Hypersensitivity Type I Flashcards
characterize type I-IV hypersensitivities by:
- name
- basic immunologic mechanism
- identify any immediate vs delayed types
- Type I - allergic/anaphylactic hypersensitivity
- IgE mediates mast cell degranulation → histamine release
- immediate onset
- Type II - cytotoxic type
- complement binds IgG / IgM bound to surface antigen → complement cascade
- Type III - immune complex type
- IgG / IgM form antigen antibody complexes that deposit in post capillary venules → become bound by compliment → complement cascade
- Type IV - cell-mediated
- T-cells stimulate cell mediated rxns by many immune cells
- delayed onset
Type I - IV hypersensitivity
- define
- describe mechanism
- give examples
describe the onset of type 1 hypersensitivity rxns
immediate onset: symptoms occur in seconds to minutes after allergen contact
discuss the general mechanism of type I hypersensitivity reactions
- allergen cross-links IgE sensitized mast cells (mast cells that already have IgE bound to their Fc-receptors from previous exposure)
- this triggers mast cell degranulation → histamine released
discuss the affects of histamine throughout the body
- GI tract: inc activity
- fluid secretion
- peristalsis → diarrhea, emesis
- lungs:
- bronchoconstriction
- mucous secretion → coughing, sneezing
- vasculature
- vasodilation → inc blood flow
- inc vascular permeability → leakage into tissues → edema
- skin
- uticaria (hives)
- atopic dermatitis
- what causes anaphylaxis?
- how is anaphylaxis treated?
- systemic allergic rxns caused by wide-spread mast cell degranulation (type I)
- tx = epinephrine
discuss the symptoms of severe allergic reaction
same type I sx, just more severe
- wide-spread vasodilation → catastrophic drop in BP
- suffocation, d/t
- air-way (bronchial) constriction
- epiglottal swelling
- GI - diarrhea / abdominal cramps / vomiting
discuss the common allergens, route of entry, and response for
- systemic anaphylaxis
- wheel and flare
- allergic rhinitis
- bronchial asthma
- food allergy
- other than common allergens, what triggers can cause allergy/anaphylactic reactions?
- how do they do this?
all induce mast cell / basophil degranulation either by
- binding cross linked IgE: lectins
-
directly increasing intracellular Ca+:
- anaphylatoxins (C3a, C5a) - complement products that are degranulators
- calcium ionophores
- radiocontrast dyes
-
drugs
- opiates: codeine, morphine
- vancomycin
-
physical contact urticaria
- cold induced
- dermatographic
other than allergens, what molecules can induce Type I hypersensitivity by binding IgEs on mast cells/basophils?
lectins
what substances increase intracellular Ca+? what does this lead to?
- this leads to mast cell degranulation → type I hypersensitivity rxn
- anaphylatoxins (C3a, C5a) - complement products that are degranulators
- calcium ionophores
- radiocontrast dyes
-
drugs
- opiates: codeine, morphine
- vancomycin
what “physical” means can induce a Type I hyper sensitivity rnx?
-
physical contact urticaria
- cold induced
- dermatographic
what is atopy?
- what causes atopy?
- how does it present?
- a genetic predisposition to make IgE
- d/t defects in IgE response genes on chromosomes 5, 6, 11
- Th2 gene cluster - chromosome 5
- MHC-II - on chromosome 6
- IgE Fc receptor - chromosome 11
- classic presentation = triad
- rhinitis
- asthma
- dermatitis
what are the stages of Type I Hypersensitivity reaction?
- sensitization
- activation
- effector phase
- late phase reaction
outline the sensitization phase of Type I Hypersensitivity rxn
- = initial exposure
- antigen ingested by APC
- antigen presented to TCR on T-helper cell (MHC-II-CD4+ binding)
- this induces expansion of Th2 T-helper cell subset
- Th2 produces IL-4 and IL-13
- IL-4 and IL-13 induces B-cells → produce IgE (class switch)
- IgE binds IgE Fc receptors on mast cells/basophils
outline the activation stage of Type I hypersensitivity
- = second exposure to antigen
- allergen binds arms of IgEs that are bound (cross linked) to mast cells / basophils, inducing
- methylation of membrane phospholipids, which
- inc intracellular Ca+ → induces Ca+ influx, which
- induces degranulation → release of mediators
outline the effectors phase of Type I hypersensitivity rxn
- response to release of mediators (formed and preformed) from mast cells/basophils
- pre-formed mediators
- histamine
- serotonin
- tryptase
- heparin
- ECF-A
- inflammatory cytokines: IL-1, TNF-a, IL-8, IL-5, IL-4
- newly synthesized mediators (produced from AA)
- leukotrienes: LTC4, LTD4, LTE4
- prostaglandins (PGF, PGE)
- prostacyclin (PGI2)
- thromboxane (TXA-2)
- platelet activating factor (PAF)
- pre-formed mediators
what pre-formed mediators are released from mast cells/basophils?
effector phase of Type I
- histamine
- serotonin
- tryptase
- heparin
- ECF-A
- inflammatory cytokines: IL-1, TNF-a, IL-8, IL-5, IL-4
what newly formed mediators are released from basophils/mast cells?
effector phase of Type I
- products of AA pathway
- leukotrienes: LTC4, LTD4, LTE4
- prostaglandins (PGF, PGE)
- prostacyclin (PGI2)
- thromboxane (TXA-2)
- platelet activating factor (PAF)
what is histamine & its effects?
pre-formed mediator
- binds to H1 receptors on smooth muscle
- bronchoconstriction
- vascular permeability / vasodilation
- binds to H2 receptors on gut
- mucous secretion
- acid release
how do anti-histamines work to nullify effects of histamine?
