Atopy and Allergic diseases .

1
Atopy and Allergic diseases .

• Prof. Mohamed Osman Gad El Rab.
• College of Medicine KKUH.

2
Terminology ???????

• 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 .

3

• 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 .

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atopy is derived from a Greek term
(atopos ) which mean out of
place .

• The term refer to
• a strong genetic
  predisposition ??????? - ???? for development of
  immediate hypersensitivity
• reactions in certain
  individuals.

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The genetics of allergy are complex , involving
interactions between several genes .

• studies of atopic families have identified
  regions
• on chromosomes 11q and 5q ??? ????????????
  ??????? ???? ????????.
• ????? ?? ???????? ??????? ?????? ??? ????????
• chromosome 11q encodes the b subunit of
• the high
  affinity IgE receptor.
• chromosome 5q contain many cytokine
  genes that
• increase
  susceptibility ?????? .

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The high- affinity IgE receptor encoded by
chromosome 11q . ?? ??????? ??? ???????? ???? (
?? ?? ?? ) ????? ??? ???? ???????? ????? ?????
??? ??????? ????????
???? ???????? ????? ? 2 ( ?? ?? ?? )
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• The 5q locus ???? contain genes for
  
• - IL-3 ,4, 5 , 9 13 .
• -These cytokines
• - promote ???? TH2 ?? ???? ????
  responses by 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.

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??????? ???? ?? ??????? ??????? ????? ??? ???
????? ??? ??????? ?? ????? ??? ????? ???????
??????? ????? ????? ??? ???????? ???????? ??
??????? ?????? ????? ????? ?? ??????? ???? ???
??? ?????-????????? ??? ??? ??? ?????? ?????
.????? ???? ??? ????? ?????? ?????? ??????? ???
????
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Allergy is a systemic disorder??? ?????
Respiratory system
Allergic rhinitis Asthma
Nose
Pharynx
Lungs
Esophagus
GIT
skin
Stomach
Food allergy
Skin
Eczema Urticaria Allergic dermatitis
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Clinical presentation ???????

• atopic individuals may present with one or
  more of the following conditions
• - allergic rhinitis.
• - allergic conjunctivitis
  ?????? ????? ??? ????? ???? ????? .
• - allergic asthma.
• - atopic dermatitis ( eczema ).

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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
  .

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Epidemiology ?????????

• The prevalence ???????? of allergic
  disease worldwide ranges
• from 30 to 40.
• There is substantial ???? evidence
  ????? that the incidence ???? of allergy is
  steadily ???????? increasing 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.

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A study in Saudi Arabia documented a
significant increase in incidence

• Allergic asthma
  
• From 8 (in 1986 ) to 23 (in 1995). ( p
  lt.0001 ).

Allergic rhinitis
From 20 (in
1986 ) to 25 ( in 1995). (p lt .003).

A.R.Al-Frayh,Z.S hakoor,M.O.GadElRab.Annal of
Allergy, Asthma Immunology,

2001,86292-296.
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• 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 ????? ???? ??? ??? indicate that by 2015
  half of all Europeans
• may be suffering from an allergy ???????? (
  ???? ???? ???? ) .

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Antigens that elicit ???? allergic
reactions are called allergens
because they have the following features

• 1. low molecular weight.
• 2. glycosylation ?? ??????? 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 .

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Common allergens associated with type 1
hypersensitivity
???? ?????? ????????
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Fungal spores (aspergillus ) common indoor
outdoor allergens ?????? ????? ????? ( ?????
????? ).
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tree pollens ( mesquite ) common outdoor
allergens in Saudi Arabia ..
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Ragweed ragweed pollens common outdoor
allergen .
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House dust mite Cockroach ????? insects
Common indoor allergens that may cause
allergy symptoms All through the year . (
perennial ) .
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Honey-bee black( fire ) ant . Common causes
of anaphylaxis ???? ???? ????????????? ( ????
????? ) ..
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Manifestations ???? of allergic disease
require two steps .

• 1. sensitization phase ???????
  ??????
• first exposure to
  allergen.
• 2. challenge phase ??????? ???????
• re-exposure to allergen .

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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 .
23
Sequence of events in immediate H/S reactions.
Repeated exposure to allergen
Activation of mast cells release of mediators
.
challenge .
24
primary ???? ?? ?????? ??? ????? and secondary
?? ?????? mediators ????? ???????????
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• 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 .

