Hypersensitivity Flashcards
1
Q
What are the functions of IL-4
A
- induce differentiation of Th2 cells
- cause class switching to IgE
2
Q
What receptor does IgE bind to on mast cells, basophils and activated eosinophils?
A
FceRI
3
Q
How is IgE synthesized?
A
IgE is synthesized from class switching
4
Q
IgE has how many constant domains
A
2
5
Q
IgE does not play a role in
A. Complement fixation B. Opsonization C. Allergic Reactions D. Defense against parasitic worms E. A & B F C & D
A
E
6
Q
When is IgE synthesized?
A
When Th2 cells secrete IL-4 which stimulates B cells to class switch and secrete IgE
7
Q
How does the adaptive immune system play a role in parasitic infections
A
Th2 cells secrete IL-4 to induce the differentiation of more Th2 cells and class switching of B cells to make IgE
8
Q
What happens to IgE once it is synthesized
A
it diffuses across vessel endothelium out of the blood to bind to mast cells
9
Q
T/F: FceRII is a high affinity receptor for IgE
A
False
*FceRI
10
Q
What chain of the FceRI receptor binds IgE
A
the alpha chain
11
Q
The _____ chain of FceRI binds IgE
A
Alpha
12
Q
Mast cells are located in all of the following locations except
A. Tissue Lining B. Vascularized Tissue C. Mucosal Tissue D. Blood E. Connective Tissue
A
D. Blood
*basophils are located in in the blood
13
Q
Mast cells are ____ lived while basophils are ____ lived
A
Short, long
14
Q
Mast cells in mucosal tissue express which protease
A
Tryptase
15
Q
Mast cells in connective tissue express which protease?
A
ChymoTryptase
16
Q
-
A
-
17
Q
Which granulocyte is mainly present in blood?
A
Basophils
18
Q
_______ on mast cells and basophils secrete cytokines that result in Th2 response and eosinophil activation
A
Toll Like receptors
19
Q
Which cytokine is responsible for Eosinophil production and activation
A
IL-5
20
Q
Eosinophils are mainly located
A. in blood
B. in tissue linings
C. in lymph
D. in connective tissues
A
D
21
Q
What structures on basophils and mast cells recognize features of pathogens
A
Toll Like Receptors
22
Q
What is the role of IL-5 in the development of immunity against parasites
A
eosinophil production and activation
23
Q
List the type of preformed mast cell mediators (3)
A
- enzyme
- toxic mediator
- cytokine
24
Q
What are the enzymatic preformed mediators of mast cells?
A
-tryptase and and chymotryptase
25
What do the mast cell enzymatic preformed mediators do?
remodel the ECM of tissue to dislodge parasite
26
What are the toxic preformed mediators of mast cells?
Histamine and Heparin and serotonin
27
What is the main effect of the release of histamine from mast cells?
-increased blood flow triggering inflammation
28
Where are H1 receptors for histamine located? What are the effects at each location?
-Vascular endothelial cells: vasodilation (increased permeability)
-Smooth Muscle cells: bronchoconstriction
Heart & Brain
29
H1 histamine receptors are located everywhere except
```
A. vascular endothelium
B. GI tract
C. Smooth Muscle
D. Heart
E. Brain
```
B.
| *H2 receptors are in the GI and vascular endothelium
30
Where are H2 receptors located?
Vascular endothelium and GI
31
H3 and H4 receptors are located
in CNS and bone marrow
32
Which cytokine is a preformed mediator secreted by mast cells?
TNF-alpha
33
What does the preformed mediator TNF-alpha do (3)
- promotes inflammation
- stimulates cytokine production
- activates endothelium to express adhesion molecules
34
What is the importance of endothelial cell activation upon TNF-alpha
It causes the cells to express adhesion molecules allowing other immune cells to enter the tissue
35
What are the categories of newly synthesized mast cell mediators (3)
- cytokines
- chemokines
- lipid mediators
36
IL-4 and IL-13 from mast cells are _______ mediators
*chart on slide 13
Newly synthesized
37
What do newly synthesized mast cell mediators cause?
Sustained effects (late phase reaction)
38
Which category of mast cell mediators are responsible for the late phase reaction
newly synthesized
39
What chemokine plays a role in mast cel newly synthesized mediators?
CCL3
40
What does CCL3 do in mast cell mediation
Attracts monocytes, macrophages and neutrophils
41
What cytokine(s) promotes eosinophil production and activation
IL-5 & IL-3
42
What cytokines are a newly synthesized mast cell mediator the stimulates and amplifies the Th2 response
IL-4 and IL-13
43
What do prostaglandins do? (3)
- cause smooth muscle contraction
- increase vascular permeability
- cause mucus secretion
44
How are leukotrienes formed?
When arachidonic acid goes through the lipogenase pathway
45
Which pathway does arachidonic acid undergo to form prostaglandins?
