This document outlines a plan to cover various topics related to allergy, including: 1) Definitions of allergy, allergens, and classifications of allergic reactions. 2) Pathogenesis and mechanisms of different types of allergic reactions, including immediate and delayed reactions, as well as Type I-IV reactions mediated by different immune effector cells and pathways. 3) Concepts of sensitization, pathophysiological stages of allergy from immunological to clinical symptoms, and examples of pseudo-allergic reactions. The document provides an overview of key concepts and classifications to guide a discussion of the immune mechanisms and presentations of different allergic diseases.

1. Allergy
The plan
1. Allergy, definition, etiology. Exo- and
endogenous allergens, their
characteristic.
2. Classification of allergic reactions.
3. Pathogenesis of allergic reactions.
Sensitization, concept, types,
pathogenesis.
4. Allergic reactions of reagenic type,
etiology, pathogenesis.

2. 6. Allergic reactions of cytotoxic type,
etiology, pathogenesis.
7. Allergic reactions of immune
complex mediated type, etiology,
pathogenesis.
8. Allergic reactions of cellular -
mediated type, etiology,
pathogenesis.
9. Hyposensitization, types,
pathogenesis.
10.Pseudo-allergic reactions, concept,
pathogenesis.
Pictures are from Robbins Pathologic basis of disease. V. Kumar, A.K.
Abbas, S.N. Fausto, 7th , 8th edition, 2007, 2010; prof. O.I. Urasova’s
lectures and internet resources

4. Органы иммунной системы
Центральные органы
лимфопоэза
ТИМУС КОСТНЫЙ МОЗГ
КРОВЬ
ЛИМФА
ТКАНИ
лимфоидные
ЛИМФОУЗЛЫ
СЕЛЕЗЕНКА
Периферические органы лимфопоэза

5. NAIVE (immunologically inexperienced)
lymphocytes - are mature lymphocytes that have
not encountered the antigen for which they are
specific.
EFFECTOR CELLS differentiated lymphocytes
after activation by antigens, perform the function of
eliminating microbes
MEMORY CELLS which live in a state of
heightened awareness and are better able to
combat the microbe in case it returns.

6. T- (thymus-derived)
lymphocytes – 60% of
blood lymphocytes
CD4 and CD8 serve as
“coreceptors” in T-cell
activation
CD4 is expressed on
approximately 60% of
mature CD3+ T cells,
which function as
cytokine-secreting helper
cells that help
macrophages and B
lymphocytes to combat
infections
CD8 is expressed on about
30% of T cells, which
function as cytotoxic
(killer) T lymphocytes
(CTLs) to destroy host
cells harboring microbes.

7. The B-cell receptor complex is composed of membrane
immunoglobulin M (IgM; or IgD, not shown), which
recognize antigens, and the associated signaling proteins
Igα and Igβ. CD21 is a receptor for a complement
component that also promotes B-cell activation
B - (bone-marrow-
derived)
lymphocytes

8. FIGURE 6-1 The principal classes of lymphocytes and their functions in
adaptive immunity.

9. Dendritic cells.
A, Cultured dendritic
cells showing the
prominent surface
projections.
B, The location of
dendritic cells
(Langerhans cells) in the
epidermis (stained blue
using an
immunohistochemical
method).
(Courtesy of Dr. Y-J. Liu,
M.D. Anderson Cancer
Center, Houston, TX.)

10. Macrophages
.
Process the antigens and present peptide fragments
to T cells. Thus, macrophages function as APCs in
T-cell activation
Are key effector cells in certain forms of cell-
mediated immunity, the reaction that serves to
eliminate intracellular microbes. In this type of
response, T cells activate macrophages and
enhance their ability to kill ingested microbes.
Participate in the effector phase of humoral
immunity, efficiently phagocytose and destroy
microbes that are opsonized (coated) by IgG or C3b.

11. NK cells kill a variety
of infected and tumor
cells, without prior
exposure to or
activation by these
microbes or tumors.

12. Migration of naive and effector T lymphocytes.
Naive T lymphocytes home to lymph nodes via high endothelial venules
(HEVs). Activated T lymphocytes, including effector and memory cells, home
to sites of infection in peripheral tissues, and this migration is mediated by E-
selectin and P-selectin, integrins, and chemokines secreted at inflammatory
sites that are recognized by chemokine receptors that are expressed on
activated T cells.
APC, antigen-presenting cell; ICAM-1, intercellular adhesion molecule 1;
VCAM-1, vascular cell adhesion molecule 1.

