Hypersensitivity Type I Flashcards
(46 cards)
1
Q
characterize type I-IV hypersensitivities by:
- name
- basic immunologic mechanism
- identify any immediate vs delayed types
A
- 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
2
Q
Type I - IV hypersensitivity
- define
- describe mechanism
- give examples
A
3
Q
describe the onset of type 1 hypersensitivity rxns
A
immediate onset: symptoms occur in seconds to minutes after allergen contact
4
Q
discuss the general mechanism of type I hypersensitivity reactions
A
- 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
5
Q
discuss the affects of histamine throughout the body
A
- 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
6
Q
- what causes anaphylaxis?
- how is anaphylaxis treated?
A
- systemic allergic rxns caused by wide-spread mast cell degranulation (type I)
- tx = epinephrine
7
Q
discuss the symptoms of severe allergic reaction
A
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
8
Q
discuss the common allergens, route of entry, and response for
- systemic anaphylaxis
- wheel and flare
- allergic rhinitis
- bronchial asthma
- food allergy
A
9
Q
- other than common allergens, what triggers can cause allergy/anaphylactic reactions?
- how do they do this?
A
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
10
Q
other than allergens, what molecules can induce Type I hypersensitivity by binding IgEs on mast cells/basophils?
A
lectins
11
Q
what substances increase intracellular Ca+? what does this lead to?
A
- 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
12
Q
what “physical” means can induce a Type I hyper sensitivity rnx?
A
-
physical contact urticaria
- cold induced
- dermatographic
13
Q
what is atopy?
- what causes atopy?
- how does it present?
A
- 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
14
Q
what are the stages of Type I Hypersensitivity reaction?
A
- sensitization
- activation
- effector phase
- late phase reaction
15
Q
outline the sensitization phase of Type I Hypersensitivity rxn
A
- = 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
16
Q
outline the activation stage of Type I hypersensitivity
A
- = 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
17
Q
outline the effectors phase of Type I hypersensitivity rxn
A
- 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
18
Q
what pre-formed mediators are released from mast cells/basophils?
A
effector phase of Type I
- histamine
- serotonin
- tryptase
- heparin
- ECF-A
- inflammatory cytokines: IL-1, TNF-a, IL-8, IL-5, IL-4
19
Q
what newly formed mediators are released from basophils/mast cells?
A
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)
20
Q
what is histamine & its effects?
A
pre-formed mediator
- binds to H1 receptors on smooth muscle
- bronchoconstriction
- vascular permeability / vasodilation
- binds to H2 receptors on gut
- mucous secretion
- acid release
21
Q
how do anti-histamines work to nullify effects of histamine?
A
- diphenhydramine (benadryl) blocks H1 stimulation (bronchoconstriction)
- cimeditine (tagamet): blocks H2 stimulation (gut mucous/acid secretion)
22
Q
what is serotonin & its effect?
A
pre-formed mediator
- functions like hsitamine
23
Q
what is tryptase & its effect?
A
pre-formed mediator
- generates anaphylatoxins (C3a and C5a) → further mast cell degranulation
24
Q
what is ECF-A & its effects?
A
pre-formed mediator
- attracts eosinophils
25
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
26
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
27
what are prostaglandins & their effect?
newly formed mediator (AA product)
* bronchoconstriction
* vasodilation
* INHIBIT platelet aggregation
28
what are thromboxanes (TXA) and their effect?
newly formed mediator (AA product)
* induce platelet aggregation
29
what are prostacyclins and their effects?
newly made mediator
* vasodilation
* INHIBIT platelet aggregation
30
what are platelet activating factors (PAF) and their effects
newly made mediator
* vasodilation
* bronchoconstriction
* INDUCE platelet aggregation
31
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)
32
prostaglandins, prostacyclins & PAF - compare/contrast effects
* vasodilation - ALL
* bronchoconstriction - ALL
* platelet aggregation
* PGIs, PGE/PGF = inhibit
* PAF = induce
33
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
34
what type I mediators are chemotactic for neutrophils?
* IL-8 (pre-made mediator)
* LTB-4 (newly made mediator)
35
what are the primary cause of anti-histamine resistant asthma?
leukotrienes
36
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**
37
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)
38
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_
39
anaphylaxis
* m/c cause?
* treatment?
* m/c cause = penicillin
* tx = epinephrine
40
urticaria (hives) - erythematous, **edematous (raised) wheels** that
* blanche with pressure
* have a systemic distribution
* are VERY PRURITIC
common manifestation of immediate (type I hypersensitivity)
41
**angioedema** (swelling) that is
* non-pitting
* PAINFUL (instead of pruritic)
* often in the face - eyes, nose, lips
common manifestation of immediately (type I) hypersensitivity
42
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**
43
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
44
what are common causes of allergies d/t environmental antigens?
* sulfur dioxide
* nitrogen oxide
* fly ash / diesel exhaust particles
45
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
46
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
