Type I Hypersensitivity

Question 1

What are the four hypersensitivity reactions and what is unique about each?

Answer 1

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

Question 2

Describe the primary pathway for inducing a Type I response

Answer 2

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

Question 3

What is one of the key modulators that mast cells use to drive responses? Does it require synthesis for secretion? Where is it stored?

Answer 3

Granules and pre-formed products. Yes, it requires synthesis from B cells and plasma cells. It is stored in the mast cell.

Question 4

In general, cytokines from mast cells drive a pro-inflammatory and type ____ immune (T helper) response

Answer 4

Th2

Question 5

How do eosinophils regulate mast cell response?

Answer 5

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

Question 6

How do antihistamines regulate mast cell response?

Answer 6

block the binding of histamine to histamine receptors found in vascular smooth muscle, endothelium, nerves, glandular tissue, etc…

Question 7

How does glocucorticoid action regulate mast cell response in
Mast cells/granulocytes
Neutrophils
Macrophages
Lymphocytes

Answer 7

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

Question 8

How does epinephrine regulate mast cell response?

Answer 8

suppress mast cell degranulation
induce smooth muscle relaxation
induce vascular constriction

Question 9

What are the two primary clinical manifestations of a Type 1 hypersensitivity reaction?

Answer 9

Anaphylaxis and Allergies (dermatitis)

Question 10

What species have the liver as a primary shock organ?

Answer 10

Dog

Question 11

What species have the lung and intestine as primary shock organs?

Answer 11

Cat, horse, pig

Question 12

What species have the lung as a primary shock organ?

Answer 12

ruminants, chicken, human

Question 13

What is anaphylaxis?

Answer 13

A severe, generalized or systemic hypersensitivity reaction.

Question 14

What is an allergic response?

Answer 14

A state of immunological sensitization to an innocuous environmental antigen that leads to an excessive immune response on re-exposure to the antigen.

Question 15

What are the causes of an allergic response (5)?

Answer 15

1. Genetic predisposition
2. Age
3. Hygeine hypothesis- helminth exposure and induction of T regs
4. Exposure
5. Secondary disease

Question 16

Common allergies seen in vet med (5)

Answer 16

Parasites and flea allergy dermatitis- 
Atopy (air contact)
Food
Inhalent
Vaccines/ drugs- haptenized

Question 17

their inciting antigen and clinical signs and distribution of pruritis in parasite and flea allergy dermatitis

Answer 17

IgE mediated in parasites

causes dermatitis, respiratory distress, diarrhea

Question 18

their inciting antigen and clinical signs and distribution of pruritis in atopy, food, and inhalent allergies

Answer 18

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

Question 19

their inciting antigen and clinical signs and distribution of pruritis in vaccine/drug allergies

Answer 19

IgE mediated response in vaccines, haptonization in drugs

Question 20

Describe how a beneficial anti-parasitic response can induce clinical disease

Answer 20

The responses can exacerbate Type I hypersensitivity responses in other diseases because of the feed forward amplification that can occur in Type I

Question 21

What is the rational behind desensitization therapy (4)?

Answer 21

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

Question 22

Will it be easier to induce tolerance in T or B cells, and which will persist longer?

Answer 22

Easier to induce tolerance in T cells and the tolerance in T cells last longer.

Question 23

What cytokine helps drive a “neuronal itch” cycle

Answer 23

IL 31

Question 24

What is the role of the JAK Stat signaling pathway in type I hypersensitivity?

Answer 24

Th2 produce IL31-> IL31 binds to cutaneous sensory nerves in the skin-> activates JAK signaling-> leads to neuronal itch