Hypersensitivity
Hypersensitivity
} Describes immune response which damage tissue or cells rather than help the host.
} classification - 4 types of hypersentivity reactions.(Gell and Coombs)
} The first 3 are mediated by antibody and the fourth by T- cells
} Allergy- is a state of heightened reactivity of the immune system to foreign substances.
Type I Hypersensitivity-IgE and mast cell
} Describes the rapid Immediate allergic reaction.
} It is caused
upon contact with antigen
against which the host has pre-existing
IgE antibody. –(exposure to an antigen more than once).
} IgE is present in very low levels in serum in most
people.
} IgE‘s half life in serum is only 2-3 days
} much of the IgE in the body is bound
to high affinity receptors (FcεRI), in the bound state the half-life is ~3 weeks.
}
} The high affinity FcεRI receptors are found on mast
cells and basophils.
} Each cell has a high density of these
receptors (40-250,000 per cell) to represent a wide spectrum of antigen
specificities .
} The cells are activated by the cross-linking
of the Fc εRI receptors to antigen via
the bound IgE molecules.
} The high affinity FcεRI
receptors are found on mast cells and basophils.
} Each cell has a high density of these
receptors (40-250,000 per cell) to represent a wide spectrum of antigen
specificities .
} The cells are activated by the
cross-linking of the Fc εRI receptors to antigen via the bound IgE molecules.
|
Primary mediators |
|
|
Histamine |
Vascular permeability, sm
contraction |
|
Serotonin |
vascular permeability, sm
contraction |
|
ECF-A |
eosinophil chemotaxis |
|
NCF-A |
neutrophil chemotaxis |
|
proteases |
mucus secretion, connective tissue
degradation |
|
Secondary mediators |
|
|
Leukotrienes |
vascular
permeability, sm contraction |
|
Prostaglandins |
vasodilation, sm contraction,
platelet activation |
|
Bradykinin |
vascular permeability, sm
contraction |
|
Cytokines |
numerous effects e.g. activation
of vascular endothelium, eosinophil recruitment and activation |
Systemic anaphylaxis
} Ingestion of nuts or seafood, insect
bites (venom), and drug injection may all cause life-threatening reactions in highly
sensitised individuals.
} Death in such cases is due to systemic
release of vasoactive mediators leading to:
} General vasodilation and smooth
muscle contraction resulting in sudden loss of blood pressure,
massive oedema and severe bronchiole constriction (systemic
anaphylaxis).
Type
II Hypersensitivity
} caused by specific antibody binding to
cell surface antigens.
} The antibodies involved- the IgM or IgG
} cause cell destruction by:
a)
Antigen
antibody complex recruits cells directly through Fc receptors- arrival of
cytotoxic cells(NKC, neutrophils, eosinophils etc damage tissue thro ADCC)
b)
Classical
pathway activated- leads to cell lysis, mast cell activation & neutrophil
recruitment
c) Except
where the reaction is autoimmune, the target cells are foreign to the host
(graft)
Examples of Type II Hypersensitivity reaction
i.
penicillin
bind erythrocytes, antibodies are produced
causing complement lysis of erythrocytes.
ii.
haemolytic
aneamia - IgG passively acquired by the feotus via the placenta cause
destruction of foetal red blood cells (RBC) by antibody dependent cellular cytotoxicity
(ADCC)
iii.
Organ
specific autoimmune diseases
} Myasthenia gravis- eyes
} Glomerulanephritis- kidney
iv.
Auto-immune cytopenias
i. Thrombocytopenia – low platelets
ii. Neutropenia –low neutrophils
Type
III Hypersensitivity-
} Mediated by antigen/antibody complex
in circulation
} mediated by immune complexes essentially
of IgG antibodies with soluble antigens.
} type 3 hypersensitivity has a lot in common
with type I except that the antibody involved is IgG
} IgG
is not prebound to mast cells, so that only preformed complexes can bind
to the low affinity FcγRIII. Mast cell activation leads to
increased vascular permeability
} The
deposited immune complexes trigger neutrophils to discharge their granule
contents which damage the surrounding endothelium and basement membranes
The Arthus reaction
} a local type III reaction.
