Transcript Atopy and Allergic diseases

Atopy and Allergic diseases .
Prof. Mohamed Osman Gad El Rab.
College of Medicine & KKUH.
Terminology ‫ التعريف‬:
Human disease caused by immune responses to
environmental antigens that lead to :
immediate reactions in the target tissues
& rapid onset of symptoms
are called :
allergic diseases .
With reference to Coombs & Gell classification of
hypersensitivity these are :
Immediate ( type I )hypersensitivity reactions .
In clinical practice these reactions are
commonly called :
allergy or atopy .
atopy : is derived from a Greek term (atopos )
which mean : out of place .
The term refer to :
a strong genetic predisposition ‫ اهبه‬- ‫استعداد‬
for development of immediate hypersensitivity
reactions in certain individuals.
The genetics of allergy are complex , involving
interactions between several genes .
studies of atopic families have identified regions
on chromosomes 11q and 5q ‫هذه الكروموسومات‬
‫المسببه لفرط الحساسيه‬.
‫وظيفه كل كروموسوم وعالقته بتكوين فرط الحساسيه‬:
chromosome 11q : encodes the b subunit of
the high affinity IgE receptor.
chromosome 5q : contain many cytokine genes that
increase susceptibility ‫ حساسيه‬.
‫‪The high- affinity IgE receptor encoded by chromosome 11q .‬‬
‫في االشخاص غير الحساسين يوجد ( اي جي اي ) ولكنه ليس عالي الجاذبيه وكثير العدد مثل‬
‫االشخاص الحساسين‬
‫مسبب الحساسيه‬
‫يرتبط ب ‪ ( 2‬اي‬
‫جي اي )‬
‫‪ contain genes for :‬موقع ‪The 5q locus‬‬
‫‪- IL-3 ,4, 5 , 9 & 13 .‬‬
‫تذكير ( من البلوك االول ) – االنترلوكين \ هو ماده كميائيه تنتج من الخاليا البيضاء وتؤثر على عده اهداف هذه االهداف هي‬
‫خاليا لها عالقه بالجهاز المناعي وتؤثر عليها اما بنتشيطها لالنقسام او تنشيطها للتحول للشكل النشط او تحويلها لشكل اخر‬
‫ترتبط‪-‬بريسيبتور خاص على جسم الخليه الهدف ‪.‬وبذلك يكون لها عالقه باثاره الجهاز المناعي اذا كثرت وهي‬
‫‪-These cytokines :‬‬
‫‪ responses by‬تي هلبر سيلز ‪ TH2‬تعزز ‪- promote‬‬
‫‪ :‬تنميه ‪enhancing‬‬
‫‪* IgE isotype switching in B cells.‬‬
‫‪* eosinophils survival .‬‬
‫‪* mast cell proliferation .‬‬
‫‪- variation in the IL-4 gene has been associated‬‬
‫‪with high levels of IgE in atopic individuals.‬‬
Allergy is a systemic disorder
‫شغل العرض‬
Respiratory
system
Nose
Esophagus
Pharynx
Allergic rhinitis
Asthma
Lungs
GIT
Food allergy
Stomach
Skin
skin
Eczema
Urticaria
Allergic dermatitis
Clinical presentation ‫االعراض‬:
atopic individuals may present with one or more of the
following conditions :
- allergic rhinitis.
- allergic conjunctivitis ‫التهاب العين وهو‬
‫دائما بسبب مناعي‬.
- allergic asthma.
- atopic dermatitis ( eczema ).
A newborn approximate risk of developing symptoms according to
family history of allergic disease :
1. no family member allergic
5-15 %.
2. one sibling allergic
25-35 %.
3. one parent allergic
20-40 %.
4. both parents allergic
40-60 %.
5. both parents allergic ,
( same symptom )
50- 70 %.
Epidemiology ‫ الوبائيات‬:
The prevalence ‫ االنتشار‬of allergic disease worldwide ranges
from 30% to 40%.
There is substantial ‫ قطعي‬evidence ‫ برهان‬that the incidence
‫ حدوث‬of allergy is steadily ‫ ببانتظام‬increasing all over the world .
