated NKs lyse
target cells with which it connected
antibody.
2.Fc receptors are expressed on
cells of monocyte-macrophage
row. Macrophages destroy cells
which antieles are present – ​​that is, this
–antibody dependent cytotoxicity
(different types of singing - thrombocytopenia and
hemolytic anemia).
Thrombocytopenia more often
appear in the form
purpura on the skin (feet,
distal parts
shins) and on mucous membranes
shells (often on
hard palate).
Damage
represent
petechiae - small, with
pin head, no
disappearing with
clicking on them
red spots.

Type 3 – immunocomplex
inflammation (IR).
When antibodies to
soluble antigens
immune systems are formed
complexes in certain
concentrations.
Typical antigens
are:
whey proteins
antigens of bacteria, viruses
mold antigens.
Emerging immune
complexes can act
local, or spread
with blood flow.
Effector mechanism
inflammatory response in this
case includes system activation
complement via the classical pathway with
stimulation of granulocytes,
damage to tissues and blood vessels.
Examples are serum sickness or
local Arthus reactions to
serum injection; vasculitis,
including lesions skin,
kidneys and joints (for example, related
with a chronic form of viral
hepatitis), or, for example. exogenous
allergic alveolitis (EAA),
which, depending on the antigen,
called "farmer's lung"
(molds), pigeon breeder's lung,
easy wavy lovers
parrots (AG feathers, excrement

Type 3 hypersensitivity according to Coombs and Gell (Coombs and Gell)

Type 3 – immunocomplex
inflammation (IR).
Diagnosis of type 3 reactions
difficult in conditions
vitro. Distinctive feature
this type of reaction is
deposition of complexes
antigen-antibody along
basement membranes of small
vessels - for example, in
renal glomeruli and
skin. Launch
system activation
complement and attraction
cells – neutrophils and
others to the place of deposition
immune complexes
leads to development
immunocomplex
Skin manifestations
immune complex vasculitis is
palpable purpura that is detectable
like small hemorrhagic papules,
capable of uniting and forming
zone of necrosis (Arthus reaction).
More often this type occurs within one
organ (for example, exogenous
allergic alveolitis), but may
develop and generalized response
Common triggers for this reaction:
Bacterial infection
Reaction to drugs
(penicillin and its derivatives)
Reaction to mold spores
Within a few hours after
exposure to these antigens appears
symptoms: malaise, fever, pain in

Type 4 hypersensitivity according to Coombs and Gell (Coombs and Gell)

Type 4 – hypersensitivity
delayed type (DTH).–
delayed reactions,
mediated by antigen-specific T helper 1
type and cytotoxic T lymphocytes.
Possible causative
the agents are ions
metals or others
low molecular weight substances
(food preservatives),
called haptens, which
become full-fledged
antigens after
interaction with the protein carrier.
Mycobacterial proteins
often cause a reaction
HRT.
Inflammatory
cellular infiltrate –
characteristic feature
HRT.
Examples – contact
dermatitis, local
erythematous nodules,
detected by
positive
tuberculin reaction,
sarcoidosis, leprosy.

TYPE
TYPE I
TYPE II
TYPE III
TYPE I V
hypersensitive
flatness; time
manifestations
10-30 minutes
3-8 hours
3-8 hours
24-48 hours
Immune
reaction
Ig E
antibodies;
Th 2
Ig G
Ig G
Th 1
macrophages
Th 1
CD 8+
macrophages
Antigen (AG)
Dissolve
washed
AG
AG,
Related to
cells
or
matrix
Dissolve
washed
AG
Dissolve
washed
AG
AG,
Related to
cells
Effector
ny
mechanism
Activation
obese
cells
Complement
and cells with
Fc γR
(phagocytes and
NK)
Complement
and cells with
Fc γR
(phagocytes
and NK)
Activation
macropha
gov
Cytotoxic
ness
Allergies Hemolytics
cue rhinitis;
what kind of anemia
asthma;
anaphylactic
Immunreaktionen
der Haut
this
System
red
lupus
Reaction to
tuberka
lin
Contact
dermatitis
Examples
15

Immediate hypersensitivity (IHT)

this phenomenon is used in
Mechanism for the first time
currently as
diagnostic method
described in 1921
allergies in vivo - skin
(Praunitz, Kustner):
samples.
Blood serum
Kustner, who suffered
allergy to fish, introduced
subcutaneously to Praunitz.
Then subcutaneously
antigens were injected into the same place
fish. On the skin
Praunitz appeared
blisters.

Stages of HNT

The first contact of the allergen with
mucous membrane or skin
leads to the formation of IgE.
Locally produced IgE
first sensitize only
local mast cells
then penetrate into the blood and
bind to fat receptors
cells in any part of the body.
On the receptors
mast cells
IgE can
persist
some
months (and
blood - only
2-3 days).

Stages of HNT

If hit again
allergen into the body
interacts with IgE,
associated with receptors
mast cells.
Such interaction
leads to degranulation
mast cells and triggering
pathochemical and further pathophysiological stages
allergic inflammation.
Because obese
cells
presented
everywhere in
body,
degranulation of them
may happen
in various tissues
and organs - skin,
lungs, eyes,
gastrointestinal tract and
etc.

HNT effector cells

APC (antigen
representing
cells)
T – lymphocytes –
helper type 2
B - lymphocytes
plasma cells,
synthesizing IgE
B - memory cells
Obese
cells and
basophils
Eosinophils
Neutrophils

Type of polarization of the immune response during HNT

GNT is characterized by
response polarization
along the Th2 pathway.
In microenvironment
naive T
lymphocyte
IL-4 is present,
produced by DC
and mast cells.
T naive cell
differentiates
in Th2,
synthesizing:
IL-4
IL-5
IL-10
IL-13.

GNT effector cells: Th2 lymphocytes
Analysis of cytokines in bronchoalveolar lavage fluid
patients with allergic bronchial asthma showed that T lymphocytes produce not only IL-5, but also IL-4 - that is
cytokine profile typical of Th2 cells:
IL-3
Growth of progenitor cells
GM-CSF
Myelopoiesis.
IL-4
IL-5
IL-6
IL-10
B cell growth and activation
Isotype switching to IgE.
Induction of MHC class II molecules.
Macrophage inhibition
Eosinophil growth
B – cell growth,
release of acute phase proteins
Inhibition of macrophage activity:
inhibition of Th1 cells
Th2

Stages of GNT: stage 1 - immunological

In response to a hit
allergen in the body
education occurs
allergen-specific
IgE,
IgE binds to IgE
-receptors on
fat surfaces
cells and basophils,
these cells become
sensitized.
Repeated hit
allergen leads to
its interaction with
Fab - fragment
IgE molecules, strong
bound by the F fragment to IgE –
fat receptor
cells and basophil,
begins
mast degranulation
cells and basophil.

Type I hypersensitivity

interaction of allergen with IgE R on the surface of fat
cells causes the release of inflammatory mediators
IgE binding to mast cell receptors
Mast cell
Granules with mediators

Hypersensitivity type I (HHT)

Immunological
stage
ends
degranulation
mast cells
or basophils -
begins
pathochemical
stage, since in
surrounding
space
are released
mediators
inflammation
Allergen
Obese
cell
Mediators
inflammation
Bound IgE

Mast cells and basophils

Paul Ehrlich – discovery of mast cells (P. Ehrlich 1878)

Mastzellen
Mast - “fattening”.
At first it was believed that mast cells
“feed” the cells adjacent to them.

