Hypersensitivity Flashcards
describe type I hypersensitivity
- sensitization
- antigen contact, typically low-dose via mucous membranes (respiratory, GI), IgE production
- elicitation (re-exposure)
- pre-formed IgE (allergen-specific) triggers mast cell activation mediator release
- reactions
- can occur within seconds-minutes of exposure
- severity ranges from irritating to fatal
describe the sensitization response
- IgE produced by plasma cells is rapidly taken up by FcER1 on tissue mast cells and circulating basophils (serum 2 days; compare to IgG, which is 21 days)
describe the early phase of the sensitization response
-
IgE crosslinking by antigen release of preformed mediators
- immedate release of histamine
- smooth muscle constriction, vasodilation, vascular leak, GI motility (increased), mucous secretion, sensory nerve activation
- immedate release of histamine
-
followed by rapid production of arachidonic acid products
- within minutes: leukotrienes, prostaglandins
describe the late phase of the sensitization response
- gene activation leads to new cytokine production ~6 hours after antigen triggering
- TNFa
- recruit inflammatory cells
- IL-3, IL-5, GM-CSF
- eosinophil production
- IL-4, IL-13
- propogate Th2 response
- TNFa
the innate responder cell in type I hypersensitivtiy is ____
describe this
the innate responder cell in type I hypersensitivtiy is eosinophils
- production of eosinophils in bone marrow driven by: IL-5 (Th2 cytokine); also IL-3 and GM-CSF
- chemotaxis from blood to tissue sites utilizes:
- IL-5
- eotaxins (CCL11, CCL24, CCL26)
- primed for activation by IL-5, eotaxins C3a/C5a
- expression of FcR for IgG, IgA, IgE
the most potent trigger for eosinophils is ____
what does it release?
the most potent trigger for eosinophils is FcR-crosslinking
- results in exocytosis of preformed toxic proteins
- major basic protein
- eosinophil cationic protein
- eosinophil-derived neurotoxin
- propagate the response:
- secrete IL-3, IL-5, GM-CSF
- secrete IL-8 (PMN attractant)
describe the manifestations of Type I Hypersensitivity
- respiratory mucosa
- allergic
- rhinitis
- asthma
- GI mucosa
- food allergy
- skin
- contact urticaria
- circulation
- anaphylaxis
describe the process of anaphylaxis
- response to systemic circulation of allergen
- IgE cross-linking on mast cells in perivascular tissue
- circulating histamine, PGs/LTs –> vasodilation, vascular leak
- high-output shock: decreased BP despite increased CO
in Type II (cytotoxic) Hypersensitivity, the damaged is mediated by _____
in type II hypersensitivity, the damage is mediated by tissue-specific IgG or IgM
describe the hapten response
- mechanism of sensitization
- a foreign agent (typically drug) acts as a hapten
- conjugates self protein modified self
- T cell/B cell response high affinity
- anti-self IgG or IgM
- on re-exposure
- hapten conjugation to self modified
- binding of IgG or IgM to modified self tissue (platelet, RBC)
- activation of normal immunoglobulin effector
summarize the antibody function and then the resulting syndrome
describe type III (immune complex) hypersensitivity
describe type IV (delayed) hypersensitivity
- group of T cell mediated responses to antigen
- direct killing of target cells (by CD8 T cells)
- indirect via activation of macrophages (CD4 T cells)
- sensitization is required
- on re-exposure: reactions occur over 1-3 days
- T cells are necessary and sufficient
____ do not have type IV reactions
athymic subjects do not have type IV reactions
describe the pathogenesis of type IV hypersensitivity
summarize hypersensitivity type I
summarize type II hypersensitivity
summarize type III hypersensitivities
summarize type IV hypersensitivities
