Type I Hypersensitivity - Hunter Flashcards
(157 cards)
1
Q
what Ig mediates type 1 hypersensitivity?
A
IgE
2
Q
What type of antigen is used in type 1 hypersensitivity?
A
soluble antigen
3
Q
What is the effector mechanism of type 1 hypersensitivity?
A
Mast-cell activation and degranulation and eosinophils
4
Q
When we think of normal hay fever allergies, what type of hypersensitivity is this
A
type 1
5
Q
is the antigen in type 1 necessarily pathogenic?
A
no, type 1 is a response to an otherwise innocuous Ag
6
Q
how long does a type 1 reaction take?
A
can begin within seconds, but most take minutes to hours
7
Q
what is the evolutionary basis for a type 1 reaction?
A
protection against metazoan parasites
8
Q
T/F: there was evolutionary pressure to create allergies
A
FUCKING FALSE
9
Q
What cell mediates killing of worms?
A
IgE activated eosinophils
10
Q
Cross-linking of anti-parasite IgE on (blank) cells cuases release of mediators that promote their expulsion
A
mast cells
11
Q
by what route do allergens access the body?
A
mucosal surfaces
12
Q
What was the selective pressure to develop IgE mediated responses?
A
Worms. Billions of people infected with worms
13
Q
Plant pollens Animal dander Mold spores dust mite feces these are all extrnisic allergens that are (blanked)
A
inhaled
14
Q
Insect venoms vaccines drugs therapeutic proteins these are all extrinsic allergens that are (blanked)
A
injected
15
Q
food
orally administered drugs both gain access how
A
ingestion
16
Q
Do all people respond the same way to the same allergen?
A
Nope
17
Q
What cells in the mucosa begin the allergy response?
A
dendritic cells
18
Q
what cytokines do DCs release when they contact allergens?
A
IL4
IL5
IL9
IL13
19
Q
Cytokines released by DCs in response to allergies promotes what T cell differentiation?
A
TH2
20
Q
Can you have allergies without a TH2 response?
A
NOPE
21
Q
What class of allergen is a protein with CHO side chains, is effective at low dose, has a low Mwt., is highly soluble, stable, and binds MHCII?
A
airborne allergens
22
Q
What is the “benefit” of airborne allergens being low dose?
A
favors activatoin of IL4 producing T cells (TH2)
23
Q
What is the benefit of allergens with low Mwt?
A
they can diffuse into the mucosa easier
24
Q
what is the benefit of allergens being highly soluble?
A
can readily elute from its parent particle
25
t/f: allergens can still be immunogenic even after they have been dessicated
true
26
why is it necessary that allergens bind MHCII?
Need a T cell response to elicit allergies
27
what macromolecule are allergens?
proteins!!
28
Describe the genetic component to allergies
You have to have the MHCII molecules that will be able to bind to allergens.
29
What Ig is used in type 2?
IgG
30
What is the Ag type in type2?
cells surface or matrix associated Ag
31
What is the effector mechanism for type 2?
Complement, FcR+ cells (phagocytes and NK cells)
32
What are two notable examples of type 2 hypersens?
penicillin allergies and chronic urticaria (FceRI chain)
33
When using the cell surface receptor type Ag, what is the effector mechanism for type 2?
Ab alters signaling
34
what Ig is used in type 3?
soluble Ag
35
What is the effector mechanisms of type 3?
complement and phagocytes
36
What is formed in type 3 that cuases vascular damage
immune complexes
37
What are two common reactions that are seen from type 3?
serum sickness and Arthus reaction
38
What hypersens type is used in most autoimmune reactions?
type 2
39
what sets type 4 apart from the other types?
its the only one that doesnt use Abs!
40
What are the three immune reactants in type 4?
1. TH1
2. TH2
3. CTLs
41
what ag is used in type 4 Th1/
soluble ag
42
what is the effector mechanism in Th1 type 4?
macrophage activation
43
What is the ag in type 4 Th2?
soluble Ag
44
What is the effector mechanism for type 4 Th2?
IgE production, eosinophil activation, mastocytosis
45
What is the ag for CTL type 4?
cell-associated ag
46
what is the effector mechanism for CTL type 4?
cytotoxicity
47
Allergic responses involve Ig(blank) class switching of B cells
IgE
48
What are the two signaling systems used between T and B cells to switch to IgE?
IL4/IL4R
| CD40/CD40L
49
Which cell carries CD40 and which CD40L?
CD40L: T cell
CD40: B cell
50
Which cell produces IL4 and which has the receptor?
T cell produces, b cell has receptor
51
From what Ig subclass are you switching to produce IgE?
IgM to igE
52
Can IgM cause allergies?
NO
53
T/F: production of IgG instead of IgE can be allergy-protective
true
54
is IgE free in plasma or cell-bound?
cell-bound, unlike other Abs
55
Does IgE have low or high plasma levels?
low
56
What does an elevated plasma IgE indicate?
the patient has allergies
57
IgE binds the FceRI receptor on which three cell types?