Stages of HNT: 2. Pathochemical stage

Degranulation of obese
cells and basophils
Selection in
surrounding
space
pre-existing in
mediator granules
inflammation
De novo synthesis
mast cells and
basophils
mediators
inflammation and inflammation
chemoattractants for
eosinophils,
lymphocytes,
neutrophils

Immune mechanism of mast cell degranulation: the allergen interacts with two IgE molecules associated with IgE receptors on the surface of the mast cell

Immune mechanism mast cell degranulation:
the allergen interacts with two IgE molecules,
associated with IgE receptors on the surface of mast cells
,

Stages of HNT: 3. Pathophysiological stage

Stage
manifestations
clinical
manifestations:
mediators
inflammation
Act on
substrates,
calling
response
reactions.
Clinical manifestations,
conditional
by the action of mediators
inflammation:
itching
hyperemia
edema
skin rashes
suffocation, etc.

GNT (IgE responses) - pathophysiology

Organeffector
Syndrome
Allergens
Path
Answer
Vessels
Anafi
laxia
Medicines
Serum
Poisons
Inside
ny
Edema; increased permeability
vessels; tracheal occlusion; collapse
vessels; death
Leather
Nettle
face down
Bee stings;
allergy specialist
You
Intrako
gentle
Local increase in blood flow and
vascular permeability.
Upper
respiratory
ways
Aller
gical
rhinitis
Pollen
plants
Home
dust
Ingala
tional
Swelling and inflammation in the nasal cavity
mucous membrane
Lower
respiratory
ways
Bronchial
asthma
Pollen
plants
Home
dust
Ingala
tional
Bronchospasm
Increased mucus production
Inflammation in the bronchi
Gastrointestinal tract
Food
allergy
Products
nutrition
Oral
ny
Nausea, vomiting, enterocolitis
30 characters
allergic
urticaria, anaphylaxis

Inflammation: history

External signs
inflammation (Cornelius
Celsus):
1. rubor (redness),
2. tumor (tumor in
in this case
swelling),
3. calor (heat),
4. dolor (pain).
(Claudius Galen 130 -
200 n. e.)
5. function laesa
(dysfunction).
Manifestations of allergic
inflammation

Manifestations of allergies

Quincke's edema

Manifestations of allergic inflammation

Early response from GNT

At an early stage
GNT (10-20 minutes)
is happening
tying
allergen with
specific
IgE associated
high affinity
fat receptor
cells and
basophils.
Happening
degranulation of mast cells and
basophils.
Contents of granules –
histamine, tryptase,
heparin, and
accumulated
metabolites
arachidonic acid
launch
inflammatory response
(swelling, redness, itching).
TC start
synthesize
chemoattractants for
eosinophils,
lymphocytes, monocytes.

Late response from GNT

If exposure
allergen (receipt into
organism) continues
then after 18-20 hours at
focus of inflammation from
peripheral blood
eosinophils migrate
lymphocytes, monocytes,
neutrophils –
cellular stage
infiltration.
Eosinophils
degranulate,
release
basic cationic
proteins are gaining
active compounds
oxygen.
Inflammation
intensifies.

Figure 12-16

Early reply
Late answer
Enter
tion
AG
30 minutes
watch

Pseudoallergy - (Greek pseudēs false)

Pathological
process, according to
clinical
manifestations
similar to GNT, but
not having
immunological
stages of development.
(“false allergy”)
The final stages of true
allergies coincide with
pseudoallergy:
pathochemical stage of release (and
de novo education)
mediators;
pathophysiological
stage –
implementation of clinical
symptoms

Non-immune mechanisms of mast cell degranulation are factors leading to destabilization of the mast cell membrane and to its degranulation (medicine

Non-immune mechanisms of mast cell degranulation –
factors leading to destabilization of the mast cell membrane and its
degranulation (medicines, nutritional supplements, stabilizers, etc.)

Comparison of HNT and HRT

1. GNT: Th0 (naive) migrate to the lymph nodes, where under
the influence of IL-4, synthesized by dendritic cells,
turn into Th 2 (T helper type 2), synthesizing IL-4
and promoting the synthesis of IgE.

Delayed-type hypersensitivity (DTH) - T h1-mediated response

Immune response mediated
CD4+Th1-type, previously
sensitized
antigen.
If this happens again
the same antigen, Th1 is synthesized
cytokines responsible for
development of inflammation during
24-48 hours.
Hypreactivated
interferon-gamma
macrophages destroy
own fabrics.
Activated
interleukin 2 and interferon gamma CD8+ T lymphocytes exhibit
its cytotoxic
properties.
Histology: under conditions
inflammations form
giant cells and special
formations - granulomas.
Example: tuberculosis,
sarcoidosis, contact
dermatitis, etc.

Comparison of HNT and HRT

2. HRT: Th0 (naive) migrate to the lymph nodes, where under the influence
IL-12, synthesized by dendritic cells, is converted into Th
1 (T helper type 1), synthesizing interferon-gamma and factor
tumor necrosis-alpha

Different types of immune responses

IL-21
IL-10
IL-6
IL-21
Th fn
IL21
Immunoglobulin synthesis
Humoral or
cell type
answer

HRT - T h1 – indirect response

At the source of infection
dendritic cells
absorb the pathogen and or its
fragments and transport
AG to the regional lymph node
– in T-dependent zones.
DCs synthesize chemokines,
attractive T naive
lymphocytes in lymph nodes
In T-dependent zones of the LU
migrate Th 0 (naive).
The cultural center is presented to them
antigenic peptide in
MHC class II molecules.
Under the influence of cytokines
(IL-12, 18,23,27 and IFN-γ)
Th 0 (naive)
differentiated at Th 1
type.
Type 1 Ths enter into
interaction
macrophages carrying
on its surface
MHC II molecules with
antigenic peptides.
Th type 1 are activated and
begin to synthesize
IFN-γ and TNF-α,
activating macrophages.

HRT - T h1-mediated response

Under the influence of gamma interferon in
genes are activated in macrophages
those responsible for activation
oxidative metabolism and genes
pro-inflammatory cytokines
Macrophages generate
oxygen radicals (nitric oxide
and etc.);
synthesize cytokines (TNF-α, IL-6,
IL-1,IFN-α).
Destruction occurs
intracellular pathogens (as well as
possible destruction of own
fabrics).
For possible
localization
inflammatory
and destructive
processes in
fabrics
is happening
process
granuloma-like
vania

Granulomas

For sarcoidosis
For tuberculosis (caseous)

Review: Types of Immune Response

Properties
Cell type response
Humoral type
answer
Cellular
cytotoxicity
Inflammatory
immune response
(hypersensitive
there is a slow
type -GZT)
Localization
antigen
In the cytosol, between
organelles
In phagocytic
vacuoles
Outside the cage
agro-industrial complex
dendritic cells
macrophages
dendritic cells
dendritic cells
In lymphocytes
Imagine
tion of AG
HLA I
HLA II
HLA II

GNT and HRT

Properties
T lymphocytes
Mediators
Cell type response
Special case
humoral
immune response Cellular
Inflammatory
GNT
cytotoxicity immune response
(IgE response)
(hypersensitive
ness
slow type
–HRT)
CD8+cytotoxic CD4+ T helper cells
cues
Transition Th 0
in Th 1
IL-2, TNF-, IFN-
IFN-,TNF-,
IL-2
CD4+ T helper cells
Transition Th 0
in Th 2
IL-4, IL-5,IL-10, IL13

GNT and HRT

Properties
Cell type response
Cellular
cytotoxic
awn
Inflammatory
immune response
(hypersensitivity
delayed type - HRT)
CellsClone
Macrophages, hyper
effectors are cytotoxic
activated
CD8+ positive interferon - ,
lymphocytes
synthesized
-(CTL)
T helper type 1
Special case
humoral
immune response - GNT
(IgE response)
B lymphocytes
turn into
plasmatic
some cells,
synthesizing IgE and in
Into the cells of memory

GNT and HRT

Property
va
Cell type response
Cellular
cytotoxicity
Special case
humoral
Inflammatory
immune response
immune response
- GNT
(hypersensitivity
(IgE response)
delayed type - HRT)
Effek
CTL:
Macrophages,
Short-lived
activated
plasmatic
perforin-granzyme
mechanism of target lysis;
which cells
new IFN- , form
we are Fas-mediated
synthesize
together with Th 1 granuloma.
antibodies class
cytolysis;
Macrophages synthesize
E, which
Cytokine mechanism
pro-inflammatory
cytotoxicity (synthesis of cytokines and release binding
high-affe
TNF-α cytotoxic
factors
nym
lymphocytes-apoptosis
bactericidal
receptors
targets)
mast cells
basophils

The role of reactions
hypersensitive
flatness in the cavity
mouth increases in
dental
some orthopedics –
at
use
foreign to
body
prosthetic
materials.
The materials themselves can cause
mechanical irritation
oral mucosa and
especially mast cells, their
degranulation (pseudoallergy).
Release of histamine and
synthesis of IL-4 and IL-5 by obese
cells can contribute
development of Th 2 type immune
answer
(IgE response and GNT may develop).

