Hypersenstivity Type I- Hunter Flashcards
1
Q
What are some secondary immune deficiencies?
A
malnutrition and immunosuppressant drugs.
2
Q
When the immune system damages itself what do we call this?
A
immunopathology due to hypersensitivity responses
3
Q
T or F
A little immunopathlogy is normal in all infection
A
T
4
Q
What is an allergy?
A
your immune system responding to innocuous stimuli.
5
Q
WHen self nonself identification is all messed up, what do you have?
A
immunopathology
6
Q
What is Type I hypersensitivity?
A
this is an allergy like asthma and allergic rhinitis.
7
Q
What is type I hypersensitivity mediated by?
A
IgE
8
Q
What are the 2 main cell types in Type I hypersensitivty?
A
Mast cells and eosinophils
9
Q
What are type II hypersensitivity disorders?
A
most are autoimmune (some type II hypersensitivity reactsion are caused by extrinsic things but mostly this category is autoimmune)
10
Q
How does type II hypersensitivity reaction work?
A
triggers IgG antibodies to bind to our own tissues and turn our immune system against ourselves (blood, tissue, ECM)
11
Q
What is type III hypersensitivity?
A
it is caused by an IgG antibody that has formed immune complexes. These antigen antibody complexes form in almost every infection but when they cannot be cleared, cause immune complex disease
12
Q
How is type IV hypersensitivity caused?
A
by CD4 and CD8 T cells (some are autoimmune and some are extrinsic)
13
Q
Why kind of hypersensitivity is found in rheumatoid arthritis?
A
Type II, III, IV
14
Q
In type 1 immediate hypersensitivity, what is the immune reactant, is the antigen soluble or insolube, what is the effector mechanism and what are some examples?
A
IgE
soluble antigen
mast-cell activation
allergic rhinitis, asthma, systemic anaphylaxis
15
Q
What do you find within mast cell granules?
A
mediators
16
Q
One of the prinicipal immune defense mechanisms against metazoan parasites (worms) is (Blank) killing by eosinophils
A
IgE
IgE can bind to worms and release the granules inside them to kill them
17
Q
How does our body expulse parasites?
A
cross-linking of anti-parasite IgE on mast cells by parasite antigen causes the release of mediators that promote expulsion of parasites
18
Q
What sucks about the IgE response that was created to bind and expulse parasites and worms?
A
it can be elicited by inocuous environmental materials (allergens)
19
Q
What is a classic way to shift THO to produce TH2
A
WORMS!!!!!
20
Q
What does histamine do in the gut?
A
causes rapid contraction, vomiting, and diarrea
21
Q
(blank) is an antigen that induces allergy
A
allergen
22
Q
Type I hypersensitivity reactions are induced by extrinisc allergens. What are some of these?
A
pollen, house dust mite, wasp, drugs, peanuts, shellfish
(pant pollens, dander, mold spores, feces, insect venoms, vaccines, drugs, therapeutic proteins, food, orally admin drugs)
23
Q
How does an allergen cause IgE production?
A
dendritic cells and other immune cells in mucosa produce IL-4, IL-5, IL-9, IL-13 in response to antigen-> and these favor TH2 differentiation.
24
Q
What will IFN gamma and IL12 stimulate?
A
TH1 cell
25
What IgG subtypes will cause fixed complement?
Ig1 an Ig3
26
ONLY (blank) induce T cell responses
Proteins
27
What do you need to make an airbone allergen that will promote TH2 cell formation that drives IgE response?
proteins in low doses that have low molecular weight and high solubility. THey must be stable and contain peptides that bind MHC class II
28
Allergy is (blank), you have the wrong MHC molecule
genetic
29
Allergic Responses involve (blank) class switching of B cells
IgE
30
Explain the allergic response
```
an allergen-specific B cell binds and internalizes allergen-> allergen peptides are presented MHC class II to CD4 Th2 cells that produce cytokines like IL-4 and express CD40L .
IL-4/IL-4R ad CD40L/CD40 co-stimulatory signaling activates the B cell and promotes isotype switiching to IgE
```
31
What are the co-stimulatory signals that activate the B cells to promote isotype switching to IgE?