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The late-phase response due to synthesis of
new mediators (PG,) LT.,) chemokines cytokines,
with Influx ????of eosinophils and T-cells .
takes 8-12 hours to develop.
The immediate response due to preformed
rapidly synthesized Mediators . start within
seconds.
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• clinical presentations
• - allergic rhinitis .
• - allergic asthma .
• - skin allergy .
• - food allergy .
• - systemic anaphylaxis .

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Allergic rhinitis

• inhaled allergens activate mucosal mast
  cells
• beneath the nasal epithelium
  .
• mediators released .
• diffuse across the mucous membranes of
  the nasal
• passages .

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The immediate reaction in allergic
rhinitis is characterized by

• 1. intense ????? itching sneezing .
• 2. local edema (leading to blocked nasal
  passages).
• 3. nasal discharge ????? ( typically rich
  in eosinophils ).
• 4. irritation ???? of the nose ( as a
  result of histamine) .

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A similar reaction to airborne allergens
deposited ???? in the conjunctiva of the eye
can result in allergic
conjunctivitis.
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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 ???? of inflammatory cells (
  including eosinophils TH2 cells ).

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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.
Lung epith. Cells . Rantes eotaxin .
These cell products act on

• Airway smooth muscle cells .
• Lung fibroblasts .
• 3. Mucous glands .

and cause airway
remodeling .
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Airway remodeling
thickening of the airway walls by hyperplasia
hypertrophy of the smooth muscle layer
Goblet cell metaplasia .
Development of fibrosis .
Increased mucus permanent narrowing of
the permanent secretion .
airways .
tissue damage.
Irreversible lung damage .
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smooth muscle contraction.
mucus plug .
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• Hyperreactive airways react to non-
  specific
• factors

chemical irritants .
smoke Strong perfumes .
sulphur dioxide air pollutants.
viral bacterial respiratory
infections .
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• 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 ).

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• local connective tissue mast cells become
  
• activated release mediators .
• mediators activate local increase
  in
• local nerve endings. vasc.
  permeability.
• - vasodilatation of
  extravasation of
• blood vessels. fluid from
  blood.
• ( redness of the skin. ) (
  Swelling of the skin.)
• this skin lesion is called
• wheal ??????-and flare ????
  reaction .

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• Acute urticaria ????? ??? ????? ???
• a disseminated ?????? form 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 ).

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Acute urticaria
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Swelling of the lipsand eyes may be associated
with urticaria . Angioedema
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• Food allergy
• A significant ??? health problem especially
  in children .
• In USA food allergy cause approximately
  30,000
• anaphylactic reactions each year ,
  including 200
• deaths .
• food allergens resist ????? digestive
  enzymes therefore reach the mucosal surface of
  the small intestine as an intact molecule .

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• Ingested allergens in food cause activation of
  mucosal
• mast cells in the gastrointestinal
  tract .
• mediators released .
• transepithelial fluid loss smooth muscle
  contraction.
• diarrhea .
  vomiting .

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• Ingested food allergens may enter the
  bloodstream
• and cause systemic reactions .
• activation of connective disseminated
  mast cell
• tissue mast cells in the
  activation .
• skin .
• urticaria .
  generalized anaphylaxis.

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• Systemic anaphylaxis ( anaphylactic
  shock).
• Allergens may be introduced directly into
  the
• bloodstream as a result of
• - penicillin injection
  ?????? ??????? ( ??? ??? ?????? ) .
• - honey-bee sting .
• disseminated ????? mast cell
  activation .

????? ????? ???????
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• massive mediator release into the blood result
  in
• wide spread increase airway
  swelling of the
• in vascular permeability .
  Constriction. larynx
• loss of blood pressure . difficulty in
  suffocation.
• (hypotension) . Breathing
  ( difficulty in breathing ).
• ?????? this condition can be rapidly
  fatal but can be controlled by immediate
  injection of epinephrine ( adrenaline ) .

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• Diagnosis ???????
• 1. skin prick test (SPT).
• 2. specific IgE measurement .
• 3. challenge tests.
• 4. elimination provocation
  tests.
• ( food allergy ).

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skin prick test
skin prick test .