Type I Hypersensitivity Flashcards
1
Q
what Ab is involved in Type I hypersensitivity reactions?
A
IgE
2
Q
what Ag is involved in Type I
A
exogenous antigens
3
Q
what is the response time for Type I?
A
15-30min (fast)
4
Q
what does a type I reaction look like?
A
wheal and flare, red, typical allergic reaction or anaphylactic shock
5
Q
what cell types are prevalent for Type I?
A
basophils and eosinophils
6
Q
examples of type I?
A
allergies, asthma, hay fever, anaphylactic shock, classic allergy
7
Q
what Ab is involved in Type II hypersensitivity reactions?
A
IgG, IgM
8
Q
what Ag is involved in Type II
A
cell surface Ag (cytotoxic hypersensitivity)
9
Q
response time for Type II
A
minutes to hours
10
Q
appearance of Type II
A
lysis and necrosis
11
Q
what cell types are prevalent for type II?
A
antibody and complement (ADCC)
12
Q
example of Type II?
A
erythroblastosis fetalis (Rh+/Rh- mom baby), goodpasture’s nephritis, blood transfusion reactions, autoimmune hemolytic anemia, myasthenia gravis
13
Q
Ab involved in type III hypersensitivity reactions?
A
IgG, IgM
14
Q
Ag involved in type III?
A
soluble Ag
15
Q
response time for type III
A
3-8 hours
16
Q
appearance of type III?
A
erythema and edema, necrosis
17
Q
cell types prevalent for type III?
A
complement and neutrophils, immune complexes!!
18
Q
examples of TypeIII
A
chronic inflammation serum sickness rheumatic fever rheumatoid arthritis systemic lupus erythematosus glomerulonephritis
19
Q
Ab associated with Type IV hypersensitivity?
A
none! is T cell mediated! Tdth cells release cytokine/chemokines
20
Q
Ag associated with type IV?
A
Ag from tissues and organs
21
Q
response time for type IV?
A
48-72 hours (delayed type hypersensitivity DTH)
22
Q
appearance of Type IV?
A
erythema and induration
23
Q
cell types prevalent for type iV?
A
monocytes and lymphocytes (activation of T cells Th and Tc)
24
Q
examples of Type IV?
A
contact dermatitis, granulomatous lesions, TB lesions, TB skin test, graft vs host disease (GVHD) (graft rejection)
25
what is atopy
genetic trait to have predisposition for hypersensitivity or allergy
26
what is an epitope?
smaller part of an antigen
27
all hypersensitivity reactions are the consequence of what?
adaptive immune response (memory)
28
mechanism of action for type I ?
Ag bound IgE induces degranulation of mast cells and basophils. Vasoactive mediators are released. (classic allergy )
29
hay fever is an example of
type I
30
asthma is an example of
type I
31
hives are an example of
type I
32
food allergies are examples of
type I
33
eczema is an example of
type I
34
what is systemic anaphylaxis?
degranulation systemically involving multiple organs
35
Type II is also called
cytotoxic hypersensitivity
36
type II MOA
Ab that is directed against cell surface Ag mediates cell destruction via complement activation or ADCC
37
what type of reaction is erythroblastosis fetalis
type II
38
blood transfusion reactions are examples of
type II
39
myasthenia gravis is an example of
type II
40
autoimmune hemolytic anemia is an example of
type II
41
type III is also known as
immune complex disease
42
MOA type III
Ag-Ab complexes deposit in various tissues that induce complement activation, which induces inflammatory response. causes a massive infiltration of neutrophils
43
what disease is a result of localized type III
arthus reaction
44
serum sickness is an example fo
type III
45
what type of reaction is rheumatic fever?
type III
46
what type of reaction is rheumatoid arthritis ?
type III
47
what type of reaction is systemic lupus erythematosus?
type III
48
glomerulonephritis is due to
type III hypersensitivity
49
type IV is called
delayed type hypersensitivity
50
MOA type IV
sensitized Tdth cells release chemokines/cytokines that help recruit and activate macrophages and/or Tc cells, these mediate direct cellular damage
51
what type of reaction is contact dermatitis?
type IV
52
what type of reaction is granulomatous leions?
type IV
53
what type of reaction is graft vs host disease (GVHD)
type IV
54
what causes TB lesions?
type IV
55
what type of reaction is the TB skin test?
type IV
56
what is FceRI?
high affinity IgE receptor found on mast cells, basophils and activated eosinophils
57
how is FceRI involved in type I Hs
the allergen binding to IgE attaches to the FceRI on mast cells (specifically), which triggers signaling for degranulation
58
how do cells isotype switch to IgE upon second exposure to antigen?