Cyclooxygenase paths
46
T/F: Leukotrienes and Prostaglandins can be blocked by aspirin
False
| *only Prostaglandins
47
Eosinophils are resident in
-connective tissue under respiratory GI and urogenital tracts
48
Which of the following cells types are exclusively involved in the late phase reaction
A. Basophils
B. Mast Cells
C. Eosinophils
C
49
Highly toxic mediators of eosinophils
A. amplify inflammatory response
B. directly kill
C. Recruit Mast Cells
B
50
What are the preformed mediators of eosinophils
- eosinophil peroxidase
- Major Basic Protein
- Eosinophil Cationic Protein
*slide 17
51
Leukotirenes and Prostaglandis are
A. Toxic protein
B. Chemokines
C. Lipid Mediator
C
52
Why are parasites more difficult to eradicate?
they are too big to be engulfed by phagocytes and they are biologically and chemically more like humans than other pathogens so they are less antigenic
53
Why are mast cells more versatile than B cell in term of their response to antigen in the context of IgE
Mast cells bind to different IgE molecules with various specificities for antigens that can be diverse in the structural and biological origin
54
How do IgE participate in protective immunity against parasites?
when IgE crosslinks on mast cell it activates mast cell degranulation which results in the release of toxic proteins to the parasite
55
Define allergy
a damaging immune response to harmless agents
56
Describe the hygiene hypothesis
Access to hygiene, vaccines and antibiotics relate to low levels of parasitic infections.
Areas with high parasitic infection rates happen to have low levels of allergies while clean areas with low parasitic infection rates tend to have HIGH allergies
57
List the factors that can predispose a person to type 1 hypersensitivity
Genetic & Environmental Factors:
- MHC class II genes
- TCR alpha locus
- IL-4
58
What are the 4 types of hypersensitivity
Immediate
Cytotoxic
Immune Complex
Delayed Type
59
What are hypersenisitities classified by
The mechanisms by which they operate
60
All of the following types of hypersensitivity are mediated by antibodies except
A. Immediate
B. Delayed Type
C. Cytotoxic
D. Immune complex
B.
| *delayed type is type IV mediated by T cells
61
Hypersensitivity reactions occur when
an already immune or sensitized person is re-exposed to the initiating allergen
62
Which types of hyperactivity is mediated by antibodies
Type 1: immediate
Type 2: cytotoxic
Type 3: Immune complex
63
T/F: Antibodies are involved in type 4 hypersensitivity
False
64
What are allergens
protein antigens that trigger allergies that resemble parasite antigen
65
How can MHC II genes predispose someone to allergies?
It can cause enhanced presentation of particular antigen, having a stronger hold for that antigen
66
How can TCR alpha locus predispose someone to allergies?
it can cause enhanced T cell recognition of allergen derived peptides
67
How can IL-4 gene predispose someone to allergies
It can cause a variation in expression of IL-4, making them more likely to have Type 1 hypersensitivity response since more IgE is made
68
What are the three stages of Type I hypersensitivity reactions?
Sensitization
Immediate Rxn
Late Phase Rxn
69
Describe how a person be come sensitized to type I hypersensitivity?
1. A person is exposed to allergen for the first time
2. Antigen is extracted and T cells are activated upon being presented with antigen via APC
3. Th2 cells secrete IL-4 to stimulate class switching in B cells to make IgM
4. IgM binds to mast cells (* the mast cells are now ready for the next time allergen enters)
* slide 33
70
What triggers mast cells to degranulate?
Crosslinking of IgE due to presence of allergen
71
What preformed mediators are active in the immediate reaction of type I hypersensitivity (3)
- histamine
- serotonin
- neutrophil/eosinophil chemotactic factor
72
What mediators are released during the late phase reaction of type 1 hypersensitivity
- leukotrienes
| - prostaglandins
73
Why is type 1 hypersensitivity referred to as immediate?
Signs and symptoms can occur in minutes after exposure
74
What are the consequences of mast cell degranulation?
When mast cell degranulates its releases mediators causing symptoms such as redness, swelling, and smooth muscle contraction. Mast cell also releases arachidonic acid to disrupt membranes
75
What are the 2 main roles of eosinophils?
