Download 1. Type I allergy

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Table 3.3 Main cytokines secreted by keratinocytes.
Classification, cytokines
Main functions
Multifunctional cytokines
IL-1a
IL-6
IL-7
IL-12
IL-15
IL-18
TNF-a
MIF
Induction of secondary cytokines
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Interleukin (IL)
Modulation of adhesion molecules
Modulation of activation and migration of T cells, B
cells and macrophages
Activation of endothelial cells and fibroblasts
Modulation of activation and migration of Langerhans
cells (IL-1a, TNF-a)
Induction of fever and acute inflammatory proteins
Chemotactic factor: associated with leukocyte migration
IL-8
Activation and migration of T cells and neutrophils
Colony stimulating factor: associated with leukocyte proliferation
GM-CSF
Activation of granulocytes, macrophages, T cells and
Langerhans cells
G-CSF
Proliferation of granulocytes
M-CSF
Proliferation of macrophages
Growth factor: associated with local cutaneous reactions
TGF-a
Proliferation of keratinocytes
b-FGF, PDGF
Proliferation of fibroblasts and endothelial cells
Suppression factor: modulates immunity
TGF-b
Suppression of keratinocytes and endothelial cells
IL-10
Suppression of immunity through Th1 cells
IL: interleukin, TNF: tumor necrosis factor, MIF: macrophage migration
inhibitory factor, GM-CSF: granulocyte macrophage colony-stimulating factor, G-CSF: granulocyte colony-stimulating factor, M-CSF: macrophage
colony-stimulating factor, TGF: tumor growth factor, b-FGF: basic fibroblast
growth factor, PDGF: platelet derived growth factor
C. Immunity, Allergic reactions
Skin is a major organ where immune/allergic reactions occur.
Various skin diseases have been increasingly understood by the
concept of immunity and allergic reactions, which are generally
classified into the four categories established by Coombs & Gell
(Table 3.4).
1. Type I allergy
Type I allergy is caused mainly by mast cells. Since a reaction
occurs 5 to 15 minutes after an antigen (allergen) is administered,
it is also called an immediate hypersensitivity. Mast cells with
IgE on the surface react to antigens, and chemical mediators such
as histamines and leukotrienes are then secreted by the mast cells
(Chapter 8). These chemical mediators enhance vascular permeability, to produce edema; in addition, they induce migration of
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Immunology of the Skin
eosinophils, to evoke inflammation. Therefore, nasal discharge,
pruritus, and bronchial asthma are induced, and blood pressure is
decreased, by vascular dilatation. A patient with these symptoms
may undergo anaphylactic shock in serious cases. The symptoms
are transient and usually subside within several hours.
Typical skin diseases caused by type I allergy are urticaria and
certain types of drug eruptions (urticarial reaction). Other factors
are involved in atopic dermatitis; however, IgE plays a pivotal or
even solo role in the pathogenetic process. Additionally, allergic
rhinitis (hay fever) and allergic bronchial asthma are common
diseases caused by type I allergy.
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2. Type II allergy
In type II allergy, antibodies are produced against the antigen
on the cell surface to which complements and cytotoxic T cells
have been activated, thereby injuring the cells. Type II allergy
induces cutaneous diseases such as autoimmune blistering diseases. In bullous pemphigoid, autoantibodies bind to BP180
(BPAG2) in the basal cell hemidesmosomes, and the basal cells
are injured by Type II allergy, resulting in blisters (Chapter 14).
A drug may function as a hapten to bind with epidermal cells
or blood cells to cause Type II allergy. Drug-induced hemolytic
anemia, thrombocytopenic purpura, and toxic epidermal necrolysis (TEN) occur by this mechanism.
Table 3.4 Classification of allergy.
Coombs classification
Type III
Type IV
Immune complex reaction
Cellular immunity
(delayed hypersensitivity)
Type II
Type I
Type of
reaction
Anaphylaxis (immediate Cytolytic reaction
hypersensitivity)
Associated
antibodies
IgE
IgG, IgM
IgG, IgM
-
Associated
immune cells
Histiocytes, basophils,
mast cells
Cytotoxic T cells, macrophages
Multinuclear leukocytes,
macrophages
Sensitized T cells,
macrophages
Complement
Unneeded
Needed
Needed
Unneeded
Target
tissues/cells
Skin, lung, intestines
Skin, erythrocytes, leukocytes,
platelets
Skin, vessel, joint, kidney,
lung
Skin, lung, thyroid gland,
central nervous system,
etc.