1. mast cells
2. basophils
3. eosinophils
58
What protein modification does IgE have?
Glycosylation
59
Allergic reactions ocurr after the (first/second) exposure to Ag
SECOND
60
What is difference in time between DTH and type 1?
type 1 happens in seconds to minutes while DTH takes at least 18 hours
61
Where do you find mast cells?
skin, all mucosal areas, and lining the blood vessels
62
Is binding a single Ig receptor sufficient to trigger a mast cell?
NO, you have a threshold of stimulation where you need either multiple epitopes of one Ag or multiple Ags binding to begin signaling
63
What are the preformed mediators in mast cell granules?
vasoactive amines (histamine) and proteases (chymase, tryptase)
64
Enzymatic modification of what lipid leads to lipid mediators?
arachidonic acid
65
Transcriptional activation within the mast cell leads to (blank) production
cytokine
66
How are the granules released from the mast cell?
Granule exocytosis
67
What are the products of the lipid mediators?
Prostaglandins (PGD2)
| Leukotrienes (LTC4)
68
How are the lipid mediators released from the mast cell?
secretion
69
What cytokines do mast cells produce? How are they released?
TNF-a, secretion
70
What is the function of the vasoactive amines?
vascular dilation, smooth muscle contraction
71
what is the function of the proteases?
tissue damage
72
what is the function of the prostaglandins?
vascular dilation
73
what is the function of the leukotrienes?
smooth muscle contraction
74
what is the function of TNF-a?
inflammation and leukocyte recruitment
75
how long does it take for granule mediators to work?
seconds to minutes
76
how long does it take for lipid mediators to work?
minutes to hours
77
how long does it take for cytokines to work?
hours
78
What is the effect of mast cell activation on the GI tract? What is the clincial result?
increased fluid secretion, increased peristalsis.
| Expulsion of GI contents (worms)
79
What is the effect of mast cell activation on the ENT system? What is the clincial result?
decreased diameter, increased mucus secretion
| Congestion and blocking of airways, swelling in nasal passages
80
What is the effect of mast cell activation on the blood vessles? What is the clincial result?
increased blood flow and permeability
edeam leading to increased lymph flow to lymph nodes, increased cells and protein in tissue, increased effector responses, HYPOTENSION AND ANAPHYLACTIC SHOCK
81
the dose and ROUTE of allergen administration determines the type of (blank)-mediated allergic reaction
IgE
82
Hi dose IV Ag leads to:
general release of histamine, SYSTEMIC ANAPHYLAXIS
83
low dose SubQ Ag leads to:
local release of histamine, hives
84
low dose inhalation of Ag leads to:
allergic rhinitis, asthma
85
Ingestion of ag leads to:
contraction of intestinal smooth muscle, outflow of fluid into gut lumen, diffuse hives or ANAPHYLAXIS
86
T/F: enzymes frequently trigger allergies
true
87
dust mite fecal protein DerP1 cleaves (blank) in tight junctions to get into the mucosa
occludin
88
DerP1 is taken up by (blank) cells adn presented for (blank) cell priming
DCs, TH2 priming
89
Where do the DCs that pick up DerP1 prime the T cells?
in the LYMPH NODES
90
Plasma from the lymph node brings back to the mucosa that saw DerP1 what three things?
plasma cells
(making IgE)
mast cells
91
What percent of Americans are allergic to dust mites?
20%
92
what two classes of molecules do eosinophils secrete?
toxic proteins
| inflammatory mediators
93
Eosinophilia occurs in patients with:
allergies!
94
What cytokine induces eosinophilia?
IL5
95
Eoxtaxins 1 and 2 (CCL11) bind to what eosinophil receptor?
CCR3
96
Do eosinophils constitutively express FceRI receptor?
No, only activated eosinophils!
97
What type of bug do eosinophils protect against?
parasites
98
describe the acute response to asthma?
1. inflammatory mediators cause increased smoth muscle secretion
2. airway obstruction from secretions
3. recruitment of cells via TNF-a
99
describe the chronic response to asthma?
1. TNF-a reacts with TH2, making IL5 and eotaxin
| 2. Mast cells and eosinophils recruited by IL5/eotaxin
100
What are the effects of chronic inflammation of the lung?
Airway remodeling and hyperreactivity
101
T/f: most allergic reactions have both an immediate and late phase response
true
102
What characterizes the immediate allergic reaction?
vasodilation, congestion, and edema
103
What characterizes the late phase allergic reaction?
inflammatory infiltrate of eosinophils, neutrophils, and T cells
104
Describe the time course and severity of the immediate vs late phase reactions?
immediate: short lived and high level
late: longer lasting and milder symptoms
105
how long does it take to develop the immediate response?
minutes in a PREVIOUSLY SENSITIZED person
106
how long does it take to develop the late phase?
2-24 hours
107
Review the whole pathway of type 1 activation (7)?