Main manifestations of allergies

Skin rashes.
Rashes and inflammation
on the mucous membrane
oral cavity.
Attacks of bronchial
asthma.
Inflammation of the parotid
salivary gland
(mumps).
Dry mouth.
Burning sensation on the tongue.

Hypersensitivity reactions in prosthetic dentistry

Using
dissimilar materials
(alloys) in the oral cavity in
liquid phase (saliva) can
create galvanic
effects,
which act as
stress factors on
commensal microorganisms,
cause a decrease
protective factors
innate immunity
Reduced resistance
oral mucosa
to pathogenic bacteria
leads to their
subsequent
colonization, in response
macrophages launch
inflammatory
process.
Pro-inflammatory
cytokines - IL-1, IL-6,
IL-8 in such cases
determined in saliva.

Hypersensitivity reactions in prosthetic dentistry

Chemical substances
prosthetic materials
may be haptens.
Haptens are not themselves
antigens. Antigens
they only become
after connecting them with
proteins of the host organism.
Conversion of haptens into
antigens, often
accompanied by
development of reactions
hypersensitivity.
More often in the mouth
HRT develops
(involving Th type 1,
hyperactivated
interferon - gamma
macrophages,
synthesizing
pro-inflammatory
cytokines,
supportive
inflammation, and - how
consequence - possible
rejection of prosthetics
designs.

Hypersensitivity reactions in prosthetic dentistry

Metals in the composition
alloys (haptens)
When combined with carrier proteins, they can
cause development
reactions
hypersensitivity.
In experiments on
guinea pigs
availability shown
varying degrees
sensitization to
metals:
chrome, nickel
cause
expressed
allergic
reaction.
cobalt and gold –
moderate reaction.
titanium and silver –
weak reaction.
aluminum is practically
does not cause
sensitization.

Hypersensitivity reactions in prosthetic dentistry

Diagnostics
possible allergies
oral mucosa (HRT) by
type of contact
dermatitis to
metals are carried out
before production
prosthetic
designs with
using
PATCH tests
Patch (from the English patch -
"patch").
According to the results of PATCH tests for severity
positive reaction
metals are distributed
in the following way:
cobalt ˃ tin ˃ zinc
˃ nickel ˃ palladium

Hypersensitivity reactions in prosthetic dentistry: PATCH tests

With a special patch for
skin surface tightly
glued plate with
applied to it in
certain places 16
commercially available
metals
Applied to skin
material is held in
within 48 hours, reaction
usually assessed through
24, 48 hours and after 1
a week
after removing the adhesive
patch.
Inflammation of the skin at the site
contact with a certain
metal reveals
hypersensitivity to
specific metal.
If this metal
use this
patient, he has a large
most likely
develop contact
dermatitis (DTH).
This method is not used
only in dentistry (others
allergens are also present
in PATCH tests).

Patch tests (patch tests) are used as a diagnostic method for contact dermatitis.

Patch tests (skin patch tests) are used
How diagnostic method with contact dermatitis.

Reaction assessment: in the presence of sensitization to contact allergens, a local reaction is observed on areas of the skin in contact with them

Reaction assessment: in the presence of sensitization to contact
allergens, on areas of skin in contact with them,
local reaction of varying degrees is observed
severity (score in “crosses”)

Is it possible for such a patient to have a metal structure installed in the oral cavity with this metal?

Questions

1.
2.
3.
Define the term “hypersensitivity.”
What types of hypersensitivity do you know?
What principle underlies the classification of types
hypersensitivity.
4. Characterize HNT
5. Describe type I hypersensitivity.
6. Describe type I I I hypersensitivity.
7. Describe type IV hypersensitivity.
8. In the pathogenesis of what diseases is HRT based?
9. How does type IV hypersensitivity differ from all other types.
10. What cells are involved in type 4 hypersensitivity?

Test questions

The main types of hypersensitivity reactions according to Gell P.,
Coombs (1969), are:





Time course for the development of type I hypersensitivity reaction:
1. 10-30 minutes
2. 3-8 hours
3. 5-15 hours
4. 45-50 hours
5. 24-48 hours

Test questions

Term of development of type I hypersensitivity reaction:
1. 10-30 minutes
2. 3-8 hours
3. 5-15 hours
4. 45-50 hours
5. 24-48 hours
Duration of development of type IV hypersensitivity reaction:
1. 10-30 minutes
2. 3-8 hours
3. 5-15 hours
4. 45-50 hours
5. 24-48 hours

Test questions

The sequence of development of type I hypersensitivity reaction includes:
1. Availability genetic predisposition to the IgE response to the allergen.
2. The allergen induces the synthesis of IgE antibodies.
3. IgE antibodies are fixed on the surface receptors of mast cells and
basophils.
4. Interaction of a re-entered allergen with IgE antibodies
on the surface of mast cells and basophils leads to their degranulation.
5. Degranulation products cause a response that is inadequate
intensity.
The sequence of development of type I hypersensitivity reaction includes:
1. Immunological stage.
2. Pathochemical stage.
3. Pathophysiological stage.
4. Stage of activation of natural killer cells.
5. Stage of activation of type 1 helper T lymphocytes.

Test questions

The main effector cells of type IV hypersensitivity are:
1. Dendritic cells
2. Type 2 helper T lymphocytes
3. Type 1 helper T lymphocytes
4. Activated macrophages as effectors
5. Activated plasma cells
What types of hypersensitivity most often develop in the cavity?
mouth when using prosthetic materials?
1. Type I hypersensitivity
2. Type I hypersensitivity
3. Hypersensitivity I I I type
4. Type IV hypersensitivity
5. Type V hypersensitivity

Test questions

What methods laboratory diagnostics in vitro are used for
detection of immediate hypersensitivity reactions in
dentistry?
1. Determination of IgE antibodies to metals in the blood
2. Lymphocyte proliferative activity activation test
3. Determination of eosinophilic cationic protein in saliva
4. Determination of T-lymphocyte subpopulations
5. Determination of tryptase in saliva
Which metals used in dentistry have the most
pronounced “allergenic” properties?
1. Gold
2. Nickel
3. Cobalt
4. Aluminum
5. Titan

Lecture 17

REACTIONSHYPERSENSITIVITY

Hypersensitivity reactions can be classified based on the immunological mechanisms that cause them.

In type I hypersensitivity reactions, the immune response is accompanied by the release of vasoactive and spasmogenic substances that act on blood vessels and smooth muscles, thus disrupting their functions.

In type II hypersensitivity reactions, humoral antibodies are directly involved in cell damage, making them susceptible to phagocytosis or lysis.

In type III hypersensitivity reactions (immune complex diseases), humoral antibodies bind antigens and activate complement. Complement fractions then attract neutrophils, which cause tissue damage.