Disorders
Urticaria, drug eruption, Bullous pemphigoid, hemolytic
anemia, idiopathic
asthma, pollinosis,
thrombocytopenic purpura, TEN,
anaphylaxis
transfusion incompatibility
Illustration of
reaction
IgE FC
receptor
antigen
cytotoxic
T cell
IgG or
IgM
IgE
cytolysis
Allergic contact dermatitis,
Cutaneous small-vessel
vasculitis, serum sickness, erythema induratum,
GVHD
glomerulonephritis
immune
complex
complements
IgG
complements
secretion of chemical
mediators such as
histamine
surface antigen
phagocytes
tissue
antigen effector
T cells
APCs
secretion of
cytokines
such as IFN-g
activated macrophage
C. Immunity, Allergic reactions
Blood group incompatibility from transfusion, autoimmune
hemolytic anemia, and Goodpasture syndrome are also Type II
allergies.
3. Type III allergy
Type III allergy occurs when antigen-antibody complexes
(immune complexes) deposit in the blood vessels and specific
sites of tissue. An infection or a drug induces immune complex
deposition, where an allergic reaction causes fibrinoid degeneration and neutrophilic infiltration; this is called cutaneous smallvessel vasculitis (Chapter 11).
Serum sickness disease, glomerular nephritis and lupus nephritis are also type III allergies.
MEMO
Phagocytic cells engulf antigens that contain
proteins of 10,000 molecular weight or
greater (complete antigen) and carry the information of the antigens to lymphocytes. That
is, non-protein substances of small molecular
weight (e.g., carbohydrates, fats, organic
compounds, metallic molecules) cannot be
antigens themselves; they are called haptens,
or incomplete antigens. Although antibodies
react to haptens individually, lymphocytes
produce such antibodies only in combination
with other proteins.
Hapten
4. Type IV allergy
Type IV allergy is inflammation caused by a reaction between
an antigen and the corresponding T cells (Th1 in particular).
There are two stages in type IV allergy: sensitization, and an
effector phase. After an initial invasion, the antigen is engulfed
by antigen-presenting cells to activate T cells in the regional
lymph nodes. At this time, memory T cells along with effector T
cells are produced in order to enable them to respond promptly to
the secondary invasion of the antigen (sensitization). In the secondary and later invasions, memory T cells are activated by the
antigen-presenting cells, and inflammation is evoked that peaks
48 hours after antigenic challenge (effector phase). Since it takes
a long time for the reaction to occur, Type IV allergy is also
② contact with the same antigen
(challenge phase: 24-48 hrs)
① first contact with antigen
(sensitization: about 1 week)
allergen (antigen)
papules, vesicles
spongiosis
cytokines
Langerhans cell
migration to
lymph node
T cell
antigen presenting
by Langerhans cell
memorization
presents
antigen information
lymph node
Fig. 3.9 Mechanism of allergic contact dermatitis.
effector
T cell (Th 1)
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edema
inflammatory-cell infiltration
telangiectasia
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Immunology of the Skin
called delayed hypersensitivity (Fig. 3.9).
Typical lesions caused by type IV allergy are allergic contact
dermatitis and graft-versus-host disease (GVHD).
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D. Immune abnormality
1. Autoimmune diseases
Immunity is a mechanism whereby self is distinguished from
non-self to exclude non-self. Therefore, autologous proteins do
not usually induce immune reactions. If there is a disturbance in
the body, antibodies (autoantibodies) are produced against autologous proteins and the immune mechanism tries to exclude self;
this phenomenon is called autoimmunity, and the diseases caused
by it are called autoimmune diseases. Autoantibodies are thought
to appear by the following mechanisms.
●Organs that have been isolated from the immune system since
the embryonic phase are exposed to the immune system for an
unknown reason and are recognized as non-self (e.g., sympathetic opthalmia, azoospermia).
●Normal tissues are degenerated by viruses or bacteria, and
antibodies are produced against the degenerated proteins (e.g.,
mycoplasma pneumonia).
●Antibodies that have been produced against specific bacteria
react with similar self antigens (cross-reaction) (e.g., rheumatic
fever).
●Immunologic homeostasis becomes dysfunctional somehow,
and lymphocytes that react against autoantigens (forbidden
clones), which are excluded in a normal state, are not excluded
(some autoimmune diseases, including systemic lupus erythematosus (SLE)).
●Regulatory T cells suffer reduced function for some reason,
and immune reactions to self become uncontrolled (some
autoimmune diseases, including SLE).
The major autoimmune diseases that are treated in dermatological practice include SLE, systemic sclerosis (SSc) and autoimmune blistering diseases such as pemphigus and pemphigoides.
2. Immunodeficiency
Immunodeficiency is subclassified into congenital and
acquired. In congenital immunodeficiency, the immune factors
are congenitally lacking. In acquired immunodeficiency the
cause is secondary – the result of a disease or treatment. Different
factors are dysfunctional in each disease, resulting in immunodeficiencies such as hypogammaglobulinemia, lymphocytopenia
and the decrease of compliment titer.
In congenital immunodeficiency diseases, the infection is often
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