Type I Hypersensitivity Flashcards
What are the four hypersensitivity reactions and what is unique about each?
Type I - Immediate - allergy / anaphylactoid; IgE and mast cell mediated
Type II - Cytotoxic hypersensitivity; Transfusion reactions
Type III - Immune complex disease; Deposition of Ab / Ag complexes
Type IV - Delayed hypersensitivity; T cell and NK mediated
Describe the primary pathway for inducing a Type I response
An allergen binds to IgE on mast cells resulting in the release of inflammatory mediators via IgE crosslinking. IgE molecules are synthesized via a Th2 response and bound to mast cells via Fc portion on IgE
What is one of the key modulators that mast cells use to drive responses? Does it require synthesis for secretion? Where is it stored?
Granules and pre-formed products. Yes, it requires synthesis from B cells and plasma cells. It is stored in the mast cell.
In general, cytokines from mast cells drive a pro-inflammatory and type ____ immune (T helper) response
Th2
How do eosinophils regulate mast cell response?
They secrete products that inhibit or break down mast cell products. They are concurrently stimulated during cytokine release from mast cells during B cell development and for IgE production
How do antihistamines regulate mast cell response?
block the binding of histamine to histamine receptors found in vascular smooth muscle, endothelium, nerves, glandular tissue, etc…
How does glocucorticoid action regulate mast cell response in Mast cells/granulocytes Neutrophils Macrophages Lymphocytes
activates genes that inhibit immune function:
mast cells/ granulocytes- decreased degranulation
neutrophils- decreased chemotaxis, margination, function/killing
Macrophages- decreased antigen processing, chemotaxis, function/killing, IL1 production
Lymphs- decreased T cell function and proliferation
How does epinephrine regulate mast cell response?
suppress mast cell degranulation
induce smooth muscle relaxation
induce vascular constriction
What are the two primary clinical manifestations of a Type 1 hypersensitivity reaction?
Anaphylaxis and Allergies (dermatitis)
What species have the liver as a primary shock organ?
Dog
What species have the lung and intestine as primary shock organs?
Cat, horse, pig
What species have the lung as a primary shock organ?
ruminants, chicken, human
What is anaphylaxis?
A severe, generalized or systemic hypersensitivity reaction.
What is an allergic response?
A state of immunological sensitization to an innocuous environmental antigen that leads to an excessive immune response on re-exposure to the antigen.
What are the causes of an allergic response (5)?
- Genetic predisposition
- Age
- Hygeine hypothesis- helminth exposure and induction of T regs
- Exposure
- Secondary disease
Common allergies seen in vet med (5)
Parasites and flea allergy dermatitis- Atopy (air contact) Food Inhalent Vaccines/ drugs- haptenized
their inciting antigen and clinical signs and distribution of pruritis in parasite and flea allergy dermatitis
IgE mediated in parasites
causes dermatitis, respiratory distress, diarrhea
their inciting antigen and clinical signs and distribution of pruritis in atopy, food, and inhalent allergies
typically presents as chronic pruritus on face and feet, and often becomes more generalized, neuronal itch
Th2 cells are significant/primary drivers
Mast cells, IgE, and histamine may be secondary component
their inciting antigen and clinical signs and distribution of pruritis in vaccine/drug allergies
IgE mediated response in vaccines, haptonization in drugs
Describe how a beneficial anti-parasitic response can induce clinical disease
The responses can exacerbate Type I hypersensitivity responses in other diseases because of the feed forward amplification that can occur in Type I
What is the rational behind desensitization therapy (4)?
Densensitization uses injections of the offending allergen in increasing doses to
promote IgG production (competes with IgE for allergen binding)
shift the immune response from a Th2 to a Th1
Increase IL10, Treg cells, and blocking antibodies
reduce clinical symptoms of the reaction
Will it be easier to induce tolerance in T or B cells, and which will persist longer?
Easier to induce tolerance in T cells and the tolerance in T cells last longer.
What cytokine helps drive a “neuronal itch” cycle
IL 31
What is the role of the JAK Stat signaling pathway in type I hypersensitivity?
Th2 produce IL31-> IL31 binds to cutaneous sensory nerves in the skin-> activates JAK signaling-> leads to neuronal itch
