Lecture 14: Type 1 Hypersensitivity Reactions Flashcards
_____: adaptive immune responses that occur in exaggerated or inappropriate forms and result in disease
Hypersensitivity reactions
What is the pathologic immune mechanism associated with Type 1 Hypersensitivity reactions?
IgE antibody
What are the two primary mechanisms of tissue injury in Type 1 Hypersensitivity reactions?
1) Activation of mast cells, basophils, eosinophils + release of their mediators (histamine, arachidonic acid, cytokines)
2) Release of O2 and N2 radicals + proteases
What mechanisms of tissue injury are common to both Type II and Type III hypersensitivity reactions?
1) Activation of complement
2) Recruitment and activation of leukocytes (neutrophils, macrophages)
If a transfusion goes poorly, what type of hypersensitivity response will often occur?
Type 2
Auto-immunity, Arthus Reaction, or Serum Sickness are associated with which hypersensitivity?
Type 3
True or False: Type III hypersensitivity reactions are antibody mediated while Type II are immune complex mediated
False -
Type II reactions are: antibody mediated cytoxic/cytolytic reactions
Type III reactions are: immune complex-mediated
IgM or IgG antibodies against
tissue or cell surface antigen is seen in which hypersensitivity reaction?
Type II
Immune complexes of
circulating antigens and IgM or IgG antibodies are seen in which hypersensitivity reaction?
Type III
Which hypersensitivity reaction is T cell mediated?
Type IV
What are the two mechanisms of tissue injury used in Type IV hypersensitivity reactions?
1) Activated macrophages,
cytokines
2) Direct target cell lysis,
cytokines
Both CD4+ T cells (delayed type hypersensitivity) and CD8+ CTLs (T cell-mediated cytolysis) are present in which hypersensitivity reaction?
Type IV
Anaphylactic and allergic
reactions are associated with which type of hypersensitivity?
Type 1
There are often adverse responses mediated by___, which includes: allergies, asthma, and anaphylaxis
IgE
____: an antigen that stimulates IgE-mediated reactions (pollen, dust,
animal dander, etc.)
allergen
_____: an adverse response provoked by an allergen, mediated by
IgE, results in vasodilation and constriction of smooth muscles (including those of the bronchus), which can result in shock and death.
Anaphylaxis
____: susceptibility of certain individuals to natural sensitization by
environmental allergens, e.g., pollen, spores, foods
___: serum from a sensitized atopic individual that contains antibodies to an allergen
Atopy
Atopic serum
____: the process of inducing an immune response resulting in an
untoward (adverse) effect – for type I hypersensitivities it is the production
of IgE
Sensitization
What are the three phases of Type 1 hypersensitivity reactions?
Stage 1: Sensitization
Stage 2: Activation
Stage 3: Effector
What are the steps of the sensitization phase?
1 - Exposure to allergen
2 - Th2 activation and IgE production
3 - IgE binds to mast cell Fc receptors
What are the steps of the activation phase?
4 - 2nd exposure to allergen
5 - allergen binds to mast cell-associated IgE
6 - signal transduction
What are the two steps of the effector phase?
7 - Mediator release (e.g. histamine)
8 - End organ effects of mediators
What are four pre-disposing factors for sensitization?
1) Allergens (antigens that tend to drive Th2 responses and IgE production)
2) Route of exposure (location of mast cells in skin, mucosa, CT)
3) Age
4) Genetic predisposition
In the second step of Type 1 Hypersensitivity reaction, ___ is synthesized.
IgE
In the second step of Type 1 Hypersensitivity reaction,
______ activation
helps B cells commit to becoming ___
Th2 CD4+ lymphocyte ; IgE
In the second step of Type 1 hypersensitivity reactions, ___, ___, and ____ strongly influence Th2-mediated B cell isotype switch and commitment to IgE production
IL-4, IL-5, and IL-13
True or False: Most individuals can make IgE but only a few become atopic
True
In the third step, IgE binds to a high affinity receptor on mast cells known as ____, thereby increasing IgE half life
FceRI
Upon 2nd exposure to an allergen, more ___ is made by memory B cells
IgE
Once allergen binds to the mast cell-associated IgE, ___ between two ___ molecules on mast cell surface occurs (signal transduction).
crosslinking; IgE molecules on mast cell surfaces
Degranulation (release) of histamine, serotonin, heparin, proteases, etc. is associated with the ___ phase
effector
True or False: In the 7th stage, there is a delayed release of newly
synthesized mediators
True
In the 7th step, mast cell activation results in
release of newly synthesized
components, such as ___, ____, and ___
Leukotrienes, Prostaglandins, Thromboxanes
In the 7th step, cytokine production also occurs, especially __ which potentiates Th2
responses.
IL-4
GM-CSF, IL-3, and IL-5 are made in the 7th step. What is their shared role?
IL-8 is also made in the 7th step. What is it’s role?
Stimulate eosinophil growth and differentiation
Leukocyte chemotaxis
True or False: Wheal and flare, vomiting and diarrhea, and enlarged nasal turbinates with blueish green mucosa are examples of mild, local symptoms of Type 1 Hypersensitivity reactions.
True
What are two examples of severe Type 1 Hypersensitivity reactions?
1) Laryngeal edema
2) Severe systemic anaphylaxis
True or False: Asthma, chronic obstructive airway, and respiratory inflammation can result due to type 1 reactions
True
How long does the initial type 1 reaction response take? late phase response?
initial response: minutes
late phase: hours
What are the three lethal outcomes of Type 1 hypersensitivity reactions?
1) Asphyxiation form laryngeal edema
2) Suffocation from bronchiolar constriction/contraction
3) Shock
Type I hypersensitivities require antibodies of
which isotype?
A. IgG
B. IgA
C. IgM
D. IgD
E. IgE
E. IgE
Sensitization requires which of the following
cell surface molecules?
A. FceRI
B. CD16
C. CD8
D. HLA-A
A. FceRI
True or False: RIST and RAST are examples of in vitro tests used to diagnose type 1 hypersensitivity reactions
True
- note: RAST is more specific
What are the two types of allergen immunotherapy?
1) SCIT
2) SLIT
What are three types of hyposensitization mechanisms?
1) blocking antibodies
2) specific suppressor T cells
3) Th2 to Th1 switch
note: not the same as Drug desensitization!
Two examples of immunotherapy?
1) Allergen immunotherapy - SCIT and SLIT
2) Hyposensitization mechanisms
If a patient is taking OTC antihistamines for their
seasonal allergies, will they still produce anti-
allergen IgE?
A. Yes
B. No
C. They never produced IgE
A. Yes