1. release toxic granular proteins that cause tissue injury
| 2. amplify inflammatory response by releasing chemokine, prostaglandins and leukotrienes
76
Prostaglandins and leukotrienes present in _____ phase reaction
late
77
How does ingestion of an allergen influence clinical presentation of type 1 hypersensitivity
-expulsion of GI tract contents (diarrhea & vomiting)
78
How does inhalation of an allergen influence clinical presentation of type 1 hypersensitivity
Expulsion of airway contents via coughing, sneezing, expulsion of phlegm
79
How does injection of an allergen influence clinical presentation of type 1 hypersensitivity
Edema and inflammation, increased flow of antigens in lymph to lymph nodes
80
Allergens in the blood trigger
systemic anaphylaxis
81
What symptoms are caused by anaphylactic shock (5)
*think about the effects of type 1 sensitivity in the different regions in the body and what occurs when allergens reach those areas but think of it on a larger scale for systemic anaphylaxis
```
Itchy rash
nausea/vomiting
drop in BP
difficult breathing
organ damage
```
82
Describe the process leading up to anaphylactic shock
antigen in bloodstream enters tissue and activates mast cells throughout body
mast cell degranulation causes the release of mediators that affect the : heart, respiratory tract and GI tract
83
What effects do inflammatory mediators have on vascular system (4)
- capillary permeability and entry of fluid into tissues
- edema
- loss of blood pressure
- reduced oxygen to tissues
84
What effects do inflammatory mediators have on respiratory system
- contraction of smooth muscles of airways
| - difficult swallowing and breathing
85
What effects do inflammatory mediators have on gastrointestinal system
- contraction of smooth muscle
| - vomiting
86
Describe how penicillin can cause systemic anaphylaxis
Penicillin is a hapten, when it binds to a RBC it is big enough to be recognized and ingested by macrophages. Macrophages present penicillin antigen to T cells which activate B cells to make IgE resulting in an immune response
87
Inhaled allergens in the ______ respiratory tract cause allergic rhinitis
Upper
88
Inhaled allergens in the ______ respiratory tract cause asthma
Lower
89
What are the acute responses of the immune system in the case of asthma
- mucosal mast cell captures antigen
| - mediators cause smooth muscle contraction, mucous production, increased blood vessel permeability
90
Chronic response in asthma is mediated by _____ and _____ products
cytokines , eosinophil
91
What are the treatments for type I allergies (3)
- prevention
- pharmacologic
- immunologic
92
What is Zolair?
Antibodies against IgE that can be administered as intervention to type I allergies
93
What is Mepolizumab?
Administered antibodies against IL-5
| *stopping eosinophil production and activation
94
Administering antibodies against IL-5 would have what effect
It would stop the production and activation of eosinophils thus reducing the late response of Type 1 hypersensitivity
95
______ cells : early response:: eosinophils: late response
mast
96
What are isohemagglutinis?
IgM antibodies directed against blood group antigen
97
What is D antigen?
The antigen that determines if a person is Rh+ or RH-
98
Which of the following are correctly matched
A. Type 1: Immune complex Hyper sensitivity
B. Type 2: cytotoxic effects
C. Type III: T cell mediated
B
99
Describe the immune complexes formed in the Arthus Reaction
| *slide 61
IgG reacts with and forms complexes with soluble proteins that activate complement
100
What are the key mediators in Type 3 hypersensitivity
Anaphylatoxins
| Chemotaxins
101
C3a and C5a are anaphylatoxins & chemotaxins that cause
edema (increased vascular permeability) and tissue damage (influx of neutrophils and platelets)
102
Cytotoxic destruction of a cell in type 2 hypersensitivity is by what mechanisms (3)
complement
opsonization
ADCC
103
A person who is blood type A has what type of isohemagglutinin?
Anti B antibodies
104
What causes agglutination
Antibodies bind to RBCs and crosslink causing the cells to come together
105
What is the main difference between IgM and IgG
IgM cant cross placenta
106
What happens in 2nd pregnancy of mom who is Rh- with Rh+ baby
IgG crosses placenta and enters fetal circulation and binds to fetal rbc
107
Treatment for hemolytic disease of newborn
RhoGam: anti Rhd antibodies---IgG against Rhd antigen is distributed.
It binds to antigen on fetal cells and destroys the hemoglobin
108
What is the immediate result of the formation of immune complexes
Complement activation
109
What is the main presentation/characteristic of Type 4 hypersensitivity
Erythema and induration due to macrophages and T cells being recruited to area in skin
110
What type compounds trigger contact dermatitis
Hapten
111
What are the cytokine mediators of Type IV hypersensitivity reactions
IFN gamma
TNF beta
monocyte/macrophage chemotactic factor
112
Induration and erythema is the classic halmark associated with
A. Type I
B. Type II
C. Type III
D. Type IV
D
113
What cell types are involved in type I hypersensitivity
Mast cells, basophils, eosinophils
114
What antibody class is involved in type I hypersensitivity?
IgE
115
What antibody class is involved in type II hypersensitivity?
IgG/ IgM
116
What antibody class is involved in type III hypersensitivity?
IgG
117
What antibody class is involved in type IV hypersensitivity?
none
118
What mechanism is associated with type II hypersensitivity?
Complement / opsonization
119
What mechanism is associated with type III hypersensitivity?
Complement and accumulation of neutrophils and platelets
120
What mechanism is associated with type IV hypersensitivity?
Th1/ CD8T cells
121
How does local type III hypersensitivity differ from systemic?
Local: immune complexes stay local and complement is activates there
Systemic: immune complexes are distributed throughout the body