IL-4/IL-4R and CD40L/CD40
32
An initial response to an allergen is (blank). Then the B cell and T cell get together to release cytokines that will cause isotype switching to IgE
IgM
33
Unlike other Igs, IgE is (blank)
cytophilic
34
Is IgE found in low or high levels in plasma?
low (.1-.4)
35
IgE binds to (blank) on mast cells, basophils, and eosinophils
FceRI
36
The amount of IgE in your plasma is misleading because the IgE that was in your plasma and is now sitting on mast cells, basophils, and eosinophils that matter. When you have massive allergy attack IgE levels will rise in your plasma.
T or F
T
37
Allergic reactions occur ony after (blank) exposure to allergens
second
38
For allergies:
Tell me what the first exposure is
Tell me what the second exposure is
First Exposure
IL-4 Drives B cells to produce IgE in response to pollen antigens. Pollen-specific IgE binds to mast cells.
Second Exposure
Acute release of mast cell contents causes allergic rhinitis (hay fever)
39
Pollen is typically produced by trees in the (blank), grass in the (blank) and weeds in the (blank)
spring
late spring to summer
fall
40
Where are mast cells found?
in the skin, all mucosal areas, lining blood vessels
41
IgE associated mast cell release will affect your (blank)
whole body.
42
How do you trigger a mast cell to release its granules?
you get enough crosslinked IgE on mast cell surface
43
What are the three pathways to release granules from mast cells?
granule exocytosis
secretion with lipid mediators
secretion with cytokines
44
How does the mast cell release vasoactive amines and proteases?
What do they do?
granule exocytosis
| causes vascular dilation and smooth muscle contraction AND tissue damage
45
How does the mast cell release prostaglandins and leukotrienes?
What do they do?
Via enzymatic modification of arachidonic acid to create lipid mediators
Vascular dilation and smooth muscle contraction
46
How does the mast cell release cytokines?
| What do they do?
```
transcriptional activation of cytokine genes
Cause inflammation (leukocyte recruitment)
```
47
What all do mast cells release?
vasoactive amine: histamine
Proteases: chymase, tryptase
Prostaglandins: PGD2
Cytokines: TNF-ALpha
48
What is released quickest to slowest with mast cells?
(vasoactive amines and proteases SECONDS TO MINUTES))-> (prostaglandins and leukotrienes MINUTES TO HOURS) -> (cytokines HOURS)
49
What does histamine cause?
vasodilation
50
Mast cell activation has different effects on different tissues. How does it affect the GI tract?
increased fluid secretion and increased peristalsis which results in expulsion of GI tract contents, diarrhea and vomiting
51
Mast cell activation has different effects on different tissues. How does it affect the eyes, nasal passages, and airways?
decreased diameter, increased mucus secretion. -> results in congestion and blockage of airways (wheezing, coughing, phlegm) swelling and mucus secretion in nasal passages
52
Mat cell activation has different effects on different tissues. How does it affect the blood vessels?
Increased blood flow and increased permeability-> results in increased fluid in tissues causing increasd flow of lymph to lymph nodes, increased cells and protein in tissue, increased effector response in tissues. Hypotension potentially leading to anaphylactic shock
53
Type I allergic reaction range from simpe nuisances to life threatening conditions. T or F
T
54
T or F
| THe dose and route of allergen administration determines the type of IgE mediated allergic reaction
T
55
What happens if you have an intravenous high dose of allergy?
general release of histamine and anaphylaxis
56
What happens if you have a subcatenous low dose of allergy?
you get local release of histamine (wheel and flare reaction)
57
What hapens if you have a low dose inhalation of allergen?
allergic rhinits (upper airway), caused by increased mucus production and nasal irritation. Asthma (lower airway) due to contraction of bronchial smooth muscle and increased mucus secretion
58
What happens if you have ingestion of an allergen?
contraction of intestinal smooth muscle induces vomiting. Outflow of fluid into gut causes diarrhea. Antigen diffuses into blood vessels and is widely disseminated causing urticaria (hives) or anaphylaxis
59
Enzymes frequently trigger (blank)
allergies
60
What do you find in fecal pellets of dust mites (dermatophagoides pteronyssimus)?