In type IV hypersensitivity reactions, tissue damage occurs, which is caused by the pathogenic effect of sensitized lymphocytes.

Type I hypersensitivity reactions - anaphylactic reactions

Type I hypersensitivity reactions can be systemic or local. A systemic reaction usually develops in response to intravenous administration an antigen to which the host is already sensitized. In this case, it often develops after a few minutes state of shock which can cause death. Local reactions depend on the place where the antigen enters and are in the nature of localized swelling of the skin ( skin allergy, urticaria), nasal and conjunctival discharge (allergic rhinitis and conjunctivitis), hay fever, bronchial asthma or allergic gastroenteritis (food allergy).

Scheme25. ReactionshypersensitivityItype- anaphylacticreactions

It is known that type I hypersensitivity reactions undergo two phases in development (Scheme 25). The first phase of the initial response is characterized by vasodilation and an increase in their permeability, as well as, depending on the location, spasm of smooth muscles or glandular secretion. These signs appear 5-30 minutes after exposure to the allergen. In many cases, the second (late) phase develops after 2-8 hours, without further

additional antigen exposure and lasts several days. This late phase of the reaction is characterized by intense infiltration of eosinophils, neutrophils, basophils and monocytes, as well as tissue destruction in the form of damage to mucosal epithelial cells.

Mast cells and basophils play main role in the development of type I hypersensitivity reactions; they are activated by cross-reacting high-affinity IgE receptors. In addition, mast cells are activated by complement components C5a and C3 (anaphylatoxins), as well as macrophage cytokines (interleukin-8), certain drugs (codeine and morphine) and physical influences (heat, cold, sunlight).

In humans, type I hypersensitivity reactions are caused by immunoglobulins of the IgE class. The allergen stimulates the production of IgE by B lymphocytes mainly in the mucous membranes at the site of antigen entry and in regional lymph nodes. IgE antibodies formed in response to an allergen attack mast cells and basophils, which have highly sensitive receptors for the Fc portion of IgE. After mast cells and basophils, attacked by cytophilic IgE antibodies, re-encounter a specific antigen, a series of reactions develops, leading to the release of a number of strong mediators responsible for the clinical manifestations of type I hypersensitivity.

First, the antigen (allergen) binds to IgE antibodies. In this case, multivalent antigens bind more than one IgE molecule and cause cross-linking of neighboring IgE antibodies. The binding of IgE molecules initiates the development of two independent processes: 1) degranulation of mast cells with the release of primary mediators; 2) de novo synthesis and release of secondary mediators, such as arachidonic acid metabolites. These mediators are directly responsible for the initial symptoms of type I hypersensitivity reactions. In addition, they include a chain of reactions that lead to the development of the second (late) phase of the initial response.

Primary mediators are contained in mast cell granules. They are divided into four categories. - Biogenic amines include histamine and adenosine. Histamine causes a pronounced spasm of the smooth muscles of the bronchi, increased vascular permeability, and intense secretion of the nasal, bronchial and gastric glands. Adenosine stimulates mast cells to release mediators that cause bronchospasm and inhibition of platelet aggregation.

- Chemotaxis mediators include eosinophilic chemotactic factor and neutrophilic chemotactic factor.

- Enzymes are contained in the granule matrix and include proteases (chymase, tryptase) and some acid hydrolases. Enzymes cause the formation of kinins and the activation of complement components (C3), affecting their precursors - Proteoglycan- heparin.

Secondary mediators include two classes of compounds; lipid mediators and cytokines. - Lipid mediators are formed due to sequential reactions occurring in the membranes of mast cells and leading to the activation of phospholipase A2. It affects membrane phospholipids, causing the appearance of arachidonic acid. Arachidonic acid, in turn, produces leukotrienes and prostaglandins.

Leukotrienes play exclusively important role in the pathogenesis of type I hypersensitivity reactions. Leukotrienes C4 and D4 are the most powerful vasoactive and spasmogenic agents known. They are several thousand times more active than histamine in increasing vascular permeability and contracting bronchial smooth muscle. Leukotriene B4 has a strong chemotactic effect on neutrophils, eosinophils and monocytes.

ProstaglandinD 2 is formed in mast cells and causes intense bronchospasm and increased mucus secretion.

Platelet activating factor(PAF) is a secondary mediator that causes platelet aggregation, histamine release, bronchospasm, increased vascular permeability and dilatation blood vessels. In addition, it has a pronounced pro-inflammatory effect. PAF has a toxic effect on neutrophils and eosinophils. In high concentrations, it activates cells involved in inflammation, causing them to aggregate and degranulate. - Cytokines play an important role in the pathogenesis of type I hypersensitivity reactions due to their ability to recruit and activate inflammatory cells. Mast cells are believed to produce a number of cytokines, including tumor necro-α factor α (TNF-α), interleukins (IL-1, IL-2, IL-3, IL-4, IL-5, IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Experimental models have shown that TNF-a is an important mediator of IgE-dependent skin reactions. TNF-α is considered a strong proinflammatory cytokine that can attract neutrophils and eosinophils, promoting their penetration through the walls of blood vessels and activating them in tissues. Finally, IL-4 is required for eosinophil recruitment. Inflammatory cells accumulating in places where a type I hypersensitivity reaction develops

pas, are an additional source of cytokines and gnetamine-releasing factors, which cause further degranulation of mast cells.

Thus, histamine and leukotrienes are rapidly released from sensitized mast cells and are responsible for immediate developing reactions characterized by swelling, mucus secretion, and smooth muscle spasm. Many other mediators are represented by leukotrienes, PAF and TNF-a. included in late phase response, recruiting an additional number of leukocytes - basophils, neutrophils and eosinophils.

Among the cells that appear in the late phase of the reaction, eosinophils are especially important. The set of mediators in them is as large as in mast cells. Thus, additionally recruited cells enhance and maintain the inflammatory response without additional antigen supply.

Regulation of hypersensitivity reactions of type I by cytokines. Firstly, IgE secreted by B lymphocytes in the presence of IL-4 plays a special role in the development of type I hypersensitivity reactions. YYA-5 and IL-6, and IL-4 is absolutely necessary for the transformation of IgE-producing B cells. The propensity of some antigens to cause allergic reactions is due in part to their ability to activate T helper 2 (Th-2) cells. On the contrary, some cytokines. formed by T helper-1 (Th-I), for example gamma interferon (INF-γ). reduce IgE synthesis. Secondly, a feature of type I sensitivity reactions is an increased content of mast cells in tissues, the growth and differentiation of which depend on certain CYTOKINES, including IL-3 and IL-4. Third, IL-5 secreted by Th-2 is critical for the formation of eosinophils from their precursors. It also activates mature eosinophils.

61 456

Types of allergic reactions (hypersensitivity reactions). Hypersensitivity of immediate and delayed type. Stages of allergic reactions. Step-by-step mechanism for the development of allergic reactions.

1. 4 types of allergic reactions (hypersensitivity reactions).

Currently, according to the mechanism of development, it is customary to distinguish 4 types of allergic reactions (hypersensitivity). All of these types of allergic reactions are generally rare in pure form, more often they coexist in various combinations or move from one type of reaction to another type.
At the same time, types I, II and III are caused by antibodies, are and belong to immediate hypersensitivity reactions (IHT). Type IV reactions are caused by sensitized T cells and belong to Delayed hypersensitivity reactions (DTH).

Note!!! is a hypersensitivity reaction triggered by immunological mechanisms. Currently, all 4 types of reactions are considered hypersensitivity reactions. However, true allergies mean only those pathological immune reactions that occur through the mechanism of atopy, i.e. according to type I, and reactions of types II, III and IV (cytotoxic, immunocomplex and cellular) types are classified as autoimmune pathology.