Th2 cells provide IL-4 that is required by B cells to switch from IgM to IgE
59
how does degranulation occur with 2nd exposure?
allergen binds IgE and crosslinks to activate signal with tyrosine phosphorylation. Ca influx causes degranulation and release of mediators
60
what do mast cells do in a 2nd exposure
release mediators that attract basophils and eosinophils,
61
what type of immune response is involved in type I
Th2 immune response
62
what polymorphic genes could be associated with Type I hypersensitivity?
1. IL-4 receptor
2. IL-4 cytokine promoter region
3. high affinity IgE receptor (FceRI)
4. class II MHC (promotes Th2 response)
5. inflammation associated genes
63
how does binding of IgE a impact its life span?
IgE attachment to mast cell FceRI increases its lifespan from days to months.
64
what are the 2 kinds of mast cells?
1. mucosal mast cell
| 2. connective tissue mast cell
65
what does mucosal mast cell produce?
tryptase
66
what does CT mast cell produce?
chymotryptase (chymase)
67
what mast cells are the only mast cells present in pt with T cell immunodeficiencies?
connective tissue mast cells
68
what toxic mediators do mast cells release?
1. histamine
| 2. heparin
69
why do mast cells release toxic mediators?
to poison parasites, increase vascular permeability, and cause smooth muscle contraction
70
why do mast cells release enzymes?
to remodel connective tissue matrix
71
what lipid mediators do mast cells release?
1. leukotrienes C4,D4,E4
| 2. platelet activating factor
72
why do mast cells release leukotrienes?
to cause smooth muscle contraction, increase vascular permeability, and cause mucus secretion
73
why do mast cells release platelet activating factor?
to attract leukocytes, amplify production of lipid mediators, and activate neutrophils, eosinophils, and platelets.
74
what major mediator of type I anaphylactic hypersensitivity do mast cells release?
ECF-A (eosinophil chemotactic factor of anaphylaxis)
75
what impact does mast cell activation have on the GI tract?
increased fluid secretion and peristalsis causing expulsion of GI contents (diarrhea and vomiting)
76
what impact does mast cell activation have on the airways?
decreased diameter and increased mucus secretion leading to congestion and blockage of airways (wheezing, coughing and phlegm) and swelling and mucus secretion in nasal passages
77
what does the decreased diameter and increased mucus secretion cause in type I ?
congestion and blockage of airways (wheezing, coughing and phlegm) and swelling and mucus secretion in nasal passages
78
what impact does mast cell activation have on blood vessels?
increased blood flow and increased permeability (vasodilation)
79
what does vasodilation and permeability cause in type I?
increased fluid in tissues causing increased flow of lymph to LN, increased cells and protein in tissues, and increased effector response in tissues
80
what are basophils in relation to type I
granulocytes that initiate Th2 responses and the production of IgE
81
what granules do basophils contain
granules that stain with basic dye like hematoxylin
82
how do basophils initiate Th2 responses?
secreting IL-4 and IL-13
83
what do eosinophils do in relation to type I
granulocytes that release toxic mediators in IgE-mediated responses
84
what do eosinophils release?
histaminases and arylsulfatases that degrade histamine and leukotrienes
85
what do arylsulfatases do
degrade leukotrienes
86
what is the purpose of eosinophils' secreted enzymes
enable control of allergic symptoms
87
what are the mediators of type I hypersensitivity?
1. histamine (preformed) (causes immediate effect)
2. eosinophil chemotactic factor (ECF-A) (preformed) (causes immediate effect)
3. prostaglandins and thromboxanes
4. leukotrienes
88
what occurs after mediators are released?
active only a few minutes, and are rapidly inactivated and slowly resynthesized
89
what is the effect of type I hypersensitivity on lung airflow
FEV/L/s changes, immediately spikes down (preformed mediators), then returns to normal, then decreases again 8 hours later (from resynthesized mediators) . is the etiology of wheezing.
90
what are the primary mediators of type I hypersensitivity?
