Mechanisms Of Hypersensitivity Type I - Bowden (completed) Flashcards
Which hypersensitivity is mediated by T cells? 4
Type IV hypersensitivity
What are the preformed granules contained within Mast Cells? 7
Histamine (2-5 pg/cell)
Serotonin
Heparin
Serine Proteases
Once activated, what are the newly formed lipid mediators? 7
Prostaglandin D2
Leukotrienes
What’s another word for lipid mediators produced from Mast Cell? 7
Eicosanoids
What Fc receptor does Mast Cells utilize? 7
FcεRI (CD 23a)
What cytokines and chemokines do Mast Cells secrete? What do these cytokines do? 7
IL-4 & IL-13 –> stimulates and amplifies Th2 cell response
IL-3, IL-5, GM-CSF –> eosinophil production and activation
CCL3 (chemokine) –> attracts monocytes, macrophages,, and neutrophils
What are some of the main actions of Mast Cells? 7
Increase vascular permeability
Smooth muscle contraction
Eosinophil production and activation
Activates platelets
What is the major contributor to tissue damage during allergic inflammation? 8
Eosinophils
What chemokines & cytokines do Eosinophils secrete? What do they do? 8
IL-3, IL-5, GM-CSF –> eosinophil activation and production
TGF-α, TGF-β –> epithelial proliferation
CXCL8 (IL-8) –> leukocyte chemotaxis
What is the role of Eosinophil peroxidase and collagenase? 8
Eosinophil Peroxidase:
triggers histamine release from mast cells
halogenates and kills targets
Eosinophil Collagenase:
remodels connective tissue matrix
What is the most pro-inflammatory leukotriene (SRS-A)? 9
LTB4
Do leukotrienes come before or after histamine into the allergic reaction?
Slower onset, after
What are the roles of Leukotrienes (SRS-A)? 9
increase capillary permeability
increase mucus production
bronchoconstriction (more powerful than histamine)
Lady Come Make Babies
What are the roles of IL-4? 10
Th2 cell growth factor
Isotype switching to IgE
Increase of VCAM-1 expression
What are the roles of IL-13? 10
airway eosinophilia (COPD, Asthma)
Mucous gland hyperplasia
airway fibrosis and remodeling
What are the roles of IL-5? 10
regulates Eosinophil production and survival
What are the roles of TNF? 10
recruits and activates inflammatory cells
alters function/growth of airway SM
What are only cells in humans that contain histamine? 11
Mast cells and basophils
What are the characteristics of Allergens? 12
Small and highly soluble
Carried via dry particles
No inflammation
Triggers Th2 response
Describe sensitization to allergen? What is another word that describes this phase? 13
Also called priming
IgE specific to the allergen is mounted on a Mast Cell
(With next exposure the mast cells are able to immediately degranulate)
What hypersensitivity is immediate?
Type I Hypersensitivity
Within the first 5 minutes what happens within a primed individual exposed to the allergen?
Preformed mediator release:
Histamine
Heparin
Tryptase
Within 5-30 minutes what happens within a primed individual exposed to the allergen? 14
Newly generated mediators:
Arachidonic Acid
Leukotriene D4
Prostaglandin D2
Within hours what happens within a primed individual exposed to the allergen? 14
Cytokines release:
IL-4
TNFα
What are the actions of histamine (biogenic amines)? 15
Vascular leak
Bronchoconstriction
Intestinal hypermotility
What is the action of Tryptase within a type I hyper sensitivity? 15
Tissue damage
What are the products excreted from eosinophils? 15
Eosinophil Collagenase
Eosinophil peroxidase
Major Basic Protein (MBP, cationic granule)
Eosinophil cationic protein (cationnic granule)
What are the common examples of type I hypersensitivity? 16
Anaphylaxis
Acute Urticaria (animal hair, insect bites, allergen testing)
Seasonal Rhinoconjunctivitis (hay fever)
Food Allergy
What happens during the Early phase of an Immediate Acute Atopic Response? 17
Allergen introduced
Cross-linking between two mIgE
Symptoms show
Inflammatory cells recruited by Mast cell cytokines
What are the early phase (immediate) symptoms of an acute atopic response? 17
Sneezing
Pruiritis
Rhinorrhea
Congestion
What happens during the Late phase of an Immediate Acute Atopic Response? 17
Influx and activation of: eosinophils, neutrophils, basophils, and Th2
10x increase in [Mast Cell] w/ increased Fcε expression
Systemic symptoms
What are unwanted consequences of Eosinophils? 18
local tissue damage
CHES - chronic hyperplastic eosinophilic sinusitis
What are the systemic symptoms that present during the last phase of a chronic atopic response? 18
fatigue
myalgia
asthma
Define Atopic Asthma? 19
airway hyper-responsiveness
characterized by BHR (Bronco-hyper reactivity)
What happens in systemic anaphylaxis? 20
dramatic increase in vascular permeability and constriction of smooth muscle
Pt can’t breath, vomitting, diarrhea, low BP
What are the five leukotrienes?
LTC4
LTD4
LTE4
LTB4 (pro-inflammatory)