A study in U.K. between 2001-2005 showed that the
incidence of patients with at least one allergic disease
increased from 18.9% to 24.2 %.
J R Soc Med. 2008, 101(11):558-563.
A study in Saudi Arabia documented a significant increase in
incidence :
Allergic asthma:
From 8% (in 1986 )
to 23% (in 1995). ( p <.0001 ).
Allergic rhinitis:
From 20% (in 1986 ) to 25% ( in 1995). (p < .003).
A.R.Al-Frayh,Z.S hakoor,M.O.GadElRab.Annal of Allergy, Asthma &Immunology,
2001,86:292-296.
* Allergic disease is the 5 th leading chronic disease
among all ages .
* And the 3rd chronic disease among children under
18 years old ; up to one child in three is affected .
* Trend ‫ الميل يشير الى انه‬indicate that by 2015 half of all
Europeans
may be suffering from an allergy ‫مساكييين ( مسوي طالع‬
) ‫ منها‬.
Antigens that elicit ‫ تثير‬allergic reactions are called allergens
because they have the following features :
1. low molecular weight.
2. glycosylation ‫ من القاموس‬: the formation of linkages
with glycosyl groups.
3. high solubility in body fluids .
4. proteins, in nature ,or chemicals bound
to proteins , and some have enzyme
activity .
Common allergens associated with type 1
hypersensitivity :
‫حبوب اللقاح للفطريات‬
Fungal spores (aspergillus )
common indoor & outdoor
allergens ) ‫بالبيت وخارج البيت ( ورانا ورانا‬.
tree pollens ( mesquite )
common outdoor allergens
in Saudi Arabia .
.
Ragweed & ragweed pollens :
common outdoor allergen .
House dust mite &
Cockroach ‫ صرصور‬insects :
Common indoor allergens that
may cause allergy symptoms
All through the year .
( perennial ) .
Honey-bee
black( fire ) ant .
Common causes of
anaphylaxis ‫ظهور شديد وفوري‬
) ‫ للحساسيه ( تفصل الحقا‬..
Manifestations ‫ ظهور‬of allergic disease require two steps .
1. sensitization phase : ‫االصابه االولى‬
first exposure to allergen.
2. challenge phase : ‫االصابه الالحقه‬
re-exposure to allergen .
Sequence of events in immediate H/S reactions.
First exposure to allergen.
Activation of TH2 cells &
stimulation of IgE class
switching in B –cells .
Binding of IgE to FcR1 on
mast cells.
sensitization .
Sequence of events in immediate H/S reactions.
Repeated exposure to allergen
Activation of mast cells :
release of mediators .
challenge .
‫من ‪ and secondary‬يصدر من الماست سيل نفسها ‪primary‬‬
‫‪:‬عوامل االنفالميشن ‪ mediators‬الخارج‬
Allergic reactions can be divided into immediate and
late- phase responses .
- the immediate response start within seconds
and is due to preformed mediators.
- the late reaction ,which takes up to 8-12 hours to
develop , is due to induced synthesis and release
of mediators & cytokines .
The late-phase
response :
The immediate
response :
due to preformed
&rapidly synthesized
Mediators .
start within seconds.
due to synthesis of
new mediators
(PG,)
LT.,) chemokines
& cytokines, with
Influx ‫تدفق‬of
eosinophils and
T-cells .
takes 8-12 hours
to develop.
clinical presentations :
- allergic rhinitis .
- allergic asthma .
- skin allergy .
- food allergy .
- systemic anaphylaxis .
Allergic rhinitis :
inhaled allergens activate mucosal mast cells
beneath the nasal epithelium .
mediators released .
diffuse across the mucous membranes of the nasal
passages .
The immediate reaction in allergic rhinitis is characterized
by :
1. intense ‫ شديده‬itching & sneezing .
2. local edema (leading to blocked nasal passages).
3. nasal discharge ‫ ( سيوله‬typically rich in eosinophils ).
4. irritation ‫ تهيج‬of the nose ( as a result of histamine) .