1. The first type (I) is atopic, anaphylactic or reagin type - caused by IgE class antibodies. When an allergen interacts with IgE fixed on the surface of mast cells, these cells are activated and the deposited and newly formed allergy mediators are released, followed by the development of an allergic reaction. Examples of such reactions are anaphylactic shock, Quincke's edema, hay fever, bronchial asthma, etc.
2. The second type (II) is cytotoxic. In this type, the body’s own cells become allergens, the membrane of which has acquired the properties of autoallergens. This occurs mainly when they are damaged as a result of exposure to drugs, bacterial enzymes or viruses, as a result of which the cells change and are perceived by the immune system as antigens. In any case, for this type of allergy to occur, antigenic structures must acquire the properties of autoantigens. The cytotoxic type is caused by IgG or IgM, which are directed against Ags located on modified cells of the body’s own tissues. The binding of Ab to Ag on the cell surface leads to the activation of complement, which causes damage and destruction of cells, subsequent phagocytosis and their removal. The process also involves leukocytes and cytotoxic T- lymphocytes. By binding to IgG, they participate in the formation of antibody-dependent cellular cytotoxicity. It is the cytotoxic type that causes the development of autoimmune hemolytic anemia, drug allergies, autoimmune thyroiditis.
3. The third type (III) is immunocomplex, in which body tissues are damaged by circulating immune complexes involving IgG or IgM, which have a large molecular weight. That. in type III, as well as in type II, reactions are caused by IgG and IgM. But unlike type II, in a type III allergic reaction, antibodies interact with soluble antigens, and not with those located on the surface of cells. The resulting immune complexes circulate in the body for a long time and are fixed in the capillaries of various tissues, where they activate the complement system, causing an influx of leukocytes, the release of histamine, serotonin, lysosomal enzymes that damage the vascular endothelium and tissues in which the immune complex is fixed. This type of reaction is the main one in serum sickness, drug and food allergies, and in some autoallergic diseases (SLE, rheumatoid arthritis and etc).
4. The fourth (IV) type of reaction is delayed-type hypersensitivity or cell-mediated hypersensitivity. Delayed reactions develop in a sensitized organism 24-48 hours after contact with the allergen. In type IV reactions, the role of antibodies is performed by sensitized T- lymphocytes. Ag, in contact with Ag-specific receptors on T cells, leads to an increase in the number of this population of lymphocytes and their activation with the release of mediators cellular immunity- inflammatory cytokines. Cytokines cause the accumulation of macrophages and other lymphocytes, involving them in the process of destruction of antigens, resulting in inflammation. Clinically, this is manifested by the development of hyperergic inflammation: a cellular infiltrate is formed, cellular basis which consists of mononuclear cells - lymphocytes and monocytes. The cellular type of reaction underlies the development of viral and bacterial infections (contact dermatitis, tuberculosis, mycoses, syphilis, leprosy, brucellosis), some forms of infectious-allergic bronchial asthma, transplant rejection reactions and antitumor immunity.

Reaction type		Development mechanism		Clinical manifestations
Type I Reagin reactions		Develops as a result of the binding of an allergen to IgE fixed on mast cells, which leads to the release of allergy mediators from the cells, which cause clinical manifestations		Anaphylactic shock, Quincke's edema, atopic bronchial asthma, hay fever, conjunctivitis, urticaria, atopic dermatitis, etc.
Type II Cytotoxic reactions		Caused by IgG or IgM, which are directed against Ag located on the cells of their own tissues. Complement is activated, which causes cytolysis of target cells		Autoimmune hemolytic anemia, thrombocytopenia, autoimmune thyroiditis, drug-induced agranulocytosis, etc.
Type III Immune complex-mediated reactions		Circulating immune complexes with IgG or IgM are fixed to the capillary wall, activate the complement system, tissue infiltration by leukocytes, their activation and production of cytotoxic and inflammatory factors (histamine, lysosomal enzymes, etc.), damaging the vascular endothelium and tissue.		Serum sickness, drug and food allergies, SLE, rheumatoid arthritis, allergic alveolitis, necrotizing vasculitis, etc.
Type IV Cell-mediated reactions		Sensitized T- lymphocytes, in contact with Ag, produce inflammatory cytokines that activate macrophages, monocytes, lymphocytes and damage surrounding tissues, forming a cellular infiltrate.		Contact dermatitis, tuberculosis, mycoses, syphilis, leprosy, brucellosis, transplant rejection reactions and antitumor immunity.

2. Hypersensitivity of immediate and delayed type.

What is the fundamental difference between all these 4 types of allergic reactions?
And the difference is in what type of immunity, humoral or cellular, these reactions are caused. Depending on this they distinguish:

3. Stages of allergic reactions.

In most patients, allergic manifestations are caused by IgE-class antibodies, therefore we will consider the mechanism of allergy development using the example of type I allergic reactions (atopy). There are three stages in their course:

• Immunological stage– includes changes in the immune system that occur upon first contact of the allergen with the body and the formation of corresponding antibodies, i.e. sensitization. If by the time At is formed the allergen is removed from the body, no allergic manifestations occur. If the allergen is re-entered or continues to be in the body, an “allergen-antibody” complex is formed.
• Pathochemical– release of biologically active allergy mediators.
• Pathophysiological– stage of clinical manifestations.

This division into stages is quite arbitrary. However, if you imagine Allergy development process step by step, it will look like this:

1. First contact with an allergen
2. IgE formation
3. Fixation of IgE on the surface of mast cells
4. Sensitization of the body
5. Repeated contact with the same allergen and formation of immune complexes on the mast cell membrane
6. Release of mediators from mast cells
7. The effect of mediators on organs and tissues
8. Allergic reaction.

Thus, the immunological stage includes points 1 - 5, pathochemical - point 6, pathophysiological - points 7 and 8.

4. Step-by-step mechanism for the development of allergic reactions.

1. First contact with an allergen.
2. Ig E formation.
   At this stage of development, allergic reactions resemble a normal immune response, and are also accompanied by the production and accumulation of specific antibodies that can combine only with the allergen that caused their formation.
   But in the case of atopy, it is the formation of IgE in response to the incoming allergen, and in increased quantities in relation to the other 5 classes of immunoglobulins, which is why it is also called Ig-E dependent allergy. IgE is produced locally, mainly in the submucosa of tissues in contact with external environment: V respiratory tract, skin, gastrointestinal tract.
3. Fixation of IgE to the mast cell membrane.
   If all other classes of immunoglobulins, after their formation, circulate freely in the blood, then IgE has the property of immediately attaching to the mast cell membrane. Mast cells are connective tissue immune cells that are found in all tissues in contact with the external environment: tissues of the respiratory tract, gastrointestinal tract, and connective tissues surrounding blood vessels. These cells contain such biological active substances like histamine, serotonin, etc., and are called mediators of allergic reactions. They have pronounced activity and have a number of effects on tissues and organs, causing allergic symptoms.
4. Sensitization of the body.
   For the development of allergies, one condition is required - preliminary sensitization of the body, i.e. emergence hypersensitivity to foreign substances - allergens. Hypersensitivity to a given substance develops upon first encounter with it.
   The time from the first contact with an allergen to the onset of hypersensitivity to it is called the period of sensitization. It can range from a few days to several months or even years. This is the period during which IgE accumulates in the body, fixed to the membrane of basophils and mast cells.
   A sensitized organism is one that contains a reserve of antibodies or T cells (in the case of HRT) that are sensitized to that particular antigen.
   Sensitization is never accompanied by clinical manifestations of allergy, since only Ab accumulates during this period. Immune complexes Ag + Ab have not yet formed. Not single Abs, but only immune complexes are capable of damaging tissue and causing allergies.
5. Repeated contact with the same allergen and the formation of immune complexes on the mast cell membrane.
   Allergic reactions occur only when the sensitized organism encounters a given allergen again. The allergen binds to ready-made Abs on the surface of mast cells and the formation of immune complexes: allergen + Ab.
6. Release of allergy mediators from mast cells.
   Immune complexes damage the membrane of mast cells, and from them allergy mediators enter the intercellular environment. Tissues rich in mast cells (skin vessels, serous membranes, connective tissue etc.) are damaged by released mediators.
   With prolonged exposure to allergens, the immune system uses additional cells to ward off invading antigens. Another row is formed chemical substances– mediators, which causes further discomfort for allergy sufferers and increases the severity of symptoms. At the same time, the mechanisms of inactivation of allergy mediators are inhibited.
7. The action of mediators on organs and tissues.
   The action of mediators determines the clinical manifestations of allergies. Systemic effects develop - dilation of blood vessels and increased permeability, mucous secretion, nervous stimulation, smooth muscle spasms.
8. Clinical manifestations of an allergic reaction.
   Depending on the organism, the type of allergens, the route of entry, the place where the allergic process occurs, the effects of one or another allergy mediator, symptoms can be system-wide (classical anaphylaxis) or localized in individual systems of the body (asthma - in the respiratory tract, eczema - in the skin ).
   Itching, runny nose, lacrimation, swelling, shortness of breath, drop in pressure, etc. occur. And the corresponding picture of allergic rhinitis, conjunctivitis, dermatitis, bronchial asthma or anaphylaxis develops.

