* Dr, HUDA IBRAHIM 21 November 2019 Lec no,6
Over immune reaction refers to excessive, undesirable (damaging, discomfort-producing and sometimes fatal) reactions produced by the normal immune system.*
Hypersensitivity reactions can be divided into four types: type I, type II, type III and type IV, based on the mechanisms involved and time taken for the reaction.
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Contact with allergen Sensitizing/priming dose Shocking dose
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Type I hypersensitivity is also known as immediate or anaphylactic hypersensitivity. The reaction may involve skin (urticaria), eyes (conjunctivitis), nasopharynx (rhinorrhea, rhinitis), bronchopulmonary tissues (asthma) and gastrointestinal tract (gastroenteritis)
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1-Reaginic antibodies: IgE mainly ,IgG4 uncommon. 2-cells :The primary cellular component in this hypersensitivity is the mast cell or basophil, have Fc receptors for reaginic antibodies. The reaction is amplified and/or modified by platelets, neutrophils and eosinophils.
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3-Allergens (antigens ):these allergens can be inhalants (house dust mites), Ingestants (egg,fish, cheese), Injectants (antibiotics, urographin), Cotnactants (wool, feather).
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* B cell
Histamine, tryptase, kininegenase, ECFALeukotriene-B4, C4, D4, prostaglandin D, PAF
Newly synthesized mediators
TH2
IL13
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*Anaphylaxis –Classical immediate reactionSensitization Most effective when Ag introduced parenterallyMay occur by any route exposure to AgMinute quantities are enoughInterval of 2-3 wks needed between sensitizing & shocking doseOnce sensitized it remains so for long timeThe shocking Ag must be same or similar to Sensitizing Ag *
Humans –Itching of scalp & tongue, flushing of skin, difficulty in breathing, nausea, vomiting, diarrhea, acute hypotension, loss of consciousness, death (rare)Causes Serum therapy, antibiotics, insect stingsTreatmentAdrenalin 0.5 ml (1 in 1000 solution) SC/IM repeated up to 2 ml in 15 min *
Mediators of anaphylaxis –Primary mediatorsPreformed contents of Mast cells & BasophilsHistamine, serotonin, eosinophils chemotactic factor of anaphylaxis (ECF-A), Neutrophil chemotactic factor (NCF), Heparin & various proteolytic enzymesSecondary mediators –Newly formed after stimulation by Mast cells, Basophils & other leucocytesSlow reacting substance of anaphylaxis (SRS-A),leukotriene , Prostaglandins & Platelet activating factors (PAF) *
Histamine –Most important vasoactive amine of Human anaphylaxis, formed from histidine found in granules. Released into skin, causes burning & itching. Causes vasodilatation & hyperemia by an axon reflex (Flare) and edema by increasing capillary permeability (Weal). Induces smooth muscle contraction of diverse tissues & organs. *
Serotonin (5-HT) –Base derived by decarbolxylation of Tryptophan.Found in intestinal mucosa, brain & platelets.Causes smooth muscle contraction, ↑ Vascular permeability. *
Chemotactic factors –ECF-A released from mast cell granules are strongly chemotactic for eosinophils. Accounts for high eosinophil counts in many hypersensitivity reactions.NCF – Attracts neutrophilsEnzymatic mediatores such as proteases & hydrolases are also released from the mast cell granules. *
Prostaglandins & leukotrienes –Derived from Arachidonic acid formed from the disruption of mast cell membraneLipoxygenase pathway - LeukotrienesCycloxygenase pathway - ProstaglandinsOne of the family of Leukotrienes isA (slow reacting substance of anaphylaxis)Prostaglandins are bronchoconstrictors, affect secretions of mucus glands, platelet adhesion, permeability, dilatation of capillaries & pain threshold. *
Platelet activating factor – PAFLow mol wt lipid released from basophilsCauses aggregation of platelets and release of their vasoactive amines *
* The common allergy
*We use standardizbed glycerinated extracts of the various allergen extracts such as house dust mite, cat and dog dander, tree, grass and pollen and fungal spores. There is also a negative saline and positive histamine control (used as a quality control reference).
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A droplet of each extract is placed on the inner aspect of the forearm about 3cm apart and we penetrate through the drop at 90 degrees to the skin using a specially modified lancet. Using firm controlled pressure and making sure not to draw blood.
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A positive result is a typically raised wheal and red flare reaction on the skin. The reactions are read after 15 to 20 minutes and a positive reaction should have at least 3mm of raised wheal.
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The reactions are read after 15 to 20 minutes and a positive reaction should have at least 3mm of raised wheal. All oral antihistamine medication should be avoided for 2 – 3 days before hand, as these suppress skin reactivity. *
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*Three distinct strategies are used to reduce the effects of allergic disease .The first strategy is that contact with allergens should be avoided.
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Symptomatic treatment is achieved with antihistamines which block histamine receptors. Chromolyn sodium inhibits mast cell degranulation, probably, by inhibiting Ca++ influx
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Late onset allergic symptoms, particularly bronchoconstriction which is mediated by leukotrienes, are treated with leukotriene receptor blockers (Singulair, Accolate) or inhibitors of the cyclooxygenase pathway (Zileutoin).
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The third strategy is immunological (immunotherapy or desensitization) is successful in a number of allergies, particularly to insect venoms and, to some extent, pollens.
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Patients are given a series of allergen injections in which the dose is initially very small and is gradually increased. This schedule of immunization can gradually convert a TH2 cell response that produces IgE into TH1 response that ceases to make IgE.
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