hypersensitivity I Flashcards
describe the stages leading to a type I hypersensitivity reaction (5)
- first exposure to antigen
- activation of TH2 cells that cause IgE class switching in B cells
- production of IgE
- binding of IgE to FceRI receptors on mast cells
- repeat exposure to antigen = mast cell degranulation
what stimulates mast cell degranulation specifically?
antigen binds to IgE (bound already to FceRI), this causes ITAM phosphorylation in the mast cell that triggers signaling cascade
3 consequences of ITAM phosphorylation in mast cells
1- granule exocytosis (vasoactive amines, proteases)
2- formation of lipid mediators through modification of arachidonic acid (PG, LT)
3- transcriptional activation of cytokine genes
what is a “unique” feature about IgE in type I hypersensitivity?
IgE will bind to FceRI before it binds to antigen
route of entry for systemic anaphylaxis, sx
intravenous (directly or via gut absorption)
laryngeal edema, circ collapse, death
route of entry for acute urticaria, sx
systemic through skin
localized increase in blood flow/swelling
route of entry for hay fever, sx
contact with conjunctiva of eyes, nose
edema of nose/eyes
route of entry for asthma, sx
inhalation into lower airways
airway inflammation, broncho-constriction, inc mucus
route of entry for food allergies, sx
oral
vomiting, diarrhea, itching, hives (rarely anaphylaxis)
common household cause of asthma
D. pteronyssimus and fecal particles due to Der p1 (cysteine protease)
how does Der p1 enter tissues?
cleaves occluding tight junctions to gain access to tissue, then it is recognized as foreign by dendritic cells
which IL are involved in allergic responses? what type of cell will induce B cell class switching to IgE?
IL-4, 5, 9, 13
TH2
knock outs of what 4 substances will inhibit allergic reactions?
IL-4, IL-13, CD40, STAT6
what are the “preformed” substances in mast cell granules? (2)
histamine
enzymes to activate MMP to break down ECM
what are the “newly synthesized” substances by mast cells? (4)
chemokines, lipid mediators, cytokines, TNF
what 2 substances are toxic to parasites?
histamine, heparin
what chemokine attracts monocytes/macrophages and neutrophils?
CCL3
ow do mast cells (and basophils) amplify the IgE response?
release IL-4 and express CD-40L to stimulates additional IgE production by plasma cells
which antibodies are bound by eosinophils?
IgA and IgG
what stimulates the production of eosinophils?
IL-5
what are the 3 levels of control for eosinophils?
1- small output from bone marrow, production increased only in response to IL-5 and TH2 cells
2- penetration of tissues by eosinophils requires specific cytokines
3- high affinity FceR1 not expressed until activated by cytokines/chemokines
___ are responsible for immediate run vs. ____ for late-phase reaction
preformed (histamine, others) newly synthesized (lipids, peptides, VEGF, cytokines)
what 2 IL cause the transformation of epithelial cells to goblet cells?
IL-9 and IL-13
acute airway response vs. chronic airway response when exposed to allergen
acute- increased mucus, bronchi-constriction
chronic- cytokines and eosinophils lead to airway remodeling
