IgE Immunity Flashcards
1
Q
Define allergy.
A
- immune response to an environmental antigen
- Type 1 hypersensitivity reaction
2
Q
Define atopy.
A
- ability to transfer reactivity via serum
- genetically predisposed to having multiple allergic response
- hereditary
3
Q
What is the central mediator of the allergic reactions?
A
IgE = itch (utricaria), sneeze (allergic rhinitis), and wheeze (asthma)
4
Q
What are the common effector cells of allergy?
A
- mast cells
- basophils
- eosinophils
5
Q
List components of an allergic reaction.
A
- IgE
- allergen
- mast cells/basophils
6
Q
Define IgE.
A
- antibody
- high affinity binding to FcE receptors on mast cells and basophils
- very low levels in serum
- normally, respond to worms and parasites
7
Q
Characterize the 2 types of mast cells.
A
McT (tryptase)
- prominent in respiratory and GI tracts
- increase with mucosal inflammation
McTC (tryptase and chymase)
- prominent in connective tissue
8
Q
List mast cell mediators of the allergic response.
A
- histamine
- prostaglandins
- leukotrienes
- cytokines (IL-3-6, 8, 10, 13)
- TNF-a
- GM-CSF
9
Q
What are properties of mast cells and basophils relevant to the allergic response?
A
- constitutively express high levels of FcE receptor
- cytoplasmic granules of vasoactive mediators, such as histamine and leukotrienes
- different phenotypic markers and lineage, but derived from HSCs
- basophils are circulating, mast cells are in tissue
10
Q
Define allergen.
A
- ubiquitous environmental proteins that can induce a hypersensitivity response in atopic individuals
- induce IgE instead of IgA/G/M
11
Q
List the types of allergens.
A
- aero - pollen, ragweed, etc.
- food - milk, egg, nuts, shellfish,
- insect venom
- drugs
12
Q
Define chitin.
A
- plant polysaccharide that is found in many allergens
- induces expression of chitinase, which can induce a degranulation
13
Q
Describe the role of genetics in the allergic response.
A
- children of 2 atopic parents are 50% likely to be atopic as well
- a multiplicity of genes must act in concert to mount an allergic response (ex: Tbet (INFg, Th1), mast cell signaling, FcE receptor avidity, TLRs on APCs)
- direct relationship between IgE serum levels, allergic reactions, and atopy
14
Q
What context is needed to get an allergic response?
A
- time (level of exposure, how long you’ve been exposed, when in life you were exposed)
- route of entry (mostly mucosal)
- genetic predisposition
15
Q
Describe the mechanism of an allergic response.
A
- contact with allergen - mostly mucosal, cutaneous, or systemic
- allergen binds to TLRs on dendritic cells
- antigen presentation on a Class II MHC to a naive T cell
- IL-4 produced by mast cells, basophils, and DCs activate the naive T cell to differentiate into a Th2 cell
- Th2 produces IL4 and activates class switching and allergen-specific antibody production from the B-cell
- IgE antibodies bind to FcE receptors on mast cells and basophils
- mast cells produce IL4 and activate B cell to make more antibodies (upregulation of CD23 on mast cells increases production of IL4)
- allergen will bind to mast cell FcEs => cross linking => signal transduction => calcium influx => degranulation
16
Q
Recall how Th2 differentiation occurs.
A
- APC makes IL4 => GATA => Th2 makes IL4, 5, 10, 13
- must occur in absence of IL12
17
Q
Characterize the FcE receptor.
A
- very high affinity binding
- the only Fc receptor that can bind to an empty antibody (no antigen required to bind)
18
Q
What happens during the immediate phase of an allergic reaction?
A
- previous exposure and sensitization is required for this to occur
- lasts 15 minutes
- vasoactive mediator release from mast cells and basophils
- synthesis and release of prostaglandins and leukotrienes
- tryptase release from mast cells activates complement
19
Q
What is the function of tryptase in the allergic response?
A
- direct complement activation
- used as serum diagnostic marker for mast cell activation during anaphylaxis
20
Q
What happens during the late phase allergic response?
