ALERGI DAN PENYAKIT ALERGI
Hipersensitif
• Reaksi imun hipersensitif
• 4 type of hypersensitif:
• Hipersensitif tipe I IgE
• Hipersensitif tipe II
• Hipersensitif tipe III
• Hipersensitif tipe IV
• Kecenderungan untuk alergen lingkungan vs IgE atopi
• Orang tua atopi 40-60%anak jadi alergi IgE
Non-IgE alergi
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Allergic disease risk genetic & environmental components
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Atopic individual higher IgE in the circulation & higher eosinophils
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Susceptibility gene for both allergic asthma and atopic excema chromosome 11q12-13
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Allergic disease
chr 5q31-33• Environmental factors may interact with genetic susceptibility to cause allergic disease.
• Hygene hypothesis:
• less hygienic environments early in childhood, help to protect against the development of atopy and allergic asthma.
children + antihelminthic had a higher prevalence of atopy
• Counter-regulation hypothesis:
• infection (especially allergen from mucosal surface) might protect against the development of atopy production IL-10 and TGF downregulate TH1 and TH2 responses .
• decreased early exposure to common microbial pathogens and commensals T reg cells << allergic response risk↑
• Regulatory T cells can control allergic responses
Ig E-mediated allergic reactions
4 Sensitization involves class switching to IgE production
on first contact with an allergen
IL-4,IL-5, IL-9, IL- 13
IL-4, IL-13 stat6
Antigen binding to lgE on mast cells or basophils leads to amplification of lgE production
dose, a route that favors IgE production.
Some allergens are not protein, i.e. filarial worms (enzyme inhibitor);
allergenic pollen- derived proteins
Effector mechanisms in Ig-E-mediated allergic reactions
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Most IgE is cell-bound and engages effector mechanisms of the immune system by different pathways from those of other antibody isotypes
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IgE/FcεR (w/o antigen) in mast cells (tissue)
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IgE/FcεR (w/o antigen) in basophil (circulation)
+ antigeninflammatory mediator, cytokines, chemokines
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Eosinophils & Basophils
• Eosinophils and basophils cause
inflammation and tissue damage in allergic reactions
• Possess receptor for cytokines (i.e. IL-5), FcγR, FcαR & C3 receptor.
• High conc. of IL5/IL-3 & GM-CSF degranulation of eosinophils and basophil inducers
• Eosinophil effector function:
• release highly toxic granule proteins and free radicals kill microorganisms and parasites & tissue damage in allergic reactions
• synthesis of chemical mediators such as prostaglandins, leukotrienes, and cytokines amplify inflammatory response by activating epithelial cells and by recruiting and activating more eosinophils and leukocytes.
Eosinophils also secrete proteins involved in airway tissue remodeling.
• Basophils
• Produce IL5, IL-3 & GM-CSF
• Low no in circulation,
• Similar function as eosinophils
Ig E-mediated allergic reactions
Immediate reaction & late phase reaction
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Immediate reaction
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IgE mediated mass cells activation
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increase
• vascular permeability,
• airway narrrowing and
• constriction of smooth muscle.
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Late phase reaction
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3-9 hours after antigen challenge:
• synthesis and release of inflammatory mediator by mast cells
• vasodilation and vascular leakage resulting in edema
Late phase reaction
Long term sequel of allergen exposure
Chronic allergic inflammation, i.e. asthma
Inflammatory mediator from mast cells recruit other leukocytes, i.e. TH2 cells and eosinophil
• Clinical symptoms produced by an IgE-mediated allergic reaction depend on
:
• the amount of allergen- specific IgE present,
• the route by which the allergen is introduced,
• The dose of allergen
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Non-IgE-mediated allergic diseases
Hipersensitive II
• Innocuous antigens binding to the surfaces of circulating blood cells , i.e penicillin, cephalosporin
+ IgG + complement
Destruction of the cells
• type Ill hypersensitivity reaction: Arthus reaction
• Serum sickness transient
• symptoms of vasculitis, nephritis, and arthritis.
Immune-complex deposition (in tissues: i.e. blood
etc)
Immune-complex + Fc receptor on
leucocyte
Leucocyte activation Tissue injury