Der P1 enzyme
61
What does the Der p1 enzyme do?
the enzyme Der p1 cleaves occludin in tight junctions and enters mucosa-> induces IgE and plasma cell formation. -> igE binds to FceRI receptor on mast cell-> reintroductin to Derp1 triggers degranulation
62
(blank) percent of n. america population is allergic to house dust mite feces.
20%
63
What do eosinophil secrete?
toxi proteins and inflammatory mediators
64
(blank) can occur in allergic patients; induced by growth factors ike (blank)
eosinophilia
| IL-5
65
(blank and blank) are chemokines made by a variety of cell types that bind to eosinophil CCR3 and recruit these cells
Eotaxins 1 and 2
66
Eosinophils bare (blank) but only in the activated state so only activated eosinophis have cytophilic IgE.
Fc3RI
67
T or F
| products of eosinophis are very potent and tightly regulated (e.g major basic protein, enzymes, leukotrienes)
T
68
Which are more potent, eosinophils or mast cells?
eosinophils
69
What is a normal value for an eosinophil count?
1%
70
What IL generates eosinophils?
IL-5
71
Eosinophils are brought to the tissue they are needed at via (blank) and (blank) signaling
Eotaxin 1 and 2 signaling
72
Eosinophils produce an incredible array of mediators that protect against ((blank) and can cause (blank)
parasites
| immunopathology
73
Allergic asthmas has what 2 components?
acute and chronic
74
How do you get a chronic allergic asthma response?
Chronic reponse caused by cytokines and eosinophil products along with IL-5 and eotaxins
75
What is the secondary intention of chronic asthma?
fibrosis and scar formation
76
Most allergic reactions have both an immediate response and a (blank) response
late phase
77
What is the immediate phase characterized by?
| What is the late phase characterize by?
IMMEDIATE PHASE
vasodilation, congestions and edema
LATE PHASE
tissue edema with eosinophils, neutrophils and T cells
78
When does the late phase reaction occur?
2-24 hours after repeat exposure to allergen
79
Tendency to make exaggerated IgE responses is called (blank)
atopy
80
A variety of genes affect atopy, what are they?
MHC II, Fc3RI, TH2 cytokines
81
(blank) factors may influence atopy.
environmental
82
Exposure to microbial pathogens promotes a (blank) deviation.
Th1
83
How are you more likely to get atopy?
if you DO NOT have a lot of environmental exposure to pathogens as a child
84
T or F
| early exposure to microorgansms will make you less likely to have allergies
T
85
Is there a susceptibility loci for allergic and autoimmune diseases?
yes it is 6P21 MHC locus
86
(blank) or (blank) skin tests are used to identify specific allergens.
intradermal
| epicutaneous
87
Which receptors do antihistamines block? What will this do to your blood vessels?
histamine H1 receptors (e.g. diphenhydramine HCl)
| cause decreased vascular permeability
88
How do you treat acute asthma?
inhaled bronchodilators (beta adrenergic receptor agonists like albuterol)-> relaxes bronchial smooth muscle
89
(blank) relieve symptoms of asthma and seasonal allergies
cysteinyl leukotriene receptors (montelukast aka Singular)
90
What leukotrienes does singular block?
D4, C4, and E4 and inhibits bronchoconstriction
91
Anaphylactic reactions are treated with (Blank)
epinephrine (adrenaline)
92
What will epinephrine do to the body?
relax bronchial smooth muscle, constrict vascular smooth muscle, reform endothelial tight junctions
93
Systemic and topical corticosteroids suppress (blank) by inhibiting transcription of many proinflammatory genes by blocking (Blank)
chronic infammation
| NFKB
94
What does parenteral mean?
occuring somewhere other than the mouth or alimentary canal
95
What should you use on an allergic patient who needs inhibition of mediators?