13. Antigen processing and display
by MHC molecules.
A, In the class I MHC pathway,
peptides are produced from
proteins in the cytosol and
transported to the endoplasmic
reticulum (ER), where they bind
to class I MHC molecules. The
peptide-MHC complexes are
transported to the cell surface
and displayed for recognition by
CD8+ T cells.
B, In the class II MHC pathway,
proteins are ingested into
vesicles and degraded into
peptides, which bind to class II
MHC molecules being
transported in the same vesicles.
The class II–peptide complexes
are expressed on the cell surface
and recognized by CD4+ T cells.

15. Humoral immunity. Naive B lymphocytes recognize antigens, and under the
influence of TH cells and other stimuli, the B cells are activated to proliferate and
to differentiate into antibody-secreting plasma cells. Some of the activated B cells
undergo heavy-chain class switching and affinity maturation, and some become
long-lived memory cells. Antibodies of different heavy-chain classes (isotypes)
perform different effector functions, shown on the right.

17. ALLERGY
is immune response accompanied
by damage to the tissues of the body (V.I.Pytsky)
The causes of allergy
are allergens
Classification of
allergens
(by A.D.Ado)
Exoallergens:
Household
Dust mites
cockroaches

18. Food

19. Medications
Layel Syndrome
Stevens – Johnson
Syndrome

20. Animal origin
dandruff and hair of animals
Bee, wasp venom
Fodder, feathers

21. Plants

22. plants

23. Pollen
Pollen of wormwood

24. • Industrial
• Microbial
• Fungal
mould

25. ENDOALLERGENS
AUTOALLERGENS
• NATURAL (PRIMARY)
• AQUIRED (SECONDARY)
Primary endoallergens
Normal tissue proteins, which didn’t
have a contact with lymphocytes during
embryogenesis. Organism doesn’t have
immune tolerance for these proteins

26. NATURAL OR PRIMARY
ENDOALLERGENS
• Nervous tissue
• lens (crystalline)

27. • Thyroid colloid
• Testis

28. Aquired or secondary
endoallergens
Proteins with changed structure:
• Infectious
• Non infectious

29. THE CONDITIONS PROMOTING
DEVELOPMENT OF ALLERGY
Social factors
vaccination, environmental polution,
widespread chemical substances,
uncontrolled administration of medications.
Organism’s peculiarities
• hereditary predisposition
• high permeability of biobarriers
• insufficiency to inactivate mediators of
allergy

30. CLASSIFICATION OF ALLERGIC
REACTIONS:
According to the rapidity and duration of
the immune response (by Kook,1930 )
I. Immediate type. Allergen sets in motion
immediate (second to minutes) immune
response, mediated by humoral
antibodies.
II. Delayed type in which the reaction is
slower in onset and develops within 24-48
hours and the effect is prolonged.
Immune response is mediated by T-
lymphocytes.

31. According to the pathogenesis (P. Gell
and R. Coombs’s classification)
• Type I – anaphylactic, reagenic type
• Type II – cytotoxic type
• Type III – immune complex mediated
type
• Type IV – cell-mediated type

32. PATHOGENESIS OF ALLERGIC
REACTIONS
1. Immunological stage (a stage of
immune reactions)
2. Pathochemical stage (a stage
of biochemical reactions)
3. Pathophysiological stage (a
stage of clinical symptoms)

33. • Formation of antibodies or
sensitized Т-lymphocytes (s-ТL) at
primary contact with allergen
(sensitization)
• Formation of complexes
allergen+antibody or allergen + s-ТL
at secondary contact with allergen
Immunological stage

34. PATHOCHEMICAL STAGE
Releasing, activation, synthesis of
biologically active substances -
mediators of allergy.

35. III. Pathophysiological stage (a
stage of clinical symptoms)
• structural and functional
disorders of organs and
tissues

36. SENSITIZATION
is formation of the high sensitivity
of an organism to certain allergen
It is characterized by formation of
specific antibodies or sensitized
Т- lymphocytes (s-ТL) to the
certain allergen.