In contrast to immediate hypersensitivity described above, delayed hypersensitivity is caused by sensitized T cells rather than antibodies. And it destroys those cells of the body on which the immune complex Ag + sensitized T-lymphocyte has been fixed.

Abbreviations in the text.

• Antigens – Ag;
• Antibodies – Ab;
• Antibodies = same as immunoglobulins(At=Ig).
• Delayed hypersensitivity - HRT
• Immediate hypersensitivity - IHT
• Immunoglobulin A - IgA
• Immunoglobulin G - IgG
• Immunoglobulin M - IgM
• Immunoglobulin E - IgE.
• Immunoglobulins- Ig;
• Antigen-antibody reaction – Ag + Ab

REACTIONSHYPERSENSITIVITY
Hypersensitivity reactions can be classified based on the immunological mechanisms that cause them.
In type I hypersensitivity reactions, the immune response is accompanied by the release of vasoactive and spasmogenic substances that act on blood vessels and smooth muscles, thus disrupting their functions.
In type II hypersensitivity reactions, humoral antibodies are directly involved in cell damage, making them susceptible to phagocytosis or lysis.
In type III hypersensitivity reactions (immune complex diseases), humoral antibodies bind antigens and activate complement. Complement fractions then attract neutrophils, which cause tissue damage.
In type IV hypersensitivity reactions, tissue damage occurs, which is caused by the pathogenic effect of sensitized lymphocytes.
REACTIONSHYPERSENSITIVITYITYPE - ANAPHYLACTICREACTIONS
Type I hypersensitivity reactions can be systemic or local. A systemic reaction usually develops in response to intravenous administration of an antigen to which the host is already sensitized. In this case, a state of shock often develops after a few minutes, which can cause death. Local reactions depend on the site where the antigen enters and are in the nature of localized swelling of the skin (skin allergies, urticaria), discharge from the nose and conjunctiva (allergic rhinitis and conjunctivitis), hay fever, bronchial asthma or allergic gastroenteritis (food allergies).
Scheme 25. ReactionshypersensitivityItype- anaphylacticreactions