- diphenhydramine (benadryl) blocks H1 stimulation (bronchoconstriction)
- cimeditine (tagamet): blocks H2 stimulation (gut mucous/acid secretion)
what is serotonin & its effect?
pre-formed mediator
- functions like hsitamine
what is tryptase & its effect?
pre-formed mediator
- generates anaphylatoxins (C3a and C5a) → further mast cell degranulation
what is ECF-A & its effects?
pre-formed mediator
- attracts eosinophils
what cytokines are released during the effector phase of Type I hypersensitivity & what do they do?
pre-formed mediators
- IL-1, INFa: induce leukocyte migration
- IL-8: attracts neutrophils
- IL-4 (also made by Th2 cells)
- sustains Th2
- IgE production
- IL-5: activate eosinophils
what pre-formed mediators effect eisonophils in the effector phase of type I? what do they do?
- ECF-A: attracts eosinophils
- IL-5 (cytokine): activates eosinophils
what are prostaglandins & their effect?
newly formed mediator (AA product)
- bronchoconstriction
- vasodilation
- INHIBIT platelet aggregation
what are thromboxanes (TXA) and their effect?
newly formed mediator (AA product)
- induce platelet aggregation
what are prostacyclins and their effects?
newly made mediator
- vasodilation
- INHIBIT platelet aggregation
what are platelet activating factors (PAF) and their effects
newly made mediator
- vasodilation
- bronchoconstriction
- INDUCE platelet aggregation
which newly made mediators in the effector phase of type I rxn
- induce platelet aggregation?
- inhibit platelet aggregation?
- induce platelet aggregation
- TXA
- PFA (platelet aggregation)
- inhibit platelet aggregation
- prostacyclins (PGI)
- prostaglandins (PGF, PGE)
prostaglandins, prostacyclins & PAF - compare/contrast effects
- vasodilation - ALL
- bronchoconstriction - ALL
- platelet aggregation
- PGIs, PGE/PGF = inhibit
- PAF = induce
what are leukotrienes and their effects?
newly made mediators (AA products made by SRS-A)
- LTC-4, LTD-4, LTE-4
- LTC-4: chemotactic for neutrophils
- LTD-4, LTE-4: bronchoconstriction
what type I mediators are chemotactic for neutrophils?
- IL-8 (pre-made mediator)
- LTB-4 (newly made mediator)
what are the primary cause of anti-histamine resistant asthma?
leukotrienes
outline the late phase of Type I rxn
- formation of inflammatory infiltrate over next 24 hours
- characterized by eosinophil degranulation
- which is due to
- ECF-A (attraction)
- IL-5 (activation)
- IgE binding Fc receptors (CD23) on surface (degranulation)
- and leads to:
-
epithelial damage, due to
- cytotoxins (major basic protein/cationic protein) → ROS → damage epithelium
-
shut-down of mast-cell products:
- histaminase → inactivates histamine
- anti-sulfatase → inhibits SRS-A release, inhibiting leukotriene production
-
epithelial damage, due to
- which is due to
- characterized by eosinophil degranulation
which component of the Type I hypersensitivty reactions inhibits histamine effects?
when/how does this occur?
anti-histaminase, made by eosinophils in the late phase (degrades histamine released from mast cells during activation phase)
what is SRS-A? how is it produced/regulated?
- made by mast-cells
- allows production of leukotrienes (newly made mediators) during effector phase
- LTB-4: neutrophil migration
- LTC-5, LTD-4, LTE-4): smooth muscle constriction
- inhibited by anti-sulfatase released by eiosinophils during the late phase
anaphylaxis
- m/c cause?
- treatment?
- m/c cause = penicillin
- tx = epinephrine
urticaria (hives) - erythematous, edematous (raised) wheels that
- blanche with pressure
- have a systemic distribution
- are VERY PRURITIC
common manifestation of immediate (type I hypersensitivity)
angioedema (swelling) that is
- non-pitting
- PAINFUL (instead of pruritic)
- often in the face - eyes, nose, lips
common manifestation of immediately (type I) hypersensitivity
what is the most common atopic disease? describe its presentation & cause
= allergic rhinitis (hay fever)
- type I hypersensitivity
- can be in context of HLA-DR2
- presentation
- congestion
- sneezing / runny nose
- itchy, watery eyes
atopic dermatitis
- hypersensitivity type
- demographic
- presentation
- dx
- both type II and type IV eczema presentations
- demographics - usually young children
- presentation
- on FACE + FLEXOR SURFACES
- scaly, itchy rashes
- dx - papules containing eosinophils
what are common causes of allergies d/t environmental antigens?
- sulfur dioxide
- nitrogen oxide
- fly ash / diesel exhaust particles
how does hyposensitization therapy work
- sub-Q & sub-lingual administration:
- both: shift away from Th2 → less IL-4/Il-13 → less IgE → BLOCKS MAST CELL DEGRNULATION
-
subcutaneous administration: shift to Th1 → more INF-y → more IgG1/IgG4
- good for bee sting allergies
-
sublingual administration: shift to Treg → more IL-10 / TGF-B
- foods, airborne allergens
drug therapy for allergies
- anti-histamines
- blocks H1 receptors
- good for urticaria, conjunctivits, rhinitis
- NOT good for
- asthma - give B-agonists, corticosteroids
- anaphylaxis - give epinephrine