37. SENSITIZATION
ACTIVE
Develops in 10-14
days after primary
contact with
allergen
Organism immune
system actively
participates in
process of specific
antibodies or s-TL
formation
PASSIVE
Develops after infusion
of serum containing
antibodies, or a
cellular suspension
with s-TL
Organism immune
system does not
participate in
formation of
antibodies and s-TL

38. TYPE I ALLERGIC REACTIONS
type I hypersensitivity
reagenic or anaphylactic type
ALLERGEN
• pollen of plants, animal and
vegetative proteins
• medications

39. Allergen
Macrophage Т-lymphocyte
В- lymphocyte
Transformation of B-lymphocytes into
plasma cells
IgE, G4 synthesis
IgE, IgG4 fixation on mast cells, basophils
Sensitization

40. Гуморальный (Th2) иммунный ответ
CD4+
Т-
клетка
В-
клет
ка
В
В
В
В
В
В
Плазмоцит
Плазмоцит
Плазмоцит
Плазмоцит
Антитела
АПК
Клональная
пролиферация
В-клеток
Негативная селекция
Тh1-клеток
IL-
10
IL-4,5,6,13
В-
клетки
памяти
CD4+
Th0
CD4+
Th2
IL-4

41. Re-exposure of allergen
(repeated contact with allergen
Formation of complexes Allergen +
antibody on a surface of mast cells
(labrocytes) or basophils

42. Pathochemical stage

43. Pathochemical stage
• Mast cells
degranulation and
releasing of:
• histamine, proteases,
heparin, chemotactic
factors for eosinophils
and neutrophils
• Formation of
leukotrienes B4C4D4 and
prostaglandins D2
from membrane
phospholipids.

44. • Migration to the zone of allergic reaction
eosinophils, neutrophils and releasing
secondary mediators: histaminase,
proteases, phospholipases etc.

45. Pathophysiological stage
• vasodilation
• increased vascular permeability
• edema
• smooth muscles contraction
•bronchospasm
•Bronchial hypersecretion of mucus
• cell injury

47. Clinical symptoms
• Anaphilactic shock
• Pollinosis (Hay
fever)
• Atopic bronchial
asthma
• Urticaria (hives)
• Quincke’s edema
• Gastroenterocolitis

48. «Весенний»
кератоконъюнктивит
(сенсибилизация к пыльцевым
аллергенам)

49. Type II Allergic reactions
(cytotoxic type)
Allergens (endoallergens)
Either normal or altered components
of cellular membranes, glomerular
basement membrane collagen etc.
Chemical substances, including drugs,
fixed on a cellular membrane (Au, Ni,
Zn, Cu, antibiotics)

50. Allergen
Macrophage Т-lymphocyte
В-lymphocyte
Transformation of B-lymphocytes into
plasma cells
IgG1, 2,3, IgM synthesis
Secondary contact with allergen

51. Basal membrane of Renal glomeruli

52. • Formation of complexes
allergen+antibody on a surface of
target cells

53. • Activation of
complement
components
• liberation of
lisosomal enzymes
(DNA-ase, RNA-ase,
elastase)
• free radicals
(О-, ОН., Н2О2)
during phagocytosis
Lysis of target
cells, destruction
of basement
membranes

54. Complement-mediated cytolysis
activation of complement components:
 С3а, С3в, С5а (opsonization)
phagocytosis
 Complex С5 - С9 formation of
channels in cellular membranes
osmotic lysis of cells

55. Complement-independent (antibody-
dependent) cytotoxicity
• а) cells coated with antibodies (IgG) are
susceptible to phagocytosis (opsonization)
• б) cells coated with antibodies activate NK-cells
(killers) having on the surface receptors to a Fc-
fragment of antibodies
NK-cell

56. Antibody-mediated cellular dysfunction
 antibodies directed against cell surface receptors
(myasthenia gravis)
 antibody mediated stimulation of cell function (Grave’s
disease). IgG acts as Thyrotropin

57. Clinical examples
Autoimmune:
hemolytic anemia
thrombocytopenia
Goodpasture syndrome
agranulocytosis

58. TYPE III ALLERGIC REACTIONS
(immune complex mediated )
ALLERGENS
BACTERIA, VIRUSES, DNA, DRUGS,
ANTISERA, SOLUBLE PROTEINS

