Transcript Immediate Hypersensitivity (Hypersensitivity type 1)

Allergy
Chapter 20
 Immediate hypersensitivity because it begins rapidly, within minutes of antigen challenge
(immediate), and has major pathologic consequences (hypersensitivity)
 In clinical medicine, these reactions are called allergy or atopy, and the associated
diseases are called allergic, atopic, or immediate hypersensitivity diseases
 A variety of human diseases are caused by immune responses to nonmicrobial
environmental antigens that involve TH2 cells, immunoglobulin E (IgE), mast cells,
and eosinophils
 Allergy is the most common disorder of immunity and affects 20% of all individuals
in the United States
General Features of Immediate Hypersensitivity Reaction
 Hallmarks of allergic diseases are the activation of Th2 cells and the production of IgE
antibody
 Strong genetic predisposition
 Allergens, are usually common environmental proteins and chemicals
 Cytokines produced byTh2 cells
 Clinical and pathologic manifestations consist of the vascular and smooth muscle reaction
that develops rapidly after repeated exposure to the allergen (the immediate
reaction) and a delayed late-phase reaction consisting mainly of inflammation
 Allergic reactions are manifested in different ways, depending on
the tissues affected, including skin rashes, sinus congestion,
bronchial constriction, abdominal pain, diarrhea, and systemic
shock (Anaphylaxis)
PRODUCTION OF IGE
 IgE antibody is responsible for sensitizing mast cells and provides recognition of antigen
for immediate hypersensitivity reactions
 Atopic individuals produce high levels of IgE in response to environmental allergens,
whereas normal individuals generally synthesize other Ig isotypes, such as IgM and IgG,
and only small amounts of lgE
The Nature of Allergens
 Antigens that elicit immediate hypersensitivity reactions (allergens) are proteins or
chemicals bound to proteins to which the atopic individual is chronically exposed
 Typical allergens include proteins in pollen, house dust mites, animal dander, foods, and
chemicals like the antibiotic penicillin
 Two important characteristics of allergens are that individuals are exposed to
them repeatedly and, unlike microbes, they do not generally stimulate the innate
immune responses that are associated with macrophage and dendritic cell secretion of
TH1- and TH17-inducing cytokines
 Chronic or repeated T cell activation in the absence of strong innate immunity
may drive CD4+ T cells toward the TH2 pathway, as the T cells themselves make
IL-4,
 These features include low to medium molecular weight (5 to 70 kD), stability,
glycosylation, and high solubility in body fluids
 Many allergens, such as the cysteine protease of the house dust mite
Dermatophagoides pteronyssinus and phospholipase A2 in bee venom, are enzymes,
but the importance of the enzymatic activity
 Polysaccharides cannot elicit these reactions unless they become attached to proteins,
and penicillin react chemically with amino acid residues in self proteins to form haptencarrier conjugates
 Specific IgE antibodies
Aero-allergens
Food allergens
 Allergic Reaction
Skin Prick Test
(SPT)
THE PROTECTIVE ROLES OF IgE- AND MAST CELL–
MEDIATED IMMUNE REACTIONS
Immunotherapy for Allergic Diseases
 Several empirical protocols have been developed to diminish specific IgE synthesis called
desensitization, small quantities of antigen are repeatedly administered subcutaneously
 IgG titers often rise, perhaps further inhibiting IgE production by neutralizing the
antigen and by antibody feedback, and induction of Treg to iduce tolerance
 Changing the predominant phenotype of antigen-specificT cells fromTH2 to TH1
 Other approaches being used to reduce IgE levels include systemic administration of
humanized monoclonal anti-IgE antibodies mentioned earlier
Allergic Diseases
Allergic Rhinitis
Allergic Rhinitis :
AR is the most common form of perennial rhinitis ( % 43 – 77 )
AR is the most common form of allergy ( 500,000,000 )
Risk factors
1 - positive family history of AR
2 – high socio-economic class
3 – total IgE > 100 before 6 year
4 – passive smoking especially before 1 yr
5 – feeding start before 6 month
6 – heavy contact with indoor allergens (esp. mite)
7 – male gender ?
8 – birth in pollination season ?
9 – first baby ( single baby ) ?
AR classification
Allergic Rhinitis
&
seasonal
perennial
&
intermittent
persistent
AR classification
1 – seasonal allergic rhinitis ( SAR ) :
- often related with outdoor allergens
- tree pollens in early spring
- grass pollens in spring & summer
- weed pollens in summer & autumn
2 – perennial allergic rhinitis ( PAR ) :
- often related with indoor allergens
- mite , cockroach , danders , mold &…
Inflammatory cells in allergic rhinitis
1 – mast cell
2 – eosinophils
3 – T lymphocyte
4 – dendritic cells & macrophages
5 – epithelial cell
Clinical manifestations :
Classic symptoms of allergic rhinitis are :
1 – sneezing
2 – itching ( itchy nose )
3 – rhinorrhea ( runny nose )
4 – blockade ( congestion )
Treatment :
1 – Environment control :
aeroallergen & food allergen
irritants
2 – pharmacotherapy :
intermittent ----- anti-H +/- decongestant
persistent ------- INCS
3 – Immunotherapy
ASTHMA

