Allergies and Hypersensitivity Flashcards
what are allergic reactions (aka hypersensitivity reactions)
- a response to Ags not associated with infection agents
- first exposure causes sensitization (IgE production)
- second exposure causes effector reaction (activation of IgE binding cells)
what is Atopy
predisposition to become IgE sensitized
Types of hypersensitivity reaction
Type I = immediate hypersensitivity
Type II = cytotoxic hypersensitivity
Type III = immune complex hypersensitivity
Type IV = delayed-type hypersensitivity
immune mediators in each type of hypersensitivity reaction
Type I = IgE mediated
Type II = IgG/IgM mediated
Type III = immune complex mediated
Type IV = T-helper or cytotoxic T-cell mediated
How do proteases work as a sensitizing agent in hypersensitivity
they break down proteins (barriers) to invade cells
what are 5 examples of IgE-mediated reactions to extrinsic antigens (type 1 hyper sensitivity)
- systemic anaphylaxis
- acute urticaria (wheal-and-flare)
- seasonal rhino conjunctivitis (hay fever)
- asthma
- food allergy
Besides in an allergic reaction, where might we encounter IgE antigens
parasites
IgE mediated allergic diseases - sensitization to an inhaled allergen (1st exposure)
- enzyme Der p1 enters mucosa via tight junctions
- Der p 1 is taken up by DC for presentation and T-cell priming in lymph node
- IgE specific for Der p 1 travels from lymph node to mucosa
- IgE binds receptor on mast cell to trigger degranulation
- Mast cell granule contents cause allergic symptoms
what happens on the first contact with an antigen
sensitization - class switching to IgE production
IgE mediated allergic diseases - effector mechanism (2nd exposure)
cross-linking of IgE bound to high-affinity receptors on mast cells upon second contact with antigen cause a faster response
how does mast cell activation and granule release affect the GI tract
increased fluid secretion and increased peristalsis lead to expulsion of gastrointestinal tract contents - diarrhea and vomitting
how does mast cell activation and granule release affect the eyes, nose and airways
decreased airway diameter and increased mucus secretion lead to congestion and blockage of airways, swelling, itching and sneezing
how does mast cell activation and granule release affect the blood vessels
increased blood flow and increased permeability leads to increased fluid in tissues and hypotension possibly leads to anaphylactic shock
classes of mast cell inflammatory mediators and their examples
enzymes: tryptase, chemise, cathepsin G, carboxypeptidase A
toxic mediator: histamine, heparin
cytokine: IL’s, GM-CSF, TNF-a
chemokine: CCL3
Lipid mediator: prostaglandins, leukotrienes, platelet-activating factor
Wheal-and-Flare reaction
swelling and redness from type 1 hypersensitivity
- use the skin prick test to determine possible allergens
Systemic anaphylaxis (e.g.from bee venom)
- bee venom penetrates skin and enters the bloodstream
- bee venom encounters mast cells within tissues and crosslinks IgE antibodies
- triggers release of mast cell contents
what is Atopic march
the progression of atopic conditions over time, beginning in childhood and continuing into adulthood
how genetic factors and the environment intertwine in producing type I reactions
high genetic susceptibility + “hygienic” = atopic
low genetic susceptibility + “less hygienic” = non-atopic
type I hypersensitivity treatments
medications that block histamine RELEASE from cells - targets the process not the product
mode of action that distinguishes each type of hypersensitivity reaction
type 1: IgE binds to mast cells and granules release contents
type 2: IgG directly attack the cell surface
type 3: antibodies (immune complexes) bind free (soluble) antigens in plasma
characteristics of type II hypersensitivity reactions
- occurs when IgG recognize cell surface molecules and bind to them, leading to destruction of cells
IgG activity in type II hypersensitivity can lead to…
- opsonization and phagocytosis
- activation of complement on recognized cells
- activation of antibody-dependent cell-mediated cytotoxicity
characteristics of type III hypersensitivity reactions
- 1-2 hours onset time
- deposition of immune complexes in tissues causes local inflammatory response known as the Arthus reaction
how does IgG cause a type III hypersensitivity reaction
- locally injected antigen in immune individual with IgG antibody
- local immune complex formation activates complement - C5a sensitizes mast cells
- activation of FcyRIII on mast cells induces degranulation and histamine release from mast cells
- local inflammation, increased fluid and protein release, phagocytosis and blood vessel occlusion
characteristics of Type IV hypersensitivity reactions
- 24-72 hours onset time
- T-cell mediated (cellular)
- can be either Th1, Th2, cytotoxic T ir T-cell mediated neutrophil inflammation
how do T-cells cause a type IV hypersensitivity reaction
- antigen is injected into subcutaneous tissue and processed by local APC
- A TH1 effector cell recognizes antigen and releases cytokines, which act on vascular endothelium
- recruitment of phagocytes and plasma to site of antigen injection causes visible lesion
after a macrophage stimulates T1H cells, how do they cause delayed-type hypersensitivity
- release chemokines to recruit macrophages to site of antigen deposition
- release IFN-y to induce expression of vascular adhesion molecules
- release of TNF-a and LT leads to local tissue destruction
examples of type III and IV hypersensitivity reactions
type III: serum sickness, arthus reaction
type IV: contact dermatitis by poison ivy, tuberculin test
what are inflammatory mediators that participate in hyper sensitivity
histamine, cytokines, PAF
when do we develop specific types of allergies
allergic dermatitis: 0-1 years
food allergies: 1-3 years
allergic rhinitis: 4-6 years
Asthma: 6-7 years