It is known that type I hypersensitivity reactions undergo two phases in development (Scheme 25). The first phase of the initial response is characterized by vasodilation and an increase in their permeability, as well as, depending on the location, spasm of smooth muscles or glandular secretion. These signs appear 5-30 minutes after exposure to the allergen. In many cases, the second (late) phase develops after 2-8 hours, without additional antigen exposure, and lasts several days. This late phase of the reaction is characterized by intense infiltration of eosinophils, neutrophils, basophils and monocytes, as well as tissue destruction in the form of damage to mucosal epithelial cells.
Mast cells and basophils play a major role in the development of type I hypersensitivity reactions; they are activated by cross-reacting high-affinity IgE receptors. In addition, mast cells are activated by complement components C5a and C3a (anaphylatoxins), as well as macrophage cytokines (interleukin-8), certain drugs (codeine and morphine) and physical influences(heat, cold, sunlight).
In humans, type I hypersensitivity reactions are caused by immunoglobulins of the IgE class. The allergen stimulates the production of IgE by B lymphocytes mainly in the mucous membranes at the site of antigen entry and in regional lymph nodes. IgE antibodies formed in response to an allergen attack mast cells and basophils, which have highly sensitive receptors for the Fc portion of IgE. After mast cells and basophils, attacked by cytophilic IgE antibodies, re-encounter a specific antigen, a series of reactions develops, leading to the release of a number of strong mediators responsible for the clinical manifestations of type I hypersensitivity.
First, the antigen (allergen) binds to IgE antibodies. In this case, multivalent antigens bind more than one IgE molecule and cause cross-linking of neighboring IgE antibodies. The binding of IgE molecules initiates the development of two independent processes: 1) degranulation of mast cells with the release of primary mediators; 2) de novo synthesis and release of secondary mediators, such as arachidonic acid metabolites. These mediators are directly responsible for the initial symptoms of type I hypersensitivity reactions. In addition, they include a chain of reactions that lead to the development of the second (late) phase of the initial response.
Primary mediators are contained in mast cell granules. They are divided into four categories.
▲ Biogenic amines include histamine and adenosine. Histamine causes a pronounced spasm of the smooth muscles of the bronchi, increased vascular permeability, and intense secretion of the nasal, bronchial and gastric glands. Adenosine stimulates mast cells to release mediators that cause bronchospasm and inhibition of platelet aggregation.
▲ Chemotaxis mediators include eosinophil chemotactic factor and neutrophil chemotactic factor.
▲ enzymes are contained in the granule matrix and include prostheses (chymase, tryptase) and some acid hydrolases. Enzymes cause the formation of kinins and the activation of complement components (C3), affecting their precursors.
▲ Proteoglycan- heparin.
Secondary mediators include two classes of compounds: lipid mediators and cytokines.
▲ Lipid mediators are formed due to sequential reactions occurring in the membranes of mast cells and leading to the activation of phospholipase A2. It affects membrane phospholipids, causing the appearance of arachidonic acid. Arachidonic acid in turn produces leukotrienes and prostaglandins.
Leukotrienes play an extremely important role in the pathogenesis of type I hypersensitivity reactions. Leukotrienes C4 and D4 are the most powerful vasoactive and spasmogenic agents known. They are several thousand times more active than histamine in increasing vascular permeability and contracting bronchial smooth muscle. Leukotriene B4 has a strong chemotactic effect on neutrophils, eosinophils and monocytes.
ProstaglandinD 2 is formed in mast cells and causes intense bronchospasm and increased mucus secretion.
Platelet activating factor(PAF) is a secondary mediator that causes platelet aggregation, histamine release, bronchospasm, increased vascular permeability and dilation of blood vessels. In addition, it has a pronounced pro-inflammatory effect. PAF has a toxic effect on neutrophils and eosinophils. In high concentrations, it activates cells involved in inflammation, causing them to aggregate and degranulate.
▲ Cytokines play an important role in the pathogenesis of type I hypersensitivity reactions due to their ability to recruit and activate inflammatory cells. Mast cells are believed to produce a number of cytokines, including tumor necrosis factor a (TNF-a), interleukins (IL-1, IL-2, IL-3, IL-4, IL-5, IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Experimental models have shown that TNF-α is an important mediator of IgE-dependent skin reactions. TNF-α is considered a strong proinflammatory cytokine that can attract neutrophils and eosinophils, promoting their penetration through the walls of blood vessels and activating them in tissues. Finally, IL-4 is required for eosinophil recruitment. Inflammatory cells that accumulate at sites of type I hypersensitivity reactions are an additional source of cytokines and histamine-releasing factors that cause further degranulation of mast cells.
Thus, histamine and leukotrienes are rapidly released from sensitized mast cells and are responsible for the immediately developing reactions characterized by edema, mucus secretion, and smooth muscle spasm. Many other mediators, represented by leukotrienes, PAF and TNF-a, are included in the late phase of the response, recruiting additional numbers of leukocytes - basophils, neutrophils and eosinophils.
Among the cells that appear in the late phase of the reaction, eosinophils are especially important. The set of mediators in them is as large as in mast cells. Thus, additionally recruited cells enhance and maintain the inflammatory response without additional antigen supply.
Regulation of hypersensitivity reactionsItypecytokines. Firstly, IgE secreted by B lymphocytes in the presence of IL-4, IL-5 and IL-6 plays a special role in the development of type I hypersensitivity reactions, and IL-4 is absolutely necessary for the transformation of IgE-producing B cells. The propensity of some antigens to cause allergic reactions is due in part to their ability to activate T helper 2 (Th-2) cells. On the contrary, some cytokines produced by T helper 1 (Th-1) cells, such as interferon gamma (INF-γ), reduce IgE synthesis. Secondly, a feature of type I hypersensitivity reactions is an increased content of mast cells in tissues, the growth and differentiation of which depend on certain cytokines, including IL-3 and IL-4. Third, IL-5 secreted by Th-2 is critical for the formation of eosinophils from their precursors. It also activates mature eosinophils.
SystemAndlocalanaphylaxis
Systemic anaphylaxis occurs after the administration of heterologous proteins, such as antisera, hormones, enzymes, polysaccharides and medicinal substances. The severity of the disease depends on the level of sensitization. The shock dose of antigen, however, can be extremely small. For example, for skin testing various forms Allergies require a minimal amount of antigen. A few minutes after exposure, itching, urticaria and skin erythema appear, then after a short time a spasm of the respiratory bronchioles develops and respiratory distress appears. Vomiting, abdominal cramps, diarrhea and laryngeal obstruction can result in shock and death of the patient. At autopsy, in some cases, swelling and hemorrhage are found in the lungs, while in others, acute pulmonary emphysema with dilatation of the right ventricle of the heart.
Local anaphylaxis called atopic allergy. About 10 % population suffers from local anaphylaxis, which occurs in response to allergens entering the body: plant pollen, animal dander, house dust and so on. Diseases that cause local anaphylaxis include urticaria, angioedema, allergic rhinitis (hay fever) and some forms of asthma. There is a family predisposition to this type of allergy.
REACTIONSHYPERSENSITIVITYIITYPE - CYTOTOXICREACTIONS
In type II hypersensitivity reactions, antibodies appear in the body that are directed against antigens located on the surface of cells or other tissue components. Antigenic determinants can be associated with the cell membrane or represent an exogenous antigen adsorbed on the surface of cells. In any case, a hypersensitivity reaction occurs as a consequence of the binding of antibodies to normal or damaged antigens on the cell surface. Three antibody-dependent mechanisms for the development of this type of reaction have been described.
Complement-dependent reactions(Diagram 26). There are two mechanisms by which antibody and complement can cause type II hypersensitivity reactions: direct lysis and opsonization. In the first case, an antibody (IgM or IgG) reacts with an antigen on the cell surface, causing activation of the complement system and activating the membrane attack complex, which disrupts the integrity of the membrane, “perforating” the lipid layer. In the second case, cells are sensitized to phagocytosis by fixing an antibody or a C3b complement fragment to the cell surface (opsonization). This type II hypersensitivity reaction most often affects blood cells (red blood cells, white blood cells and platelets), but antibodies can also be directed against extracellular structures, such as the glomerular basement membrane.
Clinically, such reactions occur in the following cases:
▲ during transfusion of incompatible blood, when donor cells react with host antibodies;
▲ with erythroblastosis of the fetus, when there are antigenic differences between the mother and the fetus, and antibodies (IgG) of the mother, penetrating the placenta, cause the destruction of the fetal red blood cells;
Scheme 26. ReactionhypersensitivityIItype- complement dependentreactions


▲ with autoimmune hemolytic anemia, agranulocytosis and thrombocytopenia, when antibodies are formed against one’s own blood cells, which are then destroyed;
▲ in some reactions to drugs, the resulting antibodies react with the drugs, forming complexes with the erythrocyte antigen.
Antibody dependent cell-associated cytotoxicity(Scheme 27) is not accompanied by complement fixation, but causes cooperation of leukocytes. Target cells coated with low concentrations of IgG antibodies are killed by unsensitized cells that possess Fc receptors. Non-sensitized cells bind target cells with receptors for the Fc fragment of IgG, and cell lysis occurs without phagocytosis. This type of cytotoxicity involves monocytes, neutrophils, eosinophils and natural killer (NK) cells. Although in most cases this type of reaction involves IgG antibodies; sometimes (eg, eosinophil-associated cytotoxicity against parasites) IgE antibodies are involved. This type of cytotoxicity is also important in transplant rejection.
Scheme 27. ReactionhypersensitivityIItype- antibody dependentrelatedWithcellscytotoxicity


Antibody-mediated cellular dysfunction. In some cases, antibodies directed against receptors on the surface of cells disrupt their functioning without causing cell damage or inflammation. For example, in myasthenia gravis, antibodies react with acetylcholine receptors in the motor end plates skeletal muscles, disrupting neuromuscular transmission and thus causing muscle weakness. On the contrary, with antibody-mediated stimulation of cell functions, Graves' disease develops. In this disease, antibodies against receptors thyroid-stimulating hormone on epithelial cells thyroid cells are stimulated, leading to hyperthyroidism. The same mechanism underlies the inactivation and neutralization reactions.
REACTIONSHYPERSENSITIVITYIIITYPE - IMMUNOCOMPLEXREACTIONS
The development of type III hypersensitivity reactions is caused by antigen-antibody complexes, which damage tissue due to their ability to activate various blood serum mediators, mainly the complement system (Scheme 28). A toxic reaction occurs when an antigen binds to an antibody either in the bloodstream (circulating immune complexes) or outside the blood vessels where the antigen can be deposited (in situ immune complexes). Certain forms of glomerulonephritis, in which immune complexes are formed in situ, begin with the implantation of antigen into the glomerular basement membrane. Complexes formed in the bloodstream cause damage when they enter the walls of blood vessels or settle in filtering structures such as the glomerular filtration. The formation of antigen-antibody complexes does not mean disease, since they occur in many immune processes and may represent a normal mechanism for antigen elimination.

There are delayed and immediate hypersensitivity. Regardless of the characteristics of the manifestations, each of them can lead to certain consequences. For example, cause anaphylaxis or dermatitis. Sensitivity has several types, which arise due to various diseases.

What is hypersensitivity?

Hypersensitivity - increased reaction immune system for any substance. It is one of the types of allergies. Occurs at any age.