Asthma is one of the most common chronic diseases, with an estimated 300
million individuals affected worldwide. Its prevalence is increasing,
especially among children

Asthma is a chronic inflammatory disorder of the airways

Asthma is not a cause for shame. Olympic athletes, famous leaders, other
celebrities, and ordinary people live successful lives with asthma
Prevalence data for childhood asthma
 Male > female ( prepubertal )
 Female > male ( postpubertal )
 Urban > rural
 Developed (western) > undeveloped countries
 Slack > white ( minimal different )
 School age > preschool age ( prevalence )
 Preschool age > School age ( incidence )
Allergy & asthma ?
Childhood
asthma
Adult
asthma
% 80 allergic
% 50 allergic
Risk factors for asthma
 atopy
 allergy to house dust mite
 allergen exposure
 family history of asthma
 early viral RTI
 passive smoking
 cigarette smoking
 maternal smoking
 prematurity
 male gender
 length of breast feeding
 food intolerance & hypersensitivity
 high dietary intake of sodium
 air pollution
 urban living
 Hygiene – hypothesis
Pathogenesis
Clinical manifestation
 The classic symptoms of asthma
cough
wheez
Chest
Thightness
chest
pain
Treatment
Atopic dermatitis (atopic eczema)
Age-specific lesions of AD
- in infants
cheek , scalp , extensors surface
- in older children & adult
flexors (politeal fossa, antecubital
fossa )
Environment factors
1 – allergens ( aeroallergen – food allergen )
2 – irritants ( detergent-soaps-low humidityhigh humidity-hot air-cold air-,… )
3 – infections ( S.A , HSV , malsseziafurfur )
4 – emotional stress
5 – endocrine factors
Vicious cycle of skin infection and AD
Decreased function
Of skin barrier
AD
Skin infections
Triggers of atopic dermatitis
Local
treatment
treatment
Systemic
treatment
Environment
control
Anaphylaxis
Etiology
 Foods : 36%
 Drug : 17%
 Insect sting : 15%
 others: 32%
( latex– exercise– cold- idiopathic)
The most common causes of
anaphylaxis
Foods
Peanut
Tree nut
Fish
Shellfish
Egg
Cows milk
wheat
Drugs
Antibiotics
Aspirin
NSAIDs
Anesthetic agents
Opioids
RCM
Clinical manifestation
 Cutaneous : 80-90%
flushing, urticaria angioedema
 Respiratory : 50-60%
hoarseness, nasal congestion, sneezing, dyspnea, cough, wheezing and laryngeal
edema
 Cardiovascular : 30-35%
hypotension,dysrrhytmia, arrhythmia, myocardial ischemia
 Gastrointestinal : 20-25%
nausea, abdominal cramping, vomiting, and diarrhea
 Miscellaneous:
headache : 5-8%, Substernal pain :4-6%, Seizure :1-2%
Treatment
 Epinephrine ( Adrenaline )
 H1 blocker ( Diphenhydramine )
 H2 blocker ( Ranitidine )
 Corticosteroid ( Hydrocortisone )
 B2 agonist ( Ventolin )
Urticaria / Angioedema
 Episodes of hives that continue for < 6 week are considered acute, and
 Those that persist for > 6 week are designated chronic
Etiology
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
(10)
(11)
(12)
(13)
Foods & food additives
Drugs
Insect bite & insect sting
Latex & other contactants
Physical agents
Infections
Transfusion reactions
CVD
Malignancy
Complement disorders
Hereditary disease ( HAE , muckle-well , … )
Systemic disease ( PV , systemic mastocytosis ,.. )
Idiopathic
Acute urticaria
IgE - mediated
Foods , drugs , insect sting , latex , …
Directly: morphine, exercise, cold, sunlight
Non-IgE-mediated
Leukotrienes change: aspirin & NSAIDS
Alternative pathway activation: RCM
Acute urticaria
Cold urticaria
Dermatographism
Solar Urticaria
Chronic urticaria
 Chronic urticaria is reported to be more common in adults, while acute urticaria is more
common in children
 Both sexes are affected; however, chronic urticaria is more common in women,
especially in middle-aged women
 CIU occurs twice as often in women as in men
Urticaria
 Male = female
Acute
urticaria
 More common in children and adolescent
 peak : 20 – 30 year
 Often due to foods & drugs
 % 15 – 20 of GP
 female > male
chronic
urticaria
 More common in middle age
 peak : 30 – 50 year
 Often idiopathic ( CIU )
 Approximately % 1
Etiology of Chronic urticaria
% 80
Idiopathic ( CIU )
% 15
Physical agents
%5
Autoimmunity , malignancy , complement
disorder , occult infections , systemic disease ,
…
Antihistamines & urticaria
Classification of angioedema without urticaria
ACE - inhibitor angioedema
HAE ( treatment )
 Treatment of HAE is difficult
 For acute attacks, C1 INH concentrate or FFP should be administered
 Intubation or tracheotomy may be necessary
 Corticosteroids and antihistamines are not helpful
 Subcutaneous adrenaline ( 0.01 ml / kg , epinephrine 1 : 1000,
max = 0.3 ml ) may be tried