A
- occurs within 6-8 hours
- requires T cell activation, IL3-5, 10, 13, TNFa, GM-CSF
- Th2 and mast cells release IL5 that recruits neutrophils and more mast cells/basophils
- IL5 also increases FcE receptor expression
- eosinophils increase release of major basic proteins, leukotrienes, cationic proteins (inflammatory)
21
Q
Define anaphylaxis.
A
- acute life-threatening reaction due to mast cell and basophil mediators
- organ = multi-systemic
- route of entry = stings, ingestion
- allergen = drug, food, venom
- Sx: shock, hypotension, wheezing, angioedema, urticaria
- can be fatal
- Tx: epinephrine shot (but in some people, can escalate response)
22
Q
Define allergic rhinitis.
A
- inhalation of allergen
- main organs = nose, eyes
- route of entry = mucosa
- allergen = pollen, dander, molds
- Sx: itchy eyes, nasal discharge, sneezing, nasal airway obstruction, inflammation
23
Q
Define urticaria/atopic dermatitis.
A
- due to mast cell degranulation and skin microvascular hyperpermeability to recruited eosinophils, etc.
- main organ = skin
- route of entry = contact, ingestion
- allergen - various foods, drugs
- Sx: hives, wheals, angioedema
- most common in ages 20-40
- can last for a few hours or days
24
Q
Define wheals.
A
- pruritic edematous plaques
25
Define asthma.
- chronic disorder of the airways
- due to episodic bronchoconstriction, increased bronchial airway sensitivity, inflammation, increased mucus secretion
- main organ = lung
- route of entry = inhalation
- allergen = pollen, dander, mold
- Sx: wheezing, coughing, SOB, chest tightness, dyspnea, tachypnea
- episodic attacks
- increasing prevalence
26
Describe how genes and environment interact to from an allergic response.
Environment
- right allergen at the right time
- small family (less exposure to various URI antigens)
- hyperhygiene (less exposure to antigens)
- antibiotics
1. Genes + environment => Treg deficiency => atopy
2. atopy + triggers => IgE => allergy
27
What can trigger an allergy response?
- reexposure
- virus
- pollutants
28
Describe the hygiene hypothesis.
- children are not getting as sick, and if they are, it is happening later in life
- large families and day care babies are exposed to more pathogens => more URIs => more Th1, downregulate Th2 => allergies are rare in these people
- early exposure to pathogens establishes the proper Th1:Th2 ratio
- worms are protective because they induce Tregs in the gut that can migrate and suppress allergy and autoimmune responses in other parts of the body later on
29
How can we detect if someone has an allergy?
- history
- skin test (more sensitive than blood test)
- RAST
30
Define RAST.
RadioAllergoSorbent Test
1. allergen bound to well
2. add patient serum
3. wash => if IgE against that antigen is present, then it will be bound
4. add radiolabeled anti-IgE antibody to detect presence of antibody against that allergen
31
What are the drawbacks to allergy testing?
- skin, blood, and RAST testing can be positive for the allergen, but if the patient does not have symptoms then they do not have that allergy
32
List treatments to allergy.
1. avoid allergen
2. pharmacological suppression via anti-histamines
3. anti-IgE therapy (anti-IgE monoclonal antibodies)
4. allergen immunotherapy (SCIT, SLIT)
5. vaccines
33
Define SCIT/SLIT.
SubCutaneous (Lingual) ImmunoTherapy
- giving shots of allergen
- causes redirecting of response
- allergen induces Th1 activation, macrophages to destroy the allergen
- allergen causes Th2 activation, and B cell makes IgG instead
34
Define allergic gastroenteropathy.
- main organ = GI
- route of entry = ingestion
- allergen = food
- Sx: pain, bloating, vomiting, diarrhea
35
Define the role of anti-IL5 drugs in allergy treatment.
anti-IL5 would stop the recruitment of eosinophils and downregulate the FcE receptor
36
Dogs vs. cats. Who is best for immunity?
- dogs expose humans to antigens => protective immunity against allergens
- if allergic to cats = all cats
- if allergic to dogs = some breeds
