Hypersensitivity 8 20 14 Flashcards
sensitization vs effector stages
sensitization is clinically silent, is primary immune response
effector is secondary immune response
hypersensitivity def
an excessive or abnormal secondary immune response to a sensitizing agent
Type I hypersensitivity rxn
formation of IgE antibody
basophils and mast cells release vasoactive mediators
ex of type I hypersensitivity rxn
ANAPHYLAXIS, allergies, some forms of bronchial asthma
Type II hypersensitivity rxn
formation of IgM and IgG binding to antigen that’s cell/matrix based
phagocytosis or lysis of target cell by complement or antibody-dependent cellular cytotoxicity
Type III hypersen rxn
SOLUBLE antigen
antigen-antibody (IgG) complexes, activated complement, attracts neutrophils
type IV hypersen rxn
sensitized T lymphocytes
Th2 helper T cells generated as a result of what? in type I hypersen
IL-4
what do Th2 helper T cells make? in type I hypersen
IL4, IL5
how long does sensitization take for allergic disease?
4 weeks
what occurs during sensitization in allergic disease
allergen is presented by antigen presenting cell to Th2 cell, which releases IL4 and IL6 to stimulate B cells to make IgE
early phase of Type I hypersensitivity response
under 15 minutes
allergen cross-links with IgE on mast cell
mast cell releases: histamine, tryptase, leukotrienes, PGD2, IL-4, other cytokines
can basophils be involved in early phase of type I hypersen response?
yes
late phase response in type I hypersen
4-6 hours after exposure (due to time needed to make cytokines)
eosinophils make leukotrienes and other products
damage to epithelium, cellular recruitment
allergens vs irritants
allergens: IgE mediated, require sensitization, affects only those sensitized to allergen, not usually dose-dependent
irritant: not mediated through IgE, dose dependent response, will affect everyone at high enough dose
ex of allergens
pollen, house dust mite, furred animals, fungi or mold
ex of irritants
tobacco smoke
exhaust fumes
perfumes
what things are release immediately from mast cells due to preformed stores?
histamine
heparin (works like histamine)
enzymes like tryptase
how are basophils diff from mast cells in type I hypersen rxn?
basophils don’t release tryptase or PGD2
what remains identifiable in the serum for up to 4 hours after release from mast cell in type I hypersen rxn?
tryptase
role of tryptase in type I hypersen rxn
remodeling of connective tissue
effects of mast cell activation? (or basophil) in type I hypersen rxn
vascular permeability is increased
bronchoconstriction
intestinal hypermotility
inflammation
tissue dammage
how are cytokines and chemokines different from histamine when released from mast cells in activation in type I hypersen rxn?
cyotkines must be made with activation, so release is delayed 4 to 6 hrs after degranulation of preformed things like histamine
Il 4 and IL13 role in type I hypersensitivity rxn
associated with Th2 cells and lead to Ig class switching in B cells to produce IgE
what cytokines in type I hypsensitivity rxn promote survival and activation of eosinophils?
IL3, IL5, GM CSF
role of TNF in type I hypersen rxn
activates endothelium and leads to adhesion molecules expression
what lipid mediators are release from mast cells in type I hypersen rnx in immediate reaction?
leukotrienes C4, D4, E4-lead to eosionphil migration, sm musc contrac, vascular permeability, mucus hypersecretion
platelet activating factor-attracts eosinophils, activates eosinophils and neutrophils and platelets
late phase of type I hypser response in mast cells has mostly what type of cells responding?
eosinophils
you get elevated eosinophil count in what conditions? (mneumonic)
NAACP: neoplasia asthma allergy connective tissue disease parasitic disease
what kind of receptor does eosinophil have?
CCR3
corticosteroids’ effect on eosinophils
apoptosis of eosinophils
reduce IL-5 production
what is IL-5 made by
Th2 lymphocytes
IL-5 has what effects in vivo?
eosinophilia
what do eosinophils secrete?
IL5
Leukotrienes B4, C4, C5
what role do eosinophils play?
kill parasites and host cells
tissue damage
clinical aspects of type I hypersen
allergic rhinitis
asthma
anaphylaxis
urticaria
allergic rhinitis
cross-linking of IgE in nasal mucosa and ocular conjunctiva with specific antigen exposure
asthma
IgE mediated disease in lower airways
leads to wheezing, shortness of breath due to airway contriction (prevents exhalation), increased mucus secretion and production
immediately after anaphylaxic event, can you skin test?
no, b/c all the IgE would be used up in the response
H1 in anaphylaxis has what effect?
smooth muscle contrac
vascular permeab
H2 in anaphylaxis has what effect?
vascular permeab
H1 & H2 in anaphylaxis have what effect?
vasodilatation, pruritis
ex of type II hypersen rxn
Goodpasture syndrome bulloud pemphigoid pernicious anemia vasculitides thrombotic phenomena acute rheumatic fever
how do immune complexes cause damage in type III hypersen?
BOTH by activating FcgammaR expressing cells and activating complement at sites of deposition
where is type III hypersen damage usually found?
kidney, vessels, joints, skin
where do small complexes in type III hypersen usually precipitate?
blood vessel walls
ex of type III hypersen rxn
Arthus rxn
serum sickness (large quantities of foreign protein injected)
Farmer’s lung (hay dust, mold spores)
systemic antigen excess (autoimmune disease, infections with antigen production)
why in serum sickness, does it take 7-10 days to get symptoms?
b/c this is the time needed to switch from IgM to IgG (IgG actually fixes complement and causes the symptoms you see)
then when you have too much IgG, no longer get complement deposition so no longer get symptoms
how can type IV hypersen by distinguished from other types of hypersen rxns?
no antibodies
what is the usual target organ for type IV hypersen rxn?
skin
how long does it take for Type IV hypersen rxn to develop?
24-72 hours
ex of type IV hypersen rxn
tuberculin response
contact hypersensitivity
What makes IL4, IL5, IL13 in type I hypersen?
mast cells
what makes eotaxin and RANTES in type I hypersen?
mast cells
what makes MBP, EDN, ECP in type I hypersen?
eosinophils
where do you see symptoms in Type I hypersen?
early phase and late phase response