} Named after Maurice Arthus- who
injected foreign proteins under the skin of animals he had already immunized
with same antigen
} Antigen/antibody complex forming within
the tissue incited an erythematous lessions after 3-6 hours
} this is because the FcγRIII is a low affinity receptor and
the reaction is slow compared with a type I reaction
} Extrinsic allergic alveolitis occurs when inhaled antigen complexes
with specific IgG in the alveoli, triggering a type III reaction in the lung,
} Complement is not required.
Type IV Hypersensitivity
} Delayed type hypersensitivity triggered
by antigen-specific T cells.
Results when an APC (dendritic cell)
displays antigen bound to MHC class II ,
to antigen specific TH1 cell patrolling the tissue
v Activated T helper cell produces cytokines-TNF-β and IFN-γ
and chemokines, recruits
macrophages, T cells & neutrophils
v The consequences are a cellular
infiltrate in which mononuclear cells (T cells and macrophages) tend to
predominate. It is usually maximal in 48-72 hours
} Initiation of this type IV immune
response may also require IgM and probably complement.
} Examples – exposure to contact with
nickel in jewellery
} P-phenyldiamine in sunscreen and hair
dyes-these 2 are confined to skin, called contact dermatitis.
Examples of type 1 reactions
Asthma
} -A common chronic disease of childhood
affecting some 5% of children or 2% in adults.
} It is a clinical disorder of increased
responsiveness of the bronchi to a variety of stimuli,
} results in airway narrowing,
} which reverses spontaneously after drug
therapy, is associated with cellular inflammation.
Cause of bronchial hyper responsiveness
} - Prolonged damage to the respiratory
epithelium (lines most of the respiratory tract)-by eosinophil-derived
mediators
} Manifests as-broncho-constriction,
inflammation, mucous production with airways plugging in response to-the
triggers, upper respiratory infections (excessive cold air, smoke and paint
fumes).
} Asthmatics - increase in mast cell density
- significant
increase in both eosinophils and T cells
} -
cytokines produced by TH cell can stimulate eosinophil production,
recruitment and
} activation.
Symptoms
} Cough (often nocturnal in children)
} Wheeze
} Shortness of breath
Measure
} - lung function tests (FEV1)
demonstrate airways obstruction- but may be normal between attacks
} -skin
prick test
} -serum
1gE levels-ELISA
Therapy
} -Anti-histamines not used in treatment
} -Education on how to inhale and optimal
delivery is NB
} wild asthma or relief of acute
shortness of breath or wheeze
} –salbutamol, -it relaxes
bronchial smooth muscle
} Salbutamol-is inhaled as an aerosol,
powder, may be taken orally in young children
Severe sthm
} Medication is required regularly
} Sodium cromoglycate may be included to stabilize mast cell.
} Inhaled corticosteroids- suppresses protanglandin and leukotriene mediators,
inflammatory
cell recruitment is inhibited.
} -Acute, severe asthmatic attacks
are a medical emergency
} -may require hospitalization-with a
demonstration of xanthines e.g. theophylline, corticosteroids.
2. Allergic Rhinitis
} -Usually begins in children or teenage
} -It affects 10% of children and 20% of
adolescents
Main Symptoms
} -nasal congestion, sneezing, itching
and discharge.
} -Allergic conjunctivitis -associated
with itchiness and excessive watering of the eyes.
} upper airways mucosa may be affected
with itchiness of palate, pharynx, hearing loss coz of middle ear fluid.
} -Pathogenesis-type1 rxns allergens-
} grass or pollens (seasonal), Smoke,
paint fumes
} house dust mite and pet furs (permanent)
combines type 1early
to late phase response
} -its NB to identify the seasons
} June-July-grass pollen
} July-August-moulds, coupled with skin
testing allows the allergens to be identified and diagnosed.
} Serum total 1gE level is raised.
} -30-40% of children with allergic
rhinitis has eosinophilia in blood.
Therapy
} Anti-Histamines-given prophylatically
before pollen season starts
} -Nasally administered sodium cromoglycate
& steroids form 2nd line treatment
} Conjunctivitis-prophylactic oral
anti-histamine of ocular drops of cromoglycate
Others
} 1. Allergic Eczema
} 2. Urticaria
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