Types of hypersensitivity:

1. First type. This includes an immediate reaction. It appears immediately after contact with an allergen irritant. The manifestation depends on the functionality of the cells that are responsible for the antigen. Including histamine. A popular immediate allergic reaction to bee venom. Diseases such as asthma, psoriasis, urticaria, eczema, occur more often with HT.
2. Second type. This reaction most often occurs due to blood group incompatibility during transfusion. The reason for its appearance is the connection of antibodies with antigens on the surface of cells. In this regard, phagocytosis occurs.
3. Third type. Most often occurs with serum sickness. In this case, disturbances appear in the immune system and the number of antigens and antibodies increases. Then the immune cells cannot independently cope with foreign bodies in the blood. If such complexes are chronic, then the person suffers from skin bacteria such as staphylococcus and streptococcus. Malaria and hepatitis (in this case B) are rare. Type 3 hypersensitivity is accompanied by neurological changes. Occurs after the use of serum for tetanus and serum sickness.
4. Type 4 (delayed hypersensitivity). Its appearance is provoked by various viruses, bacteria, and fungi that penetrate the body. Often occurs when infected with helminths. There are many in the blood inflammatory reactions, especially with the participation of T lymphocytes. These cells react negatively to the introduction of the tuberculosis vaccine (tuberculin component). arise unwanted reactions on the skin. Thus, there is a response to the penetration of foreign cells.

It is worth noting that each person experiences hypersensitivity individually. In all people, the immune system overreacts to foreign allergen cells that enter the body repeatedly and initially. This is where the term “hypersensitive” comes from.

Immediate hypersensitivity

Allergic reactions of the immediate type are quite common.

These include:

• Quincke's edema;
• bronchial asthma;
• seasonal allergies, which are accompanied by rhinitis and itching;
• almost all types of urticaria and rarely drug allergies.

Immediate hypersensitivity occurs when you first encounter an allergen. If a person experiences an allergic reaction for the first time. For example, an allergy to medicine or pollen. Antibodies focus on a specific irritant. In order for them to fully perform their function, the consent of macrophages is necessary.

Hypersensitivity reactions come in varying degrees of complexity: early and late. The immediate response depends on mast cells and basophils. After this, the participation of eosinophils begins. Initially, allergies may be characterized by a slight increase in these cells. When an allergic reaction is active, the number of eosinophils increases rapidly.

The appearance of a hypersensitivity reaction of the immune system leads to increased vascular permeability. This causes damage to the kidneys, lungs, and skin. The risk of developing vasculitis increases.

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Delayed hypersensitivity

Delayed allergic reaction – occurs due to macrophages and Th1 lymphocytes. Stimulation depends on them immune cells. This is type 4 hypersensitivity. It appears within 24-72 hours after the irritant allergen enters the body. A slow reaction provokes inflammation and tissue hardening.

There are certain forms of such a reaction. Their characteristics:

1. Contact - manifests itself within a period of up to 72 hours. Provoked by lymphocytes. In the form of a disease, the delayed type is defined as eczema and edema.
2. Tuberculin HRT occurs in the form of local reactions on the skin.
3. Granulomatous is characterized by fibrosis. Develops over 20-28 days. Epithelioid and giant cells and macrophages participate in this process. Lead to thickening of the skin.

Diseases such as tuberculosis and toxoplasmosis are infectious. A delayed hypersensitivity reaction provokes their development. In progress diagnostic studies perform subcutaneous allergy tests. The causative allergen is introduced and the reaction is observed. Use tuberculin, tularin, brucellin.

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Hypersensitivity in the human body

Hypersensitivity reactions may manifest as dysfunction of certain organs. Most often found:

• dental hypersensitivity (hyperesthesia);
• sensitivity of the glans penis;
• excessive sensitivity of the skin.

Hypersensitivity may manifest itself in a certain type and have varying degrees difficulties.

Tooth hypersensitivity

Hypersensitivity of teeth. In medicine, this type of reaction is called hyperesthesia. Easily identified by characteristic symptoms: severe pain that passes quickly. They arise due to contact of the enamel with various irritants: oral care products, toothbrushes. Pain may occur for the following reasons:

• due to cold and hot food and drinks;
• eating sweets;
• sour fruits.

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Hyperesthesia has stages of development:

• 1 – slight sensitivity that is not accompanied by pain,
• 2 – severe pain upon contact with irritants.

In the presence of last stage a person may suffer pain even when breathing cool air. Hyperesthesia belongs to the list of immediate allergic reactions. This type of reaction is encountered in at different ages. Most often it appears after 25 years. This type of hypersensitivity is constantly present. By using medicines you can achieve good results. Don't forget about quality hygiene oral cavity. In this case, it is necessary to use products for hypersensitive teeth.

Sensitivity of the glans penis

Hypersensitivity of the glans penis is familiar to many men. With this reaction comes discomfort, mainly in the intimate area. Therefore, a man has problems satisfying a woman. The type of temperament of such people is very characteristic. They are irritable, unconfident, and overly emotional. It is worth noting that hypersensitivity of the head is formed at the genetic level. If it occurs throughout life, then it is enough to limit contact with irritants. It is important to distinguish the types of hypersensitivity from premature erection and severe arousal. Condoms reduce sensitivity of the head and prolong sexual intercourse. If you constantly use lubricant, you can significantly reduce hypersensitivity.

Skin hypersensitivity. Accompanied by a strong skin reaction to various allergens. This is a pathology of the skin that provokes disorders of the central nervous system. Skin hypersensitivity reactions can manifest in different ways:

• 1 – locally;
• 2 – all over the skin.

May contribute to skin hypersensitivity the following factors and diseases:

• wounds;
• infectious skin lesions;
• burns.

Diseases such as atopic dermatitis, eczema, and neuritis provoke the development of sensitivity. They have a bad effect on the type of temperament, as a person experiences irritation and suffers from insomnia. Diseases such as tumors, meningitis, encephalitis, sclerosis indicate serious disorders of the nervous system. Because of this, a central form of hypersensitivity occurs.

There are certain types of hypersensitivity:

1. Thermal.
2. Polyesthesia.
3. Hyperplasia.
4. Paresthesia.

Type 1 occurs due to cold and thermal influences. Accompanied by strong painful sensations. Polyesthesia is easily recognized by a characteristic tingling sensation in the affected area. The patient feels that there are “goosebumps” in this place. Hyperplasia is determined severe pain at the slightest touch to the affected area. Type 4 has less strong reactions. Ischemia of the limbs may be accompanied by slight numbness. Allergic reactions of a delayed type in each patient have different symptoms and degree of difficulty. Treatment is mainly aimed at eliminating the irritant. To do this, you need to see a doctor and undergo comprehensive examination. Allergic reactions, immediate or delayed, require traditional treatment.

Delayed allergic reactions are treatable. In this case, damage to the immune system is important. To do this, it is necessary to release cells that affect changes in the functionality of tissues and all organs. Mostly, immediate type allergies manifest themselves in the form of urticaria, asthma, and Quincke's edema. Refers to type 1 hypersensitivity and requires timely treatment. The following medications are used for this:

• antihistamines, antiallergic;
• medications to suppress immunological reactions;
• medications that prevent allergy mediators from being released;
• glucocorticosteroids.

Delayed allergic reactions are treated with the following medications:

• immune suppressants;
• drugs for the treatment of systematic connective tissue diseases.

Delayed type allergies develop due to disturbances in cellular and immune function. It also depends on T-lymphocytes. A delayed reaction is also called the 4th type of hypersensitivity. Most often manifests itself in the form of autoallergic diseases, such as negative reaction to the transplant.

In such cases, the following drugs are prescribed:

• glucocorticosteroids;
• collagens;
• anti-inflammatory;
• antilymphocyte serums.

With this treatment, tissue damage is reduced and the response of immune system cells is inhibited. A delayed reaction can only be treated with such drugs. Correct dosage Your doctor will help you determine.

People who suffer from any type of hypersensitivity must follow certain hygiene rules. Cannot be used synthetic fabrics, low-quality cosmetics, detergents, perfumes, shampoos.

All cosmetic substances must be of high quality and marked “for hypersensitive skin”. If you have hyperesthesia, be sure to use a very soft toothbrush. It is usually recommended by dentists after an examination. This event will reduce sensitivity and prevent its occurrence in the future.