A similar reaction to airborne
allergens deposited ‫ تدخل‬in the
conjunctiva of the eye can
result in :
allergic conjunctivitis.
Allergic asthma :
inhaled allergens activate submucosal mast cells
in the lower airways .
mediators released within seconds & lead to :
contraction of bronchial smooth muscles.
(bronchial constriction – difficulty in breathing ).
increased secretion of mucus .
increased vascular permeability .
influx ‫ تدفق‬of inflammatory cells ( including eosinophils & TH2 cells ).
An important feature of asthma is
chronic inflammation of the airways .
This result from the influx of inflammatory cells .
TH2 cells .
IL-9 & IL-13 .
eosinophils .
Major basic protein
neutrophils .
proteolytic E.
These cell products act on
1. Airway smooth muscle cells .
2. Lung fibroblasts .
3. Mucous glands .
and cause :
airway remodeling .
Lung epith. Cells .
Rantes & eotaxin .
Airway remodeling :
Goblet cell
metaplasia .
thickening of the airway
walls by hyperplasia &
hypertrophy of the
smooth muscle layer
Increased mucus
secretion .
permanent narrowing of the
airways .
Irreversible lung damage .
Development of
fibrosis .
permanent
tissue damage.
smooth muscle
contraction.
mucus plug
.
Hyperreactive airways react to non- specific
factors:
chemical
irritants .
smoke &
Strong perfumes .
sulphur
dioxide & air
pollutants.
viral & bacterial
respiratory
infections .
Skin allergy :
manifest as : - acute urticaria .
- chronic eczema .
* allergens enter the epidermis or dermis by :
1. a stinging insect .
2. direct contact .
3. through the blood ( ingested food or drug ).
local connective tissue mast cells become
activated & release mediators .
* mediators activate
local nerve endings.
local increase in
vasc. permeability.
- vasodilatation of
blood vessels.
extravasation of
fluid from blood.
( redness of the skin. )
( Swelling of the skin.)
this skin lesion is called :
wheal ‫انتفاخ‬-and flare ‫ حمره‬reaction .
Acute urticaria : ‫تنتشر حول الجسم كله‬
a disseminated ‫ متبعثر‬form of the wheal-and- flare
reaction .
sometimes appear when ingested allergens
enter the blood stream and reach the skin .
Histamine released by mast cells in the skin
causes :
large , itchy red swellings of the skin.
( urticaria or hives ).
Acute urticaria :
Swelling of the lips
and eyes may be
associated with
urticaria .
Angioedema :
Food allergy :
A significant ‫ مهم‬health problem especially in children .
In USA food allergy cause approximately 30,000
anaphylactic reactions each year , including 200
deaths .
* food allergens resist ‫ مقاوم‬digestive enzymes &
therefore reach the mucosal surface of the small
intestine as an intact molecule .
Ingested allergens in food cause activation of mucosal
mast cells in the gastrointestinal tract .
mediators released .
transepithelial fluid loss
diarrhea .
smooth muscle contraction.
vomiting .
Ingested food allergens may enter the bloodstream
and cause systemic reactions .
activation of connective
tissue mast cells in the
skin .
urticaria .
disseminated mast cell
activation .
generalized anaphylaxis.
Systemic anaphylaxis ( anaphylactic shock).
Allergens may be introduced directly into the
bloodstream as a result of :
‫اسباب شائعه لحدوثها‬:
- penicillin injection ‫الدواء المحقون ( مهب شرط‬
) ‫ بنسلين‬.
- honey-bee sting .
disseminated ‫ منتشر‬mast cell activation .
massive mediator release into the blood result in :
wide spread increase
in vascular permeability .
airway
Constriction.
loss of blood pressure . difficulty in
(hypotension) .
Breathing
swelling of the
larynx
suffocation.
( difficulty in breathing ).
* ‫ العالج‬this condition can be rapidly fatal but can be controlled by
immediate injection of epinephrine ( adrenaline ) .
Diagnosis : ‫التشخيص‬
1. skin prick test (SPT).
2. specific IgE measurement .
3. challenge tests.
4. elimination – provocation tests.
( food allergy ).
skin prick test .
skin prick test