1. Ag exposure
2. Activation of Th2 cells and IgE switching in B Cells
3. Production of IgE by B cells
4. Binding of IgE to mast cells
5. Repeat exposure to Ag
6. Activation of mast cells and degranulations
7. Immediate and late phase reaction.
108
What is an exaggerated IgE response called?
atopy, found in more than 50% of western people
109
T/f; one gene is involved in atopy
false; a variety of genes (MHCII, FceRI receptor, Th2 cytokines)
110
t/f: environmental factors influence atopy
true
111
What is the hygeine hypothesis?
Exposure to microbial pathogens promotes a Th1 deviation
112
Where is the MHC locus located?
6p21
113
What tests do you use to determine specific allergies?
Intradermal or epicutaneous skin test
114
What receptors do anti-histamines block?
H1
115
what is the effect of histamines on blood vessels?
DECREASES vascular permeability
116
What is the effect of histamines on unmyelinated nerves?
inhibits itching
117
what receptor does albuterol bind?
B-adrenergic
118
what is the effect of albuterol?
relaxes bronchial smooth muscle
119
What is the mechanism of action of Singulair?
Blocks leukotrienes D4, C4, and E4; inhibits bronchoconstriction
120
what are the effects of epinephrine?
relaxes bronchial smooth muscle, constricts vascular smooth muslce, reforms endothelial tight junctions
121
Systemic and topical corticosterioids suppress (acute/chronic) inflammation
chronic
122
What is the mechanism of actino of corticosteroids/
block NF-kb thereby blocking transcription of proinflammatory genes
123
T/F: mast cells are important in immunity for things other than parasites
true: viruses and bacteria as well.
124
What drugs would you use to control mediator actions?
antihistamines, B-blockers, lipoxygenase inhibitors
125
What drugs would you use to control chronic inflammatory reaction
corticosteroids
126
What drugs would you use to control a TH2 response?
desensitization therapy by injections of specific antigens
127
What drugs would you use to control IgE binding to mast cells?
Anti-IgE Abs
128
In desensitization, you are shifting from IgE to (blank)
IgG
129
How is cross-linking of IgE prevented in desensitization?
anti-allergen IgG binds up the allergen
130
What T cell type is produced during desensitization?
Tregs; secrete IL10 and TGf-b that promote isotype switching
131
omalizumab humanized mouse anti-IgE blocks IgE binding to the (blank) receptor ton mast cells, basophils, and eosinophils
FceRI
132
What is the most common chronic skin disease in young children?
atopic dermatitis (eczema)
133
T/F: most patients with AD are atopic
true
134
What two bugs commonly colonize and infect pts with AD?
staph aureus and herpes simplex virus
135
Elevated serum (blank) is seen in 80-85% of patients with AD
IgE
136
(blank) cells are also elevated in AD, along with elevated TH2 cytokines (which calls these cells to the sites)
Eosinophils
137
What is the Tx of AD?
avoidance of irritants and allergens, topical corticosteroids
138
Where does eczema normally present?
around the cheeks and mouth, moves then to trunk and extremities.
139
What is the "itch that rashes"?
eczema
140
Anaphylaxis to insect stings occurs in what percent of people?
3% of adults; 1% of kids
141
sensitization to insect venom is seen in what percent of adults?
25%`
142
How do you diagnose insect sting allergies?
Venom skin tests and venom specific IgE immunoassays
143
What is the efficacy of venom immunotherapy?
75-98%
144
These are examples of what?
1. Anaphylaxis from b-lactam antibiotcs
2. halthane hepatitis
3. hypotension post protamine
4. dermatitis from sulfonamides
5. serum sickness form phenytoin/cefaclor
6. hypotension after succinylcholine
7. quinine induced thrombocytopenia
8. phenophthalein induced fixed drug eruption
9. Cisplatinum urticaria
IgE mediated drug hypersensitivity
145
drugs like penicillin can directly bind with macromolecules on cell surfaces forming (blank)
hapten-carrier complexes
146
Describe the concept of multivalency related to drug haptenation?
Multiple drug epitopes must bind at a threshold level to induce a drug specific immune response
147
The b-lactam ring in penicillin will cause what kind of reaction of lysine in proteins?
acylation
148
Is a hapten immunogenic on its own?
No, it must be conjugated to a protein
149
When penicilloyl haptens are taken up into MHC II in the presence of a danger signal from infection, (blank) cells are activated
CD4 T cells
150
The hapten activated CD4 T cell activates specific b cells to produce (blank)
IgE anti-penicilloyl Abs
151
What antibiotics share the b-lactam ring?
1.penicillin
2.carbapenems
3.cephalosporins
4.monobactams
ALL OF THESE CAN CAUSE ALLERGIC CROSS REACTIONS
152
anti-penicillin IgE arms what type of cells?
mast cells
153
What type of exposure route is the greatest antigenic load to the immune system?
Food!
154
T/F: most people develop tolerance to food allergies?
true
155
T/F: peanut allergies have tripled in the past decade in western countries
ture
156
what is the only proven therapy for food allergies?
strict avoidance
157
What is the most common form of food allergy?
fruit!!