antihistamine, beta blocker, lipoxygenase inhibitors
96
What should you use on an allergic patient who needs to reduce their inflammatory effects?
corticosteroids
97
What should you use on an allergic patient who needs to reduce their T cell levels (TH2 response)?
desensitization therapy by injections of specific antigens
98
What should you use on an allergc patient who needs to have their IgE binding to mast cells stopped?
give them anti-IgE antibodies (omalizumab) to bind to IgE and prevent it from bind to Fc receptors on mast cells
99
When can desensitization be used?
when allergen is known
100
What is the goal of desensitization?
to shift the anti-allergen response from IgE to IgG
101
How does desensitization work?
you slowly inject allergen in escalating amounts intradermally to favor IgG production. UPon exposure to allergen, anti-allergen IgG binds up allergen and prevents IgE cross linking.
102
Desensitization produces regulatory cells, and what do these cells secrete?
IL-10 and TGF-beta and promotes isotype switching to IgE
103
Larger does of allergen will do what?
switch IgE production to IgG
104
Blocking IgE binding to the high affinity IgE receptor on mast cells, basophils, and eosinophils is an interesting strategy. WHat can do this?
humanized mouse anti-IgE monoclonal antibody (omalizumab) blocks IgE binding to FC3RI.
105
What is the most common chronic skin disease of young children?
atopic dermatitis
106
Most patients with atopic dermatitis are (blank)
atopic
107
What do you usually find associated with atopic dermatitis?
staph aureus and herpes simplex, elevation of eosinophils, and TH2 cytokines
108
does venom immunotherapy work?
yes
109
What is an example of IgE mediated drug hypersensitivity?
Anaphylaxis from B-lactam antibiotics
110
```
What are these;
halothane hepatitis
hypotension after protamine
dermatitis from sulfonamids
serum sickness from phenytoin or cefaclor
hypotension after succinylcholine
quinine-induced thrombocytopenia
phenolphthalein-induced fixed drug eruption
cis-platinum-associated urticaria
```
IgE mediated drug hypersensitivity
111
A (blank) is a small molecule that can elicit an immune response only when attached to a large carrier such as a protein; the carrier may be one that also does not elicit an immune response by itself
hapten
112
Most pharmaceutical agents have simple structures and small molecular weights, most do not qualify as drug allergens. Drugs such as ((blank) can directly bind covelently with macromolecules on cell surfaces and in plasma to form hapten carrier complexes
penicillins
113
WHen direct haptenation results in a succicient density of drug epitopes (multivalency), what can happen?
you can get an immune response
114
In the case of (blank) antibioitics such as penicillin, the chritical chemical structure is the ring which is unstable and readily acylates lysine residues in proteins
Beta-lactam
115
Explain how you can get a penicillin allergy.
self proteins are tagged with penicilloyl hapten-> MHC II molecules with this protein in presence of danger signals will activate CD4 t cells that make B cells create an IgE anti-penicilloy antibody and you gen mast cell degranulation the following exposure.
116
What other three drugs should you not give someone who is allergic to penicillin?
carbapenems, cephalosporins, monobactams (cuz they all have the same Beta-lactam ring)
117
What represents the greates foreign antigenic load confronting the human immune system? how do we deal with this?
ingested food
| most individuals develop tolerance
118
What can food allergens cause?
Gi, cutaneous, and respiratory problems AND even anaphylaxis in up to 8% of children younger than 5 and app. 3.5% of general pop.
119
Can foods trigger life threatening anaphylaxis in children and adults?
yes
120
the incidence of peanut allergy has (blank) over the past decade in western countries
tripled
121
How do you treat food allergy?
avoidance
122
What is the most common allergen in adults?
| What about in children?
vegetables> fruits> peanut and wheat
Cows milk> shellfish
123
If someone has an anaphylactic reaction, why are they NOT given a skin test for that allergen immediately after the individual has recovered
because immediately after a systemic anaphylactic reaction the patient is unresponsive in a skin test owing to the massive depletion of mast cell granules and failure of the blood vesselt to respond to mediators. This is called tachyphylaxias and last for 72-96 hours