1. histamine
2. cytokines TNFa, IL-1, and IL-6
3. chemoattractants for ECF-A
4. enzymes (tryptase, chymase, cathepsin)
91
what are the secondary mediators of type I hypersensitivity?
1. leukotrienes
2. prostaglandins
3. thromboxanes
4. Th2 cytokines (IL-4, IL-5, IL-13, GM-CSF)
92
what conditions does histamine release cause?
1. allergic rhinitis
2. urticaria
3. angioedema
4. bronchospasm (acute anaphylactic reactions)
93
what does histamine cause?
1. constriction of smooth muscles
| 2. dilation of blood vessels
94
what does constriction of smooth muscle lead to?
in bronchioles, causes wheezing
| in GI, cramps and diarrhea
95
what does vasodilation lead to?
increases fluids in tissues causing swelling
96
how to treat histamine release?
antihistamines to block binding of histamine to its receptors
97
what is a H1 receptor blocker?
benadryl and claritin
98
what is a H2 receptor blocker?
cimetidine (tagamet) -- for GI
99
what is ECF-A
eotoaxin (CCL11) that is the most important chemokine in the migration of eosinophils
100
what controls the mobility of eosinophils?
CCL11, CCL5, CCL7 and CCL13 by binding to the receptor CCL3 on eosinophils
101
what do prostaglandins do?
increase capillary permeability and induce bronchoconstriction
102
what do thromboxanes do?
aggregate platelets
103
where are prostaglandins and thromboxanes derived from?
arachidonic acid via COX pathway
104
what can treat prostaglandin and thromboxane release?
COX inhibitors like ASA and celecoxib
105
what are leukotrienes
slow reacting substance of anaphylaxis (SRS-A) that are made after the crosslinking of IgE to FceRI
106
what do leukotrienes do
increase vascular permeability and increase smooth muscle contraction, ARE MAJOR MEDIATORS IN BRONCHOCONSTRICTION OF ASTHMA
107
what mediators are major cause of bronchoconstriction in asthma?
leukotrienes
108
what can inhibit leukotriene release
LTRA (leukotriene receptor antagonists) like montelukast (singulair)
109
what is the triple response of lewis (to local exposure)
1. flush due to direct vasodilation of capillaries
2. flare due to axonal reflexes and dilation of arterioles
3. wheal due to inflammation, exudates, and edema.
110
what does systemic response of lewis lead to
dilation of peripheral blood vessels in the microcirculation, leading to decrease in blood pressure and increase in HR
111
what is the most common systemic anaphylaxis?
penicillin allergy
112
what is the MOA of penicillin allergy?
beta lactam ring can be cleaved to create covalent conjugates with body proteins, makes new foreign epitopes. sometimes response is dominated by Th2 cells that help B cells make IgE specific for new epitopes. if receive penicillin a 2nd time, anaphylaxis and maybe death
113
main symptoms of type I reaction in the lungs?
asthma -- wheezing, dyspnea, tachypnea
114
allergen and route of entry of lung type I reaction ?
inhalation of pollen, house dust, animal danders
115
main symptoms of type I reaction in the nose and eyes/
allergic rhinitis, conjunctivitis or hay fever. see a runny nose, redness and itchy eyes.
116
allergen and route of entry of nose/eye type I/
pollen contact with mucous membrane
117
symptoms of type I reaction on skin?
ezcema/atopic dermatitis, urticaria causing pruritic, vesicular lesions, or pruritic bullous leisions
118
allergen and route of entry skin
uncertain maybe ingestion and various routes of various foods or drugs or unknown
119
main symptoms of type I reaction in the intestinal tract
allergic gastroenteropathy causing vomiting and diarrhea
120
main symptoms of systemic type I reaction
anaphylaxis causing shock, hypotension and wheezing
121
treatments for type I hypersensitivity
1. reduce inflammation
2. block mediator release
3. suppress immune response
4. monoclonal Ab against IgE
5. epinephrine for anaphylactic shock
122
how to reduce inflammation
antihistamines, LTRA, ASA, corticosteroids, NSAID
123
how to block mediator release
antigranulating agents (nedocromil inhalers)
124
how to suppress immune response
desensitization by allergy shots (the allergen is repeatedly injected to reduce IgE on mast cells
125
what is a monoclonal Ab against IgE?
omalizumab
