when are eosinophils involved in allergic responses
late
phases of hypersensitivity reactions
sensitisation phase effector phase immediate phase late phase: late effector phase
allergic response in airways leads to
decreased bronchial diameter and increased mucus --> nasal blockage, coughing, phlegm, asthma
what characterised an atopic patient?
- high levels of IgE - large numbers of eosinophils both in circulation and in tissues - large numbers of IL-4 secreting Th2 cells
very simply, the late effector phase of type 1 immediate hypersensitivity involves
eosinophilic activation and recruitment --> mediatorys --> epithelial cell activation, inflammatory cell recruitment and activation
how are allergens usually introduced to a patient
via a mucosal route
allergic response in skin leads to
increased fluid secretion and vasodilation --> swelling, itching and urticaria
very simply, the effector phase of type 1 immediate hypersensitivity involves
IgE binding to mast cells via FcR --> mast cell activation
what causes celiac disease
usually HLA DQ2 MHC molecule tTG2 in intestinal lamina propria normally deamidates gliadin peptides to change their glutamine side chain (positive) into glutamate (negative). This negative charge binds effectively to DQ2 on APC --> MALT --> Th1 activation --> cytokines - activate macrophages - damage to the villi
what is an allergy
an immune-mediated inflammatory response to common environmental antigens that are otherwise harmless
what molecules are in mast cell granules
histamine, heparin, tryptase +/- chymase, TNF-alpha
very simply, the sensitisation phase of type 1 immediate hypersensitivity involves
low dose allergen binds APC and basophils to activate Th2 and then initiate IgE
how do granulomas form in type 4 delayed hypersensitivity responses
macrophage activation by IFN-gamma results in the production of IL-8, IL-1 and TNF-alpha --> endothelial activation and phagocyte and lymphocyte migration --> TNF-alpha induce weight loss, granuloma formation and death of some infected macrophages
what is the allergen involved in celiac disease
gliadin component of gluten
timing of mast cell activation events
secretion of preformed mediators - 30-45 seconds synthesis and secretion of lipid mediators - 10-30 minutes synthesis and secretion of cytokines (slow)
what does the persistence of the antigen in the tissue result in
the accumulation of T cells and macrophages (via IFN-gamma) in the tissue releasing a lot of cytokines and ROS and RNS
what do eosinophils do in the allergic response
they produce: - toxic granule-derived basic proteins and free radicals --> tissue damage/remodelling. - chemical mediators --> epithelial activation, inflammatory cell recruitment and activation
what does celiac disease cause
damage to the vili of the small intestine
what is type 4 delayed hypersensitivity responses elicited by
a persistent antigenic stimulation (can be infectious agent or chemical agent)
what causes attraction and infiltration of eosinophils in allergic responses
chemokines by epithelial cells at inflammatory sites
where are mast cells located
mucosal and epithelial tissues, and near blood vessels
what is type 4 delayed hypersensitivity responses characterized by
cell mediated, heavy involvement of Th1 cells and macrophages, persistence of the antigen
allergic response in GI tract leads to
increased fluid secretion and peristalsis --> diarrhea and vomiting
what occurs in type 1 immediate hypersensitivity
an inflammatory response to allergens mediated by IgE
what causes eosinophil activation in allergic responses
IL-5 produced by Th2 and mast cells
what is the mechanism for type1 hypersensitivity
low dose allergen --> introduced via mucosal route --> DCs and basophils promote Th2 helper T cell activation via IL-4 --> TH2 cells produce IL-4, 5 and 13 --> promotes IgE secretion by B cells
how do dendritic cells and basophils activate Th2 cells in the sensitisation phase of type 1 hypersensitivity
DC binding to T cells produces IL-33 - which activate basophils --> produce IL-4 --> Th2 basophils can also be directly activated by allergen and binds T cells and produce IL-4 --> Th2
when mast cells are exposed to IgE initiated by the same allergen, what happens
IgE-FcR cross linking --> granule exocytosis (immediate effects) and synthesis of inflammatory lipid mediators (immediate effect, but slower than granules) and cytokines and chemokines (slower effect)
what are the 6 main contributors to Type 1 hypersensitivity
allergens Th2 cells IgE high affinity FcR Mast cells eosinophils
where are eosinophils normally located
in mucosal linings in very low numbers
allergic response in blood vessel leads to
increased blood flow and permeability of the blood vessels in the whole body --> increased tissue fluid and cell infiltrate --> anaphylatic shock
4 types of hypersensitivity
type 1 - immediate hypersensitivity type 2 - antibody mediated type 3 - immune complex type 4 - delayed type hypersensitivity
what are the phases of hypersensitivity
sensitization (very rapid) response (has immediate and late phases)
allergy treatment options
- adrenaline - anaphylaxis - inhaled beta-adrenergic receptor agonists - asthma - antihistamines (hives, allergic rhinitis) - corticosteroids
very simply, the late phase of type 1 immediate hypersensitivity involves
induced mediators causing cell infiltration and sustained oedema and/or SM contraction
how are mast cells sensitized
bind IgE (not bound to allergen) using high affinity FcR (very stable binding - can last for months/years)
what do the immediate phase and late phase of mast cell activation lead to
immediate - wheal and flare (localized swelling around site of challenge and BV dilation and engorgement) late - cell infiltration and sustained oedema and/or SM contraction
what does desensitization/immunotherapy involve
administration of increasing doses of allergen to achieve T cell tolerance -> switch to Th1 response
very simply, the immediate phase of type 1 immediate hypersensitivity involves
wheal and flare due to preformed mediators released by mast cells