module 09 section 01 (hypersensitivity reactions) Flashcards
define “hypersensitivity reaction”
what can result from this?
- an innapropriately exaggerated immune response causing deleterious effects,
- can result in significant tissue injury, serious disease, or death
when can a reaction be termed hypersensitive?
if it is either heightened or innapropriate in response to an antigen
what is the Gell-coombs classification system?
system that categorizes hypersensitivity reactions into 4 pathophysiological types
what are type I Gell-coombs hypersensitivity reactions?
specific antibody-mediated reaction
can type I Gell-coombs hypersensitivity reactions develop into anaphylactic responses?
yes
what is an anaphylactic response?
an allergic reaction that happens immediately and causes a life-threatening response involving the entire body
type I Gell-coombs hypersensitivity reactions occur due to the actions of:
- IgE on mast cells binds an allergen, resulting in mast cell degranulation
- C3a, C4a and C5a can also cause this type of reaction
recall that type I hypersensitivity reactions are the immediate response to an allergen. Most of these allergens are:
enzymes or glycoproteins
list 4 typcial allergens for type I hypersensitivity reactions
(1) glycoproteins Fel d 1 and Fel d 4 (common in cats)
(2) glycoprotein Fra a 1 (found in strawberries)
(3) enzyme hyaluronidase (found in honeybee venom)
(4) enzyme Der p 1 (found in feces of dust mites)
sensitization for type I hypersensitivity reactions may occur via:
(4)
- oral ingestion
- respiratory inhalation
- skin absorbtion
- intravenous (IV)
are type I hypersensitivity reactions T-cell dependent?
yes
explain the mechanism of type I hypersensitivity reactions
(1) APCs present the processed antigen to Th2 cells
- activated Th2 cells secrete IL-4 and IL-13 which induce naive B-cells to undergo class swithcing from IgM to IgG1 to IgE-secreting B-cells
(2) secreted IgE binds FcE (epsilon) receptor on mast cells
- allergen cross links two IgE antibodies bound to mast cells - resulting in mast cell degranulation
(3) mast cell degranulation results in release of mediators, including vasoactive amines - which elict biological effects within minutes
recall: during type I hypersensitivity reactions, activated mast cells release preformed molecules. What are they and what are the effects of these? (4)
(1) histamine - promotes vascular permeability and sm contraction
(2) eosinophil chemotactic factor - attracts eosinophils
(3) neutrophil chemotactic factor - attacts polymorphic nuclear cells such as mast cells, eosinophils, neutrophils
(4) proteases - increase mucus secretion and cause basement membrane damage (especially in the lungs)
do the preformed molecules secreted by mast cells cause early or late phase biological effects?
early phase
recall: during type I hypersensitivity reactions, activated mast cells synthesize new vasoactive amines. What are they and what are the effects of these? (4)
(1) platelet-activation factor - promotes aggregation of platelets, further mast cells degranulation and sm contraction
(2) leukotrienes - promote sm contraction and increase vascular permeability
(3) prostaglandins - promote sm contraction and vasodilation
(4) bradykinin - promotes sm contraction and vascular permeability (also involved in many pain pathways)
do the vasoactive amines secreted by mast cells cause early or late phase biological effects?
late phase
what are the overall effects of mediators (released by mast cells in type I hypersensitivity reactions) on bvs?
- vasodilation and increased permeability = edema (excess of fluid collecting in cavities or tissues)
- loss of fluid in the tissues can lead to anaphylactic shock
what are the overall effects of mediators (released by mast cells in type I hypersensitivity reactions) on skin?
vasodilation and edema = urticaria (hives) or eczema
what are the overall effects of mediators (released by mast cells in type I hypersensitivity reactions) on the nose/eyes?
vasodilation and increased permeability = edema, which can manifest as rhinitis and conjunctivitis
what are the clinical manifestations of type I hypersensitivity reactions? (3)
(1) atopy - predisposition to developing an allergic rxn
(2) asthma - condition where airways narrow and swell
(3) larygneal edema - characterized by swelling of the larynx
explain what atopy is in more detail.
- it’s an exaggerated IgE-mediated immune response to an environmental allergen
- it’s an inherited conditon with genetic assoication to HLA
- can lead to asthma, atopic dermatitis and allergic rhinitis
what are two hallmarks of an asthmatic reaction?
inflammation and obstructed airways
what are key pathological features of asthma? (2)
- increased recruitment of inflammatory cells (neutrophils and eosinophils)
- increased recruitment of mast cells, leading to high levels of histamine
can asthma be atopic or non-atopic? why?
can be both:
- atopic asthma (aka extrinstic asthma) = mediated by systemic IgE production in response to an allergen
- non-atopic asthma (aka intrinsic asthma) = mediated by localized IgE production but doesn’t occur in response to an allergen