59. Allergen
Macrophage Т-lymphocyte
В-lymphocyte
Transformation B-lymphocytes into
plasma cells
IgG, M synthesis
Secondary contact with allergen

60. Formation of soluble allergen+antibody complexes
(the complexes are of intermediate size and there is
antigen excess
• Circulation of
immune complexes
in blood and lymph
• Deposition of the
immune complexes
in vascular
basement
membranes

61. Mediators
• Activation of complement components,
phagocytosis activation, release of
lysosomal enzymes and free oxygen
radicals
• Degranulation of mast cells and release
of histamine, serotonin, heparin,
chemotactic factors, formation of LT
and PG, PAF
• Kinin and clotting systems activation

62. Pathophysiological stage
• Increased vascular
permeability
• Damage of cells
• thrombosis
• Inflammation

63. • Vasculitis
• Serum sickness
• Glomerulonephritis
• Rheumatic heart disease
• Farmer’s lung
• Arthus reaction – localized
area of tissue necrosis

64. Glomerulonephritis

65. TYPE IV ALLERGIC REACTIONS
(cell - mediated)
ALLERGEN
mycobacterium tuberculosis
 fungi
 parasites
 viruses
 tissue proteins of low molecular
weight and low immunogenity

66. Recognition of allergen,
Cooperation
Macrophages and lymphocytes
differentiation ThoTh1
Formation of sensitized T-L
(CD4+)
At secondary contact with
allergen activation of T-
lymphocytes and
production of
lymphokines

67. Formation and secretion
lymphokines by s-TL
• activators of macrophages (IFN-) and
granulocytes (chemotactic factors)
• activators of lymphocytes (IL-2, IL-12)
• Lymphokines which damage tissues
(TNF-)
• Antiinflammatory IL-10, TGFβ

68. Tissue damage due to:
• lymphokines
• CD8 – T-killers (with the help of perforin, which
drill holes in the target cells, thus causing osmotic
lysis; and by inducing apoptosis)
• Lysosomal enzymes

69. Allergic inflammation, granuloma
formation

70. • Tuberculin test (positive
Mantoux reaction). After
intracutaneous injection
of tuberculin, a protein-
lipopolysaccharide
component of the tubercle
bacillus, a local area of
erythema and induration
begins to appear at 8 to 12
hours, reaches a peak (1-2
cm in diameter) in 2 to7
days and there after
slowly subsides.

71. Examples
• Tuberculin test (positive Mantoux reaction).
After intracutaneous injection of tuberculin, a
protein-lipopolysaccharide component of the
tubercle bacillus, a local area of erythema and
induration begins to appear at 8 to 12 hours,
reaches a peak (1-2 cm in diameter) in 2 to7
days and there after slowly subsides.
• Brucellosis
• Candidosis
• Transplant rejection
• Contact Dermatitis

72. Hyposensitization
is decreased sensitivity to
allergen
• Specific
• Nonspecific

73. Specific hyposensitization (it is effective for
type I hypersensitivity)
• Is decreased sensitivity to the same
allergen that caused allergy (Injection of
serum using Bezredka’s method: firstly
the small amount of allergen, then the
rest).
Pathogenesis
• Formation of blocking antibodies
• Decreased synthesis of reagens
• Decreased amount of mediators

74. Nonspecific hyposensitization
is used when specific can’t be
performed.
It restores the immune reactivity.
It can be achieved by using of
antimediators, membrane stabilizators,
antioxidants, glucocorticoids.

75. PSEUDO-ALLERGIC REACTIONS
• Group of reactions, similar to allergy by
clinical symptoms, but without
immunological stage.
• Develop under the action of factors
causing mast cells degranulation and
liberation of biologically active
substances.

76. Pathogenesis
1. Due to high Histamine level
 Mast cells degranulation
 Impaired histamine breakdown
 Increased reception with food
(certain cheeses, smoked
sausages)
 Dysbacteriosis

77. 2. Disorders of the complement
system activation
Excessive activation of complement
system
Deficiency of inhibitors of complement
components
3. Disorders of arachidonic acid
metabolism
Impaired balance between prostaglandins
and leukotrienes (aspirin administration )